Lisch nodules and iris mammillations in two siblings with familial legius syndrome.

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.

Multiple Sclerosis Exacerbation Associated With High-Altitude Climbing Exposure.

The spectrum of the neurological effects of high-altitude exposure can range from high-altitude headache and acute mountain sickness, to the more severe end of the spectrum with high-altitude cerebral edema. In general, patients with known unstable preexisting neurological conditions and those patients with residual neurological deficits from a preexisting neurological condition are discouraged from climbing to high altitudes because of the risk of exacerbation or worsening of symptoms. Although multiple sclerosis exacerbations can be triggered by environmental factors, high-altitude exposure has not been reported as a potential trigger. We are reporting the case of a multiple sclerosis exacerbation presenting in an active duty U.S. Air Force serviceman upon ascending and descending Mt. Fuji within the same day.

Somatic Mosaicism of PCDH19 in a male with early infantile epileptic encephalopathy and review of the literature.

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.

Increased Intracranial Pressure in a Boy with Gorham-Stout Disease.

Gorham-Stout disease (GSD), also known as vanishing bone disease, is a rare disorder, which most commonly presents in children and young adults and is characterized by an excessive proliferation of lymphangiomatous tissue within the bones. This lymphangiomatous proliferation often affects the cranium and, due to the proximate location to the dura surrounding cerebrospinal fluid (CSF) spaces, can result in CSF leaks manifesting as intracranial hypotension with clinical symptoms to include orthostatic headache, nausea, and vertigo. We present the case of a boy with GSD and a known history of migraine headaches who presented with persistent headaches due to increased intracranial pressure. Although migraine had initially been suspected, he was eventually diagnosed with intracranial hypertension after developing ophthalmoplegia and papilledema. We describe the first known instance of successful medical treatment of increased intracranial pressure in a patient with GSD.

Three cases of Troyer syndrome in two families of Filipino descent.

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.

Tuberous sclerosis complex: Five new things.

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.

Infantile onset Vanishing White Matter disease associated with a novel EIF2B5 variant, remarkably long life span, severe epilepsy, and hypopituitarism.

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.

Epilepsy at a summer camp for children and young adults with developmental disabilities: a 3-year experience.

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.

Epileptic spasms in tuberous sclerosis complex.

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.

Efficacy and safety of rufinamide in pediatric epilepsy.

Rufinamide is a novel anticonvulsant medication approved by the US Food and Drug Administration (FDA) in 2008 for the treatment of seizures associated with Lennox-Gastaut syndrome in patients 4 years of age and older, based upon clinical trials demonstrating clinical efficacy and tolerability. Rufinamide is especially effective for tonic-atonic seizures in Lennox-Gastaut syndrome, but is subsequently proving to be safe and effective in clinical practice for a broad patient population with refractory epilepsy. Although further research and clinical experience is needed, rufinamide holds the promise to positively impact the care of children with epilepsy. In this review, we review the use of rufinamide in pediatric epilepsy, with a focus on efficacy and safety.

Brain and spinal manifestations of Miller-Dieker syndrome.

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.

Recurrent headache in military-dependent children and the impact of parent deployment.

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.

Neurologic manifestations of Angelman syndrome.

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.

Alleged cases of vaccine encephalopathy rediagnosed years later as Dravet syndrome.

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.