THE AGE ANATOMICAL AND PHYSIOLOGICAL PECULIARITIES OF THE NERVOUS SYSTEM IN CHILDREN. NEUROLOGIC EVALUATION IN CHILDREN. CONGENITAL ANOMALIES OF THE NERVOUS SYSTEM. SEMIOTICS OF THE MAIN NERVOUS SYSTEM DISORDRES IN CHILDREN. NURSING CARE OF CHILDREN WITH DISEASES OF THE NERVOUS SYSTEM.

The evaluation of the infant or child with a suspected or certain neurological disorder requires both a carefully elicited history and an accurate assessment and interpretation of physical signs. Also necessary is a working knowledge of the expected rate of growth and development of the child and the accepted range of deviation from the norm. It is essential that the history include adequate information regarding the child’s prior health, acquisition or loss of developmental milestones, family history, and social as well as physical environment. Such considerations may modify the child’s response to illness or provide clues to inciting factors.

Table

Intrauterine development of nervous system

Nervous system develops from ectoderm on the end of the 2^nd week. During the 3^d week the primary neural plate forms. Later it divides into neural tube, which later gives rise to the spinal cord and the brain, and neural crest cells, which form the peripheral nervous system, meninges, melanocytes, and adrenal medulla. The most intensive dividing of nervous cells takes place during the period from 10^th till 18^th weeks of gestation that is the critical period of formatting of central nervous system. Any insult (e.g., infectious, metabolic, toxic, or vascular disorders) sustained during this period is likely to impair brain growth.

The age peculiarities of nervous system

The brain is the most morphologically developed organ at birth, but its functional abilities are immature. The brain weight consists 1/9 of body weight in newborns. It doubles by the end of 1 year and is equal 1/11-1/12 of body weight, at the age of 5 years – 1/13-1/14 and in adult – 1/40 of body weight.

The brain tissue is characterized by rich vascularization, but the back-flow of blood is weak that courses easy development of brain edema and collecting of toxin substances.

The neurocyte needs as much as in 22 times more oxygen than any somatic cell. That is why lots of diseases in infancy lead to development of hypoxic encephalopathy.

The amount of cerebrospinal fluid in newborn is equal 30-40 ml, in 12 month – 40-60 ml, and it enlarges to 150 ml by reaching adolescence.

Circulation Ways of Cerebrpspinal fluid

Lumbar Cerebrospinal Fluid

Determination	Children’s age
	by 14 days	from 14 days to 3 mo	4-6 mo	older 6 mo
Colour	bloody, xanthochromic	colourless	colourless	colourless
Transparency	transparent	transparent	transparent	transparent
Cells count (in 1 ml) lymphocytes Neutrophils	1-10 mainly lymphocytes	1-8 mainly lymphocytes	1-7 80-85 % 3-5 %	1-3 80-85 % 3-5 %
Protein	0.4-0.8 g/l	0.2-0.5 g/l	0.18-0.36 g/l	0,16-0,24 g/l
Pandi reaction	“+”,“++”	“+”	“+”,“-”	“-”
glucose (40-60 % of serum glucose level)	1.70-3.90 mmol/l	2.20-3.90 mmol/l	2.20-4.40 mmol/l	2.20-4.40 mmol/l
Chlorides	179.2-201.6 mmol/l	179.2-201.6 mmol/l	184.8-201.6 mmol/l	184.8-201.6 mmol/l
cerebrospinal pressure				130-180

The adult person has got 16 billion of neurocytes. At birth the quantity of mature neurocytes is 25% of the amount of all undifferentiated cells situated in the brain. By the end of the 6^th month they reach 66 %, and at the age of 1 year – 90-95 %. At 18 months all 100 % of neurocytes are similar to those of adult. That is why the proper nutrition, development, caring of the child and absence of diseases are so important during this period.

Neurologic evaluation in children

History Chief Complaint.

It is instructive to report the presenting symptom in the words of the child or, when this is not possible, the parent or caretaker. Citing the problem in its simplest terms emphasizes the importance of the child's own perception of his or her illness and also encourages an approach that considers all relevant disease mechanisms rather than focusing prematurely on a specific diagnosis. For example, a child who is "not walking right" may be experiencing symptoms of rapid ventricular enlargement; drug intoxication; midline cerebella dysfunction; spinal cord compression; peripheral neuropathy; primary muscle disease; or traumatic or inflammatory disease of bones, joint, or soft tissue of the lower limb.

Present Illness.

When eliciting an historical account of the child's present illness the examiner must attempt to define the disease process with respect to both time course and localization within the nervous system. Before focusing on a specific diagnosis, answers to each of the following questions should be found: (1) is the disease acute or chronic? (2) Is the disease static or progressive? (3) Is the disease focal or diffuse?

The history of the present illness should incorporate information provided by child and parents as well as observations of other individuals such as teachers, baby sitters, referring physicians or other health care providers. Information that the child fails to achieve expected milestones; a progressive disease in which previously acquired skills are lost; or a recurrent illness in which, despite dramatic symptoms or signs, the child returns to his or her baseline level of function should be reported. Warning or premonitory symptoms are particularly relevant when evaluating paroxysmal or intermittent illnesses such as migraine or epilepsy. Exacerbating or ameliorating factors should also be sought. Inquiry should be made into associated systemic complaints such as nausea, weight loss, fever, pallor, and visceral enlargement. Results of previous diagnostic studies should be obtained to avoid untimely delays or repetition of costly or invasive procedures.

Past History.

If not already elicited in the history of the present illness, the past history should include details of the mother's pregnancy, length of gestation, exposure to drug or substance abuse, and complications of labor and delivery. A chronologic account of growth and development will often provide critical information regarding the onset and tempo of neurological impairment. Specific details regarding acquisition of language, cognitive and social skills, and motor milestones may help distinguish a global or pervasive syndrome from one that affects a more restricted area of function. Changes in school performance and level of activity or personality may be illuminating. Inquiry also should be made regarding common infectious diseases, transfusions, immunizations, trauma, and exposure to environmental toxins, and unusual dietary habits.

Family History.

Health status of immediate family members should be elicited. History of unusual birthmarks or tumors may provide clues regarding a possible neurocutaneous syndrome. Specific inquiry should be made into family history of seizures, migraine, neuromuscular disease, learning disability, or early infant demise. When positive for one or more of the above, a sketch of the family pedigree may help delineate the pattern of inheritance.

Physical Examination.

Height, weight, and head circumference should be measured and recorded on appropriate standardized grids preferably with previously obtained values. In the case of the child in whom a large head size is of concern, serial measurements are of particular interest in order to distinguish a benign process from the consequences of increased intracranial pressure. Enlargement of anterior and posterior fontanels or diastasis of cranial sutures are other signs that may occur in the absence of symptoms of intracranial hypertension. A careful funduscopic examination should be attempted in every child being evaluated for a neurological disorder, noting the presence or absence of optic disc elevation, atrophy, vascular engorgement, hemorrhage, or abnormal retinal pigmentation. It should be remembered, however, that the optic discs might appear entirely normal early in the course of acute, life-threatening elevation of intracranial pressure. The spine should be examined for the presence of head tilt, neck stiffness, resistance to flexion of the hips with the knees extended ("straight leg raising", Kernig sign), tenderness or spasm of the paraspinal muscles, unusual dimples, skin tags, or palpable defects of the vertebral column. Scoliosis and limb asymmetry should also be noted. Cardiac auscultation should be performed, especially in the setting of possible cerebrovascular disease or brain abscess. Visceral enlargement noted on examination of the abdomen may provide critical information in the child with acute loss of neurological function resulting from a systemic malignancy or with developmental delay from an inborn error of metabolism. Examination of the skin for areas of abnormal pigmentation is best accomplished with the child completely disrobed. Axillary and other intertrigenous regions should not be overlooked because "freckles" in these areas may help identify the child with neurofibromatosis. Illumination of the skin with ultraviolet light may accentuate depigmented "ash leaf spots" associated with tuberous sclerosis. Although 50% or more of children with these neurocutaneous syndromes may represent new mutations, examination of the parents may yield important data for purposes of genetic counseling or clarification of an otherwise uncertain diagnosis.

Neurological Examination

With the exception of emergent situations such as status epilepticus or coma, the neurological examination should be enjoyable for both child and examiner. Every effort should be made to put the child and parents at ease.

The initial phase and often most revealing aspect of the neurological examination consists of observation. The child should be observed at play, interacting with parents, moving about the room, and exploring the surroundings while the history is being taken. Deliberate attention should be directed to social skills, attention span, and quantity of motor activity. Observing their reactions to the child in the examining room can also make a preliminary assessment of the parents’ expectations and coping skills.

The neurological examination, while recorded in a stereotyped orderly fashion, must be performed in a manner that is flexible and adapted to accommodate each child at his or her own level of function and development. Tasks requiring the greatest level of attention are best done early in the session, whereas potentially uncomfortable tests such as eliciting a Babinski sign are deferred until the end of the examination. By following these basic guidelines, even subtle deficits may be detected by the careful examiner.

Mental Status

The mental status examination includes assessment of level of alertness; orientation with respect to awareness of self, place, and time; mood; affect; expressive and receptive language; abnormal thought content (i.e., hallucinations or delusions); memory; problem solving; and abstract reasoning and insight. More than other aspects of the neurological examination, mental status must be evaluated in the context of what is expected for age and level of development. When indicated, more detailed evaluation of cognitive function and academic achievement should be assessed by a trained individual using standardized test instruments.

Stance and Locomotion

Whether the task is maintaining an upright sitting position on the floor or toddling down the corridor, the ability of a child to maintain his posture against gravity and to move about should be noted. The presence of trunk and proximal hip girdle weakness may be revealed by a "waddling" gait or by "climbing up the thighs" when arising from the floor (Gower maneuver). Loss of proprioception or awareness of joint position can be demonstrated as loss of balance provoked by eye closure (Romberg sign). Peripheral neuropathy may be manifested by impairment of dorsiflexion of the feet at the ankles, leading to either a "slapping" gait or inability to "walk on the heels". Dystonic postures of the upper limb, toe walking or torsion of the foot are frequently seen with a hemiparetic gait because of corticospinal tract involvement or with torsion dystonia.

Motor System

Examination of the motor system includes assessment of muscle power, tone, and bulk, often the earliest signs of weakness are those detected by simply noting persistent asymmetries in the child's spontaneous activities. Thus, disuse or paucity of movement of one arm in an infant may be an early sign of significant hemiparesis. Games in which the child is asked to hold his or her arms out like "Superman" or as if to "catch some raindrops" while closing the eyes may elicit drift or pronation of the weaker limb. Muscle tone is estimated by the amount of resistance or recoil encountered while gently moving the limbs through their expected ranges of motion. Although increased muscle tone is considered a hallmark of lesions of the upper motor neuron (i.e., motor cortex and corticospinal tract), injury to the brain or spinal cord often produces decreased muscle tone acutely with increased tone or "spasticity". Palpation enables the examiner to better appreciate the presence of muscle pseudohypertrophy as in Duchenne muscular dystrophy, loss of muscle bulk as in spinal muscular atrophy.

Sensory System

Assessment of sensory function should be attempted even when cooperation is limited by young age. Observation of withdrawal to light touch or grimacing in response to noxious stimuli will provide a gross estimate of sensory level in an infant. In children older than 2 or 3 years patience will permit testing of perception of light touch, temperature, vibration, and joint position. Pain perception can be evaluated using the sharp edge of a broken sterile cotton swab. Care should be exerted to avoid breaking the skin or otherwise alarming the child. Safety pins or other sharp objects should be used only if sterility of the test object can be assured.

http://www.medicanalife.com/watch_video.php?v=1a11101438ea8f9

Reflexes Table

Myotactic or muscle stretch reflexes, inaccurately referred to as deep tendon reflexes, can be elicited at virtually all ages. Although absent or difficult to elicit in certain otherwise normal individuals, loss of muscle stretch reflexes is an early and frequently persistent sign of acquired neuropathies such as Guillain-Barre syndrome or vincristine toxicity. In contrast, muscle stretch reflexes are usually preserved late into the course of most primary muscle disorders. Muscle stretch reflexes are considered to be pathologic when asymmetric, clearly exaggerated, or accompanied by reduplication of the muscle contraction referred to as clonus. Other pathologic reflexes not mediated through the myotactic arc include the Babinski sign. Persistence of certain primitive reflexes such as the Moro, grasp, rooting and sucking well beyond the ages at which they are normally extinguished may be a sign of diffuse cerebral dysfunction.

http://www.medicanalife.com/watch_video.php?v=8c949dfde7510ce

http://www.medicanalife.com/watch_video.php?v=06fea3768fd62c5

Cerebella System

Performance of certain maneuvers such as touching finger-to-nose and heel-to-knee-to-shin requires smooth regulation of the force and velocity of contraction of agonist and antagonist muscle groups while maintaining stable posture of the remainder of the body during the course of the task. Decomposition of such coordinated activities leads to typical signs of cerebella impairment.

Summary.

Neurologic evaluation of infants and children requires a detailed history, careful observation of the patient, and accurate interpretation of symptoms and physical signs. Ultimately, the data derived in this process should provide a tentative localization of the site of dysfunction within the nervous system and also a chronologic profile of disease progression. While laboratory and imaging studies are often necessary to establish a diagnosis, an accurate history and physical examination are mandatory in order to determine what studies are appropriate and how a definitive diagnosis may be made in the safest, least invasive, and most efficient manner.

Syndromes of nervous system disorder

.

1. Microcephaly

2. Hydrocephalus

3. Erb Palsy

4. Cerebral Palsy

5. Seizures syndrome

6. Tic syndrome

7. Meningitis

8. Syndrome meningism

Congenital defects of the nervous system

Congenital malformations of the nervous system are common, frequently contributing to spontaneous abortion or fetal death. They often occur in association with other anomalies, particularly ones involving midline structures (e.g., lip and palate), the heart, and the integument (e.g., skin, ears, and digits). Some of these syndromes are caused by chromosome defects, and a number of anomalies are traceable to another genetic defect, but the majority has no proved etiology. Each developmental anomaly results from an error during a critical stage of neural differentiation; this may affect closure, flexion, or neuron migration.

Hydrocephalus

Hydrocephalus is a pathologic condition in which the volume of CSF within the ventricles is increased as a result of a blockage of CSF outflow. In communicating hydrocephalus, CSF exits the ventricular system but is not absorbed. Noncommunicating hydrocephalus results from a blockage within the ventricular system such as at the level of the aqueduct of Sylvius, aqueductal stenosis, obstruction of the foramina of Luschka and Magendie, postinfectious ventriculitis, intraventricular hemorrhage. Congenital hydrocephalus develops in uterus and is manifested soon after birth; acquired forms are secondary to viral or bacterial infections and hemorrhage. Tumors are the most common cause of acquired hydrocephalus in children and adolescents.

As the cerebral ventricles enlarge, increased intracranial pressure develops and the head becomes progressively enlarged. In the infant, the main signs of hydrocephalus are enlargement of head circumference, dilated scalp veins, wide open and bulging anterior fontanel, separated suture lines, positive Macewen sign (cracked-pot sound (resonance)) and “setting sun” sign, sluggish pupils, high pitched cry and delay of developmental milestones; lethargy, irritability and vomiting are late signs. When an infant's head circumference exceeds the ninety eighth percentile for normal head size, a CT scan is the diagnostic procedure of choice.

Hydrocephalus is treated by diverting the ventricular CSF to the abdomen (ventriculoperitoneal shunt) or to the heart (ventriculoatrial shunt). The intellectual potential of children with hydrocephalus is related to the etiology (e.g., infection or intraventricular hemorrhage or premature birth). The severity of hydrocephalus, as measured by the thinness of the cortical mantle, influences development less than the associated cerebral injury. The mean intelligence quotient (IQ) of children with hydrocephalus of all etiologies is lower than that of the general population, but the range includes many normal children. Verbal IQ scores tend to be better than performance IQ scores in individuals with hydrocephalus.

Hydrunencephaly (absence of the cerebral mantle) is a major anomaly of the cerebrum caused by injury during the prenatal period. The precise etiology is unknown, but the mechanisms may include vascular, infectious, toxic, traumatic, and genetic factors. These infants may look remarkably unaffected at birth, with normal head size and basic primitive reflexes. The head usually begins to enlarge in the early weeks of life, and progression of normal developmental milestones does not occur. CT scan and EEG are necessary to distinguish maximal hydrocephalus from hydrunencephaly.

Microcephaly

The diagnosis of microcephaly we make when a head circumference is 3 SD or more below the mean for sex and age or the one that is not increasing with age.

Etiology. The cause of microcephaly may be chromosomal (genetic) disorders, TORCHS-infections (Toxoplasmosis, Rubella, Cytomegalovirus, Neonatal Herpes Virus, Syphilis and other intrauterine infections), fetal alcohol syndrome, fetal exposure to chemical toxins, medicines and ionizing radiation during the first 2 trimesters, severe malnutrition in early infancy, some metabolic disorders, a head trauma and degenerative central nervous system disorders.

Clinical Findings:

- chest circumference exceeds head circumference in the full term newborn or infant up to 6 months of age;

- there may be marked backward slope of the forehead with the narrowing of the temporal diameter and occipital flattening. This is indicative of hereditary microcephaly;

- there may be present disproportionably large ears, asymmetrical skull, the palate may be high-arched and the teeth may be dysplastic.

Diagnostic tests:

Karyotyping may be informative for a variety of chromosomal and hereditary disorders.

TORCHS-screening is the important diagnostic procedure in this case as well as screening for aminoacid abnormalities.

Skull radiography is administered in case of dysmorphic syndromes and intrauterine infections. CT brain scanning may discover calcification, malformations or brain atrophy.

Erb Palsy.

Erb Palsy is the birth damage of the upper (C 5-6) roots of the brachial plexus.

Etiology: Erb Palsy occurs as a result of traction injury of brachial plexus, secondary to breech delivery or cephalopelvic disproportion.

Clinical manifestation of Erb palsy in newborn are internal rotation of the arm with pronation of the forearm; absent or diminished biceps reflex; absence of Moro reflex but normal grasp and normal forearm strength on the affected side; possible sensory defect over the lateral aspect of the arm.

Cerebral Palsy.

Cerebral Palsy is a nonprogressive disorder of the developing brain characterized by disorders of posture and movement.

Classification. There are 6 forms of cerebral palsy: spastic, athetosis, rigid, ataxia, tremor, and mixed.

Etiology. The precise etiology is unknown. The frequent cause of cerebral palsy is the affection of exogenous or endogenous teratogenic factors during antenatal period. Asphyxia, cardiorespiratory arrest and intraventricular hemorrhage are the most frequent cause of the disease in perinatal period.

The frequency of cerebral palsy is approximately 2 per 1000 live births.

Clinical findings depend on age of a child. Early manifestations are very subtle:

a) feeding difficulties;

b) behavioral disturbances;

c) difficult diapering;

d) asymmetries in movement;

e) persisting primitive reflexes;

f) scissoring;

g) hypo-, hypertonia.

Later presentations include: motor delay, excessive and prolonged primitive reflexes; absent postural responses; asymmetries; hyperreflexia; ankle clonus; contractures; persistent toe walking; pathologic reflexes. Associated deficits are processing impairments, communicative disorders, learning disabilities, mental retardation, strabismus, deafness, and oral motor dysfunction.

Diagnostic tests. Making the diagnosis depends heavily upon birth and developmental histories and multiple physical and neurological examinations over time. CT, EEG or MRI may be informative. Laboratory tests, which must be administered, are urine-screening tests for aminoacid disorders and organic aciduria, chromosomal studies, serum muscle enzymes, muscle biopsy.

http://www.youtube.com/watch?v=p5VNdy7_nIM

Febrile Seizures

Febrile seizures are generalized tonic-clonic seizures usually lasting less than 15 minutes associated with an acute, benign febrile illness. They are the most common seizure disorder of childhood. Their incidence is 3 to 4 %.

Etiology. Cause of febrile seizures is uncertain. Many episodes of febrile seizures occur at upward phase of temperature. They occur in children between 9 months and 6 years but most frequently between 18 months and 3 years.

Clinical Findings.

Febrile seizures usually occur in children with fever 38^o C (102 F) or above. They may be the first manifestations of illness. Febrile seizures have tonic-clonical character and less than 15 minutes duration. No evidence of any disease of the central neurvous system in anamnesis of vitae (developmental history) is present.

Diagnostic tests:

focuses on finding causes for fever;

examination of the cerebral spinal fluid if meningitis is suspected;

EEG;

Treatment of Febrile Seizures

1. Usually seizure activity has ceased by the time the child is examined, if not then anticonvulsant therapy, e.g., diazepam should be given.

2. Measures to reduce body temperature should be taken: -sponging; -antipyretic therapy.

3. Treat underlying infection.

4. 20-30 % children have recurrent febrile seizures.

5. Both short-term and prolonged anticonvulsant prophylaxis for the prevention of recurrent febrile convulsions is controversial.

Seizure Disorder.

Seizure (convulsion) is defined as a paroxysmal involuntary disturbance of the brain function that may be manifested as an impairment or loss of consciousness, abnormal motor activity, behavioral abnormalities, sensory disturbances, or autonomic dysfunction

Etiology. Potential causes of seizure may be a trauma, infection, asphyxia, genetic disorders, biochemical factors, metabolic disorders, intracranial hemorrhage, and intracranial tumors.

Clinical Findings.

There are two kinds of seizures - general and partial.

Partial seizures are caused by abnormal electric discharges. There is no interruption in consciousness with simple seizures; usually impairs with complex seizures.

Simple partial seizures. There are abnormal orderly sequence movements of an arm or a leg (Jacksonian march); consciousness usually maintained; a patient has olfactory or auditory sensations; it may be tachycardia, diaphoresis, flushing, nausea or pallor, vomiting and weakness; a child is anger or fearful, sometimes a patient has hallucinations. The length of seizure is approximately 10 to 20 seconds.

Complex partial seizures: originates in a circumscribed portion of one cerebral hemisphere with an impaired level of consciousness. It may begin with a simple partial seizure and progress to brief unconscious period. Some children have an aura of visual or auditory sensations (unpleasant feelings). It may be nausea, vomiting or weakness. Amnesic automatisms are common features (nondirective walking, running, rubbing objects repetitively). The length of seizure is approximately 1 to 2 minutes.

Generalized seizures. Bilateral cerebral cortical involvement is always accompanied by some degree of unconsciousness. There are five types of generalized seizures: absence, generalized tonic-clonic seizures, myoclonic seizures, atonic seizures and infantile spasms.

Absence (petit mal) is a brief period of unconsciousness (lasting seconds) with cessation of any motor activity; transient staring episode may be an only manifestation. It also may look as “lip smacking” or eye blinking. Often mistaken as learning disability, inattention or behavioral problem. It may occur several times a day. It is uncommon prior to age 5 years and is more common in girls.

Generalized tonic-clonic (grand mal) is the most common seizure; it may be preceded by an aura. Tonic phase is characterized by rigidity, extension of the extremities and fixed jaws; cessation of respirations, non-reactive dilated pupils. It usually lasts less than 1 minute. Clonic phase follows tonic phase and is characterized by the rhythmic jerking of all the extremities; expiratory grunts may be evident in addition to bowel and bladder incontinence, it usually lasts several minutes, but can vary. Postictal phase - semiconscious initially and may sleep for a few minutes to several hours. May be associated with visual and speech difficulties. May awaken with severe headache, fatigue and generalized muscle soreness. May be precipitated by infections, fatigue, fever, stress, and drugs.

Myoclonic seizures are generalized brief abrupt muscle contractions with duration of a few seconds; seizures may be clustered with several in one day or can be seizure-free for weeks.

http://www.youtube.com/watch?v=8bsmlX82X24

Atonic seizures are sudden loss of muscle tone with possible loss of consciousness; may cause a child to drop to the floor (“drop attacks”).

Infantile spasms are brief flexions of the neck, trunk and or legs lasting for a few seconds. May experience hundreds each day. Infantile spasms are rare disorder with onset during the first year of life (peak age of onset is between ages 4 and 12 months). Prognosis for normal development is poor.

Diagnostic tests: complete neurological examination and physical examination, EEG, CT scan, MRI, SPECT, PET, neuropsychological testing.

Tic Disorders.

Tic disorders are abrupt, brief, involuntary, repetitious, stereotyped movements or vocalization, they ranging from mild, transitory condition to complex, persistent, disabling set of behaviors.

There are two types of tic disorders:

transient tic disorders (retrospective diagnosis), duration of tics for less than 1 year, occurs in 5 to 24 % of school children;

chronic tic disorders present for more than 1 year.

Etiology. The cause of tic disorders is unknown. Chronic tics are related to an inherited neurochemical imbalance. Transient tics are commonly related to stress.

Clinical Findings:

a) facial tics - eye blinking, nose twitching, lip licking, grimacing etc;

b) complex tics - finger snapping, jumping, hitting, and skipping;

c) vocal tics - throat clearing, barking, grunting, coughing, humming, echolalia, coprolalia.

Characteristic of tic - have wax and wane, worsen during stress, change over time, occur while awake and asleep.

http://www.youtube.com/watch?v=Nf6WkZAH84w

CENTRAL NERVOUS SYSTEM INFECTIONS

General Considerations

There are few areas of clinical medicine in which early recognition of signs and symptoms of disease, appropriate use of diagnostic studies, and prompt institution of specific medical intervention are of greater importance than with infections of the central nervous system. Despite improvements in diagnostic methods and the advent of more effective antibiotics, infections of the central nervous system remain a significant source of childhood morbidity and mortality, particularly in infants and children under 3 years of age in whom immunologic defense mechanisms are less well developed and clinical signs more protean.

Acute Meningitis

Acute meningitis is the most common bacterial infection of the central nervous system in childhood.

Etiology.

The most common causes of meningitis are bacterial pathogens (group B Streptococci, gram-negative enteric bacilli (Klebsiella, Enterobacter, and Serratia species), Escherichia coli, Listeria monocytogenes, Haemophilus influenzae type b, Neisseria meningitidis, Streptococcus pneumoniae); viral agents; rare fungal, tuberculosis, and spirochetes pathogens.

Pathogenesis

Colonization or infection of the upper respiratory tract with the bacteria responsible for meningitis occurs at some time or another in the majority of otherwise normal infants and children. In most children who have respiratory tract infection with these organisms, symptoms are either mild or inapparent. In a few, however, infection of a respiratory focus leads to invasion of the blood. For unknown reasons, some children fail to clear the bloodstream of these organisms, and seeding of the meninges occurs. From this focus, infection ensues with subsequent development of characteristic clinical features of acute inflammation of the meninges and brain.

Signs and Symptoms

Beyond the newborn period, the highest age-specific attack rates occur between 3 and 8 months. The incidence remains high, however, up to 4 years of age. Signs and symptoms of bacterial meningitis are largely dependent on the age of the child and duration of illness prior to initiation of definitive therapy.

Infants under 1 month of age tend to exhibit irritability, lethargy, unusual cry, seizure, poor feeding, and vomiting. High fever and signs of meningeal irritation may be absent.

Meningitis in infants older than 4 months typically produces fever, stiff neck, irritability and seizures, and signs of increased intracranial pressure, including a bulging anterior fontanel, vomiting. As a result of the rapidity of onset, funduscopic changes are usually absent at the time of diagnosis. Papilledema early in the course of therapy is sufficiently unusual to suggest the possibility of complications such as thrombosis of a venous sinus, a large subdural effusion, brain abscess, or hydrocephalus.

Symptoms of headache, muscle and back pain, stiff neck, and photophobia can often be elicited in older children. In addition to resistance of the neck to forward flexion, other signs of meningeal irritation include Kernig sign and Brudzinski sign. Kernig sign consists of resistance and pain on extension of the leg at the knee with the patient on his back and the hips flexed perpendicular to the trunk. Brudzinski sign consists of spontaneous flexion of the knee and hip provoked by passive flexion of the neck. Other manifestations of systemic bacterial infection include pneumonia, pericarditis, otitis media, septic arthritis, and buccal cellulites, skin eruptions ranging from maculopapules to petechiae and purpura; cranial nerve involvement.

Brudzinski sign

Step 1 Step 2

Kernig sign

Step 1 Step 2

Diagnostic tests.

Funduscopy;

Lumbar puncture and examination of cerebrospinal fluid;

Blood cultures;

Cultures of the nose and throat;

CT scan.

Table

Common cerebrospinal fluid finding in meningitis

Determination	Normal Range	Syndrome meningism	Viral meningitis	Bacterial meningitis
colour	colourless	colourless	colourless	milk, greenish
transparency	transparent	transparent	transparent	turbid
Cells count (in 1 ml) lymphocytes neutrophils	1-3 80-85 % 3-5 %	1-3 80-85 % 3-5 %	20-1000 80-100 % 0-20 %	1000-15000 0-60 % 40-100 %
protein	0,16-0,24 g/l	0,16-0,45 g/l	0,33-1,0	0,66-16,0
Pandi reaction	“-”	“-”	“+“, “++”	“+++“, “++++”
cerebrospinal pressure	130-180	200-250	200-300	200-300

Cerebrospinal fluid finding examination

Initial CSF studies should include cell count (WBCs and RBCs) and differential cell count. Approximately 60% of the WBCs may be polymorpho-nuclear leukocytes. By 1 month of age counts fall to 10 WBCs/mm³ or less. The presence of one or more polymorphonuclear (PMN) leukocytes/ mm³ may be considered abnormal, although a single PMN leukocyte may be seen in 5% of normal children without meningitis. Higher numbers of WBCs may be considered abnormal although not always indicative of meningitis. Other conditions leading to elevated WBC counts in the CSF include resolving subarachnoid hemorrhage, previous injection of myelography contrast, intrathecal medication, and neurosurgical procedures.

CSF glucose and protein concentrations should be measured and serum glucose level obtained for comparison. The CSF glucose concentration should normally be about 66% of a simultaneously obtained serum glucose level. CSF protein concentration may be spuriously elevated by blood introduced into the specimen either during or before the lumbar puncture. The level of CSF protein in normal individuals beyond the second month of life is less than 40 mg/dl.

Smears of centrifuged CSF should be Gram-stained and, when indicated, stained for mycobacteria. CSF should be cultured on a blood agar plate, a chocolate agar plate, and in broth. Additional cultures and agglutination and antigen studies may also be appropriate, depending on the clinical picture.

In certain patients, the initial examination of CSF does not distinguish between bacterial meningitis and a viral process. In such cases the WBC count is less than 1000/mm³, 60% to 70% of the cells are polymorphonuclear, the CSF glucose concentration is normal, and the Gram-stained smear is negative.

Lumbal puncture

Bedside Ultrasonography for Lumbar Puncture 

Overview

Lumbar puncture is a common emergency department procedure used to obtain information about the cerebrospinal fluid (CSF) for diagnostic and, less commonly, therapeutic reasons. Please refer to the full article on Lumbar Puncture for more details on the lumbar puncture procedure.

Lumbar puncture is typically performed via “blind” surface landmark guidance. The surface landmark technique is reported to be successful in a high percentage of attempted lumbar punctures; however, surface landmark identification of underlying structures has been shown to be accurate only 30% of the time.Unsuccessful identification of proper landmarks often leads to increased difficulty in obtaining CSF, if the procedure is performed, and a higher rate of complications. Few alternatives are available in these cases. If available, fluoroscopic-guided lumbar puncture may be performed. If not, treatment is sometimes initiated empirically without obtaining CSF. Disadvantages of using fluoroscopy include limited availability or necessary transport of the patient outside of the emergency department, inability to directly visualize the spinal canal, and inherent radiation exposure.

However, the use of bedside ultrasonography for the identification of the pertinent landmarks for lumbar puncture is a safe and easy alternative to the blind technique.Additionally, ultrasound may be used in advance of attempted lumbar puncture in order to predict ease of performance or anticipated difficult lumbar puncture.Ultrasound-guided lumbar puncture was originally reported over 30 years ago in Russian literature, and it is routinely used by many anesthesiologists for epidural and spinal anesthesia.

Ultrasound-guided lumbar puncture is most helpful in those patients in whom surface landmark–guided lumbar puncture is difficult (eg, patients who are obese or have spinal disorders). According to recent studies, bedside ultrasonography helped operators identify the pertinent landmarks for lumbar puncture approximately 75% of the time in obese patients.It is an available and helpful modality that can decrease the number of attempts and minimize complications.Ultrasonographic guidance has been shown to increase the overall success rate of lumbar puncture and to reduce the operator's perceived difficulty of performing the procedure. This is particularly true in patients with a body mass index (BMI) of 30 or more.

Additionally, studies in neonates and children have used bedside ultrasonography to attempt to determine optimal positioning for lumbar puncture. Using ultrasound to measure the interspinous space at L3-L4 and L4-L5 in varying positions, the lumbar spine was found to be maximally positioned in both neonates and children in the seated position with flexed hips versus the lateral recumbent position with neck flexion.A study in adults would be needed to make a similar recommendation regarding optimal position for lumbar puncture; however, the sitting position may be optimal in adults as well as children.

Indications

• Ultrasonographic guidance may be beneficial in all patients who require lumbar puncture.
• Ultrasonographic guidance is most helpful in those patients in whom lumbar puncture is challenging because of the inability to adequately palpate necessary landmarks (eg, patients who are obese or have spinal disorders).

Contraindications

• Ultrasonography is safe and painless, with virtually no inherent risks.

Anesthesia

• No anesthesia is required when using bedside ultrasonography to identify appropriate landmarks.
• Local anesthesia is, however, required prior to performing the actual lumbar puncture. Equipment

• Ultrasound machine with a high-frequency 5-10 MHZ probe (small parts probe) for use on patients with normal weight and a low-frequency 2-4 MHZ probe (abdominal probe) for use on patients with elevated body mass index (BMI)
• Transducing gel
• Sterile or other skin marking pen
• Equipment needed for the lumbar puncture itself

Positioning

• The lateral decubitus or sitting position may be used, depending on the patient's status and provider preference.
• The patient remains in the selected position during ultrasonographic identification of landmarks and the lumbar puncture procedure.

Technique

Position the patient as described above.

To find the interspinous space, place the ultrasound probe with the probe marker toward the clinician's left side in the transverse plane over the midline of the back at the level of the iliac crests, as shown below.

Ultrasound probe in transverse position.

In this view, the spinous processes appear as distinct hyperechoic structures with associated acoustic shadows. Identifying the spinous processes identifies the midline of the spine. Centering this shadow on the screen places the probe directly over the midline of the spine, as shown below.

Transverse ultrasound image of the lumbar spine demonstrating a midline dorsal spinous process. Note its characteristic crescent-shaped, hyperechoic spine with posterior acoustic shadowing.

With the probe in the position described above, mark the midline of the spine at the center of the probe using a surgical marker or pen. Then drag the probe superiorly or inferiorly to the next spinous process and again mark the midline of the spine. Make marks appropriately large and visible so that they can be easily located and extended once the ultrasound probe is removed. Although these ultrasound images are obtained in the transverse plane, these markings are made and connected in the sagittal plane.

Next, rotate the transducer into the sagittal (or longitudinal) plane with the probe marker pointing toward the patient's head. The probe should be parallel to the direction of the spine and placed directly between the spinous processes that were just marked, as depicted in the image below.

Ultrasound probe in sagittal position.

The spinous processes are seen as crescent-shaped, hyperechoic, upward convexities occurring at the same depth as the shadowing noted on the transverse view, as shown below. The gap between the hyperechoic convexities is the interspinous space.

Sagittal view of the interspinous space. The superior dorsal spinous process is seen on the left side of the image while the inferior dorsal spinous process is seen on the right side of the image. The acoustic shadows generated define the superior and inferior borders of the interspinous space.

Center the interspinous space on the screen and then mark the level of the middle of the interspinous space on both sides of the probe. Since the probe is in the sagittal plane, these marks are made in the transverse plane, slightly to the left and right of the center of the probe. Again, make the marks appropriately large and visible so that they can be easily located and extended.

Remove the ultrasound probe and extend the transverse and sagittal skin markings until they intersect. The point of intersection of these lines represents the middle of the interspace and the most ideal location at which to insert the lumbar puncture needle, as depicted below.

Final patient markings.

Instruct the patient not to move after ultrasonographic landmark identification. Take care to perform the lumbar puncture procedure immediately after marking out the middle of the interspinous space. If the patient moves substantially, the ultrasound-guided markings may be less accurate or helpful. If the patient moves substantially, consider repeating the above technique and making repeat markings on the patient.

Pearls

• Use alcohol to clean the area before attempting to mark the skin. This eliminates ultrasound conducting gel and natural skin oils that may lessen or obscure the ink.
• Use permanent or semi-permanent skin markers so that marks are not removed when the area is later prepared for the sterile lumbar puncture.
• If the area is to be sterilized before the appropriate landmarks are identified with ultrasonography, then the use of a sterile probe cover and sterile marking pen are required.

Complications

• Use of bedside ultrasonography to identify pertinent landmarks poses virtually no risks or complications.
• Possible limitations include lack of ultrasound machine availability and the time required by clinicians to develop the comfort and skill necessary to perform ultrasound-guided procedures.

Anencephaly

Overview

Anencephaly is a serious developmental defect of the central nervous system in which the brain and cranial vault are grossly malformed. The cerebrum and cerebellum are reduced or absent, but the hindbrain is present. Anencephaly is a part of the neural tube defect (NTD) spectrum. This defect results when the neural tube fails to close during the third to fourth weeks of development, leading to fetal loss, stillbirth, or neonatal death.

Anencephaly, like other forms of NTDs, generally follows a multifactorial pattern of transmission, with interaction of multiple genes as well as environmental factors, although neither the genes nor the environmental factors are well characterized. In some cases, anencephaly may be caused by a chromosome abnormality, or it may be part of a more complex process involving single-gene defects or disruption of the amniotic membrane. Anencephaly can be detected prenatally with ultrasonography and may first be suspected as a result of an elevated maternal serum alpha-fetoprotein (MSAFP) screening test. Folic acid has been shown to be an efficacious preventive agent that reduces the potential risk of anencephaly and other NTDs by approximately two thirds.

Pathophysiology

In the normal human embryo, the neural plate arises approximately 18 days after fertilization. During the fourth week of development, the neural plate invaginates along the embryonic midline to form the neural groove. The neural tube is formed as closure of the neural groove progresses from the middle toward the ends in both directions, with completion between day 24 for the cranial end and day 26 for the caudal end. Disruptions of the normal closure process give rise to NTDs. Anencephaly results from failure of neural tube closure at the cranial end of the developing embryo. Absence of the brain and calvaria may be partial or complete.

Most cases of anencephaly follow a multifactorial pattern of inheritance, with interaction of multiple genes as well as environmental factors. The specific genes that are most important in NTDs have not yet been identified, although genes involved in folate metabolism are believed to be important. One such gene, methylenetetrahydrofolate reductase (MTHFR), has been shown to be associated with the risk of NTDs. In 2007, a second gene, a membrane-associated signaling complex protein called VANGL1, was also shown to be associated with the risk of neural tube defects.

A variety of environmental factors appear to be influential in the closure of the neural tube. Most notably, folic acid and other naturally occurring folates have a strong preventive effect. Folate antimetabolites, maternal diabetes, maternal obesity, mycotoxins in contaminated corn meal, arsenic, and hyperthermia in early development have been identified as stressors that increase the risk of NTDs, including anencephaly.

Causes

Anencephaly is usually an isolated birth defect and not associated with other malformations or anomalies. The vast majority of isolated anencephaly cases are multifactorial in their inheritance pattern, implicating multiple genes interacting with environmental agents and chance events.

Inadequate folic acid

Adequate folic acid consumption during pregnancy is protective against anencephaly. Exposure to agents that interfere with normal folate metabolism during the critical period of neural tube development (up to 6 weeks after last menstrual period) increases the likelihood of an NTD.

Valproic acid, an anticonvulsant, and other antimetabolites of folic acid have been shown to increase the chance of an NTD when exposure occurs in early development. While these induced NTDs are usually spina bifida, the chance of anencephaly is probably increased as well.

IDDM

Maternal type 1, or pregestational insulin-dependent diabetes mellitus (IDDM), confers a significant increase in the risk for NTDs, and it also delays production of alpha-fetoprotein (AFP) during pregnancy. Maternal serum AFP is used as a screening test to detect NTDs, and adjustment of the expected values for AFP in maternal serum must be made if the patient is known to have IDDM. Presumably, well-controlled IDDM confers a lower risk for NTDs, while gestational diabetes does not appear to be associated with any significant increase in NTD risk. The degree of diabetic control is generally monitored using hemoglobin A1c levels.

Maternal hyperthermia

Maternal hyperthermia has been associated with an increased risk for NTD; therefore, pregnant women should avoid hot tubs and other environments that may induce transient hyperthermia. Similarly, maternal fever in early gestation also has been reported as a risk factor for anencephaly and other NTDs.

Genetics

While most NTDs are associated with a multifactorial model of inheritance, rare cases of NTDs are transmitted in an autosomal dominant or autosomal recessive manner in certain families. Such families may have children or fetuses with spina bifida, anencephaly, or other subtypes of NTDs. In families with a pedigree suggestive of autosomal dominant inheritance, reproduction is clearly only possible for the individuals with spina bifida, since death occurs early in the life of individuals with anencephaly.

Anencephaly may be associated with the unbalanced form of a structural chromosome abnormality in some families. In these cases, other malformations and birth defects that are not usually found in isolated cases of anencephaly may be present.

Amniotic band disruption sequence

Amniotic band disruption sequence is a condition resulting from rupture of the amniotic membranes. This can cause disruption of normally formed tissues during development, including the structures of the head and brain. Anencephaly caused by amniotic band disruption sequence is frequently distinguishable by the presence of remnants of the amniotic membrane. Recurrence risk for anencephaly caused by this mechanism is lower, and the risk is not modified by the use of folic acid.

Epidemiology

Considerable geographical variation in neural tube defects (NTDs) rates exists, with noted hot spots in Guatemala, northern China, Mexico, and parts of the United Kingdom. Hispanic and non-Hispanic whitesare affected more frequently than women of African descent , and females are affected more frequently than males. Anencephaly is determined by the 28th day of conception and is therefore invariably present at the time of birth.

In the United States, the average birth prevalence of anencephaly is approximately 1.2 per 10,000 births, with a gradient of increasing frequency from the West Coast to the East Coast. The frequency during pregnancy is considerably higher than the birth prevalence, with estimates as high as 1 case per 1000 pregnancies. Such pregnancies often end in early pregnancy loss, spontaneous abortion, fetal death, or pregnancy termination.

Within the United States, South Carolina has historically reported the highest birth prevalence of NTDs, with a rate that has been approximately double that of the national average. The rate of NTDs in South Carolina has fallen dramatically following the introduction of aggressive campaigning for periconceptional folic acid supplementation, fortification of wheat flour, and increased periconceptional vitamin supplementation.The reason for a higher occurrence of NTDs in South Carolina compared with other areas of the country is not known.

In 1990-1991, a cluster of NTDs was reported in Brownsville, Texas.This primarily Hispanic population was targeted for surveillance as well as an intensive folic acid supplementation campaign directed at prevention of recurrences. Since that time, it has been generally accepted that the Hispanic population has an increased risk of anencephaly and other NTDs compared with other racial/ethnic populations in the United States, although the reasons have not been identified.

In families that have previously experienced a pregnancy affected with anencephaly, the use of folic acid supplements at a dose 10 times higher than what is generally advised for the general population (4 mg/day vs 400 mcg/day) is recommended. In the South Carolina study, more than 300 pregnancies have been followed from women with a prior NTD-affected pregnancy who received the higher dose of folic acid supplements as part of the follow-up program with no recurrences of NTDs observed.

Study of NTDs in the United States by the Centers for Disease Control and Prevention shows a significant reduction of anencephaly and other NTDs following the introduction of fortification of wheat flour with folic acid. During the period of 1996-2001, there was a 23% decline in spina bifida and anencephaly combined, with spina bifida declining by 24% and anencephaly by 21%.

Prognosis

Anencephaly is lethal in all cases because of the severe brain malformation that is present. A significant proportion of all anencephalic fetuses are stillborn or are aborted spontaneously.

The neonate's prognosis when born alive is exceptionally poor; death of a live child is unavoidable and most often occurs during the early neonatal period.

History and Physical Examination

Anencephaly is readily apparent at birth because of the absence of the cranial vault and portions of the cerebrum and cerebellum. Facial structures are generally present and appear relatively normal. The cranial lesion occasionally is covered by skin, but usually it is not. When the lesion is covered with skin, prenatal screening using maternal serum alpha-fetoprotein (MSAFP) is ineffective. Babies are frequently stillborn, and spontaneous abortion during pregnancy is common. Although the features of anencephaly are readily evident, physical examination for anomalies not related directly to the anencephaly is indicated to evaluate the possible need for cytogenetic studies. When additional malformations are present, the likelihood of cytogenetic abnormalities is increased.

Lab Studies

Maternal serum alpha-fetoprotein (MSAFP) screening during the second trimester of pregnancy is an effective screening tool for identification of the vast majority of cases of anencephaly in women with or without a positive family history or other risk factors for neural tube defects.

Amniotic alpha-fetoprotein (AFAFP) testing during the late first trimester and second trimester of pregnancy is a diagnostic biochemical test for anencephaly. False positives from AFAFP can be excluded based on the results of testing for acetylcholinesterase (ACHE), which should be clearly positive for open anencephaly.

Laboratory studies are not performed postnatally in most cases of isolated anencephaly. Cytogenetic testing can exclude trisomy 13 as well as unbalanced structural chromosome abnormalities.

Imaging Studies

Prenatal 2-dimensional ultrasonography has steadily improved over the years and has superseded maternal serum alpha-fetoprotein measurements as a screening tool. Since ossification of the cranial vault is not consistently apparent prior to the completion of the 12th week of pregnancy, anencephaly should not be diagnosed by ultrasonography any earlier than this.

In the first trimester, absent calvarium, reduced crown-rump length, absent or exposed neural tissue with lobular appearance (exencephaly), and absence of the normal head contour geometry with the orbits demarcating the upper border of the face (coronal view) are associated with anencephaly. Later in pregnancy, polyhydramnios may arise as a result of reduced swallowing of the amniotic fluid.

Postnatal MRI findings have included absence of the cranial vault, supretentorial structures, and the cerebellum.

Treatment & Management

Because anencephaly is a lethal condition, heroic measures to extend the life of the infant are contraindicated. The physician and medical care team should focus on providing a supportive environment in which the family can come to terms with the diagnosis and make preparations for their loss.

Families who are not aware of the diagnosis of anencephaly prior to birth or for whom the diagnosis is still fresh probably will need extra emotional support and possibly grief counseling. Families who have had some time to adjust to the diagnosis prior to delivery and who have had an opportunity to begin the grieving process ahead of time may seem well prepared, but they also will need adequate time to grieve and come to closure. The presence of family, friends, or clergy may be helpful in many cases.

Families often want to hold the baby after delivery, even if the baby is stillborn, and families wanting photographs of the baby with the family are not unusual. A cap or head covering of some sort is useful to minimize the visual impact of the malformation. Some families want to see the lesion, and this may help to dispel mental pictures, which are often worse than the actual malformations. In most cases, direct personal contact with the baby may help the parents to actualize the medical information they have been given and may help in the process of grief resolution.

If parents have chosen a name for the baby, they may be comforted if the doctor refers to the baby by name.

Feelings of guilt are normal responses of parents of a baby with serious birth defects. The involvement of genetic counselors, if available, may be particularly useful to parents in this situation because of their experience in dealing with a wide range of birth defects.

With timely prenatal diagnosis of this lethal disorder, the option of pregnancy termination should be presented to the couple. For couples who elect to continue the pregnancy, the possibilities of preterm labor, polyhydramnios, failure to progress, and delayed onset of labor beyond term also should be discussed.

Families commonly inquire about organ donation after the diagnosis of anencephaly. This cannot practically be arranged without crossing the lines of ethical care. Patients should be affirmed in their desires to see something meaningful come from the tragedy of having a pregnancy affected with anencephaly.

Pregnancy care

All patients diagnosed prenatally with a fetus affected by anencephaly should be offered a consultation with a care provider who is skilled in delivering grave information and is knowledgeable about recurrence risk, prevention, screening, and diagnostic testing options for future pregnancies.

Although a geneticist or genetics counselor is an ideal source and may be best suited for exploring family history, an experienced maternal fetal medicine physician or properly trained obstetrician may provide requisite information, especially in regions of the United States where there are inadequate numbers of geneticists or genetic counselors. Specific information related to the management of an ongoing pregnancy should be discussed during this consultation.

Once a diagnosis of anencephaly is made, pregnancy management varies according to the gestational age at diagnosis. At pre-viable gestational ages, the option of pregnancy termination should be among those discussed. The gestational age limits for this procedure are state specific and subject to the training and skill of the physician available to perform the pregnancy termination.

When patients choose not to proceed with pregnancy termination or when the pregnancy has progressed to a viable gestational age such that pregnancy termination is no longer an option (except in rare locations throughout the United States), attention should be focused on whether the labor will be induced or spontaneous and, if the former, at what gestational age.

Due to the physical stresses of pregnancy compounded by the emotional stress of carrying a fetus with a lethal birth defect, or because of the identification of medical conditions (eg, preeclampsia) that may complicate any pregnancy, labor induction may be considered.

Focused discussions directed at neonatal resuscitation efforts should be held in advance of labor. These discussions should include a discussion of neonatal procedures used to resuscitate neonates, the cost of these measures, and alternatives to aggressive resuscitation. It is often best to include a neonatologist in these discussions. Clear documentation of these discussions is warranted. When delivery is planned in a hospital setting, labor and delivery nurses, obstetric care providers, and pediatric/neonatal attendants should be informed of the patient’s wishes for her child.

Because of the lethal nature of this condition, tocolysis (medical management to reduce uterine contractions) in an effort to prevent preterm birth is not a reasonable option, nor is cesarean delivery.

The pregnancy management of a child with lethal and nonlethal birth defects can be complicated by available resources. In addition to having a wealth of experience in dealing with grieving patients, some delivering hospitals are vastly more experienced in the management of pregnancies complicated by known lethal fetal birth defects. For this reason we recommend that babies with anencephaly be delivered at such centers, when possible.

Consultations

Every couple with a child who has anencephaly should consult with a geneticist and/or a genetic counselor to obtain information regarding recurrence risks, prevention, screening, and diagnostic testing options for future pregnancies and to assess the family history. Ideally, a genetic counselor should be consulted prenatally and should remain involved, as needed, until the family comes to closure after the conclusion of the pregnancy. Genetic counselors are trained and are general skillful in helping a family work through the complex psychosocial issues that are commonly encountered in a new diagnosis of anencephaly.

Diet

Folic acid supplementation and/or a folate-enriched diet prior to and during future pregnancies are recommended. Obtaining enough folates from diet alone to effectively prevent recurrences in future pregnancies is extremely difficult.

Prevention

The recurrence risk for NTDs, in general, is 2-4% in subsequent pregnancies. For families with multiple occurrences of NTDs, recurrence risks may be higher and must be determined on a case-by-case basis.

Folic acid supplementation has been shown to be an effective means of lowering recurrence risks for future pregnancies. For women who desire pregnancy and have had a child with an NTD with their current partner, supplementation with 4 mg of folic acid daily is indicated, beginning at least 3 months prior to conception.

For all other women and girls of reproductive age, regardless of family history, 0.4 mg (or 400 mcg) per day of folic acid supplementation is appropriate; this amount of folic acid is found in most over-the-counter multivitamins. Folic acid supplementation at these levels is estimated to prevent two thirds of both recurrent and new cases of NTD.

Increased folate intake also may be achieved through diet; however, the bioavailability of natural folates in foods is often lower than that of folic acid. In the United States, wheat flour is fortified with a small amount of folic acid, but it is not enough to achieve maximal preventive benefits against NTD for a woman with an average diet.

Because of the large number of pregnancies that are not actively planned and the early gestational age at which neural tube development occurs, folate supplementation should be encouraged for all girls, beginning at puberty, in order to establish this practice before entering the childbearing years.

Prenatal ultrasound and amniocentesis should be offered to any couple with a prior pregnancy affected with an NTD. Maternal serum prenatal screening with AFP is available throughout the United States and most developed countries for identification of NTDs. Positive serum screening should be followed with diagnostic testing to exclude the presence of NTDs. Since 90-95% of NTDs occur in families without a positive history, such screening is appropriate for all pregnant patients and should not be reserved only for those with a positive history.

Anencephaly cannot be treated in utero; thus, pregnancy termination is the only intervention available to prevent the birth of a child with anencephaly that has been diagnosed prenatally. Supportive care should be provided for families, irrespective of the option they choose.

Complications

Anencephaly is uniformly fatal. Polyhydramnios is a common complication during pregnancy, and patients may experience significant discomfort from the abdominal distention that accompanies this condition. Risk of preterm labor is increased.

Because the pituitary gland may be absent in persons with anencephaly, spontaneous precipitation of labor may be delayed; therefore, the risk of the pregnancy progressing into the postterm period is significant. Labor may need to be induced in these cases. The rate of abnormal fetal presentations during delivery is increased.

Neonatal Meningitis 

Background

Despite the development of effective vaccines, useful tools for rapid identification of pathogens and potent antimicrobial drugs, neonatal meningitis continues to contribute substantially to neurological disability worldwide.

The persistence of neonatal meningitis results from increases in the numbers of infants surviving premature delivery and from limited access to medical resources in developing countries. In addition, the absence of specific clinical findings makes diagnosis of meningitis more difficult in neonates than in older children and adults. Moreover, a wide variety of pathogens are seen in infants as a consequence of the immaturity of their immune systems and intimate exposure to possible infection from their mothers.

This review focuses on common presentations of treatable bacterial and viral meningitis in the neonatal period, defined as the period from birth to 44 weeks after conception. Common central nervous system (CNS) infections caused by bacteria and viruses (eg, herpes simplex virus [HSV]) are emphasized. Meningitides caused by HIV and fungi are excluded, as are those caused by other organisms implicated in congenital CNS damage (eg, cytomegalovirus [CMV] and Toxoplasma).

Pathophysiology

Neonates are at greater risk for sepsis and meningitis than other age groups are because of the following deficiencies in humoral and cellular immunity and in phagocytic function:

• Infants younger than 32 weeks’ gestation receive little of the maternal immunoglobulin received by full-term infants
• Inefficiency in the neonates’ alternative complement pathway compromises their defense against encapsulated bacteria
• T-cell defense and mediation of B-cell activity are also compromised
• Deficient migration and phagocytosis by neutrophils contribute to neonatal vulnerability to pathogens of even low virulence

Etiology

Common bacterial pathogens

Among US neonates, group B streptococci (GBS) are the most commonly identified causes of bacterial meningitis, implicated in roughly 50% of all cases. Escherichia coli accounts for another 20%. Thus, identification and treatment of maternal genitourinary infections is an important prevention strategy.Listeria monocytogenes is the third most common pathogen, accounting for 5-10% of cases; it is unique in that it exhibits transplacental transmission.

Studies suggest that in underdeveloped countries, gram-negative bacilli—specifically, Klebsiella organisms and E coli —may be more common than GBS. In a series from Africa and South Asia, Tiskumara et al noted that 75% of cases of late-onset meningitis were due to gram-negative bacilli.In a review of studies from Asia, Africa, and Latin America, Zaidi et al reported that the most common organisms were Klebsiella species, E coli, and Staphylococcus aureus.

With the widespread use of intrapartum antibiotic prophylaxis since 1996 in developed countries, the incidence of early-onset GBS infection has decreased, whereas the incidence of late-onset disease has remained fairly constant.However, from 2003 to 2006, the Centers for Disease Control and Prevention (CDC) reported a slight increase in early-onset disease in the United States, particularly in the African American population; the reasons for this are unclear.

Herpes simplex virus

As many as 95% of viral infections caused by HSV result from intrapartum transmission, with occasional postnatal exposure occurring through oropharyngeal shedding or cutaneous shedding of virus by parents or hospital contacts. Late presentation in the second postnatal week is more commonly seen than early presentation of disseminated disease.

Emerging pathogens

As cases of neonatal enteroviral sepsis and aseptic meningitis come to be more frequently recognized, reporting and identification of more virulent serotypes as they affect infants are likely to play a growing role.As many as 12% of neonates may be infected with this family of viruses. Although many of these babies are asymptomatic, enterovirus may be responsible for as many as 3% of neonates who present with a sepsislike picture.More recently, human parechovirus-3 has been implicated in an increasing number of neonates with meningitis. While related to the enterovirus family, this pathogen is not detected with enteroviral polymerase chain reaction (PCR) studies performed on cerebrospinal fluid (CSF).

Enterobacter sakazakii has been identified as an emerging pathogen in neonates. This bacterium is most typically associated with the ingestion of contaminated reconstituted formula. It has been reported with increasing frequency in the past few years, prompting the US Food and Drug Administration (FDA) to publish warnings of possible contamination of dried formula.

Epidemiology

In industrialized countries, the incidence of bacterial meningitis is approximately 0.3 per 1000 live births.The incidence of HSV meningitis is estimated to be 0.02-0.5 cases per 1000 live births.Because of testing limitations, the worldwide incidence of neonatal meningitis is difficult to determine with accuracy. However, a study of neonatal infections in Asia (based on data collected from China, Hong Kong, India, Iran, Kuwait, and Thailand) reported estimated incidences of neonatal meningitis that ranged from 0.48 per 1000 live births in Hong Kong to 2.4 per 1000 live births in Kuwait.Another publication that looked at neonatal infections in Africa and South Asia reported figures ranging from 0.8 to 6.1 per 1000 live births.

These numbers are believed to underestimate the true incidence of neonatal meningitis in underdeveloped countries, given the lack of access to health care facilities in these areas.

Prognosis

Survivors of neonatal meningitis are at significant risk for moderate to severe disability. Some 25-50% have significant problems with language, motor function, hearing, vision, and cognition; 5-20% have future epilepsy.Survivors are also more likely to have subtle problems, including visual deficits, middle-ear disease, and behavioral problems.As many as 20% of children identified as normal at 5-year follow-up may have significant educational difficulties lasting into late adolescence.

Poor prognostic indicators include low birth weight, prematurity, significant leukopenia or neutropenia, high levels of protein in the cerebrospinal fluid (CSF), delayed sterilization of the CSF, and coma.Seizures lasting longer than 72 hours and the need for inotropes predict moderate-to-severe disability or death with 88% sensitivity and 99% specificity.

Bacterial meningitis

In developed countries, mortality from bacterial meningitis among neonates declined from almost 50% in the 1970s to less than 10% in the late 1990s. However, a corresponding decrease in morbidity rate did not occur.

In a prospective sample of more than 1500 neonates surviving to the age of 5 years, the prevalence of motor disabilities (including cerebral palsy) was 8.1%, that of learning disability was 7.5%, that of seizures was 7.3%, and that of hearing problems was 25.8%.No problems were reported in 65% of babies who survived GBS meningitis and in 41.5% of those who survived E coli meningitis.

HSV meningitis

Mortality among neonates with HSV infection of the CNS is 15%. Of these cases, 25-40% will have culture-proven CSF infection. The 2 HSV serotypes (HSV-1 and HSV-2) carry the same risk of mortality. However, HSV-2 is more commonly associated with morbidity, including cerebral palsy, mental retardation, seizures, microcephaly, and ophthalmic defects.Although the use of acyclovir has reduced the morbidity and mortality associated with HSV infection, neurological sequelae are likely in 50% of neonates with HSV meningitis.

Pediatric Aseptic Meningitis

Background

Pediatric aseptic meningitis is an inflammation of the meninges caused mainly by nonbacterial organisms, specific agents, or other disease processes. Aseptic meningitis (including viral meningitis) is the most common infection of the central nervous system (CNS) in the pediatric population, occurring most frequently in children younger than 1 year. Despite advances in antimicrobial and general supportive therapies, CNS infections remain a significant cause of morbidity and mortality in children.

Because the classic signs and symptoms are often absent, especially in younger children, diagnosing pediatric CNS infections is a challenge to the emergency department (ED). Even when such infections are promptly diagnosed and treated, neurologic sequelae are not uncommon. Clinicians are faced with the daunting task of distinguishing the relatively few children who actually have CNS infections from the vastly more numerous children who come to the ED with less serious infections.

Pathophysiology

Organisms colonize and penetrate the nasopharyngeal or oropharyngeal mucosa, survive and multiply in the blood stream, evade host immunologic mechanisms, and spread through the blood-brain barrier. Infection cannot occur until colonization of the host has taken place (usually in the upper respiratory tract). The mechanisms by which circulating viruses penetrate the blood-brain barrier and seed the cerebrospinal fluid (CSF) to cause meningitis are unclear.

Viral infection causes an inflammatory response but to a lesser degree than bacterial infection does. Damage from viral meningitis may be due to an associated encephalitis and increased intracranial pressure (ICP).

The pathophysiology of aseptic meningitis caused by drugs is not well understood. This form of meningitis is infrequent in the pediatric population.

Etiology

Although many agents and conditions are known to be associated with pediatric aseptic meningitis, often a specific cause is not identified, because a complete diagnostic investigation is not always completed. Viruses are the most common cause, and enteroviruses (EVs) are the most frequently detected viruses. The use of molecular diagnostic techniques (eg, polymerase chain reaction [PCR] assay) has significantly increased diagnostic accuracy.

Viruses

EV is a frequent cause of febrile illnesses in children. Other viral pathogens include paramyxovirus, herpesvirus, influenza virus, rubella virus, and adenovirus. Meningitis may occur in as many as 50% of children younger than 3 months with EV infection. EV infection can occur at any time during the year but is associated with epidemics in the summer and fall.

Viruses associated with aseptic meningitis include the following:

• EV 71, EV 70, EV 75
• Polioviruses types 1, 2, and 3
• Coxsackievirus type A (23 serotypes) and type B (6 serotypes)
• Echoviruses (31 serotypes; see the image below)
• Human parechoviruses (HPeV) (6 serotypes; HPeV types 1 and 2 were previously classified as echovirus types 22 and 23 within the genus Enterovirus)
• Arbovirus (eastern, western, and Venezuelan equine encephalitis viruses; Powassan virus; California group viruses [primarily LaCrosse virus]; St. Louis encephalitis virus; West Nile virus; and Colorado tick fever)
• Mumps virus
• Herpes simplex virus (HSV) types 1 and 2
• Cytomegalovirus (CMV)
• Epstein-Barr virus (EBV)
• Human herpesvirus type 6 (HHV6) and type 7 (HHV7)
• Varicella-zoster virus (VZV)
• Adenovirus types 3 and 7
• Human immunodeficiency virus (HIV)
• Lymphocytic choriomeningitis (associated with contact with guinea pigs, hamsters, and pet mice)
• Rhinovirus
• Measles virus
• Rubella virus
• Influenza A and B viruses, including H1N1
• Parainfluenza virus
• Parvovirus B19
• Rotavirus
• Coronavirus
• Variola virus
• FlavavirusSkin lesions due to echovirus type 9 on neck and chest of young girl. Echoviruses belong to genus Enterovirus and are associated with illnesses including aseptic meningitis, nonspecific rashes, encephalitis, and myositis.

Viral vaccines

Viral vaccines related to aseptic meningitis include the following:

• Mumps vaccine
• Measles-mumps-rubella (MMR) vaccine
• Polio vaccine
• Rabies vaccine
• Yellow fever vaccine

Nonpyogenic bacteria

Certain bacterial infections may give rise to aseptic meningitis (eg, partially treated bacterial meningitis or brain abscess). Nonpyogenic bacteria associated with aseptic meningitis include the following:

• Mycobacterium tuberculosis
• Leptospira
• Treponema pallidum
• Borrelia (relapsing fever, Lyme disease)
• Nocardia
• Bartonella
• Atypical mycobacteria
• Brucella

Other organisms

Atypical organisms associated with aseptic meningitis include the following:

• Chlamydia
• Rickettsia
• Mycoplasma

Parasites associated with aseptic meningitis include the following:

• Roundworms
• Tapeworms
• Flukes
• Amoebae
• Toxoplasma

Fungal meningitis is rare but may occur in immunocompromised patients; children with cancer, previous neurosurgery, or cranial trauma; or premature infants with low birth rates. Most cases occur in children who are inpatients receiving antibiotic therapy. Fungi associated with aseptic meningitis include the following:

• Candida
• Histoplasma
• Cryptococcus

Additional organisms associated with aseptic meningitis include the following:

• Blastomyces dermatitidis
• Coccidioides immitis
• Alternaria species
• Aspergillus species
• Cephalosporium species
• Cladosporium trichoides
• Drechslera hawaiiensis
• Paracoccidioides brasiliensis
• Petriellidium boydii
• Sporotrichum schenckii
• Ustilago species
• Zygomycetes species

Diseases and other conditions or events

Diseases associated with aseptic meningitis include the following:

• Leukemia
• Behçet disease
• Systemic lupus erythematosus (SLE)
• Sarcoidosis
• Sj ö gren syndrome
• Dermoid and epidermoid cysts
• CNS tumor
• Kawasaki disease
• Recurrent benign endothelioleukocytic aseptic meningitis (Mollaret meningitis)
• Neonatal-onset multisystem inflammatory disorder (one of the cryopyrin-associated periodic syndromes [CAPS])

Other conditions or events associated with aseptic meningitis include the following:

• Immunoglobulin replacement therapy
• Heavy metal poisoning
• Intrathecal agents
• Foreign bodies (eg, shunt or reservoir)
• Drugs

Epidemiology

United States Statistics

The incidence of aseptic meningitis in the United States has been estimated to be approximately 75,000 cases per year. Before the introduction of the MMR vaccine program, the mumps virus was the most common cause, accounting for 5-11 of 100,000 cases of meningitis; it now accounts for approximately 0.3 of 100,000 cases, and EV has become the most common cause. In a North American study from 1998-1999, most cases occurred between July and October.

International Statistics

In a university clinic in Mainz, Germany, from 1986-1989, 12 (10.3%) of 117 cases of acute aseptic meningitis were due to the mumps virus, 3 (7.7%) were due to Borrelia burgdorferi, 3 (2.6%) were due to tick-borne encephalitis, and 2 (1.7%) were due to (HSV).Ninety-one (77.8%) cases were due to other causes. Sixty-four percent of cases occurred in the spring and summer.

In a tertiary care children’s hospital in Athens, Greece, 506 cases of aseptic or viral meningitis were reviewed from 1994 through 2002; the estimated annual incidence was 17 cases per 100,000 children younger than 14 years.Most cases occurred during summer (38%) and autumn (24%), and 47 of 96 patients (48.9%) had positive results for enteroviral RNA on CSF polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF).

The Austrian reference laboratory for poliomyelitis received 1,388 stool specimens for EV typing from patients with acute flaccid paralysis or aseptic meningitis between 1999 and 2007; 201 samples from 181 cases were positive for nonpoliomyelitis EV.The mean patient age was 5-6 years, with 90% of cases in children younger than 14 years. Aseptic meningitis was identified in 65.6% of the cases. Echovirus 30 was the most frequent viral cause of aseptic meningitis, due to an epidemic in 2000, followed by coxsackievirus B types 1-6 and EV 71.

Age-related demographics

Aseptic meningitis is more common in children than in adults. In the Mainz study, 69% of the patients were aged 5 years or older,and in the Athens study, the median age was 5 years (range, 1 month to 14 years).However, in a Korean study, a higher incidence was reported in individuals younger than 1 year (10% of total affected) and in individuals aged 4-7 years (44.1%).

Sex-related demographics

Until comparatively recently, no sex predilection had been reported for EV infection, although reactivation of HSV-2 infection occurs mostly in adults (with a female-to-male ratio of 6:1). In the Mainz study, 66% of the patients were male.

A Korean study of 2201 children reported a male-to-female ratio of 2:1.In Japan, an outbreak of aseptic meningitis caused by echovirus type 30 in 54 patients showed a male-to-female ratio of 2.2:1.The Athens study also showed a higher prevalence in males, with a male-to-female ratio of 1.8:1.

Race-related demographics

In a South African study, the median age of white children with aseptic meningitis (64 months) was significantly greater than that of nonwhite children (45 months) and that of black children (26 months).

Prognosis

Full recovery is usual after uncomplicated viral aseptic meningitis. Most cases resolve within 7-10 days.

Recurrence is possible (known as Mollaret, or benign recurrent meningitis). Associated viruses include Epstein-Barr virus (EBV), coxsackieviruses B5 and B2, echoviruses 9 and 7, herpes simplex virus (HSV)-1 and HSV-2, and human immunodeficiency virus (HIV).

Overall mortality and morbidity for aseptic meningitis are unclear. In a Taiwanese study of EV 71 infections, 78 of 408 hospitalized children died.Of children with rhombencephalitis due to EV infection, 14% died.

Subsequent studies suggested better outcomes. In both a Canadian study of 802 patients (1998-99)and a Korean study of 2201 children (1987-2003),no deaths were reported. In the Athens study of 506 children, no serious complications or deaths were reported.

Pediatric Bacterial Meningitis 

Practice Essentials

Signs and symptoms

The 3 classic symptoms (less likely in younger children):

• Fever
• Headache
• Meningeal signs

Symptoms in neonates:

• Poor feeding
• Lethargy
• Irritability
• Apnea
• Listlessness
• Apathy
• Fever
• Hypothermia
• Seizures
• Jaundice
• Bulging fontanelle
• Pallor
• Shock
• Hypotonia
• Shrill cry
• Hypoglycemia
• Intractable metabolic acidosis

Symptoms in infants and children:

• Nuchal rigidity
• Opisthotonos
• Bulging fontanelle
• Convulsions
• Photophobia
• Headache
• Alterations of the sensorium
• Irritability
• Lethargy
• Anorexia
• Nausea
• Vomiting
• Coma
• Fever (generally present, although some severely ill children present with hypothermia)

Diagnosis

Definitive diagnosis is based on the following:

• Bacteria isolated from the CSF obtained via lumbar puncture
• Meningeal inflammation demonstrated by increased pleocytosis, elevated protein level, and low glucose level in the CSF

Bacterial meningitis score

Components of the bacterial meningitis scoreare as follows:

• Positive CSF Gram stain
• CSF absolute neutrophil count 1000/µL or higher
• CSF protein level 80 mg/dL or higher
• Peripheral blood absolute neutrophil count 10,000/µL or higher
• History of seizure before or at the time of presentation

Management

IV antibiotics are required; if cause is unknown, agents can be based on child’s age, as follows:

• < 30 days, ampicillin and an aminoglycoside or a cephalosporin
• 30-60 days, ampicillin and a cephalosporin; because Streptococcus pneumoniae may occur in this age range, consider vancomycin instead of ampicillin
• In older children, a cephalosporin or ampicillin plus chloramphenicol with vancomycin (needs to be added secondary to the possibility of S pneumoniae)

Guidelines and recommendations

Infectious Diseases Society of America:

• Vancomycin plus either ceftriaxone or cefotaxime
• Duration of therapy:
• Neisseria meningitidis - 7 days
• Haemophilus influenzae - 7 days
• Streptococcus pneumoniae - 10-14 days
• S agalactiae (GBS) - 14-21 days
• Aerobic gram-negative bacilli - 21 days or 2 weeks beyond the first sterile culture (whichever is longer)
• Listeria monocytogenes - 21 days or longer

American Academy of Pediatrics:

• Duration of therapy should not be shorter than 5-7 days for meningococcus, 10 days for H influenzae, and 14 days for S pneumoniae

Prevention

Preventive therapy has been shown to reduce mortality and morbidity and consists of the following:

• Chemoprophylaxis: Rifampin, ceftriaxone, ciprofloxacin; ciprofloxacin and ceftriaxone are more effective against resistant strains of Neisseria meningitidis up to 4 weeks after treatment
• Haemophilus influenzae type b (Hib): Rifampin chemoprophylaxis for contacts of index cases of invasive Hib disease; MenHibrix provides immunization against Hib and meningococcal serogroups C and Y
• Neisseria meningitidis: Quadrivalent (ie, A, C, Y, W-135) meningococcal conjugate vaccine recommended for high-risk groups

Acute bacterial meningitis. This axial nonenhanced CT scan shows mild ventriculomegaly and sulcal effacement.

Acute bacterial meningitis. This axial T2-weighted MRI shows only mild ventriculomegaly.

Acute bacterial meningitis. This contrast-enhanced, axial T1-weighted MRI shows leptomeningeal enhancement (arrows).

Background

Pediatric bacterial meningitis is a life-threatening illness that results from bacterial infection of the meninges. Because bacterial meningitis in the neonatal period has its own unique epidemiologic and etiologic features, it will be discussed separately in this article as necessary.

Beyond the neonatal period, the 3 most common organisms that cause acute bacterial meningitis are Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b (Hib). Since the routine use of Hib, conjugate pneumococcal, and conjugate meningococcal vaccines in the United States, the incidence of meningitis has dramatically decreased.

Although S pneumoniae is now the leading cause of community-acquired bacterial meningitis in the United States (1.1 cases per 100,000 population overall), the rate of pneumococcal meningitis is 59% lower than it was before the introduction of the conjugate pneumococcal vaccine in 2000. The incidence of disease caused by S pneumoniae is highest in children aged 1-23 months and in adults older than 60 years.

Predisposing factors include respiratory infection, otitis media, mastoiditis, head trauma, hemoglobinopathy, human immunodeficiency virus (HIV) infection, and other immune deficiency states.

Meningitis is a life-threatening illness and leaves some survivors with significant sequelae. Therefore, meticulous attention must be paid to appropriate treatment and monitoring of these patients. Patients require hospitalization for antibiotic therapy and appropriate support. Adequate fluid administration is necessary to maintain perfusion, especially cerebral perfusion. Fluid restrictions (to prevent cerebral edema) may be more harmful because patients may be under resuscitated. Antibiotics must be promptly administered.

The emergence of penicillin-resistant S pneumoniae has resulted in new challenges in the treatment of bacterial meningitis.

Pathophysiology

Bacteria reach the subarachnoid space via a hematogenous route and may directly reach the meninges in patients with a parameningeal focus of infection.

Once pathogens enter the subarachnoid space, an intense host inflammatory response is triggered by lipoteichoic acid and other bacterial cell wall products produced as a result of bacterial lysis. This response is mediated by the stimulation of macrophage-equivalent brain cells that produce cytokines and other inflammatory mediators. This resultant cytokine activation then initiates several processes that ultimately cause damage in the subarachnoid space, culminating in neuronal injury and apoptosis.

Interleukin (IL)–1, tumor necrosis factor alpha (TNF-a), and enhanced nitric oxide production play critical roles in triggering inflammatory response and ensuing neurologic damage. Infection and inflammatory response later affect penetrating cortical vessels, resulting in swelling and proliferation of the endothelial cells of arterioles. A similar process can involve the veins, causing mural thrombi and obstruction of flow. The result is an increase in intracellular sodium and intracellular water.

The development of brain edema further compromises cerebral circulation, and this effect can result in increased intracranial pressure (ICP) and uncal herniation. Increased secretion of antidiuretic hormone (ADH), resulting in the syndrome of inappropriate antidiuretic hormone secretion (SIADH), occurs in most patients with meningitis and causes further retention of free water. These factors contribute to the development of focal or generalized seizures.

Severe brain edema also causes midline structures to shift caudally and become entrapped in the tentorial notch or foramen magnum. Caudal shifts produce herniation of the parahippocampal gyri, cerebellum, or both. These intracranial changes appear clinically as an alteration of consciousness and postural reflexes. Caudal displacement of the brainstem causes palsy of the third and sixth cranial nerves. If untreated, these changes result in decortication or decerebration and can progress rapidly to respiratory and cardiac arrest.

Neonatal meningitis

Bacteria from the maternal genital tract colonize the neonate after rupture of membranes, and specific bacteria, such as group B streptococci (GBS), enteric gram-negative rods, and Listeria monocytogenes, can reach the fetus transplacentally and cause infection. Furthermore, newborns can also acquire bacterial pathogens from their surroundings, and several host factors facilitate a predisposition to bacterial sepsis and meningitis.

Bacteria reach the meninges via the bloodstream and cause inflammation. After arriving in the central nervous system (CNS), bacteria spread from the longitudinal and lateral sinuses to the meninges, the choroid plexus, and the ventricles.

IL-1 and TNF-a also mediate local inflammatory reactions by inducing phospholipase A₂ activity, initiating the production of platelet-activating factor and the arachidonic acid pathway. This process results in production of prostaglandins, thromboxanes, and leukotrienes. Activation of adhesion-promoting receptors on endothelial cells by these cytokines attracts leukocytes, and the release of proteolytic enzymes from the leukocytes results in altered blood-brain permeability, activation of the coagulation cascade, brain edema, and tissue damage.

Inflammation of the meninges and ventricles produces a polymorphonuclear response, an increase in cerebrospinal fluid (CSF) protein content, and utilization of glucose in CSF. Inflammatory changes and tissue destruction in the form of empyema and abscesses are more pronounced in gram-negative meningitis. Thick inflammatory exudate causes blockage of the aqueduct of Sylvius and other CSF pathways, resulting in both obstructive and communicating hydrocephalus.

Etiology

Causes in different age groups

Neonates

Bacteria are often acquired from the maternal vaginal flora. Gram-negative enteric flora and GBS are the dominant pathogens. In premature newborns who receive multiple antibiotics, those on hyperalimentation, and those who undergo various surgical procedures, Staphylococcus epidermidis and Candida species are uncommon but are reported in greater frequency in neonates. L monocytogenes is another well-known but fairly uncommon causative pathogen.

Early-onset GBS meningitis occurs during the first 7 days of life as a consequence of maternal colonization and the absence of protective antibody in the neonate; it is often associated with obstetric complications. The disease is seen most often in premature or low-birth-weight babies. Pathogens are acquired before or during the birth process.

Late-onset meningitis is defined as disease occurring after 7 days of life. Causes include perinatally acquired and nosocomial pathogens. Streptococcus agalactiae (GBS) is classified into 5 distinct serotypes: Ia, Ib, Ic, II, and III. Although these serotypes occur with almost equal frequency in the early onset of disease, serotype III causes 90% of late-onset disease.

Use of respiratory equipment in the nursery increases the risk of infection caused by Serratia marcescens,Pseudomonas aeruginosa, and Proteus species. Invasive devices predispose infants to the infections caused by S epidermidis and Pseudomonas, Citrobacter, and Bacteroides species.

Infection with Citrobacter diversus, Citrobacter koseri, Salmonella species, and Proteus species, though uncommon, carries a high mortality. These patients often develop brain abscesses, particularly those with Citrobacter, in whom meningitis produces brain abscesses in 80-90% of cases.

Infants and children

In children older than 4 weeks, S pneumoniae and N meningitidis are the most common etiologic agents. Hib has essentially disappeared in countries where the conjugate vaccine is routinely used.

Causative organisms

Streptococcus pneumoniae

S pneumoniae is a gram-positive, lancet-shaped diplococcus that is the leading cause of meningitis. Of the 84 serotypes, numbers 1, 3, 6, 7, 14, 19, and 23 are the ones most often associated with bacteremia and meningitis. Children of any age may be affected, but the incidence and severity are highest in very young and elderly persons.

In patients with recurrent meningitis, predisposing factors are anatomic defects, asplenia, and primary immune deficiency. Often, the history includes recent or remote head trauma. This organism also has a predilection for causing meningitis in patients with sickle cell disease, other hemoglobinopathies, and functional asplenia. Immunity is type-specific and long-lasting.

S pneumoniae colonizes the upper respiratory tract of healthy individuals; however, disease often is caused by a recently acquired isolate. Transmission is person-to-person, usually via direct contact; secondary cases are rare. The incubation period is 1-7 days, and infections are more common in winter, when viral respiratory disease is prevalent. The disease often results in sensorineural hearing loss, hydrocephalus, and other central nervous system (CNS) sequelae. Prolonged fever despite adequate therapy is common with S pneumoniae meningitis.

Effective antimicrobial therapy can eradicate the organism from nasopharyngeal secretions within 24 hours. However, pneumococci have developed resistance to a variety of antibiotics; this development is seen worldwide. Rates of resistance to penicillin range from 10% to 60%. Multicenter surveillance of pneumococci isolated from the cerebrospinal fluid (CSF) has found resistance rates of 20% to penicillin and 7% to ceftriaxone.

Penicillin resistance in pneumococci is due to alterations in enzymes necessary for growth and repair of the penicillin-binding proteins; thus, beta-lactamase inhibitors offer no advantage. Penicillin-resistant pneumococci are often resistant to trimethoprim-sulfamethoxazole, tetracyclines, chloramphenicol, and macrolides. However, selected third-generation cephalosporins (eg, cefotaxime and ceftriaxone) do exhibit activity against most penicillin-resistant pneumococcal isolates.

At present, all pneumococcal isolates remain susceptible to vancomycin and various oxazolidinones. Several of the fluoroquinolones (eg, levofloxacin), though contraindicated in children, have excellent activity against most pneumococci and achieve adequate CNS penetration.

Tolerance, a trait distinct from resistance, is the term used to characterize bacteria that stop growing in the presence of antibiotic yet do not lyse and die. Pneumococci that are tolerant of penicillin and vancomycin have been described in literature, and a subsequent link to recrudescent meningitis was described in 1 child. The overall incidence and clinical impact of such bacterial strains are unknown. However, the possibility of tolerance should be kept in mind in cases of recurrent pneumococcal meningitis.

Neisseria meningitidis

N meningitidis is a gram-negative, kidney bean–shaped organism that is frequently found intracellularly. Organisms are grouped serologically on the basis of capsular polysaccharide; A, B, C, D, X, Y, Z, 29E, and W-135 are the pathogenic serotypes. In developed countries, serotypes B, C, Y, and W-135 account for most childhood cases. Group A strains are most prevalent in developing countries and have resulted in epidemics of meningococcal meningitis throughout the world, as well as outbreaks in military barracks.

The upper respiratory tract frequently is colonized with meningococci, and transmission is person-to-person via direct contact with infected droplets of respiratory secretions, often from asymptomatic carriers. The incubation period is generally less than 4 days (range, 1-7 days).

Most cases occur in infants aged 6-12 months; a second, lower peak occurs among adolescents. A petechial or purpuric rash frequently is seen. Mortality is significant in patients who have a rapidly progressive fulminant form of the disease. Normocellular CSF also has been reported in patients with meningococcal meningitis. Most deaths occur within 24 hours of hospital admission in patients who have features associated with poor prognosis, such as the following:

• Hypotension
• Shock
• Neutropenia
• Extremes of age
• Petechiae and purpura of less than 12 hours’ duration
• Disseminated intravascular coagulation (DIC)
• Acidosis
• Presence of the organism in white blood cells (WBCs) on peripheral smear
• Low erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) level
• Serogroup C disease

Higher rates of fatality and physical sequelae (eg, scarring and amputation) are reported in survivors of serogroup C disease. Long-term sequelae are rare in patients who have an uneventful hospital course.

Haemophilus influenzaetype b (Hib)

Hib is a pleomorphic gram-negative rod whose shape varies from a coccobacillary form to a long curved rod. Hib meningitis occurs primarily in children who have not been immunized with Hib vaccine; 80-90% of cases occur in children aged 1 month to 3 years. By age 3 years, a significant number of nonimmunized children acquire antibodies against the capsular polyribophosphate of Hib, which are protective.

The mode of transmission is person-to-person via direct contact with infected droplets of respiratory secretions. The incubation period generally is less than 10 days. Current mortality is less than 5%. Most fatalities occur during the first few days of the illness.

Plasmid-mediated resistance to ampicillin due to the production of beta-lactamase enzymes by bacterium is increasingly being reported: 30-35% of Hib isolates are now ampicillin-resistant. As many as 30% of cases may have subtle long-term sequelae. Administration of dexamethasone early in treatment reduces morbidity and sequelae.

Listeria monocytogenes

L monocytogenes causes meningitis in newborns, immunocompromised children, and pregnant women. The disease also has been associated with the consumption of contaminated foods (eg, milk and cheese). Most cases are caused by serotypes Ia, Ib, and IVb. Signs and symptoms in patients with listerial meningitis tend to be subtle, and diagnosis often is delayed. In the laboratory, this pathogen can be misidentified as a diphtheroid or a hemolytic streptococcus.

Other organisms

S epidermidis and other coagulase-negative staphylococci frequently cause meningitis and CSF shunt infection in patients with hydrocephalus or those who have undergone neurosurgical procedures. Immunocompromised children can develop meningitis caused by Pseudomonas, Serratia,Proteus, and diphtheroids.

Risk factors

Risk factors for bacterial meningitis include the following:

• Age
• Low family income
• Attendance at day care
• Head trauma
• Splenectomy
• Chronic disease
• Children with facial cellulitis, periorbital cellulitis, sinusitis, and septic arthritis have an increased risk of meningitis.
• Maternal infection and pyrexia at the time of delivery are associated with neonatal meningitis

Use of Hib and pneumococcal vaccines decreases the likelihood of infection from these agents.

Epidemiology

United States statistics

The advent of vaccine has changed the incidence of pediatric bacterial meningitis. Before the routine use of the pneumococcal conjugate vaccine, the incidence of bacterial meningitis in the United States was about 6000 cases per year; roughly half of these were in pediatric patients (≤18 years). N meningitidis caused about 4 cases per 100,000 children (aged 1-23 months). The rate of S pneumoniae meningitis was 6.5 cases per 100,000 children (aged 1-23 months). Today, disease caused by H influenzae, S pneumoniae, and N meningitidis is much less common.

The advent of universal Hib vaccination in developed countries has led to the elimination of more than 99% of invasive disease. Protection continues even when Hib is coadministered with other vaccines. Just as important, the vaccine continues to confer immunity into later childhood.

A similar effect occurs with pneumococcal vaccine. Given at ages 2, 4, and 6 months, this vaccine has reduced invasive disease by more than 90%. Age groups most affected are those younger than 2 years and those aged 2-5 years. This was proven in a surveillance study in Louisville, Kentucky.Nearly half of cases of pneumococcal disease are caused by nonvaccine serotypes.

Vaccine for Neisseria, however, has not been efficacious in younger children. This is due to poor immunogenic response. Current recommendations target immunization for children older than 2 years and high-risk patients with asplenic and terminal complement deficiencies. In addition, young adults living in close quarters, such as dormitories or military barracks, will benefit.

A study analyzing reported cases of bacterial meningitis among residents in 8 surveillance areas of the Emerging Infections Programs Network during 1998-2007 found a 31% decrease in meningitis cases during this period and an increase in median patient age from 30.3 years in 1998-1999 to 41.9 years in 2006-2007; the case fatality rate did not change significantly.Overall, approximately 4100 cases of bacterial meningitis occurred annually in the United States from 2003 to 2007, with approximately 500 deaths.

The incidence of neonatal bacterial meningitis is 0.25-1 case per 1000 live births (0.15 case per 1000 full-term births and 2.5 cases per 1000 premature births). Approximately 30% of newborns with clinical sepsis have associated bacterial meningitis.

After the initiation of intrapartum antibiotics in 1996, the national incidence of early-onset GBS infection decreased substantially, from approximately 1.8 cases per 1000 live births in 1990 to 0.32 case per 1000 live births in 2003.

International statistics

Worldwide, the use of H influenzae type B and pneumococcal vaccines is increasing at a rate faster than that observed with the use of hepatitis B vaccines.

In a survey by the Hib and Pneumococcal Working Group, the incidence of meningitis in 2000 varied in different regions of the world. The overall incidence of pneumococcal meningitis was 17 cases per 100,000, with the highest incidence in Africa, at 38 cases per 100,000, and the lowest incidence in Europe, at 6 cases per 100,000.The overall death rate was 10 cases per 100,000. The death rate was highest in Africa, at 28 cases per 100,000, and lowest in Europe and Western Pacific regions, at 3 cases per 100,000.

A similar trend was identified for Hib meningitis.The overall incidence of Hib meningitis in 2000 was 31 cases per 100,000. The African region had the highest rate, at 46 cases per 100,000, and Europe had the lowest, at 13 cases per 100,000. The overall death rate was 13 cases per 100,000. The highest death rate was in Africa, at 31 cases per 100,000, and the lowest was in Europe, at 4 cases per 100,000.

Age-, sex-, and race-related demographics

Pediatric bacterial meningitis is most common in children younger than 4 years, with a peak incidence in those aged 3-8 months.

Male infants have a higher incidence of gram-negative neonatal meningitis. Female infants are more susceptible to L monocytogenes infection. S agalactiae (GBS) affects both sexes equally.

Bacterial meningitis occurs more frequently in black, Native American, and Hispanic children; this is thought to be related to socioeconomic rather than racial factors.

Prognosis

Mortality and morbidity depend on the infectious agent, the age of the child, the child’s general health, and the promptness of diagnosis and treatment. Despite improvements in antibiotic and supportive therapy, death and complication rates remain significant.

Overall mortality for bacterial meningitis is 5-10% and varies according to the causative organism and the patient’s age. In neonates, mortality is 15-20%, whereas in older children, it is 3-10%. Of the meningitides caused by the most common pathogens, S pneumoniae meningitis has the highest mortality, at 26.3-30%; Hib meningitis has the next highest, at 7.7-10.3%; and N meningitidis has the lowest, at 3.5-10.3%.

As many as 30% of children have neurologic sequelae. This rate varies by organism, with S pneumoniae being associated with the highest rate of complications. One study indicated that the complication rate from S pneumoniae meningitis was essentially the same for penicillin-sensitive strains as for penicillin-resistant strains; this study also showed that dexamethasone did not improve outcomes.

Prolonged or difficult-to-control seizures, especially after hospital day 4, are predictors of a complicated hospital course with serious sequelae. On the other hand, seizures that occur during the first 3 days of illness usually have little prognostic significance.

Approximately 6% of affected infants and children show signs of DIC and endotoxic shock. These signs are indicative of a poor prognosis.

Studies have documented the development of profound bilateral hearing loss, which may occur in as many as 4% of all bacterial meningitis cases.Sensorineural hearing loss is one of the most frequent problems. Children at greatest risk for hearing loss include those with evidence of increased ICP, those with abnormal findings on computed tomography (CT), males, those with low CSF glucose levels, those with S pneumoniae infection , and those with nuchal rigidity.

Because many of the children affected are very young and lack mature cognitive and motor skills, some of the sequelae may not be recognized for years. In a study that followed children who recovered from meningitis for 5-10 years, 1 of every 4 school-aged meningitis survivors had either serious and disabling sequelae or a functionally important behavior disorder or neuropsychiatric or auditory dysfunction that impaired their performance in school.

For tuberculous meningitis, morbidity and mortality are related to the stage of the disease. The rate of significant morbidity is 30% for stage I, 56% for stage II, and 94% for stage III.

Pediatric First Seizure 

Overview

Population-based estimates suggest that every year 25,000-40,000 children in the United States experience a first unprovoked seizure.Using the International League Against Epilepsy (ILAE) definition, this includes multiple seizures within a 24-hour period if the child returns to baseline consciousness between episodes.

Most of these children never experience a recurrence . However, a seizure may be the initial presentation of a more serious medical condition or subsequent epilepsy. Epilepsy is a condition in which a child has 2 or more seizures without a proximal cause for the seizures (unprovoked seizures).

When evaluating a child who has experienced a first seizure, the clinician needs to address the following:

• An identifiable etiology
• The most appropriate therapy
• The prognosis

For more information, see the following:

• Epilepsy and Seizures
• Benign Childhood Epilepsy
• First Adult Seizure
• EEG in Status Epilepticus
• Epileptiform Normal Variants on EEG
• EEG Video Monitoring

Potential Seizure Etiologies

Identification of the underlying seizure etiology helps to identify appropriate treatment options and the prognosis for the child. In evaluating the child after a first seizure, the first consideration should be determining if the seizure was provoked or unprovoked. In the case of provoked seizures, treatment should include identifying and treating the underlying etiology.

Provoked seizures

Some etiologies of provoked (symptomatic) childhood seizures include central nervous system (CNS) infections, metabolic alterations, head trauma, and structural abnormalities.

CNS infections, such as meningitis, encephalitis, and empyema, can present with seizures. Identifying and treating the underlying infection is imperative.

Metabolic alterations can precipitate seizures and can be directly treatable targets. In children who are receiving intravenous (IV) fluids, are diabetic, or who may otherwise be prone to electrolyte abnormalities, consider evaluating glucose, sodium, and calcium levels. For patients with chronic hyponatremia, rapid sodium correction should be avoided to prevent central pontine myelinolysis. Also consider obtaining toxicology screens to evaluate for medication or toxic exposures.

Head trauma can precipitate seizures and requires immediate evaluation with appropriate neuroimaging studies to rule out hemorrhage, contusion, or other serious injuries.

Structural abnormalities, such as congenital cerebral malformations, ischemic or hemorrhagic strokes, tumors or other mass lesions are less common etiologies of seizures, but can be ruled out with appropriate neuroimaging studies.

Febrile seizures

Febrile seizures are convulsions in infants and children triggered by a fever in the absence of CNS infection. Febrile seizures affect 4-5% of children aged 6 months to 6 years. These occur in association with a high fever, typically above 38.5°C (101.3°F), although some believe the rate of change in body temperature is more provoking than the absolute temperature in febrile seizures. There is often a positive family history of febrile seizures in other family members. A second episode occurs in 33% of children, and only 50% of those have a third episode. Few children, approximately 3-6%, with febrile seizures develop afebrile seizures or epilepsy. Electroencephalography (EEG) and neuroimaging are generally not warranted.Further evaluation may be required for complex febrile seizures, which include seizures that are greater than 15 minutes in duration, have focal onset, or occur multiple times within 24 hours or within a febrile illness.

Epileptic syndromes

An exhaustive list of seizure types and pediatric epilepsy syndromes is beyond the scope of this article. However, familiarity with some of the most common seizure types can aid the clinician in obtaining an appropriate workup and evaluation.

Infantile spasms typically begin in infants aged 4-8 months (although earlier and later presentations do occur) and consist of clusters of myoclonic spasms, typically upon awakening or falling asleep. The presentations can be more subtle and include slight eye flutter or head drop. If infantile spasms are suspected, appropriate diagnosis and swift management is essential to improve developmental outcome.

Absence epilepsy, also known as petit mal epilepsy, is manifested by frequent (as many as 100 times per day or more) episodes of brief staring spells, often with fluttering of the eyelids, lasting only a few seconds (typically up to 15 seconds) at a time. Following a typical absence seizure, patients return immediately to their baseline mental status. Absence seizures are primarily generalized in onset. The diagnosis can be assisted by classic EEG features and hyperventilation trial, which often provokes the seizures.

Benign rolandic epilepsy occurs in children aged 3-13 years.The typical presentation is a seizure characterized by perirolandic or perisylvian sensorimotor features including speech arrest or guttural sounds and facial numbness or twitching, which may progress to generalized tonic-clonic activity. The majority of seizures occur during sleep or upon awakening. Classic EEG features can aid in the diagnosis of this syndrome.

Other benign partial epilepsies of childhood include benign occipital epilepsy of childhood (Gastaut syndrome), in which visual symptoms predominate, and Panayiotopoulos syndrome, in which autonomic changes, vomiting, sweating, and pallor are prominent ictal symptoms.

Juvenile myoclonic epilepsy (JME) may present in the teen years. In JME, individuals may present with generalized tonic-clonic seizures, myoclonic jerks (typically seen within hours of awakening), and staring spells.

For more information regarding specific pediatric epilepsy syndromes, please refer to the International League Against Epilepsy.

Clinical Evaluation

Because medical personnel often do not witness the first seizure, eyewitness accounts are a crucial step in evaluation. Collect information on what the patient was doing just before the seizure (eg, association with sleep onset or arousal from sleep). Seizure while watching television or flickering lights may suggest a photosensitive seizure.

An accurate description of seizure semiology can help differentiate between specific seizure types. One should ask about alteration of consciousness, lateralizing signs (eg, eye deviations, head turning, focal clonus) or automatisms (eg, lip smacking, picking at clothes, gestures such as fumbling or tapping).An accurate description of seizure semiology at onset is particularly important, as this might give clues to whether a generalized seizure actually had a partial onset.

If possible, getting the patient’s account of the event can provide further diagnostic clues.

For example, olfactory or epigastric aura are suggestive of temporal lobe epilepsy, while visual hallucinations can occur with occipital lobe seizures.

In addition to events immediately surrounding the seizure, it is important to gather any history of recent illnesses, antibiotic treatment (which may raise suspicion for a partially treated meningitis), recent travel, recent head injury, chemical or toxin exposures, and intake of medications, supplements, alcohol, and/or illicit drugs.

Obtain a family history of epilepsy or febrile seizures, particularly among first-degree relatives. Elicit a history of fever, chronic medical conditions (eg, diabetes), medications, behavioral or dietary changes, and recent or remote history of head trauma or CNS infections. A developmental history is important in assessing possible etiologies and risk of future events.

A thorough general and detailed neurologic examination should be performed. In particular, the patient should be evaluated for the following:

• Fever or other abnormalities in vital signs
• Signs suggestive of trauma or the presence of an intracranial shunt
• Dysmorphic features and abnormal neurodevelopment
• Papilledema, suggesting increased intracranial pressure
• Nuchal rigidity or other signs of meningismus (specific signs of meningitis may be absent in children, particularly in neonates and infants younger than 6 mo)
• Skin features such as port-wine stain, facial angiofibromas, hypopigmented macules, or shagreen patch suggestive of neurocutaneous syndrome, or petechial rash suggestive of meningococcal infection
• Focal neurologic deficits, which may be indicative of an underlying focal structural lesion or postictal Todd paresis

Laboratory Evaluation

Initial laboratory evaluation of a first seizure can include serum studies for levels of glucose, electrolytes, calcium, and magnesium and for toxicology. The American Academy of Neurology (AAN) recommends that clinicians use their clinical judgment.

While it is not routinely tested, prolactin may help to distinguish seizures from nonepileptogenic events.

Give particular attention to the laboratory evaluation of the neonate, as glucose and calcium abnormalities can be observed in the first week of life. When a metabolic abnormality is suspected in the neonate, consider a basic metabolic evaluation with serum ammonia, serum lactate and pyruvate, serum for amino acids, and urine for organic acids. Further metabolic studies should be guided by the history, examination, and clinical course.

Lumbar Puncture

Strongly consider a lumbar puncture (LP) in patients who have fever and either meningeal signs (neck pain, Kernig or Brudzinski sign) or altered mental status. If increased intracranial pressure is suspected, obtain rapid imaging before performing the lumbar puncture, as there may be a risk of inducing cerebral herniation with space-occupying lesions or obstructive hydrocephalus.

The American Academy of Neurology (AAN) recommends LP be performed in any child with persistent changes in mental status who is younger than 6 months or any child with meningeal signs.For many years ,the role of lumbar puncture in infants aged 6-12 months has been controversial. These children are still too young to exhibit reliable meningeal signs. However, widespread immunization against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae has mitigated the risk of meningitis in this population.

In the American Academy of Pediatrics 2011 guidelines, LP is an option when an infant in this age-group is considered deficient in immunization and if immunization status cannot be determined.Other elements of the presentation, such as failure to return to baseline, may also prompt LP in this age group.

Neuroimaging

The role of neuroimaging in a child with new-onset afebrile seizures is controversial. Emergent neuroimaging should be performed when there is a high clinical suspicion for a condition requiring immediate intervention, such recent head trauma, recurrent seizures, focal or new neurologic deficits, and papilledema. Neuroimaging should also be considered if the patient has not returned to baseline. In marked distinction to the adult population seen in the emergency department, afebrile seizures in children are not commonly associated with abnormal neuroimaging.

Clinically significant neuroimaging abnormalities have been reported in 2% of children presenting with first afebrile seizure without focal features or predisposing conditions.The decision of whether or not to obtain neuroimaging in these cases should be made on an individual basis, and an electroencephalogram (EEG) can be helpful. For example, a focal EEG may increase suspicion for a structural abnormality. Patients who have clearly defined epileptic syndromes, such as petit mal epilepsy or benign rolandic epilepsy, do not necessarily require neuroimaging. American Academy of Neurology (AAN) practice parameters recommend nonurgent imaging after initial seizure in situations in which there is a significant cognitive or motor impairment, unexplained abnormalities on the neurological examination, partial-onset seizures, an EEG inconsistent with a benign or primary generalized epilepsy, and in patients younger than 1 year.

If neuroimaging is obtained, MRI is the preferred method of imaging to avoid radiation exposure while providing more detailed diagnostic information.However, CT is still frequently obtained based on available resources.

Electroencephalogram

Electroencephalogram (EEG) can be useful in the acute setting if there is a concern for subclinical seizures (electrographic seizures without clinical correlate) or if the patient has persistent altered mental status. An EEG is also important if a nonreactive patient received paralytics for intubation and does not show awakening in the critical care unit after an expected timeframe. Clinical signs such as appropriate pupil reactivity and withdrawal to pain/stimulation can be helpful clues that the patient is not in continuous nonconvulsive status epilepticus. Long-term (24 h or greater) EEG monitoring should be considered to identify nonconvulsive seizures in at-risk patients, including infants or children with persistent unexplained altered mental status.

If the child is clinically stable, it may not be necessary to perform the EEG on an emergent basis. However, EEGs are an important tool in determining prognosis (see Long-Term Prognosis) for future seizures and should be strongly considered for all children with a first seizure on a nonurgent basis.In the nonacute setting, there is still debate as to whether an EEG performed within the first 24 hours is more sensitive to identify epileptiform abnormalities. However, current practice does not mandate early EEG, as untreated patients with epilepsy tend to have persistent EEG abnormalities. EEG yield can be increased by including sleep and activating procedures, such as hyperventilation and photic stimulation. If there is a high suspicion for a seizure disorder and routine EEG is normal, repeat EEG or prolonged EEG monitoring can be obtained. Repeating the EEG a second time may increase the sensitivity to 80-90%.

It is important to remember that an EEG does not determine whether the patient had a seizure, as this is a clinical diagnosis. EEGs may be abnormal in up to 10% of healthy individuals, and 50% of patients with epilepsy have a normal first EEG. EEGs can be helpful in classifying seizure types and identifying epilepsy syndromes with specific electroclinical features, such as benign rolandic epilepsy or juvenile myoclonic epilepsy. This classification system can help both with prognosis and determining appropriate anticonvulsant therapy. For more information regarding EEG findings in specific childhood epilepsy syndromes, see EEG in Common Epilepsy Syndromes.

Management

As mentioned above, in the case of provoked seizures, treatment should include identifying and treating the underlying etiology. The aspects relevant to the decision of whether or not to initiate anticonvulsant drug therapy after first seizure is discussed.

Acute anticonvulsant therapy

The decision of whether or not to initiate anticonvulsant treatment after a first seizure must be based on the clinical scenario and risks and benefits determined for the individual patient. In general, anticonvulsant drugs are used to decrease the probability of recurrent seizures; however, they have not been found to prevent the development of epilepsy after first seizure.

In patients presenting in status epilepticus or in acutely ill children (eg, seizures associated with encephalitis), in which the chance of a recurrent seizure is high, medications that can be administered quickly through intravenous access (IV) access, such as benzodiazepines, fosphenytoin, phenobarbital, valproic acid, or levetiracetam are useful. A prescription for rectal diazepam (Diastat) for use at home if patients have a recurrent prolonged seizure in the future may be useful.

In some situations, such as simple febrile seizures, the risks and potential side effects of chronic anticonvulsant therapy may outweigh the benefits, and treatment is not typically offered.

Chronic anticonvulsant therapy

The decision of whether to treat with long-term anticonvulsant therapy after a first unprovoked seizure requires consideration of the risks of medication adverse effects and psychological stigma against the risk of recurrent seizure. Decisions must be made on an individualized basis and should involve discussions with the patient and family.

As a care guideline, most pediatric neurologists would not start chronic anticonvulsants after a first-time seizure, unless prominent risk factors for epilepsy (eg, cerebral palsy, mental retardation, brain structural lesions, abnormal EEG) are known to exist.Even if increased recurrence risk is determined, many neurologists would delay starting chronic anticonvulsants until a second unprovoked seizure occurred, establishing adequate frequency of seizures to warrant medication.

This general practice is guided by data from both adult and pediatric studies, which show that delayed treatment of seizure disorders does not reduce the likelihood of seizure freedom and may spare some individuals from long-term antiepileptic drug treatment.

If anticonvulsant medications are initiated, the choice of medication should be made based on seizure type. Some medications have been shown to be highly efficacious for some types of seizures but worsen other types. For example, carbamazepine can be helpful against partial seizures but can exacerbate generalized absence seizures.

In most childhood epilepsies, anticonvulsant prophylaxis is maintained until the child is seizure-free for 1-2 years or until an appropriate age when the child would no longer be expected to be at risk of having seizures.

Patients at risk of seizures or lapses of consciousness who are old enough to drive must be carefully evaluated and reported to state authorities per mandates of individual state laws. Find out more information at the Epilepsy Foundation.

Long-Term Prognosis

Giving a definitive prognosis after a single seizure is difficult, but some general rules do apply, based on epidemiologic data.

In general, children who have a single, short, generalized seizure along with normal neurologic development and normal findings on neurologic examination are estimated to have a 24% risk of having another seizure within 1 year and a 36% chance of having a second seizure within 3 years. In these children, if the electroencephalogram (EEG) is found to be normal, the risk of seizure recurrence is estimated to decrease to approximately 15% within 1 year and 26% within 3 years. If the EEG is found to be abnormal, approximately 41% will have another seizure within 1 year and 56% within 3 years.

Children with developmental problems, structural central nervous system (CNS) lesions, or focal neurologic deficits have a 37% risk of having another seizure within 1 year and 60% risk of having another seizure within 3 years.

If a child has a second unprovoked seizure, the risk for further seizures is greater than 50%, even among children without other risk factors.Identifying the seizure as part of a syndrome has additional predictive value. For example, patients with simple febrile seizures will likely have spontaneous remission as they enter school-age years; however, patients with juvenile myoclonic epilepsy are likely to have lifelong seizure recurrence.

Patient Education

Inform the patient's family about the following:

• Steps to be taken in the event of a second seizure
• Seizure precautions
• Appropriate follow-up
• Organizations that can provide more information

In the event of a second seizure

If a child has a second seizure, place the child in a lateral decubitus position to allow gravity to pull secretions and the tongue out of the airway. Attempt to keep the neck straight to keep the airway most open. Place no objects in the child's mouth.

Most seizures last for less than 2 minutes; however, if a seizure lasts longer than 5 minutes, the child should be transported to an emergency department for administration of medications to stop the seizures. If the seizure is the second unprovoked seizure (eg, no fever, drug exposure, or proximate head trauma), contact the patient's primary physician or neurologist, because anticonvulsant therapy is frequently indicated.

Seizure precautions

Children with the possibility of a having a second seizure should not engage in activities that are potentially harmful. They should not be allowed to take unsupervised baths (because of the risk of drowning) or to climb higher than 5 feet. Supervised swimming, bike riding (helmeted), and playing video games are considered by most neurologists to be safe activities.

Driving age patients should refrain from driving until deemed safe and seizure-free, according to the laws of their state. For example, in the State of Wisconsin, patients need to be seizure-free for 3 months before they can resume driving, whereas in Arkansas, patients need to be seizure-free for 1 year. For individual state regulations, see the Epilepsy Foundation Web site.

Follow-up

After a single seizure, an appointment should be made with the child's primary care physician or a neurologist. This is useful to address any further questions the family has, review the need for further diagnostic testing, and discuss any further therapy. Families should also be encouraged to learn basic cardiopulmonary resuscitation (CPR). CPR training according to the American Heart Association (AHA) or American Red Cross is highly recommended to all families.

References

а) Basic

1. Manual of Propaedeutic Pediatrics / S.O. Nykytyuk, N.I. Balatska, N.B. Galyash, N.O. Lishchenko, O.Y. Nykytyuk – Ternopil: TSMU, 2005. – 468 pp.

2. Kapitan T. Propaedeutics of children’s diseases and nursing of the child : [Textbook for students of higher medical educational institutions] ; Fourth edition, updated and

translated in English / T. Kapitan – Vinnitsa: The State Cartographical Factory, 2010. – 808 pp.

3. Nelson Textbook of Pediatrics /edited by Richard E. Behrman, Robert M. Kliegman; senior editor, Waldo E. Nelson – 19^th ed. – W.B.Saunders Company, 2011. – 2680 p.

b) Additional

1. www.bookfinder.com/author/american-academy-of-pediatrics

2. www.emedicine.medscape.com

3. http://www.nlm.nih.gov/medlineplus/medlineplus.html