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)

The spatial distribution of metabolite signal intensities can be measured within entire sections of the brain by proton magnetic resonance spectroscopic imaging (1H-MRSI). A group of six patients (4 unrelated girls and 2 brothers from 5 families) with childhood ataxia with diffuse CNS hypomyelination (CACH) underwent long-echo-time, single-slice 1H-MRSI. Relative to controls, there was a decrease in the signal intensity of N-acetylaspartate, choline, and creatine throughout the white matter in all six patients. We identified lactate signals in white matter in three of them with advanced disease. The degree of white matter involvement was not homogeneous over the entire patient group, but did correlate with clinical presentation. Deep and posterior white matter tended to be more involved. There were no 1H-MRSI abnormalities in the gray matter. 1H-MRSI findings suggest that this syndrome is secondary to a metabolic defect causing hypomyelination, axonal degeneration, and, in the most compromised cases, accumulation of lactate. This study shows that CACH is not limited to girls.
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PMID:Proton magnetic resonance spectroscopic imaging in childhood ataxia with diffuse central nervous system hypomyelination. 764 53

Amongst 21 children with unclassified white matter diseases three patients could be characterised by an identical clinical picture, magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) findings as a probably distinct entity. Following a normal early development they later showed rapidly progressive motor symptoms (ataxia, spasticity) leading to severe handicap within one or two years after onset. Later on bulbar symptoms, optic atrophy and epileptic seizures occurred. The MRI showed a diffuse homogeneous hypodensity of the white matter almost identical to the signal of the ventricles. MRS revealed a near total absence of N-acetylaspartate, choline and creatine and an increase of lactate and glucose. One girl and one boy were siblings, indicating an autosomal recessive trait.
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PMID:Diffuse white matter disease in three children: an encephalopathy with unique features on magnetic resonance imaging and proton magnetic resonance spectroscopy. 830 12

Linkage and DNA analysis, magnetic resonance (MR) imaging, and single-voxel proton MR spectroscopy were obtained in 10 members of an Italian kindred with spinocerebellar ataxia type 1 (SCA1). The size of the basis pontis, cerebellar hemispheres, middle cerebellar peduncles, and medulla oblongata were decreased in 4 members carrying the SCA1 gene, compared with 6 unaffected subjects. Diffuse signal changes in the pons and cerebellum were observed only in the carrier with the longest disease duration and greatest disability. The N-acetylaspartate/creatine ratio and the choline/creatine ratio in the basis pontis were markedly decreased in 2 symptomatic SCA1 carriers and moderately decreased in 2 asymptomatic SCA1 carriers, compared with the unaffected family members and a control group of 10 healthy volunteers. Minor decreases in the N-acetylaspartate/creatine ratio and the normal choline/creatine ratio were observed in the cerebellar hemisphere of the SCA1 carriers. Reduction of the N-acetylaspartate/creatine ratio, demonstrated by MR spectroscopy in the pons, is likely to reflect a loss of neuronal viability and might represent a biochemical marker of SCA1 more sensitive than brainstem and cerebellum atrophy and signal changes shown by MR imaging.
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PMID:Proton magnetic resonance spectroscopy in an Italian family with spinocerebellar ataxia type 1. 948 66

Using proton magnetic resonance spectroscopy (1H-MRS) and single photon emission CT (SPECT), the cerebellum of patients with olivopontocerebellar atrophy (OPCA) and of age-matched control subjects was studied. A spectrum was collected from a 27 cm3 (3 x 3 x 3 cm) voxel in the cerebellum containing white and gray matters in order to measure the distribution and relative signal intensities of N-acetylaspartate (NAA), creatine (Cre) and choline (Cho). In the cerebellum of the patients with OPCA, mean NAA/Cre ratios for OPCA patients were significantly decreased compared with normal control subjects (OPCA, 1.01 +/- 0.247; controls, 1.526 +/- 0.144: p < 0.001). Mean NAA/Cho ratios for OPCA patients were slightly decreased (OPCA, 1.285 +/- 0.228; controls 1.702 +/- 0.469: p < 0.06). Cho/Cre ratios valued in the cerebellum of OPCA patients were not significantly different from those in normal controls (OPCA, 0.793 +/- 0.186; controls, 0.946 +/- 0.219). The ratio of RI count in the cerebellum to that in the occipital lobe was significantly decreased in OPCA patients (OPCA, 0.947 +/ 0.096; controls, 1.06 +/- 0.063: p < 0.01). Cerebellar signs were assessed including gait ataxia, limb ataxia, dysarthria, saccadic pursuit, and nystagmus separately or in combination. In patients with more severe ataxic gait and dysarthria. MRS revealed slightly lowered NAA/Cre ratio. There was no significant correlation between NAA/Cre ratio and severity of other clinical signs. The MRS and SPECT findings give a confirmative evidence of hypofunction in cerebellum of patients with OPCA.
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PMID:[Proton magnetic resonance spectroscopy and single photon emission CT in patients with olivopontocerebellar atrophy]. 974 73

A 55-year-old woman, who had two episodes of difficulty in putting a key into a keyhole probably due to optic ataxia at age 52 and 54 years old, developed speaking errors and was admitted to our hospital. She was 152.5 cm in height and 52.5 kg in weight. Neurological examination revealed right homonymous hemianopsia and sensory aphasia. A CSF examination revealed lymphocytic pleocytosis of 88/microliter. Serum lactate and pyruvate were remarkably increased after an aerobic exercise test. A few ragged-red fibers were present in the biopsied brachial biceps muscle. Brain MRI by FLAIR method showed scattered high signal lesions in the left temporal lobe, bilateral parieto-occipital lobes, left insular cortex and left thalamus. The left superficial temporal lesion was enhanced by gadolinium-DTPA. The proton MRS demonstrated the lactic acid peak as well as the decrease of NAA/choline ratio (0.38) in the left parieto-occipital region. Thus, she was diagnosed as a case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and successfully treated with ubidecarenone (150 mg/day). Six months later, she again developed seizure, right hemiparesis and deterioration of aphasia and presented again CSF lymphocytic pleocytoses of 15/microliter. Brain MRI demonstrated new lesions in the left temporoparietal lobes, left insular cortex and left corona radiata. Therefore, CSF pleocytosis appeared to be associated with stroke-like episodes in this case. Although the mechanism of CSF pleocytosis remains to be elucidated, it may involve the breakdown of blood-brain barrier caused by mitochondrial dysfunction. Otherwise, an inflammatory process similar to that in cases of Leber disease, who developed multiple sclerosis-like additional lesions in the central nervous system, may also take place in MELAS.
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PMID:[A case of MELAS showing CSF pleocytosis associated with stroke-like episodes]. 986 8

The objective of this study was to investigate cerebellar metabolism in patients with autosomal dominant cerebellar ataxia type 1 (ADCA-I) carrying two distinct mutations of spinocerebellar ataxia (SCA). Non-invasive image-guided proton magnetic resonance spectroscopy imaging (1H-MRSI) was performed in 4 patients with SCA2, and 3 patients carrying the SCA6 mutation. For MRSI, we employed a spin-echo sequence (TR = 1500 msec, TE = 135 msec, slice thickness = 15 mm, FOV = 240 mm) and a stimulated-echo sequence (TR = 1500 msec, TE = 20 msec, slice thickness = 15 mm, FOV = 240 mm). Measures included the peak integral ratios of neuronal and glial markers [N-acetylaspartate (NA) to creatine (Cr), choline-containing compounds (CHO) to Cr, and lactate (LAC) to Cr]. We found NA:Cr ratios were significantly lower in patients with SCA2 (40.4% lower) compared to patients carrying the SCA6 mutation. CHO:Cr ratios differed between the two mutations using short echo time (30.8% lower in SCA2), but not when applying long echo time 1H-MRSI. Measurements using long echo time revealed LAC peaks in all SCA2 patients. 1H-MRSI revealed metabolic differences between SCA2 and SCA6 patients. NA:Cr ratios were significantly lower in patients with the SCA2 mutation compared to the SCA6 mutation, and LAC signals were obtained in the cerebella of SCA2 patients. In addition, CHO:Cr ratios showed different behavior using short and long TE, indicating differences in relaxation times of choline compounds in SCA2.
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PMID:Proton magnetic resonance spectroscopic imaging reveals differences in spinocerebellar ataxia types 2 and 6. 1127 99

Congenital disorders of glycosylation, formerly called carbohydrate-deficient glycoprotein syndrome, may present in infancy with slowly progressive neurologic deficits including cognitive impairment, ataxia, pigmentary retinal degeneration, and neuropathy. The metabolic defect is in N-linked oligosaccharide synthesis, and diagnosis is made by a serum transferrin isoelectric focusing. We reviewed the neurologic course of 10 children with congenital disorders of glycosylation (ages 13 months to 7 years). All had severe developmental delay and ataxia; none walked unassisted, and the highest level of communication was simple sign language in one patient. Five of 10 children had seizures (absence, complex partial, tonic clonic). Only one patient has had strokelike episodes, despite reports that they are common in this population. The underlying basis of these episodes has been hypothesized to be coagulopathy due to dysfunctional, incorrectly glycosylated coagulation factors. This 5-year-old patient with congenital disorders of glycosylation type Ia had two strokelike episodes, with evolving hemiparesis over 5 to 6 days' duration, followed by focal tonic-clonic seizures. Coagulation studies were normal. Electroencephalography showed transient hemispheric polymorphous delta-range slowing and suppression. Magnetic resonance imaging revealed corresponding cortical swelling. Magnetic resonance angiography was normal. Magnetic resonance spectroscopy revealed a decrease in the N-acetylaspartate peak, suggesting neuronal loss, with normal lactate peak. The neuroradiologic data do not support a thrombotic, embolic, or hemorrhagic basis for strokelike episodes in carbohydrate-deficient glycoprotein syndrome; other mechanisms must be considered.
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PMID:Neurologic course of congenital disorders of glycosylation. 1141 5

Vacuolating megalencephalic leukoencephalopathy (VML) with subcortical cysts is a neurodegenerative disorder clinically characterized by megalencephaly with onset in the first year of life, progressive ataxia, spasticity and relatively spared cognitive function. Conventional MRI findings consist of diffusely abnormal cerebral white matter with subcortical cysts. Recent single-voxel proton MR spectroscopy studies have shown mild metabolic abnormalities in the white matter. We report here a combined proton MR imaging and MR spectroscopic imaging (1H-MRSI) study on 2 new, unrelated patients with this rare disorder. 1H-MRSI examinations, which can provide simultaneously metabolic information from many different brain regions, showed inhomogeneous decreases in all normally detected metabolites with significant widespread decreases in the ratio of N-acetylaspartate to creatine+phosphocreatine and concomitant small increases in lactate in the white matter of both hemispheres. Metabolic abnormalities were milder in the frontal white matter and more severe in the posterior white matter. The 1H-MRSI pattern of the gray matter was normal in both patients. In one patient, a subsequent 1H-MRSI examination (performed 3 years after the first) confirmed the presence of widespread decreases in the ratio of N-acetylaspartate to creatine+phosphocreatine in the white matter. We conclude that severe metabolic abnormalities can be found in the white matter of VML patients. This suggests that, despite the apparently mild clinical course, a severe neurodegenerative process may occur in the white matter of these patients.
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PMID:Severe metabolic abnormalities in the white matter of patients with vacuolating megalencephalic leukoencephalopathy with subcortical cysts. A proton MR spectroscopic imaging study. 1143 63

We report on two children with bilateral thalamic astrocytomas. The first patient developed psychomotor regression at the age of 20 months followed by rapidly progressive ataxia, intention tremor, slurred speech, and bouts of drowsiness. Magnetic resonance imaging (MRI) of the brain showed swelling and high signal intensity in both thalami accompanied by supratentorial hydrocephalus. The second patient presented with progressive cerebellar ataxia, headache, and vomiting at the age of 11 years. MRI of the brain revealed symmetrical, hyperintense and sharply delineated swelling of both thalami. Additional lesions were seen in the cerebellum and the right temporal lobe. In both cases proton magnetic resonance spectroscopy (MRS) of the lesions showed a striking decrease of the neuronal marker N-acetylaspartate, an increase of choline-containing compounds, and a minimal lactate peak. Stereotactic biopsies from the thalamus of the first patient and from a cerebellar lesion of the second patient finally revealed glial tumors, namely a diffuse astrocytoma of World Health Organization (WHO) grade II in the first patient and an anaplastic astrocytoma of WHO grade III in the second patient. We conclude that the clinical manifestations and MRI patterns of bilateral thalamic astrocytomas are very similar to those of encephalitis and neurometabolic disorders and should therefore be included in the differential diagnosis of these encephalopathies.
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PMID:Diagnostic difficulties in childhood bilateral thalamic astrocytomas. 1257 91

A 37-year-old macrocephalic woman was investigated for increasing gait disturbance due to longstanding spasticity and ataxia. MRI showed widespread bilateral increase in signal from cerebral white matter on T2-weighted images. Numerous subcortical cysts were visible in anterior-temporal and parietal regions. These clinical and neuroradiological features are those of megalencephalic leukoencephalopathy with subcortical cysts (MLC), a recently delineated white-matter disease with onset in childhood. Quantitative localised proton MR spectroscopy of white matter revealed marked reduction of N-acetylaspartate, creatine, and choline with normal values for myo-inositol, consistent with axonal loss and astrocytic proliferation. Diffusion tensor imaging showed an increased apparent diffusion coefficient and reduced anisotropy in affected white matter pointing to reduced cell density with an increased extracellular space. These findings are in line with histological changes alterations known to occur in MLC.
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PMID:Megalencephalic leukoencephalopathy with subcortical cysts in an adult: quantitative proton MR spectroscopy and diffusion tensor MRI. 1268 14


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