Theme: Mononeuritis. Neuralgia. Polyneuritis. Polyneuropathy.

The principles of rehabilitation of the patients with neurological pathology.

ANATOMY OF THE PERIPHERAL NERVES

Motor nerve fibers originate from the anterior horn cells of the spinal cord and leave the cord through the anterior nerve root. The sensory fibers originate from neurons in the posterior root ganglia and enter the spinal cord through the posterior nerve root. The anterior and posterior nerve roots unite distal to the cord to form a mixed spinal nerve (Fig. 19-1). Both anterior and posterior nerve roots are covered by dura as they leave the spinal cord up to the point of exit from the spinal canal where the dura becomes continuous with the epineurium covering the mixed spinal nerve. The mixed spinal nerves unite in the cervical and lumbar areas to form the cervical, brachial, and lumbosacral plexuses. Each plexus gives rise to a number of individual mixed nerves, which are distributed to the periphery to supply muscle, skin, and blood vessels.

Each nerve contains numerous nerve fibers. The central portion of each nerve fiber consists of an axon that contains axoplasm. Axoplasm is a complex structure containing mitochondria, endoplasmic reticulum, Golgi apparatus, neurotubules, and neurofilaments, which are individual nonanastomotic fibrils that extend the entire length of the axon. The surface of the axon is covered by a limiting membrane called the axolemmaand by the myelin sheath external to the axolemma. The myelin sheath is derived from the cytoplasm of the Schwann cell and surrounds the axonin concentric layers. Large myelinated axons are either motor axons or sensory axons subserving the modalities of touch, vibration, andproprioception. Small myelinated axons serve pain and temperature, while so-called unmyelinated axons, which are invested by the Schwann cell membrane without sheath

formation, carry pain and deeper ill-defined sensation. The myelin sheath is not a continuous structure but consists of sections, each derived from a single Schwann cell, which are separated by small gaps known as nodes of Ranvier. Electrical impulses are conducted by a series of "jumps" from node to node, a method known as saltatory conduction. This means that the speed of conduction is related to the distance between the nodes. Rapidly conducting axons have relatively few nodes, which are far apart. Axons that conduct more slowly have many nodes, which are close together along the extent of the axon. The so-called unmyelinated nerve fibers are very slow-conducting fibers. Axons are also capable of conducting proteins from the perineurium or cell body to the periphery, and it is known that this conduction is two-directional. There is a functional relationship between the Schwann cells and axons. Schwann cells will not survive without the presence of axons, although axons will survive in the absence of Schwann cells, but their function is markedly altered. Mixed peripheral nerves consist of many thousands of axons, each separated by a fine connective tissue called the endoneurium. Axons are collected in bundles or fascicles surrounded by perineurium, and fascicles are separated by a thicker connective tissue known as the epineurium.

Diseases of the peripheral nerves may produce changes in axons or in the myelin sheath. Axonal changes are of two types, axonal (wallerian) degeneration and axonal dystrophy. Axonal degeneration occurs following severance or infarction of a peripheral nerve. The axon dies up to the level of the first internode above the site of trauma, which may be followed by chromatolysis in the perikaryon or cell body of the neuron. Themyelin distal to the site of trauma disintegrates and is digested and removed. If the cell body does not die, axonal regeneration occurs by the regrowth of nerve fibrils, which attempt to make contact with the peripheral axolemma and re-establish the previous peripheral connections. If the axolemma is destroyed, degeneration is haphazard and may result in the development of a painful, traumatic neuroma. Once the neurofibrilshave regenerated, the Schwann cells reinvest the axon with myelin. A number of nutritional and metabolic disorders are associated with a second type of axonal damage called axonal dystrophy in which there is a gradual dying back of the axons from the periphery. This is commonly seen in diabetic neuropathy but also occurs in alcoholism and in many toxic conditions.¹

Segmental demyelination occurs when there is primary involvement and death of the Schwann cell. The neuron, including the perikaryon andaxon, remains normal, and axonal continuity is maintained. In some cases Schwann cell regeneration occurs, but the nodes of Ranvier are situated closer together than before demyelination. Remyelination is occasionally followed by hypertrophy of the Schwann cells, which surroundaxons in an "onion ring" fashion. Hypertrophic change occurs in hereditary motor and sensory neuropathies (HMSN) type I-peroneal muscular atrophy, Charcot-Marie-Tooth disease; HMSN type II-Dejerine-Sottas disease; chronic inflamma-tory demyelinating neuropathy; and occasionally in acromegaly.  Demyelination is a feature of some

hereditary neuropathies and the Guillain-Barre syndrome. Mixed types of peripheral neuropathy with both axonal degeneration and demyelination can occur.

Several clinical patterns of peripheral neuropathy are recognized. These include:

1.  Mononeuropathy.   Mononeuropathy   implies   involvement of one peripheral nerve. This is commonly the result of trauma but also occurs indiabetes  mellitus  and  in  infarction  of peripheral nerves (e.g., in polyarteritis nodosa).

2.  Polymononeuropathy   (mononeuritis   multiplex). Polymononeuropathy is a term used to describe involvement of several individual nerves in a haphazard fashion. The etiology is the same as for mononeuropathy.

3.  Radiculoneuropathy. A radiculoneuropathy is involvement of the nerve root as it emerges from the spinal cord. This is commonly seen withherniated discs or with epidural masses (e.g., tumor).

4.  Plexitis. A plexitis is an inflammation of a plexus such as the brachial plexus (brachial plexitis).

5.  Polyneuritis.  In polyneuritis or polyneuropathy there is a symmetrical involvement of peripheral nerves. The most common causes are diabetes mellitus and alcoholism. There are, however, numerous causes of peripheral neuropathy and the identification of the etiological agent may be difficult in unusual cases.

Neuropathies, no matter what their cause and type, present with specific signs and symptoms. Involvement of motor axons produces muscle wasting and weakness followed by atrophy and the appearance of fasciculations. The tendon reflexes supplied by the affected nerve are depressed or absent. Involvement of sensory axons produces impairment of sensation with dysethesias or paresthesias. Involvement of axonssupplying autonomic function produces loss of sweating, alteration in bladder function, constipation, and impotence in the male. Reflex sympathetic dystrophy, a very painful peripheral dysesthesia, is probably related to disturbance of the autonomic system in the spinal cord and the peripheral nerves.

Definition

      It is multiple symmetrical lesions of peripheral nerves, associated with motor, sensory and autonomic – trophic disorders mainly in distal parts of extremities. If there is any infection among etiological factors this pathology of peripheral nerves is called polyneuritis. If there is an intoxication or hereditary factor in etiology it is known as polyneuropathy. 

Classification.

I. Etiological

A. Polyneuritis

1.    Infectious

a.    Bacterial (neuropathy of leprosy, lues, leptospirosis and so on)

b.    Infectious – allergic (at scarlet – fever, infectious mononucleosis, diphtheria).

B. Polyneuropathy

1.    Allergic (vaccinal, serum)

2.    Toxic (bacterial, exogenous, iatrogenic)

3.    Dismetabolic (diabetic, uremic, alcoholic, hepatic)

4.    Paraneoplastic

5.    Inherited

6.    Ischemic

7.    Radial

II. Morphological

1.    Axonal

2.    Periaxonal

3.    Interstitial

III. Clinical

1.    Motor

2.    Sensory

3.    Sensitive

4.    Autonomic

5.    Mixed

Common clinical picture of all polyneuritis and polyneuropathies.

One of the common features of all polyneuropathies and polyneuritis is the presence of polyneuritic syndrome that includes three types of disorders:

1). Motor disorders (these ones prevail at motor form) such as flaccid paralysis or paresis with hypotonia, hypotrophia and hyporeflexia.

2). Sensory disturbances in distal parts of extremities such as subjective (pain, parasthesia) and objective (anesthesia or hyposthesia of superficial and deep types of sensation) disorders.

a). Sensory form is developed when superficial sensation is lost

b). Sensitive form is developed when deep sensation suffers.

c). Autonomic – trophic disorders are dominant at autonomic form.

In case of any polyneuritis or polyneuropathy the presence of polyneuritic syndrome is obligate, although every polyneuritis or polyneuropathy has its own clinical peculiarities.

The peculiarities of clinical picture of polyneuritis.

1). Luetic polyneuritis

         Sensitive forms (deep muscle – joint and vibration sensation suffers) prevail

         Sensitive ataxia dominates in clinical picture

         Diagnosis: serum reactions of Wasserman, RIF

              In treatment Penicillinum long – active antibiotics are used.

              2). Leptospirosis polyneuritis

         Polyneuritic disorders are developed on the background of specific somatic clinical picture

         Diagnosis: serum reaction

              In treatment antibacterial medications are used.

             3). Leprosis polyneuritis.

         Sensation is lost spot – likely

         There are roductive – inflammatory infiltrates and spots on skin

          At first pain and temperature sensation suffers, then tactile one is involved

         There are severe autonomic disorders (ulcers, bone deformations)

Leprosy

This condition is rare in the United States and Europe but is still one of the most common causes of neuropathy worldwide.

The disease is the result of infection by Mycobacterium leprae and appears in two forms, the tuberculoid type and the leprous type of leprosy. The form of the disease appears to depend on the immune response of the patient, but in either case, the incubation period may be as long as 10 years before symptoms appear.

In tuberculoid leprosy, there are skin lesions consisting of macules that are relatively few in number, and superficial nerves are affected and may be palpably enlarged. Occasionally, larger nerves such as the median, ulnar, common peroneal, and facial nerves are involved.

In leprous leprosy, the skin lesions are more numerous and the earlobes are affected, as are the dorsal surfaces of the hands, forearms, feet, and anterolateral aspects of the legs. These areas show sensory loss. In addition, there may be a symmetrical peripheral neuropathy.

The condition is diagnosed by muscle biopsy, although the diagnosis can be anticipated in patients with appropriate symptoms in tropical countries.

Treatment

1 Diaminodiphenylsulphone (dapsone) 400 mg/day. Alternatives include rifampin, streptomycin, and isonicotinic acid hydrazide. Chloroquine may also be of benefit.

2. Acute   mononeuritis   may   respond   to   corticosteroids.

             4). Brucelosis polyneuritis

         Superficial sensation on the extremities suffers spot – likely

         Muscular pain

         Asthenic syndrome

         The other organs are involved

         Typical profession

         (+) Reaction of Rait – Hedelson

             In treatment antibacterial medications are used.

             5). Viral polyneuritis (Flu – associated one and so on)

         It is developed on the background of upper respiratory ways disease and fever.

         The onset is acute (in course of 2 – 3 days)

         Severe intoxication

         CNS is often involved (meningoencephalomyelopolyradiculoneuritis)

         Sensory forms without paresis are the most typical ones

         Flaccid paralysis are very rare

         Renovation of nerves’ function takes up to 1 – 2 months

The peculiarities of polyneuropathies’ clinical picture.

I.          Allergic: - Guillain – Barre

-          Those associated with collagenous diseases

-          vaccinal

  1).  Guillain – Barre polyneuropathy – it is an acute autoimmune auto-allergic disease. In most cases it is developed after infections, trauma and surgery.

The peculiarities of clinical picture:

1.    There is flaccid tetraparesis, much more expressed in proximal parts of extremities.

2.    IX, X, VII CN’s are often involved (bulbar syndrome with respiratory disturbances)

         There are respiratory disorders in case of between ribs nerves involvement.

         Sensory disorders are slightly expressed or absent

         It is often associated with meningoradicular syndrome, (+) Kernig, Lasseg, Neri signs.

         Protein – cell dissociation in CSF

         The course of the disease has its own peculiarities:  the clinical picture develops rapidly during 7 – 10 days. By the way, the more rapidly it is developed, the better it will regress. In case of typical course of the disease ¾ of all patients recover completely. In case of severe course of the disease (with bulbar and respiratory disorders) convalescence lasts up to 1 – 2 years and 17 % of all patients still have severe motor disorders even after 5 years.

Treatment:

-          desintoxication

-          dehydration

-          desensibilization

-          plasmaferesis (8 – 10 seances)

-          Glucocorticoids

Guillain-Barre Syndrome (Acute Inflammatory Demyelinating Polyneuropathy)

Definition

The Guillain-Barre syndrome is an acute, symmetrical, ascending polyneuropathy frequently occurring 1 to 3 weeks and occasionally up to 8 weeks after an acute infection.

Etiology and Pathology

The Guillain-Barre syndrome often follows a nonspecific respiratory or gastrointestinal illness but has also been described after a number of specific infections such as cytomegalovirus, Epstein-Barr virus, enterovirus, Campylobacter jejuni or mycoplasma, and after immunization. The disease is believed to be due to lymphocytic sensitization to peripheral nerve antigen. There is diffuse, patchy, segmental demyelination of peripheral nerves. Light microscopy reveals an intense lymphocytic, inflammatory infiltrate at the sites of demyelination.

Clinical Features There is a worldwide incidence of 1.6 to 1.9 cases per 100,000 population per year. More than 50 percent of cases have a clear history of an upper respiratory infection 1 to 3 weeks prior to the onset of neuropathy and an antecedent gastroenteritis is not uncommon. Other antecedent conditions include immunizations, surgical procedures, pneumonia, influenza, tonsillitis, and exanthema of childhood.

The syndrome often begins with myalgia or paresthesias of the lower limbs followed by weakness. About one-third of those affected develop lower limb weakness, which ascends to involve pelvic girdle, abdominal, thoracic, and upper limb muscles. Examination shows symmetrical weakness of muscles with loss of tone and flaccidity. Tendon reflexes are absent. The seventh cranial nerve is frequently involved, and bilateral facial weakness is common. Involvement of the other cranial nerves may result in ptosis or facial myokymia. Dysarthria, dysphagia, and diplopiadevelop in severe cases. The degree of sensory involvement varies, but this is disproportionately less than the muscle involvement.

The paralysis may progress for about 10 days and then remain relatively unchanged for about 2 weeks. The recovery phase is much slower and may take from 6 months to 2 years for completion.

Complications

1.    Respiratory impairment occurs in about 50 percent of patients and respiratory failure in at least 33 percent of patients.

2.    Autonomic instability may present as urinary retention in the early stages of the disease. Fluctuations in blood pressure, orthostatichypotension, and a rare complication of persistent hypertension are late events.

3.    Bulbar palsy should always be considered when bilateral facial weakness is present.

4.    Pain presenting as myalgia in the lower limbs is an early symptom in some cases, but pain may be a prominent symptom throughout the acute phase of the illness, requiring appropriate and adequate therapy.

5.    Secondary infection is a risk with pneumonia complicating respiratory insufficiency and in creased risk of urinary tract infection and infecteddecubitus ulcers.

6.    Immobility  predisposes  to  deep  venous thrombosis in the lower limbs and pulmonary embolism.

7.    Similarly, immobility and failure to change position increase the risk of skin breakdown and decubitus ulcers.

8.    Fluid and electrolyte imbalance is not unusual when intake is restricted to parenteral fluids because of bulbar palsy.

9.    Papilledema is a rare complication; the cause is unknown.

10.    Relapse is uncommon unless treatment is inadequate.

11.    Recurrence has been reported, but many of these patients may have had chronic inflammatory demyelinating   polyneuropathy  presenting   with   a rather acute onset, rather than the Guillain-Barre syndrome.

Variants

Guillain-Barre syndrome may occasionally present with a descending paralysis of pharyngeal cervical brachial muscles rather than the typical ascending paralysis. Other variants include paraparesis with normal strength and reflexes in the upper limbs and an initial severe midline back pain. The Miller-Fisher syndrome of ophthalmoplegia, bilateral facial weakness, severe ataxia, absence of tendon reflexes but only mild limb weakness is believed to be another variant of Guillain-Barre syndrome although optic neuropathy may also occur in this condition.

Diagnostic Procedures

1.    The   CSF  cell   count   may   be   normal, or there may be a mild lymphocytic pleocytosis in the early stages of the disease. The protein content begins to rise after the first week of the illness and continues to rise for several weeks to levels above 100 mg/dL.

2.    Nerve conduction studies show conduction velocities less than 60 percent of normal in most cases. Distal and motor latencies are prolonged, and proximal stimulation of nerves shows a decrease in

amplitude, owing to dispersion of the action potential or conduction block. F-wave responses may be absent or show prolonged latency.

3. About 10 percent of patients show incomplete recovery. A prolonged period (more than 3 weeks) from maximal weakness to initial improvement, associated with reduced motor nerve conduction velocities and evidence of denervation by electromyography, are indicative of a possible incomplete recovery.

Differential Diagnosis

1.    Poliomyelitis  is  characterized by  initial fever and severe myalgia followed by asymmetrical flaccid paralysis of muscles. There is an initial CSF pleocytosis, and there is no sensory involvement.

2.    Botulism often occurs in a group situation with ingestion of home-canned food. Symptoms begin with diplopia.

3.    In heavy metal neuropathy, the onset of weakness is much slower. There is a history of exposure to heavy metals in industry in most cases.

4.    Periodic paralysis is characterized by sudden onset of generalized paralysis without respiratory involvement and hypo- or hyperkalemia.

5.    Acute polymyositis. There is an acute onset of proximal symmetrical weakness. A rash is often present in dermatomyositis. The sedimentation rate and creatine phosphokinase levels are elevated.

6.    Tick paralysis is a flaccid paralysis without respiratory involvement that usually occurs in childhood. Examination will reveal a tick attached to the skin. There is rapid recovery after removing the tick.

7.    Acute intermittent porphyria. Acute respiratory paralysis can occur suddenly in this condition. The urine shows the presence ofporphobilinogen, and serum delta aminolevulinic acid is elevated.

8.    Myasthenia gravis does not present as an ascending paralysis.

9.    An    acute   inflammatory   demyelinating polyneuropathy may be associated with HIV zero conversion,   acquired  immunodeficiency  syndrome (AIDS)-related complex (ARC), or AIDS.

Treatment

1.    Good nursing care is essential to prevent the development of pressure sores.

2.    Retention of urine may occur in the early stages and require bladder catheterization.

3.    Respiratory insufficiency should be anticipated in all cases with vital capacity recorded by spirometry q6h. When the readings show a progressive decrease in vital capacity, the procedure should be performed q4h, then every hour when the reading is marginal. In the male patient weighing 70 kg assuming a minimal requirement of 10 mL/kg, a vital capacity of 1 L requires intubation and assisted ventilation. The critical level in a female weighing 50 kg is 750 mL vital capacity. Critical levels are higher in obese and emphysematous patients.

4.    Physical therapy should be given from the initial stages of the disease beginning with passive movements to prevent adhesions around the joints. The program should be increased with more active participation by the patient as soon as there are signs of recovery.

5.    There is no evidence that corticosteroids are beneficial and some evidence shows a detrimental effect in controlled studies.⁵⁶

6.    Plasmapheresis is an effective therapy and treatment consists of exchanging 200 or 250 mL of plasma per kg body weight on alternate days over a 7- to 10-day period.⁵⁷ Treatment beginning within a week of onset of weakness is most beneficial, and delay beyond 2 weeks is likely to be ineffective. Because mild cases of Guillain-Barre syndrome do not require plasmapheresis, treatment can be delayed until the patient can no longer walk or shows signs of respiratory or bulbar involvement. However, treatment should begin at an early stage in cases known to be associated with severe deterioration, for example, after rabies vaccination, surgery, or when there is a short interval between antecedent events and onset   of   symptoms.   Limited   relapse   has   been reported from 5 to 42 days after plasmapheresis.⁵⁸ Retreatment is effective.Plasmapheresis is occasionally associated with hypotension and cardiac arrhythmias. Thrombosis, hemorrhage, or sepsis are low-risk complications.

7. Intravenous immunoglobulin (IVIG) has displaced plasmapheresis as the first choice in therapy in many institutions. The IVIG patients have fared better than plasmapheresis-treated patients in controlled studies, and IVIG has fewer adverse effects.⁵⁹ However, IVIG has been associated with significant increase in relapse rate, although these episodes are usually mild. Spacing IVIG therapy over a 7- to 10-day period rather than 5 consecutive days reduces the relapse rate.

Prognosis Complete recovery occurs in 85 percent of cases, but the process is slow, lasting several months or as long as 18 months in some cases. Respiratory insufficiency proposes a life-threatening situation, which can be minimized by the early use of an efficient, modern ventilator. A few patients show partial recovery and then develop prominent signs of peripheral neuropathy. Relapse in the early phase of the illness is not unusual, but relapse weeks or months after recovery suggests that the initial attack may have been a particularly acute episode of recurrentpolyneuropathy, such as chronic inflammatory demyelinating polyneuropathy.

Axonal Variant of Guillain-Barre Syndrome

There are occasional examples of cases clinically indistinguishable from Guillain-Barre syndrome that show axonal degeneration rather than demyelination. The CSF proteinxell dissociation is present and the course is often but not invariably benign. The conduction follows a C. jejuni orLegionella infection in some cases. Diagnosis is established by stool culture for C. jejuni and by electromyogram demonstration of primary axonal disease in Legionella infections.

Treatment Treatment is as for classical Guillain-Barre syndrome.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Definition Chronic inflammatory demyelinating polyradiculoneuropathy is a chronic polyneuropathy in which there is steady progression, intermittent progression, or a relapsing and remitting course over a period of years.

This condition in the past has been described as idiopathic neuritis, nonfamilial hypertrophic neuritis, nonfamilial Dejerine-Sottas disease, relapsing neuritis, and recurrent neuritis.

Etiology and Pathology

There is often a history of a preceding infectious process or an injection of a foreign protein, but some cases of CIDP develop in an apparently well individual without a history of prior infection, immunization, or vaccination. Nevertheless, the condition is believed to be an autoimmune response directed against the Schwann cells of the peripheral nerve.

The affected nerves show mononuclear cell infiltration with segmental demyelination and a reactive hyperplasia of Schwann cells producinghypertrophic neuropathy. The involvement is often predominantly proximal involving both sensory and motor nerve roots.

Brainstem involvement has been described in some cases with degeneration of neurons, microglial proliferation, and perivascular lymphocyticinfiltration.

Clinical Features

Symptoms of sensory involvement and motor weakness occur with equal frequency. Sensory symptoms usually consist of numbness andparesthesias in the hands and feet. Pain is less frequent but occurs in some cases. Motor weakness may be proximal⁶² (difficulty in rising from a chair, lifting arms above the head) or distal (poor grip, tripping due to foot drop). Intercostal, diaphragmatic, and bulbar weakness occur in less than 20 percent of cases. The course may be progressive, intermittent, or relapsing and remitting.

Weakness and wasting occur in both proximal and distal muscles and are of equal extent. Sensory loss involving touch, pinprick, vibration, and position sense occurs in symmetrical fashion in upper and lower limbs. Signs of brainstem involvement are not uncommon and include Argyll Robertson pupils, Horner syndrome, diplopia, nystagmus, depressed corneal reflexes, sensory loss over the face, bilateral facial weakness,dysarthria and dysphagia, weakness of the tongue, and intention tremor in the upper limbs. Papilledema occurs in a small number of cases. Hyporeflexia or areflexia are observed in most

patients, but hyperreflexia can occur when brainstem involvement is extensive. The peripheral nerves are palpably enlarged when the demyelinating process extends more peripherally and involves the ulnar or median nerve at the elbow.

The disease may progress to severe disability with confinement to a wheelchair or bed in a minority of cases. Most patients remain ambulatory but handicapped by the disease. Death may occur from intercurrent infection after several years in severely debilitated patients.

Diagnostic Procedures

1.    The white blood cell count and erythrocyte sedimentation rate are normal, but there may be an elevation of gamma globulin on serum proteinelectrophoresis.

2.    On lumbar punctures, the CSF has a normal cell content or a mild pleocytosis of less than 75 cells per dL. The cell content is predominantlylymphocytic, but some polymorphonuclear cells are present on occasion. The protein content is usually elevated and may be in excess of 500 mg/dL. The gamma globulin content is elevated in some cases.

3.    Nerve conduction velocities of both motor and sensory nerve fibers are usually but not invariably slowed.

4.    Sural nerve biopsy shows evidence of demyelination with mononuclear cell infiltration of the epineurium  and  endoneurium,  edema  of the en-doneurium, and Schwann cell proliferation (onion bulb formation). Teased fibers show evidence of demyelination and remyelination.

5.    The MRI scans have demonstrated evidence of demyelination in the brain in some cases of CIDP suggesting that a combined syndrome of central and peripheral demyelination may exist.

Treatment

I. Corticosteroids. There is no doubt that corticosteroids are beneficial in CIDP,⁶¹ but the benefit may be short-lived and long periods of treatment are needed in some cases. This usually results in adverse effects. Tapering to a maintenance dose of steroids to delay the onset of side effects can be attempted, but long-term treatment at high dose seems to be necessary in some cases.

2.    Plasmapheresis is an effective alternative to corticosteroids. This is a safe and effective therapy in children and adults.

3.    Intravenous and immunoglobulin therapy is currently recommended as  an effective, preferred treatment for CIDP⁶⁴-⁶⁵ in adults and in children.⁶⁶ Improvement may be sustained for many months in some cases; others show a short-lived response of 2 weeks to 3 months. However, the response to repeated courses' of immunoglobulin therapy is sustained, and in many cases, a hundred courses have been reported without decline in efficacy or the development of adverse reactions.

4.    Other   immunosuppressive    agents    have been reported to improve CIDP. There are no controlled studies to date, but the most promising agent appears to be cyclophosphamide, either orally or by pulsed intravenous administration. Cyclosporine A is another immunosuppressantreported to be of benefit when there is a lack of response to steroids, plasmapheresis, or immunoglobulin.⁶⁷

Prognosis

Spontaneous recovery has been observed in a small number of cases. Some patients respond to corticosteroids, while others show initial improvement, then apparently fail to respond to further treatment. A number of patients fail to respond to corticosteroids and die from respiratory failure or intercurrent infection several years after the onset of the disease.

    2). Polyneuropathy at collagenous diseases

    One of the most common polyneuropathy in this group is the one associated with periarteriitis nodosis.

The peculiarities of clinical picture

         The disease starts as multiple mononeuropathy (there are signs of different nerves involvement, for example n. ulnaris, n. medianus and so on)

         Later clinical picture of polyneuritic syndrome is developed

Somatic changes

         The typical changes of internal organs (especially those well blood supplied, such as kidneys, GIT, heart.

         Long lasting hyperemia

         Skin rash

         Inflammatory changes in blood

         Polyarthalgia

         Cachexy

Diagnosis is put after morphological investigation of muscles.

To treat such patient Corticoids, Cytostatics are used.

3). Vaccinal polyneuropathy

Usually this group of the disease is developed after the usage of anti rabies vaccine (as an allergic reaction on vaccinal myelin.

The peculiarities of clinical picture:

         The clinical picture of serum disease with fever and arthalgia develops with the 4- th – 6 – th injection

         The symptoms of brain and spinal cord lesion appear (such as delirium, cross – eye, CN’s lesion (bulbar syndrome, facial neuropathy), pelvic disorders)

         Polyneuritic syndrome appears in 2 – 6 days

The treatment of such patients includes Glucocorticoids.

II. Toxic polyneuropathy.

1.        Bacterial – toxic (dyphtheric polyneuropathy, botulinum polyneuropathy)

2.        Iatrogenic

3.        Exogenous (Pb, As, Hg, at POC poisoning)

TOXIC NEUROPATHIES

Toxins are usually ingested or inhaled and may cause damage to peripheral nerves by attacking neurons, resulting in nerve cell death; by damaging Schwann cells, producing demyelination; or by directly damaging axons, producing distal axonal degeneration. Ax-onal degeneration is by far the most common reaction and is usually insidious in onset following steady exposure to toxic substances. The lower limbs are affected before the upper limbs, and there is gradual development of sensory loss with a stocking type of hypalgesia. This is associated with loss of the ankle jerk. Muscle wasting and weakness develop later. Recovery is slow once toxic exposure ceases, because axonal regeneration is a slow process, and many patients show residual disabilities for months or years. Examination shows slowing of motor nerve conduction, and the CSF protein is normal. Many substances produce toxic neuropathies. The most common encountered in clinical practice include chloramphenicol,disulfiram, isoniazid, nitrofurantoin, and phenytoin. Industrial or environmental toxins include acrylamide monomer, arsenic, lead, thallium, carbondisulfide, JV-hexane, organophosphates, methylbromide, methyl-A^-butylketone, triorthocresyl phosphate, polychlori-nated biphenyls, and /3-amino-propionitrile.

Toxic neuropathies with segmental demyelina-tion or following neuronal death are rare. Demyeli-nating peripheral neuropathy has been described in buckthorn poisoning, and the neuropathy associated with mercury poisoning is believed to follow destruction of nerve cells in the dorsal root ganglia.

1. Dyphtheric polyneuropathy

Diphtheria   

Approximately 10 percent of patients develop signs of neuropathy during diphtheria epidemics. Nerve involvement is the result of the neurotropicproperties of the diphtheria toxin. There are three types of involvement:

1. Early involvement with paralysis of the palate and failure of accommodation occurring within a few days of the onset of the illness.

2.  Delayed mononeuropathy or polymononeuropathy in which palatal involvement is followed by paralysis of muscles in any part of the body. (This may occur in a series with recovery of function in one area followed by paralysis of a different muscle group.)

3.  A condition resembling Guillain-Barre syndrome.

Dyphtheric toxinum is fixed mainly in peripheral nerves and its nuclei, anterior roots, root nerves.

The clinical picture is developed on the background of upper respiratory ways diphtheria in 5 – 6 days. Sometimes diphtheria is diagnosed afterwards because of the peculiarities of polyneuritic syndrome development.

The peculiarities of clinical picture.

         At the beginning of the disease there are accommodation paralysis and other eye movements disorders with development of diplopia and strabismus

         Bulbar syndrome (IX – X CN’s are involved) with respiratory disorders and pneumonia.

         Heart – vascular disorders (bradycardia, myocarditis with arythmia, tachycardia)

         In a 1 month polyneuropathy of lower extremities is developed. Mainly it is sensory – motor form.

         Polyneuropathy of upper extremities could be developed in a month afterwards.

In treatment anti dyphtheric serum and Glucocorticoids are used.

2). Botulinum polyneuropathy

The main point of action of botulinum poison is the place of nervous – muscular synapse (as the poison doesn’t come through the haemato-encephalic barrier). In this case the mechanism of acetylcholine metabolism is destroyed. Thus in the base of polyneuritic syndrome at botulinum polyneuropathy is nervous – muscular deficiency.

The peculiarities of clinical picture.

         The symptoms of the disease appear in a few hours after the usage of spoiled food stuffs (canned goods, sassages)

         Vomiting, diarrhea, stomachache, skin dryness.

          Then midriasis, accommodation paralysis, diplopia, swallow and speech disorders, neck muscles weakness appear.

Diagnosis is put after the results of biological test on mice. Usually blood, vomiting stuffs are used in order to find out the type of the toxin.

In treatment specific serum is used. In case of non-adequate treatment the patients die in 50% of all cases.

3). Jatrogenic polyneuropathy.

This group of the diseases is developed after usage of medications of different groups (Cytostatics, Glucocorticoids, Izoniasidum)

In case of Izoniasidum polyneuropathy there is the deficiency of vitamin B6. That’s why phthisiatrician should prescribe vitamin B6 with Izoniasidum.

THE INFLAMMATORY NEUROPATHIES

The inflammatory neuropathies are a group of peripheral neuropathies of various etiologies, characterized by an inflammatory response involving the peripheral nerve. The most important inflammatory neuropathies are herpes zoster, diphtheric, infectious mononucleosis, human immunodeficiency virus (HIV) infection, acute  inflammatory  demyelinating  polyneuropathy (Guillain-Barre syndrome) and chronic inflammatory demyelinating polyneuropathy (CIDP).

Herpes Zoster (Shingles)

Definition

Herpes zoster is an acute, painful mononeuropathy associated with a vesicular eruption in the distribution of the affected nerve.

Etiology and Pathology

The infective agent is the varicella virus. Herpes zoster may represent an infection by recently acquired varicella virus in an individual who has a declining immunity to the virus or a recrudescence of activity by latent varicella virus in the presence of declining immunity.

The viral activity is predominantly located in the dorsal root ganglia or sensory ganglia of the cranial nerves. The ganglia are swollen and show areas of necrosis. There is a marked inflammatory response with necrosis of neurons. The ventral (motor) nerve root is occasionally involved, and inflammatory changes may spread to the spinal cord or brainstem. The vesicles in the skin contain herpes virus, and the surrounding area shows a polymorphonuclear infiltration due to secondary bacterial infection.

Clinical Features

Herpes zoster is a disease of adults and rarely affects children. There is an increased incidence in patients with altered immunity due to such conditions as malignancy, HIV infection, Hodgkin disease, and leukemia. The condition presents with fever followed by pain in the distribution of the involved nerve. Vesicles appear in the affected area within 24 h and are soon involved by secondary bacterial infection, which results in severe regional lymphodermatitis. The pain usually begins to subside after a few days but may persist for months (postherpetic neuralgia). The pustules heal, and crusts separate after about 3 weeks, leaving pigmented scars.

Herpes zoster is not confined to sensory symptoms. Motor weakness from ventral root involvement occurs in 5 to 10 percent of patients.

Complications

1. Involvement of the ophthalmic division of the fifth cranial nerve is frequently associated with corneal ulceration (Herpes zoster ophthalmicus)and

may result in severe damage to the cornea. This condition is occasionally followed by retinal and intracranial arteritis, producing additional visual loss and contralateral hemiparesis.

2.    Herpes zoster involvement of the geniculate ganglion produces a painful vesicular rash involving the pinna, external auditory meatus, and eardrum   followed   by   ipsilateral   facial   paralysis (Ramsay-Hunt syndrome).

3.    Sacral nerve involvement may be associated with loss of bladder and anal sphincter control.

4.    Herpes   zoster   encephalitis   is   probably more common than has been thought in the past. Careful neurological examination may reveal subtle signs of intention tremor or gait ataxia, which should be regarded as encephalitic in origin. However, it is not unusual to find a CSF pleocytosis in the early stages of herpes zoster mononeuropathy.

5.    Retrograde spread of the virus from the posterior root ganglion into the spinal cord occasionally produces an acute transverse myelitis. This may result in permanent cord damage with major neurological deficits. Herpes zoster myelitis usually occurs in immunocompromised individuals.

Differential Diagnosis

It is extremely difficult to diagnose herpes zoster before the characteristic vesicles appear. The pain may mimic many acutely painful conditions such as pleurisy, pericarditis, perforated peptic ulcer, appendicitis, renal colic, and herniated lumbar disc.

Diagnostic Procedures

1.    The white blood cell count is often elevated in the presence of secondary infection.

2.    Lumbar puncture will reveal a lymphocytic pleocytosis in many cases. If there is clinical evidence of CNS involvement, the CSF abnormality is indicative of encephalitis.

Treatment

1.    Herpes zoster is a systemic illness and patients should be treated with bed rest.

2.    Adequate   analgesia  is   mandatory.   Narcotics are often required in the early stages.

3.    Acyclovir 800 mg q4h orally or famciclovir 500 mg q8h is very effective in aborting an attack of herpes zoster.

4.    A course of corticosteroids such as prednisone 80 mg daily for 7 days will produce rapid relief from pain in many cases. However, these antiviral agents must be given within 48 h of onset of herpes zoster.

5.    Local application of calamine lotion or calodion, or application of a cream containing acyclovir or capsaicin, and avoidance of contact with clothing or bedclothes help to relieve pain and itching.

6.    Herpes   zoster   encephalitis   should   be treated with acyclovir or famciclovir intravenously.

7.    The    rare     occurrence    of    transverse myelitis or vasculitis may respond to intravenous acyclovir or famciclovir.

8.    Postherpetic neuralgia is a most debilitating condition, particularly in elderly patients. The condition may persist for many months, but the patient should be informed that it will eventually subside. There is no single effective remedy, but some patients obtain relief from topical capsaicincream or subcutaneous interferon injections.  Carbamazepine (Tegretol), gabapentin 300 mg q8h increasing to 3600 mg per day if necessary for pain control, or phenytoin (Dilantin) may also be effective. These drugs may be used in combination if necessary. Alternatives include amitriptyline (Elavil) beginning  10 mg q.h.s. and slowly   increasing   by   10-mg   increments   up   to 175-200 mg if necessary. A rapid increase in dosage leads to unacceptable dry mouth, resulting in rejection of the medication, particularly by elderly patients.

Infectious Mononucleosis

This condition is occasionally complicated by mononeuropathy or by peripheral neuropathy resembling acute inflammatory demyelinatingpolyneuropathy (Guillain-Barre syndrome) (see below).

Sarcoid Neuropathy

Sarcoidosis is a recognized cause of symmetrical peripheral neuropathy, often associated with cranial nerve involvement, erythema nodosa,lymphadenopathy, relapsing uveitis, parotitis, and hypercalcemia. The peripheral neuropathy may be predominantly motor sensory or mixed in type. Other signs of sarcoidosis may be present.

Diagnostic Procedures

1.  Biopsy of the involved site or sural nerve biopsy.

2.  Elevated serum angiotensin converting enzyme, abnormal serum immunoglobulin, and elevated alkaline phosphatase are often but not always present.

3.  Hypopituitarism, diabetes insipidus, and hypothalamic involvement are occasional complications.

4.  The cerebrospinal fluid is often abnormal with a mononuyclear pleocytosis, elevated protein content, presence of oligoclonal bands, and reduced glucose content.

Treatment Corticosteroid therapy is usually effective. Relapse is not unusual and repeated courses of steroids may be necessary.

4. Exogenous polyneuropathy.

a).  Lead polyneuropathy

Peculiarities.

         Contact with lead (in those persons who are working in lead enterprises, printing ones and so on). When the concentration of lead in blood is more then 80 mg per 100 ml of blood.

         Lead asthenia

         Intestinal colic

         Dark blue bordering on the gum

         The symptoms of toxic hepatitis

         Usually the peripheral nerves of upper extremities are involved (such as radial one)

         In lower extremities usually peroneal nerve suffers

         Sensory disorders are not well expressed and in most cases they are subjective ones (muscle, bone and joints’ pain)

In treatment complexions are used: Calcii tetacini 10% i/v, Unitiol; general treatment.

b). Arsenic polyneuropathy.

It is developed at acute or chronic poisoning. Acute one is characterized by enteritis associated with polyneuritis.

Peculiarities.

         Sensory disorders prevail (pain, parasthesia, cramps, feet and hands hyperesthesia, poliesthesia)

         Atrophy of interostal spaces on hands and feet

         Sensetive ataxia is often developed because of the deep sensation disturbances

         CN’s lesion (VIII, II, sometimes III, VII)

         Trophic disorders: feet and hands edema, white strips on nails

In treatment unitiolum and desintoxication are used.

c). Hydrargyrum polyneuropathy.

         Enteral disorders

         Fever

         General cerebral symptoms

         Polyneuritic syndrome

         Cerebellum

         And extrapyramidal disturbances

In treatment complexions and general therapy are used.

5. Polyneuropathy at POS.

At this type of polyneuropathy there is the blockage of cholinestherase. As a result the activity of acetylcholine increases.

An acute poisoning is associated with general somatic clinical picture. And in 2 – 3 weeks in 20 % of all patients polyneuropathy is developed.

Clinical picture.

         Diffuse fasciculations

         Stomachache

         Bradycardia with hypotonia

         Autonomic horror

         Respiratory disorders

         Lung edema

         Loss of consciousness

         Hyperkinesis

         Seizures

         Coma, death

The severity of polyneuropathy depends on the stage of intoxication in acute period, on hepatitis and nephritis clinical picture.

In polyneuropathic syndrome motor disorders are dominant. Sometimes neurological symptoms are associated with sphincter and cerebellar symptoms. Recovery is very slow. There is high percentage of disability.

Emergency: reactivators of cholinestherase: Dipiroxime, Izonitrozide, Atropinum i/v

III. Dismetabolic polyneuropathies.

1. Alcoholic polyneuropathy.

It is developed in 32 – 97 % of all patients with chronic alcoholism. Among all types of polyneuropathy alcoholic one takes 36 – 40 %. In pathogenesis of this disease an important role belongs to the vitamin B deficiency because of the liver and gastro – intestinal tract disorders.

Besides alcohol directly influences on neuronal metabolism. Thus alcoholic polyneuropathy is demonstrational alimentary- toxic polyneuropathy.

According to the course of the disease there are acute and chronic form of the disease. At acute one paresis is developed rapidly, while at chronic one clinical picture manifests gradually.

The peculiarities of clinical picture.

         At first lower, then upper extremities suffer

         There is well expressed lesion of peroneal nerve: feet extensors weakness, specific gait disorders

         At the beginning stretch reflexes increase, then decrease and sometimes even disappear.

         Ankle reflexes disappear at the early beginning of the disease.

         Sensory disturbances at first are irritating: pain, parasthesia, hyperesthesia and hyperpathy dominate.

         There is sensitive ataxia because of the deep sensation disturbances.

         Polyneuropathy is associated with amnestic Corsakov syndrome

         There are internal organs’ changes – chronic hepatitis, cirrhosis and so on.   

In treatment high doses of vitamin B, desintoxication, liver protectors, Berlition, Dialipon are used.

2. Diabetic polyneuropathy.

This type of polyneuropathy is developed in 65 – 70 % of all patients with diabetes.

The peculiarities of clinical picture.

1.    Sensory disturbances on lower and upper extremities such as parasthesia, hyperesthesia, hypesthesia and pain are dominant.

2.    There are autonomic disorders: dryness of skin, an- or hyperhydrosis, trophic ulcers and so on.

3.    Knee and ankle reflexes are lost at the beginning of the disease.

4.    Severe paresis is very rare in this case.

5.    There is visceral form of diabetic polyneuropathy with progressive autonomic insufficiency.

6.    It is one of the most light and slowly progressive polyneuropathy.

IV. Paraneoplastic polyneuropathies.

The disease is developed on the background of malignant tumors or 2 – 3 years before the final diagnosis.

Sometimes polyneuropathy appears before or just after surgery.

V. Hereditary polyneuropathies.

1. Charkot – Marie – Tooth neural amyotrophy

2. Intersticial polyneuritis in children

3.    Hereditary sensory radiculopathy

4.    Lipidosis polyneuropathies

Hereditary Motor and Sensory Neuropathies (HMSN)

HMSN Type I or CMT I: Peroneal Muscular Atrophy—Charcot-Marie-Tooth Disease

Definition This is a genetically determined, chronically symmetrical polyneuropathy.

Etiology and Pathology

The condition is usually inherited as an autosomal dominant trait with mi-croduplication of a segment of chromosome 17 or trisomy of a large region of chromosome 17. In either case, there is an abnormality of the peripheral myelin protein 22 gene (PMP-22 gene) and an abnormal expression of PMP-22 protein, producing abnormal function of the Schwann cell, affecting myelination of nerves with hypophosphorylation ofneurofilament proteins and axons. There are hypertrophic changes in the myelin with onion bulb formation. Rare autosomal recessive or X-linked recessive forms of the disease have been recognized.

Clinical Features

The disease has a prevalence of 1 per 2500 and usually presents in the first or second decade, with slowly progressive weakness of distal muscles in the lower extremities, leading to foot drop. Weakness and wasting of the small muscles of the hands develop later and spread to the forearm muscles. Sensory impairment to all modalities occurs in the feet and hands. Tendon reflexes are usually absent. The wasting of muscles in the lower extremities may eventually spread to the lower thighs, giving an inverted bottle appearance. However, this appearance is not universally present and calf muscle hypertrophy has been reported in a few cases.²⁹ Peripheral nerves are palpable in about one-third of cases. All show high arched feet, which may be the only manifestation of the disease in family members who have a forme fruste of the disease. The life span is normal; but there is a wide range in severity of clinical signs.³⁰ Consequently, a significant number of patients experience impaired respiratory function in the advanced stages of the disease.³¹ This carries implications for the management of anesthesia and postoperative monitoring. Tremor, parkinsonism, and dystonia have been reported in some cases. Thus, there is a wide range of signs and symptoms in HMSN type I, but only a minority of patients who have this disease will eventually require wheelchair assistance.

The peculiarities of clinical picture.

1.    It is inherited according to the dominant or recessive type.

2.    It manifests in middle age and slowly progresses

3.    Dystal amyotrophy and lower extremities weakness prevail

4.    The lower extremities look like turned over its head bottle

5.    The foot looks like Friedreich one

Diagnostic Procedures

1.    Nerve conduction velocities are decreased below 40 m/s with velocities uniform between nerves or nerve segments. Compound action potentials are low in amplitude and dispersed.

2.    The cerebrospinal fluid (CSF) is normal.

3.    Respiratory function tests are indicated in patients who are in the advanced stages of the disease and who are being screened for possible surgical procedures.

4.    Electrocardiography   (ECG)   and   cardiac evaluation is advised under similar circumstances.

Mitral valve prolapse occurs in at least 50 percent of patients.

5.    Sural nerve biopsy indicates a hypertrophic neuropathy with frequent onion bulb formation in many cases.

6.    Somatosensory evoked potentials and visual evoked potentials are abnormal in some patients, indicating central nervous  system (CNS) involvement.

Treatment

There is no specific treatment for HMSN type I. Patients with foot drop may benefit from ankle-foot orthoses. Orthopedic procedures may be considered in some cases, or tendon transplant in either feet or hands may improve function in those who have severe weakness affecting the extremities.

HMSN Type II, Axonal Type, of Charcot-Marie-Tooth Disease

This condition is usually inherited as an autosomal dominant trait, but it can be inherited as an X-linked dominant or X-linked recessive trait.Linkage to markers on chromosomes Ip has been described.³⁷ Clinically, onset is later and progression slower than HMSN type I. There is less involvement of upper extremities. A variant HMSN HE has been described, with diaphragmatic and vocal cord paralysis. Sural nerve biopsies show axonal loss with mild demyelination, compatible with wallerian degeneration. Nerve conduction velocities are normal or slightly slowed, but there is marked diminution of amplitude. Electromyography shows denervation. The CSF is normal.

Treatment There is no effective treatment for this condition. The measures as described for HMSN type I apply.

HMSN Type III (Dejerine-Sottas)

This autoso mal recessive neuropathy is characterized by severe demyelination and early onset. Walking and other milestones are delayed, and the patient is wheelchair dependent in the late teens. There is severe atrophy of distal muscles and a marked sensory ataxia. High arched feet and kyphoscoliosis are prominent. Nerves show thin myelin sheaths with onion bulb formation around small myelinated fibers. Motor nerve conduction velocities are very slow or unrecordable. Sensory action potentials are absent. The CSF protein is markedly elevated.

Treatment Treatment is as described for HMSN type I.                                                             

HMSN   Type   IV,   Refsum   Disease   (Heredopathia Atactica Polyneuritiformis) 

A rare disorder of inheritance, this autosomal recessive trait     i results from a deficiency of phytanic acid oxidase. The disease presents in the first or third decades with  a slowly progressive polyneuropathy associated with cerebellar ataxia, ichthyosis, cataracts, pigmentary retinopathy, pes cavus, hammer toes, and cardiac conduction defects. Examination shows anosmia, nystagmus, hearing loss, ataxia, and palpablehypertrophic changes in peripheral nerves. The CSF protein is elevated. Motor and sensory nerve conduction velocities are very slow. There is elevation of serum phytanicacid.

Treatment A diet low in phytanic acid is required.

HMSN Type V This is an autosomal sensory afferent motor axonal polyneuropathy with steady pro-gression and spastic paraparesis.

HMSN Type VI    As for type I, with optic atrophy.

HMSN Type VII As for type II, with pigmentary retinopathy and normal phytanic acid metabolism.

HMSN Type VIII Peripheral neuropathy and spinal cerebellar degeneration.

The syndrome of the hereditary motor and sen-sory neuropathies is incomplete, with several recent additions to the list of these hereditary diseases. All are rare.

Hereditary Sensory Neuropathies

Type I

This autosomal dominant sensory neuropathy is associated with chronic decrease in small myelinated and unmyelinated fibers. Symptoms begin in the third decade with progressive loss of sensation in the distal lower limbs, slowly extending proxi-mally. Upper extremity involvement is late and mild. There may be painless ulceration of the feet, lightning pains, and mild distal muscle wasting.

Type II (Morvan Disease)

The condition is similar to type I and is inherited as an autosomal recessive trait. There is marked decrease in myelinated axons and a moderate loss of unmyelinated fibers. The condition begins in infancy or childhood, with loss of all sensation distally in the limbs. Severe dystrophicchanges and anhidrosis occur in the limbs and tonic pupils, neuropathic joints, and unrecognized fractures can develop in some cases.

Type III (Reilly-Day Syndrome)

This condition is inherited as an autosomal recessive trait with symptoms presenting in infancy. There is episodic cyanosis, vomiting, fever, decreased lacrimation, hy-perhidrosis, episodic hypotension, and fluctuating temperature. Examination shows a dissociated sensory impairment with loss of temperature and pain sensation. This results in corneal ulceration, painless skin ulcerations or infection, and Charcot joints. There is generalized areflexia. The prognosis was poor, but use of antibiotics and control of infection has increased survival. There are reports of improvement in adult survivors.

Type IV (Hereditary Anhydrotic Sensory Neuropathy)

This rare autosomal recessive neuropathy is characterized by mental retardation, insensitivity to pain and temperature, anhidrosis, and episodicpyrexia.

Type V  

As for type IV, with normal mentation.

Other hereditary sensory neuropathies beginning in childhood or adolescence, associated with spastic paraplegia, or with prominent loss of small myelinated fibers, or associated with hereditary ataxias such as Friedrich's ataxia, have been described.

Familial Amyloid Neuropathy

Amyloidosis may be familial, primary, or secondary. Hereditary (familial) amyloidosis is inherited as an

autosomal dominant trait and has been classified into four types based on clinical features and geographical location.⁴⁹ Types I and II are characterized by mutations in the transthyretin gene, resulting in an abnormality in the constituent amyloid fiber or protein transthyretin.⁵⁰ Type III is associated with a variant form of apolipoprotein A-l and type IV with an abnormality in gelsolin, an actin-binding protein.

Clinical Features

Type I develops in the third or fourth decade with a progressive, painful sensorimotor neuropathy, affecting lower limbs more than upper limbs, and often associated with carpal tunnel syndrome, autonomic neuropathy, and ulceration of the feet. The type II familial amyloidosis develops in the fourth or fifth decade, with peripheral neuropathy affecting the upper limbs more than the lower limbs, and carpal tunnel syndrome. Type III is characterized by severe sensorimotor neuropathy affecting upper and lower limbs, with severe amyloidosis. Type IV familial amyloidosispresents with cranial nerve palsies and a lattice dystrophy of the cornea.

Diagnostic Procedures

1.  Sural nerve biopsy will show deposits of amyloid in the perineurium and endoneurium.

2.  Amyloid has an apple green birefringence after staining with Congo red when viewed microscopically under crossed polarized light.

3.  Amyloid can be detected in blood using radioimmunoassay and enzyme-linked immunosorbent assay techniques.

Treatment Liver transplantation has produced regression of amyloid deposits in several patients.

HE PERIPHERAL NEUROPATHIES

NEUROPATHIES OF THE CRANIAL NERVES

The Third, Fourth, and Sixth Cranial Nerves

Lesions of the third, fourth, and sixth cranial nerves are conveniently considered together because of the proximity of origin of these nerves in thebrainstem and the close relationship in their course through the cranial cavity to supply the extraocular muscles and intrinsic muscles of the eye. Involvement of the third, fourth, and sixth nerve nuclei or the proximal portion of these nerves in the brainstem is usually associated with other signs of brainstem dysfunction. One example is Mobius syndrome, an hereditary condition in which there is dysplasia of the nuclei of the oculomotor and seventh cranial nerves. Other causes of oculomotor palsies include brainstem trauma, encephalitis, syphilis, Wernicke encephalopathy, tumor, infarction, multiple sclerosis, and the spinocerebellar degenerations. Involvement of the oculomotor nerves in the posterior fossa is common with increased intracranial pressure (ICP) associated with herniation of the uncus of the temporal lobe over the free edge of the tentorium. This produces pressure on the third nerve as it crosses the tentorial edge resulting in unilateral dilatation of the pupil, followed by paralysis of the extraocular movements supplied by the third nerve. Other causes of third, fourth, and sixth nerve involvement in the posterior fossa include meningitis, syphilis, polyneuritis, diabetes mellitus, and extra axial tumors. Diabetic mononeuropathy involving the third nerve usually produces paralysis of the extraocular movements supplied by the third nerve with sparing of the pupil. This condition is believed to be due to infarction of the outer layer of the third nerve, which contains the motor fibers supplying extraocular muscles, while the inner core of fibers supplying the constriction of the pupil is preserved.

Isolated sixth nerve palsies are often due to diabetes mellitus or pontine infarction and usually resolve within 3 months. Chronic isolated sixth nerve palsies lasting 6 months or more have been described following lumbar puncture, trauma, raised ICP, and arachnoiditis. Other causes include syphilis, sarcoidosis, and metastatic tumor. Primary tumors include pontine glioma, chordoma, chondrosarcoma, and meningioma in theposterior fossa. The sixth nerve may be compressed by an intracavernous aneurysm, pituitary tumor, or nasopharyngeal carcinoma and isoccasionally involved in temporal arteritis.The third, fourth, and sixth nerves are vulnerable to pressure in the lateral wall of the cavernous sinus.The more common causes include aneurysms of the internal carotid artery and pituitary or parapitu-itary tumors. Compression of the third nerve has been reported from a persistent trigeminal artery and is occasionally seen as a reversible condition in ophthalmoplegic migraine.

The nerves may be involved at the level of the superior orbital fissure, which may be narrowed by inflammation, by Paget disease, or by growth of a nearby tumor, usually a meningioma. Orbital involvement of the third, fourth, and sixth nerves may follow trauma with fracture of the orbital bones. Other causes include orbital cellulitis, abscess, and temporal arteritis. Transient paralysis of the sixth nerve is sometimes seen in infants and children and is a benign condition of unknown etiology. A similar condition is sometimes induced by the use of prochlorperazine (Compazine) in children. Cyclic oculomotor paralysis is a rare condition encountered in children in which there is paralysis of extraocularmovements supplied by the third nerve associated with ptosis lasting for a period varying from several seconds to several minutes.

The Fifth Cranial Nerve (Trigeminal Nerve)

Trigeminal Neuralgia (Tic Douloureux)

Definition Trigeminal neuralgia is a condition characterized by sudden, severe, lancinating pain occurring in the distribution of the trigeminalnerve.

Etiology and Pathology

 Trigeminal neuralgia is probably syndromic and may be due to:

1. Degenerative changes in the trigeminal (gasserian) ganglion, producing paroxysmal discharge of neurons.

2.  Pressure on the trigeminal nerve root by an aberrant or arteriosclerotic vessel, by a tumor, particularly a meningioma located in the posterior fossa³ or by displacement of the brainstem by a contralateral tumor with compression of the trigeminal nerve against a bony structure.

3.  Increased angulation of the nerve root over the petrous bone caused by demineralization at the base of the skull in the elderly with upward movement of the petrous pyramid.

4.  Demyelination of the most proximal portion of the trigeminal nerve root or demyelination affecting the spinal tract in the brainstem in patients with multiple sclerosis. (A similar condition occurs in patients with tabes dorsalis).

5.  Familial trigeminal neuropathy has been described in  the  setting  of hereditary peripheral  neuropathies, especially HMSN type I, Charcot-Marie-Tooth disease.⁴

6.  Paroxysmal discharges of the neurons of the spinal nucleus of the trigeminal nerve. (This concept suggests that trigeminal neuralgia is a form of seizure activity occurring at the brainstem level secondary to degenerative or vascular changes affecting the neurons of the spinal nucleus.)

Clinical Features

The disease predominantly occurs in middle-aged and elderly patients. The occurrence of trigeminal neuralgia in the younger individual suggests the diagnosis of multiple sclerosis, tumor, or aneurysm. The disorder is somewhat more common in women. The condition is characterized by paroxysms of pain occurring in the maxillary or mandibular division of the trigeminal nerve with later spread from one division to involve the other division. Involvement of the ophthalmic division is rare and occurs in less than 5 percent of cases. Trigeminal neuralgia may involve both sides of the face, but paroxysms never occur simultaneously on the two sides. In established cases the pain may be provoked by touching the face, chewing, talking, drinking, brushing the teeth, shaving, or the movement of air across the affected side of the face. Patients recognize certain "trigger points," which will produce a typical paroxysm of pain if stimulated. Established cases exhibit sudden, severe paroxysms of pain with cessation of speech and contortion of the face often accompanied by a cry of distress. The attacks are short-lived with long periods of freedom in the early stages, but the paroxysms gradually become longer and closer together in time. This leads to constant dread of the next attack with depression, suicidal thoughts, and weight loss.

The neurological examination is normal.

The peculiarities of clinical picture.

         Pain paroxysms that are caused by the movements of mimic muscles, talking, eating, face washing. They can continue up to 1 – 2 min.

         Pain tics – facial hyperkinesis

         Trigger points – touching of these points can cause severe pain



Diagnostic Procedures

1.  The patient should have radiographs or a CT scan of the base of the skull with visualization of the foramen ovale. Enlargement of the foramenovale suggests the possibility of intracranial or extracranial tumor.

2.  If there is a suspicion of the presence of tumor or aneurysm, a high-resolution computed tomography (CT) scan of the base of the skull and posterior fossa should be performed.

Treatment

-          anti seizures medications (Finlepsin)

-          Analgesics

-          Non steroid drugs

-          Acupuncture

Medical treatment using earbamazepine (Tegretol) is successful in most cases. It should be given in small doses initially and gradually increased to effect, beginning with 100 mg at night and increasing by 100 mg every 3 days until the patient is receiving 800 to 1600 mg in three divided doses daily. The slow introduction of earbamazepine will permit the establishment of therapeutic levels of the drug, without the development of unpleasant adverse effects. See Chapter 4 for further information on the use of earbamazepine.

Phenytoin (Dilantin) is less effective than earbamazepine in the control of trigeminal neuralgia but should be used to treat patients who are unable to tolerate earbamazepine. Phenytoin is also useful as an adjunct when earbamazepine produces significant but incomplete control of pain. The dosage of phenytoin should be sufficient to produce therapeutic plasma concentrations of the drug.

Baclofen, benzodiazepines, gabapentin, or pi-mozide 4 to 12 mg daily are occasionally effective when earbamazepine and phenytoin fail to control trigeminal neuralgia.

A number of surgical procedures are currently advocated for the treatment of trigeminal neuralgia. These include alcohol injection of individual nerves or the trigeminal ganglion. This form of treatment relieves pain, but the patient must clearly understand that alcohol injection produces anesthesia, and pain loss is associated with loss of sensation in the affected area of the face. Nerve regeneration often occurs after 6 months with return of the pain in some cases. Other surgical procedures include percutaneous radiofrequency or glycerol trigeminal ganglio-lysis andsuboccipital craniotomy with microvascular decompression of the trigeminal nerve, which has the advantage of relieving pain without producing anesthesia. When the latter is not feasible, partial sensory rhizotomy with sectioning of one-third to one-half of the cross-section area of the sensory root, 2 to 5 mm from the pons, produces complete relief from neuralgic pain in about 50 percent of cases.

Prognosis

The majority of cases of trigeminal neuralgia can be controlled medically with carba-mazepine but many patients have to continue taking the drug for a prolonged period. An attempt at withdrawal should be made when the patient has been pain free for 6 months. This is successful in some cases.

The Seventh Cranial Nerve Bell's Palsy

Definition Bell's palsy is the acute onset of an isolated facial paralysis of the peripheral type.

Etiology and Pathology

The etiology of Bell's palsy is unknown, but the disease is believed to be the result of a viral infection involving the geniculate ganglion. It is possible that some cases are due to activation of a latent herpes simplex infection.

Pathological changes consist of inflammation and edema of the facial nerve in the facial canal. This produces increasing pressure on the nerve with paralysis of function followed by wallerian degeneration of axons.

Clinical Features

Bell's palsy usually occurs in middle-aged and elderly individuals. There is frequently a history of exposure to cold temperatures or drafts preceding the onset of facial paralysis. Most patients give a history of pain or ache in the region of the stylomastoid foramen immediately behind the angle of the mandible some 24 to 48 h before the appearance of the facial paralysis. The paralysis is usually appreciated for the first time on awakening in the morning, and there is a steady progression to severe weakness or total loss of function involving one side of the face. The affected side of the face sags and the eye cannot be closed because of paralysis of the orbicularis occuli. Weakness of the cheek allows food to accumulate between the teeth and the side of the mouth. There is often excess watering of the eye because of inability to move secretions across the cornea to the lacrimal duct. When the edema on the facial nerve extends proximally with involvement of the chorda tympani, there may be loss of taste. Further proximal extension produces hyperacusis because of paralysis of the nerve to the stapedius, and involvement of thegeniculate ganglion results in loss of lacrimation and a dry eye. Complaints of numbness or sensory change over the face and the presence of nystagmus suggest involvement of both the trigeminal nerve and the vestibular division of the eighth nerve in some cases of Bell's palsy. The characteristics of seventh nerve paralysis due to lesions at particular sites and common etiologies are listed in Table 19-1.

Diagnostic Procedures

Some determination of prognosis can be obtained by observation of evoked responses on stimulating the facial nerve as it emerges from thestylomastoid foramen. The demonstration of a good evoked response on stimulating the facial nerve indicates a good prognosis. Complete loss of excitability on stimulation indicates a poorer prognosis.

Treatment

Treatment in acute period

1.    Dehydration (Euphillinum, Lasix, Dexamethasonum i/v)

2.    Anti-inflammatory therapy (Glucocorticoids)

3.    Non steroid anti-inflammatory drugs (Diclofenac, Movalis, Naclofen, Messulid)

4.    Fonoforesis with Hydrocortisonum

5.    Microcirculation improving (Actovegin, Solkoseril, Pentoxiphillin)

At recovery:

1.    Massage

2.    Electrophoresis with Proserinum, Nicotin acid

3.    Warming procedures

4.    Biostimulants (Plasmol, Aloe)

5.    Vitamins B, PP

6.    Acupuncture

The initial discomfort can be relieved with aspirin or aspirin and codeine compounds. The use of oral corticosteroids in the treatment of Bell's palsy is controversial. However, some studies indicate improvement with corticosteroids, which can be given in a single dose of methylpred-nisolone (Medrol) 80 mg initially with a gradual reduction of dosage over the 7-day period. Patients who are unable to close the eyelids should be treated with methylcellulose eyedrops q4h, and the eye should be protected by a patch until there is a return of eyelid function.

Prognosis

The majority of patients with Bell's palsy make a complete recovery over a period of 2 to 3 weeks. The remaining 15 percent show some loss of function, including persistent facial weakness, facial spasm, ectropion, and excess lacrimation sometimes called "crocodile tears" caused by regeneration and passage of axons destined for the salivary glands to the lacrimal gland. In the older age group, hyperacusis, and a very dense paralysis are associated with a poorer prognosis.

Table 19-1

Seventh nerve paralysis

Site	Characteristics	Etiology
Supranuclear lesions	Weakness of the contralateral, lower face	Lesion involving corticobulbar tract above pons
Nuclear or pontine lesion	Total facial paralysis on side of lesion Impaired salivary secretion Taste intact Impaired lacrimation same side Associated paralysis of sixth or fifth nerve on same side Eyes may be conjugately deviated toward side of lesion Possible internuclearophthalmoplegia Possible contralateralhemiparesis	Congenital: Mobius syndrome Infectious: encephalitis, rabies, meningitis Nutritional: Wernicke encephalopathy Neoplastic: pontine gliomaVascular: infarction, hemorrhage Degenerative: multiple sclerosis, syringobulbia, amyotrophic lateral sclerosis
Extracranial incerebellopontine angle	Total facial paralysis on side of lesion Hearing loss on side of lesion Episodic vertigo Corneal reflex depressed on side of lesion Impaired salivary secretion Impaired lacrimation on side of lesion	Inflammation: meningitis, tuberculosis, syphilis, fungiNeoplastic: acoustic neuroma, meningioma dermoid, chordoma, meningeal carcinomatosisVascular: aneurysm of basilar artery Degenerative: multiple sclerosis
Extracranial in facial canal		Traumatic: fractures involving petrous temporal bone
a. Between internal auditorymeatus and geniculateganglion	Total facial paralysis same side Hearing loss same side Impaired lacrimation same side Impaired salivary secretion Taste lost anterior two-thirds tongue same side	Infectious: otitis media, mastoiditis, Bell's palsy (see below), herpes zoster of geniculate ganglion (Ramsey-Hunt syndrome) (see Chap. 19-27),sarcoidosis, Guillain-Barre syndrome (bilateral)
b. Between geniculateganglion and origin of nerve to stapedius	Total facial paralysis same side Impaired salivary secretion Taste lost anterior two-thirds tongue same side Hyperacusis	Metabolic: diabetes mellitus Neoplastic: cholesteatoma, epidermoid temporal bone tumors, parotid gland tumors, leukemic deposits in facial canal
c. Between origin of nerve tostapedius and origin of chorda tympani	Total facial paralysis same side Impaired salivary secretion Taste lost anterior two-thirds tongue same side
d. Distal to origin of chorda tympani	Total facial paralysis same side only

Herpes Zoster of the Geniculate Ganglion — Ramsay Hunt Syndrome

Geniculate Neuralgia

Definition Geniculate neuralgia is characterized by episodes of severe lancinating pain occurring in the region of the pinna and external auditory canal.

Etiology and Pathology

The etiology of this condition is unknown and is believed to be due to a neuralgia affecting the nervus intermedius. The bipolar neurons of the nervus intermedius are located in the geniculate ganglion and the afferent axons enter the spinal tract of the trigeminal nerve. The peripheral fibers are distributed to the external auditory canal and the pinna. There may also be some distribution to deeper structures of the face and hard palate.

Clinical Features

Patients experience spasmodic attacks of severe pain in the region of the pinna and external auditory canal. The pain is occasionally felt in the throat, deep in the face, and in the orbit.

Treatment Same as for trigeminal neuralgia. Surgical excision of the geniculate ganglion has been performed in refractory cases.

Facial Myokymia  

Hemifacial Spasm

Definition Hemifacial spasm is an irregular contraction of the muscles supplied by the facial nerve on one side.

Etiology and Pathology

Hemifacial spasm is due to an irritative lesion of the facial nerve and is comparable to trigeminal neuralgia in many ways. The most common cause is believed to be compression of the facial nerve as it emerges from the brainstem by an aberrant or arteriosclerotic vessel. Other causes include multiple sclerosis, an aneurysm of the basilar artery, and tumor or arachnoiditis in the cerebellopontine angle.

Clinical Features

Hemifacial spasm usually begins with irregular contractions affecting the orbicularis oculi and gradually spreads to involve all of the muscles supplied by the facial nerve on one side. The condition is always unilateral, and the movements are irregular, lasting for a few seconds to a few minutes with periods of freedom. Hemifacial spasm is increased by tension and emotional upset. Atypical facial pain may occur in some cases and suggests the presence of neoplasm. There are no other abnormalities on neurological examination.

Treatment

Carbamazepine (Tegretol) and phenytoin (Dilantin) are rarely successful in controlling hemifacial spasm. Surgical treatment is indicated whenhemifacial spasm becomes unacceptable to the patient. This consists of exposure of the facial nerve in the posterior fossa with identification of the compressive lesion, usually a tortuous arteriosclerotic artery.

Loss of Taste

Loss of taste has been described in some cases of Bell's palsy and also occurs in other conditions. Ageusia or dysgeusia, loss or disorder of taste, has been described after an upper respiratory tract infection and is presumably due to a viral neuritis. Other causes include exposure to certain drugs including D-penicillamine, griseofulvin, phenylbutazone, oxyphedrine, and carbamazepine. Loss of taste causes considerable distress to patients and should always be differentiated from loss of smell because most patients confuse these two senses. There is no specific treatment for loss of taste, although the use of oral zinc preparations has been suggested.

The Eighth Cranial Nerve

The majority of eighth nerve neuropathies are due to the toxic effect of drugs. A number of antibiotics, particularly the aminoglycosides, are reported to cause eighth nerve degeneration. Streptomycin and gentam-icin affect the vestibular division of the nerve, while neomycin, vancomycin, streptomycin, and kanamycin affect the auditory division of the nerve. Most cases follow parenteral administration of the antibiotic, but toxic neuropathy has been reported following topical application of creams containing kanamycin.

There is a rare, familial degenerative neuropathy affecting the cochlear division of the eighth nerve, which is characterized by progressive deafness. This may be associated with myoclonus and sensory peripheral neuropathy in some cases.

Vertigo

Definition An illusion of self-motion caused by dysfunction of the vestibular system and its connections.

Etiology and Pathology

In benign positional vertigo, free-floating particles (otoliths) or clumps of otoliths (canaliths) in the endolymphatic compartment of the posterior horizontal or superior semicircular canals displace the cupula and excite ampullary nerves producing benign positional vertigo. Other disorders of vestibular function, such as vestibular neuritis or Meniere's disease, can affect the vestibular system and are associated with intense vertigo. An acoustic neuroma or aberrant artery pressing on the vestibular nerve are recognized causes of vertigo. Migrane or vertebrobasilarinsufficiency involving the vestibular nuclei and the brainstem produce recurrent vertigo. Pontine infarction, cerebellar infarction or cerebellarhemorrage are often accompanied by acute vertigo and profound ataxia.

Clinical Features

Benign positional vertigo consists of brief episodes of vertigo on changing the positon of the head. Attacks of vertigo are also brief invertebrobasilar insufficiency when they are accompanied by signs of brainstem dysfunction. However, vertigo is prolonged in brainstem orcerebellar infarction or cerebellar hemorrage.

Treatment Treatment should be directed at the underlying cause. Antiveitiginous drugs are of limited value.

Disabling Positional Vertigo

Etiology and Pathology

This condition results from vascular compression of the vestibular division of the eighth nerve.

Clinical Features

There is a constant sensation of vertigo, often associated with nausea, which increases in intensity over time. Symptoms are exacerbated by activity and relieved by bed rest; there is little relief from sedation. The patient has a sensation of constant motion and drifts to one side when walking. There is a progressive sensorineural hearing loss.

Treatment The response to microvascular decompression of the eighth nerve is excellent in most cases.

The Ninth Cranial Nerve Glossopharyngeal Neuralgia

Definition Glossopharyngeal neuralgia is the occurrence of spasms of pain in the sensory distribution of the ninth and tenth cranial nerves.

Etiology and Pathology

The cause is unknown but is presumed to be pressure on or entrapment of the ninth and tenth cranial nerves. Glossopharyngeal neuralgia has occurred following acute infection of the pharynx but has also been related to compression at many sites, including the cerebellopontine angle, jugular foramen, base of the skull, pharynx, and tonsils.

Clinical Features

The patient experiences spasms of pain in the pharynx, often radiating into the ear. The attacks may be precipitated by swallowing, coughing, chewing, talking, sneezing, turning the head to one side, or touching the tragus of the ear. The attacks are usually brief but may last for several minutes in severe cases. Remissions are common. The neurological examination is normal.

Attacks are occasionally associated with bradycardia, cardiac arrhythmias, hypertension, and syncope due to associated vagal stimulation.Hypersecretion of the parotid gland has been reported.

Diagnostic Procedures

A diligent search should be made for a compressive lesion in the area of the cerebellopontine angle or at the base of the skull using magnetic resonance imaging (MRI) or CT scanning, which provides clear views of the jugular foramen.

Treatment

Most cases respond to carba-mazepine (Tegretol) as described under trigeminal neuralgia. Intracranial sectioning of the glossopharyngealnerve has been performed in intractable cases. This procedure entails a section of the upper two rootlets of the vagus nerve and may be associated with postoperative hypotension and cardiac arrhythmias.

The Tenth Cranial Nerve

Superior Laryngeal Neuralgia

This rare condition is associated with episodic lancinating pain radiating over the side of the neck. The disorder is believed to be the result of entrapment of the superior laryngeal nerve as it pierces the hyothyroid membrane. Patients experience pain in the anteromedial aspect of the neck radiating up behind the angle of the mandible on to the face extending as high as the zygoma.

The diagnosis can be established by injection of a local anesthetic into the superior laryngeal nerve as it pierces the hyothyroid membrane. This procedure will produce temporary relief. Most patients respond to carbamazepine (Tegretol). Refractory cases require sectioning of the superiorlaryngeal nerve at the level of the hyothyroid membrane.

The Eleventh Cranial Nerve

The 11-th cranial nerve (accessory nerve) is subject to injury by trauma or surgical procedures or by compression due to tumors or enlarged lymph nodes in the posterior triangle of the neck. The most common cause of injury is lymph node biopsy with accidental damage to the nerve. Involvement of the accessory nerve produces paralysis and wasting of the trapezius with inability to elevate the arm above the horizontal plane without external rotation. There may be pain in the neck and shoulder.

Patients may require analgesics and the use of an arm sling to relieve shoulder pain. Compression may be relieved by surgical procedures.

The Twelfth Cranial Nerve

The hypoglossal nerve is occasionally injured in surgical procedures of the neck. This produces hemiatrophy of the tongue with deviation of the tongue toward the side of the lesion on tongue protrusion.

THE CERVICAL PLEXUS

Anatomy

The cervical plexus is formed by looped connections between the anterior primary rami of CI, C2, C3, C4, and C5 on the anterior aspect of thelevator scapuli and scalenus medius muscles. Branches from C2 supply the sternocleidomastoid, while C3 and C4 supply the levator scapuli. The phrenic nerve is derived fromC3, C4, and C5 and supplies the diaphragm. The most important sensory branch is the greater occipital nerve, which arises from C2. The lesser occipital nerve arises from C2, and the greater auricular nerves arise from C2 and C3. All supply the posterior aspect of the scalp. The transverse cervical and supraclavicular nerves (C2, C3, and C4) supply the neck and the anterior portion of the chest wall down to the level of the T2 dermatome.

Occipital Neuralgia

Definition Occipital neuralgia is characterized by pain occurring in the cutaneous distribution of the greater occipital nerve.

Etiology and Pathology

The greater occipital nerve may be compressed in the neck by cervical spondylosis. It is occasionally injured during hyper-extension-fiexion injuries of the neck, which result in contusion of the nerve root as it passes through the intervertebral foramen.

Clinical Features

The patient complains of constant pain in the distribution of the greater occipital nerve over the posterior aspect of the scalp. The nerve is tender to palpation in its course over the occipital bone.

Diagnostic Procedures

Occipital neuralgia is frequently misdiagnosed as a "headache." The correct diagnosis can be established by relief of symptoms with local injection of the occipital nerve as it passes over the occipital bone.

Treatment

Early cases may respond to the application of ice packs or heat to the upper cervical area and the use of analgesics. Anti-inflammatory agents such as naproxen 500 mg bid may help. When the pain persists, the greater occipital nerve can be injected with local anesthesia and a corticosteroid such as 40 mg methylprednisolone (Medrol), which frequently produces permanent relief of symptoms.

Lesions of the Phrenic Nerve

The phrenic nerve arises from the anterior primary rami of C3, C4, and C5 and passes from the neck into the thorax to supply the diaphragm. The nerve may be damaged during traumatic injury to the cervical spine with contusion or tearing of the anterior primary rami of C3, C4, and C5. The nerve is occasionally involved in chronic meningitis, arachnoiditis, and cervical spondylosis. Compression by tumors of the neck, aneurysmsof the major vessels, or enlarged lymph nodes in the neck are additional causes of phrenic paralysis. Compression in the thorax by tumors and enlarged lymph nodes or an aneurysm of the aorta in the mediastinum can also cause phrenic nerve paralysis.

Mononeuropathy of the phrenic nerve has occasionally been reported following viral pneumonia, diphtheria, and exposure to such toxins as alcohol and lead. Unilateral paralysis of the diaphragm usually produces few symptoms and the condition is often diagnosed in the evaluation of patients with tumors or enlarged lymph nodes in the neck or thorax. The sensory fibers of the phrenic nerve can be stimulated by subphrenicconditions such as subphrenic abscess, cholecystitis, pancreatitis, and carcinoma of the pancreas, or by intrathoracic inflammatory conditions producing diaphragmatic pleurisy. This produces referred pain experienced over the shoulder on the same side as the lesion. Peripheral irritation may result in persistent singultus (hiccough). This condition responds to small doses of thorazine and medial cords, so named because of their relationship to the axillary artery. The trunks and cords give origin to a number of individual nerves supplying motor, sensory, andautonomic fibers to the upper thorax, shoulder, and upper limb (Fig. 19-2).

Birth Injuries to the Brachial Plexus

Etiology and Pathology

The brachial plexus may be damaged by excessive lateral traction on the head with the shoulders fixed during a difficult delivery or by excessive downward traction on the shoulders with the head fixed in a breech delivery. Both of these maneuvers produce an increase in the angle between the shoulder and the head and exert pressure on the roots of the brachial plexus.

Clinical Features

Three types of injury can occur. These include:

1.  Injury to the roots of C5 and C6 (Erb's paralysis).

2.  Injury to the roots of C8 and Tl (Klumpke paralysis).

3.  Combined upper  and  lower root  injury  (Erb-Duchenne-Klumpke paralysis).

ERB'S PARALYSIS Erb's paralysis is characterized by paralysis involving the deltoid (abduction); biceps, brachialis, and supinator (elbow flexion); and supraspinatus and infraspinatus (external rotation). The infant presents with absence of movement of the affected arm. The muscles fail to develop, and the arm and shoulder assume the typical posture of adduction, inward rotation, and pronation of the forearm and hand some months after birth. There are loss of the biceps and brachioradialis reflexes and a small area of sensory loss over the upper lateral aspect of the arm.

THE BRACHIAL PLEXUS

Anatomy The brachial plexus is formed by the anterior divisions of C5, C6, C7, C8, and Tl with some variable contribution from C4 and T2. The plexus consists of superior, middle, and inferior trunks, which divide and reunite to form lateral, posterior,

TREATMENT

1.  All joints of the arm should be moved through a full range of motion several times a day.

2.  The upper limb should be splinted in abduction with the elbow flexed to 90° and the forearm in midsupination.

3. Orthopedic surgical measures, including partial section of the pectoralis major and pronator teres should be considered in children who do not recover.

PROGNOSIS Recovery occurs in about 50 percent of cases.

KLUMPKE PARALYSIS

This type of paralysis is rare. Klumpke paralysis is characterized by paresis of the wrist, finger flexion, and small muscles of the hand. The fingers become extended, but the elbow is flexed. There is sensory impairment over the inner aspect of the forearm and hand. Horner syndrome develops when there is avulsion of the cervical nerve roots.

COMBINED PARALYSIS The combined upper (Erb) and lower (Klumpke) paralysis is extremely rare. It is characterized by paralysis of the shoulder and hand. The arm is wasted and cold, with dependent edema, and Horner syndrome is present.

Traumatic Injury to the Brachial Plexus

Injury to the brachial plexus is common in gunshot wounds, knife wounds, competitive sports, and automotive accidents, particularly motorcycle accidents. The plexus may be stretched and damaged by carrying heavy loads on the shoulders or by prolonged backward displacement of the shoulders during coma and occasionally during general anesthesia. Traumatic injury includes:

1.    A fall onto the apex of the shoulder and the side of the head. This injury abruptly increases the angle between the shoulder and the head and produces stretching or tearing of the nerve roots C5 and C6. This results in loss of abduction of the arm at the shoulder (deltoid, supraspinatus) and weakness of flexion at the elbow (biceps, brachialis). The biceps reflex is depressed.

2.    A blow to the angle between the shoulder and the neck. This may also produce weakness of shoulder movement because of damage to the upper cord of the brachial plexus. This is associated with inability to elevate the shoulder because of damage to  the accessory nerve and paralysis of the trapezius muscle.

3.    A fall on the front of the shoulder. This type of injury may cause sudden extension of the shoulder with compression of the lower cord of thebrachial plexus, resulting in pain and paresthesias on the medial aspect of the arm, forearm, and hand (C8,T1).

4.    A blow to the anterior axilla. This can injure the axillary nerve producing paralysis or paresis of the deltoid muscle. A similar injury damaging the musculocutaneous nerve will result in weakness of the biceps and brachialis muscles with loss of flexion at the elbow and a sensory loss on the lateral aspect of the arm and forearm to the wrist.

5.    When the force of an injury is directed upward into the axilla with the arm abducted, the entire contents of the axilla may be severely contused. The posterior cord of the brachial plexus is most vulnerable under these circumstances, resulting in loss of medial rotation of the arm (subscapularis), absence of abduction (deltoid), and paralysis of the triceps and dorsiflexors of the wrist.

6.    Dislocation of the shoulder may damage the contents of the axilla, particularly the circumflex nerve, with paralysis of abduction of the arm (deltoid).

7.    Gunshot wounds and knife wounds to the axilla or in the supraclavicular area often sever nerves and  produce  permanent  damage  to  the brachial plexus.

8.    Disability may be temporary if the plexus is contused, subjected to pressure by a hematoma, or stretched during coma or general anesthesia.

9.    Traction injuries to the brachial plexus may be associated with spinal nerve root avulsions. Prognosis is poor in many of these cases, unless treated by nerve transfer using donor nerves such as the medial pectoral, long thoracic, or subscapular nerves.

10.    Traction on the brachial plexus can occur in patients with flaccid hemiplegia following a stroke. This condition can be prevented by early physical therapy and the use of a sling when the patient is out of bed sitting in a chair or walking.

Brachial Neuritis

Definition Brachial neuritis is characterized by a sudden paralysis of muscles supplied through the brachial plexus and is often associated with painful dysesthesia of the arm.

Etiology and Pathology

The condition occurs in known viral infections (herpes zoster, Ep-stein-Barr virus), following injection of tetanus toxoid, in putative viral infections, and as an autoimmune disorder following a surgical procedure. Pathological changes are not well described. In herpes zoster infections the posterior root ganglia are involved.

Clinical Features

There is an acute or subacute onset of pain that extends into the shoulder, upper arm, or forearm, followed by weakness, muscle wasting, and sensory loss corresponding to the involved nerves, cords, trunks, or nerve roots. Upper brachial plexus (C5, C6), lower brachial plexus (C8, Tl) or whole plexus involvement can occur. The early symptoms are followed by the appearance of the typical rash within a few days in cases associated with herpes zoster. The phrenic and recurrent laryngeal nerves are occasionally involved.

Diagnostic Procedures

1.  Other causes of severe pain, such as an acute herniated cervical disc, should be excluded.

2.  Electromyography   will   demonstrate   multifocal denervation.

Treatment

1.  The condition is often very painful, requiring adequate doses of opioid analgesics for pain control.

2.  A short course of oral corticosteroids may reduce the duration of the pain.

3.  Cases of herpes zoster infection should be treated with acyclovir, famciclovir, or valacyclovir.

4.  Physical therapy should be initiated once the pain is controlled to prevent joint stiffness and adhesions.

Prognosis

Most patients recover completely. Postsurgical cases are often ascribed to stretching or compression of the brachial plexus during the surgical procedure. Many such cases are examples of brachial neuritis following surgery and are not traumatic. This has important medicolegalimplications.

Inherited Brachial Plexus Neuropathy

This unusual autosomal dominant neuropathy presents with recurrent episodes of paralysis of an upper limb. Symptoms occur within 7 days of a systemic infection, immunization, or childbirth. There does not appear to be a precipitating factor in many cases. The patient complains of pain in the shoulder and upper limb followed by weakness, then atrophy over a 2-week period. Recovery is satisfactory and often complete. Occasionally an attack can present as a lumbar plexopathy or seventh nerve palsy.

There are no neurological symptoms and no neurological signs, apart from the brachial plexus involvement. Some patients have hypertelorismand prominent epicanthic folds.

Electromyography demonstrates multifocal lesions in the brachial plexus with axonal degeneration. There is no evidence of generalized neuropathy.

Treatment Treatment includes control of pain and passive therapy to the affected shoulder until recovery occurs.

Inherited Tendency to Pressure Palsy

This rare autosomal dominant condition, also called tomaculous neuropathy, is associated with episodic pressure palsies often precipitated by relatively minor trauma. There is evidence of generalized neuropathy. Nerve conduction studies show slowed conduction and multifocalconduction block compatible with a demyelinating neuropathy. Pathological changes consist of segmental demyelination and hypertrophy. The genetic abnormality and inherited tendency to pressure palsy has been assigned to chromosome 17. Consequently, there is a relationship to HMSN type I, but the two conditions are quite distinct.

Treatment Physical therapy is recommended. There is no response to corticosteroids.

Neoplastic Involvement of the Brachial Plexus

Etiology and Pathology

Neoplastic involvement of the brachial plexus can occur due to direct extension of a bronchial carcinoma from the apex of the lung, direct extension of a breast carcinoma through the axilla, and with pressure from neoplastic lymph nodes.

Clinical Features

There is usually infiltration of or pressure on the lower trunk or medial cord of the brachial plexus. This produces severe pain in the shoulder and axilla and down the medial aspect of the upper limb with wasting of the small muscles of the hand and Horner syndrome (Pancoast syndrome).

Treatment

1.  The condition is very painful and the patient needs adequate doses of opioid analgesics (i.e. morphine sulphate 10 to 15 mg IM q4-6h) to reduce pain.

2.  An attempt should be made to control the neoplastic process by irradiation and chemotherapy.

Radiation  Damage to the  Brachial  Plexus

Radiation therapy to the axilla, for the treatment of carcinoma of the breast, may be followed by fibrosis and traction on the brachial plexus. In addition, the vasa nervorum may be damaged producing an ischemic neuropathy. The symptoms are similar to neoplastic involvement of thebrachial plexus, and the differential diagnosis can be very difficult.

Treatment

If metastatic recurrence can be ruled out, the patient can be treated with carba-mazepine (Tegretol) 200 mg ql2h, increasing slowly to 600 mg ql2h. Carbamazepine can be combined with phenytoin if this drug produces additional benefit.

Amitriptyline beginning 10 mg q.h.s. and increasing slowly to 200 mg daily if necessary decreases or abolishes pain in some cases. Gabapentin beginning 300 mg q8h and increasing by stages to as high as 3600 mg in 24 hours will control if not abolish pain and can be used in conjunction with analgesics. A fentanyl patch beginning 25 μg and changing every 3 days with an increase in dosage to 50 ^ig, 75 μg, or 100 ^g will relieve pain in many intractable situations. A subcutaneous morphine pump with adjustable delivery system can be installed in selected patients.

Surgical treatment to free the affected nerves from scar tissue may be necessary.

Differential Diagnosis The differential diagnosis includes wasting of the small muscles of the hand (Table 19-2).

Table 19-2

Differential diagnosis of wasting of small muscles of the hand

1.  Anterior horn cells (acute): poliomyelitis

2.  Anterior horn cells (chronic): amyotrophic lateral sclerosis, syringomyelia, peroneal muscular atrophy

3.  Nerve roots: arachnoiditis, pachymeningitis, herniated cervical disc, cervical spondylosis, extramedullary tumors

4.  Brachial plexus: trauma, brachial neuritis, metastatic infiltration, post radiation fibrosis

5.  Median nerve: trauma, carpal tunnel syndrome

6.  Ulnar nerve: trauma, tardy ulnar palsy, cubital tunnel syndrome

7.  Muscle: polymyositis, rheumatoid arthritis, distal form of dystrophy

Neuropathies of Individual Nerves of the Brachial Plexus

Lesions of the Long Thoracic Nerve

The long thoracic nerve arises from the anterior nerve roots of C5, C6, and C7 and supplies the serratus anterior muscle. The nerve may be damaged by trauma or by carrying heavy loads. It is occasionally involved by acute (probably viral) neuritis and may be severed during mastectomy. Injury to the nerve results in winging of the scapula. The scapula is medially rotated, and the acromioclavicular joint is displaced posteriorly during pushing or lifting movements of the upper limb.

Lesions  of  the   Suprascapular   Nerve 

 The suprascapular nerve arises from the upper trunk of the brachial plexus (C4, C5, C6) and passes through the suprascapular notch to the posterior aspect of the scapula to supply the supraspinatus and infraspinatus muscles. Entrapment of the nerve as it passes through thesuprascapular notch beneath the suprascapular ligament may occur. Injury to the nerve is characterized by pain in the posterolateral aspect of the shoulder and wasting and weakness of the supraspinatus and infraspinatus producing weakness of abduction and external rotation of the arm. The diagnosis is confirmed by electromyography. The nerve may be infiltrated in the suprascapular notch with 2 niL of 1% lidocaine followed by 40 mg methylprednisolone. If the steroid infiltration is not successful after two injections, the suprascapular ligament should be divided surgically.

Lesions   of  the   Musculocutaneous   Nerve

The musculocutaneous nerve arises from the lateral cord of the brachial plexus (C5, C6) and supplies the biceps, brachialis, and coracobrachialis muscles. The sensory distribution includes the anterior and posterior aspects of the lateral forearm from the elbow to the wrist. The musculocutaneous nerve may be injured in trauma to the shoulder area or following strenuous exercise such as rowing.¹⁶

Injury to the nerve is characterized by:

1.  Wasting of the flexor muscles of the upper arm and weakness of elbow flexion.

2.  Weakness of supination of the forearm.

3.  Sensory loss of a small area on the lateral aspect of the forearm.

4.  Loss of the biceps reflex.

The patient should wear a full arm sling. Physical therapy should be initiated to maintain range of motion.

Lesions of the Axillary Nerve (Circumflex Nerve)

The axillary nerve arises from the posterior cord of the brachial plexus (C5, C6) and supplies the deltoid and teres minor. The sensory distribution is localized to a small quadrilateral area on the upper lateral aspect of the arm.

The nerve may be injured by direct trauma to the axilla, by penetrating wounds of the axilla, and by fracture of the neck of the humerus. Isolated neuritis is not uncommon, particularly following immunizations or injection of a serum.

The patient develops weakness and wasting of the deltoid with flattening of the contour of the shoulder. There is inability to abduct the arm and weakness of external rotation. Sensory loss occurs over a small area on the upper lateral aspect of the arm.

Lesions of the Radial and Posterior Interosseous Nerves

Anatomy

The radial nerve is an extension of the posterior cord of the brachial plexus (C5, C6, C7, C8). It arises in the axilla, enters the spiral groove of thehumerus, and terminates at the level of the lateral condyle of the humerus by dividing into a superficial branch and the posterior interosseousnerve. The radial nerve supplies the triceps, anconeus, brachioradi-alis, and extensor carpi radialis longus in the arm. The nerve also supplies forearm muscles through its posterior interosseous branch including the extensor carpi radialis brevis, supinator, extensor digitorum, extensor digiti minimi, extensor policis brevis, and extensor indices. The sensory distribution includes the lower dorsal forearm, dorsal and lateral aspect of the hand and thumb, and the index and lateral aspect of the middle fingers (except the distal two phalanges).

Etiology The radial nerve is frequently injured by pressure in the axilla when falling asleep with the arm draped over the back of a chair (Saturday night paralysis), by pressure from a crutch, from penetrating injuries of the axilla, or with dislocation of the head of the humerus. A fracture of thehumerus can damage the radial nerve in the spiral groove. The nerve is frequently involved in lead neuropathy.

The posterior interosseous nerve is subject to pressure as it passes through the supinator muscle just below the elbow. The nerve is subject to entrapment at the same site in the supinator muscle and may be injured in fractures of the forearm as it lies on the interosseous membrane.

Clinical Features

The clinical features depend on the location of the injury and are as follows:

1. Radial nerve. When the radial nerve is injured, wrist drop (paralysis of extensor) associated with paralysis of extension of the elbow (triceps), weakness of elbow flexion (brachioradialis), weakness of supination (supinator), and paralysis of extension of fingers, thumb, and wrist occur.

2.    Interruption of radial nerve just below the branch to the brachioradialis. Same as 1 above, except extension of the elbow remains intact and there is some ability to supinate the forearm.

3.    Posterior interosseous nerve. Injury of the posterior interosseous nerve is characterized by progressive atrophy and weakness of the extensor muscles of the forearm. There is loss of extension of the fingers, but wrist drop does not occur because of preservation of the extensor carpi radialis. Entrapment of the nerve is associated with pain and tenderness on the lateral aspect of the elbow and is one of the causes of "tennis elbow."

4.    Sensory loss is often restricted to the dorsal surface of the thumb and the adjacent radial half of the dorsal surface of the hand.

The symptoms of lesion Radial nerve.

         Forearm extensors weakness

         Hand extensors weakness

         Fingers basal phalanx extensors weakness

         Impossible supination

          Impossible adduction of thumb

         Lost sensation on dorsal thumb surface and in space between the I st and II nd small bones

Diagnostic Procedures Electromyographic abnormalities of the involved muscles indicate the level of involvement of the radial nerve.

Treatment

The wrist should be splinted in extension. Physical therapy is important to prevent contractures of the fingers. Entrapment at the elbow can be treated by injection of 2 mL of 1% lidocaine and 40 mg methylprednisolone (Medrol) or by surgically freeing the nerve in intractable cases.

Lesions of the Ulnar Nerve

Anatomy

The ulnar nerve is the largest branch of the medial cord of the brachial plexus (C8, Tl). The nerve passes down the medial aspect of the upper arm in close relation to the brachial artery, then inclines backward to enter the ulnar groove at the posterior aspect of the medial epicondyle of thehumerus. The ulnar nerve enters the forearm between the two heads of the flexor carpi ulnaris and continues under the cover of that muscle to the wrist, where it crosses the flexor retinaculum and divides into superficial and deep branches, which terminate in the hand.

The ulnar nerve supplies the flexor carpi ulnaris and the medial half of the flexor digitorum profundus in the forearm. The deep branch of the ulnarnerve supplies the adductor pollicis, interossei, third and fourth lumbricals, palmaris brevis, abductor oppo-nens and flexor digiti quinti, and the deep head of the flexor pollicis brevis in the hand.

The sensory distribution through the superficial branch of the ulnar nerve includes the ulnar side of the fourth finger, the whole of the fifth finger on the palmar surface, and the distal two phalanges of the fourth and fifth fingers on the dorsal surface of the hand.

Etiology The ulnar nerve may be injured as follows:

1.  At the elbow by:

a.  Fracture   of  the   medial   epicondyle   of  the humerus.

b.  Progressive valgus deformity of the elbow following fracture of the lateral epicondyle, producing stretching of the ulnar nerve behind the medial   epicondyle   and   paralysis   occurring many years after the original injury to the elbow (tardy ulnar palsy).

c.  Pressure on the ulnar nerve in the ulnar groove behind the medial epicondyle occurring as an occupational problem (e.g., truck driving or in sedentary occupations where individuals "lean" on the elbow).

d.  Pressure on the ulnar nerve during prolonged surgical operations under general anesthesia.

e.  Entrapment of the ulnar nerve as it passes between  the  aponeuroses  connecting  the  two heads of the flexor carpi ulnaris muscle just distal to the medial epicondyle (cubital tunnel syndrome).

2.  At the wrist by repeated trauma to the wrist in certain industrial occupations, by compression of the ulnar nerve in long distance bicycle or motorcycle riders, or by fracture of the wrist. Rare causes of ulnar nerve involvement at the wrist include arteritis of the ulnar artery, hemorrhage secondary to hemophilia or the use of anticoagulants, and tumors of the wrist.¹⁹

Clinical Features

Ulnar nerve palsy is characterized by: 1.  Atrophy of the hypothenar muscles.

2.  Atrophy of the interossei.

3.  Development of a "claw hand" with extension of the metacarpophalangeal joints and flexion of the interphalangeal joints of the second and third fingers and flexion of the metacarpophalangeal joints (paralysis of the third and fourth lumbosacral) and the interphalangeal joints of the fourth and fifth digits.

4.  Paralysis of the flexor carpi ulnaris, if the ulnar nerve is involved above the middle third of the forearm, producing radial deviation of the hand on flexion of the wrist and weakness of ulnar deviation of the hand.

The symptoms of lesion Ulnar nerve.

         Hand flexors weakness

         The IV th and V th fingers distal phalanx extensors weakness

         Thumb abductors weakness

         Hypothenar hypotrophy

         Hand looks like bird paw

         The patient cannot scrawl with the nail of the V th finger, play on the piano and keep the sheet of paper with the I st and II nd fingers

         Anesthesia in the V th finger and hypothenar

Diagnostic Procedures

1.  Compression of the ulnar nerve at the elbow can be demonstrated by recording delayed nerve conduction in the elbow segment of the nerve.

2.  Compression of the ulnar nerve at the wrist produces an increased distal latency recorded in the abductor digiti quinti  and the  first dorsal  interosseous muscle.

Differential Diagnosis The differential diagnosis includes other causes of wasting of the small muscles of the hand (see Table 19-2).

Treatment

1.  Splinting is applied to prevent development of a claw hand deformity.

2.  Repetitive trauma to the elbow should be prevented by transplanting the ulnar nerve from the ulnar groove to the front of the elbow.

3.  Simple surgical decompression of the ulnar nerve in the cubital tunnel is required in cases of cubital tunnel syndrome.

4.  Repetitive trauma to the ulnar nerve at the wrist should be avoided. Where appropriate, scar tissue should be excised and other conditions compressing the nerve should be treated.

Prognosis There is usually good restoration of function following adequate treatment of ulnar nerve palsy.

Lesions of the Median Nerve

Anatomy

The median nerve arises from the lateral and medial cords of the brachial plexus. The nerve is closely related to the brachial artery as it passes down to the elbow and into the cubital fossa. It continues down the forearm connected to the deep surface of the flexor digitorum sublimis and enters the palm of the hand in close relationship to the pal-maris longus tendon by passing beneath the flexor retinaculum.

The median nerve supplies all the flexor muscles of the forearm, except the flexor carpi ulnaris and the medial half of the flexor digitorumprofundus.

The abductor pollicis brevis, flexor pollicis bre-vis, opponens pollicis, and the first two lumbricals are innervated by the median nerve in the hand. A palmar cutaneous branch arises from the median nerve in the lower part of the forearm and pierces the fascia above the transverse carpal ligament to supply sensory fibers to the proximal portion of the palm of the hand. The median nerve then passes beneath the transverse carpal ligament and supplies sensory fibers to the thumb, index, middle, and radial half of the ring finger on the palmar aspect of the hand and to the distal portion of the radial two-thirds of the palm of the hand (Fig. 19-3). The "all median" hand, an anatomical variation in which most of the sensation to the hand is derived from the median nerve, is not uncommon.

The symptoms of lesion Medial nerve.

         Impossible pronation

         Hand flexors weakness (especially of the I, II and III fingers)

         Thenar hypotrophy

         Hand looks like monkey paw

         Disability to opposite the thumb to the rest fingers

         Disability to make a fit as a result of thumb flexors weakness

         + mill sign

         Anesthesia on hands palm surface except the half of the IV th and V th finger

         Severe autonomic disorders

Lesions of the Anterior Interosseous Nerve

The anterior interosseous nerve arises from the median nerve in the cubital fossa, passes between the two heads of the pronator teres, and descends on the interosseous membrane to the wrist. It supplies the flexor pollicis longus, flexor digitorum profundus, and pronator quadratus.

This nerve is occasionally involved in traumatic injury to the forearm, including extensive lifting, high combined fractures of the ulna and radius, or following cardiac catheterization through the antecubital fossa. Symptoms consist of pain in front of the elbow radiating down the forearm and weakness of the flexor pollicis longus and the flexor digitorum profundus in the index finger. There are no sensory changes because the anteriorinterosseous nerve does not carry sensory fibers from the skin. Pressure on the median nerve in the cubital fossa exaggerates the pain. This condition is frequently mistaken for "tennis elbow," particularly when there is entrapment of the anterior interosseous nerve between the two heads of the pronator teres. The cubital fossa should be explored with decompression by neurolysis of the nerve from the elbow through the upper third of the forearm.

Carpal Tunnel Syndrome The carpal tunnel syndrome is characterized by fluctuating numbness, paresthesia, and pain in the hand due to compression of the median nerve at the wrist. Approximately 80 percent of cases occur in women and the condition is a common temporary phenomenon during pregnancy.

Table 19-3

The carpal tunnel syndrome

1.  Hereditary: hereditary neuropathy with liability to pressure palsy: HMSN type III

2.  Traumatic: dislocation, fracture, hematoma of forearm, wrist or hand. Wrist sprain. Direct blow to wrist following hand surgery for hand trauma.Occupational causes: repetitive percussion to wrist or repetitive flexion and extension of wrist

3.  Infection: tenosynovitis, tuberculosis, sarcoidosis

4.  Metabolic: amyloidosis, gout

5.  Endocrine: acromegaly, estrogen or androgen therapy, diabetes mellitus, hypothyroidism, pregnancy                 ,

6.  Neoplastic: ganglion cysts, lipoma, metastatic infiltration, myeloma

7.  Collagen vascular diseases: rheumatoid arthritis, polymyalgia rheumatica, scleroderma, systemic lupus erythematosus

8.  Degenerative: osteoarthritis

9.  Iatrogenic: radial artery puncture, insertion of a vascular shunt for dialysis, hematoma, complications of anticoagulant therapy

ETIOLOGY AND PATHOLOGY

There are many causes of compression of the median nerve at the wrist (Table 19-3).

The median nerve is confined in a relatively limited space as it passes beneath the transverse carpal ligament (flexor retinaculum) to enter the hand. Pressure on the nerve leads to obstruction of the venous circulation and edema. This in turn produces ischemia, increasing pressure on the nerve, and ischemic atrophy of nerve fibers.

CLINICAL FEATURES

The earliest symptoms consist of numbness and paresthesias in the sensory distribution of the median nerve in the hand (thumb, index, middle, and lateral half of the ring fingers). Later an ill-defined pain develops, involving the hand and wrist but also extending up into the forearm and often as high as the shoulder. The pain is worse at night, and the patient may hang the hand over the side of the bed or massage the hand in an effort to obtain relief. Complaint of weakness is a late event and is characterized by the inability to unscrew bottle caps or grip properly. Examination may show some wasting of the thenar eminence. Sensory loss is confined to the cutaneous distribution of the median nerve. This area occasionally includes the ring and little fingers if the patient has an anomaly known as the "all median hand," where the cutaneous distribution of the median nerve involves all of the fingers.

DIAGNOSTIC PROCEDURES

1.  Electromyography may reveal fibrillations in the muscles of the thenar eminence. Lumbrical sparing can occur in some cases.

2.  The distal latency of the median nerve is prolonged, indicating interference with conduction at the wrist.

3.  Sensory nerve conduction velocities and the sensory distal latency are prolonged on stimulating the digital nerves of the index finger.

4.  Thyroid function tests should be obtained since hypothyroidism is not unusual in carpal tunnel syndrome.

TREATMENT

1.  Identified causes should be removed or treated.

2.  Temporary and occasionally permanent relief can be obtained by corticosteroid injection around the median nerve in the carpal tunnel. The area around the nerve is infiltrated with 2 to 3 mL of 1% lido-caine followed by an injection of 40 mg methyl-prednisolone.

3.  Patients   who  fail   to  respond  to   injection   of corticosteroids performed on two occasions can obtain relief by surgical division of the transverse carpal ligament.

4.  A newer technique of endoscopic carpal tunnel release  is  now  available,  with  less  postoperative pain and earlier return to work.²¹ The prognosis is excellent if the cause is removed or treated and the affected nerve is released within the carpal tunnel.

Reflex Sympathetic Dystrophy (RSD) (Causalgia, Shoulder-Hand Syndrome, Sudeck's Atrophy)

Definition This results from an augmented response to injury of a body part attributed to sympathetic overactivity owing to uncontrolled stimulation at the spinal cord level.

Pathogenesis

Trauma leads to a stimulation of pain fibers (alpha, delta, and C fibers), which synapse in the dorsal horn gray matter (substantia gelatinosa) of the spinal cord. There is a secondary relay through the spinothalamic tract to the thalamus, but there are also axons that synapse with sympathetic efferents. Overstimulation of these efferent fibers leads to a peripheral inflammatory response with liberation of pain, producingpeptides such as calcitonin gene-related peptide, neurokinin A and B, substance P, and histamine. This leads to further stimulation of afferent alpha, delta, and C fibers, and reflex activity is established. It is recognized that this is a simplistic description of possible mechanisms in a very complex situation that is currently under intense review.

Clinical Features

Trauma is the most common predisposing factor in RSD.²² However, other conditions have been associated with RSD, including myocardialinfarction, cerebral infarction, brainstem infarction, spinal cord injury, spinal cord surgery, cervical spondylosis, lumbar radiculopathy, and neoplasms, particularly of the spinal cord.

There are three signs of RSD:

Stage I: Severe pain, usually following trauma, which may be relatively minor; the pain increases with emotional stress. The presence of allodynia (pain on light touch or contact with clothing) and hy-perpathia (increased sensitivity to normal stimuli) are features of the condition.

Dusky mottling or erythematous skin changes can occur. The skin is cool.

Swelling and edema of the affected area, followed by dystrophic skin changes and brittle nails, is usually present. Hyperhidrosis andhypertrichosis are features.

Stage II: Skin changes with a thin skin that is bright and shiny, cool and dusky in appearance. Involuntary tremor, muscle spasms, dystonia, and inability to initiate movements may occur.

Stage III: Progressive skin and subcutaneous tissue atrophy and development of a claw hand occur when that area is affected.

Diagnostic Procedures

1. Radiography of the underlying bone shows patchy osteopenia.

2.  Bone scintillography shows increased blood flow, increased blood pooling, and increased periarticular uptake in the affected area.

3.  A sympathetic stellate ganglion block will abolish the pain in many cases.

4.  Nerve conduction studies are usually normal but may be significantly slowed in damaged nerves when there is an entrapment condition of the digital nerves in the hand, which may mimic the pain of reflex sympathetic dystrophy.

Treatment

1.  The patient should be placed in daily physical therapy to improve mobility, and adequate pain medication should be given as needed.Transcutaneous electrical stimulation may be helpful in some cases.

2.  When the conservative treatment fails, the use of corticosteroids may be of benefit. This is usually given as prednisone or an equivalent 20 mg q8h decreasing the dose by 5 mg every 4 days.

3.  Amitriptyline beginning 10 mg q.h.s. and increasing slowly by 10-mg increments to avoid adverse affects to 150 to 200 mg q.h.s. will control the pain in many intractible cases.

4.  When medical treatment of this type has failed, sympathetic nerve interruption should be considered.  This  can  be  performed  by  sympathetic blocking using medications such as phenoxyben-zamine, bretylium, and reserpine.

5.  If this fails, surgical sympathectomy should be considered.

6.  Gabapentin 300 mg q8h increasing by 300-mg increments daily up to 3600 mg per day is effective in producing pain control in some patients.

Prognosis   The majority of patients have spontaneous resolution or respond to sympathectomy.

The Lumbar Plexus

The lumbar plexus is a relatively simple plexus formed by the union of the anterior primary rami of LI, L2, L3, and L4 within the substance of thepsoas muscle (Fig. 19-4). Lesions of the lumbar plexus are relatively rare because the nerves are well protected within the substance of thepsoas muscle. However, the plexus may be injured by penetrating wounds or by pressure from a psoas abscess or metastatic neoplasm. Irritation of the rami gives rise to pain in the corresponding dermatome. Destruction of rami leads to muscle weakness and wasting in the appropriate myotome.

Lesions of the Iliohypogastric Nerve

The iliohypogastric nerve arises from the anterior primary ramus of LI. The nerve may be injured as it pierces the internal oblique muscle just above the anterior iliac spine. Entrapment has also been described at this site. The patient presents with pain, paresthesias, and a small area of sensory deficit on the abdominal wall just above the pubic symphysis. Entrapment may be treated by injecting the nerve with a local anesthetic and a corticosteroid at the point where the nerve penetrates the internal oblique muscle.

Lesions of the Ilioinguinal Nerve

The ilioinguinal nerve arises from the anterior primary ramus of LI and traverses the abdominal wall between the transverse and internal oblique muscles to emerge through the superficial inguinal ring. The nerve supplies muscular branches to the abdominal muscles and cutaneous branches to the skin over the canal, the abdominal wall immediately above the pubic symphysis, the root of the penis, the upper part of the scrotum, and a small area on the adjacent medial aspect of the thigh.

The nerve may be compressed by enlarged lymph nodes in the inguinal area and is occasionally cut during herniorrhaphy. Herpes zoster involvement is not uncommon. The patient develops pain or sensory loss in the anatomic distribution of the nerve. Vesicles occur in the same distribution in cases of herpes zoster. Paralysis of the internal oblique muscle may predispose to an indirect inguinal hernia.

Lesions of the Genitofemoral Nerve

The genitofemoral nerve is formed within the psoas muscle by the junction of two branches arising from the anterior primary rami of LI and L2. It accompanies the iliac vessels to the level of the inguinal ligament and divides into a genital branch and a femoral branch. The genital branch enters the deep inguinal ring, traverses the inguinal canal, and supplies the cremasteric muscle, the scrotum, and the skin of the adjacent part of the thigh. The femoral branch enters the thigh beneath the middle of the inguinal ligament and supplies sensation over the femoral triangle. This nerve may also be compressed by enlarged lymph nodes or cut during herniorrhaphy. Pain or sensory loss occur in the anatomical distribution of the genitofemoral nerve.

Lesions of the Lateral Cutaneous Nerve of the Thigh

The lateral cutaneous nerve of the thigh arises from the anterior primary rami of L2 and L3, penetrates the psoas muscle, and crosses the iliacus to the anterior superior iliac spine. It enters the thigh between the two attachments of the inguinal ligament, penetrates the fascia lata, and divides into two branches about 10 mm below the inguinal ligament. The anterior branch supplies sensation to the lateral part of the anterior aspect of the thigh as far as the knee. The posterior branch supplies the upper two-thirds of the lateral aspect of the thigh and the lateral aspect of the buttock.

Etiology and Pathology

The nerve is prone to compression (entrapment) as it passes between the two attachments of the inguinal ligament or where it pierces the fascia lata. This condition seems to occur more frequently in diabetics or in individuals who suddenly gain or lose weight.

Clinical Features

Compression of the lateral cutaneous nerve of the thigh results in what is referred to as meralgia paresthetica. The patient complains of pain,paresthesias, and numbness in the distribution of the nerve.

Treatment

1.  All constricting items around the waist should be removed and an ice pack applied for 30 min tid, to the site of constriction, where the lateral cutaneous nerve penetrates the fascia lata.

2.  Administration of a nonsteroidal anti-inflammatory drug for 7 to 14 days may relieve symptoms.

3.  Those who fail to respond should receive infiltration of the area of entrapment with 1 % lidocaine and 40 to 80 mg methylprednisolone (Medrol), which produces permanent cure in a majority of patients.

4.  Refractory patients require surgical resection of a 4 cm length of the nerve where it exits the pelvis.

Lesions of the Obturator Nerve

The obturator nerve is formed by the union of branches from L2, L3, and L4. The nerve emerges from the medial border of the psoas muscle and descends through the obturator foramen to enter the thigh, where it divides into anterior and posterior branches. The obturator nerve supplies muscular branches to the adductor longus, gracilis, adductor brevis, obturator externus, adductor magnus, and (occasionally) pectineus. The cutaneous distribution is to the medial aspect of the thigh.

The obturator nerve may be injured by trauma, including fractures of the femur and gunshot wounds, and following difficult labor. A carcinoma of the cervix, rectum, or bladder may also involve the obturator nerve. The patient presents with weakness of adduction of the thigh with a tendency to abduction of the thigh when walking. Sensory loss occurs in the anatomic distribution of the nerve.

Lesions of the Femoral Nerve

The femoral nerve arises within the substance of the psoas muscle from the anterior primary rami of L2, L3, and L4. It passes downward and beneath the inguinal ligament to enter the thigh lateral to the femoral artery where it divides into a number of branches. One of these branches, the saphenous nerve, accompanies the femoral vessels in the femoral canal and continues down the leg on the medial aspect of the knee joint to terminate over the medial malleolus and the medial aspect of the foot.

The femora] nerve supplies muscular branches to the iliacus, pectineus, sartorius, quadriceps femoris, and adductor longus. The cutaneous branches supply the anterior thigh (intermediate and medial cutaneous nerves of thigh) and the medial aspect of the leg and foot (saphenousnerve).

Etiology and Pathology

1.  Trauma: fracture of the femur and pelvis, gunshot wounds, hematoma of the psoas muscle from injury or manipulation.

2.  Infection: psoas abscess, sarcoidosis, diphtheria, herpes zoster.

3.  Neoplasia: compression by pelvic tumor or metastases.

4.  Vascular   damage:   compression   by   an   aortic aneurysm, polyarteritis nodosa.

5.  Hemorrhage:      spontaneous      bleeding      with hematoma formation in leukemia, hemophilia, or other bleeding diathesis.

6.  Iatrogenic damage: hematoma of the psoas muscle or femoral canal during anticoagulant therapy.

The Sacral Plexus

The sacral plexus is formed by the union of the nerve roots L4, L5, SI, S2, S3, and S4 anterior to the piriformis muscle, which separates it from the lateral part of the sacrum. The most important branches include the superior gluteal nerve (L4, L5, and SI), the inferior gluteal nerve (L5, SI, and S2), the posterior cutaneous nerve of the thigh (SI, S2, and S3), the sciatic nerve (L4, L5, SI, S2, and S3), and the pudendal nerve (S2, S3, and S4).

Lesions of the Superior Gluteal Nerve 

 The superior gluteal nerve leaves the pelvis through the greater sciatic foramen and supplies the gluteus medius and gluteus minimus. These two muscles act as abductors and medial rotators of the thigh. The nerve may be injured by wounds of the buttocks and is occasionally involved in fractures of the pelvis and by metastatic tumors within the pelvis. Involvement produces paralysis of the gluteus medius and minimus resulting in lateral rotation of the lower limb at rest and flexion of the trunk toward the affected side when walking.

Lesions of the Inferior Gluteal Nerve  

The inferior gluteal nerve enters the buttocks below the piriformis muscle and supplies the gluteus maximus. This muscle is responsible for extension of the hip, and paralysis produces difficulty in rising from a sitting position and difficulty in climbing stairs. There is marked atrophy of the affected buttock.

Lesions of the Posterior Cutaneous Nerve of the Thigh

The posterior cutaneous nerve of the thigh leaves the pelvis through the sciatic foramen and passes down the buttock and thigh on the medial aspect of the sciatic nerve. The posterior cutaneous nerve of the thigh supplies sensation to the posterior aspect of the thigh as far as the popliteal fossa. The nerve is often injured in gunshot wounds and penetrating wounds of the thigh and is occasionally injured by injections of irritating material. Damage to the nerve gives rise to a sensory deficit in the back of the thigh, the lateral part of the perineum, and the lower portion of the buttock.

Lesions of the Pudendal Nerve

The pudendal nerve leaves the pelvis through the greater sciatic foramen below the piriformis muscle and passes forward into the ischiorectalfossa. The nerve is occasionally injured in fractures of the pelvis. Damage produces sensory loss in the perineum and scrotum on the side of the lesion. Bilateral lesions produce bladder disturbances with urinary incontinence and overflow.

Lesions of the Sciatic Nerve

The sciatic nerve is the main branch of the sacral plexus and leaves the pelvis through the greater sciatic foramen to enter the buttock. The nerve then passes down the posterior aspect of the thigh to the popliteal fossa, where it divides into the tibial and common peroneal nerves.Compressive lesions of the sciatic nerve produce sciatic pain, which is distributed down the posterior aspect of the thigh, often radiating into the calf and the foot. The most common cause is herniation of a lumbar disc between L4 and L5, or L5 and SI. Other causes of sciatic nerve compression are listed in Table 19-4. The sciatic nerve may be injured by penetrating wounds of the buttocks, thigh, or popliteal fossa. Sciatic nerve paralysis has also been described in association with a fracture of the femur or posterior dislocation of the femoral head. Complete interruption of the sciatic nerve produces a useless lower limb with loss of ability to flex and extend the foot at the ankle, loss of flexion and extension of the toes, and loss of inversion and eversion of the foot. Movement of the lower limb produces a flail-like movement of the foot at the ankle. In addition, there is impairment of flexion at the knee due to paralysis of the biceps femoris, semitendinosus, and semimembranosus,although some movement is still possible by contraction of the sartorius and gracilis muscles supplied by the femoral and obturator nerves, respectively. Extension of the knee is preserved. There is marked sensory loss below the knee with the exception of the medial aspect of the leg and ankle, which is innervated by the saphenous nerve. Wounds of the middle portion of the posterior aspect of the thigh produce loss of function confined to the common peroneal and tibial nerve with preservation of the nerve to the hamstrings. In these cases, flexion of the knee is preserved.

The symptoms of lesion Sciatic nerve

         Complete paralysis of foot and toes

         Impossible flexion in knee joint and shin – foot joint

         Shin and hip atrophy

Table 19-4

Causes of sciatic nerve lesions (other than lumbar disc herniation)

1.  Nerve root involvement

a.  Cauda equina: herpes zoster, arachnoiditis, tumors of the cauda equina, subarachnoid hemorrhage

b.  Vertebrae and intervertebral foramina: compression fractures or fracture dislocation, spondylosis, lumbosacral stenosis, tuberculosis, Pagetdisease, metastatic tumors

2.  Sacral plexus

Trauma with fracture of the pelvis, psoas abscess, pelvic abscess, direct extension of pelvic carcinoma, retroperitoneal metastasis, aneurysm of iliac vessels or branches, pregnancy

3.  Gluteal area

Trauma from penetrating wounds, fracture of the pelvis, fracture of the femur, dislocation of the femoral head, traumatic hematoma, traumaticaneurysm of the inferior gluteal artery

4.  Thigh

Penetrating wounds, injection of drugs into sciatic nerve, sciatic nerve entrapment

5.  General involvement

Diabetes mellitus, polyarteritis nodosa

Lesions of the Common Peroneal Nerve  

The common peroneal nerve arises in the posterior aspect of the thigh as one of the two terminal branches of the sciatic nerve. The commonperoneal nerve is injured by penetrating wounds of the lower portion of the posterior aspect of thigh or popliteal fossa. It is occasionally involved in fractures of the lower portion of the femur or the head of the fibula. Symptoms consist of foot drop with a tendency to invert the foot due to unopposed action of the tibialis posterior. There are a high-steppage gait, wasting of the muscles of the anterior compartment of the leg, and a sensory loss extending over the lateral aspect of the leg and dorsum of the foot.

The symptoms of lesion Peroneal nerve.

         Feet and toes extensors weakness

         Feet adductors weakness

         Typical gait – cock like

         Anesthesia of external edge of shin and dorsal surface of feet

Lesions of the Superficial  Peroneal Nerve

This nerve arises at the level of the bifurcation of the common peroneal nerve just below the neck of the fibula. The nerve passes down the leg anterior to the fibula between the peroneal and extensor digitorum longus muscles. Lesions of the superficial peroneal nerve produce paralysis of the peroneal muscles with loss of eversion of the foot and a tendency to invert the foot on dorsiflexion. There is a variable sensory loss over the lower lateral aspect of the leg and dorsum of the foot.

Lesions of the Deep Peroneal  Nerve  

The deep peroneal nerve arises just below the head of the fibula as one of the two terminal branches of the common peroneal nerve. The deepperoneal nerve passes onto the interosseous membrane between the tibia and fibula and then courses downward to the ankle supplying the muscles of the anterior compartment of the leg with the exception of the peroneal group. This nerve is commonly affected by pressure over the head of the fibula, often by sitting with the legs crossed for a prolonged period of time. Deep peroneal nerve paralysis produces weakness of the dorsiflexors of the foot and extensors of the toes resulting in foot drop, steppage gait, weakness of the muscles of the anterior compartment of the leg, and a sensory deficit confined to the contiguous surfaces of the first and second toes.

Lesions of the Tibial Nerve

Tibial nerve lesions are infrequent, but the nerve is occasionally injured or compressed by cysts or hematomas of the popliteal fossa. There are weakness of plantar flexion and adduction of the foot with a sensory loss involving the sole of the foot.

The symptoms of lesion Tibial nerve

 Feet and toes extensors weakness

         Feet abductors weakness

         Disability to walk on tip toes

         Anesthesia on sole and external surface of the feet

The Posterior Tibial Nerve (Tarsal Tunnel Syndrome)

The posterior tibial nerve is subject to compression as it passes beneath the flexorretinaculum, which forms the roof of the tarsal tunnel at the ankle. The nerve usually divides into medial and lateral plantar nerves in the tarsal tunnel, and symptoms of compression depend on the degree of involvement of these two nerves. Symptoms consist of pain and paresthesias of the sole of the foot, which are aggravated by walking or prolonged standing. There is no weakness, but there may be some wasting of the adductor hallucis. The pain may be aggravated by pressure over the posterior tibial nerve just below the medial malleolus.

Treatment consists of infiltration of the tarsal tunnel with 1% xylocaine followed by 40 mg methyl-prednisolone (Medrol). Surgical division of the flexor retinaculum is indicated in intractable cases.

Plantar Nerves and Interdigital Nerves 

The plantar nerves are occasionally involved by inflammatory conditions such astenosynovitis. The interdigital nerves are subject to compression as they cross the heads of the metatarsal bones. The interdigital nerve to the third and fourth toes is most commonly involved with the development of a traumatic neuroma. Symptoms consist of severe episodic pain radiating to the contiguous surfaces of the third and fourth toes (Morton's metatarsalgia). The condition may improve following infiltration with local anesthesia and methylprednisolone, but excision of the traumatic neuroma is required in most cases.

Multifocal Motor Neuropathy (MMN)

Definition This is a rare, predominantly motor peripheral neuropathy with a superficial resemblance to motor neuron disease.⁶⁸

Etiology and Pathology It is probably an autoimmune neuropathy. Involved nerves show focal enlargement, occasionally tumor-like swellings. There is chronic demyelination with onion bulb formation.

Clinical Features  

This is a predominantly motor neuropathy with subtle, patchy sensory loss. Muscle weakness is confined to the distribution of individual affected nerves with motor weakness, atrophy, fasciculations, and cramps. Bulbar involvement is rare, and there are no signs of motor neuron involvement. The disease begins in young adults and involves distal upper limb muscles initially, with slow progression to a more generalized involvement over many years.

Diagnostic Procedures

1.  Motor conduction studies show multifocal conduction block confined to motor axons, usually in the forearms and hands⁷⁰ with occasionally more widespread, milder conduction changes.

2.  Antibodies to GM1 ganglioside occur in 50 to 70 percent of patients.

Treatment There is a good response to long-term immunoglobulin therapy.⁷¹ Relapse can occur. Steroids and plasmapheresis are not effective.

PERIPHERAL NEUROPATHIES IN VASCULAR DISEASE

Although peripheral neuropathy is not unusual in patients with atherosclerotic cerebrovascular disease, such cases are nearly always due to diabetic neuropathy. Peripheral neuropathy of vascular origin is relatively rare and is related almost exclusively to arteritis. The term "arteritis"includes polyarteritis nodosa, Wegener's granulomatosis, giant cell arteritis, rheumatoid arthritis, Sjogren syndrome, and systemic lupuserythematosus (SLE). However, the neuropathy in SLE may be the result of immune complex deposition, antiphospholipid antibodies, or antineural antibodies, rather than an "arteritis." The neuropathies associated with angiopathies may present as a mononeuropathy or diffuse symmetrical peripheral neuropathy.

Diagnosis may require sural nerve biopsy when other signs of disease are lacking and the patient presents with neuropathy alone.

Treatment with corticosteroids is usually effective in giant cell arteritis but may be of less or of no benefit in polyarteritis nodosa and in the other arteri tides. The neuropathy of SLE may respond to monthly infusions of intravenous cyclophosphamide.⁷³

NEUROPATHIES COMPLICATING HIV INFECTION

Four distinct peripheral neuropathies have been recognized clinically or electrophysiologically in up to 35 percent of patients with HIV infection. However, the incidence is likely to be underestimated because many patients with AIDS have a subclinical peripheral neuropathy.

1.    The distal symmetrical peripheral neuropathy is the most frequently encountered neuropathy in AIDS. This condition presents with distal sensory loss consisting of numbness, burning, and paresthesias in the toes, extending up the lower limbs, followed by sensory impairment in the fingers. There is mild weakness of the intrinsic muscles of the feet and marked skin changes distally in the lower limbs, with thinning of the skin, hair loss, and later development of a dusky discoloration and pedal edema. Reflexes are lost at the ankle but preserved at the knees.

2.    Chronic      inflammatory      demyelinating polyneuropathy can develop in AIDS.

3.    Mononeuropathy multiplex with abrupt onset, patchy weakness and sensory loss occurs in AIDS. Cranial nerve involvement is often present in these cases. In the early stages of HIV infection, spontaneous resolution can occur. In advanced infection, with CD4 counts below 50 per cubic millimeter,   the   neuropathy   may   progress   rapidly   to quadriparesis.⁷⁶

4.    Progressive polyradicular neuropathy involving the lumbosacral nerve roots produces subacute   progressive   motor   and   sensory   loss,  with impairment of bladder and bowel  sphincter control. Some cases are the result of cytomegalovirus infection.

Diagnostic Procedures

1. The CSF is normal in distal symmetrical peripheral neuropathy and multineuropathy multiplex

but abnormal in CIDP and progressive polyradicular neuropathy.

2.  Electrophysiologic studies are abnormal in all four conditions.

3.  Sural nerve biopsies are abnormal in CIDP and symmetrical peripheral neuropathy.

4.  All patients have antibodies to HIV in the serum.

5.  The sedimentation rate is usually elevated.

6.  Polyclonal elevation of serum immunoglobulins is present in most cases.

Treatment

1.  Patients   with   CIDP   respond   to   prednisone, plasmapheresis,  or intravenous immunoglobulin therapy.

2.  Polyradicular neuropathy or mononeuritis multiplex, owing to a cytomegalovirus, requires early treatment with ganciclovir.

3.  Treatment of distal symmetrical peripheral neuropathy  requires  amitryptyline,  desipramine,  or gabapentin for pain and an ankle-footorthosis for distal weakness.

PARANEOPLASTIC NEUROPATHIES

Peripheral neuropathies are not unusual complications in patients suffering from carcinoma. The neuropathy may be directly related to the presence of the carcinoma, may be a nonmetastatic phenomenon, or may be a complication of chemotherapeutic treatment. A number of other conditions—for example, multiple myeloma, macroglobulinemia, cryoglobulinemia—may be accompanied by a progressive and often severe peripheral neuropathy.

Carcinomatous Peripheral Neuropathy  

Two forms of peripheral neuropathy have been described in association with neoplasia and must be considered to be paraneoplastic effects of cancer in that there is no direct involvement of the peripheral nerve by the neoplastic process. The most common form of carcinomatousperipheral neuropathy is a symmetrical sensorimotor neuropathy that affects the extremities, producing distal weakness and symmetrical sensory loss. The condition is slowly progressive. There is a rarer sensory neuropathy occasionally encountered in association with malignancy. This condition begins with sensory loss involving the extremities and progresses in a chronic fashion with involvement of all four limbs. The condition sometimes becomes arrested about 3 months after onset and does not show further progression after that time.

Critical Illness Polyneuropathy

Definition This diffuse polyneuropathy occurs in critically ill patients with a delay in weaning the patient from ventilatory support once the critical illness is under control.

Etiology and Pathology The etiology is obscure. No toxic, metabolic, vascular, or nutritional factors have been identified.

Clinical Features

The salient feature is failure to withdraw mechanical ventilatory aid when the systemic illness has improved. Improvement occurs first in the upper limb and proximal limb, followed by the respiratory muscles and later by the distal lower limb musculature.

Diagnostic Procedures The diagnosis can be established by electromyography, which shows widespread denervation and by nerve conduction studies.

Treatment The patient should receive all care necessary for a ventilator-dependent patient until recovery returns.

NUTRITIONAL NEUROPATHIES

Nutritional peripheral neuropathies occur in patients who are subjected to chronic deprivation of essential food constituents. These neuropathies have occurred traditionally during famine or during imprisonment and starvation. Under modern conditions they are more likely to be seen in individuals who follow strict, unbalanced diets, in food faddists, in cases of deliberate starvation to lose weight, in persons who have had alimentary bypass operations, and in alcoholics who obtain the bulk of food calories from alcohol.

Beriberi (Thiamine) Neuropathy

Definition Beriberi neuropathy is a symmetrical, distal motor and sensory neuropathy due to chronic vitamin B_: deficiency.

Etiology and Pathology

Vitamin Bj is essential for the metabolism of carbohydrate, and both the CNS and peripheral nervous system are almost entirely dependent on carbohydrate for energy requirements. Vitamin Bj deficiency may be due to:

1.  Inadequate diet:  famine,  starvation,  food fads, anorexia nervosa, bulimia

2.  Poor diet: alcoholism, vegetarians

3.  Poor   absorption:   celiac   disease,   adult   sprue, chronic diarrhea

4.  Destruction of thiamine: presence of thiaminosis in fish and certain vegetables, thiaminolytic bacilli in the gastrointestinal tract; prevention ofphosphorylation by thiamine antimetabolites such as pyrithi amine

Vitamin B^ deficiency results in failure of formation thiamine pyrophosphate, which acts as a cocarboxy-lase in the conversion of pyruvate to active acetate. Thiamine pyrophosphate also acts in the conversion of α-ketoglutarate to succinyl-CoA. Thiamine deficiency interferes with the citric acid cycle, and energy release is severely restricted. There is a failure of breakdown of glycose-y-phosphate into the pentose-phosphate shunt due to a lack of thiamine pyrophosphate, which acts as a coenzyme of transketolase in this cycle.

There is a concomitant loss of myelin sheaths and axonal degeneration with Schwann cell proliferation beginning distally and extending proximally.

Clinical Features

Patients complain of distal paresthesias, dysesthesias (burning feet), and muscle cramps beginning 2 to 6 months after the beginning of consistent vitamin B_; deficiency. These symptoms

may be accompanied by lethargy, anorexia, nausea, and vomiting. Early symptoms are followed by development of foot drop and steppage gait leading to paraplegia. There is an ascending glove-and-stocking sensory loss. The patient is severely ataxic and reflexes are absent. Weakness may extend to proximal muscles; muscle atrophy is late. Cranial nerve involvement usually involves the vagus nerve producing tachycardia, hoarseness, and dysphagia, and the facial nerve with bilateral facial weakness.

Acute beriberi is rare and presents with acute vomiting and tachycardia followed by rapidly ascending paralysis involving the lower, then the upper limbs. There is a high risk of death from acute heart failure. "Wet" beriberi is a subacute condition with pericardial, pleural, and peritoneal effusions, severe peripheral edema, and peripheral neuropathy.

Diagnostic Procedures

1.  Red blood cell transketolase activity is decreased.

2.  Serum pyruvate and lactate levels are elevated.

3.  Nerve   conduction   velocity   measurements   are slowed. An electromyogram shows evidence of denervation.

Treatment Thiamine 100 mg ql2h should be given by intramuscular injection. The prognosis is excellent.

Neuralgia in Pregnancy

Pregnancy may be associated with a number of neuralgias, which tend to occur in the later months of pregnancy and resolve after delivery. These neuralgias include meralgia paresthetica, carpal tunnel syndrome, sciatic neuralgia, and intercostal neuralgia.

Intercostal neuralgia may produce severe pain in the chest or upper abdomen, which may lead to an erroneous diagnosis of heart disease or acute intraabdominal disease. The pain is usually exacerbated by movements that stretch the affected nerves, and there may be an area of sensory change in the affected dermatome. Relief may be obtained by temporary nerve block following an injection of a local anesthetic. The prognosis is excellent. The neuralgias of pregnancy resolve in the immediate postpartum period.