Woong-Woo Lee

An 8-Year Follow-up on the Effect of Subthalamic Nucleus Deep Brain Stimulation on Pain in Parkinson Disease

IMPORTANCE Pain is a common and distressing feature in Parkinson disease (PD). The major indication of subthalamic nucleus deep brain stimulation (STN DBS) is motor complications in advanced PD; however, pain reduction after STN DBS has been noted. OBJECTIVE To evaluate the long-term effect of STN DBS on pain in PD. DESIGN, SETTING, AND PARTICIPANTS Twenty-four patients who underwent STN DBS at the Movement Disorder Center at Seoul National University Hospital from June 1, 2005, through March 31, 2006, were studied. The assessments of pain were performed preoperatively and 8 years after surgery. Because 13 of the total 24 patients had additional 2-year postoperative data, the serial change between the preoperative and the 2- and 8-year follow-ups after surgery was also evaluated. MAIN OUTCOMES AND MEASURES Motor symptoms were assessed using the Unified Parkinsons Disease Rating Scale and the Hoehn and Yahr staging scale. The severity of pain was scored according to an ordinal scale ranging from 0 (absent) to 10 (maximal pain) in 7 parts of the body (head, neck, trunk, and the upper and lower extremities on each side of the body). For each body part, the quality of pain was grouped into 1 of 4 categories: dystonic, musculoskeletal, radiculoneuritic, and central. RESULTS Sixteen of the 24 patients (67%) experienced pain at baseline when not taking medication (off-state). All off-state pain at baseline improved or disappeared at 8 years after surgery. The number of body parts with pain was 21 at baseline and decreased to 11 at 8 years after the surgery. The mean (SD) and median scores of the off-state pain were 6.2 (2.5) and 7.0 at baseline and improved to 3.5 (2.2) and 2.5 at 8 years after the surgery, respectively. However, new pain developed in 18 of 24 patients (75%) during the 8-year follow-up period. The number of body parts with newly developed pain was 47, and the mean (SD) and median scores for new pain were 4.4 (3.0) and 3.0, respectively. The types of new pain at 8 years were musculoskeletal in 11 patients, central in 4 patients, radiculoneuritic in 3 patients, and dystonic in 1 patient. CONCLUSIONS AND RELEVANCE Pain associated with PD is improved by STN DBS, and the beneficial effect persists after a long-term follow-up of 8 years. In addition, new pain, especially the musculoskeletal type, developed in most patients, becoming a long-term distressing problem.

Musculoskeletal problems in Parkinson's disease: Neglected issues

BACKGROUND To identify the prevalence and clinical features of musculoskeletal problems in patients with Parkinson disease (PD) compared to controls. METHODS 400 PD patients and 138 age- and sex-matched controls were interviewed by physicians about their musculoskeletal problems. RESULTS The prevalence of musculoskeletal problems was significantly higher in the PD group than in the control group (66.3% vs. 45.7%, P < 0.001). Commonly involved body sites were the low back, knee, and shoulder in that order. The low back was more frequently involved in the PD group than in the control group (44.3% vs. 24.6%, P < 0.001), and the shoulder tended to be more involved in the PD group than in the control group (15.0% vs. 8.7%, P = 0.061). However, the knee was similarly involved in both group (12.3% vs. 18.0%, P = 0.121). Among the past diagnoses associated with musculoskeletal problems, frozen shoulder, low back pain, osteoporosis and fracture were more common in the PD group than in the control group (P < 0.05). Older age, female, and a higher score on the Unified Parkinsons Disease Rating Scale I & II were associated with musculoskeletal problems in the PD group. Only 26.8% of the PD patients and 52.5% of the controls with musculoskeletal problems answered that their musculoskeletal problems were recovering. Furthermore, musculoskeletal problems in the PD group tended to receive less treatment than that of the control group (P = 0.052). CONCLUSION Musculoskeletal problems were more common in the PD group than in the controls. Furthermore, despite PD patients having a higher prevalence, they did not receive adequate treatment.

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.

Clinical Spectrum of Dopa-Responsive Dystonia and Related Disorders

Dopa-responsive dystonia (DRD) has a classic presentation of childhood or adolescent-onset dystonia, mild parkinsonism, marked diurnal fluctuations, improvement with sleep or rest, and a dramatic and sustained response to low doses of L-dopa without motor fluctuations or dyskinesias. However, there have been many papers on patients with a wide range of features, which report them as DRD mainly because they had dystonic syndromes with L-dopa responsiveness. Many mutations in the dopaminergic system have been found as molecular genetic defects. Therefore, the clinical and genetic spectra of DRD are unclear, which lead to difficulties in diagnostic work-ups and planning treatments. We propose the concept of DRD and DRD-plus to clarify the confusion in this area and to help understand the pathophysiology and clinical features, which will help in guiding diagnostic investigations and planning treatments. We critically reviewed the literature on atypical cases and discussed the limitations of the gene study.

Perverted head-shaking and positional downbeat nystagmus in patients with multiple system atrophy†

The diagnosis of multiple system atrophy (MSA) is mainly based on the clinical criteria, which are often of little assistance in the early stages of the disease. Positional downbeat nystagmus (pDBN) and perverted head‐shaking nystagmus (pHSN), possible signs of cerebellar dysfunction, may be useful in differentiating MSA from other parkinsonian disorders. To investigate the occurrences of pDBN and pHSN in patients with MSA compared with those in patients with Parkinsons disease (PD). A total of 127 consecutive patients with MSA and 274 patients with PD underwent a video‐oculographic recording of head‐shaking and positional nystagmus over a year. The occurrences of pDBN and pHSN were higher in MSA than in PD. pDBN was more frequently observed in MSA with overt cerebellar signs than in those without, but the occurrence of pHSN did not differ between the MSA groups. pHSN was more frequently observed in MSA‐p without overt cerebellar signs than in PD, but there was no difference in the occurrence of pDBN between them. The presence of pHSN and pDBN may be a clue for the diagnosis of MSA, and pHSN may be helpful in differentiating MSA‐p from PD when the patients do not have overt cerebellar features.

Influence of Propofol and Fentanyl on Deep Brain Stimulation of the Subthalamic Nucleus

We investigated the effect of propofol and fentanyl on microelectrode recording (MER) and its clinical applicability during subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. We analyzed 8 patients with Parkinsons disease, underwent bilateral STN DBS with MER. Their left sides were done under awake and then their right sides were done with a continuous infusion of propofol and fentanyl under local anesthesia. The electrode position was evaluated by preoperative MRI and postoperative CT. The clinical outcomes were assessed at six months after surgery. We isolated single unit activities from the left and the right side MERs. There was no significant difference in the mean firing rate between the left side MERs (38.7±16.8 spikes/sec, n=78) and the right side MERs (35.5±17.2 spikes/sec, n=66). The bursting pattern of spikes was more frequently observed in the right STN than in the left STN. All the electrode positions were within the STNs on both sides and the off-time Unified Parkinsons Disease Rating Scale part III scores at six months after surgery decreased by 67% of the preoperative level. In this study, a continuous infusion of propofol and fentanyl did not significantly interfere with the MER signals from the STN. The results of this study suggest that propofol and fentanyl can be used for STN DBS in patients with advanced Parkinsons disease improving the overall experience of the patients. Graphical Abstract

Relative contribution of SCA2, SCA3 and SCA17 in Korean patients with parkinsonism and ataxia

We examined the relative significance of SCA2, SCA3 and SCA17 in Koreans patients with parkinsonism and ataxia. We recruited patients with either parkinsonism (n = 524; PD = 386 and MSA = 138) or ataxia (n = 44) as their main clinical feature for two years. These patients were screened for SCA2, SCA3 and SCA17. Six cases carried SCA2; one, SCA3; and eight, SCA17. In SCA2 patients, one patient exhibited MSA-P phenotype, and the other five exhibited ataxia. The single patient with SCA3 showed ataxia. In SCA17 patients, one patient presented ataxia, the other seven patients showed parkinsonism (three PD and four MSA-P). Dopamine transporter (DAT) imaging was performed in a subset of ataxic or parkinsonian SCA2 or SCA17, all of whom showed decreased DAT binding. In Korean population, the mutation frequencies of SCA2 and SCA17 were similar. SCA2 was a more significant cause of ataxia, whereas SCA17 was a more significant cause of parkinsonism. Contribution of SCA3 to parkinsonism was insignificant.

EXTRAPYRAMIDAL SIGNS ARE A COMMON FEATURE OF SPINOCEREBELLAR ATAXIA TYPE 17

Spinocerebellar ataxia type 17 (SCA17) is a CAG repeat expansion disorder in the TATA-binding protein (TBP) gene.1 Previous studies have shown that SCA17 is a rare cause of ataxia, especially in the East.2,3 SCA17 may show nonataxic manifestations, such as choreic movement, cognitive decline, dystonia, parkinsonism, and pyramidal tract signs. Previously we reported that SCA17 is not rare among our parkinsonian patients (0.9%).4 Thus, we examined the frequency of SCA17 among Korean patients with ataxia or chorea as a main phenotype. ### Methods. Gene samples obtained from the Movement Disorder Gene Bank of Seoul National University Hospital collected until April 2007 were analyzed. All patients were native Koreans. Written informed consent was obtained from all subjects before blood sampling for gene studies, and the genetic study was approved by our Institutional Review Board. Patients with a positive gene test for SCA1, 2, 3, 6, 7, dentatorubropallidoluysian atrophy, or Huntington disease (HD) were excluded. In both groups, acquired causes were excluded. We did not exclude the patients with familial history of ataxia or chorea. Finally, 661 ataxia patients and 98 chorea patients were included (2 patients had both ataxia and chorea). The method of gene analysis used is described in the previous report.4 ### Results. The 2 patients with both ataxia and chorea were found to have …

Unconstrained detection of freezing of Gait in Parkinson's disease patients using smartphone

Freezing of gait (FOG) is a common motor impairment to suffer an inability to walk, experienced by Parkinsons disease (PD) patients. FOG interferes with daily activities and increases fall risk, which can cause severe health problems. We propose a novel smartphone-based system to detect FOG symptoms in an unconstrained way. The feasibility of single device to sense gait characteristic was tested on the various body positions such as ankle, trouser pocket, waist and chest pocket. Using measured data from accelerometer and gyroscope in the smartphone, machine learning algorithm was applied to classify freezing episodes from normal walking. The performance of AdaBoost.M1 classifier showed the best sensitivity of 86% at the waist, 84% and 81% in the trouser pocket and at the ankle respectively, which is comparable to the results of previous studies.

Correction: Automatic Classification of Tremor Severity in Parkinson’s Disease Using a Wearable Device. Sensors 2017, 17, 2067

Hyoseon Jeon 1, Woongwoo Lee 2 ID , Hyeyoung Park 2, Hong Ji Lee 1, Sang Kyong Kim 1, Han Byul Kim 1, Beomseok Jeon 2 and Kwang Suk Park 3,* 1 The Interdisciplinary Program for Bioengineering, Seoul National University, Seoul 03080, Korea; nulpurunhs@bmsil.snu.ac.kr (H.J.); hongjidan@bmsil.snu.ac.kr (H.J.L.); skkim@bmsil.snu.ac.kr (S.K.K.); hahanbyul@bmsil.snu.ac.kr (H.B.K.) 2 Department of Neurology and Movement Disorder Center, Seoul National University Hospital, Seoul 03080, Korea; w2pooh@daum.net (W.L.); 0907bluelove@naver.com (H.P.); brain@snu.ac.kr (B.J.) 3 Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 03080, Korea * Correspondence: pks@bmsil.snu.ac.kr; Tel.: +82-2-2072-3135; Fax: +82-2-3676-2821