MR-guided focused ultrasound thalamotomy for lithium-induced tremor: a case report and literature review

Drug-induced tremor is a common side effect of lithium with an occurrence of approximately 25% of patients. Cessation of the offending drug can be difficult, and many medical treatments for drug-induced tremor are ineffective. Deep brain stimulation (DBS) has been shown in a limited number of case reports to effectively reduce drug-induced tremor, however, which remains an invasive therapeutic option. MR-guided focused ultrasound (MRgFUS) thalamotomy is an FDA-approved non-invasive treatment for essential tremor (ET). To the best of our knowledge, MRgFUS thalamotomy has never been reported to treat drug-induced tremor. Here, we present a case of a left-handed 55-year-old man with a progressive, medically refractory lithium-induced tremor of the bilateral upper extremities. The patient underwent MRgFUS thalamotomy targeting the right ventral intermediate nucleus (VIM) of the thalamus to treat the left hand. There was almost complete resolution of his left-hand tremor immediately following MRgFUS. There were no side effects. The patient continues to show excellent tremor control at 90-day follow-up and remains free from side effects. This case demonstrates MRgFUS thalamotomy as a possible novel treatment option to treat drug-induced tremor

Effects of exercise on sleep spindles in Parkinson's disease

BackgroundIn a randomized, controlled trial, we showed that high-intensity rehabilitation, combining resistance training and body-weight interval training, improves sleep efficiency in Parkinson's disease (PD). Quantitative sleep EEG (sleep qEEG) features, including sleep spindles, are altered in aging and in neurodegenerative disease.ObjectiveThe objective of this post-hoc analysis was to determine the effects of exercise, in comparison to a sleep hygiene, no-exercise control group, on the quantitative characteristics of sleep spindle morphology in PD.MethodsWe conducted an exploratory post-hoc analysis of 24 PD participants who were randomized to exercise (supervised 3 times/week for 16 weeks) versus 26 PD participants who were assigned to a sleep hygiene, no-exercise control group. At baseline and post-intervention, all participants completed memory testing and underwent polysomnography (PSG). PSG-derived sleep EEG central leads (C3 and C4) were manually inspected, with rejection of movement and electrical artifacts. Sleep spindle events were detected based on the following parameters: (1) frequency filter = 11–16 Hz, (2) event duration = 0.5–3 s, and (3) amplitude threshold 75% percentile. We then calculated spindle morphological features, including density and amplitude. These characteristics were computed and averaged over non-rapid eye movement (NREM) sleep stages N2 and N3 for the full night and separately for the first and second halves of the recording. Intervention effects on these features were analyzed using general linear models with group x time interaction. Significant interaction effects were evaluated for correlations with changes in performance in the memory domain.ResultsA significant group x time interaction effect was observed for changes in sleep spindle density due to exercise compared to sleep hygiene control during N2 and N3 during the first half of the night, with a moderate effect size. This change in spindle density was positively correlated with changes in performance on memory testing in the exercise group.ConclusionsThis study is the first to demonstrate that high-intensity exercise rehabilitation has a potential role in improving sleep spindle density in PD and leading to better cognitive performance in the memory domain. These findings represent a promising advance in the search for non-pharmacological treatments for this common and debilitating non-motor symptom

Effects of deep brain stimulation on quantitative sleep electroencephalogram during non-rapid eye movement in Parkinson’s disease

IntroductionSleep dysfunction is frequently experienced by people with Parkinson’s disease (PD) and negatively influences quality of life. Although subthalamic nucleus (STN) deep brain stimulation (DBS) can improve sleep in PD, sleep microstructural features such as sleep spindles provide additional insights about healthy sleep. For example, sleep spindles are important for better cognitive performance and for sleep consolidation in healthy adults. We hypothesized that conventional STN DBS settings would yield a greater enhancement in spindle density compared to OFF and low frequency DBS.MethodsIn a previous within-subject, cross-sectional study, we evaluated effects of low (60 Hz) and conventional high (≥130 Hz) frequency STN DBS settings on sleep macroarchitectural features in individuals with PD. In this post hoc, exploratory analysis, we conducted polysomnography (PSG)-derived quantitative electroencephalography (qEEG) assessments in a cohort of 15 individuals with PD who had undergone STN DBS treatment a median 13.5 months prior to study participation. Fourteen participants had unilateral DBS and 1 had bilateral DBS. During three nonconsecutive nights of PSG, the participants were assessed under three different DBS conditions: DBS OFF, DBS LOW frequency (60 Hz), and DBS HIGH frequency (≥130 Hz). The primary objective of this study was to investigate the changes in sleep spindle density across the three DBS conditions using repeated-measures analysis of variance. Additionally, we examined various secondary outcomes related to sleep qEEG features. For all participants, PSG-derived EEG data underwent meticulous manual inspection, with the exclusion of any segments affected by movement artifact. Following artifact rejection, sleep qEEG analysis was conducted on frontal and central leads. The measures included slow wave (SW) and spindle density and morphological characteristics, SW-spindle phase-amplitude coupling, and spectral power analysis during non-rapid eye movement (NREM) sleep.ResultsThe analysis revealed that spindle density was significantly higher in the DBS HIGH condition compared to the DBS LOW condition. Surprisingly, we found that SW amplitude during NREM was significantly higher in the DBS LOW condition compared to DBS OFF and DBS HIGH conditions. However, no significant differences were observed in the other sleep qEEG features during sleep at different DBS conditions.ConclusionThis study presents preliminary evidence suggesting that conventional HIGH frequency DBS settings enhance sleep spindle density in PD. Conversely, LOW frequency settings may have beneficial effects on increasing slow wave amplitude during sleep. These findings may inform mechanisms underlying subjective improvements in sleep quality reported in association with DBS. Moreover, this work supports the need for additional research on the influence of surgical interventions on sleep disorders, which are prevalent and debilitating non-motor symptoms in PD

Artificial Intelligence and Neurology - Opportunities and Challenges in Pakistan

The field of artificial intelligence (AI) has undergone rapid development in neurological disorders over the past few decades. AI relies on large volumes of high-quality data. As a result, their use in low-resource settings has been limited due to the lack of a digitized health care system. This article will address the challenges and opportunities involved in implementing AI for neurological care in Pakistan, as well as discuss the types of digital health care data and the benefits of applying AI in resource-limited countrie

Image_1_Effects of deep brain stimulation on quantitative sleep electroencephalogram during non-rapid eye movement in Parkinson’s disease.tiff

IntroductionSleep dysfunction is frequently experienced by people with Parkinson’s disease (PD) and negatively influences quality of life. Although subthalamic nucleus (STN) deep brain stimulation (DBS) can improve sleep in PD, sleep microstructural features such as sleep spindles provide additional insights about healthy sleep. For example, sleep spindles are important for better cognitive performance and for sleep consolidation in healthy adults. We hypothesized that conventional STN DBS settings would yield a greater enhancement in spindle density compared to OFF and low frequency DBS.MethodsIn a previous within-subject, cross-sectional study, we evaluated effects of low (60 Hz) and conventional high (≥130 Hz) frequency STN DBS settings on sleep macroarchitectural features in individuals with PD. In this post hoc, exploratory analysis, we conducted polysomnography (PSG)-derived quantitative electroencephalography (qEEG) assessments in a cohort of 15 individuals with PD who had undergone STN DBS treatment a median 13.5 months prior to study participation. Fourteen participants had unilateral DBS and 1 had bilateral DBS. During three nonconsecutive nights of PSG, the participants were assessed under three different DBS conditions: DBS OFF, DBS LOW frequency (60 Hz), and DBS HIGH frequency (≥130 Hz). The primary objective of this study was to investigate the changes in sleep spindle density across the three DBS conditions using repeated-measures analysis of variance. Additionally, we examined various secondary outcomes related to sleep qEEG features. For all participants, PSG-derived EEG data underwent meticulous manual inspection, with the exclusion of any segments affected by movement artifact. Following artifact rejection, sleep qEEG analysis was conducted on frontal and central leads. The measures included slow wave (SW) and spindle density and morphological characteristics, SW-spindle phase-amplitude coupling, and spectral power analysis during non-rapid eye movement (NREM) sleep.ResultsThe analysis revealed that spindle density was significantly higher in the DBS HIGH condition compared to the DBS LOW condition. Surprisingly, we found that SW amplitude during NREM was significantly higher in the DBS LOW condition compared to DBS OFF and DBS HIGH conditions. However, no significant differences were observed in the other sleep qEEG features during sleep at different DBS conditions.ConclusionThis study presents preliminary evidence suggesting that conventional HIGH frequency DBS settings enhance sleep spindle density in PD. Conversely, LOW frequency settings may have beneficial effects on increasing slow wave amplitude during sleep. These findings may inform mechanisms underlying subjective improvements in sleep quality reported in association with DBS. Moreover, this work supports the need for additional research on the influence of surgical interventions on sleep disorders, which are prevalent and debilitating non-motor symptoms in PD.</p

Table_1_Effects of deep brain stimulation on quantitative sleep electroencephalogram during non-rapid eye movement in Parkinson’s disease.docx

IntroductionSleep dysfunction is frequently experienced by people with Parkinson’s disease (PD) and negatively influences quality of life. Although subthalamic nucleus (STN) deep brain stimulation (DBS) can improve sleep in PD, sleep microstructural features such as sleep spindles provide additional insights about healthy sleep. For example, sleep spindles are important for better cognitive performance and for sleep consolidation in healthy adults. We hypothesized that conventional STN DBS settings would yield a greater enhancement in spindle density compared to OFF and low frequency DBS.MethodsIn a previous within-subject, cross-sectional study, we evaluated effects of low (60 Hz) and conventional high (≥130 Hz) frequency STN DBS settings on sleep macroarchitectural features in individuals with PD. In this post hoc, exploratory analysis, we conducted polysomnography (PSG)-derived quantitative electroencephalography (qEEG) assessments in a cohort of 15 individuals with PD who had undergone STN DBS treatment a median 13.5 months prior to study participation. Fourteen participants had unilateral DBS and 1 had bilateral DBS. During three nonconsecutive nights of PSG, the participants were assessed under three different DBS conditions: DBS OFF, DBS LOW frequency (60 Hz), and DBS HIGH frequency (≥130 Hz). The primary objective of this study was to investigate the changes in sleep spindle density across the three DBS conditions using repeated-measures analysis of variance. Additionally, we examined various secondary outcomes related to sleep qEEG features. For all participants, PSG-derived EEG data underwent meticulous manual inspection, with the exclusion of any segments affected by movement artifact. Following artifact rejection, sleep qEEG analysis was conducted on frontal and central leads. The measures included slow wave (SW) and spindle density and morphological characteristics, SW-spindle phase-amplitude coupling, and spectral power analysis during non-rapid eye movement (NREM) sleep.ResultsThe analysis revealed that spindle density was significantly higher in the DBS HIGH condition compared to the DBS LOW condition. Surprisingly, we found that SW amplitude during NREM was significantly higher in the DBS LOW condition compared to DBS OFF and DBS HIGH conditions. However, no significant differences were observed in the other sleep qEEG features during sleep at different DBS conditions.ConclusionThis study presents preliminary evidence suggesting that conventional HIGH frequency DBS settings enhance sleep spindle density in PD. Conversely, LOW frequency settings may have beneficial effects on increasing slow wave amplitude during sleep. These findings may inform mechanisms underlying subjective improvements in sleep quality reported in association with DBS. Moreover, this work supports the need for additional research on the influence of surgical interventions on sleep disorders, which are prevalent and debilitating non-motor symptoms in PD.</p

Comparison of Serum Dkk1 (Dickkopf-1) and bone mineral density in patients on bisphosphonate treatment versus no treatment

Complex pathways affect bone metabolism at the cellular level, and a balance between osteoblast and osteoclast activity is critical to bone remodeling. One of the major pathways affecting bone metabolism is Wnt/?-catenin signaling, and its disturbances lead to a wide range of bone abnormalities. An important antagonist of this pathway is Dickkopf-1 (Dkk1). Higher Dkk1 levels have been associated with increased bone loss due to inhibition of Wnt pathway. Currently, bisphosphonates are the most commonly used agents to treat primary osteoporotic patients. This study demonstrates the effect of bisphosphonates on Dkk1 levels and its correlation with bone mineral density (BMD). Eighty patients with low BMD were recruited and divided into 2 groups of 40 each (bisphosphonate treatment group and control group). The mean Dkk1 level in the treatment group was significantly reduced to 2358.18 vs 3749.80pg/mL in the control group (p&lt;0.001). Pearson correlation coefficient showed negative correlation between Dkk1 and BMD at lumbar spine (r=?0.55) and femoral neck in the control group; however, no such correlation was found in the treatment group (r=?0.05). Hence, bisphosphonate therapy leads to reduction in Dkk1 levels, but it does not correlate with BMD in such patients.<br/