The effect of istradefylline for Parkinson’s disease : A meta-analysis

Adenosine A2A receptor antagonists are an alternative treatment strategy for Parkinson’s disease. Several randomized placebo controlled studies have tested the effect of A2A receptor antagonist istradefylline, and more robust evidence has been acquired. This meta-analysis aimed to provide evidence for its efficacy and safety on patients with Parkinson’s disease. After a systematic literature search, we calculated the pooled standardized mean difference and risk ratio for continuous and dichotomous variables, respectively. Further, sensitivity analyses were performed to confirm the effect estimated by meta-analyses. Publication bias was assessed by funnel plot and deviation of intercept. Six studies satisfied our inclusion criteria. Istradefylline (40 mg/day) decreased off time and improved motor symptoms of Parkinson’s disease in homogeneous studies. Istradefylline at 20 mg/day decreased off time and improved motor symptoms, but heterogeneity was found in the analysis of the former among studies. There was a significant effect of istradefylline on dyskinesia in homogeneous studies. Publication bias, however, was observed in the comparison of dyskinesia. Other adverse events showed no significant difference. The present meta-analysis suggests that istradefylline at 40 mg/day could alleviate off time and motor symptoms derived from Parkinson’s disease. Dyskinesia might be worsened, but publication bias prevents this from being clear

Zolpidem therapy in dystonia

Although there are some newly developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1 (ω1), was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5–20 mg) in 34 patients suffering from miscellaneous types of dystonia using the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous two successive visits). After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2 ± 7.9 to 5.5 ± 5.0 (P = 0.042). Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8, 17.8, and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome, and hand dystonia including musician’s. Drowsiness was the dose-limiting factor

Efficacy of Zolpidem for Dystonia: A Study Among Different Subtypes

Although there are some newly developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1 (ω1), was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5–20 mg) in 34 patients suffering from miscellaneous types of dystonia using the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous two successive visits). After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2 ± 7.9 to 5.5 ± 5.0 (P = 0.042). Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8, 17.8, and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome, and hand dystonia including musician’s. Drowsiness was the dose-limiting factor

Cervical root sonography to differentiate multifocal motor neuropathy from ALS

To explore suggestive evidence of focal proximal demyelination in multifocal motor neuropathy (MMN) without overt evidence of conduction block, we conducted sonographical assessment of cervical nerve roots in 9 MMN patients, 22 ALS patients, and 17 control subjects. The mean diameters of the C5 and C6 roots in MMN patients were significantly larger than those in ALS and controls, especially on the clinically dominant side. Although non-specific, sonography can be a potentially useful diagnostic procedure to support the diagnosis of MMN, even when overt conduction block is lacking

MIBG Predicts Falls in PD

Background: Falls are associated with poor prognosis in patients with Parkinson's disease (PD). Although several factors related to falls were reported in patients with PD, objective predictors of falls are not identified. We aimed to determine whether 123I-meta-iodobenzylguanidine (MIBG) cardiac scintigraphy could be a useful biomarker to predict falls. Methods: Forty-five patients with PD were enrolled in this study. These subjects were followed up more than 5 years after MIBG scintigraphy and were divided into two groups: one with decreased uptake of MIBG and the other without decreased uptake of MIBG. The cut-off value for the delayed heart-to-mediastinum ratio was 1.8. Kaplan-Meier analysis and a log-rank test were performed to test the predictive power of MIBG cardiac scintigraphy for falls. Univariate analysis was selected because we did not have appropriate data for adjustment, such as motor and cognitive assessment. Results: The group with decreased uptake of MIBG had a significantly higher incidence of falls than that without decreased uptake of MIBG (P = 0.022, log-rank test). Conclusions: Although the limitations of this study were lack of several key factors including motor and cognitive assessment, MIBG cardiac scintigraphy may be used to predict falls in patients with PD

Texture analysis of myopathy

Given the recent technological advent of muscle ultrasound (US), classification of various myopathic conditions could be possible, especially by mathematical analysis of muscular fine structure called texture analysis. We prospectively enrolled patients with three neuromuscular conditions and their lower leg US images were quantitatively analyzed by texture analysis and machine learning methodology in the following subjects : Inclusion body myositis (IBM) [N=11] ; myotonic dystrophy type 1 (DM1) [N=19] ; polymyositis/dermatomyositis (PM-DM) [N=21]. Although three-group analysis achieved up to 58.8% accuracy, two-group analysis of IBM plus PM-DM versus DM1 showed 78.4% accuracy. Despite the small number of subjects, texture analysis of muscle US followed by machine learning might be expected to be useful in identifying myopathic conditions

Long-Term Follow-Up of 12 Patients Treated with Bilateral Pallidal Stimulation for Tardive Dystonia

Tardive dystonia (TD) is a side effect of prolonged dopamine receptor antagonist intake. TD can be a chronic disabling movement disorder despite medical treatment. We previously demonstrated successful outcomes in six patients with TD using deep brain stimulation (DBS); however, more patients are needed to better understand the efficacy of DBS for treating TD. We assessed the outcomes of 12 patients with TD who underwent globus pallidus internus (GPi) DBS by extending the follow-up period of previously reported patients and enrolling six additional patients. All patients were refractory to pharmacotherapy and were referred for surgical intervention by movement disorder neurologists. In all patients, DBS electrodes were implanted bilaterally within the GPi under general anesthesia. The mean ages at TD onset and surgery were 39.2 ± 12.3 years and 44.6 ± 12.3 years, respectively. The Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) performed the preoperative and postoperative evaluations. The average BFMDRS improvement rate at 1 month postoperatively was 75.6 ± 27.6% (p < 0.001). Ten patients were assessed in the long term (78.0 ± 50.4 months after surgery), and the long-term BFMDRS improvement was 78.0 ± 20.4%. Two patients responded poorly to DBS. Both had a longer duration from TD onset to surgery and older age at surgery. A cognitive and psychiatric decline was observed in the oldest patients, while no such decline ware observed in the younger patients. In most patients with TD, GPi-DBS could be a beneficial therapeutic option for long-term relief of TD

ALS clinically presenting with PMA

Amyotrophic lateral sclerosis (ALS) primarily affects upper and lower motor neurons. Phosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) inclusion bodies are reportedly a pathological hallmark of sporadic ALS. Here, we present an atypical case of sporadic ALS that progressed very slowly, persisted for 19 years, and clinically appeared to only affect the lower motor neurons; however, upper motor neuron degeneration was detected on autopsy. Furthermore, no inclusion bodies positive for phosphorylated TDP-43, ubiquitin, fused in sarcoma, or SOD1 were detected in the CNS. We performed exome-sequencing data analysis but found no genetic disorders. This was therefore an unusual case of lower motor neuron-predominant ALS without TDP-43 pathology or known gene-disease associations. We also reviewed autopsied ALS cases that progressed slowly and had no phosphorylated TDP-43 or ubiquitin positive inclusions and present the clinicopathological features of such cases. Based on these results, there may be a sporadic ALS subgroup that progresses slowly and shows 76 no accumulation of phosphorylated TDP-43

シンコウセイ ニ ゾウアク オ キタシ ケッカンナイ チリョウ オ シコウ シタ ミギナイ ケイドウミャク ヘイソク ノ 1レイ

A ７７-year-old man was admitted to our hospital in July ２００９ with monoparesis of the left upper extremity. His magnetic resonance images（MRI）demonstrated multiple infarction in the right temporoparietal lobe, and his emergent cerebral angiography revealed total occlusion of the right internal carotid artery（ICA）at the origin. We diagnosed atherothrombotic infarction and started to treat with antiplatelet drugs. But, his symptoms were gradually progressing despite medical treatment and his MRI showed an enlargement of ischemic lesion８days after admission. Because the hemodynamic enlargement due to ICA occlusion and DWI-PWI mismatch was detected, we performed emergent PTA（percutaneous transluminal angioplasty）and CAS（carotid artery stent placement）at that time. The ICA was completely recanalized without any complications. His symptoms were getting better, and his cerebral blood flow improved at rest on single photon emission computed tomography（SPECT）６days after treatment. He was transferred to another hospital１７days after the onset. This case experience suggests that endovascular revascularization can be considered as potential treatment for symptomatic ICA occlusion based on atherosclerosis even in the subacute stage of the stroke patients

Texture in aging

Texture analysis characterizes regions in an image by their texture content and has been utilized to infer the underlying structures of medical images such as skeletal muscles. Although potentially useful in tissue diagnosis and assessing disease progression of neuromuscular diseases, the use of texture analysis in such purposes are limited, due to lack of information such as effects of aging. Thus, we performed texture analysis of medial gastrocnemius in healthy individuals form their 20s to late 80s. Among the 283 texture features in 6 classes, the features related to histogram, co-occurrence matrix, absolute gradient, and wavelet were correlated to age in 17-40% of the parameters, while none of the features related to run-length matrix and autoregressive model had significant correlation to age. This study showed that age-dependency in many texture features are present and need to be taken into account in elucidating the clinical significance. By contrast, the features related to run-length matrix and autoregressive model could have clinical utility