Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Serum iron parameters were measured in a group of schizophrenic patients who had developed acute neuroleptic-induced dystonia (N = 17) and in control patients with no history of extrapyramidal disorders (N = 16). No differences were found between the two groups for iron, ferritin or transferrin levels. 2. Iron status was estimated in 44 schizophrenic patients starting treatment with high-potency neuroleptics before and after 3 weeks of medication. In the 6 patients developing dystonia serum iron levels as well as other iron parameters did not differ from the values observed in the remaining 38 patients either on admission or after neuroleptic treatment. In each group the haematological profile was not modified by neuroleptic medication. 3. These results do not support an association between low serum iron and the occurrence of neuroleptic-induced dystonic reactions.
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PMID:Iron status in schizophrenic patients with acute neuroleptic-induced dystonic reactions. 797 59

Hallervorden-Spatz disease is an autosomal recessive disorder which usually begins in childhood, progresses irreversibly and leads to death in early adulthood. The main manifestations are extrapyramidal signs, such as, dystonia and rigidity, pyramidal signs and mental deterioration. Pathological changes are found mainly in globus pallidus. They are characterized by (1) pigmentation with iron, and (2) numerous spheroids which represent abnormal axonal swelling. The cause of the disease is not clear but excessive iron storage may contribute to pathogenesis. The patients are treated symptomatically. The definite diagnosis is difficult and is made post mortem. Recently, however, characteristic MRI findings has been reported, which may be useful for the diagnosis during life.
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PMID:[Hallervorden-Spatz disease]. 827 77

We gave three adult rhesus monkeys seven IV injections of manganese chloride at approximately 1-week intervals. We evaluated neurologic status by serial clinical examinations and performed a levodopa test if the animal developed features of basal ganglia dysfunction. After the animals were killed, we performed neuropathologic, neurochemical, and laser microprobe mass analysis (LAMMA) studies. Two of three animals developed a parkinsonian syndrome characterized by bradykinesia, rigidity, and facial grimacing suggestive of dystonia but not tremor. Neither animal responded to levodopa. Autopsy demonstrated gliosis primarily confined to the globus pallidus (GP) and the substantia nigra pars reticularis (SNr). We detected focal mineral deposits throughout the GP and SNr, particularly in a perivascular distribution. LAMMA studies noted that mineral deposits were primarily comprised of iron and aluminum. The severity of pathologic change correlated with the degree of clinical dysfunction. These studies demonstrate that, in contrast to Parkinson's disease (PD) and MPTP-induced parkinsonism, manganese primarily damages the GP and SNr and relatively spares the nigrostriatal dopaminergic system. Further, the results suggest that Mn-induced parkinsonism can be differentiated from PD and MPTP-induced parkinsonism by the clinical syndrome and response to levodopa. The accumulation of iron and aluminum suggests that iron/aluminum-induced oxidant stress may contribute to the damage associated with Mn toxicity.
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PMID:Manganese intoxication in the rhesus monkey: a clinical, imaging, pathologic, and biochemical study. 861 20

TH is a tetrahydrobiopterin-requiring, iron-containing monooxygenase. It catalyses the conversion of L-tyrosine to L-dopa, which is the first, rate-limiting step in the biosynthesis of catecholamines (dopamine, noradrenaline and adrenaline), the central and sympathetic neurotransmitters and adrenomedullary hormones. The cofactor of TH is tetrahydrobiopterin, which is synthesized from GTP in three steps. The TH gene consists of 14 exons only in humans and 13 exons in animals. Human TH exists in four isoforms (hTH1-4) that are produced by alternative mRNA splicing from a single gene. A single mRNA and protein corresponding to hTH1 exists in non-primates. Monkey TH exists in two isoforms, corresponding to hTH1 and hTH2. TH activity is regulated in the short term by feedback inhibition of catecholamines in competition with tetrahydrobiopterin, and by activation and deactivation due to phosphorylation and dephosphorylation, mainly at Ser-19 and Ser-40 of hTH1. The multiple TH isoforms in humans and monkeys have additional phosphorylation, resulting in more subtle regulation. In long-term regulation under stress conditions, TH protein is induced. CRE and AP1 in the 5' flanking region of the TH gene may be the main functional elements for TH gene expression. TH may be closely related to the pathogenesis of neurological diseases, such as dystonia and Parkinson's disease, psychiatric diseases, such as affective disorders and schizophrenia, as well as cardiovascular diseases. The TH gene may prove useful in gene therapy to compensate for decreased levels of catecholamines in neurological diseases, for example, for supplementation of dopamine in Parkinson's disease.
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PMID:Tyrosine hydroxylase: human isoforms, structure and regulation in physiology and pathology. 882 46

Hallervorden-Spatz disease (HSD) is an uncommon disorder, progressive and degenerative of the basal ganglia. It begins in the first or second decade of life and is characterized by a dominant extrapiramidal signs, dystonia and progressive dementia. It is autosomic recessive, although sporadic cases are seen in 15%. There is no biological marker for the disease. The post-mortem findings include iron deposits in the globus pallidum and pars reticulata of the substantia nigra. Magnetic resonance imaging (MRI) in T2 shows symmetric hypointense lesions in both globus pallidum with a hyperintense center: giving the "tiger's eye" sign. This is the first case reported in Mexico of sporadic HSD with typical clinical and MRI findings.
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PMID:[A case of Hallervorden-Spatz disease with magnetic resonance imaging data]. 976 92

Idiopathic Parkinson's disease (IPD) represents a common neurodegenerative disorder. An estimated 2% of the U.S. population, age 65 and older, develops IPD. The number of IPD patients will certainly increase over the next several decades as the baby-boomers gradually step into this high-risk age group, concomitant with the increase in the average life expectancy. While many studies have suggested that industrial chemicals and pesticides may underlie IPD, its etiology remains elusive. Among the toxic metals, the relationship between manganese intoxication and IPD has long been recognized. The neurological signs of manganism have received close attention because they resemble several clinical disorders collectively described as extrapyramidal motor system dysfunction, and in particular, IPD and dystonia. However, distinct dissimilarities between IPD and manganism are well established, and it remains to be determined whether Mn plays an etiologic role in IPD. It is particularly noteworthy that as a result of a recent court decision, methylcyclopentadienyl Mn tricarbonyl (MMT) is presently available in the United States and Canada for use in fuel, replacing lead as an antiknock additive. The impact of potential long-term exposure to low levels of MMT combustion products that may be present in emissions from automobiles has yet to be fully evaluated. Nevertheless, it should be pointed out that recent studies with various environmental modeling approaches in the Montreal metropolitan (where MMT has been used for more than 10 years) suggest that airborne Mn levels were quite similar to those in areas where MMT was not used. These studies also show that Mn is emitted from the tail pipe of motor vehicles primarily as a mixture of manganese phosphate and manganese sulfate. This brief review characterizes the Mn speciation in the blood and the transport kinetics of Mn into the central nervous system, a critical step in the accumulation of Mn within the brain, outlines the potential susceptibility of selected populations (e.g., iron-deficient) to Mn exposure, and addresses future research needs for Mn.
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PMID:Manganese: brain transport and emerging research needs. 1085 40

We studied a 27-year-old woman who died after a 6-year history of progressive dementia, dystonia, ataxia, apraxia, spasticity, choreoathetosis, visual and auditory hallucinations, and optic atrophy. Magnetic resonance imaging showed decreased intensity in the globus pallidus, substantia nigra, and dentate nuclei in T2-weighted images, supporting the clinical diagnosis of neurodegeneration with brain iron accumulation type 1 (NBIA-1; formerly known as Hallervorden-Spatz syndrome). At autopsy the brain showed mild frontotemporal atrophy and discoloration of the globus pallidus and the substantia nigra pars reticularis. Histologically, features typical of NBIA-1 were found including widespread axonal spheroids and large deposits of iron pigment in the discolored regions. Additionally, excessive numbers of Lewy bodies (LBs) were found throughout all examined brain stem and cortical regions. LBs of both types, as well as Lewy neurites in this case of NBIA-1, were strongly labeled by antibodies against alpha-synuclein. These findings give further evidence that accumulation of alpha-synuclein is generally associated with LB formation, i.e., in Parkinson's disease, dementia with Lewy bodies and NBIA-1. The case presented here is particularly notable for its high number of LBs in all areas of the cerebral cortex.
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PMID:Alpha-synuclein accumulation in a case of neurodegeneration with brain iron accumulation type 1 (NBIA-1, formerly Hallervorden-Spatz syndrome) with widespread cortical and brainstem-type Lewy bodies. 1104 80

Neurologic manifestations are rarely described in hereditary hemochromatosis (HH). We describe three patients with HH and movement disorders. Patient 1, a 69-year-old man, had a 13-year history of disabling cerebellar syndrome, action tremor and myoclonus, and secondary dementia. Patient 2 was a 40-year-old man with a 9-year history of cerebellar syndrome, head and arm tremor, and cervical dystonia. Patient 3, a 75-year-old woman, had a 5-year history of rapidly disabling parkinsonian syndrome unresponsive to levodopa. The diagnosis of HH was established in the three patients by iron tests, evidence of a C282Y mutation, and, in two patients, by liver biopsy. High-field T2-weighted magnetic resonance imaging showed hyperintense signals in hemispheric white matter in patient 1, cerebellar atrophy in patient 2, and cerebellar and cerebral atrophy in patient 3 and no significant hypointense signals in the three patients. Phlebotomies and symptomatic treatments did not change the course of the disease. Our cases are compared with the five previously reported observations of HH with movement disorders. This rare association is one cause of the chronic acquired non-Wilsonian hepatocerebral degeneration syndromes and represents a separate entity from aceruloplasminemia. The pathophysiologic mechanism of movement disorders in HH is unresolved. No hepatic insufficiency and portosystemic encephalopathy is evidenced in our cases, whereas the putative role of abnormal iron load remains to be ascertained. HH should be investigated more systematically in patients with movement disorders.
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PMID:Clinical report of three patients with hereditary hemochromatosis and movement disorders. 1110 6

Transcranial sonography is a new diagnostic tool, allowing not only the evaluation of cerebral arteries but also the two-dimensional display of the brain parenchyma. In this review we will summarize basics of the application, the ultrasound anatomy of the brain and sonographic findings in some movement disorders. While in normal adults basal ganglia nuclei are hypoechogenic, they are hyperechogenic in certain basal ganglia disorders. In Parkinson's disease, for example, the substantia nigra can be depicted as a distinctly echogenic area. An elevated echogenicity of the lentiform nuclei was noticed in patients with primary adult-onset dystonia. In both disorders the altered echogenicity may arise from higher heavy metal tissue content (i.e. iron in Parkinson's disease and copper in primary dystonia). Our findings converge to the hypothesis that transcranial ultrasound sensitively detects pathological metal accumulation not identified by other neuroimaging techniques (CT and MRI) and therefore provides new insights in the diagnosis of basal ganglia disorders. The implications of these findings for the understanding of the pathogenesis and its usefulness for the early diagnosis of movement disorders are outlined.
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PMID:Neuroimaging in basal ganglia disorders: perspectives for transcranial ultrasound. 1121 89

Magnetic resonance imaging (MRI) has enabled ante mortem diagnosis of Hallervorden Spatz disease (HSD). Childhood-onset cases are the most common type and usually present with progressive dystonia and dementia. The duration of illness is 15 to 20 years, leading to death. Presentation in adulthood and infancy have also been reported, however again the progression is usually inexorable. We present a 30-year-old woman who developed cognitive and motor developmental delay from the age of 8 months. There was further cognitive decline in her late teenage years with seizures and then more recent motor decline with dystonia. The imaging appearance was of iron deposition in the globus pallidus and substantia nigra leading to a diagnosis of HSD. The increased availability of MRI has allowed more cases of HSD to be diagnosed in life but as our case illustrates classification of the disease may need to be further examined.
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PMID:How broad is the phenotype of Hallervorden-Spatz disease? 1124 May 70


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