M1 and Cerebellar tDCS for MSA-C: a Double-Blind, Randomized, Sham-Controlled, Crossover Study.

The effect of transcranial direct current stimulation (tDCS) for cerebellar-dominant multiple-system atrophy (MSA-C) is not well elucidated, yet. This study aimed to investigate the effect of tDCS on the primary motor cortex (M1) and cerebellum in patients with MSA-C. We recruited probable MSA-C patients and performed three single sessions of tDCS at each visit in random order (M1, cerebellum or sham). Cerebellar ataxia was evaluated with the International Cooperative Ataxia Rating Scale (ICARS) and objective gait and static balance analyses both before and after each stimulation session. Additionally, we also evaluated the factors related with objective improvement from each stimulation. Sixteen participants were enrolled, and one dropped out after 2 sessions of stimulation due to consent withdrawal. The gait velocity, step time and single support time all significantly improved after the M1 and cerebellar tDCS treatment compared with the sham stimulation while there was no difference in the improvement of ICARS and posturography results among 3 stimulations. In terms of the related factors with improvement of gait velocity, the disease duration, baseline gait speed and single support times were correlated after M1 stimulation, while a higher ICARS score and baseline gait speed in cerebellar stimulation. There were no adverse effects reported after the tDCS sessions. Our results demonstrated that both M1 and cerebellar tDCS demonstrated benefits for MSA-C patients without significant complications. Considering the different related factors with improvement at each stimulation, the mechanism would be different between M1 and cerebellar stimulations.

Sex differences in gastrointestinal dysfunction among patients with Parkinson's disease.

BACKGROUND AND OBJECTIVE: Sex differences in gastrointestinal dysfunction have not been systematically analyzed in patients with Parkinson's disease (PD). This study was aimed to investigate the sex differences in gastrointestinal dysfunctions among the patients with PD using a multicenter trial dataset. METHODS: We analyzed the baseline data of prospectively enrolled set of patients with gastrointestinal dysfunctions. Possible sex differences in gastrointestinal symptoms assessed on the Nepean Dyspepsia Index-Korean Version (NDI-K), gastrointestinal symptom diary, and Bristol stool scale were analyzed in association with clinical PD severity and antiparkinsonian drug dosages by multiple linear regression models. We also performed post hoc analysis of the dyspepsia symptom sub-items, adjusting for multiple comparisons. RESULTS: Sixty-six of the 144 participants were female (45.8%). There were no differences in age, PD duration, Hoehn and Yahr stage, and daily dopaminergic medication dosages between sexes. NDI-K symptom and dyspepsia scores were correlated with the activity of daily living in females but not in males. In the multiple regression analysis controlling for all possible variables, female patients were shown to have worse gastrointestinal symptoms than males. When we performed post hoc analysis of the dyspepsia symptoms, inability to finish a regular meal and nausea were significantly worse in female patients. Gastrointestinal symptom diary supported that female patients more frequently complained of early fullness and bloating in the upper abdomen after meals than males, and burning pain in upper abdomen was more severe in female patients. CONCLUSION: Gastrointestinal dysfunctions may differentially affect female and male PD patients.

The emerging genetic diversity of hereditary spastic paraplegia in Korean patients.

Hereditary Spastic Paraplegias (HSP) are a group of rare inherited neurological disorders characterized by progressive loss of corticospinal motor-tract function. Numerous patients with HSP remain undiagnosed despite screening for known genetic causes of HSP. Therefore, identification of novel genetic variations related to HSP is needed. In this study, we identified 88 genetic variants in 54 genes from whole-exome data of 82 clinically well-defined Korean HSP families. Fifty-six percent were known HSP genes, and 44% were composed of putative candidate HSP genes involved in the HSPome and originally reported neuron-related genes, not previously diagnosed in HSP patients. Their inheritance modes were 39, de novo; 33, autosomal dominant; and 10, autosomal recessive. Notably, ALDH18A1 showed the second highest frequency. Fourteen known HSP genes were firstly reported in Koreans, with some of their variants being predictive of HSP-causing protein malfunction. SPAST and REEP1 mutants with unknown function induced neurite abnormality. Further, 54 HSP-related genes were closely linked to the HSP progression-related network. Additionally, the genetic spectrum and variation of known HSP genes differed across ethnic groups. These results expand the genetic spectrum for HSP and may contribute to the accurate diagnosis and treatment for rare HSP.

Extra-basal ganglia iron content and non-motor symptoms in drug-naïve, early Parkinson's disease.

BACKGROUND: Although iron dyshomeostasis is associated with Parkinson's disease (PD) pathogenesis, the relationship between iron deposition and non-motor involvement in PD is not fully understood. In this study, we investigated basal ganglia and extra-basal ganglia system iron contents and their correlation with non-motor symptoms in drug-naïve, early-stage PD patients. METHODS: We enrolled 14 drug-naïve, early-stage PD patients and 12 age/sex-matched normal controls. All participants underwent brain magnetic resonance imaging to obtain the effective transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM). Deep brain structures, including the nucleus accumbens, caudate nucleus, putamen, globus pallidus, thalamus, hippocampus, and amygdala, were delineated using the FSL-FIRST; the substantia nigra, red nucleus, and dentate nucleus were segmented manually. Inter-group differences in R2* and QSM values, as well as their association with clinical parameters of PD, were investigated. RESULTS: Substantia nigra and putamen R2* values were significantly higher in PD patients than in normal controls, despite no significant difference in QSM values. Regarding the non-motor symptom scales, PD sleep scale score negatively correlated with R2* values in the red nucleus and right amygdala, Scales for Outcomes in Parkinson's disease-Autonomic scores were positively correlated with R2* values in the right amygdala and left hippocampus, and cardiovascular sub-score of Non-Motor Symptoms Scale for PD was positively associated with the QSM value in the left hippocampus. CONCLUSION: In this study, iron content in the extra-basal ganglia system was significantly correlated with non-motor symptoms, especially sleep problems and dysautonomia, even in early-stage PD.

Double-Blind, Randomized, Placebo-Controlled Trial of DA-9701 in Parkinson's Disease: PASS-GI Study.

OBJECTIVES: This study aimed to assess the efficacy of DA-9701 on gastrointestinal symptom-related quality of life in patients with Parkinson's disease on stable dopaminergic medications. METHODS: This multicenter, double-blind, placebo-controlled, phase 4 trial included a total of 144 patients with Parkinson's disease with gastrointestinal dysfunctions based on predefined criteria. Participants were randomized to take either DA-9701 or placebo for 4 weeks, and then both groups were administered DA-9701 for an additional 8 weeks while antiparkinsonian medications were unchanged. The primary outcome measure was gastrointestinal symptoms and related quality-of-life changes assessed on the Korean Nepean dyspepsia index after 4 and 12 weeks of therapy. We also evaluated the impact of DA-9701 therapy on parkinsonian motor symptoms at each time point. RESULTS: The gastrointestinal symptom-related quality-of-life score significantly improved in the DA-9701-treated group compared with the placebo-treated group after 4weeks (adjusted P = 0.012 by linear mixed effect model analysis). The overall gastrointestinal symptom and dyspepsia sum scores improved at 12 weeks after intervention in the DA-9701-first treated group (adjusted P = 0.002 and 0.014, respectively) and also in the placebo-first treated group (adjusted P = 0.019 and 0.039) compared with the baseline. Parkinsonian motor severity was not significantly affected by DA-9701 treatment in both groups at 4 and 12 weeks after intervention. There were no drug-related serious adverse events throughout the trial. CONCLUSIONS: DA-9701 therapy improved gastrointestinal symptom-related quality of life, and 12 weeks of daily administration can relieve the overall severity of gastrointestinal symptoms in patients with Parkinson's disease without affecting motor symptoms. (Clinical trial identifier: NCT02775591.) © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Type 1 Sialidosis Patient With a Novel Deletion Mutation in the NEU1 Gene: Case Report and Literature Review.

Recent advances in next-generation sequencing technologies have uncovered the genetic backgrounds of various diseases. Type 1 sialidosis (OMIM#256550) is a rare autosomal recessive lysosomal storage disease caused by a mutation in the NEU1 (OMIM * 608272) gene. In this study, we aimed to review the previous reports of type 1 sialidosis and compare those with the first case of type 1 sialidosis in Korea. A 36-year-old woman presented with progressive ataxia, myoclonus, and seizure since the age of 12. Whole-exome sequencing revealed a pathogenic missense variant c.928G > A (p.D310N) and novel c.15_16del (p.P6Qfs*21) of the NEU1 gene as final causal candidate as compound heterozygotes. We reviewed the literature and selected the clinical reports of genetically confirmed type 1 sialidosis patients. A total of 45 patients in 17 reports were identified. Cherry-red spot, myoclonus, ataxia, and seizure were reported in 51.2%, 100.0%, 87.8%, and 73.7% of patients, respectively. Abnormalities of cognitive function, EEG, and brain MRI and visual symptoms were reported in 22.2%, 40.7%, 66.7%, and 70.2% of patients, respectively. Overall, our patient showed similar clinical features to previous type 1 sialidosis patients, but she did not complain of visual symptoms despite having cherry-red spots. We summarize the clinical features of type 1 sialidosis and report the first case of type 1 sialidosis with novel deletion variant in the NEU1 gene in the Korean population. Our study suggests the importance of ophthalmologic examinations in patients with myoclonus, ataxia, and seizure who do not complain of visual symptoms.

Neuropsychiatric Traits Associated with Refractory Impulse Control Disorder in Parkinson's Disease.

INTRODUCTION: Impulse control disorder (ICD) in Parkinson's disease (PD) is a critical nonmotor symptom with personality or neuropsychiatric traits contributing to ICD. OBJECTIVE: This study aimed to identify predictive traits for persistent or paradoxical aggravation of ICD after dopamine agonist substitution therapy for ICD in PD. METHODS: We conducted a case-control study using a database of a multicenter intervention trial for ICD in PD. The poor-outcome group was defined by showing paradoxical increases in ICD behaviors after the substitution of dopamine agonists with levodopa. We analyzed the pre-intervention personality traits associated with the poor outcome and also evaluated the risk traits for refractory ICD using a receiver-operating characteristic (ROC) curve analysis. RESULTS: The poor-outcome group showed higher levels of anger expression (p =0.007) and obsessive-compulsive traits (p =0.009) compared with the good-outcome group at the pre-intervention state. In the ROC curve analysis, the Obsessive-Compulsive Inventory showed the highest area under the curve with 80.0% sensitivity and 74.3% specificity in discriminating against the poor-outcome group. CONCLUSIONS: Our results suggest that assessment of obsessive compulsiveness may be useful for predicting the refractoriness of ICD behaviors in planning an interventional treatment for ICD in PD.

Inflammatory mediators resulting from transglutaminase 2 expressed in mast cells contribute to the development of Parkinson's disease in a mouse model.

This study aimed to investigate the role of transglutaminase 2 (TG2) expressed in mast cells in substantia nigra (SN) in Parkinson's disease (PD) model or human PD patients. C57BL/6 mice received 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by ip injection to induce PD. Bone marrow-derived mast cells (BMMCs) were adoptively transferred to TG2 knockout (KO or TG2-/-) mice by iv injection 1 day before MPTP injection or stimulated by 1 methyl-4-phenylpyridinium (MMP+). KO-MPTP mice showed reduced expression of tyrosine hydroxylase (TH) and dopamine (DA) transporter (DAT) and loss of TH+ DA neurons, and expression of markers (c-kit, tryptase, FcεRI), mediators' release (histamine, leukotrienes, cytokines), and TG2 related to mast cells, and co-localization of DA neuronal cells and mast cells in SN tissues or release of mediators and TG2 activity in SN tissues and sera versus those in WT (wild type)-MPTP or BM + KO-MPTP mice. KO-MPTP mice reversed the alterations of behavior. KO-BMMCs-transferred KO-MPTP (BM + KO-MPTP) mice had restoration of all the responses versus the KO-MPTP mice. MPP+-stimulated BMMCs had increased mediators' release, which were inhibited by TG2 inhibitor (R2 peptide). All the mediators and TG2 activity were also increased in the sera of human PD patients. The data suggest that TG2 expressed in mast cells recruited into SN tissues might contribute to neuroinflammation, which is known as one of the important features in pathogenesis of PD, via up-regulating the release of various mediators.

Validation of the Korean Version of the Scales for Outcomes in Parkinson's Disease-Sleep.

BACKGROUND: Sleep problems commonly occur in patients with Parkinson's disease (PD), and are associated with a lower quality of life. The aim of the current study was to translate the English version of the Scales for Outcomes in Parkinson's Disease-Sleep (SCOPA-S) into the Korean version of SCOPA-S (K-SCOPA-S), and to evaluate its reliability and validity for use by Korean-speaking patients with PD. METHODS: In total, 136 patients with PD from 27 movement disorder centres of university-affiliated hospitals in Korea were enrolled in this study. They were assessed using SCOPA, Hoehn and Yahr Scale (HYS), Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Sleep Scale 2nd version (PDSS-2), Non-motor Symptoms Scale (NMSS), Montgomery Asberg Depression Scale (MADS), 39-item Parkinson's Disease Questionnaire (PDQ39), Neurogenic Orthostatic Hypotension Questionnaire (NOHQ), and Rapid Eye Movement Sleep Behaviour Disorder Questionnaire (RBDQ). The test-retest reliability was assessed over a time interval of 10-14 days. RESULTS: The internal consistency (Cronbach's α-coefficients) of K-SCOPA-S was 0.88 for nighttime sleep (NS) and 0.75 for daytime sleepiness (DS). Test-retest reliability was 0.88 and 0.85 for the NS and DS, respectively. There was a moderate correlation between the NS sub-score and PDSS-2 total score. The NS and DS sub-scores of K-SCOPA-S were correlated with motor scale such as HYS, and non-motor scales such as UPDRS I, UPDRS II, MADS, NMSS, PDQ39, and NOHQ while the DS sub-score was with RBDQ. CONCLUSION: The K-SCOPA-S exhibited good reliability and validity for the assessment of sleep problems in the Korean patients with PD.

Association between White Matter Lesions and Non-Motor Symptoms in Parkinson Disease.

BACKGROUND: There are only few studies exploring the relationship between white matter lesions (WMLs) and non-motor symptoms in Parkinson disease (PD). This study aimed to investigate the association between WMLs and the severity of non-motor symptoms in PD. METHODS: The severity of motor dysfunction, cognitive impairment, and non-motor symptoms was assessed by various scales in 105 PD patients. We used a visual semiquantitative rating scale and divided the subjects into four groups: no, mild, moderate, and severe WMLs. We compared the means of all scores between the four groups and analyzed the association between the severity of WMLs and the specific domain of non-motor symptoms. RESULTS: The non-motor symptoms as assessed by the Non-Motor Symptoms Scale, Parkinson's Disease Questionnaire (PDQ-39), Parkinson's Disease Sleep Scale, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Neuropsychiatric Inventory (NPI), and Parkinson Fatigue Scale (PFS) were significantly worse in the patients with moderate and severe WMLs than in those without WMLs. Compared with the no WML group, the scores for motor dysfunction were significantly higher in the mild, moderate, and severe WML groups. The scores for cognitive dysfunction were significantly higher in the patients with severe WMLs than in those without WMLs. The severity of WMLs showed linear associations with PFS, BDI, BAI, NPI, and PDQ-39 scores. The severity of WMLs also correlated linearly with scores for motor and cognitive dysfunction. CONCLUSIONS: Among the non-motor symptoms, fatigue, depression, anxiety, and quality of life were significantly affected by WMLs in PD. Confirmation of the possible role of WMLs in non-motor symptoms associated with PD in a prospective manner may be crucial not only for understanding non-motor symptoms but also for the development of treatment strategies.

Characteristic Motor and Nonmotor Symptoms Related to Quality of Life in Drug-Naïve Patients with Late-Onset Parkinson Disease.

BACKGROUND/AIMS: Unlike young-onset Parkinson disease (YOPD), characteristics of late-onset PD (LOPD) have not yet been clearly elucidated. We investigated characteristic features and symptoms related to quality of life (QoL) in LOPD patients. METHODS: We recruited drug-naïve, early PD patients. The patient cohort was divided into 3 subgroups based on patient age at onset (AAO): the YOPD group (AAO <50 years), the middle-onset PD (MOPD) group, and the LOPD group (AAO ≥70 years). Using various scales for motor symptoms (MS) and non-MS (NMS) and QoL, we compared the clinical features and impact on QoL. RESULTS: Of the 132 enrolled patients, 26 were in the YOPD group, 74 in the MOPD group, and 32 in the LOPD group. Among parkinsonian symptoms, patients in the LOPD group had a lower score on the Korean version of the Montreal Cognitive Assessment than the other groups. Logistic regression analysis showed genitourinary symptoms were related to the LOPD group. Linear regression analysis showed both MS and NMS were correlated with QoL in the MOPD group, but only NMS were correlated with QoL in the LOPD group. Particularly, anxiety and fatigue affected QoL in the LOPD group. CONCLUSION: LOPD patients showed different characteristic clinical features, and different symptoms were related with QoL for LOPD than YOPD and MOPD patients.

Effect of Dual-Mode and Dual-Site Noninvasive Brain Stimulation on Freezing of Gait in Patients With Parkinson Disease.

OBJECTIVE: To investigate the effect of dual-mode noninvasive brain stimulation (NIBS) with high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex of the lower leg and anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex compared with rTMS alone in patients with Parkinson disease (PD) with freezing of gait (FOG). DESIGN: Randomized, double-blind, controlled study. SETTING: Outpatient rehabilitation clinics. PARTICIPANTS: Patients diagnosed as having PD with FOG (N=32). INTERVENTIONS: Patients in the dual-mode group underwent 5 consecutive daily sessions of dual-mode NIBS with high-frequency rTMS and tDCS simultaneously, whereas patients in the rTMS group underwent high-frequency rTMS and sham tDCS. MAIN OUTCOME MEASURES: Assessments of FOG and motor, ambulatory, and cognitive function were performed 3 times: at baseline before NIBS, immediately after NIBS, and 1 week after cessation of NIBS. RESULTS: Serious adverse effects were not observed in either group. Significant changes over time were observed in FOG, motor function, and ambulatory function in each group; however, there was no significant difference between the 2 groups. Executive function showed significant improvement after NIBS only in the dual-mode group. CONCLUSIONS: These results suggest the potential for dual-mode NIBS to modulate 2 different cortices simultaneously. Dual-mode NIBS might be considered a novel therapeutic approach for patients with PD.

Differential Progression of Midbrain Atrophy in Parkinsonism: Longitudinal MRI Study.

AIMS: To elucidate different patterns of progression of midbrain atrophy in patients with Richardson's syndrome (RS), progressive supranuclear palsy-parkinsonism (PSP-P), and Parkinson's disease (PD) using magnetic resonance imaging (MRI)-based visual rating indexes. METHODS: We recruited 12 patients with PSP-RS, 12 with PSP-P, and 23 with PD for whom MRIs had been followed up for at least 2 years (mean ± SD, 4.9 ± 1.6 years) after the initial MRI. MRI-based visual rating indexes were used to estimate midbrain atrophy, including the ratio of the pontine to midbrain tegmental areas (P/M ratio) on a midsagittal image, the length between the interpeduncular fossa and the center of the cerebral aqueduct at the midmammillary-body level (MTEGM) on axial images, and the morning glory sign. RESULTS: Initially, there were no differences in MRI-based visual rating indexes between PSP-P and PD, while PSP-RS showed a higher P/M ratio and lower MTEGM compared with PSP-P and PD. In PD, the P/M ratio and MTEGM remained stable with disease progression. However, the extent of changes between initial and follow-up indexes was similarly greater for both PSP-RS and PSP-P than for PD. Finally, PSP-P showed a higher P/M ratio and lower MTEGM compared with PD in the follow-up, while PSP-RS still exhibited the most profound changes. CONCLUSIONS: Midbrain atrophy progresses differentially in patients with PSP-RS, PSP-P, and PD. Longitudinal measurements of midbrain atrophy using MRI-based visual rating indexes can help distinguish patients with PSP-P from those with PSP-RS and PD.

Gender Differences of Nonmotor Symptoms Affecting Quality of Life in Parkinson Disease.

BACKGROUND/AIMS: Gender differences of health-related quality of life (HRQoL) in patients with various disorders have been reported. Various nonmotor symptoms (NMSs) also affect the patients' lives and HRQoL, even in the early stages of Parkinson disease (PD). Our study aimed to identify whether there are gender differences of HRQoL in PD patients in the early stages, and which NMSs are associated with HRQoL depending on gender. METHOD: Eighty-nine PD patients (47 males, 42 females) and 36 healthy controls were enrolled. We evaluated HRQoL, NMSs, and their associations in each gender. RESULT: The total Parkinson Disease Quality of Life Questionnaire and Beck Anxiety Inventory scores were higher in female patients than in male patients. The correlation analysis revealed no association between NMSs and HRQoL in male patients. In female patients, HRQoL was highly correlated with depression, and moderately associated with fatigue. CONCLUSIONS: Gender differences of an association between HRQoL and NMSs exist in PD. We found that fatigue and depression were the main determinants of poor HRQoL in female patients even in the early stages. We suggest that a gender-specific therapeutic approach is important, and it is necessary to pay special attention to the predictors associated with causing poor HRQoL.

Atrophy of the Cerebellar Vermis in Essential Tremor: Segmental Volumetric MRI Analysis.

Postmortem studies of essential tremor (ET) have demonstrated the presence of degenerative changes in the cerebellum, and imaging studies have examined related structural changes in the brain. However, their results have not been completely consistent and the number of imaging studies has been limited. We aimed to study cerebellar involvement in ET using MRI segmental volumetric analysis. In addition, a unique feature of this study was that we stratified ET patients into subtypes based on the clinical presence of cerebellar signs and compared their MRI findings. Thirty-nine ET patients and 36 normal healthy controls, matched for age and sex, were enrolled. Cerebellar signs in ET patients were assessed using the clinical tremor rating scale and International Cooperative Ataxia Rating Scale. ET patients were divided into two groups: patients with cerebellar signs (cerebellar-ET) and those without (classic-ET). MRI volumetry was performed using CIVET pipeline software. Data on whole and segmented cerebellar volumes were analyzed using SPSS. While there was a trend for whole cerebellar volume to decrease from controls to classic-ET to cerebellar-ET, this trend was not significant. The volume of several contiguous segments of the cerebellar vermis was reduced in ET patients versus controls. Furthermore, these vermis volumes were reduced in the cerebellar-ET group versus the classic-ET group. The volume of several adjacent segments of the cerebellar vermis was reduced in ET. This effect was more evident in ET patients with clinical signs of cerebellar dysfunction. The presence of tissue atrophy suggests that ET might be a neurodegenerative disease.

24-Hour Ambulatory Blood Pressure Monitoring in SWEDDs Patients With Parkinsonism.

BACKGROUND: Patients diagnosed with Parkinson's disease (PD) on clinics who subsequently turn out to have normal dopamine transporter images have been referred to as scans without evidence of dopaminergic deficits (SWEDDs) patients. Cardiovascular autonomic dysfunction has frequently been reported in PD. In this study, we determined the similarities and differences in cardiac autonomic dysfunction between SWEDDs and PD patients. This study investigated whether 24-hour ambulatory blood pressure monitoring (24-hour ABPM) can help identify possible cases with SWEDDs. METHODS: We enrolled 28 SWEDDs patients, 46 patients with PD, and 30 healthy controls. To evaluate cardiac autonomic function, 24-hour ABPM was performed on all subjects. Cardiac metaiodobenzylguanidine (MIBG) scintigraphy was performed on the SWEDDs and PD subjects. RESULTS: The percentage nocturnal decline in blood pressure differed significantly among SWEDDs patients, PD patients, and controls (p<0.05). In addition to the abnormal nocturnal BP, regulation (nondipping and reverse dipping) was significantly higher in SWEDDs and PD subjects than in the control subjects (p<0.05). There was no significant correlation between the % nocturnal blood pressure reduction and parameters of cardiac MIBG uptake ratio. However, orthostatic hypotension was significant correlated with the nocturnal blood pressure dip (%), nocturnal blood pressure patterns, and the cardiac MIBG uptake ratio (early and late) in combined SWEDDs and PD subjects. CONCLUSIONS: Pathologic nocturnal blood pressure regulation and nocturnal hypertension, known characteristics of PD, are also present in SWEDDs. Moreover, cardiac sympathetic denervation should not be attributed to cardiac autonomic dysfunction in SWEDDs patients. As with PD patients, the SWEDDs patients studied here tended to have cardiac autonomic dysfunction.

Uremic parkinsonism with atypical phenotypes and radiologic features.

Uremic encephalopathy with bilateral basal ganglia lesions has been reported as an acute neurometabolic disease which shows reversible clinical course and brain imaging features. The exact nature and pathophysiology have not been well established. We encountered two patients who showed a relapsing and aggravating course and an atypical phenotype including parkinsonism with paroxysmal dystonic head tremor and acute onset monoparesis of the lower extremity. They also showed unusual radiological findings which revealed combined lesions in the basal ganglia and cortex, persistent hemorrhagic transformation, and focal ischemic lesion in the internal capsule. Herein, we present the unusual phenomenology with atypical radiologic findings and suggest the possible multifactorial pathogenesis of uremic encephalopathy.

Dysport and Botox at a ratio of 2.5:1 units in cervical dystonia: a double-blind, randomized study.

We aimed to compare Dysport (abobotulinumtoxinA, Ipsen Biopharm, Slough, UK) and Botox (onabotulinumtoxinA, Allergan, Irvine, CA, USA) at a 2.5:1 ratio in the treatment of cervical dystonia (CD). A Dysport/Botox ratio of lower than 3:1 was suggested as a more appropriate conversion ratio, considering its higher efficacy and more frequent incidence of adverse effects not only in the treatment of CD but also in other focal movement disorders. A randomized, double-blind, multicenter, non-inferiority, two-period crossover study was done in CD, with a duration of at least 18 months. Patients were randomly assigned to treatment for the first period with Dysport or Botox, and they were followed up for 16 weeks after the injection. After a 4-week washout period, they were switched to the other formulation and then followed up for 16 weeks. The primary outcome was the changes in the Tsui scale between the baseline value and that at 1 month after each injection. A total of 103 patients were enrolled, and 94 completed the study. Mean changes in the Tsui scale between baseline and 4 weeks after each injection tended to favor Botox; however, this was not statistically significant (4.0 ± 3.9 points for the Dysport treatment vs. 4.8 ± 4.1 points for Botox; 95% confidence interval, -0.1-1.7; P = 0.091). The mean change of the Toronto western spasmodic torticollis rating scale score, the proportion of improvement in clinical global impression and patient global impression, and the incidences of adverse events were not significantly different between the two treatments. With regard to safety and efficacy, Dysport was not inferior to Botox in patients with CD at a conversion factor of 2.5:1. [clinicaltrial.gov: NCT00950664]

Vestibular Performance During High-Acceleration Stimuli Correlates with Clinical Decline in SCA6.

In spinocerebellar ataxia type 6 (SCA6), the vestibular dysfunction and its correlation with other clinical parameters require further exploration. We determined vestibular responses over a broad range of stimulus acceleration in 11 patients with SCA6 (six men, age range=33-72 years, mean age±SD=59±12 years) using bithermal caloric irrigations, rotary chair, and head impulse tests. Correlations were also pursued among disability scores, as measured using the International Cooperative Ataxia Rating Scale, disease duration, age at onset, cytosine-adenine-guanine (CAG) repeat length, and the gain of the vestibulo-ocular reflex (VOR). In response to relatively low-acceleration, low-frequency rotational and bithermal caloric stimuli, the VOR gains were normal or increased regardless of the severity of disease. On the other hand, with relatively high-acceleration, high-frequency head impulses, there was a relative increase in gain in the mildly affected patients and a decrease in gain in the more severely affected patients and gains were negatively correlated with the severity of disease (Spearman correlation, R=-0.927, p<0.001). Selective decrease of the vestibular responses during high-acceleration, high-frequency stimuli may be ascribed to degeneration of either the flocculus or vestibular nuclei. The performance of the VOR during high-acceleration, high-frequency head impulses may be a quantitative indicator of clinical decline in SCA6.