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 34-year-old female patient suffering from multiple sclerosis was treated with thalamic electrostimulation for right dominant brachial ataxia and intention tremor. At the end of the fourth year, the energy of the battery of the impulse generator was depleted. However, the patient was able to use her hands without major impairment with the stimulator OFF; due to a stable reduction of the degree of ataxia and intention tremor. The opposite thalamus received an electrode that was never activated because of a permanent thalamotomy effect. Thus, it can be concluded that restoration of function by means of deep brain stimulation might have been beneficial towards achieving a reorganization and stabilization of subcortico-cortical and cerebellar circuitry, supporting the process of self-repair in this patient with a less aggressive course of multiple sclerosis. However, scientific proof has yet to be found. This exceptional observation emphasizes the need for longterm studies.
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PMID:Improvement of upper limb ataxia and intention tremor allowing cessation of thalamic electrostimulation after four years. 1558 98

Carriers of premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene are spared the major neurodevelopmental symptomatology of fragile X syndrome patients carrying a full mutation (>200 repeats). In a proportion of premutation carriers, the repeat expansion is associated with a specific neurological profile involving intention tremor, ataxia, intellectual decline compatible with dementia syndrome, Parkinsonism and autonomic dysfunction at older age, commonly referred to as fragile-X-associated tremor/ataxia syndrome (FXTAS). Typical CNS changes include hyperintense signals on T2 weighted magnetic resonance images and the presence of ubiquitin-positive intranuclear neuronal inclusions. A knock-in mouse model with a (CGG)98 repeat in the premutation range has been generated and shown to exhibit elevated Fmr1 mRNA levels and ubiquitin-positive intranuclear neuronal inclusions, suggesting it may be a valid model for the human disease. Given the specific clinical profile of FXTAS patients, the expanded CGG repeat model was assessed for cognitive, behavioural and neuromotor performance at different ages (20, 52 and 72 weeks). The Morris water maze task exposed age-dependent decline of visual-spatial memory. Open field recordings revealed decreased exploration of the centre of the arena in the oldest group of expanded CGG repeat mice, potentially reflecting increased anxiety. Neuromotor tasks primarily showed decline of performance on the accelerating rotarod with age in the premutation carriers but not in control littermates. The age-dependent cognitive decline and neuromotor disturbances may be related to the progressive cognitive and behavioural difficulties observed in FXTAS patients.
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PMID:Cognitive decline, neuromotor and behavioural disturbances in a mouse model for fragile-X-associated tremor/ataxia syndrome (FXTAS). 1587 60

Carriers of premutation within the FMR1 gene are typically normal intellectually, although a limited number of them have been reported to have either learning disabilities or mild dysmorphic features. A neurological condition involving intention tremor, ataxia and cognitive decline has recently been identified among older males carrying premutation alleles of the FMR1 gene, including grandfathers of children affected with fragile X syndrome. Characteristic findings from magnetic resonance imaging include cerebral and cerebellar volume loss and altered signal intensities of the middle cerebellar peduncles. This syndrome may represent one of the more common causes of tremor, ataxia and dementia among older males. The diagnosis of FXTAS is straightforward if a family at high genetic risk could be identified. Thus genetic counseling should be offered to such family.
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PMID:[Fragile X-associated tremor/ataxia syndrome]. 1598 Nov 62

A cerebellar neuroaxonal dystrophy in working collie sheep dogs from two properties in New Zealand and one property in Australia is described. Clinical signs developed from 2-4 months of age and included hypermetria, wide-based stance, difficulty in maintaining balance, intention tremor and ataxia. Numerous spheroids, associated with mild Wallerian degeneration, were present in the central cerebellar, adjacent peduncular and folia white matter, and associated cerebellar roof and lateral vestibular nuclei. The history of several affected pups in litters from successive matings of the same sire and dam is suggestive of an autosomal recessive mode of inheritance.
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PMID:Suspected inherited cerebellar neuroaxonal dystrophy in collie sheep dogs. 1603 Aug 83

The FMR1 gene is involved in two different syndromes: Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome (FXTAS). Fragile X syndrome is a childhood disease and is associated with mental retardation as the main clinical characteristic, whereas FXTAS develops in men and women over 50 years of age. FXTAS represents a new form of inclusion disorder with a high prevalence in the general population. The neurologic phenotype of FXTAS includes intention tremor and ataxia. Associated features are dementia, parkinsonism, neuropathy, and autonomic dysfunction. Elevated FMR1 transcripts have been proposed as the molecular basis of the pathogenic mechanism leading to FXTAS. This review discusses recent developments in the clinical phenotype, prevalence and screening, animal models, and molecular mechanisms of RNA-based pathogenesis in FXTAS.
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PMID:FXTAS: a progressive neurologic syndrome associated with Fragile X premutation. 1613 24

We report a 60-year-old man with a 6-year history of tremor in his hands. He noted the onset of short of breath and gait disturbance in 1994; both of these symptoms were slowly progressive. Then recently he developed fever two months prior to the present admission. He was admitted to the rheumatology department of our hospital and neurological consultation was asked on December 13, 2000. On neurologic examination, he showed Gottron sign and fine crackle in both lungs. Pertinent neurological findings were bilateral dysmetria in finger-to-nose and heel-to-knee tests and a broad-based gait. In addition, he showed intention tremor in upper extremities more on the left. Romberg sign was positive. Deep tendon reflexes were decreased. Vibratory sensation was reduced at the wrists. The patient's hemoglobin was 11.1 g/dl, with a mean corpuscular volume of 92.0 fl. Vitamin B12 level was 190 (reference range, >230 pg/ml). Serum lactic acid, pyruvic acid and ceruloplasmin were slightly elevated. Chest X-ray showed interstitial pneumonia. Muscle biopsy showed grouping of small angular fiber. Brain MRI showed diffuse atrophy of the cerebral cortex and the cerebellum hemisphere. Thalamotomy did not improve his tremor. He was admitted again in November 2001. General worsening of his neurological findings was observed. IL2-receptor was markedly elevated. Serum anti-Hu, Yo and Ri antibodies were negative. An anaplastic carcinoma was found in his jejunum. He died from respiratory failure in February 2002. He was discussed in a neurological CPC and the chief discussant arrived at a conclusion that the patient had paraneoplastic syndrome. Other diagnosis entertained included MERRF, GSS, Ramsay Hunt syndrome, subacute combined degeneration, spinocerebellar degeneration. Majority of the participants thought that paraneoplastic syndrome was most likely. Post-mortem examination revealed poorly differentiated carcinoma in the small intestine. Myeline pallor was noted in the posterior and the lateral columns in the thoracic spine. Neuronal cell loss was observed in the Purkinje cell and granular cell layer in the cerebellum. Sural nerve demonstrated loss of myelinated fibers and grouping of small fibers. Neuropathological findings were consistent with Friedreich ataxia; nevertheless, no mutation was reported in frataxin in Japan. The neuropathologist concluded that neuropathological diagnosis was a spinocerebellar ataxia with neuropathological similarities to Friedreich ataxia.
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PMID:[A 60-year-old man with intention tremor as an initial symptom followed by cerebellar ataxia, peripheral neuropathy and dementia]. 1614 16

A 75-year-old man had progressive difficulty with walking, intention tremor, ataxia, and mild cognitive deficits. MRI scan ofthe brain showed symmetrical hyperintensities in the middle cerebellar peduncles. DNA analysis ofthe fragile-X gene revealed an expansion of 150-200 repetitions in the FMR1-gene, compatible with a premutation in the fragile-X gene. Two years later, after progression of the symptoms, the patient was admitted to a nursing home. The clinical picture of intention tremor, parkinsonism and ataxia with white matter lesions and atrophy on MRI occurs in carriers of this premutation and has recently been described as the fragile-X-associated tremor/ataxia syndrome. Recognition of this clinical picture is important for the patient but also for the relatives, since female carriers of the premutation have an increased risk of offspring with the fragile-X syndrome.
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PMID:[Progressive ataxia and cognitive deficits caused by premutation in the fragile-X-mental retardation gene]. 1627 33

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder that affects carriers, principally males, of premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. Clinical features of FXTAS include progressive intention tremor and gait ataxia, accompanied by characteristic white matter abnormalities on MRI. The neuropathological hallmark of FXTAS is an intranuclear inclusion, present in both neurons and astrocytes throughout the CNS. Prior to the current work, the nature of the associations between inclusion loads and molecular measures (e.g. CGG repeat) was not defined. Post-mortem brain and spinal cord tissue has been examined for gross and microscopic pathology in a series of 11 FXTAS cases (males, age 67-87 years at the time of death). Quantitative counts of inclusion numbers were performed in various brain regions in both neurons and astrocytes. Inclusion counts were compared with specific molecular (CGG repeat, FMR1 mRNA level) and clinical (age of onset, age of death) parameters. In the current series, the three most prominent neuropathological characteristics are (i) significant cerebral and cerebellar white matter disease, (ii) associated astrocytic pathology with dramatically enlarged inclusion-bearing astrocytes prominent in cerebral white matter and (iii) the presence of intranuclear inclusions in both brain and spinal cord. The pattern of white matter pathology is distinct from that associated with hypertensive vascular disease and other diseases of white matter. Spongiosis was present in the middle cerebellar peduncles in seven of the eight cases in which those tissues were available for study. There is inclusion formation in cranial nerve nucleus XII and in autonomic neurons of the spinal cord. The most striking finding is the highly significant association between the number of CGG repeats and the numbers of intranuclear inclusions in both neurons and astrocytes, indicating that the CGG repeat is a powerful predictor of neurological involvement in males, both clinically (age of death) and neuropathologically (number of inclusions).
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PMID:Neuropathology of fragile X-associated tremor/ataxia syndrome (FXTAS). 1633 42

The fragile X mental retardation 1 gene (FMR1) mutation causes two disorders: fragile X syndrome (FXS) in those with the full mutation and the fragile X-associated tremor/ataxia syndrome (FXTAS) in some older individuals with the premutation. FXS is caused by a deficiency of the FMR1 protein (FMRP) leading to dysregulation of many genes that create a phenotype with ADHD, anxiety, and autism. FXTAS is caused by the elevation of FMR1-mRNA to levels 2 to 8 times normal in the premutation. This causes an RNA gain of function toxicity leading to brain atrophy, white matter disease, neuronal and astrocytic inclusion formation, and subsequent ataxia, intention tremor, peripheral neuropathy, and cognitive decline. The neurobiology and pathophysiology of FXS and FXTAS are described in detail.
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PMID:Lessons from fragile X regarding neurobiology, autism, and neurodegeneration. 1651 73

There is no established treatment for the neurological features of the recently discovered fragile X-associated tremor/ataxia syndrome (FXTAS). Fifty-six patients with FXTAS completed a questionnaire to determine whether any medications had been effective for neurological symptoms. Of 11 subjects with definite FXTAS, 8 (70%) were on medications for their neurological symptoms, whereas most subjects with possible or probable FXTAS, 31 (70%) of 45 subjects, were not on medications. Although no therapy was uniformly effective for intention tremor, ataxia, Parkinsonism, memory loss, or anxiety, some subjects with intention tremor or Parkinsonism reported improvement with medications frequently used in other movement disorders. Overall, all 22 subjects on medications reported improvement in one or more symptoms. Lack of insight, recall bias, and cognitive impairment may have resulted in an underestimation of the beneficial effect of medical therapy. This study suggests that patients with FXTAS can derive improvement from medication treatment for some of their symptoms.
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PMID:Symptomatic treatment in the fragile X-associated tremor/ataxia syndrome. 1677 16


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