Dystonia in musicians an unrecognized cause of career loss

Musician’s dystonia is a task-specific focal dystonia affecting approximately 1% of all professional musicians. Dystonia develops in all types of instruments (keyboards, strings, woodwind, brass and percussions), presenting as focal dystonia of the hand or as embouchure dystonia. There is an association between the musical instrument and the localization of dystonia (piano and guitar players are affected in the right hand,violinists and violists in the left hand). Genetic predisposi­tion and a variety of triggering factors,such as trauma,compressed nerve,emotional stress and mainly overuse of the hand due to marked increase in practice time,are implicated for the development of the focal dystonia. Treatment of musician’s dystonia is currently symptomatic and includes drugs, botulinum toxin injections, pedagogical training, relaxation techniques, ergonomic changes and psychotherapy. The results of the treatment are more or less unsatisfactory and a proportion of profes­sional musicians are forced to change career

LRRK2 and Parkinson’s disease

The identification of the leucine-rich repeat kinase 2 (LRRK2) gene was a breakthrough in the area of Parkinson’s disease (PD) genetics. Mutations throughout the whole gene have been associated with both familial and sporadic PD, in unprecedented percentages, with G2019S mutation being today the most common genetic cause of the disease. This review will describe current knowledge on G2019S mutation, the multidomain structure of LRRK2 protein, its function and implication in PD pathogenesis

Association of the cerebral dopamine neurotrophic factor (CDNF) gene intron 1 polymorphism rs11259365 with Parkinson’s disease in the Greek population

Cerebral dopamine neurotrophic factor (CDNF) is a newly identified neurotrophic factor. In this study, we examined the CDNF rs11259365 polymorphism in 53 Greek patients with sporadic Parkinson’s disease (PD) and 52 control subjects, using a PCR-RFLP method. No association was found between this polymorphism and PD, in the Greek population

Case Report Miller-Fisher Syndrome: Are Anti-GAD Antibodies Implicated in Its Pathophysiology?

Miller-Fisher syndrome (MFS) is considered as a variant of the Guillain-Barre syndrome (GBS) and its characteristic clinical features are ophthalmoplegia, ataxia, and areflexia. Typically, it is associated with anti-GQ1b antibodies; however, a significant percentage (>10%) of these patients are seronegative. Here, we report a 67-year-old female patient who presented with the typical clinical features of MFS. Workup revealed antibodies against glutamic acid decarboxylase (GAD) in relatively high titers while GQ1b antibodies were negative. Neurological improvement was observed after intravenous gamma globulin and follow-up examinations showed a continuous clinical amelioration with simultaneous decline of anti-GAD levels which finally returned to normal values. This case indicates that anti-GAD antibodies may be associated with a broader clinical spectrum and future studies in GQ1b-seronegative patients could determine ultimately their clinical and pathogenetic significance in this syndrome

Two Novel KRIT1 and CCM2 Mutations in Patients Affected by Cerebral Cavernous Malformations: New Information on CCM2 Penetrance

Wide comprehension of genetic features of cerebral cavernous malformations (CCM) represents the starting point to better manage patients and risk rating in relatives. The causative mutations spectrum is constantly growing. KRIT1, CCM2, and PDCD10 are the three loci to date linked to familial CCM development, although germline mutations have also been detected in patients affected by sporadic forms. In this context, the main challenge is to draw up criteria to formulate genotype-phenotype correlations. Clearly, genetic factors determining incomplete penetrance of CCM need to be identified. Here, we report two novel intronic variants probably affecting splicing. Molecular screening of CCM genes was performed on DNA purified by peripheral blood. Coding exons and intron-exon boundaries were sequenced by the Sanger method. The first was detected in a sporadic patient and involves KRIT1. The second affects CCM2 and it is harbored by a woman with familial CCM. Interestingly, molecular analysis extended to both healthy and ill relatives allowed to estimate, for the first time, a penetrance for CCM2 lower than 100%, as to date reported. Moreover, heterogeneity of clinical manifestations among those affected carrying the same genotype further confirms involvement of modifier factors in CCM development

Novel mutation of the PRNP gene of a clinical CJD case

BACKGROUND: Transmissible spongiform encephalopathies (TSEs), a group of neurodegenerative diseases, are thought to be caused by an abnormal isoform of a naturally occurring protein known as cellular prion protein, PrP(C). The abnormal form of prion protein, PrP(Sc )accumulates in the brain of affected individuals. Both isoforms are encoded by the same prion protein gene (PRNP), and the structural changes occur post-translationally. Certain mutations in the PRNP gene result in genetic TSEs or increased susceptibility to TSEs. CASE PRESENTATION: A 70 year old woman was admitted to the hospital with severe confusion and inability to walk. Relatives recognized memory loss, gait and behavioral disturbances over a six month period prior to hospitalization. Neurological examination revealed Creutzfeldt-Jakob disease (CJD) related symptoms such as incontinence, Babinski sign and myoclonus. EEG showed periodic sharp waves typical of sporadic CJD and cerebrospinal fluid analysis (CSF) was positive for the presence of the 14-3-3-protein. As the disease progressed the patient developed akinetic mutism and died in the tenth month after onset of the disease symptoms. Unfortunately, no autopsy material was available. PRNP sequencing showed the occurrence of a point mutation on one allele at codon 193, which is altered from ACC, coding for a threonine, to ATC, encoding an isoleucine (T193I). CONCLUSION: Here we report a novel mutation of the PRNP gene found in an elderly female patient resulting in heterozygosity for isoleucine and threonine at codon 193, in which normally homozygosity for threonine is expected (T193). The patient presented typical clinical symptoms of CJD. EEG findings and the presence of the 14-3-3 protein in the CSF, contributed to CJD diagnosis, allowing the classification of this case as a probable CJD according to the World Health Organization (WHO) accepted criteria

Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis

Objectives:To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease.Methods:A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated for bilateral caudate and putamen for each case. The right:left asymmetry index and striatal asymmetry index was calculated.Results:Scans were available from 37 cases of monogenetic Parkinson's disease (7 glucocerebrosidase (GBA) mutations, 8 alpha-synuclein, 3 LRRK2, 7 PINK1, 12 Parkin). The asymmetry of radioligand uptake for Parkinson's disease with GBA or LRRK2 mutations was greater than that for Parkinson's disease with alpha synuclein, PINK1 or Parkin mutations.Conclusions:The asymmetry of radioligand uptake in Parkinsons disease associated with GBA or LRRK2 mutations suggests that interactions with additional genetic or environmental factors may be associated with dopaminergic neuronal loss

Genetics of familial Parkinson's disease

Parkinson’s disease (PD) is a complex, heterogenous neurodegenerative disorder. In the last century, the genetic contribution to the risk of PD was controversial. Recently, the identification of mutations in a-synuclein (SNCA), parkin (PARK2), ubiquitin C-terminal hydrolase L1 (UCHL1), PTEN-induced kinase 1 (PINK1), DJ-1, nuclear receptorrelated 1 (Nurr1) and leucine-rich repeat kinase 2 (LRRK2) genes has confirmed the role of genetics in familial forms of PD. These genetic findings have greatly advanced our knowledge on the pathophysiological background of familial PD. In addition to these genes, several other loci have been implicated in PD, although the responsible genes have not been identified, yet. Possible interactions between various already known or new candidate genes and the influence of environmental agents on the expression of PD-linked genes are in the scrutiny of recent genetic studies

The production and comprehension of verbs with alternating transitivity by patients with non-fluent aphasia

Background: Recent studies revealed that aphasic speakers have difficulties with the production of the intransitive (unaccusative) variant of verbs entering transitivity alternations. A key point of the current interpretations of these difficulties concerns the movement operations taking place at surface syntax, namely, the A-movement operation (Bastiaanse & van Zonneveld, 2005; Bastiaanse, 2008; Thompson, 2003). Aim: The present study revisits the issue of processing verbs with alternating transitivity in non-fluent aphasia in Greek, a language with rich morphology and relatively free word order, which lacks A-movement. In addition, in Greek, unaccusative verbs appear with different voice morphology: One class of intransitive variants of alternating verbs bears active morphology, another one non-active morphology and a third one can surface with both. The presence of non-active voice has been argued to correspond to the presence of a voice projection in syntax of these variants, while the variants that bear active morphology are not associated with a voice projection at the level of syntax. This study investigates the ability of non-fluent aphasic speakers to produce and comprehend verbs entering transitivity alterations and explores the role of active vs. non-active morphology and word order in the performance of aphasic speakers. Methods & Procedures: We tested five non-fluent patients and fifteen control participants. We used two tasks supported by pictures: an elicited production task and a comprehension task. The experimental material consisted of fifteen transitive and fifteen unaccusative verbs (marked for active, and/or non-active voice morphology) in sentence contexts. Outcomes & Results: The results indicated that (i) the aphasic speakers performed better on the production and comprehension of transitives than of unaccusatives, (ii) they showed significantly lower performance on the comprehension of unaccusatives with active morphology than on unaccusatives with non-active morphology, and finally (iii) they produced transitive (S)VO structures instead of the unaccusative ones. Conclusion: We suggest, in agreement with other researchers (for example, Schwartz, Linebarger, Saffran, & Pate, 1987) that aphasic individuals overuse a mapping strategy that associates the theta roles of agent and theme with syntactic subject and object respectively, as they produce transitive (S)VO structures, to a large extent, instead of unaccusatives. In addition, as they had difficulties with unaccusative verbs marked for active voice, we suggest that they could not successfully interpret unaccusative verbs with active voice morphology as non-agentive structures

Assessment of manual motor performance in Parkinson's disease

The purpose of our study was to assess manual motor performance in patients with Parkinson’s disease (PD) by means of simple instrumental timed tests and compare these findings with normative data. Ninety seven right-handed PD patients and 80 matched controls participated in the study. Motor dexterity was assessed by means of the following instruments: 1) Tapping board, 2) Dual Tally, and 3) Purdue Pegboard. PD patients performed worse than normal controls in all instrumental timed tests (p = 0.0001). However this difference was not always maintained in the group of PD patients who were older than 71 years.Finally we explored the relationship between motor disability and instrumental test scores in a subgroup of PD patients who were younger than 70 years. A negative correlation between UPDRS score and instrumental test scores was significant for all tests. ANOVA exploration of the differences in instrumental test scores between different stages of the disease showed significant differences for Tapping Board, Dual Tally left, Purdue Pegboard at 15 sec bilateral and Purdue Pegboard at 30 sec right. Performance in these tests deteriorated as stage progressed.Our findings indicate that the instrumental timed tests studied can be used reliably for manual motor performance assessment in PD patients under the age of 70 year