Pediatric Neurology

·         Trough serum drug levels should be obtained to detect subtherapeutic or toxic concentrations. It is most helpful to check the serum level right before the dose, preferably in the morning before any medication is given. An inadequate serum concentration is the most common cause of persistent seizures, but drug toxicity, especially with phenytoin, may also manifest by deteriorating seizure control.

·         A paradoxic worsening of seizure control by various AEDs has been noted for decades. Mechanisms may include nonspecific effects of drug intoxication. In addition, specific medications may exacerbate specific seizure types. For example, carbamazepine may worsen the absence, myoclonic, and astatic seizures seen in generalized epilepsy syndromes; phenytoin and vigabatrin may also worsen generalized seizures; and gabapentin and lamotrigine may worsen myoclonic seizures.

·         CP:

Apgar scores correlate poorly with the ultimate diagnosis of cerebral palsy.

During the first year of life, hypotonia is more common than hypertonia in patients who are ultimately diagnosed with the disease.

Keep an eye on the eyes: As many as 75% of children with cerebral palsy have ophthalmologic problems (e.g., strabismus, refractive errors).

Spastic hemiplegia is the most common type of cerebral palsy that is associated with seizures.

Monitor regularly for hip subluxation, especially in patients with spastic diparesis, because earlier identification assists therapy.

·         Hydrocephalus ex vacuo describes increases in volume without increased CSF pressure, which is seen in conditions of reduced cerebral tissue (e.g., malformation, atrophy).

·         Moyamoya, which is Japanese for "puff of smoke," refers to the cerebral angiographic appearance of patients with this primary vascular disease that results in stenosis of the internal carotid artery. It also occurs in a wide variety of conditions, such as neurofibromatosis type 1, sickle cell disease, Down syndrome, and tuberous sclerosis, in addition to the idiopathic condition that is endemic in Japan. Because it is a chronic condition, fine vascular collaterals can develop, and it is these collaterals that create the "puff of smoke" appearance on angiography.

·         The persistent vegetative state is "a form of eyes-open permanent unconsciousness in which the patient has periods of wakefulness and physiological sleep/wake cycles, but at no time is the patient aware of himself or herself or the environment." If this state persists for >3 months in children, the long-term outlook is grim.

The minimally conscious state occurs on emergence from this vegetative state, and a patient must demonstrate a reproducible action in one or more of four types of behavior: (1) simple command following; (2) gestural or verbal "yes/no" responses; (3) intelligible verbalization; or (4) purposeful behaviors.

·         Rolandic((central, midtemporal, centrotemporal, or sylvian) ) epilepsy is an idiopathic localization-related epilepsy that represents 10-15% of all childhood seizure disorders.

It begins in school-aged children (4-13 years old) who are otherwise healthy and neurologically normal.

Seizures are idiopathic or familial (autosomal dominant inheritance with age-dependent penetrance).

Seizures may be simple or complex and partial or generalized. Classically, there is a history of one-sided facial paresthesias and twitching and drooling that may be followed by hemiclonic movements or hemitonic posturing. Consciousness is typically preserved. The seizures are primarily nocturnal and may secondarily generalize.

Often referred to as "benign" because the individual is developmentally normal, seizures are usually rare and nocturnal, and they most often resolve after puberty.

·         Atypical absence (most common in Lennox-Gastaut syndrome)

EEG: 2-Hz (or slower) spike and wave

Observations: Gradual onset and ending; frequency is more cyclic; unresponsive with more prolonged and pronounced atonic, tonic, myoclonic, or tonic activity

·         The GLUT-1 deficiency syndrome, which was previously referred to as the glucose transporter protein deficiency syndrome, was first described in 1991. The clinical phenotype is variable, but the child usually presents symptoms during the first years of life with seizures and delays of motor and mental development. The head circumference decelerates during the first years of life. The diagnosis should be suspected if CSF reveals low glucose (and lactate) concentrations without evidence of inflammation and blood sugars are normal.

·         Complex migraines are those migraine headaches that are accompanied by transient neurologic signs or symptoms. These include hemiplegic migraine, ophthalmoplegic migraine (orbital pain with third nerve palsy), acute confusional state, and the "Alice in Wonderland" syndrome (hallucinations and distortion of object size). The most common form is basilar artery migraine, which has a variety of symptoms, including blurred vision, vertigo, ataxia, dysarthria, and loss of consciousness.

·         Familial hemiplegic migraine, as its name implies, is an autosomal dominant disorder that is clinically characterized by transient hemiparesis followed by migraine headache. About 20% are affected by permanent cerebellar signs. Mutations in CACNA1A (which encodes a neuronal calcium channel) on chromosome 19 is found in half of affected families.

·         Alternating hemiplegia of childhood is a rare disorder of intermittent, alternating hemiplegia that presents during early childhood and that is characterized by abnormal eye movement and dystonic episodes followed by hemiplegia. There may be an autonomic prodrome, and recovery takes from hours to days. Children with early onset typically have greater developmental delay and movement disorders.

·         Although pyridoxine-dependent seizures are rare, a trial dose of pyridoxine should be administered intravenously to infants with recurrent seizures of uncertain etiology. If possible, simultaneous EEG recording should be performed to document the cessation of seizure activity and the normalization of the EEG within minutes of pyridoxine treatment. Infants with pyridoxine-dependent epilepsy may have profound autonomic dysfunction (apnea, bradycardia, and hypotension) in response to initial pyridoxine administration and should be monitored carefully.

·         Port-wine stains can occur as isolated cutaneous birthmarks or, particularly in the areas underlying the birthmark, in association with structural abnormalities in the following areas: (1) the choroidal vessels of the eye, thereby leading to glaucoma; (2) the leptomeningeal vessels of the brain, thus leading to seizures (Sturge-Weber syndrome); and (3) hemangiomas in the spinal cord (Cobb syndrome).

·         Incontinentia pigmenti is an X-linked dominant disorder that is associated with seizures and mental retardation. The condition is presumed to be lethal to boys in utero because nearly 100% of cases are female.

Stage 1-Vesicular stage: Lines of blisters are present on the trunk and extremities of the newborn that disappear in weeks or months. They may resemble herpetic vesicles. Microscopic examination of the vesicular fluid demonstrates eosinophils.

Stage 2-Verrucous stage: Lesions develop in the patient around age 3-7 months of age that are brown and hyperkeratotic, resembling warts; these disappear over 1-2 years.

Stage 3-Pigmented stage: Whorled, swirling (marble-cake-like), macular, hyperpigmented lines develop. These may fade over time, leaving only remnant hypopigmentation in late adolescence or adulthood (which is sometimes considered a fourth stage).

·         Hypotonia with weakness: Think abnormality in anterior horn cell or peripheral neuromuscular apparatus.

Hypotonia without weakness: Think brain or spinal-cord disturbance.

·         Juvenile (and adult) myasthenia gravis is caused by circulating antibodies to the AChR of the postsynaptic neuromuscular junction. Occurrence is rare before the age of 2 years. Congenital myasthenia gravis is a nonimmunologic process. It is caused by morphologic or physiologic features affecting the pre- and postsynaptic junctions, including defects in ACh synthesis, endplate acetylcholinesterase deficiency, and endplate AChR deficiency. Neonatal myasthenia gravis refers to the transient weakness that occurs in infants of mothers with myasthenia gravis.

·         Usual cause of stridor in a child with myelomeningocele is dysfunction of the vagus nerve, which innervates the muscles of the vocal cords.

·         Porencephaly is an acquired abnormality that is seen as an outpouching from the ventricular system. It usually results from a parenchymal bleed, infarct, or infection. Schizencephaly, a "split brain," is a congenital migrational defect and is a cleft in one or both hemispheres from the surface of the brain down to the ventricular surface. Lissencephaly means "smooth brain," one in which there are few if any gyri formed on the brain's surface. This is a severe migrational disorder of two types. Type I involves the brain and can be part of the Miller-Dieker malformation. Type II is seen in association with severe muscle disease.

·         Hypomelanosis of Ito was originally described as a purely cutaneous disease with a swirling pigmentary pattern, but subsequent reports have included a frequent association with multiple extracutaneous manifestations, mostly of the central nervous and musculoskeletal systems. Neurologic complications include mental retardation, autism, brain malformations, microcephaly, and epilepsy. Miscellaneous chromosomal mosaicisms have been demonstrated in some but not all affected persons. Additional, associated abnormalities include limb length discrepancies, facial hemiatrophy, scoliosis, sternal abnormalities, dysmorphic facies, and genitourinary and cardiac abnormalities.

·         The subependymal germinal matrix is the most common site for IVH in VLBW babies; venous hemorrhagic infarction of the white matter, which shares some of the pathogenesis with germinal matrix hemorrhage, may contribute. In term infants, bleeding originates in the choroid plexus of the lateral ventricle.

·         A single scan on the fourth day of life would be expected to detect >90% of IVHs.

Grade I: Germinal matrix hemorrhage only

Grade II: IVH without ventricular dilatation

Grade III: IVH with ventricular dilatation

Grade IV: Grade III hemorrhage plus intraparenchymal involvement

·         Cerebral Injury on MRS: An elevated N-acetylaspartate to total creatine ratio is associated with a higher likelihood of a normal outcome at 18 months. Most important, the presence of a lactate peak predicts an abnormal outcome with a sensitivity of 100% and a specificity of 80%.

·         Two malignant epilepsy syndromes beginning in the neonatal period are characterized by refractory seizures, a suppression-burst EEG, and a poor prognosis. Early infantile epileptic encephalopathy (Ohtahara syndrome) is associated with tonic seizures and structural lesions, and early myoclonic epilepsy (Aicardi's syndrome) is associated with myoclonic seizures and metabolic etiologies.