Ocular motor and vestibular dysfunction in central nervous system lymphoma.

BACKGROUND AND PURPOSE: Diagnosis of lymphoma involving the central nervous system (CNS) is challenging. This study aimed to explore the abnormal vestibular and ocular motor findings in CNS lymphoma. METHODS: A retrospective search of the medical records identified 30 patients with CNS lymphoma presenting ocular motor and vestibular abnormalities from four neurology clinics of university hospitals in South Korea (22 men, age range 14-81 years, mean 60.6 ± 15.2). The demographic and clinical features and the results of laboratory, radiological and pathological evaluation were analyzed. RESULTS: Patients presented with diplopia (13/30, 43%), vestibular symptoms (15/30, 50%) or both (2/30, 7%). In 15 patients with diplopia, abnormal ocular motor findings included ocular motor nerve palsy (n = 10, 67%), internuclear ophthalmoplegia (n = 2, 13%), external ophthalmoplegia (n = 2, 13%) and exophoria (n = 1, 7%). The vestibular abnormalities were isolated in 14 (82%) of 17 patients with vestibular symptoms and included combined unilateral peripheral and central vestibulopathy in three from lesions involving the vestibular nuclei. CNS lymphoma involved the brainstem (53%), cerebellum (33%), leptomeninges (30%), deep gray nuclei (23%) or cranial nerves (17%). Two patients showed the "double-panda" sign by involving the midbrain. CONCLUSIONS: This study expands the clinical and radiological spectra of CNS lymphoma. Neuro-ophthalmological and neuro-otological evaluation may guide the early diagnosis of CNS lymphoma.

Lambert-Eaton myasthenic syndrome (LEMS) in a patient with lung cancer under treatment with pembrolizumab: a case study.

Pembrolizumab is an immune checkpoint inhibitor (ICI) against the programmed death-1 receptor. Herein, we introduce a rare adverse effect during using pembrolizumab. We present the case of an 80-year-old man with biopsy-proven unresectable double primary squamous cell carcinoma and large cell neuroendocrine carcinoma of the lung. After using pembrolizumab for 10 months, he complained of muscle weakness of both upper and lower extremities. In a nerve conduction study, the repetitive nerve stimulation test in the abductor digiti minimi was diagnostic of Lambert-Eaton myasthenic syndrome (LEMS): low in the amplitude of compound muscle action potential (1.4 mV), 28.6% decrement in the 5-Hz stimulation, and 579% increment in the 50-Hz stimulation. The disease did not progress after the discontinuation of pembrolizumab, even without any anti-cancer treatment for 12 months. We believe our clinical experience of this rare and unexpected adverse effect should be shared.

Alternating Hemiplegia of Childhood in Korea: a Case Report.

Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disorder characterized by recurrent paroxysmal hemiplegic attacks that affect one or the other side of the body. Up to 74% of patients with AHC have a pathologic variant in the ATP1A3 gene. After the introduction of next-generation sequencing, intermediate cases and atypical cases have expanded the clinical spectrum of ATP1A3-related disorders. Herein, we report the first case of AHC in Korea. A 33-year-old man visited our hospital with recurrent hemiplegic and dystonic episode after his first birthday. He was completely normal between episodes and did not have any ataxia, but brain magnetic resonance imaging showed cerebellar atrophy. He also had pes planovalgus deformity. Whole exome sequencing revealed a heterozygous G947R variant in the ATP1A3 gene (c.2839G > C, rs398122887), which is a known pathologic variant. This atypical case of AHC demonstrates the importance of the clinical approach in diagnosing ATP1A3-related disorders.

Smoking Cessation, Weight Change, and Risk of Parkinson's Disease: Analysis of National Cohort Data.

BACKGROUND AND PURPOSE: To determine whether the postcessation weight gain modifies the protective effect of smoking on the development of Parkinson's disease (PD). METHODS: This nationwide cohort study included 3,908,687 Korean males aged ≥40 years who underwent at least 2 health checkups biennially between 2009 and 2015. They were grouped into current smokers; quitters with body mass index (BMI) increase, maintenance, and decrease; and never smokers. The occurrence of incident PD was tracked, and Cox proportional-hazard models were used to adjust for potential confounding factors. We also analyzed the impact of weight change regardless of smoking status in the study population. RESULTS: There were 6,871 incident PD cases observed during the 13,059,208 person-years of follow-up. The overall risk of PD was significantly lower in quitters than in never smokers [hazard ratio (HR)=0.78, 95% confidence interval (CI)=0.70-0.86]. The risk of PD was still lower in quitters with BMI increase (HR=0.80, 95% CI=0.65-0.98) and in those with BMI maintenance (HR=0.77, 95% CI=0.68-0.87). This tendency was also observed in quitters with BMI decrease (HR=0.76, 95% CI=0.55-1.06), although it was not as robust as in the other two groups. With respect to weight change alone, BMI increase (HR=1.10, 95% CI=1.02-1.18) but not BMI decrease (HR=1.06, 95% CI=0.98-1.14) significantly increased the PD risk compared to BMI maintenance. CONCLUSIONS: Postcessation weight gain in males did not offset the protective impact of smoking on PD development, although overall weight gain predicted an increased risk of PD.

Patient selected goals and satisfaction after bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

Assessing patient goals is crucial in understanding patient centered outcomes and satisfaction. However, patient goals may change throughout treatment. Our objective is to identify the changes in patient-selected goals of Parkinson's disease (PD) patients undergoing bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and examine the relationship among patient-selected goal achievement, standard DBS outcome measures, and overall patient satisfaction. Seventy-five patients undergoing bilateral STN-DBS listed three patient-selected goals before surgery. After six months, patients were asked to restate the three goals and to rate the degree of goal achievement and the overall satisfaction of surgery. The three most frequently selected goals were "dyskinesia", "gait disorder", and "medication off duration". After six months, 80.0% of patients could not accurately recall their pre-DBS goals. "Dyskinesia" was the most consistently selected goal, more patients selected "tremor" and "less medication" at post-DBS compared to pre-DBS, and less patients selected "gait disorder" at post-DBS compared to pre-DBS. 74.7% of patients reported overall satisfaction by stating they were "very much" or "much better after surgery". Patient satisfaction significantly correlated with goal achievement (r = 0.640; p < 0.001). Interestingly, change in UPDRS motor scores did not correlate with patient satisfaction (r = 0.100; p = 0.395). Although recalled goals do not accurately represent the pre-surgical goals, the achievement score for recalled goals significantly correlated with patient satisfaction. Patient goals change due to many reasons. Therefore, follow-up patient counseling to discuss goals and outcomes is important in improving patient satisfaction after STN-DBS.

Sex differences in smoking, alcohol consumption, and risk of Parkinson's disease: A nationwide cohort study.

OBJECTIVE: We assessed the influence of sex on the effects of smoking and alcohol consumption on the risk of Parkinson's disease (PD). METHODS: This population-based cohort study examined data of 6,795,816 Koreans aged ≥40 years from the Korean National Health Insurance Service database who completed a national program for general health check-up at 2009. For a maximum 9 years' observation period, incident PD was tracked, and hazard ratios and 95% confidence intervals (CIs) were computed using the Cox proportional hazard models, adjusted for potential confounding factors for each sex group. We tested interactions on the addictive scale by estimating the relative excess risk due to interaction (RERI). RESULTS: 3,400,538 men and 3,395,278 women generated 24,365,694 and 24,754,154 person-years, respectively. A total of 13,223 men (0.39%) and 14,818 women (0.44%) developed PD during follow-up. Current smoking and alcohol independently reduced the risk of PD in both sexes. Current male smokers tended to have a lower risk of PD than current female smokers at equal smoking intensity (P < 0.0001 for interaction) and duration (P < 0.0001 for interaction). In contrast, at equal alcohol intakes, PD risk tended to be lower in female drinkers than in male drinkers (P < 0.0001 for interaction). A superadditive interaction between smoking and alcohol was found in current male smokers (RERI, 0.19; 95% CI, 0.04 to 0.34; P = 0.015) and female ex-smokers (RERI, 0.42; 95% CI, 0.09 to 0.76; P = 0.014). CONCLUSION: Our data suggest sex-related differences in individual and joint impacts of smoking and alcohol intake on the risk of PD.

Determinants of Functional Independence or Its Loss following Subthalamic Nucleus Stimulation in Parkinson's Disease.

OBJECTIVE: This study aimed to describe the change in functional status following bilateral subthalamic nucleus stimulation (STN-DBS) in Parkinson's disease (PD) and to identify predictors of postoperative functional dependence. METHODS: We included PD patients with bilateral STN-DBS who had complete Schwab & England Activities of Daily Living (S&E ADL) Scale data at baseline and 6 months after surgery from our prospective registry. Functional dependence was defined as an S&E ADL score of less than 80%. All data were collected from the on-medication state and on-stimulation state (after surgery). Logistic regression analyses were performed to determine the factors predictive of functional dependence after surgery. RESULTS: A total of 196 patients were included. At baseline, 41 patients were functionally dependent and the other 155 were functionally independent. Among the patients with preoperative dependence, 32 (78%) became functionally independent after surgery, and this conversion was associated with a lower baseline axial score (p = 0.012). Among the patients with preoperative independence, 21 (14%) developed postoperative dependence, and this conversion was associated with a higher baseline axial score (p = 0.013) and its smaller improvement (p < 0.001). Female sex (odds ratio [OR] 3.214; 95% confidence interval [CI] 1.210-8.542; p = 0.019) and a higher baseline axial score (OR 1.184; 95% CI 1.056-1.327; p = 0.004) significantly predicted the risk of postoperative functional dependence. CONCLUSIONS: We found that functional status following bilateral STN-DBS is closely related to preoperative axial symptoms. When loss of independence is a potential target for STN-DBS, clinicians should take into consideration the severity of axial impairment before surgery.

Peripheral blood inflammatory markers in early Parkinson's disease.

The aim of this study was to characterize peripheral inflammatory markers in patients with early Parkinson's disease (PD) and to explore whether these markers contribute to motor and non-motor symptoms. We collected serum from patients with early PD (n = 58) and from healthy control subjects (n = 20). The following inflammatory markers were measured: interleukin (IL)-1ß, IL-2, IL-6, IL-10, tumor necrosis factor-α, and high-sensitivity C-reactive protein. The Movement Disorders Society Unified Parkinson's Disease Rating Scale part 3 and Hoehn and Yahr stage were used to assess motor symptoms, and the Non-motor Symptoms Scale, the Cross-Cultural Smell Identification Test, the Montreal Cognitive Assessment, and the Composite Autonomic Symptom Score 31 (COMPASS-31) were used to assess non-motor symptoms. The levels of IL-1ß, IL-2, and IL-6 were higher in the PD group than in the control group. However, only IL-1ß among those markers remained significant after Bonferroni correction (P = 0.024). In the PD group, the anti-inflammatory cytokine IL-10 levels correlated positively with the COMPASS-31 score (r = 0.277, P = 0.035), whereas no correlation was found between the other inflammatory marker levels and motor or non-motor symptoms. Among the domains of the COMPASS-31, the IL-10 levels correlated only with the gastrointestinal domain (r = 0.358, P = 0.006). Our results suggest increased peripheral inflammation in the early stage of PD, but the role of inflammation in motor and non-motor symptoms is unclear. Although we found a correlation between IL-10 levels and gastrointestinal symptoms, this finding may simply reflect a protective response against inflammatory processes associated with the disease.

Spinal Myoclonus Responding to Continuous Intrathecal Morphine Pump.

Spinal myoclonus is a sudden, brief, and involuntary movement of segmental or propriospinal muscle groups. Spinal myoclonus has occasionally been reported in patients undergoing opioid therapy, but the pathophysiology of opioid-induced myoclonus has not been elucidated yet. Here, we present two patients with spinal segmental myoclonus secondary to ischemic and radiation myelopathy. Conventional medications did not help treat persistent myoclonus in both legs. Continuous intrathecal morphine infusion was implanted for pain control in one patient, which relieved spinal myoclonus entirely. This experience led to the application of this method with a second patient, leading to the same gratifying result. Spinal myoclonus reemerged as soon as the morphine pumps were off, which confirmed the therapeutic role of opioids. In contrast to the opioid-induced myoclonus, these cases show a benefit of opioids on spinal myoclonus, which could be explained by synaptic reorganization after pathologic insults in the spinal cord.