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)

Hallervorden-Spatz disease is an extremely rare cause of dystonia that carries a poor prognosis. A case occurring in an 11-year-old girl with progressive extra-pyramidal symptoms since infancy is described. The clinical picture and typical radiological findings are described.
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PMID:Hallervoredn-Spatz disease. 1689 88

We asked whether a movement disorder could be elicited by deprivation of pantothenic acid (PA; vitamin B5), the substrate for the enzyme pantothenate kinase 2 (PANK2), which is deficient in the inherited neurological disorder PKAN (pantothenate kinase-associated neurodegeneration formerly called Hallervorden-Spatz syndrome). This study was undertaken because mice made null for Pank2 failed to show the neurological manifestations of the human disease. Wild-type and Pank2 mutant mice were fed pantothenic acid-deficient diets and were monitored for general health, fertility and movement compared with animals on control diets over time. Mice of both genotypes on PA-deficient diets exhibited poor grooming, greying of fur and decreased body weight. With PA deprivation, wild-type mice manifested azoospermia (a phenotype also seen in Pank2 mice) as well as a movement disorder with a low-lying pelvis and slow steps. Rear limbs appeared to drag and occasionally extended into unnatural postures for 16-17 s duration, possibly indicative of dystonia. Movement disruption probably also occurs in PA-deprived Pank2 mutant mice, but they died precipitously before undergoing detailed analysis. Remarkably, restoration of dietary PA led to recovery of general health and grooming, weight gain, reversal of the movement disorder, and reappearance of mature sperm within 4 weeks. This study confirms the primacy of PA metabolism in the mechanism of disease in PKAN. PA deprivation provides a useful phenocopy for PKAN and allows us to test pharmacological and other interventional strategies in the treatment of this devastating disease.
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PMID:Deprivation of pantothenic acid elicits a movement disorder and azoospermia in a mouse model of pantothenate kinase-associated neurodegeneration. 1742 53

Intrathecal baclofen (ITB) has evolved into a standard treatment for severe spasticity of both spinal and cerebral origin. The accumulated promising data from reported series of patients receiving ITB therapy together with the fact that spastic hypertonia commonly coexists with other neurological disorders have constituted a solid basis for offering this kind of treatment to patients suffering from other movement disorders. These include motor disorders such as dystonia, amyotrophic lateral sclerosis, status dystonicus, Hallervorden-Spatz disease, Freidreich's ataxia, "stiff-man" syndrome, but also vegetative states after revere brain trauma, anoxic encephalopathy or other pathology and more recently, various chronic pain syndromes. In this article, on the basis of the established applications of ITB therapy, we review the important emerging indications of this rewarding neuromodulation method and attempt to identify its future potential beneficial role in other chronic and otherwise refractory neurological disorders.
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PMID:Intrathecal baclofen in current neuromodulatory practice: established indications and emerging applications. 1769 70

Hallervorden-Spatz syndrome is a rare autosomal recessive disorder that involves progressive extrapyramidal manifestations. Classical and atypical clinical presentations are known. Clinical details of patients admitted to the neurology ward or attending the movement disorder clinic of the All India Institute of Medical Sciences between January 2001 and July 2007 were reviewed. Sixteen patients (9 males and 7 females) were included in the study (median age 14 years; range 6-25). The most common clinical presentation was limb or cranial onset progressive dystonia. The patients with early onset had more frequent truncal and axial dystonia, including retrocollis, oromandibular-facial dystonia and chorea, dysarthria, pyramidal signs, gait disturbance, cognitive impairment, delay in milestones, retinitis pigmentosa, optic atrophy, oculomotor abnormalities, positive family history and acanthocytosis. Although rare, cerebellar ataxia, behavioural abnormalities, parkinsonism and apraxia of eyelid opening were exclusively seen in late onset patients. The present study highlights the heterogeneity of this disease entity and also describes certain unusual clinical features.
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PMID:Clinical spectrum of Hallervorden-Spatz syndrome in India. 1905 77

Neurodegeneration with brain iron accumulation type 1 (previously known as Hallervorden-Spatz syndrome) is a rare neurodegenerative disorder characterised by its typical clinical and radiological features. We present a case of an adolescent girl with rapidly progressive dystonia in whom the diagnosis of the above disorder was made prior to radiological investigation. This report has been made to highlight the diagnostic relevance of a good history and clinical examination. This is particularly important in a developing country where diagnostic radiological investigations are expensive.
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PMID:Generalised dystonia: clinical diagnosis is possible. 1949 81

Hallervorden-Spatz disease (HSD) is a rare autosomal-recessive hereditary disorder characterized by the early onset of progressive movement alterations, including dystonia, rigidity, choreoathetosis, and mental deterioration. HSD is also associated with a variety of psychiatric symptoms, primarily depression and mental deterioration. However, psychosis has rarely been reported as a major symptom of HSD. We report two siblings who presented psychiatric symptoms as major clinical presentations, accompanied by ataxic and spastic gait, dysarthria, and typical neuroimaging findings of HSD. A 14-year-old girl presented complex motor tics, stereotypic behavior and anxiety symptoms. Her older brother, a 16-year-old boy, presented prominent auditory hallucinations, persecutory delusions and social withdrawal symptoms. Psychiatric symptoms were improved after atypical antipsychotic treatment. HSD is a rare disease but should be carefully considered in the diagnosis of patients with both motor disorder and various psychiatric symptoms.
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PMID:Psychiatric disorder in two siblings with hallervorden-spatz disease. 2004

In humans overlap between various neurodegenerative disorders is a well known phenomenon. We reported a case of a 77-year-old woman with parkinsonism, dystonia, psychiatric symptoms and progressing dementia misdiagnosed at the age of 51 years as Parkinson's disease. Histopathological examination of the patient's brain performed 26 years after the disease onset revealed numerous axonal spheroids and iron deposits in structures of the nigro-pallido-striatal system that enabled to diagnose neurodegeneration with brain iron accumulation (NBIA) (former Hallervorden-Spatz syndrome), and changes characteristic for Alzheimer's disease (AD). NBIA is a group of rare clinically and genetically heterogeneous diseases of the extrapyramidal system which common feature is abnormal iron storage in the basal ganglia. Disturbed iron metabolism is also one of the hypothetical patho-mechanisms of AD. A coexistence of morphological changes characteristic for AD and NBIA in our patient suggests that similar molecular mechanisms may be involved in pathogenesis of various neurodegenerative processes, especially in disorders with iron dyshomeostasis. This case contributes also to the increasing evidence of NBIA heterogeneity.
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PMID:Dementia means number of things - the overlap of neurodegeneration with brain iron accumulation (NBIA) and Alzheimer changes: an autopsy case. 2060 94

The 2 major types of neurodegeneration with brain iron accumulation (NBIA) are the pantothenate kinase type 2 (PANK2)-associated neurodegeneration (PKAN) and NBIA2 or infantile neuroaxonal dystrophy (INAD) due to mutations in the phospholipase A2, group VI (PLA2G6) gene. We have recently demonstrated clinical heterogeneity in patients with mutations in the PLA2G6 gene by identifying a poorly defined subgroup of patients who present late with dystonia and parkinsonism. We report the clinical and genetic features of 7 cases with PLA2G6 mutations. Brain was available in 5 cases with an age of death ranging from 8 to 36 years and showed widespread alpha-synuclein-positive Lewy pathology, which was particularly severe in the neocortex, indicating that the Lewy pathology spread corresponded to Braak stage 6 and was that of the "diffuse neocortical type". In 3 cases there was hyperphosphorylated tau accumulation in both cellular processes as threads and neuronal perikarya as pretangles and neurofibrillary tangles. Later onset cases tended to have less tau involvement but still severe alpha-synuclein pathology. The clinical and neuropathological features clearly represent a link between PLA2G6 and parkinsonian disorders.
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PMID:Widespread Lewy body and tau accumulation in childhood and adult onset dystonia-parkinsonism cases with PLA2G6 mutations. 2061 3

Pharmacological therapy has had limited success in the treatment of most major neurological diseases. This has motivated the development of a number of novel surgical approaches designed to ameliorate drug-induced side effects or pharmacoresistant symptoms. Deep brain stimulation (DBS) has been quite successful in controlling both the cardinal motor manifestation of Parkinson's disease and the side effects of prolonged levodopa therapy. This has encouraged the application of DBS technology to treat a number of other neurodegenerative conditions, including secondary dystonia associated with pantothenate kinase-associated neurodegeneration (PKAN, formerly Hallervorden-Spatz syndrome), chorea associated with Huntington's disease, and most recently, cognitive decline associated with Alzheimer's type dementia. We review the rationale, indications and outcomes of neuromodulation for selected neurodegenerative conditions. In addition to DBS, we discuss select small molecule and gene-based neuromodulatory approaches. Ongoing study of basic pathophysiological mechanisms may eventually allow directed primary prevention of some of these diseases, but until then, invasive neuromoduation will likely continue to play an ever-increasing role in the delivery of the most advanced care for patients with these debilitating conditions.
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PMID:Neuromodulation for neurodegenerative conditions. 2327 4

Authors describe clinical features, CT scan and MRI findings of 4 Egyptian boys (3 brothers from one sibship and a sporadic case) with Hallervorden-Spatz syndrome (HSS). These patients presented around the age of 10-years-old with rigidity, dystonia, dysarthria, mental deterioration with loss of previously acquired skills and choreoathetotic movements. The 3 brothers developed seizures around the age of 16 and the older brother died at the age of 20. Although, the CT scan of the 3 brothers showed bilateral symmetrical calcification of the basal ganglia, the MRI of the 4 cases demonstrated bilateral symmetrical hyperintense areas surrounded by hypointense areas in the globus pallidus giving the characteristic "eye-of-the-tiger" sign. Based on the clinical and MRI picture, these 4 cases could be the atypical type of HSS. However, calcification of globus pallidus is an associated finding in these cases. This is the second report in the literature with this association. In addition, we present the results of the use of antioxidants, L-dopa and Botulinum toxin injections in the management of these cases.
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PMID:Hallervorden-Spatz syndrome. Variable imaging findings. 2337 30


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