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Volume 12(2); May 2019
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Review Article
Altered Gut Microbiome and Intestinal Pathology in Parkinson’s Disease
Han-Lin Chiang, Chin-Hsien Lin
J Mov Disord. 2019;12(2):67-83.   Published online May 30, 2019
DOI: https://doi.org/10.14802/jmd.18067
  • 11,025 View
  • 681 Download
  • 47 Citations
AbstractAbstract PDF
Parkinson’s disease (PD) is a common neurodegenerative disorder arising from an interplay between genetic and environmental risk factors. Studies have suggested that the pathological hallmarks of intraneuronal α-synuclein aggregations may start from the olfactory bulb and the enteric nervous system of the gut and later propagate to the brain via the olfactory tract and the vagus nerve. This hypothesis correlates well with clinical symptoms, such as constipation, that may develop up to 20 years before the onset of PD motor symptoms. Recent interest in the gut–brain axis has led to vigorous research into the gastrointestinal pathology and gut microbiota changes in patients with PD. In this review, we provide current clinical and pathological evidence of gut involvement in PD by summarizing the changes in gut microbiota composition and gut inflammation associated with its pathogenesis.
Original Articles
Asymptomatic Hearing Impairment Frequently Occurs in Early-Onset Parkinson’s Disease
Kuldeep Shetty, Syam Krishnan, Jissa Vinoda Thulaseedharan, Manju Mohan, Asha Kishore
J Mov Disord. 2019;12(2):84-90.   Published online April 5, 2019
DOI: https://doi.org/10.14802/jmd.18048
  • 10,065 View
  • 222 Download
  • 8 Citations
AbstractAbstract PDF
Objective
Recent reports of hearing impairment in Parkinson’s disease (PD) have suggested that auditory dysfunction could be a non-motor manifestation of PD. These reports were based on observations of elderly patients for whom presbycusis may, to some extent, have contributed to hearing dysfunction. Therefore, we aimed to explore the auditory functions in younger patients with PD. Methods We conducted a case-control study in a relatively younger (< 55 years of age at study time) population of PD patients and healthy volunteers to test whether auditory dysfunction is a significant non-motor dysfunction in PD. Pure tone audiometry (PTA) and brainstem evoked response audiometry (BERA) were performed in all participants. Results None of the patients or controls reported hearing deficits. Fifty-one patients with PD and 50 healthy volunteers who were age- and gender-matched to the patients participated. PTA-detected hearing impairment was found in 64.7% of patients and 28% of controls (p < 0.001) for both low-mid and/or high frequencies. Hearing impairment was more frequent in the younger subgroups of patients than age-matched controls, while the frequency of hearing impairment was similar in older groups of subjects. BERA was not different between patients and controls. Conclusion Asymptomatic auditory dysfunction is a common non-motor manifestation of early-onset PD and more frequent in younger patients, indicating that it may be independent of aging. The mechanism underlying this dysfunction appears to be peripheral, although a central dysfunction cannot be ruled out based on the findings of this study.
Characterization of Vitamin B12 Supplementation and Correlation with Clinical Outcomes in a Large Longitudinal Study of Early Parkinson’s Disease
Cameron Dietiker, Soeun Kim, Yunxi Zhang, Chadwick W. Christine
J Mov Disord. 2019;12(2):91-96.   Published online May 30, 2019
DOI: https://doi.org/10.14802/jmd.18049
  • 5,338 View
  • 140 Download
  • 4 Citations
AbstractAbstract PDF
Objective
In Parkinson’s disease (PD), vitamin B12 levels are lower, and comorbid B12 deficiency has been associated with the development of neuropathy and early gait instability. Because little is known about B12 supplement use in PD, we sought to evaluate its use in a large PD cohort and, as an exploratory analysis, to determine whether baseline characteristics or disease progression differed according to B12 supplementation.
Methods
We utilized data collected as part of the National Institutes of Health Exploratory Trials in PD (NET-PD) Long-term Study (LS-1), a longitudinal study of 1,741 participants. We stratified subjects into 4 groups according to daily supplement use: no B12, multivitamin (MVI) containing < 100 μg B12, B12 ≥ 100 μg, and MVI + B12 ≥ 100 μg. Clinical outcomes were assessed at 3 years for each group using the Unified Parkinson’s Disease Rating Scale (UPDRS), its subscores, and selected individual questions.
Results
Of the 1,147 participants who completed the 3-year visit, 41% took an MVI, 2% took B12, 3% took MVI + B12, and 54% reported taking no supplements. At 3 years, no significant differences in clinical outcomes were observed. However, there was a trend toward lower hazard ratios for developing sensory symptoms (UPDRS Item 17) in the MVI (p = 0.08) and B12 + MVI (p = 0.08) groups compared to that in the no supplement group.
Conclusion
These results show that supplementation with vitamin B12 ≥ 100 μg is uncommon in early PD. The finding of a trend toward a lower hazard ratio for the development of sensory symptoms in those taking an MVI or B12 + MVI warrants further study.
Pilot Study for Considering Subthalamic Nucleus Anatomy during Stimulation Using Directional Leads
Takashi Asahi, Kiyonobu Ikeda, Jiro Yamamoto, Hiroyuki Tsubono, Shuji Sato
J Mov Disord. 2019;12(2):97-102.   Published online April 5, 2019
DOI: https://doi.org/10.14802/jmd.18054
  • 4,495 View
  • 181 Download
  • 6 Citations
AbstractAbstract PDF
Objective
Directional leads are used for deep brain stimulation (DBS). Two of the four contacts of the leads are divided into three parts, enabling controlled stimulation in a circumferential direction. The direction of adverse effects evoked by DBS in the subthalamic nucleus (STN) and stimulation strategies using directional leads were evaluated. Methods Directional leads were implanted into the bilateral STN of six parkinsonian patients (1 man, 5 women; mean age 66.2 years). The contact centers were located within the upper border of the STN, and the locations were identified electrically using microrecordings. Adverse effects were evaluated with electrical stimulation (30 μs, 130 Hz, limit 11 mA) using the directional part of each lead after surgery, and the final stimulation direction was investigated. Unified Parkinson’s disease rating scale (UPDRS) scores were evaluated before and after DBS. Results Fifty-six motor and four sensory symptoms were evoked by stimulation; no adverse effect was evoked in 14 contacts. Motor and sensory symptoms were evoked by stimulation in the anterolateral direction and medial to posterolateral direction, respectively. Stimulation in the posteromedial direction produced adverse effects less frequently. The most frequently used contacts were located above the STN (63%), followed by the upper part of the STN (32%). The mean UPDRS part III and dyskinesia scores decreased after DBS from 30.2 ± 11.7 to 7.2 ± 2.9 and 3.3 ± 2.4 to 0.5 ± 0.8, respectively. Conclusion The incidence of adverse effects was low for the posteromedial stimulation of the STN. Placing the directional part of the lead above the STN may facilitate the control of dyskinesia.
Nonmotor and Dopamine Transporter Change in REM Sleep Behavior Disorder by Olfactory Impairment
Jee-Young Lee, Eun Jin Yoon, Yu Kyeong Kim, Chae Won Shin, Hyunwoo Nam, Jae Min Jeong, Han-Joon Kim, Beomseok Jeon
J Mov Disord. 2019;12(2):103-112.   Published online May 30, 2019
DOI: https://doi.org/10.14802/jmd.18061
  • 4,747 View
  • 179 Download
  • 8 Citations
AbstractAbstract PDFSupplementary Material
Objective
It is unclear whether the decline in dopamine transporters (DAT) differs among idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with different levels of olfactory impairment. This study aimed to characterize DAT changes in relation to nonmotor features in iRBD patients by olfactory loss.
Methods
This prospective cohort study consisted of three age-matched groups: 30 polysomnography-confirmed iRBD patients, 30 drug-naïve Parkinson’s disease patients, and 19 healthy controls without olfactory impairment. The iRBD group was divided into two groups based on olfactory testing results. Participants were evaluated for reported prodromal markers and then underwent 18F-FP-CIT positron emission tomography and 3T MRI. Tracer uptakes were analyzed in the caudate, anterior and posterior putamen, substantia nigra, and raphe nuclei.
Results
Olfactory impairment was defined in 38.5% of iRBD patients. Mild parkinsonian signs and cognitive functions were not different between the two iRBD subgroups; however, additional prodromal features, constipation, and urinary and sexual dysfunctions were found in iRBD patients with olfactory impairment but not in those without. Tracer uptake showed significant group differences in all brain regions, except the raphe nuclei. The iRBD patients with olfactory impairment had uptake reductions in the anterior and posterior putamen, caudate, and substantia nigra (p < 0.016 in all, adjusted for age), which ranged from 0.6 to 0.8 of age-normative values. In contrast, those without olfactory impairment had insignificant changes in all regions ranging above 0.8.
Conclusion
There was a clear distinction in DAT loss and nonmotor profiles by olfactory status in iRBD.
Heterogeneous Patterns of Striatal Dopamine Loss in Patients with Young- versus Old-Onset Parkinson’s Disease: Impact on Clinical Features
Seok Jong Chung, Han Soo Yoo, Yang Hyun Lee, Phil Hyu Lee, Young H. Sohn
J Mov Disord. 2019;12(2):113-119.   Published online May 30, 2019
DOI: https://doi.org/10.14802/jmd.18064
  • 5,129 View
  • 128 Download
  • 13 Citations
AbstractAbstract PDFSupplementary Material
Objective
Ample evidence has suggested that age at onset of Parkinson’s disease (PD) is associated with heterogeneous clinical features in individuals. We hypothesized that this may be attributed to different patterns of nigrostriatal dopamine loss.
Methods
A total of 205 consecutive patients with de novo PD who underwent 18F-FP-CIT PET scans (mean follow-up duration, 6.31 years) were divided into three tertile groups according to their age at onset of parkinsonian motor symptoms. Striatal dopamine transporter (DAT) availability was compared between the old- (n = 73) and young-onset (n = 66) groups. In addition, the risk of developing freezing of gait (FOG) and longitudinal requirements for dopaminergic medications were examined.
Results
The old-onset PD group (mean age at onset, 72.66 years) exhibited more severe parkinsonian motor signs than the young-onset group (52.58 years), despite comparable DAT availability in the posterior putamen; moreover, the old-onset group exhibited more severely decreased DAT availability in the caudate than the young-onset group. A Cox regression model revealed that the old-onset PD group had a higher risk for developing FOG than the young-onset group [hazard ratio 2.523, 95% confidence interval (1.239–5.140)]. The old-onset group required higher doses of dopaminergic medications for symptom control than the young-onset group over time.
Conclusion
The present study demonstrated that the old-onset PD group exhibited more severe dopamine loss in the caudate and were more likely to develop gait freezing, suggesting that age at onset may be one of the major determinants of the pattern of striatal dopamine depletion and progression of gait disturbance in PD.
Brief communication
The Effect of Globus Pallidus Interna Deep Brain Stimulation on a Dystonia Patient with the GNAL Mutation Compared to Patients with DYT1 and DYT6
Jong Hyeon Ahn, Ah Reum Kim, Nayoung K. D. Kim, Woong-Yang Park, Ji Sun Kim, Minkyeong Kim, Jongkyu Park, Jung-Il Lee, Jin Whan Cho, Kyung Rae Cho, Jinyoung Youn
J Mov Disord. 2019;12(2):120-124.   Published online May 30, 2019
DOI: https://doi.org/10.14802/jmd.19006
  • 4,055 View
  • 122 Download
  • 9 Citations
AbstractAbstract PDFSupplementary Material
Objective
The aim of this study was to investigate the efficacy of globus pallidus interna deep brain stimulation (GPi-DBS) for treating dystonia due to the GNAL mutation.
Methods
We provide the first report of a dystonia patient with a genetically confirmed GNAL mutation in the Korean population and reviewed the literature on patients with the GNAL mutation who underwent GPi-DBS. We compared the effectiveness of DBS in patients with the GNAL mutation compared to that in patients with DYT1 and DYT6 in a previous study.
Results
Patients with the GNAL mutation and those with DYT1 had higher early responder rates (GNAL, 5/5, 100%; DYT1, 7/7, 100%) than did patients with DYT6 (p = 0.047). The responder rates at late follow-up did not differ statistically among the three groups (p = 0.278). The decrease in the dystonia motor scale score in the GNAL group was 46.9% at early follow-up and 63.4% at late follow-up.
Conclusion
GPi-DBS would be an effective treatment option for dystonia patients with the GNAL mutation who are resistant to medication or botulinum toxin treatment.
Letters to the editor
Task-Specific Oromandibular Dystonia in a Telemarketer
SeonDeuk Kim, Hyeyun Kim
J Mov Disord. 2019;12(2):125-127.   Published online April 5, 2019
DOI: https://doi.org/10.14802/jmd.18030
  • 3,600 View
  • 72 Download
  • 2 Citations
PDFSupplementary Material
Recurrent Belly Dancer’s Dyskinesia with Pregnancy
Belal Aldabbour, Islam E’Leimat, Kefah Alhayek, Aiman Momani
J Mov Disord. 2019;12(2):128-129.   Published online April 5, 2019
DOI: https://doi.org/10.14802/jmd.18055
  • 4,080 View
  • 82 Download
  • 1 Citations
PDF
A Case of Ascending and Descending Stair-Specific Dystonia
Talia Arceri, Jeffrey Ratliff
J Mov Disord. 2019;12(2):130-131.   Published online April 5, 2019
DOI: https://doi.org/10.14802/jmd.18057
  • 4,245 View
  • 73 Download
  • 2 Citations
PDFSupplementary Material
Alternating Hemiplegia of Childhood in a Person of Malay Ethnicity with Diffusion Tensor Imaging Abnormalities
Ai Huey Tan, Tien Lee Ong, Norlisah Ramli, Li Kuo Tan, Jia Lun Lim, Mohamad Addin Azhan, Azlina Ahmad-Annuar, Khairul Azmi Ibrahim, Zariah Abdul-Aziz, Laurie J. Ozelius, Allison Brashear, Shen-Yang Lim
J Mov Disord. 2019;12(2):132-134.   Published online May 30, 2019
DOI: https://doi.org/10.14802/jmd.18063
  • 3,344 View
  • 50 Download
  • 1 Citations
PDFSupplementary Material
Manganism without Parkinsonism: Isolated Unilateral Upper Limb Tremor in a Welder
Shweta Prasad, Uzma Shamim, Akanksha Minj, Mohammed Faruq, Pramod Kumar Pal
J Mov Disord. 2019;12(2):135-137.   Published online April 5, 2019
DOI: https://doi.org/10.14802/jmd.18068
  • 3,544 View
  • 85 Download
  • 1 Citations
PDFSupplementary Material

JMD : Journal of Movement Disorders