Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case note study of 90 children with tuberous sclerosis showed that 56 had taken nitrazepam for seizures for from one month to 13 years. In 38 children nitrazepam was withdrawn but only two had immediate major seizures. Given that sleepiness, deterioration in motor skills, or ataxia seems to be associated in some children with treatment with nitrazepam, doctors may wish to review their long term prescriptions of this drug in children with tuberous sclerosis.
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PMID:Prolonged use of nitrazepam for epilepsy in children with tuberous sclerosis. 392 2

Thirty-one patients, aged 12.6 +/- 5.6 years, with refractory seizures for 8 +/- 4.3 years, were treated with adjunctive vigabatrin. Twenty-four percent had a > 50% reduction in seizure frequency (95% one-sided confidence interval). Generalized myoclonic, atonic, and tonic clonic and partial, with and without secondary generalization, seizures were all reduced at a mean dose of 70 +/- 38 mg/kg/day. Comparison of vigabatrin therapy duration, for partial and generalized seizure groups, utilizing Kaplan-Meier methodology showed similar survival times. Vigabatrin therapy was ineffective in the four children with tuberous sclerosis. Transient somnolence, ataxia and dizziness were the most frequent side effects. A severe aggressive agitation occurred in three patients, and necessitated discontinuation of vigabatrin in one patient. Vigabatrin was as effective in generalized as in partial seizures in this study. Clinical utility may be limited by unacceptable behavioral side effects in some patients.
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PMID:Vigabatrin in childhood epilepsy: comparable efficacy for generalized and partial seizures. 882 92

Cerebellar involvement in tuberous sclerosis is rare and generally nonsymptomatic. The authors describe a cerebellar tuber in a 5-year-old boy with tuberous sclerosis. A CT scan at age 2 years showed the characteristic cortical, white matter, and subependymal lesions of tuberous sclerosis. At 5 years, when the patient was symptomatic with ataxia, the CT and MRI scans revealed additionally the presence of a right cerebellar enhancing lesion with edema. A total surgical resection was undertaken. The cerebellar lesion was very firm and demonstrated marked disorganization of neuronal architecture in the cerebellar folia, with bizzare ectopic neurons in the molecular and granule cell layers and white matter, along with calcification, gliosis, and Rosenthal fiber deposition. Balloon cells with glassy, pale, eosinophilic cytoplasm were also present. There was a marked loss of myelin in the white matter, with significant vacuolation and gliosis. Electron microscopy documented abundant lysosomal inclusions, prominent rough endoplasmic reticulum and Golgi complexes, microtubules, intermediate filaments, and synaptic contacts. While there is much speculation as to the precise nature of cerebellar pathology in tuberous sclerosis, this case demonstrates conclusively that the cerebellar lesions reflect anomolous neuronal development and migration akin to supratentorial lesions and can rarely be symptomatic.
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PMID:Cerebellar pathology in tuberous sclerosis. 980 58

Tuberous sclerosis (TS) is caused by point mutations in the TSC1 or TSC2 genes on chromosomes 9q33-34 or 16p13, respectively. Clinical manifestations can be quite variable but are primarily limited to cutaneous, neurologic, and cardiovascular abnormalities. Phenotypes range from neurologically devastated to those with silent lesions. A 34-year-old patient with genetically documented TSC1 developed progressive ataxia over a decade, without TS lesions to correlate with this finding. After evaluation of common causes including long-term antiepileptic regimens, DNA testing for hereditary ataxias was performed and revealed the presence of an additional mutation on chromosome 9. The patient was homozygous for the Friedreich ataxia (FA) mutation, with 500 and 700 GAA repeats in the FRDA gene on chromosome 9q13. There is no established relationship between these two disorders and the occurrence of two mutations on the same chromosome is probably coincidental but emphasizes the importance of searching for additional genetic causes when the phenotype does not fit with an established genetic diagnosis.
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PMID:Coexistence of tuberous sclerosis and Friedreich ataxia. 1517 20

Lamotrigine is a broadly effective antiepileptic drug in mono- and add-on therapy for children and adolescents with focal and generalized epilepsies. Some epileptologists consider lamotrigine as the drug of primary choice in older school children and adolescents because of its good tolerability (no increase of body weight, no impairment of cognitive functions, due to new data probably no teratogenic properties). Lamotrigine can be used with good efficacy in numerable epilepsy diseases, such as tuberous sclerosis, juvenile neuronal lipofuscinosis and Rett syndrome. The first studies show that lamotrigine is also effective in children under 2 years of age. For therapy of difficult-to-treat epilepsies the combination of lamotrigine with valproate has proved as especially useful. This clinical observation is supported by new results of animal experiments. The dose-dependant and typical CNS side effects vertigo, ataxia, nausea, tremor and diplopia are found most frequently. The rate of allergic skin rashes which was very high before 1998 has decreased markedly by new dosage guidelines and is now as low as in older antiepileptic drugs. Lamotrigine does not impair cognitive functions, especially not memory and language. It has mood-stabilizing features and may improve quality of life. In animal experiments lamotrigine shows antiepileptogenic and neuroprotective effects.
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PMID:[Optimizing epilepsy therapy in children and adolescents with lamotrigine]. 1603 48

Autism is a neurodevelopmental disorder consisting of a constellation of symptoms that sometimes occur as part of a complex disorder characterized by impairments in social interaction, communication and behavioral domains. It is a highly disabling disorder and there is a need for treatment targeting the core symptoms. Although autism is accepted as highly heritable, there is no genetic cure at this time. Autism is shown to be linked to several genes and is a feature of some complex genetic disorders, including fragile X syndrome (FXS), fragile X premutation involvement, tuberous sclerosis and Rett syndrome. The term autism spectrum disorders (ASDs) covers autism, Asperger syndrome and pervasive developmental disorders (PDD-NOS) and the etiologies are heterogeneous. In recent years, targeted treatments have been developed for several disorders that have a known specific genetic cause leading to autism. Since there are significant molecular and neurobiological overlaps among disorders, targeted treatments developed for a specific disorder may be helpful in ASD of unknown etiology. Examples of this are two drug classes developed to treat FXS, Arbaclofen, a GABA(B) agonist, and mGluR5 antagonists, and both may be helpful in autism without FXS. The mGluR5 antagonists are also likely to have a benefit in the aging problems of fragile X premutation carriers, the fragile X -associated tremor ataxia syndrome (FXTAS) and the Parkinsonism that can occur in aging patients with fragile X syndrome. Targeted treatments in FXS which has a well known genetic etiology may lead to new targeted treatments in autism.
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PMID:TARGETED TREATMENTS IN AUTISM AND FRAGILE X SYNDROME. 2316 7