Shay Menascu

Epilepsy in Rett syndrome---the experience of a National Rett Center.

Purpose:  Rett syndrome (RTT), an X‐linked, dominant neurodevelopmental disorder caused by mutations in the methyl‐CpG‐binding protein 2 (MECP2) gene, presents with acquired microcephaly, autistic regression, hand usage loss, and stereotypies. Epilepsy is frequent and has been reported to correlate with mutation type, general disease severity, and BDNF polymorphism. Our purpose was a comprehensive description of epilepsy features and course in RTT.

Parry-Romberg syndrome presenting as status migrainosus.

Parry-Romberg is a rare syndrome of unknown origin, characterized by hemiatrophy of the face including subcutaneous tissue, skeletal muscle, and bones, along with various ocular and central nervous system abnormalities. Some investigators consider that injury to the sympathetic fibers of the trigeminal nerve is a cause for evolution of this syndrome. Various central nervous system symptoms have been reported in correlation with the syndrome, including epilepsy and hemiparesis. These symptoms were related to ipsilateral (or, less frequently, contralateral) facial lesions, and in a few case reports were consistent with Rasmussens encephalitis-like lesions. Many clinical features overlap between facial linear scleroderma and en coup de sabre syndrome, which is characterized by localized inflammation leading to atrophy of the skin and subcutaneous tissues mainly on one side of the face; such overlap can lead to confusion in diagnosis. Furthermore, central nervous system involvement has been reported in en coup de sabre syndrome, leading to further misdiagnosis. The distinction between these two disorders is much disputed. Detailed here is the case of a child who had been diagnosed with en coup de sabre syndrome presenting with severe status migrainosus. Subsequent pathologic clinical, and neuroimaging findings led to a diagnosis of Parry-Romberg syndrome. This diagnosis is set in the context of the similarities, contradictions, and growing confusion between the two syndromes.

Neurologic Presentation in Children with Ataxia-Telangiectasia: Is Small Head Circumference a Hallmark of the Disease?

OBJECTIVE To define the neurologic characteristics and course of ataxia-telangiectasia (A-T). STUDY DESIGN Retrospective cross-sectional chart study of 57 children (ages 2 to 19 years) followed at an A-T clinic. Cerebellar and extracerebellar symptoms were graded according to degree of functional impairment. Head circumferences were plotted from the charts and z-scores were calculated and compared with that of family members. RESULTS Ataxia was present in 87.7%, followed by dysarthria (82.1%), dysmetria (75.4%), bradykinesia (69.2%), hyperkinetic movements (58.9%), and dystonia (15.8%). All features aggravated with age. The most striking clinical observation in our patients was low head circumference (z-score below 1), which was present in 60.9%; 17% had true microcephaly (z-score below 2). Microcephaly appeared postnatally, was proportionate to height and weight, and did not correlate with severity of ataxia or genotype. CONCLUSIONS In addition to cerebellar ataxia, extrapyramidal symptoms, especially bradykinesia, were frequent and disabling. Microcephaly is an integral part of A-T; understanding its pathogenesis may shed light on the mechanism by which ATM mutation causes dysfunction in the nervous system.

The Many Faces of Glut1 Deficiency Syndrome

Glucose transporter protein type 1 deficiency syndrome is a metabolic disorder manifesting as cognitive impairment, acquired microcephaly, epilepsy, and/or movement disorder caused by mutations in the SLC2A1 gene. We describe a cohort of isolated and familial cases of glucose transporter protein type 1 deficiency syndrome, emphasizing seizure semiology, electroencephalographic (EEG) features, treatment response and mutation pathogenicity. SLC2A1 mutations were detected in 3 sporadic and 4 familial cases. In addition, mutations were identified in 9 clinically unaffected family members in 2 families. The phenotypic spectrum of glucose transporter protein type 1 deficiency is wider than previously recognized, with considerable intra-familial variation. Diagnosis requires either hypoglycorrachia followed by SLC2A1 sequencing or direct gene sequencing. A ketogenic diet should be the first line of treatment, but more flexible diets, like the Atkins modified diet, can also be followed. Carbonic anhydrase inhibitors, such as acetazolamide or zonisamide, can be effective for seizure control.

Serum Biochemical Markers for Brain Damage in Children with Emphasis on Mild Head Injury

Despite the high incidence of mild pediatric head injuries, only within the past few years has there been increased interest and research in this area. This interest began when the findings from research done in adult patients showed that the effects of mild closed head injuries could interfere significantly with higher cognitive functioning, which impacted daily activities and employment. Traumatic brain injury (TBI) often involves a combination of mechanical trauma and local hypoxemia, on which serum biomarker concentrations may provide critical therapeutic data to time the brain injury. Biochemical serum markers after TBI may be used as a source for the identification of the injury, the extent of the injury and the time of its occurrence, and even for identifying its most likely outcome. This article discusses current research and theories regarding biochemical serum markers in brain injury with an emphasis on their impact on and utility in mild head injury in children.

Brain Lesion Load and Anatomic Distribution in Patients With Juvenile Clinically Isolated Syndrome Predicts Rapidly Advanced to Multiple Sclerosis

The aim was to assess brain lesion load and anatomical distribution in patients with juvenile clinically isolated syndrome and define magnetic resonance imaging (MRI) variables associated with rapidly advancing to multiple sclerosis. Patients were followed for one year after disease onset. Patients who experienced a second relapse were defined as those who rapidly advanced to multiple sclerosis. In all, 46 juvenile patients with a clinical presentation suggestive of multiple sclerosis were evaluated; 21 with gadolinium-enhancing lesions on initial brain MRI were excluded as they had already fulfilled the diagnosis criteria for multiple sclerosis. A total of 25 patients, 10 males and 15 females (mean ± SE age at onset 15.6 ± 0.6 years), met the definition of clinically isolated syndrome. The presence of a corpus callosum lesion at onset significantly differentiated between sustained clinically isolated syndrome and patients who rapidly advanced to multiple sclerosis.

PO-0846 Tumefactive Demyelinating Lesions In Juvenile-onset Multiple Sclerosis

Background The pathogenesis of large demyelinating lesions is still controversial. Atypical tumefactive demyelinating lesions (TDL) associated with acute inflammation, peri-lesional oedema and gadolinium ring enhancement are infrequently described in patients with juvenile-onset multiple sclerosis (MS). Objective To describe the clinical, imaging and micro-structural metrics of TDLs and chronic MS lesions in patients with juvenile-onset MS. Methods Ten patients diagnosed with MS were analysed for the presence of TDLs and chronic non enhancing MS lesions. The MS lesions were defined by a region of interest encircling the lesion centre on 2–3 consecutive slices. DTI images were acquired along 31 independent orientations using a single shot echo-planar imaging sequence. Results Four patients with 6 TDL, developed acute neurological symptomatology. The two girls presented with acute ataxia and aphasia, and the two boys with severe ataxia. Three patients progressed rapidly to develop seizures, became stuporotic and were admitted to the paediatric intensive care unit. Brain MRI demonstrated six TDLs. Analysis of the whole group (10 patients) disclosed 21 chronic non enhancing lesions. Assessment of DTI metrics of TDL as compared to chronic MS lesions disclosed significant differences. Conclusion TDL are a possible presentation of demyelinating disorders, posing a diagnostic and therapeutic dilemma towards neoplastic lesions. The micro-structural analysis of TDL suggests a severe tissue disruption probably due to the acute inflammatory process and oedema. Our analysis provides metrical tools that together with MR spectroscopy and perfusion may aid to identify accurately TDLs, potentially sparing young patients unnecessary and possibly debilitating brain biopsy.