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Parkinsonism
Kinds of Parkinsonism Terms modified by Parkinsonism Selected AbstractsFamilial paroxysmal exercise-induced dystonia: atypical presentation of autosomal dominant GTP-cyclohydrolase 1 deficiencyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 6 2010RUSSELL C DALE Paroxysmal exercise-induced dystonia (PED) is one of the rarer forms of paroxysmal dyskinesia, and can occur in sporadic or familial forms. We report a family (male index case, mother and maternal grandfather) with autosomal dominant inheritance of paroxysmal exercise-induced dystonia. The dystonia began in childhood and was only ever induced after many minutes of exercise, and was never present at rest, or on initiation of movements. In addition, family members suffered restless legs syndrome (RLS), depression, and adult-onset Parkinsonism. The index case had low cerebrospinal fluid neurotransmitters and pterins. The PED and RLS stopped on initiation of l -Dopa therapy. Both live family members were found to have a nonsense mutation (p.E84X) in exon 1 of the GTP-cyclohydrolase 1 (GCH-1) gene. We propose that GCH-1 mutations should be considered a genetic cause of familial PED, especially if additional clinical features of monoaminergic deficiency are present in affected individuals. [source] Acculturation is associated with the prevalence of tardive dyskinesia and akathisia in community-treated patients with schizophreniaACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2008S. Sundram Objective:, Ethnicity is a risk factor for tardive dyskinesia (TD) and other antipsychotic drug-induced movement disorders (ADIMD). It is unclear whether this association is mediated through genetic, environmental or cultural factors individually or in combination. This pilot study aimed to explore this interaction by determining if acculturation in migrant groups contributed to the prevalence of ADIMD. Method:, Culturally diverse but relatively genetically homogeneous (white Caucasian) patients with schizophrenia (n = 40) treated at a single site were assessed for the presence of ADIMD and level of acculturation. Results:, Higher levels of acculturation correlated with an increased prevalence of TD and akathisia but not Parkinsonism. The level of acculturation significantly predicted TD. Conclusion:, This study identifies for the first time that acculturation significantly contributes to the prevalence of TD and akathisia but not Parkinsonism in culturally diverse migrant populations and must be accounted for when explaining ethnic variation in rates of ADIMD. [source] Interest in genetic testing in pallido-ponto-nigral degeneration (PPND): a family with frontotemporal dementia with Parkinsonism linked to chromosome 17EUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2001C. A. McRae The specific mutation on the tau gene responsible for a neurodegenerative disease known as pallido-ponto-nigral degeneration (PPND) was recently located. PPND family members are at risk for an autosomal dominant form of frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17). This study investigated whether individuals in this family would consider presymptomatic genetic testing. Surveys were sent to 66 at-risk individuals in the family; replies were received from 20 (30%). Family members were asked if they would consider having testing now or in the future, and to indicate their reasons for and against proceeding with testing. Fifty per cent (n=10) of those who were at risk and who responded indicated they would consider testing now, and 55% (n=11) would think about it in the future. The most frequently cited reasons to proceed with testing were to ,collaborate with research' (70%) and to ,know if my children are at risk' (45%). The most frequently cited reason not to pursue testing was ,I can enjoy my life more fully by not knowing' (50%). Results suggest that interest in determining whether they will manifest PPND is generally low among at-risk members of this family, despite wide support and participation in other research studies. [source] A two-fold difference in the age-adjusted prevalences of Parkinson's disease between the island of Als and the Faroe IslandsEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2000L. Wermuth With the aim of comparing the previously found high prevalence of idiopathic Parkinson's disease (PD) in the Faroe Islands with the prevalence of PD in an area of Denmark, we used the same case-finding methods for case ascertainment and the same strict criteria to diagnose PD on the island of Als. During the last year before the prevalence date (1 January 1998), we found in various registries from pharmacies, hospital, private neurologist and general practioners 121 patients with suspected Parkinsonism out of 56 839 inhabitants on the island of Als. After exclusion of those who had other diseases, a total of 79 patients were left for further examinations. Among these we found 58 with PD. The overall prevalence of PD was estimated to be 102.0 and the age-adjusted prevalence to be 98.3 per 100 000 persons compared with 187.6 and 209.0 in the Faroe Islands. Compared with the previous results from the Faroe Islands (prevalence date 1 July 1995) we found an even lower mean age at onset of PD symptoms and at onset of treatment, a lower proportion of definite PD and a lower average dose of levodopa. We therefore conclude that the two-fold higher prevalence in the Faroe Islands than on the island of Als was not due to an early diagnosis and a higher ascertainment of cases with mild PD, which was suggested as being one possible explanation for our previous finding of a high prevalence of PD in the Faroe Islands. [source] Juvenile Parkinsonism: a term in search of an identityEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2000J. W. Langston No abstract is available for this article. [source] Helicobacter Hypothesis for Idiopathic Parkinsonism: Before and BeyondHELICOBACTER, Issue 5 2008R. John Dobbs Abstract We challenge the concept of idiopathic parkinsonism (IP) as inevitably progressive neurodegeneration, proposing a natural history of sequential microbial insults with predisposing host response. Proof-of-principle that infection can contribute to IP was provided by case studies and a placebo-controlled efficacy study of Helicobacter eradication. "Malignant" IP appears converted to "benign", but marked deterioration accompanies failure. Similar benefit on brady/hypokinesia from eradicating "low-density" infection favors autoimmunity. Although a minority of UK probands are urea breath test positive for Helicobacter, the predicted probability of having the parkinsonian label depends on the serum H. pylori antibody profile, with clinically relevant gradients between this "discriminant index" and disease burden and progression. In IP, H. pylori antibodies discriminate for persistently abnormal bowel function, and specific abnormal duodenal enterocyte mitochondrial morphology is described in relation to H. pylori infection. Slow intestinal transit manifests as constipation from the prodrome. Diarrhea may flag secondary small-intestinal bacterial overgrowth. This, coupled with genetically determined intense inflammatory response, might explain evolution from brady/hypokinetic to rigidity-predominant parkinsonism. [source] Role of Chronic Infection and Inflammation in the Gastrointestinal Tract in the Etiology and Pathogenesis of Idiopathic ParkinsonismHELICOBACTER, Issue 4 2005Part 1: Eradication of Helicobacter in the Cachexia of Idiopathic Parkinsonism ABSTRACT Background., Neuronal damage in idiopathic parkinsonism may be in response to ubiquitous occult infection. Since peptic ulceration is prodromal, Helicobacter is a prime candidate. Aim., To consider the candidature of Helicobacter in parkinsonism with cachexia. Methods., We explore the relationship between being underweight and inflammatory products in 124 subjects with idiopathic parkinsonism and 195 controls, and present the first case-series evidence of efficacy of Helicobacter eradication, in parkinsonism advanced to the stage of cachexia. Results., Association of a low body mass index with circulating interleukin-6 was specific to parkinsonism (p = .002), unlike that with antibodies against Helicobacter vacuolating-toxin and cytotoxicity-associated gene product (p < .04). Marked reversibility in both cachexia and disability of idiopathic parkinsonism followed Helicobacter heilmannii eradication in one case, Helicobacter pylori eradication in another, follow-up being , 3.5 years. The latter presented with postprandial bloating, and persistent nausea: following eradication, radioisotope gastric-emptying returned towards normal, and upper abdominal symptoms regressed. Reversibility of their cachexia/disability contrasts with the outcome of anti- Helicobacter therapy where eradication repeatedly failed (one case), and in non- Helicobacter gastritis (three cases). Anti-parkinsonian medication remained constant. Intestinal absorption and barrier function were normal in all. Conclusion., Categorization, according to presence or absence of Helicobacter infection, was a useful therapeutic tool in late idiopathic parkinsonism. [source] Role of Chronic Infection and Inflammation in the Gastrointestinal Tract in the Etiology and Pathogenesis of Idiopathic ParkinsonismHELICOBACTER, Issue 4 2005Part 2: Response of Facets of Clinical Idiopathic Parkinsonism to Helicobacter pylori Eradication. ABSTRACT Background., Links between etiology/pathogenesis of neuropsychiatric disease and infection are increasingly recognized. Aim., Proof-of-principle that infection contributes to idiopathic parkinsonism. Methods., Randomized, double-blind, placebo-controlled efficacy study of proven Helicobacter pylori eradication on the time course of facets of parkinsonism. Intervention was 1 week's triple eradication therapy/placebos. Routine deblinding at 1 year (those still infected received open-active), with follow-up to 5 years post-eradication. Primary outcome was mean stride length at free-walking speed, sample size 56 for a difference, active vs. placebo, of 3/4 (between-subject standard deviation). Recruitment of subjects with idiopathic parkinsonism and H. pylori infection was stopped at 31, because of marked deterioration with eradication failure. Interim analysis was made in the 20 who had reached deblinding, seven of whom were receiving antiparkinsonian medication (long- t1/2, evenly spaced) which remained unchanged. Results., Improvement in stride-length, on active (n = 9) vs. placebo (11), exceeded size of effect on which the sample size was calculated when analyzed on intention-to-treat basis (p = .02), and on protocol analysis of six weekly assessments, including (p = .02) and excluding (p = .05) those on antiparkinsonian medication. Active eradication (blind or open) failed in 4/20, in whom B-lymphocyte count was lower. Their mean time course was: for stride-length, ,243 (95% CI ,427, ,60) vs. 45 (,10, 100) mm/year in the remainder (p = .001); for the ratio, torque to extend to flex relaxed arm, 349 (146, 718) vs. 58 (27, 96)%/ year (p < .001); and for independently rated, visual-analog scale of stance,walk videos (worst,best per individual , 0,100 mm), ,64 vs. ,3 mm from anterior and ,50 vs. 11 lateral (p = .004 and .02). Conclusions., Interim analysis points to a direct or surrogate (not necessarily unique) role of a particular infection in the pathogenesis of parkinsonism. With eradication failure, bolus release of antigen from killed bacteria could aggravate an effect of ongoing infection. [source] Biochemical aspects of the neuroprotective mechanism of PTEN-induced kinase-1 (PINK1)JOURNAL OF NEUROCHEMISTRY, Issue 1 2008Ryan D. Mills Abstract Mutations in PTEN-induced kinase 1 (PINK1) gene cause PARK6 familial Parkinsonism. To decipher the role of PINK1 in pathogenesis of Parkinson's disease (PD), researchers need to identify protein substrates of PINK1 kinase activity that govern neuronal survival, and establish whether aberrant regulation and inactivation of PINK1 contribute to both familial Parkinsonism and idiopathic PD. These studies should take into account the several unique structural and functional features of PINK1. First PINK1 is a rare example of a protein kinase with a predicted mitochondrial-targeting sequence and a possible resident mitochondrial function. Second, bioinformatic analysis reveals unique insert regions within the kinase domain that are potentially involved in regulation of kinase activity, substrate selectivity and stability of PINK1. Third, the C-terminal region contains functional motifs governing kinase activity and substrate selectivity. Fourth, accumulating evidence suggests that PINK1 interacts with other signaling proteins implicated in PD pathogenesis and mitochondrial dysfunction. The most prominent examples are the E3 ubiquitin ligase Parkin, the mitochondrial protease high temperature requirement serine protease 2 and the mitochondrial chaperone tumor necrosis factor receptor-associated protein 1. How PINK1 may regulate these proteins to maintain neuronal survival is unclear. This review describes the unique structural features of PINK1 and their possible roles in governing mitochondrial import, processing, kinase activity, substrate selectivity and stability of PINK1. Based upon the findings of previous studies of PINK1 function in cell lines and animal models, we propose a model on the neuroprotective mechanism of PINK1. This model may serve as a conceptual framework for future investigation into the molecular basis of PD pathogenesis. [source] Does the historical literature on encephalitis lethargica support a simple (direct) relationship with postencephalitic Parkinsonism?,MOVEMENT DISORDERS, Issue 9 2010Joel A. Vilensky PhD Abstract This article and the subsequent one suggest that the currently accepted view of a simplistic (direct) relationship between encephalitis lethargica (EL) and postencephalitic Parkinsonism (PEP) is based on a incomplete evaluation of the epidemic period literature. In this article we provide a detailed analysis of the literature from the period that demonstrates that Parkinsonism was not initially part of acute EL symptomatology, that PEP was not typically the prevailing type of chronic EL and that oculogyric crises were never part of acute EL symptomatology and not initially associated with PEP. The second paper uses these finding, and also examines the clinical justifications for concluding that all patients with PEP had prior acute episodes of EL, to reevaluate the presumed direct etiologic relationship between EL and PEP. © 2010 Movement Disorder Society [source] Parkinsonism in patients with a history of amphetamine exposureMOVEMENT DISORDERS, Issue 2 2010Chadwick W. Christine MD Abstract We recently found a higher rate of prolonged amphetamine exposure in patients diagnosed with Parkinson's disease (PD) than in spouse/caregiver controls. Since distinguishing features have been described in some patients with parkinsonism due to environment exposures (e.g., manganese), we sought to compare the clinical features of patients with PD with prolonged amphetamine exposure with unexposed patients with PD. Prolonged exposure was defined as a minimum of twice a week for ,3 months, or weekly use ,1 year. We reviewed the clinical records of patients with PD who had participated in a telephone survey of drug and environmental exposures and compared the clinical features of patients with a history of prolonged amphetamine exposure to patients who had no such exposure. Records were available for 16 of 17 (94%) patients with prior amphetamine exposure and 127 of 137 (92%) of those unexposed. Age at diagnosis was younger in the amphetamine-exposed group (49.8 ± 8.2 years vs. 53.1 ± 7.4 years; P < 0.05), but other features, including presenting symptoms, initial and later treatments, development of motor fluctuations, and MRI findings were similar between these groups. Because we did not detect clinical features that differentiate parkinsonism in patients with prolonged amphetamine exposure, research to determine whether amphetamine exposure is a risk factor for parkinsonism will require detailed histories of medication and recreational drug use. © 2009 Movement Disorder Society [source] A molecular basis for the increased vulnerability of substantia nigra dopamine neurons in aging and Parkinson's disease,MOVEMENT DISORDERS, Issue S1 2010C. Savio Chan PhD Abstract Parkinson's disease (PD) is a common neurodegenerative disorder of unknown etiology. There is no cure or proven strategy for slowing the progression of the disease. Although there are signs of pathology in many brain regions, the core symptoms of PD are attributable to the selective degeneration of dopaminergic neurons in the substantia nigra pars compacta. A potential clue to the vulnerability of these neurons is an increasing reliance with age upon L-type Ca2+ channels with a pore-forming Cav1.3 subunit to support autonomous activity. This reliance could pose a sustained stress on mitochondrial ATP generating oxidative phosphorylation, accelerating cellular aging and death. Systemic administration of isradipine, a dihydropyridine blocker of these channels, forces dopaminergic neurons in rodents to revert to a juvenile, L-type Ca2+ channel independent mechanism to generate autonomous activity. This "rejuvenation" confers protection against toxins that produce experimental Parkinsonism, pointing to a potential neuroprotective strategy for PD. Their decades-long track record of safe use in the treatment of hypertension makes dihydropyridines particularly attractive as a therapeutic tool in PD. © 2010 Movement Disorder Society [source] Dopamine transporter single photon emission computerized tomography in the diagnosis of dementia with Lewy bodies,MOVEMENT DISORDERS, Issue S2 2009FRCP, Rodney W.H. Walker PhD Abstract Dementia with Lewy bodies (DLB) is part of the spectrum of Lewy body disorders. However, it may be difficult to diagnose patients who have dementia but no Parkinsonism. Visual and semiquantitative assessment of the nigrostriatal dopaminergic nerve terminals in the putamen and caudate nuclei can be obtained with single photon emission computerized tomography (SPECT) using ligands that bind to the dopamine transporter molecule in the membranes of the nigrostriatal nerve terminals. This can be employed as a means of identifying subclinical degeneration of nigrostriatal neurones in patients with suspected DLB, increasing the probability of the diagnosis. In several studies, the sensitivity and specificity of abnormal dopamine transporter scans with regard to diagnosing probable DLB are better than 75 and 90%, respectively. This communication outlines the evidence for this and discusses some of the advantages, potential disadvantages, and areas of uncertainty with regard to the use of dopamine transporter SPECT in DLB diagnosis. © 2009 Movement Disorder Society [source] Parkinsonism and impulse control disorder: Presentation of a new progranulin gene mutationMOVEMENT DISORDERS, Issue 4 2009Sui H. Wong MRCP [source] Haplotype analysis of the PARK 11 gene, GIGYF2, in sporadic Parkinson's disease,MOVEMENT DISORDERS, Issue 3 2009Greg T. Sutherland PhD Abstract Familial Parkinsonism (PARK) genes are strong candidates for conferring susceptibility to common forms of PD. However, most studies to date have provided little evidence that their common variants substantially influence disease risk. Recently, mutations were described in the gene, GIGYF2 (TNRC15), located at the PARK11 locus (2q37.1). Here, we use a haplotype tagging approach to examine common variation in the GIGYF2 gene and PD risk. PD cases (n = 568) and age and gender-matched control subjects (n = 568) were recruited from three specialist movement disorder clinics in Brisbane (Australia) and the Australian electoral roll. Twelve tagging SNPs were assessed in all subjects and haplotype and genotype associations were explored. Overall our findings suggest that common genetic variants of GIGYF2 do not significantly affect sporadic PD risk in Australian Caucasians. © 2008 Movement Disorder Society [source] Parkinsonism in polycythaemia vera probably due to manganismMOVEMENT DISORDERS, Issue 16 2008Andrea Pratesi MD [source] Parkinsonism and dystonia caused by the illicit use of ephedrone,A longitudinal study,MOVEMENT DISORDERS, Issue 15 2008Marianna Selikhova MD Abstract A neurological syndrome characterized by levodopa unresponsive bradykinesia, retropulsion with falls backwards, dysarthria, gait disturbance, dystonia, and emotional lability was identified in 13 male opiate addicts following the prolonged intravenous use of ephedrone (methcathinone), a central nervous stimulant prepared from pseudoephedrine, potassium permanganate, and vinegar. The natural history, response to treatment, and clinical features has been studied, and MR and dopamine transporter SPECT brain imaging were carried out. Pubic hair was sampled for manganese. The clinical and radiological picture closely resembled previous reports of chronic manganese poisoning and increased mean manganese level in pubic hair observed for at least 1 year after cessation of ephedrone. Odor identification was intact. Cognitive assessment showed a mild executive dysfunction and a mild depression. DaTSCANs were all normal. The neurological syndrome bears some similarities to PSP but differs from Parkinson's disease. Delayed neurological progression despite discontinuation of ephedrone occurred in one-third of cases. Ephedrone poisoning should be considered as a possible cause of secondary Parkinsonism in young adults, particularly from Eastern Europe. © 2008 Movement Disorder Society [source] The clinical spectrum of freezing of gait in atypical parkinsonism,MOVEMENT DISORDERS, Issue S2 2008Stewart A. Factor DO Abstract Freezing of gait (FOG), commonly seen in advanced Parkinson's disease (PD), has been classified as its fifth cardinal feature. However, its presence frequently leads to a misdiagnosis of PD. FOG is actually more common in atypical parkinsonism (AP): including vascular Parkinsonism (VP), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), dementia with Lewy bodies (DLB), and higher level gait disorders (HLGDs). VP is the result of multiple small vessel infarcts (lacunar state or Binswanger's disease), particularly involving the frontal, parietal, and basal ganglia regions. Approximately 50% have FOG (often referred to as lower body parkinsonism). FOG is also common in neurodegenerative forms of AP, present in 45,57%. Of these, FOG is present in 53% of PSP, 54% MSA, 54% DLB, 25% CBD, and 40% HLGD. It is generally seen in the late stages. There are two syndromes closely associated with AP that are dominated by FOG; pure akinesia (PA) and primary progressive freezing gait (PPFG). PA is characterized by akinesia of gait (including FOG), writing, and speech. Tremor, rigidity, dementia, and response to levodopa are notably absent. PPFG is defined by early FOG (often the initial feature) that progresses to include postural instability. It is accompanied by bradykinesia, rigidity, postural tremor, dementia, and levodopa unresponsiveness. Both syndromes are heterogeneous but PSP seems to be the most common cause. CBD and DLB can also present as PPFG. FOG is a common feature of AP and although typically occurring late in disease may also be an early symptom. © 2008 Movement Disorder Society [source] Parkinsonism and cognitive impairment following chronic exposure to potassium cyanideMOVEMENT DISORDERS, Issue 3 2008Massimiliano Di Filippo MD [source] A South African mixed ancestry family with Huntington disease-like 2: Clinical and genetic featuresMOVEMENT DISORDERS, Issue 14 2007Soraya Bardien PhD Abstract Huntington disease-like 2 (HDL2) is a neurodegenerative disorder caused by an expansion of a CTG repeat in the junctophilin-3 gene (JPH3). A limited number of HDL2 families have been reported, all of apparently Black African ancestry. We report on a South African family that presented with progressive dementia and a movement disorder affecting numerous family members. Genotyping of the JPH3 CTG repeat revealed pathogenic expansions in three affected individuals. Whereas HDL2 is thought to be clinically indistinguishable from Huntington disease (HD), 2 of the patients in this study presented with clinical symptoms that differed substantially from HD; one had myoclonus and the other had Parkinsonism. Moreover, brain magnetic resonance imaging scans of these patients showed imaging features atypical for HD. Mitochondrial DNA and Y-chromosome DNA analysis on a family member showed that his maternal and paternal ancestries are typical of that found among the South African mixed ancestry or colored population. A difference in the distribution of CTG repeats between Caucasian and Black individuals was detected. We conclude that the phenotype of HDL2 is broad and can differ from that of typical HD. The diagnosis therefore should be considered in a wide spectrum of neuropsychiatric and abnormal movement presentations. © 2007 Movement Disorder Society [source] Genetic analysis of SCA 2 and 3 repeat expansions in essential tremor and atypical ParkinsonismMOVEMENT DISORDERS, Issue 13 2007Eng-King Tan MD Abstract Anecdotal reports suggest that patients with spinocerebellar ataxia (SCA 2) patients can present with postural tremor with ataxia. We determined the prevalence of SCA2 and SCA3 mutations in a cohort of ET and atypical Parkinsonism patients. A total of 277 subjects comprising of 177 ET and 100 atypical Parkinsonism were examined. We identified one positive case of SCA3 among those who were diagnosed with ET, yielding a prevalence of 0.5%, but a zero prevalence among our atypical Parkinsonism patients. No study subjects carried an abnormal SCA2 repeat expansion. Our study highlights that SCA3 can present initially with ET symptoms, expanding the spectrum of genetic diseases that can be associated with ET-like phenotype. Routine screening for SCA2 and SCA3 in ET and atypical Parkinsonism patients may not be cost effective. However, in the long-term follow-up of patients who present with an ET phenotype, clinicians should be vigilant for other neurological signs, which may be point to an alternate diagnosis. © 2007 Movement Disorder Society [source] Valproate-induced Parkinsonism in epilepsy patientsMOVEMENT DISORDERS, Issue 1 2007Dominic Jamora MD Abstract We systematically examined 226 epilepsy patients in a tertiary-referral center and found 6 (5.04%) to have valproate-induced Parkinsonism. There was a significantly higher prevalence of patients with Parkinsonism in the group of patients treated with valproate compared to those who were on other antiepileptic drugs (6 [5.04%] of 119 vs. 0 [0%] of 107; ,2 = 5.54; P = 0.025). These six patients had been on valproate for more than 3 years (mean, 75.67 ± 25.32 months) at an average dose of 750 ± 273.86 mg/day. The valproate doses were decreased or discontinued with supplementation from another antiepileptic medication. The mean UPDRS motor score significantly improved from 10.67 ± 5.1 to 4.75 ± 2.75 (P < 0.05). There was no relapse of seizures. Clinicians working in tertiary-referral centers should have a high index of suspicion for valproate-induced Parkinsonism. Early recognition and switching into another antiepileptic medication may help reduce unnecessary suffering in these patients. © 2006 Movement Disorder Society [source] Neurodegenerative overlap syndrome: Parkinsonism and motor neuron disorderMOVEMENT DISORDERS, Issue 1 2007Akiko Imamura MD [source] Prolonged residual catatonia or prolonged neuroleptic-induced Parkinsonism following catatonic stupor in a patient with manic,depressive illnessMOVEMENT DISORDERS, Issue 1 2007Kazumasa Suzuki MD [source] Unresolved issues relating to the Shaking Palsy on the celebration of James Parkinson's 250th birthdayMOVEMENT DISORDERS, Issue S17 2007Andrew J. Lees MD Abstract James Parkinson's Essay on the Shaking Palsy published in 1817 provided the first clear clinical description for the disorder now known throughout the world by his name. His primary reason for publishing his monograph shortly before his retirement from medical practice was to draw the medical profession's attention to a malady, which had not yet been defined as a nosological entity. He also hoped that the eminent anatomists of the day would be stimulated to elucidate the pathological lesion responsible for the clinical picture and that this in turn might lead to a rational cure. The concept of Parkinson's disease remains clinically based and successive generations of neurologists have refined and embellished Parkinson's seminal descriptions. Narrative accounts by affected individuals have also helped physicians understand what it is like to live with Parkinson's disease. For many years, the pathological hallmarks of Parkinson's disease were disputed and there were few clinico-pathological reports with adequate clinical description. However, most neurologists now link severe loss of nigral cells in the ventrolateral tier of the pars compacta of the substantia nigra with bradykinesia and the presence of Lewy bodies in a number of discrete brain stem and cortical regions with Parkinson's disease. There are many unanswered clinical questions relating to Parkinson's disease including the striking heterogeneity and frequent limb asymmetry. It also remains somewhat uncertain whether Parkinson's disease is ever truly unilateral by the time of clinical presentation and whether the hand rather than the foot is the most common site of onset. Hyposmia and visual hallucinations are helpful pointers in distinguishing Parkinson's disease from atypical Parkinsonism and should be specifically enquired about in the history. Simple reliable cultural-specific smell identification batteries are an urgent need and target of clinical research. It remains to be determined whether Alzheimer type dementia as opposed to a dysexecutive syndrome should be considered a part of Parkinson's disease and further detailed clinico-pathological correlative studies are needed. It is also unclear whether autosomal dominant monogenetic Parkinsonism due to synuclein or LRRK-2 mutations will prove to be identical clinically with Parkinson's disease and for the present it is wiser to regard Parkinson's disease as a sporadic disorder. Parkinson was an active political reformer and if alive today would certainly be campaigning to translate more effectively the rich seam of neuroscientific research of the last decade into therapeutic benefits for the rising number of people who are developing the shaking palsy as a result of increasing longevity in the developed world. © 2007 Movement Disorder Society [source] Gene expression changes in postmortem tissue from the rostral pons of multiple system atrophy patientsMOVEMENT DISORDERS, Issue 6 2007Anna Jelaso Langerveld PhD Abstract Multiple system atrophy (MSA) is a neurodegenerative disease characterized by various degrees of Parkinsonism, cerebellar ataxia, and autonomic dysfunction. In this report, Affymetrix DNA microarrays were used to measure changes in gene expression in the rostral pons, an area that undergoes extensive damage in MSA, but not other synucleinopathies. Significant changes in expression of 254 genes (180 downregulated and 74 upregulated) occurred in pons tissue from MSA patients when compared with control patients. The downregulated genes were primarily associated with biological functions known to be impaired in Parkinson's disease (PD) and other neurological diseases; for example, downregulation occurred in genes associated with mitochondrial function, ubiquitin-proteasome function, protein modification, glycolysis/metabolism, and ion transport. On the other hand, upregulated genes were associated with transcription/RNA modification, inflammation, immune system function, and oligodendrocyte maintenance and function. Immunocytochemistry, in conjunction with quantitative image analysis, was carried out to characterize ,-synuclein protein expression as glial cytoplasmic inclusions in the pontocerebellar tract in rostral pons tissue and to determine the relationship between the amount of aggregated ,-synuclein protein and changes in specific gene expression. Of the regulated genes, 86 were associated with the amount of observed aggregated ,-synuclein protein in the rostral pons tissue. These data indicate that cells in the pons of MSA patients show changes in gene expression previously associated with the substantia nigra of PD patients and/or other neurological diseases, with additional changes, for example related to oligodendrocyte function unique to MSA. © 2007 Movement Disorder Society [source] Parkinsonism and essential tremor in a family with pseudo-dominant inheritance of PARK2: An FP-CIT SPECT studyMOVEMENT DISORDERS, Issue 4 2007Maria Teresa Pellecchia MD Abstract We report a family with 5 affected individuals manifesting either essential tremor (ET), Parkinsonism, or both, consistent with pseudo-dominant inheritance of PARK2. Two homozygotes presented postural and kinetic tremor several years before the onset of Parkinsonism. Postural and kinetic tremor mimicking ET was the only feature in 1 homozygous and 2 heterozygous carriers of the mutation. Striatal dopamine transporter density was reduced in accordance with phenotype and number of mutated alleles. In 3 homozygotes and 1 heterozygote, a 2-year follow-up single photon emission computed tomography suggested no progression of nigrostriatal deficit. © 2006 Movement Disorder Society [source] Treatable fluctuating Parkinsonism and dementia in a patient with a dural arteriovenous fistulaMOVEMENT DISORDERS, Issue 3 2007Miyuki Kajitani MD [source] Parkinsonism due to lamotrigineMOVEMENT DISORDERS, Issue 12 2006Patrick Santens MD [source] Open-label pilot study of levetiracetam (Keppra) for the treatment of chorea in Huntington's diseaseMOVEMENT DISORDERS, Issue 11 2006FAAN, Theresa A. Zesiewicz MD Abstract The objective of this study is to evaluate the tolerability and preliminary efficacy of levetiracetam (LEV) in reducing chorea in Huntington's disease (HD) patients in a prospective open-label pilot study. Nine HD patients with chorea were treated with LEV in doses up to 3,000 mg/day for up to 48 days. The primary endpoint measure was the Unified Huntington's Disease Rating Scale (UHDRS) chorea subscore. The mean dose (±SD) of LEV at endpoint was 2,583.3 ± 1,020.6 mg/day. Mean UHDRS chorea score decreased from 12.6 ± 3.0 at baseline to 6.7 ± 4.3 at endpoint (P = 0.01). There was no significant change in UHDRS total motor scores (38.8 ± 11.4 at baseline and 33.6 ± 26.7 at endpoint; P = 0.24). Somnolence contributed to a 33% drop-out rate, and 3 patients developed Parkinsonism. Results of this open label study suggest that LEV may be efficacious in reducing chorea in HD patients. © 2006 Movement Disorder Society [source] | |||||||||||||||||||||||||||||||