Gwanhee Ehm

Should genetic testing for SCAs be included in the diagnostic workup for MSA

Objective: To examine the prevalence of mutations in spinocerebellar ataxia (SCA) genes in patients who were clinically diagnosed with multiple system atrophy (MSA). Methods: Genetic tests for SCA were performed in 302 of 528 patients who met the diagnostic criteria for MSA based on clinical features. Generally, when a patient had cerebellar symptoms or cerebellar atrophy on neuroimaging, genetic tests for SCA types 1, 2, 3, 6, 7, and 17, and dentatorubropallidoluysian atrophy were done, and when a patient had parkinsonism without cerebellar symptoms, genetic tests for SCA types 2, 3, and 17 were done. Results: Mutations in SCA genes were found in 22 of the 302 patients (7.3%) with SCA17 comprising more than half of the mutation-positive cases. The age at disease onset in these 22 patients was not different compared with the 280 patients without mutations (55.9 ± 9.3 vs 59.2 ± 8.9, p = 0.102). All patients had urinary symptoms, and 10 patients also had orthostatic dizziness or orthostatic hypotension. A family history was reported in only 3 patients. Of note, dream enactment behavior suggesting REM sleep behavior disorder was reported in 9 of the 11 patients (81.8%) asked. Conclusions: The high proportion of patients with SCA mutations in this study indicates that genetic testing for SCA should be included for patients with MSA, especially for patients with cerebellar dysfunctions.

Long-Term Clinical Outcome of Internal Globus Pallidus Deep Brain Stimulation for Dystonia

Background GPi (Internal globus pallidus) DBS (deep brain stimulation) is recognized as a safe, reliable, reversible and adjustable treatment in patients with medically refractory dystonia. Objectives This report describes the long-term clinical outcome of 36 patients implanted with GPi DBS at the Neurosurgery Department of Seoul National University Hospital. Methods Nine patients with a known genetic cause, 12 patients with acquired dystonia, and 15 patients with isolated dystonia without a known genetic cause were included. When categorized by phenomenology, 29 patients had generalized, 5 patients had segmental, and 2 patients had multifocal dystonia. Patients were assessed preoperatively and at defined follow-up examinations postoperatively, using the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) for movement and functional disability assessment. The mean follow-up duration was 47 months (range, 12–84) Results The mean movement scores significantly decreased from 44.88 points preoperatively to 26.45 points at 60-month follow up (N = 19, P = 0.006). The mean disability score was also decreased over time, from 11.54 points preoperatively to 8.26 points at 60-month follow up, despite no statistical significance (N = 19, P = 0.073). When analyzed the movement and disability improvement rates at 12-month follow up point, no significant difference was noted according to etiology, disease duration, age at surgery, age of onset, and phenomenology. However, the patients with DYT-1 dystonia and isolated dystonia without a known genetic cause showed marked improvement. Conclusions GPi DBS is a safe and efficient therapeutic method for treatment of dystonia patients to improve both movement and disability. However, this study has some limitations caused by the retrospective design with small sample size in a single-center.

Bilateral Deep Brain Stimulation of the Subthalamic Nucleus under Sedation with Propofol and Fentanyl

Awakening during deep brain stimulation (DBS) surgery may be stressful to patients. The aim of the current study was to evaluate the effect on MER signals and their applicability to subthalmic nucleus (STN) DBS surgery for patients with Parkinson’s disease (PD) under sedation with propofol and fentanyl. Sixteen consecutive patients with PD underwent STN-DBS surgery with propofol and fentanyl. Their MER signals were achieved during the surgery. To identify the microelectrodes positions, the preoperative MRI and postoperative CT were used. Clinical profiles were also collected at the baseline and at 6 months after surgery. All the signals were slightly attenuated and contained only bursting patterns, compared with our previous report. All electrodes were mostly located in the middle one third part of the STN on both sides of the brain in the fused images. Six months later, the patients were improved significantly in the medication-off state and they met with less dyskinesia and less off-duration. Our study revealed that the sedation with propofol and fentanyl was applicable to STN-DBS surgery. There were no significant problems in precise positioning of bilateral electrodes. The surgery also improved significantly clinical outcomes in 6-month follow-up.

Liquid levodopa-carbidopa in advanced Parkinson's disease with motor complications

While levodopa, carbidopa, ascorbic acid solution (LCAS) therapy has been used in patients with advanced Parkinsons disease (PD) for many years, long-term follow-up data is scarce. The present study aimed to determine the long-term retention rate for LCAS therapy, and to identify the causes of LCAS therapy withdrawal. Our study included a series of 38 patients with PD (14 men and 24 women) who underwent LCAS treatment between 2011 and 2013 to alleviate motor complications that were not satisfactorily controlled by optimized conventional anti-parkinsonian treatment at the Seoul National University Hospital. All patients were admitted to educate them about and initiate LCAS treatment for 2-5days, and were then followed up as outpatients. The mean follow-up duration was 12.8months, and three main reasons for LCAS treatment discontinuation were worsening of wearing-off symptoms (8 patients), persistent dyskinesia (4 patients), and poor drug adherence (4 patients). Fourteen patients (36.8%) maintained the LCAS treatment after 12months, and were categorized as the treatment-retention group. The mean percentage of on time without dyskinesia significantly increased from 33.6±17.6% to 57.0±27.7% after LCAS initiation (p=0.016) in the treatment-retention group. Twelve patients (31.6%) were still receiving LCAS treatment after 30months. LCAS treatment can be a non-device assisted therapeutic option for patients who have no access to advanced therapies such as deep brain stimulation and infusional treatments.

Hypothyroidism-induced Reversible Encephalopathy as a Cause of Aggravation of Parkinsonism and Myoclonus in Parkinson’s Disease

Background Myoclonus and encephalopathy are unusual in patients with Parkinson’s disease (PD). Case report We describe the case of a 59-year-old male with PD who developed myoclonus and encephalopathy. Underlying hypothyroidism was revealed after admission and treated with levothyroxine. Myoclonus and encephalopathy were completely resolved following thyroid hormone replacement. Discussion Hypothyroidism can cause reversible myoclonus and encephalopathy along with unusual aggravation of parkinsonism symptoms in patients with PD.

Acupuncture does not protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced damage of dopaminergic neurons in a preclinical mouse model of Parkinson’s disease

Acupuncture treatment, a complementary and alternative medicine, is associated with a suggested neuroprotective effect in previous preclinical studies of Parkinson’s disease (PD); however, results from human clinical trials have been mixed or unsuccessful. Recent systematic reviews of translational neuroprotective studies showed that the supposed efficacy is confounded by low methodological quality, particularly by a lack of randomization and concealed allocation. We sought to replicate previous experimental findings with a study design that mitigates the introduction of bias, including randomization, blinded outcome measures, sham acupuncture application, and allocation concealment by blinded neurotoxin administration. We performed 12 sessions of manual acupuncture at acupoint GB34 (yanglingquan) in mice that were administered the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxin for five consecutive days. In this animal model of PD, acupuncture treatment did not attenuate tyrosine hydroxylase-immunoreactive neuronal death, depletion of striatal dopamine levels, or reduced striatal tyrosine hydroxylase expression. Our results indicate that acupuncture is not neuroprotective against nigrostriatal loss in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of PD.