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Spinocerebellar ataxia (SCA) presents heterogeneous clinical phenotypes, and parkinsonism is reported in diverse SCA subtypes. Both levodopa responsive Parkinson disease (PD) like phenotype and atypical parkinsonism have been described especially in SCA2, SCA3, and SCA17 with geographic differences in prevalence. SCA2 is the most frequently reported subtype of SCA related to parkinsonism worldwide. Parkinsonism in SCA2 has unique genetic characteristics, such as low number of expansions and interrupted structures, which may explain the sporadic cases with low penetrance. Parkinsonism in SCA17 is more remarkable in Asian populations especially in Korea. In addition, an unclear cutoff of the pathologic range is the key issue in SCA17 related parkinsonism. SCA3 is more common in western cohorts. SCA6 and SCA8 have also been reported with a PD-like phenotype. Herein, we reviewed the epidemiologic, clinical, genetic, and pathologic features of parkinsonism in SCAs.

Both genetic and environmental factors are important in the pathogenesis of Parkinson＇s disease. As α-synuclein is a major constituent of Lewy bodies, a pathologic hallmark of Parkinson＇s disease, genetic aspects of α-synuclein is widely studied. However, the influence of dietary factors such as quercetin on α-synuclein was rarely studied. Herein we aimed to study the neuroprotective role of quercetin against various toxins affecting apoptosis, autophagy and aggresome, and the role of quercetin on α-synuclein expression. PC12 cells were pre-treated with quercetin（100, 500, 1,000 μM） and then together with various drugs such as 1-methyl-4-phenylpyridinium（MPP＋; a free radical generator）, 6-hydroxydopamine（6-OHDA; a free radical generator）, ammonium chloride（an autophagy inhibitor）, and nocodazole（an aggresome inhibitor）. Cell viability was determined using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltertazolium bromide（MTT） assay. Apoptosis was detected by annexin V-fluorescein isothiocyanate and propidium iodide through the use of fluorescence activated cell sorter. α-Synuclein expression was detected by western blot assay and immunohistochemistry. The role of α-synuclein was further studied by knocking out α-synuclein using RNA interference. Cell viability increased at lower concentrations（100 and 500 μM） of quercetin but decreased at higher concentration（1,000 μM）. Quercetin exerted neuroprotective effect against MPP＋, ammonium chloride and nocodazole at 100 μM. MPP＋ induced apoptosis was decreased by 100 μM quercetin. Quercetin treatment increased α-synuclein expression. However, knocking out α-synuclein exerted no significant effect on cell survival. In conclusion, quercetin is neuroprotective against toxic agents via affecting various mechanisms such as apoptosis, autophagy and aggresome. Because α-synuclein expression is increased by quercetin, the role of quercetin as an environmental factor in Parkinson＇s disease pathogenesis needs further investigation.

The effect of subthalamic deep brain stimulation (STN DBS) on cognition in Parkinson’s disease (PD) remains controversial, and it is unclear which factors are related to cognitive decline and dementia after STN DBS, especially over the long term. To this end, we analyzed the cognitive outcome of 103 non-demented patients with PD who were followed-up for at least 12 months after bilateral STN DBS surgery. Preoperatively, the patients were evaluated with the Unified Parkinson's Disease Rating Scale and neuropsychological tests. The rate of global cognitive decline and the incidence of dementia during follow-up for up to 7 years (mean 42.4 ± 24.5 months) were calculated, and preoperative clinical and neuropsychological factors associated with postoperative global cognitive decline or dementia were analyzed. The prevalence of mild cognitive impairment (MCI) and its relation to later cognitive decline or dementia were also evaluated. The annual decline in the mini–mental state examination score was 0.4 ± 1.7 with impaired attention and executive function and a higher levodopa equivalent dose at baseline being the predictors of a faster global cognitive decline after STN DBS. Dementia developed in 13 patients with an incidence rate of 35.7 per 1,000 person-years. Impaired executive function at baseline predicted dementia. At baseline, 63.1 % of the patients had PD-MCI, and these patients were more likely to develop dementia than those without PD-MCI. This study showed that dysfunctions in the frontostriatal circuitry at baseline were associated with a risk of subsequent global cognitive decline and dementia in patients with PD who underwent STN DBS. In addition, preoperative PD-MCI was a risk factor for dementia after STN DBS.

The standard assessment method for tremor severity in Parkinson's disease is visual observation by neurologists using clinical rating scales. This is, therefore, a subjective rating that is dependent on clinical expertise. The objective of this study was to report clinicians' tendencies to under-rate Parkinsonian tremors in the less affected hand. This was observed through objective tremor measurement with accelerometers. Tremor amplitudes were measured objectively using tri-axis-accelerometers for both hands simultaneously in 53 patients with Parkinson's disease during resting and postural tremors. The videotaped tremor was rated by neurologists using clinical rating scales. The tremor measured by accelerometer was compared with clinical ratings. Neurologists tended to under-rate the less affected hand in resting tremor when the contralateral hand had severe tremor in Session I. The participating neurologists corrected this tendency in Session II after being informed of it. The under-rating tendency was then repeated by other uninformed neurologists in Session III. Kappa statistics showed high inter-rater agreements and high agreements between estimated scores derived from the accelerometer signals and the mean Clinical Tremor Rating Scale evaluated in every session. Therefore, clinicians need to be aware of this under-rating tendency in visual inspection of the less affected hand in order to make accurate tremor severity assessments.

Freezing of gait (FOG) is one of the most disabling symptoms in Parkinsonism. Open-label studies have suggested that intravenous (IV) amantadine is effective against FOG resistant to dopaminergic therapy in Parkinson's disease (PD). We evaluated the efficacy of IV amantadine on FOG resistant to dopaminergic therapy. This was a randomized, double-blind, placebo-controlled, cross-over study on IV amantadine. The placebo (normal saline) and amantadine (400 mg/day) were injected for 2 days with a 52-hour washout period. The instruments for the outcome measures were the Freezing of Gait Questionnaire (FOGQ), Unified Parkinson's disease rating Scale (UPDRS), and the duration of the 4×10 m walking test. The placebo arm was compared to the amantadine arm. Ten patients were enrolled but two patients withdrew, one from each arm. The FOGQ and UPDRS scores and the duration of the 4×10 m walking test improved in both arms compared to the baseline (P<0.05 in all). However, there were no differences in these values between the amantadine arm and placebo arm (P = 0.368, P = 0.583, P = 0.206, respectively). Follow-up measures 2 weeks after discharge in an open-label study showed the beneficial effects of an amantadine tablet on FOG (FOGQ, P = 0.018; UPDRS, P = 0.012 respectively). This double blind, placebo-controlled study did not show the efficacy of IV amantadine on FOG when compared with the placebo. This study provides Class II evidence due to small sample size for the lack of benefit of IV amantadine on FOG resistant to dopaminergic therapy Clinicaltrials.gov NCT01313819.

Background As increasing numbers of deep brain stimulation (DBS) procedures are performed, rare abnormal findings on postoperative images that are not attributable to well-known complications are reported. Between 2005 and 2012, we encountered several symptomatic patients with transient abnormal low-attenuation lesions on postoperative computed tomography (CT) scans. The aim of this study was to clarify this rare phenomenon using chronological observations and to suggest a feasible mechanism. Results In this period, seven (3.2 %) patients displayed transient increased low-attenuation signals, circumferentially surrounding the DBS electrodes and extending into the subcortical white matter. All these patients suffered from unexpected but transient neurological symptoms during the postoperative period. The abnormal low-attenuation lesions only disappeared completely a considerable time after the clinical symptoms had disappeared, without treatment in most patients. Conclusions We report here our chronological observations of acute brain reactions after DBS procedures, which we believe are neither infectious nor vascular, but are possibly caused by the mechanical breakdown of the blood–brain barrier by microelectrode recordings or by anchored DBS electrodes. These lesions are thought to constitute a self-limiting disorder requiring no further treatment.

[...]they described that understanding PARK2 alternative splicing could open up new scenarios for the resolution of some parkinsonian syndrome.

Follow-up MRI of the brain showed symmetrical tiny lesions in the bilateral substantia nigra (figure B), with mild diffuse cerebellar and brainstem atrophy. 18FP-CIT PET study showed a reduced uptake in the bilateral putamen, more pronounced on the left (figure C). Post-encephalitic parkinsonism is a rare condition described in patients with encephalitis by the Japanese B virus, St Louis virus, West Nile virus, and HIV, and also in patients with encephalitis lethargica.1 It may develop in the acute phase of encephalitis, improving with time, or develop as a delayed form, possibly through immune mechanisms.2 Antiparkinsonian treatment, including levodopa, is usually very effective in both conditions.

The number of deep brain stimulation (DBS) hardware complications has increased during the past decade. In cases of abnormally high lead impedance with no evidence of a macroscopic fracture, optimal treatment options have not yet been established. Here, we present the case of a 49-year-old woman with a 12-year history of Parkinson's disease who received bilateral subthalamic nucleus DBS in March 2006. The patient showed good control of parkinsonism until December 24, 2010, when she awoke with abrupt worsening of parkinsonian symptoms. At telemetric testing, lead impedances were found at >2,000 Ω in all four leads on the left side. Fracture of a lead or an extension wire was suspected. However, radiological screening and palpation revealed no macroscopic fracture. In June 2011, the implantable pulse generator (IPG) was changed under local anesthesia without any complications. Postoperatively, her parkinsonism immediately improved to the previous level, and the lead impedance readings by telemetry were also normalized. The disconnection of the neurostimulator connector block and the hybrid circuit board of the IPG was confirmed by destructive analysis. The present report illustrates that a staged approach that starts with simple IPG replacement can be an option for some cases of acute DBS effect loss with high impedance, when radiological findings are normal, thereby sparing the intact electrodes and extension wires.