Generalized Dystonia/Parkinsonism and Double-Doughnut Sign in Dengue Encephalitis.
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ABSTRACT:
SUBMITTER: Mishra A
PROVIDER: S-EPMC7328428 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Investigation of expression profile in XDP brains. Keywords: an XDP patient and neurologically normal control
2006-02-03 | GSE3064 | GEO
Project description:Investigation of expression profile in XDP brains. Experiment Overall Design: Comparison between XDP and control tissues.
2008-06-12 | E-GEOD-3064 | biostudies-arrayexpress
Project description:Although dystonias are a common group of movement disorders, the mechanisms by which brain dysfunction results in dystonia are not understood. Rapid-onset Dystonia-Parkinsonism (RDP) is a hereditary dystonia caused by mutations in the ATP1A3 gene. Affected individuals can be free of symptoms for years, but rapidly develop persistent dystonia and Parkinsonism-like symptoms after a stressful experience. Using a mouse model, we found that an adverse interaction between the cerebellum and basal ganglia can account for the symptoms of these individuals. The primary instigator of dystonia was the cerebellum, whose aberrant activity altered basal ganglia function, which in turn caused dystonia. This adverse interaction between the cerebellum and basal ganglia was mediated through a di-synaptic thalamic pathway that, when severed, alleviated dystonia. Our results provide a unifying hypothesis for the involvement of cerebellum and basal ganglia in the generation of dystonia and suggest therapeutic strategies for the treatment of RDP.
| S-EPMC3430603 | biostudies-literature
Project description:Mutations in the ATP1A3 gene (the ?-3 subunit of the Na+/K+ ATPase) are associated with rapid-onset dystonia-parkinsonism; alternating hemiplegia of childhood; and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS syndrome). The authors report 3 cases with pleiotropic movement disorders, including a novel mutation in a patient who presented with ataxia and dysphagia. Case 1 had a history of attention deficit hyperactivity disorder and developed dysphagia, chorea, and limb dystonia after a febrile illness at age 12 years. Case 2 presented with limb dystonia at age 26 years and dysarthia and dysphagia after a febrile illness. Case 3 had a history of learning disability and developed progressive ataxia with cerebellar atrophy at age 20 years. In all cases, deleterious mutations were identified in ATP1A3. They illustrate wide phenotypic variability, including chorea and ataxia. New cases are likely to be diagnosed as knowledge about the phenotypic spectrum expands.
| S-EPMC6178757 | biostudies-literature
Project description:BackgroundPhospholipase-associated neurodegeneration (PLAN) caused by PLA2G6 mutations is a recessively inherited disorder with three known phenotypes: the typical infantile onset neuroaxonal dystrophy (INAD); an atypical later onset form (atypical NAD); and the more recently recognized young-onset dystonia-parkinsonism (PLAN-DP).Case reportWe report the clinical, radiological, and genetic findings of a young Pakistani male with PLAN-DP. We review 11 previously published case reports cited in PubMed, and summarize the demographic, clinical, genetic, and radiological data of the 23 patients described in those articles.DiscussionPLAN-DP presents with diverse motor, autonomic, and neuropsychiatric features and should be considered in the differential diagnosis of patients with young-onset neurodegenerative disorders.
| S-EPMC4503963 | biostudies-literature
Project description:BackgroundJuvenile forms of parkinsonism are rare conditions with onset of bradykinesia, tremor and rigidity before the age of 21 years. These atypical presentations commonly have a genetic aetiology, highlighting important insights into underlying pathophysiology. Genetic defects may affect key proteins of the endocytic pathway and clathrin-mediated endocytosis (CME), as in DNAJC6-related juvenile parkinsonism.ObjectiveTo report on a new patient cohort with juvenile-onset DNAJC6 parkinsonism-dystonia and determine the functional consequences on auxilin and dopamine homeostasis.MethodsTwenty-five children with juvenile parkinsonism were identified from a research cohort of patients with undiagnosed pediatric movement disorders. Molecular genetic investigations included autozygosity mapping studies and whole-exome sequencing. Patient fibroblasts and CSF were analyzed for auxilin, cyclin G-associated kinase and synaptic proteins.ResultsWe identified 6 patients harboring previously unreported, homozygous nonsense DNAJC6 mutations. All presented with neurodevelopmental delay in infancy, progressive parkinsonism, and neurological regression in childhood. 123 I-FP-CIT SPECT (DaTScan) was performed in 3 patients and demonstrated reduced or absent tracer uptake in the basal ganglia. CSF neurotransmitter analysis revealed an isolated reduction of homovanillic acid. Auxilin levels were significantly reduced in both patient fibroblasts and CSF. Cyclin G-associated kinase levels in CSF were significantly increased, whereas a number of presynaptic dopaminergic proteins were reduced.ConclusionsDNAJC6 is an emerging cause of recessive juvenile parkinsonism-dystonia. DNAJC6 encodes the cochaperone protein auxilin, involved in CME of synaptic vesicles. The observed dopamine dyshomeostasis in patients is likely to be multifactorial, secondary to auxilin deficiency and/or neurodegeneration. Increased patient CSF cyclin G-associated kinase, in tandem with reduced auxilin levels, suggests a possible compensatory role of cyclin G-associated kinase, as observed in the auxilin knockout mouse. DNAJC6 parkinsonism-dystonia should be considered as a differential diagnosis for pediatric neurotransmitter disorders associated with low homovanillic acid levels. Future research in elucidating disease pathogenesis will aid the development of better treatments for this pharmacoresistant disorder. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
| S-EPMC8425408 | biostudies-literature
Project description:Preliminary evidence from postmortem studies of X-linked dystonia-parkinsonism (XDP) suggests tissue loss may occur first and/or most severely in the striatal striosome compartment, followed later by cell loss in the matrix compartment. However, little is known about how this relates to pathogenesis and pathophysiology. While MRI cannot visualize these striatal compartments directly in humans, differences in relative gradients of afferent cortical connectivity across compartments (weighted toward paralimbic versus sensorimotor cortex, respectively) can be used to infer potential selective loss in vivo. In the current study we evaluated relative connectivity of paralimbic versus sensorimotor cortex with the caudate and putamen in 17 individuals with XDP and 17 matched controls. Although caudate and putamen volumes were reduced in XDP, there were no significant reductions in either "matrix-weighted", or "striosome-weighted" connectivity. In fact, paralimbic connectivity with the putamen was elevated, rather than reduced, in XDP. This was driven most strongly by elevated putamen connectivity with the anterior insula. There was no relationship of these findings to disease duration or striatal volume, suggesting insula and/or paralimbic connectivity in XDP may develop abnormally and/or increase in the years before symptom onset.
| S-EPMC5842648 | biostudies-other
Project description:We describe a sporadic case of atypical parkinsonism-dystonia of subacute onset at the age of 16 years in a male from a consanguineous family. He showed marked orofacial dystonia, levodopa-induced dyskinesia, and a stereotyped bilateral eye-pressing movement disorder. We combined Sanger sequencing of candidate genes, homozygosity mapping, and whole-exome sequencing. A homozygous mutation was identified disrupting a splice site in exon 5 of the DJ1 (PARK7) gene. Clinical details and a video are provided. DJ1 mutations are a rare cause of atypical complex parkinsonism. Exome sequencing is efficacious in identifying the causal gene variant.
| S-EPMC6182985 | biostudies-literature
Project description:Background and objectivesRapid-onset dystonia-parkinsonism (RDP) is caused by mutations in the ATP1A3 gene, which codes for the α-3 subunit of the Na+ /K+ ATPase. It has been characterized by rapid-onset bulbar dysfunction, limb dystonia, bradykinesia, and a rostrocaudal spatial gradient of expression, usually after a physiologic trigger. We reexamined whether these features were in fact characteristic.MethodsWe characterized phenotypic variation within a cohort of 50 ATP1A3 mutation-positive individuals (carriers) and 44 mutation-negative family members (noncarriers). Potential participants were gathered through referral for clinical suspicion of RDP or alternating hemiplegia of childhood. Inclusion criteria were having a ATP1A3 mutation or being a family member of such an individual.ResultsWe found RDP is underdiagnosed if only "characteristic" patients are tested. Rapid onset and bulbar predominance were not universally present in carriers. Among those with at least mild symptoms of dystonia, rostrocaudal severity gradient was rare (7%). Symptoms began focally but progressed to be generalized (51%) or multifocal (49%). Arm (41%) onset was most common. Arms and voice were typically most severely affected (48% and 44%, respectively). Triggers preceded onset in 77% of the participants. Rapid onset, dystonia, parkinsonism, bulbar symptoms, headaches, seizures, frontal impairment, and a history of mood disorder and a history of psychosis were more common in carriers. Approximately half of the proband mutations occurred de novo (56%).ConclusionsOur findings suggest that patients should not be excluded from ATP1A3 testing because of slow onset, limb onset, absent family history, or onset in middle adulthood. RDP should be strongly considered in the differential for any bulbar dystonia. © 2019 International Parkinson and Movement Disorder Society.
| S-EPMC6879786 | biostudies-literature
Project description: Not available
| S-EPMC8680895 | biostudies-literature