Search

Legius syndrome is characterized by numerous café‐au‐lait macules and intertriginous freckling, but typically lacks the distinctive tumor manifestations of neurofibromatosis type 1. We report two siblings with Legius syndrome and Lisch nodules illustrating the importance of eye surveillance in these patients.

Purpose of review: Tuberous sclerosis complex (TSC) is a variably expressed neurocutaneous genetic disorder characterized by hamartomatous growths in multiple organ systems. Neurologic involvement often confers the most severe symptoms, and can include epilepsy, increased intracranial pressure from hydrocephalus, intellectual deficits, and autism. The purpose of this review is to provide a neurologically focused update in the diagnosis and treatment of these complications in patients with TSC. Recent findings: We highlight 5 new areas of understanding in TSC: the neurobiology of TSC and its translation into clinical practice, vigabatrin in the treatment of infantile spasms, the role of tubers and epilepsy surgery, the treatment of subependymal giant cell astrocytomas, and TSC-related neuropsychiatric disorders. Summary: These recent advances in diagnosis and treatment give our patients with TSC and their families hope for the future for improved care and possible preventive cures, to the end goal of improving quality of life.

Troyer syndrome is a complex hereditary spastic paraplegia (HSP) due to a mutation in SPG20 first reported in the Old Amish population. A genetic mutation in SPG20 is responsible for a loss of function of the protein spartin in this disease. Since its initial report, this syndrome has also been reported in Turkish and Omani families. Here we report the case of three patients of Filipino descent with Troyer syndrome. Whole exome sequencing (WES) identified a homozygous mutation c.364_365delAT which predicts p.Met122Valfs*2 in SPG20. This is the same mutation identified in affected patients from the Omani and Turkish families, and is the first report of this syndrome in the Filipino population. Although Troyer syndrome has characteristic phenotypic manifestations it is likely underdiagnosed due to its rarity and we expect that WES will lead to identifying this disease in other individuals. © 2016 Wiley Periodicals, Inc.

1. Brian M. Faux, MD*,† 2. Abraham W. Suhr, MD‡ 3. David T. Hsieh, MD*,† 1. *Department of Pediatrics, 2. †Division of Pediatric Neurology, 3. ‡Department of Ophthalmology, San Antonio Military Medical Center, Ft Sam Houston, TX. After an unremarkable pregnancy, a term baby boy is delivered without complications. The newborn examination is notable only for a flat facial vascular birthmark involving nearly the entire distribution of the left trigeminal nerve, with some patchy involvement of the left upper torso, as well as involvement of the right upper eyelid (Fig 1). The patient otherwise acts well and has no abnormal movements. No notable similar dermatologic findings are reported within the family. Figure 1. A port-wine birthmark involved nearly the entire (V1, V2, V3) distribution of the left trigeminal nerve, the upper eyelid, and partly the V1 distribution of the right trigeminal nerve. The clinician discusses the possibility of ophthalmologic and neurologic complications with the family. They choose to defer neuroimaging. Ophthalmology consultation initially reveals suspicious findings for glaucoma, with mildly elevated intraocular pressure in both eyes and myopic cycloplegic refraction. The infant initially is closely observed because both optic nerves appear healthy, but by age 3 months, therapy for glaucoma is initiated. At age 5 months, the boy presents in status epilepticus with generalized clonic convulsions, which are aborted with intravenous lorazepam. Upon hospital admission, magnetic resonance imaging (MRI) of the brain reveals diffuse leptomeningeal enhancement of the left temporal and parietal lobes and prominence of the left choroid plexus (Fig 2), confirming the clinical diagnosis of Sturge-Weber syndrome (SWS). After a hospital course of progressive mental status improvement without recurrence of seizures, the boy is discharged on phenobarbital and later transitioned to oxcarbazepine. Figure 2. T1-weighted axial brain magnetic resonance imaging with gadolinium contrast reveals diffuse left temporal and parietal leptomeningeal enhancement (white arrow) and prominence of the left …

The reader is encouraged to write possible diagnoses for each case before turning to the discussion. We invite readers to contribute case presentations and discussions. Please use the Submit and Track My Manuscript link on the Pediatrics in Review homepage: http://pedsinreview.aappublications.org . A 34-month-old boy with known global developmental delays from Saudi Arabia is being evaluated after a first afebrile seizure. The seizure is described as full body shaking for 30 seconds with full recovery after a brief postictal period. There is no family history of neurologic disease and no known consanguinity. At birth there was a transient neonatal encephalopathy. At 6 months of age, persistent hypotonia prompted an evaluation for genetic and metabolic disorders and brain magnetic resonance imaging (MRI), the results of which were reportedly normal. Perinatal hypoxic-ischemic injury had been suggested as the likely cause of his neonatal encephalopathy and developmental delays. Currently, these delays include absent expressive language with only simple comprehension. He sat and crawled at approximately 2 years of age and only recently started cruising. His family is especially distressed by the fact that he sleeps very little and awakens several times at night. Physical examination reveals no obvious dysmorphic features except for mild prognathism. There are no cutaneous lesions suggestive of a neurocutaneous disorder. His head circumference is 47.4 cm (10th percentile), whereas height and weight are in the 50th percentile. He is alert and attentive to his environment and responsively smiles and laughs frequently. Axial hypotonia is noted in the presence of normal strength. Deep tendon reflexes are normal. Gait is wide and consists of a couple independent steps. The result of subsequent brain MRI is normal. Electroencephalography (EEG) reveals runs of posterior high-voltage slowing with admixed sharp waves. Additional genetic evaluation confirmed the diagnosis. A small head circumference relative to the …

The comprehensive care of children with epilepsy involves not only the treatment of seizures but also enhancement of their quality of life. Children with developmental disabilities are often unable to attend traditional summer camps because of safety concerns, as their prevalence of epilepsy is high and tends to be more severe. The goal of the current study is to describe our epilepsy experience at a summer camp adapted for children with developmental disabilities, with which the U. S. military has had a long-standing relationship. A retrospective chart review of all children and young adults attending summer sessions between 2008 and 2010 was performed. A total of 1,526 camp sessions were attended by 818 campers (mean 13.7 years), with 32.3% of campers having epilepsy. Of campers with epilepsy, 46.6% had cerebral palsy, 57.6% intellectual disability, and 28.8% autism spectrum disorders. Seizure frequency was at least weekly in 21.2% and at least daily in 13.3%. A history of status epilepticus was reported in 34.9%. There were seven camp infirmary visits because of seizures (incidence 1.4%), including two for status epilepticus. Thus, despite a high prevalence of severe epilepsy, in the setting of appropriate safety precautions, a safe camp experience can be provided, as seizure-related complications are rare.

Angelman syndrome is a neurogenetic disorder characterized by the loss or reduction of the ubiquitin-protein ligase E3A enzyme. Angelman syndrome results from a deletion or mutation of the maternally inherited 15q11.2-13.1 region, paternal uniparental disomy of chromosome 15, or an imprinting error. Epilepsy is common and may present with multiple seizure types, including nonconvulsive status epilepticus. Seizures are often intractable and typically require broad-spectrum antiepileptic medications. Dietary therapy has also proved successful in Angelman syndrome. Electroencephalographic patterns include notched δ and rhythmic θ activity and epileptiform discharges. Sleep disorders are also common, often characterized by abnormal sleep-wake cycles. Movement disorders are nearly universal in Angelman syndrome, most frequently presenting with ataxia and tremor. Neurocognitive impairment is always present to varying degrees, and expressive speech is typically severely affected. Individuals with Angelman syndrome often manifest psychiatric comorbidities including hyperactivity, anxiety, and challenging behaviors such as aggression and self-injury. We focus on a comprehensive whole-child approach to the diagnosis and long-term clinical care of individuals with Angelman syndrome.

Status epilepticus (SE), defined by either a prolonged seizure or a prolonged period of recurrent seizures without a return to baseline in-between seizures, is a neurological emergency frequently encountered in the pediatric intensive care unit (PICU). Pediatric SE, in addition to itself leading to PICU admission, occurs commonly in critically ill children. The clinical manifestations of SE are increasingly being recognized as presenting in a widely heterogeneous manner, particularly in the PICU. Subtler presentations can include altered mental status with or without suggestive motor movements. Thus, the initial fundamental task in managing pediatric SE is astute recognition and diagnosis, which often requires both clinical acumen and electroencephalography. This, in turn, allows for prompt management with concurrent evaluation and treatment. In this article, we will review the diagnosis, evaluation, and treatment of SE occurring in the setting of the PICU, with a focus on bringing the reader up-to-date on these topics.

Early infantile epileptic encephalopathy-9 (EIEE9) linked to mutations of the PCDH19 gene on the X chromosome was once thought to only affect females. Clinical features of the mutation include early onset of variable types and frequency of recurrent cluster of seizures, mild to profound intellectual disability, autistic traits, psychiatric features, and behavioral disturbances. PCDH19 pathogenic variants usually occur via an unusual X-linked pattern where heterozygous females are affected, but hemizygous males are asymptomatic. Somatic mosaic males for PCDH19 mutations are affected with EIEE9; since this discovery, four somatic mosaic males have been reported. We report the fifth confirmed male with somatic mosaicism of a novel pathogenic variant c.2147+2 T>C located in the splice site of Intron 1 of the PCDH19 gene, which continues to support that cellular interference is responsible for the pathogenic mechanism. The importance of our report is to provide significant knowledge about this rare cause of epilepsy in males, guide subsequent functional studies on males portraying an EIEE9 phenotype that have been potentially misdiagnosed, targeted therapeutic approaches, and further elucidation of this complex and interesting genetic disorder.

The ketogenic diet is the treatment of choice for epilepsy in certain disorders of brain metabolism, particularly glucose transporter type 1 deficiency and pyruvate dehydrogenase deficiency. The International Ketogenic Diet Study Group has listed several other conditions for which the ketogenic diet has been reported as being consistently more beneficial than average and for which the diet could be offered earlier. Whether efficacy in these conditions is due in part to the broad-spectrum efficacy of the ketogenic diet or due to mechanisms specific to these conditions is still under investigation. This chapter covers the use of dietary therapies for the treatment of epilepsy in certain genetic disorders, including Angelman syndrome and tuberous sclerosis complex, as listed by the International Ketogenic Diet Study Group, and in addition the chapter considers the use of epilepsy dietary therapies in patients with Rett syndrome and Sturge-Weber syndrome.

Seizure semiology in infants defies the typical characteristics and classification schemata that have been developed for older children and adults. A clear classification system is a necessary first step to facilitate proper diagnosis, choice of treatment, and determination of prognosis. This is an especially challenging task with seizures in infants. A semiologic system based upon simple descriptive terms has been proposed, which the neurologist and pediatrician will recognize as closer to clinical experience.

A working understanding of antiepileptic drug development, critical appraisal of drug trial design, and interpretation of study results are fundamental for the neurologist and epileptologist, to incorporate newer anticonvulsant medications into clinical practice. In this Journal Club, we evaluate a phase III study by Krauss et al.1 that demonstrates efficacy and safety of adjunctive perampanel for refractory partial-onset seizures.

4-year-old boy from Singapore, while on vacation in the United States (fi rst to Georgia and then Washington, D.C.), was evaluated for a subacute progressive ascending weakness. Five days before, he had noted the onset of vague paresthesias and muscular pains beginning in the distal left leg and later in the distal right leg. There was a gradual progression of diffi culties with walking during the next 5 days.

Vanishing White Matter disease (VWM) is an inherited progressive leukoencephalopathy caused by mutations in the genes EIF2B1-5, which encode for the 5 subunits of the eukaryotic initiation factor 2B (eIF2B), a regulator of protein synthesis. VWM typically presents with acute neurological decline following febrile infections or minor head trauma, and subsequent progressive neurological and cognitive regression. There is a varied clinical spectrum of VWM, with earlier onset associated with more severe phenotypes. Brain magnetic resonance imaging is usually diagnostic with diffusely abnormal white matter, progressing over time to cystic degeneration. We are reporting on a patient with infantile onset VWM associated with three heterozygous missense variants in EIF2B5, including a novel missense variant on exon 6 of EIF2B5 (D262N), as well as an interstitial duplication at 7q21.12. In addition, our case is unusual because of a severe epilepsy course, a novel clinical finding of hypopituitarism manifested by hypothyroidism and adrenal insufficiency, and a prolonged life span with current age of survival of 4 years and 11 months.

Our objective is to determine the prevalence of recurrent headaches in military-dependent children and to study the changes in headache frequency, severity, and duration during a parental deployment. Recurrent headaches are common in children and are often intensified by stressful life events. Military-dependent children are subjected to unique stressors, most significantly parental wartime deployment. No studies have evaluated the effect of deployment on somatic complaints, to include headaches. We conducted a parental, cross-sectional questionnaire-based study in patients aged 5 to 17 years who were seen in the pediatric or adolescent clinics at a regional military medical center. The overall prevalence of recurrent headaches in the preceding 12 months was 30%. Almost half reported headache worsening in frequency, severity, or duration over the previous 12 months, whether a parent was deployed or not. For children who had experienced parental deployment, younger children and females were affected more often. Younger females had the highest rates of headache worsening. This trend may indicate a more detrimental effect of parental deployment on childhood headache in certain populations.

Summary Purpose To characterize epileptic spasms (ES) occurring after the age of two years in patients with tuberous sclerosis complex (TSC), particularly treatment response to vigabatrin (VGB), which is extremely effective for infantile spasms (IS) in TSC. Methods The authors retrospectively reviewed 19 patients with TSC and ES. Medical records were assessed for clinical and treatment data, neurocognitive, EEG, MRI data, and genetic analyses. Results Of 391 patients with TSC, 19 (4.8%) had ES. Of those with detailed clinical data, six had infantile spasms that persisted after 2 years old, six recurred after an initial remission of infantile spasms (range 2–24 years old), and four occurred de novo over the age of two (range 2–20 years old). All concurrently had other seizure types. One had hypsarrhythmia on EEG. All had brain MRI stigmata typical of TSC. Thirteen had a mutation in TSC2 , and one in TSC1 . Six patients became spasm-free with medication treatment, including four with VGB, one with VGB in combination with the low glycemic index dietary treatment, and one with felbamate. Five became spasm-free after epilepsy surgery. VGB was not effective for seven patients. The majority continued to have refractory epilepsy. Conclusions ES are not uncommon in patients with TSC, especially those with TSC2 mutations. ES in TSC occur in the setting of other seizure types and refractory epilepsy. Hypsarrhythmia is rare. VGB can be effective, but the success of VGB for ES in TSC is not equivalent to that of IS in TSC.

Dravet syndrome is a rare epileptic encephalopathy linked to mutations in SCN1A (neuronal sodium channel α1 subunit) and characterized by an onset in infancy with polymorphous seizure types and developmental decline. It was reported recently that a proportion of patients previously diagnosed with alleged vaccine encephalopathy might possess SCN1A mutations and clinical histories that enabled a diagnosis of Dravet syndrome, but these results have not been replicated. We present here the cases of 5 children who presented for epilepsy care with presumed parental diagnoses of alleged vaccine encephalopathy caused by pertussis vaccinations in infancy. Their conditions were all rediagnosed years later, with the support of genetic testing, as Dravet syndrome. We hope that these cases will raise awareness of Dravet syndrome among health care providers who care for children and adolescents and aid in earlier recognition and diagnosis.

To investigate the presenting characteristics of new-onset afebrile seizures in infants (age 1-24 months) and the yield of neuroimaging.Prospective data were obtained from a standardized evaluation and management plan mandated by a critical care pathway. A total of 317 infants presented with new-onset afebrile seizures between 2001 and 2007. EEG was performed on 90.3%, head CT was obtained on 94%, and MRI was obtained on 57.4%.We found half of the infants had partial features to their seizures, yet evidence for primary generalized seizures was rare. The majority had more than 1 seizure upon presentation. Seizures in this age group tended to be brief, with 44% lasting less than 1 minute. EEG abnormalities were found in half. One-third of CTs were abnormal, with 9% of all CTs requiring acute medical management. Over half of MRIs were abnormal, with cerebral dysgenesis being the most common abnormality (p0.05). One-third of normal CTs had a subsequent abnormal MRI-only 1 resulted in altered medical management.Infantile seizures are usually brief, but commonly recurrent, and strong consideration should be made for inpatient observation. Acute imaging with CT can alter management in a small but important number of infants. Due to the superior yield, strong consideration for MRI should be given for all infants, as primary generalized seizures are rare, and there is a high rate of cerebral dysgenesis.

An 8-year-old boy with suspected psychogenic seizures was admitted for video-EEG monitoring. A stereotypical spell manifested as bilateral swinging extremity movements, and the patient proclaimed, “I’m doing the disco!” (video on the Neurology ® Web site at www.neurology.org). Right frontal-central rhythmic, sharp, fast activity (figure, A and B) was observed. MRI revealed seizure-related right frontal primary …

Bilateral paramedian thalamic and mesencephalic infarcts are infrequently reported in adults, and to our knowledge, has never been reported in a child. The presumed etiology is an occlusion of the artery of Percheron, an uncommon vascular variation, in which a single common trunk from one of the P1 segments of the posterior cerebral artery provides bilateral irrigation to the paramedian thalami and midbrain. Bilateral paramedian thalamic and mesencephalic infarcts in adults are associated with symptoms of decreased arousal, vertical gaze paresis, mood changes, and memory difficulties. Although some improvement of these symptoms does occur, complete recovery is rare. We present here a full-term male neonate, whose right-hand sided clonic seizures on day-of-life 2 prompted neuroimaging, which revealed bilateral paramedian thalamic and mesencephalic infarcts, suggestive of an occlusion of the artery of Percheron.

Editor’s note: Each month, this department features a discussion of an unusual diagnosis in genetics, radiology, or dermatology. A description and images are presented, with the diagnosis and an explanation of how the diagnosis was determined following. As always, your comments are welcome. A 2-year-old male was evaluated for developmental delay, irritability, and failure to thrive. Past medical history was also remarkable for recurrent upper respiratory infections, reactive airway disease, and gastroesophageal reflux. Prenatal history and family history were unremarkable. Examination revealed an alert, non-dysmorphic child with significant truncal hypotonia and with appendicular spasticity and dystonia.ABOUT THE AUTHORSDavid T. Hsieh, MD, is a Fellow, Department of Neurology, Children’s National Medical Center, Washington, D.C. Andrea L. Gropman, MD, is Assistant Professor, Department of Pediatrics and Neurology, Georgetown University Hospital. Phillip L. Pearl, MD, is Associate Professor, Department of Neurology, Children’s National Medical Center, Center for Neuroscience Research. Address correspondence to: David T. Hsieh, MD, Department of Neurology, Children’s National Medical Center, 111 Michigan Ave. NW, Washington, DC 20010; or fax 202-476-5226.The authors have disclosed no relevant financial relationships.The views expressed in this article are those of the author(s) and do not reflect the official policy or position of the U.S Air Force, Department of Defense, or the U.S. Government.

A 6-month-old infant with LIS1 17p13.3 deletion-positive Miller-Dieker syndrome (MDS) presented with increased seizures in the setting of a Pseudomonal and Enterococcal urinary tract infection and a buttock abscess associated with a lumbosacral dermal sinus tract. MRI of the neuraxis revealed lissencephaly (figure 1), a tethered cord without lipoma or other mass (figure 2A), and an infected lumbosacral dermal sinus tract. Communication with the spinal canal could not be appreciated (figure 2B). The dermal sinus was explored and found not to extend into the spinal canal. This tract was excised and the lateral abscess drained. Tethered cord release is planned upon resolution of infection.

An 8-year-old boy developed near complete ophthalmoplegia (video and figure 1), sparing the pupils, with mild gait ataxia, and areflexia. Miller Fisher syndrome was diagnosed after high titers of anti-GQ1b IgG, which are highly disease specific,1 …