Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Individuals with fragile X mental retardation 1 (FMR1) premutation (55 to 200 CGG repeats) are typically unaffected by fragile X syndrome. However, a subgroup of older males with the premutation have developed a neurological syndrome, which usually begins between 50 and 70 years and is associated with a progressive intention tremor and/or ataxia manifested by balance problems, frequent falling, and Parkinsonian symptoms, such as masked facies, intermittent resting tremor, and mild rigidity. This finding has been termed the fragile X-associated tremor/ataxia syndrome (FXTAS) and has brought focus to the aging process in individuals with the FMR1 mutation. The premutation is associated with elevated messenger RNA levels leading to the formation of intranuclear inclusions in neurons and astrocytes associated with FXTAS. This review is a summary of our experience with FXTAS in male carriers of the premutation.
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PMID:Aging in individuals with the FMR1 mutation. 1500 Jun 74

Fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder, was described recently among male carriers of expanded alleles (55-200 CGG repeats; premutation range) of the fragile X mental retardation 1 (FMR1) gene. Major features of the syndrome include intention tremor, gait ataxia, and parkinsonism in men over 50 years of age. This disorder is believed to be relatively common, possibly affecting 1 in 3,000 men over the age of 50 years in the general population. This raises the possibility that some patients presenting with essential tremor (ET) may harbor expanded FMR1 alleles. We screened 81 ET patients (40 males, 41 females) for expanded FMR1 alleles to determine whether ET is associated with such alleles. None of the ET cases had the premutation genotype. CGG repeat sizes ranged from 5 to 47 repeats within this study population, suggesting that expanded FMR1 alleles are uncommon among patients with ET. Screening of movement disorder patients with other clinical features of FXTAS (e.g., ataxia and parkinsonism) may be more likely to yield expanded FMR1 alleles.
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PMID:Screen for expanded FMR1 alleles in patients with essential tremor. 1530 Jun 58

Recently, Hagerman et al described the occurrence of a late-onset neurological disorder in five male carriers of the fragile-X (FMR-1) premutation. The major characteristics of this disorder, designated the Fragile-X Tremor Ataxia Syndrome (FXTAS), are progressive intention tremor, cerebellar ataxia and cognitive decline. Most cases of FXTAS published thus far were ascertained through families with a known fragile-X proband. Since cerebellar ataxia is one of the main cardinal features, we performed FMR-1 premutation screening in 122 male patients, older than 50 years, who were referred to us for testing of the spinocerebellar ataxia (SCA 1, 2, 3, 6, 7) genes and who were found to be negative. In this group of patients, we found five patients with an FMR-1 premutation. In four of them, a definite diagnosis of FXTAS could be made, based on the proposed diagnostic clinical and radiological criteria for FXTAS. In light of these figures, we recommend that FMR-1 analysis should be included in the molecular diagnostic work-up in the group of male ataxia patients older than 50 years.
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PMID:Screening for FMR-1 premutations in 122 older Flemish males presenting with ataxia. 1549 37

Deficient eye and hand movements are present in patients with multiple sclerosis. In the present study, eye and hand movements were simultaneously measured during visually guided wrist step-tracking tasks in 16 patients with intention tremor and 15 healthy controls. The coupling between eye and hand movements was analyzed during simultaneous eye-hand tracking, and interactions were studied by comparing the coordinated eye-hand condition with isolated eye- or hand-tracking conditions. Despite movement abnormalities, the onset of eye and hand movements was highly correlated and an invariant coupling between the saccadic completion time and hand peak velocity was found, suggesting that the temporal coupling was very much preserved. The differences between the experimental tracking conditions suggest that, in MS patients with intention tremor, the ocular system influenced the hand movements. Intention tremor amplitude was reduced when there was no preceding saccadic eye movement, whereas conversely, eye movements were not affected by different hand tremor severity.
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PMID:Interaction between eye and hand movements in multiple sclerosis patients with intention tremor. 1571 34

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

Intention tremor due to multiple sclerosis is clinically similar to cerebellar tremor. This study investigated, in 14 multiple sclerosis patients, the relationship between intention tremor severity and the lesion load in different infratentorial regions. Tremor amplitude was quantified during step-tracking tasks. The lesion load was measured on magnetic resonance images using an automated segmentation method. Intention tremor amplitude was significantly related to lesion load in the brainstem but not in the cerebellum. Specifically, tremor amplitude correlated with the lesion load in the contralateral pons, and patients with more severe tremor in both arms had a greater lesion load bilaterally in the pons. These results support the view that multiple sclerosis intention tremor is related to dysfunction of cerebellar inflow and/or outflow pathways.
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PMID:Relationship between multiple sclerosis intention tremor severity and lesion load in the brainstem. 1605 43

Disabling intractable tremor occurs frequently in patients with multiple sclerosis (MS). There is currently no effective medical treatment available, and the results of surgical intervention have been variable. Thalamotomy has been the mainstay of neurosurgical therapy for intractable MS tremor, however the popularisation of deep brain stimulation (DBS) has led to the adoption of chronic thalamic stimulation in an attempt to ameliorate this condition. With the goal of examining the relative efficacy and adverse effects of these two surgical strategies, we studied twenty carefully selected patients with intractable MS tremor. Thalamotomy was performed in 10 patients, with chronic DBS administered to the remaining 10. Both thalamotomy and thalamic stimulation produced improvements in postural and intention tremor. The mean improvement in postural tremor at 16.2 months following surgery was 78%, compared with a 64% improvement after thalamic stimulation (14.6 month follow-up) (P > 0.05). Intention tremor improved by 72% in the group undergoing thalamotomy, a significantly larger gain than the 36% tremor reduction following DBS (P < 0.05). Early postoperative complications were common in both groups. Permanent complications related to surgery occurred in four patients overall. Following thalamotomy, long-term adverse effects were observed in three patients (30%), and comprised hemiparesis and seizures. Only one patient in the thalamic stimulation group experienced a permanent deficit (monoparesis). We conclude that thalamotomy is a more efficacious surgical treatment for intractable MS tremor, however the higher incidence of persistent neurological deficits in patients receiving lesional surgery may support the use of DBS as the preferred surgical strategy.
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PMID:Thalamotomy versus thalamic stimulation for multiple sclerosis tremor. 1609 58

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


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