Peds Neuro Syndromes

Question 1

mutations in filamin A

Answer 1

Mutations of filamin A have been linked to the presence of bilateral periventricular heterotopias, enlarged cistern magna and thinning or agenesis of the corpus callosum. In adolescents and adults, screening for an aortic aneurysm should be performed.

Question 2

molar tooth sign

Answer 2

Molar tooth sign is associated with Joubert’s syndrome. The molar tooth sign, which is the result of the thickening and horizontalization of the superior cerebellar peduncle and a deep interpeduncular fossa, can also be seen in several other disorders including Dekaban-Arima syndrome, Senior-Loken syndrome, and COACH (cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis).

Question 3

What disease is associated with leptomeningeal angiomas?

Answer 3

Leptomeningeal angioma is observed with Sturge Weber Syndrome.

Question 4

Myoclonic epilepsy of infancy

Answer 4

Myoclonic epilepsy of infancy (MEI) is a generally benign generalized myoclonic seizure disorder occurring in otherwise healthy infants, some of whom (about 25%) have a history of isolated febrile convulsions. They do not occur in clusters, and are not associated with tonic-clonic seizures.

Question 5

treatment of duchenne’s

Answer 5

Only daily oral corticosteroids have been shown to prolong ambulation in Duchenne muscular dystrophy (DMD). The effect is to induce small amounts of dystrophin, not as an anti-inflammatory treatment, so other dosing strategies are not helpful. Intravenous gentamicin has been proposed for one of the rare point mutations causing DMD.

Question 6

Zellweger syndrome

Answer 6

Zellweger syndrome presents in infancy, and affected individuals have characteristic facial features with high forehead, hypoplastic supraorbital ridges, and midface hypoplasia. Severe weakness, hypotonia, and seizures are common. Diagnosis is confirmed by elevated levels of saturated and unsaturated very long-chain fatty acids in body fluids.

Question 7

schizencephaly

Answer 7

Schizencephaly is also a neuronal migration disorder with expected association of seizures and developmental delay.
Unilateral closed-lip schizencephaly carries nearly a 70% risk for epilepsy.

Question 8

cerebrovascular disease in sickle cell

Answer 8

Cerebrovascular disease occurs in 25% of sickle cell disease. Eighty percent of events occur at or before age 15 and most are caused by a progressive cerebral vasculopathy that can be partially arrested by chronic transfusion therapy to keep hemoglobin S below 30%. Most events are thrombotic.

Question 9

cerebellar mutism

Answer 9

Cerebellar mutism, also called posterior fossa syndrome, is a complication of any surgical procedure within the posterior fossa, but more likely to occur following surgeries that involve tumor resection, particularly if the vermis is involved. While various cranial nerve palsies may be seen, the syndrome is also seen without other evidence of structural damage. Typically, onset of severe dysarthria progressing to mutism is delayed hours to days after initial surgical recovery. Severe irritability is common. Recovery takes weeks to months and may never be complete, as many children with this manifestation show ongoing cognitive and behavioral problems years after successful surgery.

Question 10

spasmus nutans

Answer 10

The combination of dysconjugate, highly variable nystagmus, head nodding and head tilt, without ophthalmologic abnormalities, and with normal neuroimaging, is diagnostic of spasmus nutans. Latent nystagmus is a jerk nystagmus that is evoked or enhanced by covering one eye. Congenital nystagmus is usually conjugate and suppressed by convergence (in contrast to spasmus nutans, which is typically increased by convergence). Opsoclonus describes chaotic, conjugate saccades, seen classically in the paraneoplastic syndrome associated with neuroblastoma. Decompensated strabismus would not produce a paroxysmal movement disorder

Question 11

Benign idiopathic neonatal convulsions

Answer 11

Benign idiopathic neonatal convulsions are an autosomal dominant disorder which has been strongly linked to potassium channel defects resulting from mutations of the genes KCNQ2 and KCNQ3. The normal exam makes hypoxia unlikely as most are lethargic. Most children with metabolic disorders are lethargic or even comatose. Benign rolandic epilepsy presents in adolescence.

Question 12

SMA I

Answer 12

Spinal muscular atrophy I usually presents with hypotonia, areflexia, paradoxical respiration with narrow upper chest, tongue fasciculations, and progresses to difficulty swallowing, then respiratory distress.

Question 13

medullablastoma/other posterior fossa masses

Answer 13

The typical presentation of a medulloblastoma is a midline posterior fossa mass which is hyperdense on noncontrast CT and enhances uniformly with contrast. On MRS, choline and taurine are increased. The clinical presentation is often due to the secondary hydrocephalus. Pilocytic astrocytomas also tend to occur in the posterior fossa but generally have a significant cystic component. An ependymoma would tend to be more clearly associated with the ventricle as would a choroid plexus papilloma.

Question 14

early infantile epileptic encephalopathy (Ohtahara syndrome)

Answer 14

The combination of tonic spasms and a burst suppression EEG is consistent with the syndromic diagnosis of early infantile epileptic encephalopathy (Ohtahara syndrome). This syndrome, which can also include fragmentary myoclonic jerks and partial seizures, frequently evolves into West syndrome at about 4 to 6 months of age. Etiological causes have included brain malformations as well as metabolic syndromes, such as glycine encephalopathy and mitochondrial disorders.

Question 15

TB meningitis

Answer 15

Tuberculous meningitis typically presents in toddlers with initially nonspecific febrile illness but if not recognized progresses to hydrocephalus and infarcts in the region of basilar perforators. Unfortunately, when diagnosis is delayed, prognosis is poor.

Question 16

botulism

Answer 16

Infantile botulism usually presents between 3 and 18 weeks of age. The disease is caused by the Clostridium botulinum toxin, which blocks acetylcholine release. Clinical features include constipation, hypotonia, areflexia, poor suck, impaired pupillary response to light, and ophthalmoplegia. The infants are often breast-fed. Diagnosis is made by EMG with repetitive nerve stimulation, causing an incremental response and isolation of C. botulinum toxin in the stool.

Question 17

kernicterus

Answer 17

This clinical picture describes the classic tetrad of chronic bilirubin encephalopathy (kernicterus): severe athetosis, perceptive high tone deafness, supranuclear palsy of upward gaze, and enamel hypoplasia of the incisor teeth.

Question 18

autosomal dominant nocturnal frontal lobe epilepsy

Answer 18

The nocturnal seizures associated with autosomal dominant nocturnal frontal lobe epilepsy are typically brief and consist of an aura that has been described as fear or forced thinking with associated hyperkinetic or tonic movements. Consciousness can be maintained during an event. These events do tend to cluster. The disorder has an autosomal dominant inheritance pattern and is associated with mutations in the neuronal nicotinic acetylcholine receptor.

Question 19

Freidreich ataxia

Answer 19

Hallmarks of Friedreich ataxia are a combination of weakness, ataxia, absent tendon jerks, Babinski sign, and abnormal position sense. Romberg sign is the best indication of loss of position sense, not cerebellar functioning. Hammer toes, pes cavus deformities, and scoliosis are frequent findings.

Question 20

Rolandic epilepsy

Answer 20

The seizure pattern described is one of benign rolandic epilepsy, for which the EEG signature is central-temporal spikes, particularly in sleep, often bilateral independent.

Question 21

Joubert syndrome

Answer 21

This clinical picture describes a typical presentation and MRI findings of Joubert syndrome; in which there is hypoplasia of the cerebellar vermis. The most common features of this syndrome include hyperpnea, hypotonia, oculomotor apraxia, ataxia, and intellectual disability. Other neurologic manifestations include seizures.

Question 22

LINCL v NCL

Answer 22

The conjunctival biopsy shows typical curvilinear bodies. This strongly suggests late-infantile neuronal ceroid lipofuscinosis (LINCL). Visual loss in LINCL often follows seizure onset by several years, and is accompanied by gradual progression of dementia. In contrast, juvenile NCL generally presents with visual loss, followed years later by seizures and dementia.

Question 23

Metachromatic leukodystrophy

Answer 23

Metachromatic leukodystrophy is an autosomal recessive disorder, and in its imaging usually demonstrates involvement of the periventricular and deep white matter with relative sparing of the U-fibers. Neurocognitive symptoms can be the primary presentation in the late juvenile onset form, with relatively subtle signs on the neurological examination (long tract signs alone are common).

Question 24

MRI findings of NF1 and NF2

Answer 24

Plexiform neurofibromas, gliomas of hypothalamus and optic chiasm, and punctate “UBOs” on MRI, are associated with neurofibromatosis 1 (NF1); schwannomas on cranial nerves are associated with NF2.

Question 25

Tuberous sclerosis

Answer 25

the lesion pictured is a depigmented macule associated with tuberous sclerosis. Of the choices, only subependymal nodular lesions are associated with tuberous sclerosis.

Question 26

sturge-weber

Answer 26

The presence of a facial angioma in the distribution of the ophthalmic division of the trigeminal nerve, in a child who presents with a unilateral, throbbing headache and neurologic deficits, is suggestive of the diagnosis of Sturge-Weber syndrome. In this syndrome, leptomeningeal angioma may represent an embryonic remnant of the venous plexus that failed to regress. The leptomeningeal angioma is most frequently unilateral, overlying the parietal and occipital lobes, and ipsilateral to the facial angioma. The presence of leptomeningeal angioma confirms the diagnosis of Sturge-Weber syndrome, which is often complicated by headache, stroke-like episodes, hemianopsia, glaucoma, and intellectual disability.

Question 27

Rett syndrome

Answer 27

Rett syndrome is seen in young girls and is characterized by developmental arrest, stereotypic hand movements, deceleration of head growth and loss of communication skills. It is an X-linked disorder and 80% to 85% of classic Rett syndrome patients will have an abnormality in the MECP2 gene, while approximately 50% of atypical Rett patients will have an abnormality of this gene.

Question 28

Niemann-Pick disease type C

Answer 28

Niemann-Pick disease type C is characterized by autosomal recessive inheritance with gradual and progressive neurologic deterioration. Patients have variable hepatosplenomegaly, and progressive neurodegeneration. Findings include vertical supranuclear (usually downgaze) palsy, ataxia, dystonia, seizures, gelastic cataplexy, and dementia.

Question 29

myelination in neonates through infants

Answer 29

At birth in the healthy full term neonate, the posterior limb of the internal capsule should be myelinated. Between 2 and 4 months of age, there should be evidence on MRI of myelination of the splenium of the corpus callosum, optic radiations, and cerebellar white matter. Myelination in the frontal white matter is not evident until between 4-6 months of age.

Question 30

Smith-Lemli-Opitz Syndrome

Answer 30

This clinical picture describes a typical presentation of Smith-Lemli-Opitz Syndrome. Brain abnormalities in this disorder of cholesterol synthesis (mutation of the 3-b-hydroxysterol-d-7 reductase gene) range from microencephaly, hypoplasia of the frontal lobes (holoprosencphaly), abnormal gyration, and cerebella hypoplasia.

Question 31

Menkes disease

Answer 31

Menkes disease (trichopoliodystrophy) is a disorder of copper transport resulting from a mutation in a copper transporting adenosine triphosphatase. Clinical features include hypotonia, poor feeding, and medically refractory seizures. The expected laboratory finding to confirm the diagnosis is a low serum copper and ceruloplasmin level.

Question 32

Moro reflex

Answer 32

For a normally developing child, the Moro reflex should disappear by 6 months. Abnormalities of the Moro reflex include abnormal persistence beyond 6 months and an asymmetric Moro reflex (reflecting dysfunction of the side which doesn’t activate).

Question 33

Angelman syndrome

Answer 33

The most common cause is a de novo deletion of the 15q11-q13 region, from the maternally derived chromosome 15

Question 34

galactosemia

Answer 34

Galactosemia is caused by absent Galactose-1-phosphate uridylyltransferase (GALT) enzyme, and results in elevation of erythrocyte galactose-1-phosphate levels. The majority of cases are diagnosed by newborn screen prior to onset of symptoms, and are treated by switching the affected infant to a lactose-free formula. If left untreated, neonates may present with abnormal liver function, failure to thrive, hyperbilirubinemia and hypoglycemia. Neurologic complications include neonatal encephalopathy and seizures. Urine test for reducing substances is positive, secondary to presence of sugars other than glucose in the urine.

Question 35

nemaline myopathy

Answer 35

The most common presentation of nemaline myopathy is congenital hypotonia. Affected children are usually quite bright, but exhibit a characteristic open-mouth appearance. Extraocular muscles are not affected, and muscle weakness is static throughout life. alpha actin 1gene mutations

Question 36

myotonic dystrophies and myotonias genetics

Answer 36

The vignette provides a classic description of a mother with myotonic dystrophy type 1 and anticipation in her son. A trinucleotide repeat expansion in the untranslated 3’ region of DMPK causes myotonic dystrophy type I. An expansion in CNBP causes myotonic dystrophy type 2 that does not typically show anticipation. CLCN1 mutations result in myotonia congenita. SCN4A mutations cause hypokalemic and hyperkalemic periodic paralysis, paramyotonia, myotonia congenital, and myasthenic syndrome. CHAT mutations result in a rare presynaptic congenital myasthenic syndrome.

Question 37

walker warburg syndrom

Answer 37

Walker Warburg syndrome is an example of an alpha-dystroglycanopathy. Named genetic causes are increasing, and include POMT and POMGnT1. The spectrum of alpha-dystroglycanopathies can vary, with some labelled as “muscle-eye brain” disease, and others in the more severe spectrum as Walker Warburg. Characteristic features in these disorders include cobblestone lissencephaly and muscle disease with elevated creatine phosphokinase often in the thousands, and eye involvement. A kinked brainstem is a pathognomonic finding.

Question 38

Self-limited (formally “benign”) focal epilepsy of childhood

Answer 38

Self-limited (formally “benign”) focal epilepsy of childhood with centrotemporal sharp waves presents from 2 to 13 years of age. About 20% of patients only have one seizure and in two thirds of the cases seizures are infrequent. Children with this disorder are neurologically normal, and the majority of patients outgrow the disorder. Oxcarbazepine is the treatment of choice, if treatment is necessary.

Question 39

lennox-gastaut syndrome

Answer 39

Patients with Lennox-Gastaut syndrome have multiple types of seizures, such as tonic, atypical absence, and atonic, with age of onset of 1 to 8 years. The EEG reveals slow spike-and-wave discharges of 1.5 Hz to 2 Hz. Most children are intellectually disabled, and approximately 70% have an identifiable cause for the cognitive delay and epilepsy.

Question 40

MELAS

Answer 40

MELAS–mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes–is one of several mitochondrial encephalopathies. In cases where a clear maternal inheritance has been established, there is a mutation in the mitochondrial tRNA leu. Cranial CT and MR scans in patients with MELAS reveal infarct-like areas bilaterally in the posterior cerebrum and almost always hypodensities or calcifications in the basal ganglia region.

Question 41

Aicardi syndrome

Answer 41

Aicardi Syndrome includes agenesis of the corpus callosum and “punched out” retinal colobomata. It is associated with infantile spasms, failure to thrive, and developmental regression. It is an x-linked dominant condition presumed to be fatal in males. The findings of the characteristic colobomas in the peripheral retina are diagnostic.

Question 42

opsoclonus-myoclonus syndrome

Answer 42

Opsoclonus-myoclonus syndrome, also called myoclonic encephalopathy of infancy, has characteristic conjugate eye movements called opsoclonus. The myoclous usually begins in the limbs, is worse with activity, and often has low amplitude, which can make it difficult to distinguish from ataxia. If untreated, many children will develop truncal myoclonus. 50% of patients have an underlying occult neuroblastoma. The movement is believed to be from autoantibodies that occur either against neuroblastoma or an infectio

Question 43

ataxia-telangectasia

Answer 43

Ataxia-telangiectasia is an autosomal recessive disorder characterized by deterioration of immune functioning, frequently including immunoglobulin A deficiency and absent tonsils. Gait disorder typically includes both ataxic and dystonic features early on. Choreoathetosis occurs later in some children. Patients with ataxia-telangiectasia are prone to develop infection and lymphomas. Family members who are heterozygous for the ataxia-telangiectasia gene are prone to breast and colon cancers.

Question 44

Pompe disease

Answer 44

Acid maltase deficiency (“Pompe disease”) is a lysosomal glycogen storage disease that affects practically all tissues and results from a defect of 1,4-glucosidase (acid maltase). Hypotonia, failure to thrive, and decreased reflexes develop during the first few months of life. Cardiomegaly is prominent in infantile forms, which more commonly present with pulmonary insufficiency. Unlike other glycogenoses, the liver is normal in size or only slightly enlarged, and there are no abnormalities of glucose homeostasis. PAS-positive glycogen is seen in membrane-bound vacuoles in muscle, hepatocytes, and Schwann cells, but no abnormalities are seen in myelin sheaths.

Question 45

kleine-levin syndrome

Answer 45

1Kleine-Levin syndrome; a disorder that predominantly affects adolescent males and is of varying duration. Symptoms include hyperphagia, hypersomnolence, cognitive changes, and mood disorder. The majority of cases follow infection. Pathology typically is localized to the hypothalamic region.

Question 46

dopa-responsive dystonia

Answer 46

The patient described has dystonia affecting his lower extremities with worsening in the latter portions of the day consistent with diurnal variation. This is consistent with dopa-responsive dystonia, which is most commonly caused by a mutation in GTP cyclohydrolase (GCH1). As dopa-responsive dystonia in children can have a variable presentation, it is generally recommended that pediatric patients with a primary dystonia, as described in this patient with normal MRI and no history of delivery or pregnancy complications, be trialed on levodopa-carbidopa. Patients with dopa-responsive dystonia typically respond to low doses of levodopa, and continue to respond to medication, even as adults.

Question 47

AEDs

• That exacerbate myoclonic Szs?
• That exacerbate absence Szs?

Answer 47

AEDs that may exacerbate myoclonic seizures:

• carbamazepine
• gabapentin
• lamotrigine
• pregabalin
• tiagabine
• vigabatrin.

AEDs that may exacerbate absence szs:

• gabapentin
• tiagabine
• vigabatrin