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A cirurgia reconstrutiva da mama após a mastectomia total ou parcial pode ser realizada com tecidos autólogos ou implantes mamários, e cada um tem seu próprio conjunto de complicações. A cirurgia estética da mama inclui aumento, redução e mastopexia e é realizada usando dispositivos protéticos ou técnicas de rearranjo tecidual. A maioria das mulheres não apresentam complicações significativas, no entanto, uma série de problemas pode ocorrer a qualquer momento após a cirurgia reconstrutiva ou estética da mama. O risco de algumas complicações aumenta para certos fatores do paciente (por exemplo, tabagismo, obesidade) e outros associados ao tratamento do câncer de mama (radioterapia). Outros fatores que influenciam a taxa de complicações incluem tipo de mastectomia, tipo de implante, tipo de retalho, uso de lipoenxertia, tamanho da mama (implantado) e cirurgia abdominal prévia (retalho transverso do músculo reto abdominal). As taxas de complicações precisas podem ser difíceis de identificar e de comparar entre os estudos devido a variáveis como diferentes tipos de reconstrução, experiência do cirurgião e fatores e comorbidades do paciente, bem como a duração do acompanhamento do paciente.

Although cancer survival rates are improving, pediatric patients with cancer still face numerous stressors. Using an integrative approach, a literature review was conducted to identify stressors and synthesize effective coping strategies among pediatric patients with cancer. The CINAHL® Complete, ProQuest, and PubMed® databases were searched for relevant studies using key terms. Eight studies were included in the final analysis. Three factors contributing to everyday stressors of pediatric patients with cancer and four major coping categories were identified.

Purpose Cerebellar connectivity is thought to be abnormal in cervical dystonia (CD) and other dystonia subtypes, based on evidence from imaging studies and animal work. The authors investigated whether transcranial magnetic stimulation-induced cerebellar brain inhibition (CBI), a measure of cerebellar efficiency at inhibiting motor outflow, is abnormal in patients with CD and/or is associated with clinical features of CD. Because of methodological heterogeneity in CBI reporting, the authors deployed additional controls to reduce potential sources of variability in this study. Methods Cerebellar brain inhibition was applied in 20 CD patients and 14 healthy control subjects. Cerebellar brain inhibition consisted of a cerebellar conditioning stimulus delivered at four different interstimulus intervals (ISIs) before a test stimulus delivered to hand muscle representation in the motor cortex. The average ratio of conditioned to unconditioned motor evoked potential was computed for each ISI. Cervical dystonia clinical severity was measured using the Toronto Western Spasmodic Torticollis Rating Scale. Control experiments involved neuronavigated transcranial magnetic stimulation, neck postural control in patients, and careful screening for noncerebellar pathway inhibition via cervicomedullary evoked potentials. Results There was no difference between CBI measured in healthy control subjects and CD patients at any of the four ISIs; however, CBI efficiency was significantly correlated with worsening CD clinical severity at the 5 ms ISI. Conclusions Cerebellar brain inhibition is a variable measure in both healthy control subjects and CD patients; much of this variability may be attributed to experimental methodology. Yet, CD severity is significantly associated with reduced CBI at the 5 ms ISI, suggestive of cerebello-thalamo-cortical tract dysfunction in this disorder.

Highlights • PD with mild behavioral impairment revealed deficits in cognitive flexibility. • Brain activities during a set-shifting task linked with MBI in PD was evaluated. • PD-MBI revealed reduced activity in the prefrontal and posterior parietal cortices. • The prefrontal activity was associated with cognitive impairment in PD-MBI. • High MBI-C score was associated with reduced deactivation in the hippocampus., Mild behavioral impairment (MBI) is a neurobehavioral syndrome characterized by later life emergence of sustained neuropsychiatric symptoms, as an at-risk state for incident cognitive decline and dementia. Prior studies have reported that neuropsychiatric symptoms are associated with cognitive abilities in Parkinson’s disease (PD) patients, and we have recently found a strong correlation between MBI and cognitive performance. However, the underlying neural activity patterns of cognitive performance linked to MBI in PD are unknown. Fifty-nine non-demented PD patients and 26 healthy controls were scanned using fMRI during performance of a modified version of the Wisconsin card sorting task. MBI was evaluated using the MBI-checklist, and PD patients were divided into two groups, PD-MBI and PD-noMBI. Compared to the PD-noMBI group and healthy controls, the PD-MBI group revealed less activation in the prefrontal and posterior parietal cortices, and reduced deactivation in the medial temporal region. These results suggest that in PD, MBI reflects deficits in the frontoparietal control network and the hippocampal memory system.

Objective:To assess effects of caffeine on Parkinson disease (PD).Methods:In this multicenter parallel-group controlled trial, patients with PD with 1–8 years disease duration, Hoehn & Yahr stages I–III, on stable symptomatic therapy were randomized to caffeine 200 mg BID vs matching placebo capsules for 6–18 months. The primary research question was whether objective motor scores would differ at 6 months (Movement Disorder Society–sponsored Unified Parkinson's Disease Rating Scale [MDS-UPDRS]–III, Class I evidence). Secondary outcomes included safety and tolerability, motor symptoms (MDS-UPDRS-II), motor fluctuations, sleep, nonmotor symptoms (MDS-UPDRS-I), cognition (Montreal Cognitive Assessment), and quality of life.Results:Sixty patients received caffeine and 61 placebo. Caffeine was well-tolerated with similar prevalence of side effects as placebo. There was no improvement in motor parkinsonism (the primary outcome) with caffeine treatment compared to placebo (difference between groups −0.48 [95% confidence interval −3.21 to 2.25] points on MDS-UPDRS-III). Similarly, on secondary outcomes, there was no change in motor signs or motor symptoms (MDS-UPDRS-II) at any time point, and no difference on quality of life. There was a slight improvement in somnolence over the first 6 months, which attenuated over time. There was a slight increase in dyskinesia with caffeine (MDS-UPDRS-4.1+4.2 = 0.25 points higher), and caffeine was associated with worse cognitive testing scores (average Montreal Cognitive Assessment = 0.66 [0.01, 1.32] worse than placebo).Conclusion:Caffeine did not provide clinically important improvement of motor manifestations of PD (Class I evidence). Epidemiologic links between caffeine and lower PD risk do not appear to be explained by symptomatic effects.Clinicaltrials.gov identifier:NCT01738178.Classification of evidence:This study provides Class I evidence that for patients with PD, caffeine does not significantly improve motor manifestations.

ObjectiveTo evaluate the associations of mild behavioral impairment (MBI) with cognitive deficits and patterns of gray matter changes in Parkinson disease (PD).MethodsSixty patients with PD without dementia and 29 healthy controls underwent a cognitive neuropsychological evaluation and structural MRI scan. MBI was evaluated with the MBI Checklist (MBI-C), a rating scale designed to elicit emergent neuropsychiatric symptoms in accordance with MBI criteria. We divided the patients with PD into 2 groups: 1 group with high MBI-C scores (PD-MBI) and the other with low MBI-C scores (PD-noMBI).ResultsAmong 60 patients with PD, 20 were categorized as having PD-MBI (33.33%). In healthy controls, no participants met the MBI cut-point threshold. The PD-MBI group had significantly lower Montreal Cognitive Assessment and z scores in all 5 domains and the global score compared to healthy controls and those with PD-noMBI. In addition, all cognitive domains except language and global cognition negatively correlated with the MBI-C total score in all patients with PD. For cortical structures, the PD-MBI group revealed middle temporal cortex thinning and decreased volume compared with the PD-noMBI group, and decreased volume in this area negatively correlated with the MBI-C total score.ConclusionsThe impaired cognitive function over all domains and atrophy in the temporal area in the PD-MBI group are in line with posterior cortical circuit deficits in PD, which have been associated with a faster rate of progression to dementia. These initial results suggest that MBI might be an early and important marker for incident cognitive decline and dementia in patients with PD.

A 56-year-old woman presented with headache, vomiting for 3 days, and right hearing loss, tinnitus, and dysphagia over 3 months. Examination showed decreased right palate elevation and atrophy of right sternocleidomastoid, trapezius, and tongue with rightward tongue deviation, indicating Collet-Sicard syndrome (involving cranial nerves IX–XII in jugular foramen and hypoglossal canal).1 Hearing loss suggested auditory canal extension. Imaging showed a right skull base mass in keeping with glomus tumor (figures 1 and 2). Given surgical risks, radical radiotherapy was performed, arresting tumor growth. Glomus jugulare tumors, hypervascular paragangliomas, are the most common tumors in the jugular foramen and can extend into the middle ear (jugulotympanicum).2

Metronidazole (Flagyl®) is an antimicrobial agent commonly used in clinical practice. Although it is generally well tolerated with minimal side effects, there are a host of still under-recognized neurologic complications of metronidazole treatment. The following review is aimed at summarizing current literature pertaining to metronidazole-induced neurotoxicity including clinical syndromes, neuroradiological findings, prognosis and proposed pathophysiology. Recognition of the neurotoxic effects of metronidazole is critical as prompt discontinuation is generally associated with full clinical recovery and radiological resolution. Complications neurologiques du metronidazole. Le metronidazole (Flagyl®) est un agent antimicrobien utilise couramment en pratique clinique. Bien qu'il soit generalement bien tolere et que ses effets secondaires soient minimes, il existe une myriade de complications neurologiques du traitement par le metronidazole qui ne sont pas toujours reconnues. Le but de cette revue constitue un sommaire de la litterature actuelle concernant la neurotoxicite induite par le metronidazole dont les syndromes cliniques, les constatations neuroradiologiques, le pronostic et l'hypothese physiopathologique expliquant cette neurotoxicite. Il est important d'identifier ces effets neurotoxiques du metronidazole etant donne que l'arrět immediat du traitement est generalement associe a une guerison clinique complete et a la disparition des signes radiologiques.

The presence and potential etiologies of peripheral neuropathy (PN) in patients with Parkinson's Disease (PD) is unknown. We examined for presence of PN in patients with PD. From a PD patient population of 500 patients screened for features of symptomatic PN, patients were further selected for clinical, electrophysiological, and laboratory studies related to PN. This PD patient population with idiopathic PN (PD-IPN) was compared to a group of PD patients without PN (PD-only), and a large group of patients without PD with idiopathic PN (IPN) for abnormalities in Cbl, fasting homocysteine (Hcy), and fasting methylmalonic acid (MMA) levels. PD-IPN and IPN patients identified with abnormalities in Cbl, Hcy, or MMA levels were treated with intramuscular Cbl for 1 to 2 years. Of 49 PD patients with symptomatic PN, 34 patients (69%) had PD-IPN, and 32/34 (94%) had abnormal Hcy or MMA levels as compared to 26/258 (10%) of IPN patients. Cumulative lifetime L-dopa dosage and fasting MMA levels were associated with PN severity. Cbl therapy led to improvements in Hcy and MMA levels in all groups, and PN in PD-IPN patients stabilized during therapy. PN in PD patients may be associated with iatrogenic Cbl metabolic abnormalities. Alternatively PN may be a peripheral nervous system manifestation of PD.

Pathological gambling (PG) has been identified in patients with Parkinson's disease (PD) treated with dopamine agonists suggesting that dysregulation of brain dopaminergic activity may contribute to the development of gambling problems. The current study was undertaken to further establish the prevalence of problem and PG in patients with PD, identify any clinical correlates, and determine if psychiatric or substance use co-morbidity contributes to the increased prevalence of problem and PG. A cross-sectional survey of 140 serially recruited moderate to severe PD patients was undertaken utilizing the Canadian Problem Gambling Index, Alcohol Use Disorders Identification Test, Drug Abuse Screening Test, Beck Depression Inventory, Beck Anxiety Inventory, and Mini-Mental State Exam augmented by chart review, completed over an 8 month period. The 12 month prevalence of problem and PG in PD was 9.3% compared to 1.6% in the general population within a comparably aged sample. The increased prevalence of problem and PG in the PD group was related to dopamine agonist use and younger age, but not co-morbidity. Most subjects with problem and PG reported their gambling increased after being diagnosed with PD and starting treatment. The results suggest that brain dopaminergic activity is involved in the underlying neurobiology of problem and PG.

Identifying measures that are associated with the cytosine-adenine-guanine (CAG) expansion in individuals before diagnosis of Huntington disease (HD) has implications for designing clinical trials.To identify the earliest features associated with the motor diagnosis of HD in the Prospective Huntington at Risk Observational Study (PHAROS).A prospective, multicenter, longitudinal cohort study was conducted at 43 US and Canadian Huntington Study Group research sites from July 9, 1999, through December 17, 2009. Participants included 983 unaffected adults at risk for HD who had chosen to remain unaware of their mutation status. Baseline comparability between CAG expansion (≥37 repeats) and nonexpansion (37 repeats) groups was assessed. All participants and investigators were blinded to individual CAG analysis. A repeated-measures analysis adjusting for age and sex was used to assess the divergence of the linear trend between the expanded and nonexpanded groups. Data were analyzed from April 27, 2010, to September 3, 2013.Huntington disease mutation status in individuals with CAG expansion vs without CAG expansion.Unified Huntington's Disease Rating Scale motor (score range, 0-124; higher scores indicate greater impairment), cognitive (symbol digits modality is the total number of correct responses in 90 seconds; lower scores indicate greater impairment), behavioral (score range, 0-176; higher scores indicate greater behavioral symptoms), and functional (Total Functional Capacity score range, 0-13; lower scores indicate reduced functional ability) domains were assessed at baseline and every 9 months up to a maximum of 10 years.Among the 983 research participants at risk for HD in the longitudinal cohort, 345 (35.1%) carried the CAG expansion and 638 (64.9%) did not. The mean (SD) duration of follow-up was 5.8 (3.0) years. At baseline, participants with expansions had more impaired motor (3.0 [4.2] vs 1.9 [2.8]; P .001), cognitive (P .05 for all measures except Verbal Fluency, P = .52), and behavioral domain scores (9.4 [11.4] vs 6.5 [8.5]; P .001) but not significantly different measures of functional capacity (12.9 [0.3] vs 13.0 [0.2]; P = .23). With findings reported as mean slope (95% CI), in the longitudinal analyses, participants with CAG expansions showed significant worsening in motor (0.84 [0.73 to 0.95] vs 0.03 [-0.05 to 0.11]), cognitive (-0.54 [-0.67 to -0.40] vs 0.22 [0.12 to 0.32]), and functional (-0.08 [-0.09 to -0.06] vs -0.01 [-0.02 to 0]) measures compared with those without expansion (P .001 for all); behavioral domain scores did not diverge significantly between groups.Using these prospectively accrued clinical data, relatively large treatment effects would be required to mount a randomized, placebo-controlled clinical trial involving premanifest HD individuals who carry the CAG expansion.

Peak-dose dyskinesias are abnormal movements that usually occur 1 h after oral administration of levodopa, and often complicate chronic treatment of Parkinson's disease. We investigated by PET with [11C]raclopride whether Parkinson's disease progression modifies the striatal changes in synaptic dopamine levels induced by levodopa administration, and whether this modification, if present, could have an impact on the emergence of dyskinesias. We found that, 1 h after oral administration of standard-release 250/25 mg of levodopa/carbidopa, levodopa-induced increases in synaptic dopamine levels (as estimated by striatal changes in [11C]raclopride binding potential) correlated positively with duration of Parkinson's disease symptoms (for the caudate nucleus, r = 0.79, P < 0.001; for the putamen, r = 0.88, P < 0.0001). Patients with peak-dose dyskinesias had larger 1-h increases in synaptic dopamine levels than stable responders, but there were no between-group differences in [11C]raclopride binding 4 h post-levodopa. The corresponding (time x group) interaction term in the repeated measures analysis of covariance was significant, even after adjusting for between-group differences in duration of Parkinson's disease symptoms (for the caudate nucleus, P = 0.030; for the putamen, P = 0.021). Our results indicate that, at the synaptic level, an identical dose of levodopa induces increasingly larger 1-h changes in dopamine levels as Parkinson's disease progresses. Large levodopa-induced increases in synaptic dopamine concentration can lead to dramatic changes in receptor occupancy, which may be responsible for the emergence of peak-dose dyskinesias in Parkinson's disease.

Dopa-responsive dystonia (DRD) is a lifelong disorder in which dopamine deficiency is not associated with neuronal loss and therefore it is an ideal human model for investigating the compensatory changes that occur in response to this biochemical abnormality. Using positron emission tomography (PET), we examined the (±)-α-[11C]dihydrotetrabenazine ([11C]DTBZ) binding potential of untreated DRD patients and normal controls. Two other PET markers of presynaptic nigrostriatal function, d-threo-[11C]methylphenidate ([11C]MP) and 6-[18F]fluoro-L-dopa ([18F]-dopa), and [11C]raclopride were also used in the study. We found increased [11C]DTBZ binding potential in the striatum of DRD patients. By contrast, no significant changes were detected in either [11C]MP binding potential or [18F]-dopa uptake rate constant. In addition, we found evidence for increased dopamine turnover in one DRD patient by examining changes in [11C]raclopride binding potential in relation to levodopa treatment. We propose that the increase in [11C]DTBZ binding likely reflects the dramatic decrease in the intravesicular concentration of dopamine that occurs in DRD; upregulation of vesicular monoamine transporter type 2 (VMAT2) expression may also contribute. Our findings suggest that the striatal expression of VMAT2 (as estimated by [11C]DTBZ binding) is not coregulated with dopamine synthesis. This is in keeping with a role for VMAT2 in other cellular processes (i.e., sequestration and release from the cell of potential toxic products), in addition to its importance for the quantal release of monoamines. Synapse 49:20–28, 2003. © 2003 Wiley-Liss, Inc.

Background: Transplanted striatal cells have been demonstrated to survive, grow, establish afferent and efferent connections, and improve behavioral signs in animal models of Huntington’s disease (HD). Objective: To evaluate feasibility and safety and to provide preliminary information regarding the efficacy of bilateral human fetal striatal transplantation in HD. Methods: Seven symptomatic patients with genetically confirmed HD underwent bilateral stereotactic transplantation of two to eight fetal striata per side in two staged procedures. Tissue was dissected from the lateral half of the lateral ventricular eminence of donors 8 to 9 weeks postconception. Subjects received cyclosporine for 6 months. Results: Three subjects developed subdural hemorrhages (SDHs) and two required surgical drainage. One subject died 18 months after surgery from probable cardiac arrhythmia secondary to severe atherosclerotic cardiac disease. Autopsy demonstrated clearly demarcated grafts of typical developing striatal morphology, with host-derived dopaminergic fibers extending into the grafts and no evidence of immune rejection. Other adverse events were generally mild and transient. Mean Unified HD Rating Scale (UHDRS) motor scores were 32.9 ± 6.2 at baseline and 29.7 ± 7.5 12 months after surgery ( p = 0.24). Post-hoc analysis, excluding one subject who experienced cognitive and motor deterioration after the development of symptomatic bilateral SDHs, found that UHDRS motor scores were 33.8 ± 6.2 at baseline and 27.5 ± 5.2 at 12 months ( p = 0.03). Conclusions: Transplantation of human fetal striatal cells is feasible and survival of transplanted cells was demonstrated. Patients with moderately advanced HD are at risk for SDH after transplantation surgery.

Background:An urgent neurology assessment clinic was created at our institution to improve access to prompt neurological assessment, and has been in operation for over a decade. We assessed its timeliness and impact.Methods:The clinic database was examined retrospectively for trends in the volume and waiting time to assessments, neurologic diagnoses, and whether neurologic assessment changed patients’ diagnoses. Before and after implementation, the frequency of emergency department neurology assessments and hospital admissions for neurological investigation were compared.Results:In the first decade, 25145 referrals were received; 12460 patients were accepted and assessed within an average of 3.8 working days. The most common problems seen included headache and seizure (20.2% each). Overall, 44.6% of assessments resulted in a change to the referring diagnosis; this proportion varied by the type of problem seen (from 10.5% for seizures to 92.5% for psychiatric disturbances). From the pre- to post-opening periods, there were fewer emergency room neurological assessments (35.7% reduction) and fewer hospital admissions for neurological investigation (4.4/week to 2.2/week, 50% reduction).Conclusions:The urgent neurology clinic model at our institution has provided excellent service, including wait times of a few days, to a catchment of over two million Canadians for over a decade; clinic assessments have affected diagnoses and patient care.

Surgery for movement disorders (MD) has experienced a renaissance over the past decade due to technological advances, greater comprehension of physiology of the basal ganglia, development of reliable disease severity scales, and multicentre clinical trials. While surgery for Parkinson disease (PD) usually receives the bulk of attention and discussion, contemporary surgical results for dystonia are more impressive and seem to be associated with fewer complications than that for PD. The surgical management of Huntington disease and Tourette syndrome remains experimental although a few reports have suggested benefit.

Genetic imprinting refers to the phenomenon whereby the precise expression of a specific trait (or disease) may depend on the sex of the transmitting parent. The purpose of the present project was to investigate the possibility for the involvement of genetic imprinting in Tourette syndrome (TS), a disease of the central nervous system in which many cases show evidence of an autosomal dominant mode of inheritance. The justification for the study arose from the noted variable expression of the associated symptoms in TS. Through the method of chart review, information regarding sex of the transmitting parent, age of onset of motor tics, as well as associated symptoms, was gathered from patients with a clear family history of TS consistent with autosomal dominant mode of transmission. No evidence was found for genetic imprinting in TS. The potential criticisms and implications of this finding are discussed. © 1994 Wiley-Liss, Inc.

A 54-year-old man presented with a 3-day history of difficulty speaking and an unsteady gait after having a generalized tonic-clonic seizure. He had been taking oral metronidazole for bronchiectasis for 2 months before presentation (estimated cumulative dose of about 60 g). His medical history

Objectif: L'orientation des patients atteints de troubles du mouvement vers la neurochirurgie pour stimulation cerebrale profonde a ete examinee afin de determiner si la proportion de ces patients par sexe etait representative de cette proportion dans notre population et pourquoi un certain nombre de ces patients ne subissent pas l'intervention. Methodes: Il s'agit d'une analyse retrospective de l'information demographique sur les patients orientes en chirurgie contenue dans notre base de donnees et obtenue egalement d'une revue detaillee de dossiers. Resultats: Bien qu'un nombre presque egal d'hommes et de femmes soient atteints de troubles du mouvement, seulement 31% des 91 patients orientes en chirurgie etaient des femmes. La chirurgie n'a pas ete effectuee chez soixante et un pour cent d'entre eux, la plupart du temps pour des raisons medicales, soit un declin cognitif chez 21%, des problemes de nature psychiatrique chez 5% et de nature neurologique chez 42%. Conclusions: Un peu moins du tiers des patients orientes vers la chirurgie pour un trouble du mouvement n'ont pas subi cette chirurgie pour des raisons medicales. Cette constatation souligne l'importance d'une evaluation globale par une equipe multidisciplinaire de tous les patients candidats a la chirurgie stereotaxique. Il est interessant de noter que les femmes etaient sous-representees parmi les patients orientes vers la chirurgie. Pour que tous les patients eligibles aient la possibilite d'y avoir acces, l'education des medecins et des patients et des strategies differentes pour rejoindre les femmes pourraient permettre a un plus grand nombre de patients d'en beneficier.

Contexte: Les ataxies spinocerebelleuses (ASCs) constituent un groupe heterogene de maladies neurodegeneratives tant au point de vue genetique qu'au point de vue clinique. Leur frequence relative est tres variable selon le groupe ethnique et le lieu geographique. Objectifs: 1) determiner la frequence d'ASCs hereditaires et sporadiques debutant chez l'adulte chez des patients frequentant une clinique de desordres du mouvement ; 2) evaluer si on retrouve chez ces patients des premutations du gene FMR1 causant le syndrome de retard mental du X fragile. Methodes: Nous avons procede a une revue retrospective de dossiers de patients chez qui un diagnostic d'ASC de l'adulte a ete pose. Des tests de biologie moleculaire ont ete faits pour detecter des anomalies des genes responsables de l'ASC de type 1, 2, 3, 6, 7 et 8, de l'atrophie dentato-rubro-pallido-luysienne (ADRPL), de l'ataxie de Friedrich (AF) ainsi que l'expansion de FMR1. Resultats: 69 patients appartenant a 60 familles differentes ont ete identifies. Chez 21 familles (35%), l'heredite etait autosomique dominante (AD) et chez 2 (3.3%) l'heredite etait autosomique recessive (AR). Une histoire familiale positive mal definie etait presente chez 9 familles (15%). La maladie semblait sporadique chez 26 patients (43,3%). Chez les familles ou l'heredite etait AD, la mutation la plus frequents etait une mutation du gene ASC3 (23,8%) suivie d'ASC2 (14,3%) et d'ASC6 (14,3%). Une mutation du gene ASC1 et ASC8 a ete identifiee chez 4,8% des patients. Une mutation du gene de l'AF a ete identifiee dans un pedigree ou la maladie etait pseudo dominante et dans un ou la maladie etait AR. Chez un cas sporadique on a trouve une mutation du gene ASC3. Les tests pour l'ADRPL et le FMR 1 etaient negatif. Conclusion: Une histoire familiale positive etait presente chez 53,3% des patients atteints d'ASC adulte. Un diagnostic genetique specifique a pu etre etabli chez 61,9% des pedigrees ou l'heredite etait dominante et une mutation du gene ASC3 etait l'anomalie la plus frequente, suivie d'ASC2 et d'ASC6. Le rendement etait faible chez les cas sporadiques. La premutation du gene responsable du syndrome du X fragile n'etait pas responsable de l'ASC chez nos cas.

Huntington's disease (HD) is a progressive disorder with no known cure. We report two-year postoperative positron emission tomography (PET) data from 7 HD patients who underwent intrastriatal fetal transplantation. Patients showed widespread reductions in glucose uptake with no significant change over 2 years. Dopamine receptor binding was significantly reduced in HD striatum. D1 binding did not change significantly following transplantation, but there was a significant loss of D2 binding. These findings may reflect loss of graft viability and/or disease progression. There was no significant relationship between changes in PET and clinical function. In summary, there was no benefit from transplantation.

Spinocerebellar ataxia type 2 (SCA2) has been recognized recently as an uncommon cause of parkinsonism, an alternate presentation to the typical cerebellar disorder. This research review summarizes the existing literature on parkinsonism-predominant presentation SCA2 and presents new clinical cases of patients with this condition. Various phenotypes are noted in this subtype of SCA2, including parkinsonism indistinguishable from idiopathic Parkinson's disease (PD), parkinsonism plus ataxia, motor neuron disease, and postural tremor. In several kindreds with multiple affected family members, the SCA2 expansion segregated with disease; in addition, several single cases of parkinsonism with and without a family history are also described. The number of repeats in symptomatic patients ranged from 33 to 43. Interruption of the CAG repeat with CAA, CGG, or CCG was found in some individuals, possibly stabilizing the repeat structure and accounting for the relative stability of the repeat size across generations in some families; allele length is not necessarily indicative of trinucleotide repeat architecture. Positron emission tomography scanning in one family showed reduced fluorodopa uptake and normal to increased raclopride binding with a rostrocaudal gradient similar to that found in idiopathic PD. This review emphasizes the importance of testing for SCA2 in patients with parkinsonism and a family history of neurodegenerative disorders. Testing for SCA2 is also important in studies of inherited parkinsonism.

Dopa-responsive dystonia (DRD) is a lifelong disorder in which dopamine deficiency is not associated with neuronal loss and therefore it is an ideal human model for investigating the compensatory changes that occur in response to this biochemical abnormality. Using positron emission tomography (PET), we examined the (+/-)-alpha-[(11)C]dihydrotetrabenazine ([(11)C]DTBZ) binding potential of untreated DRD patients and normal controls. Two other PET markers of presynaptic nigrostriatal function, d-threo-[(11)C]methylphenidate ([(11)C]MP) and 6-[(18)F]fluoro-L-dopa ([(18)F]-dopa), and [(11)C]raclopride were also used in the study. We found increased [(11)C]DTBZ binding potential in the striatum of DRD patients. By contrast, no significant changes were detected in either [(11)C]MP binding potential or [(18)F]-dopa uptake rate constant. In addition, we found evidence for increased dopamine turnover in one DRD patient by examining changes in [(11)C]raclopride binding potential in relation to levodopa treatment. We propose that the increase in [(11)C]DTBZ binding likely reflects the dramatic decrease in the intravesicular concentration of dopamine that occurs in DRD; upregulation of vesicular monoamine transporter type 2 (VMAT2) expression may also contribute. Our findings suggest that the striatal expression of VMAT2 (as estimated by [(11)C]DTBZ binding) is not coregulated with dopamine synthesis. This is in keeping with a role for VMAT2 in other cellular processes (i.e., sequestration and release from the cell of potential toxic products), in addition to its importance for the quantal release of monoamines.

Inherited ataxias are a heterogeneous group of disorders characterized by autosomal dominant and recessive inheritance. Recent advances in genetic research have resulted in an improved comprehension of their clinical presentation. Autosomal dominant cerebellar ataxias (ADCAs) include spinocerebellar ataxias (SCAs) and dentatorubral-pallidoluysian atrophy (DRPLA); six of these have been found to be trinucleotide repeat disorders. Episodic ataxia, types 1 and 2, are at present recognized to be channelopathies, caused by point mutations. Friedreich’s ataxia (FA) which is an autosomal recessive disorder, resulting from a a unique trinucleotide repeat, is now recognized to have a wide age of onset and clinical spectrum. Ataxia-telangiectasia (AT), also an autosomal recessive cerebellar ataxia, is characterized by immunodeficiency. In this article, the genetic and clinical characteristics of these diseases are reviewed in detail.

The discovery of the Huntington's disease (HD) gene has provided the impetus to determine the association between the triplet repeat sequences and clinical manifestations of the disease. The present study is directed toward determining the relationship between the triplet repeat sequences and severity of the neurodegenerative process. Nineteen HD postmortem cases were evaluated for neuropathological changes as well as for the number of trinucleotide repeat sequences, each in a blinded fashion. Each case was assigned a gross grade according to the scale of Vonsattel and colleagues (1985); neuronal counts were then performed on both the caudate and the putamen. For 7 of the postmortem cases, blood had been collected prior to death and was analyzed for the HD gene. For the 12 remaining cases for which blood was unavailable, DNA from the frontal neocortex and striatum was extracted from frozen or formalin-fixed paraffinized tissue and subsequently analyzed for the HD gene. When correlation was made for age at death, greater numbers of trinucleotide repeats were associated with greater neuronal loss, in both the caudate (r = 0.9641, p < 0.001) and the putamen (r = 0.9652, p < 0.001). When correction was made for disease duration, the correlation was again significant, for both the caudate (r = 0.6396, p < 0.01) and the putamen (r equals; 0.6710, p < 0.001). This suggests that in HD, longer trinucleotide repeat length is associated with a faster rate of deterioration and greater pathological severity. A comparison of trinucleotide repeat length in different brain regions in 4 of the HD postmortem cases associated with greater numbers of repeats consistently demonstrated fewer repeats in the cerebellum than in the frontal cortex, striatum or blood.

Patients with Parkinson's disease (PD) are known to experience autonomic nervous system dysfunction: this disruptive symptomatology includes urinary urgency, frequency, and nocturnal polyuria. Anticholinergic and tricyclic medications can be beneficial in controlling these urinary symptoms, but have unpleasant side effects in some patients. Desmopressin has been used to treat nocturnal polyuria successfully in a number of conditions, such as central diabetes insipidus, enuresis, and autonomic failure. The purpose of the present study was to assess the efficacy of desmopressin in patients with PD with significant nocturia. Eight patients were recruited into the study. They were first asked to establish a baseline of number of nocturnal voids; the patients were then prescribed the intranasal form of desmopressin and asked to continue to record the number of nocturnal voids. The five patients who completed the trial demonstrated clinically and statistically significant reductions in the frequency of nocturnal voids. One patient became hyponatremic and confused during desmopressin administration; his symptoms resolved soon after the desmopressin was discontinued. Two patients failed to complete the trial due to compliance problems. Thus, desmopressin appears to be a safe and effective medication for nocturnal polyuria in PD.

Huntington’s Disease (HD) is a progressive degenerative disorder of the central nervous system inherited as an autosomal dominant trait. Clinically, the disorder is characterized by choreoathetosis (with age of onset typically in the late thirties or early forties) and neuropsychiatric disturbance. The striatum is particularly vulnerable to the degenerative disease process, with selective loss of medium spiny neurons and decreased levels of associated neurotransmitters, including substance P, GABA, met-enkephalin and dynorphin. Although the underlying pathophysiology is unknown, recent theories concerning pathogenesis have involved mitochondrial abnormalities and excitotoxin-mediated damage. The gene for HD has recently been discovered and characterized as an unstable CAG trinucleotide repeat sequence on the short arm of chromosome 4 (now known as IT 15). The direct test now available for the HD gene has facilitated disease diagnosis, particularly for those with unclear family history or chorea of uncertain origin; presymptomatic testing is also available. Management of affected individuals is unsatisfactory as only symptomatic control is available. However, as the effect of the genetic abnormality may soon be known, specific treatment of the disorder may become available in the near future.

Autosomal dominant dopa-responsive dystonia (DRD) is mainly caused by mutations in GCH1 , which encodes GTP cyclohydrolase I (GTPCH), the enzyme in the biosynthesis of tetrahydrobiopterin (BH4; the cofactor for tyrosine hydroxylase [TH]).1 However, because of incomplete penetrance of GCH1 mutations in GTPCH-deficient DRD, it cannot be predicted whether an individual with a GCH1 mutation will develop DRD symptoms. Because dopamine is a prolactin-inhibiting factor and hyperprolactinemia was reported in patients with autosomal recessive BH4 deficiency,2-4⇓⇓ we compared serum prolactin levels between untreated patients with a heterozygous GCH1 mutation and asymptomatic carriers of the mutation in a three-generation DRD family to evaluate whether the prolactin level relates to the symptomatic state of DRD. We also determined prolactin concentration in a dopa-naive compound heterozygote for GCH1 mutations in the DRD family who developed relatively severe symptoms (dystonia with motor delay). The study was approved by the review board of the Centre for Addiction and Mental Health. After obtaining written informed consent, we conducted direct sequencing of GCH1 using genomic DNA from peripheral leukocytes,5 and measured serum prolactin levels by standard enzyme-immunoassay. Blood samples were …

Objective: In this study we evaluated medication reconciliation and ordering of dopamine blocking medications in Parkinson9s disease (PD) patients admitted to hospital. Background Patients with PD are often admitted to acute care hospitals with a variety of medical and surgical issues. Their care providers in such situations are often not the physicians in charge of their PD care, and as a result, there is a potential for lack of familiarity with PD treatment regimens. Design/Methods: Patients of the Movement Disorders Clinic residing in Calgary with PD were cross-referenced with the Calgary hospital admissions database for 2010. Medication reconciliation of PD medications at admission was examined for medication total dosage, scheduling, omission, and formulation (either long acting(CR), or immediate release(IR)). Ordering of dopamine blocking medications, either metoclopramide or neuroleptics was also assessed. Results: 403 patients of the MDC were screened. 55 admissions for 44 PD patients were analyzed. In 44/55(80%), medication reconciliation discrepancies or prescription of dopamine blocking medications were noted. 53/55(96.4%) of admissions were for patients taking levodopa. Of these 53, 26/53(49.0%) had differences between pre-admission and admission levodopa orders: in 3/53(5.7%) no levodopa was ordered; 15/53(28.3%) had dosage differences; 8/53(15.1%) had scheduling differences; and 12/53(22.6%) were ordered the incorrect formulation. 19/55(34.5%) of admissions were for patients who were on PD medications in addition to levodopa:7/19(36.8%) had differences in the ordering of these medications at the time of admission. Dopamine blocking agents were ordered during 24/55(43.6%) admissions. Conclusions: Our study identifies deficiencies in the in-hospital prescribing of medications for patients with PD. This includes a failure to seamlessly continue usual PD medications when patients are admitted, and perhaps of even greater concern, the inappropriate addition of dopamine blocking agents during their hospital stay. Widespread education of providers and safe-prescribing protocols are urgently needed to address these unsafe care issues. Disclosure: Dr. Wiltshire has nothing to disclose. Dr. Furtado has nothing to disclose. Dr. Ghali has nothing to disclose. Dr. Kraft has nothing to disclose.

The authors describe an Alberta family with levodopa-responsive parkinsonism without cerebellar abnormalities. Genetic testing showed expanded repeats for SCA-2; other mutations for parkinsonism were excluded. The expanded allele shows interruption of the CAG repeat with CAA. PET in two affected members showed reduced fluorodopa uptake in striatum and normal raclopride binding. Families with autosomal dominant, levodopa-responsive parkinsonism should be tested for the SCA-2 mutation.