Brain regional glucose uptake changes in isolated cerebellar cortical dysplasia: qualitative assessment using coregistrated FDG-PET/MRI.

We aimed to assess brain regional glucose uptake (rGlcU) changes in children with isolated cerebellar cortical dysplasia (CCD) using 18-fluoro-deoxy-glucose positron emission tomography (FDG-PET). Six children aged 9 months to 11 years at the time of diagnosis, carrying isolated CCD (with no other associated posterior fossa or supratentorial malformation) underwent a brain FDG-PET and a subsequent 3DT1-weighted MRI for coregistration. The MRIs acquired previously at the time of diagnosis were reviewed to record the cerebellar dysplastic features and classify the patients as having minor, moderate, or severe CCD. The individual rGlcU was assessed qualitatively on coregistrated FDG maps. Clinical data from birth, including neurological and neuropsychological (verbal and motor skills) disturbances, were recorded. We found rGlcU changes within the cerebellum of four patients matching with the location and extent of structural abnormalities: hypometabolism in three patients with severe CCD involving the vermis and both cerebellar hemispheres and focal hypermetabolism in one patient with moderate CCD associated with a nodular heterotopic gray matter. No obvious rGlcU changes were found in the two patients with minor CCD involving the vermis only. Supratentorial rGlcU changes found commonly involved the basal ganglia bilaterally. Coregistrated FDG-PET/MRI technique is useful in detecting cerebellar cell dysfunction associated with isolated CCD. Our results enhance the need for multimodal and quantitative studies to better evaluate local and remote functional disturbances caused by CCD.

Neuropsychological evaluation and follow-up of children with cerebellar cortical dysplasia.

AIM: To describe neuropsychological disturbances and the developmental course associated with cerebellar cortical dysplasia (CCD). METHOD: The neuroimaging findings from 10 children (five males, five females; aged 3-10 y) with CCD were reviewed and classified. These children all underwent clinical neurological examination and neuropsychological assessment (NPA) on admission, then were followed for an average of 6 years using the cognitive Wechsler Scale, Vineland Adaptive Behavior Scales, and Rey-Osterrieth Complex Figure/McCarthy Drawing subtests. RESULTS: Based on magnetic resonance imaging, CCD was categorized as minor (n = 4), moderate (n = 1), and severe (n = 5). The first NPA disclosed mental retardation* in six (profound, three; moderate, one; mild, two) and normal intelligence in four (low, two; average, one; high, one), but with verbal/performance dissociation in three cases. Socio-adaptive functions were altered in all children except one. Visuospatial abilities were delayed in eight children. In the follow-up, no progression was observed in the three cases with profound mental retardation, whereas the remainder showed homogeneous or disharmonic progression, including improvement or deterioration of verbal/performance function. Cognitive impairment and evolution was not associated with the degree of cerebellar involvement. INTERPRETATION: The neuropsychological profile and evolution associated with CCD do not appear to be predictable, and some features might improve over time.

Infantile epileptic encephalopathy with late-onset spasms: report of 19 patients.

PURPOSE: Late-onset spasms (LOS) are epileptic spasms starting after the first year of life. Our aim was to assess the electroclinical features and the follow-up of the patients with this particular type of epileptic seizure. METHODS: We retrospectively included all patients with LOS confirmed by electroencephalography between 1989 and 2008. Clinical and electroencephalographic findings at diagnosis and during follow-up were collected. The Vineland scale was used to evaluate the neuropsychological outcome. RESULTS: We report 19 patients with LOS of 240 patients with recorded epileptic spasms. Eighteen patients had an epileptic encephalopathy with late-onset spasms. The ictal electroencephalography (EEG) showed a focal or generalized discharge of triphasic slow-waves, slow-spikes, or slow spikes-waves with fast activities. The interictal EEG usually showed focal or generalized slow-waves or slow spikes-waves without hypsarhythmia. LOS were controlled in only six patients. Three developed typical Lennox-Gastaut syndrome and 10 had a severe epileptic encephalopathy. Neuropsychological outcome was evaluated in 15 patients with the Vineland scale. Cognitive functions were normal in only one patient, whereas severe cognitive delay was observed in 12 of 15. CONCLUSION: Epileptic spasms may appear after the age of one. They are more frequently observed in patients with epileptic encephalopathy. In few patients this type of seizure was observed before the patients fulfill Lennox-Gastaut syndrome criteria. In one patient, we diagnosed a focal epilepsy with seizures occurring in cluster. When LOS are related to an epileptic encephalopathy, this epileptic syndrome seems to be linked to refractory epilepsy and severe cognitive outcome unrelated to the etiology.

Levetiracetam-induced depression in a 5-year-old child with partial epilepsy.

Depression in children and adolescents with epilepsy is common. Depression worsen quality of life in epilepsy patients. Neurobiological, social, and iatrogenic factors may play a role in depressive disorder development. We report a patient with partial epilepsy secondary to neonatal stroke, who developed depressive disorder as a result of levetiracetam (LEV) treatment. Our report illustrates the possible implication of iatrogenic factors in depression among epilepsy patients. However, recent data suggest that LEV may be effective in case of affective disorders. We discuss the factors linking epilepsy with depression. Because of its high incidence and its multiple physiopathologic factors, psychiatric comorbidity should be always assessed in pediatric epileptic patients.

Hot water epilepsy occurring at temperature below the core temperature.

A 6-year-old girl had water reflex epilepsy occurring at lower temperature than the core temperature. Seizures episodes consisted of a loss of consciousness absence followed by left predominant hypotonia with right fronto-temporal high voltage slow waves on the ictal-EEG. Seizures were only observed when the water was poured on scalp or face. Neuropsychological evaluation showed frontal dysfunction (Rey's figure). MRI study was normal. Oxcarbazepine permitted the disappearance of seizures and an improvement of executive disorders. In this case, the pathophysiological mechanism cannot be a hyperthermic related event. The temperature control as treatment of hot-water epilepsy could be used after the exploration of its implication in seizure induction.

Dystrophinopathy caused by mid-intronic substitutions activating cryptic exons in the DMD gene.

In the course of a mutation search performed by muscle dystrophin transcript analysis in 72 Duchenne and Becker Muscular Dystrophies (DMD/BMD) patients without gross gene defect, we encountered four unrelated cases with additional out-of-frame sequences precisely intercalated between two intact exons of the mature muscle dystrophin mRNA. An in silico search of the whole dystrophin genomic sequence revealed that these inserts correspond to cryptic exons flanked by one strong and one weak consensus splice site and located in the mid-part of large introns (introns 60, 9, 1M, and 62, respectively). In each case we identified an intronic point mutation activating the cryptic donor or acceptor splice site. The patients exhibited a BMD/intermediate phenotype consistent with the presence of reduced amounts of normally spliced transcript and normal dystrophin. The frequency of this new type of mutation is not negligible (6% of our series of 65 patients with 'small' mutations). It would be missed if the exploration of the DMD gene is exclusively performed on exons and flanking sequences of genomic DNA.

Benign myoclonic epilepsy in infants: electroclinical features and long-term follow-up of 34 patients.

PURPOSE: Benign myoclonic epilepsy in infants (BMEI) is a rare epileptic syndrome characterized only by generalized myoclonic seizures (MSs) in normal children during the first 2 years. Our aim was to assess the electroclinical features and the follow-up of this syndrome. METHODS: BMEI was confirmed by electroencephalogram (EEG) in four neuropediatric units in France between 1981 and 2002. Clinical and electroencephalographic findings at diagnosis and during the follow-up were collected. The Vineland scale or Wechsler scale or both were used to perform neuropsychological evaluations. RESULTS: We report 34 patients with BMEI characterized by MSs occurring many times a day. The ictal EEG showed a generalized discharge of polyspikes, polyspikes-and-waves, or spikes-and-waves. The interictal EEG was usually normal. A family history of febrile seizures (FSs) or epilepsy was noted in six patients. A history of FSs was noted in 11 patients. Eleven patients had reflex MSs. Monotherapy with valproic acid was effective in 23 of 30 treated patients. The onset of epilepsy was known in all patients. Four patients had seizures after the initial symptoms. Juvenile myoclonic epilepsy developed in two patients, and cryptogenic partial epilepsy in another. Neuropsychological outcome was evaluated in 20 patients (10 with Wechsler scales and 17 with the Vineland scale). Cognitive functions were normal in 17 patients, whereas developmental delay was observed in three others. CONCLUSIONS: BMEI is clinically characterized by myoclonic seizures involving the upper part of the body, occurring many times a day. The ictal EEG showed a generalized discharge of polyspikes, polyspikes-and-waves, or spikes-and-waves. The interictal EEG was usually normal. Reflex MSs were frequently observed, suggesting that two distinctive syndromes are not necessary. BMEI may be followed by juvenile myoclonic epilepsy. Despite a generally favorable neuropsychological outcome, mental retardation can be observed more frequently than in the general population.