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)

We reviewed 153 episodes of cobalamin deficiency involving the nervous system that occurred in 143 patients seen over a recent 17-year period at 2 New York City hospitals. Pernicious anemia was the most common underlying cause of the deficiency. Neurologic complaints, most commonly paresthesias or ataxia, were the first symptoms of Cbl deficiency in most episodes. The median duration of symptoms before diagnosis and treatment with vitamin B12 was 4 months, although long delays in diagnosis occurred in some patients. Diminished vibratory sensation and proprioception in the lower extremities were the most common objective findings. A wide variety of neurologic symptoms and signs were encountered, however, including ataxia, loss of cutaneous sensation, muscle weakness, diminished or hyperactive reflexes, spasticity, urinary or fecal incontinence, orthostatic hypotension, loss of vision, dementia, psychoses, and disturbances of mood. Multiple neurologic syndromes were often seen in a single patient. In 42 (27.4%) of the 153 episodes, the hematocrit was normal, and in 31 (23.0%), the mean corpuscular volume was normal. Neutropenia and thrombocytopenia were unusual even in anemic patients. In nonanemic patients in whom diagnosis was delayed, neurologic progression frequently occurred although the hematocrit remained normal. In 27 episodes, the serum cobalamin concentration was only moderately decreased (in the range of 100-200 pg/ml) and in 2 the serum level was normal. Neurologic impairment, as assessed by a quantitative severity score, was judged to be mild in 99 episodes, moderate in 39 and severe in 15. Severity of neurologic dysfunction before treatment was clearly related to the duration of symptoms prior to diagnosis. In addition, the hematocrit correlated significantly with severity, independent of the longer duration of symptoms in nonanemic patients. Four patients experienced transient neurologic exacerbations soon after beginning treatment with cyanocobalamin, with subsequent recovery. Followup evaluation was adequate to assess the neurologic response to vitamin B12 therapy in 121 episodes. All patients responded, and in 57 (47.1%), recovery was complete, with no remaining symptoms or findings on examination. The severity score was reduced by 50% or greater after treatment in 91% of the episodes. Residual long-term moderate or severe neurologic disability was noted following only 7 (6.3%) episodes. The extent of neurologic involvement after treatment was strongly related to that before therapy as well as to the duration of symptoms. The percent improvement over baseline neurologic status after treatment was inversely related to duration of symptoms and hematocrit. Some evidence of response was always seen during the first 3 months of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurologic aspects of cobalamin deficiency. 164 56

We report a case of sporadic olivopontocerebellar atrophy (OPCA) with marked laterality of cerebellar atrophy and degenerative changes in the corticopontine tract. A 35-year-old man was admitted to our hospital for evaluation of titubation, gait disturbance, dysarthria, and urinary and fecal incontinence. Neurological examination showed a wide based gait, slurred speech, truncal ataxia, slightly saccadic ocular movement, and finger-to-nose incoordination, greater on the right than the left. Deep tendon reflexes were hyperactive and preserved with the right side greater than the left. Bilateral Babinski signs were present, and the patient had neurogenic bladder without orthostatic hypotension. Cranial MRI showed atrophy of the cerebellum with right dominance and of the pons. On T2- and PD-weighted images, high-intensity areas were detected at the left internal capsule, crus cerebri and ventral pons. These findings were compatible with the right dominance of the clinical symptoms. The high intensity area detected at the posterior internal capsule was more extensive than that seen in patients with motor neuron disease. This finding may coincide with the degenerative changes in the corticopontine tract. Moreover, 99mTc-HMPAO-SPECT showed the crossed cerebello-cerebral diaschisis (CCCD) pattern, which indicates the decreased CBF in the right cerebellar hemisphere and the left frontal lobe. These findings may reflect degenerative changes in the corticopontine tract in OPCA.
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PMID:[Neuroradiological findings of sporadic olivopontocerebellar atrophy with marked laterality and degenerative changes in the corticopontine tract]. 899 39

Thoracolumbar intervertebral disk disease (IVDD) is a common, important cause of paraspinal hyperesthesia, pelvic limb ataxia, paraparesis, paraplegia, and urinary and fecal incontinence in dogs. A companion article reviewed pathophysiology, epidemiology, physical examination, and emergency medical therapy. This article addresses the diagnosis, prognosis, and treatment of dogs with thoracolumbar IVDD.
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PMID:Canine thoracolumbar invertebral disk disease: diagnosis, prognosis, and treatment. 1941 98

Thoracolumbar intervertebral disk disease (IVDD) is a common, important cause of paraspinal hyperesthesia, pelvic limb ataxia, paraparesis, paraplegia, and urinary and fecal incontinence in dogs. Research offers insights into the pathophysiology, diagnosis, prognosis, and treatment of this disorder. The comparative efficacy of many familiar therapies remains unknown and controversial. This article reviews the pathophysiology and epidemiology of this condition and the examination and emergency medical therapy of dogs with suspected thoracolumbar IVDD.
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PMID:Canine thoracolumbar invertebral disk disease: pathophysiology, neurologic examination, and emergency medical therapy. 1941 99

This retrospective case series examined the effectiveness of spinal segmental stabilisation, with or without decompression, in nine dogs with neurological deficits associated with dorsal hemivertebrae. Data on signalment, preoperative neurological status, imaging findings, surgical techniques and outcome were evaluated. All cases occurred in young or adult, small-breed dogs with neurological signs ranging from progressive moderate pelvic limb ataxia to non-ambulatory paraparesis. Six dogs also showed urinary and faecal incontinence. In each dog, one or more dorsal thoracic hemivertebra(e) were detected by radiography and MRI. In all dogs, hemivertebra(e) were associated with kyphosis and reduced vertebral canal diameter. All dogs were surgically managed with spinal segmental stabilisation, using Steinmann pins and orthopaedic wires and/or sutures attached to the spinous processes. Three dogs also underwent additional decompressive surgery. Post-operative follow-up ranged from 1.5 to 5.5 years. Immediate or delayed post-operative complications occurred in three dogs, including implant migration or loosening. Eight dogs showed long-term gait improvement, with resolution of incontinence if previously present. At 2-6 years post-surgery, four dogs were neurologically normal, three had mild residual ataxia, one had moderate ambulatory paraparesis, and one dog relapsed 3.5 years after surgery, resulting in severe paraparesis. Spinal segmental stabilisation techniques, with or without decompression, can result in satisfactory outcomes in small dogs with hemivertebrae and mild to moderate neurological signs. Further adaptations might be required to avoid implant loosening and allow continued growth in immature dogs.
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PMID:Surgical treatment of dorsal hemivertebrae associated with kyphosis by spinal segmental stabilisation, with or without decompression. 2524 46

Cerebral choline metabolism is crucial for normal brain function, and its homoeostasis depends on carrier-mediated transport. Here, we report on four individuals from three families with neurodegenerative disease and homozygous frameshift mutations (Asp517Metfs*19, Ser126Metfs*8, and Lys90Metfs*18) in the SLC44A1 gene encoding choline transporter-like protein 1. Clinical features included progressive ataxia, tremor, cognitive decline, dysphagia, optic atrophy, dysarthria, as well as urinary and bowel incontinence. Brain MRI demonstrated cerebellar atrophy and leukoencephalopathy. Moreover, low signal intensity in globus pallidus with hyperintensive streaking and low signal intensity in substantia nigra were seen in two individuals. The Asp517Metfs*19 and Ser126Metfs*8 fibroblasts were structurally and functionally indistinguishable. The most prominent ultrastructural changes of the mutant fibroblasts were reduced presence of free ribosomes, the appearance of elongated endoplasmic reticulum and strikingly increased number of mitochondria and small vesicles. When chronically treated with choline, those characteristics disappeared and mutant ultrastructure resembled healthy control cells. Functional analysis revealed diminished choline transport yet the membrane phosphatidylcholine content remained unchanged. As part of the mechanism to preserve choline and phosphatidylcholine, choline transporter deficiency was implicated in impaired membrane homeostasis of other phospholipids. Choline treatments could restore the membrane lipids, repair cellular organelles and protect mutant cells from acute iron overload. In conclusion, we describe a novel childhood-onset neurometabolic disease caused by choline transporter deficiency with autosomal recessive inheritance.
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PMID:Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration. 3233 75