Sleep seasonality in alpha-synucleinopathies: A comparative study with non-neurological sleep disorder patients.

INTRODUCTION: It is unknown if seasonal variation in daylight affects sleep in patients with alpha-synucleinopathies. Our objectives were to assess month of the year related changes in polysomnography (PSG) data in patients with Parkinson 's disease (PD), Lewy Body Dementia (LBD) and isolated REM sleep behavior disorder (iRBD). METHODS: We collected PSG data from 64 PD, 30 LBD and 24 iRBD patients attending a sleep laboratory in Lisbon, Portugal, during 10 years. Each was classified according to the month of the year PSG was performed and compared with a control patient with sleep disorder, but no evidence of other neurological disorder, matched for sex, age group and PSG month. The influence of month in PSG data was assessed with mixed linear regression analysis. RESULTS: In alpha-synucleinopathies, month showed significant interaction with N2 stage time and percentage (increase from December to April) and N3 time (peak in May). REM sleep percentage increased significantly from Spring to middle Summer. In the control group, there were significant interactions regarding Total Sleep Time and Sleep Efficiency (drop during wintertime), N2 time and REM % (increase in April and May) and Apnea-Hypopnea Index (AHI) (peak in June). There were significant associations between the term group*month and sleep efficiency and AHI, with larger monthly variation in the control group. CONCLUSION: Seasonality had a larger impact in stage architecture in alpha-synucleinopathies, and in total sleep time, sleep efficiency and the severity of OSA in the control group. Different sleep dysfunction mechanisms could explain differences in seasonal variation.

Parkinson's disease patients' perspective on telephone visits during the COVID-19 pandemic.

Telemedicine is a promising modality to provide specialized care in periods when attendance is challenged, as recently observed during the Coronavirus disease 2019 (COVID-19) pandemic. We aimed to evaluate the satisfaction with telemedicine visits in a group of Parkinson´s disease (PD) patients during the COVID-19 pandemic, as well as to identify demographic or clinical factors associated with higher telemedicine satisfaction. Retrospective cohort study of PD patients who attended telemedicine visits at Centro Hospitalar de Lisboa Ocidental, from March 1, 2020 until March 31, 2021. An eleven-question telephone survey was used to assess satisfaction with telemedicine visits. Patients' answers were dichotomized into "satisfied" or "not satisfied" to study the factors associated with satisfaction with telemedicine. Mann-Whitney U for continuous variables and chi-square tests for categorical variables were performed to compare data between the two groups. Linear regression was used to study the factors associated with being satisfied with telemedicine. A total of 111 patients (87%) accepted to participate in this survey. The majority (n = 74.67%) reported being satisfied with telemedicine visits. Patients preferred a combination of in-person and telemedicine visits (n = 43.39%). Male gender (p < 0.001) and employed patients (p < 0.001) were associated with higher satisfaction. In the linear regression, therapeutic changes deemed clear (p < 0.014) and considering the absence of neurological examination non-detrimental (p < 0.001) were associated with a higher degree of satisfaction with telemedicine. Most patients are satisfied with telemedicine visits, even in urgent implementation due to the COVID-19 pandemic. Moreover, telemedicine does not pose a hurdle to a paradigm shift away from conventional in-person appointments.

Obstructive Sleep Apnea and Other Vascular Risk factors' Impact on Non-Motor Symptoms in Parkinson's Disease.

Background: Previous studies revealed an association between vascular comorbidities and obstructive sleep apnea (OSA) and the severity of motor and cognitive symptoms in Parkinson's disease (PD). However, there is a lack of studies assessing the entire spectrum of non-motor symptoms (NMS). Objective: To investigate the relationship between vascular comorbidities and NMS in PD patients. Methods: Patients were assessed at baseline and 4 years later with the Non-Motor Symptom Assessment Scale, Parkinson's Psychosis Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment, and Apathy scale. After tetrachoric correlation matrix, we conducted linear regression models (adjusted for age, gender, disease duration, and UPDRS-III) to investigate the relationship between vascular comorbidities and NMS. Results: In 73 PD patients, (mean disease duration 7.1 [5.3]), 57% had hypertension, 44% body mass index >25, 44% elevated cholesterol, 15% diabetes mellitus, 15% OSA, 14% cigarette-smoking history, 8% prior stroke, and 8% coronary disease. Cognition, psychotic symptoms, apathy, urinary function, and miscellaneous domains significantly worsened at the 4-year follow-up. OSA was significantly associated with higher severity of hallucinations/illusions at baseline and with a more severe deterioration of attention/memory, psychotic symptoms, and apathetic mood at the 4-year follow-up. At baseline, but not at follow-up, hypertension was negatively associated with miscellaneous domain scores and coronary disease with autonomic function scores (gastrointestinal tract and urinary function domains). Conclusion: Among PD-associated comorbidities, OSA was the main factor of decline. In addition to cognitive impairment, OSA might also potentially worsen psychotic symptoms and apathy. Treatment of OSA could be a strategy to improve these important NMS.

Sleep stability in isolated rapid eye movement sleep behavior disorder, Parkinson's disease, and dementia with Lewy bodies.

BACKGROUND: Non-REM sleep symptoms remain poorly understood in alpha-synucleinopathies. AIMS: The aims of the study were to compare sleep stability and transitions, arousals, and sleep cycle structure between isolated rapid eye movement (REM) sleep behavior disorder (iRBD), Parkinson's disease (PD), and dementia with Lewy Bodies (DLB). MATERIALS AND METHODS: Sleep transition and stability measures were assessed in one-night video-polysomnography records. Transition measures were the number of shifts between Wake and REM, Wake and NREM, and REM and NREM. Stability measures were the number of passages within the same sleep stage. We assessed arousals, the number/duration of sleep cycles (defined as a sequence of any NREM stage to REM), and the duration of N3 and REM sleep in each cycle. These variables were compared between two sets of groups (PD vs. DLB vs. iRBD and RDB+ vs. RBD-). RESULTS: We assessed 54 PD, 24 DLB, and 21 iRBD patients (54 RBD+, 22 RBD-). There were no significant differences regarding sleep stability measures. Arousal indices in N1 and N2 stages were significantly higher in PD compared with iRBD. 24% of the sample did not have any sleep cycle. PD had significantly fewer cycles than iRBD. Differences became non-significant when adjusting for medication. There was no effect of group or time of night in REM or N3 duration. There were no significant differences between RBD+ and RBD-. DISCUSSION: There were no significant differences in stability/transition measures. Arousals and disturbance in sleep cycling were higher in PD, but the difference was no longer significant after adjusting for medication. CONCLUSION: Different alpha-synucleinopathies have a similar degree of non-REM sleep instability, but medication could worsen symptoms in PD.

Progression in Parkinson's Disease: Variation in Motor and Non-motor Symptoms Severity and Predictors of Decline in Cognition, Motor Function, Disability, and Health-Related Quality of Life as Assessed by Two Different Methods.

BACKGROUND: Parkinson's disease (PD) is multi-symptom disease with variable progression. OBJECTIVES: We performed a longitudinal study to address the evolution of motor symptoms (MS) and non-motor symptoms (NMS), predictors of motor-, cognitive-, disability-, and health-related quality of life (HRQL) status and the relative usefullness of a battery of separate NMS scales (BSS) versus the Non-Motor Symptom Scale (NMSS). METHODS: Seventy-two patients were assessed at baseline and 4 years later with the NMSS and BSS. We assessed the following outcomes: cognition (Montreal Cognitive Assessment scale [MoCA]), disability (Unified Parkinson's Disease Rating Scale Part II [UPDRS II], Schwab and England [S&E]), motor dysfunction (Unified Parkinson's Disease Rating Scale Part III [UPDRS III], Hoehn and Yahr [HY]), and HRQL (EuroQol [EQ] EQ-vertical visual analogue scale [VAS] and EQ-Index). Statistical analysis included a comparison between scales scores at both time points and multivariate regression analysis to calculate the impact of each baseline symptom in outcomes. NMSS and BSS were introduced in separate models. RESULTS: NMSS Domain 4: perception/hallucinations, Parkinson's Psychosis Questionnaire, Apathy Scale, NMSS Domain 7: urinary, S&E, UPDRS II, HY, and MoCA scores worsened significantly. Dementia increased to a 4-year prevalence of 39.8%. In the multivariate model using BSS, cognitive state variation was significantly predicted by baseline HY, EQ-Index, and S&E. Using the NMSS, MoCA change was significantly associated with NMSS Domain 4: perceptions/hallucination score, cognitive status with UPDRS III score, HRQL with NMSS Domain 4: perception/hallucinations score, and S&E. CONCLUSION: Our study suggests that NMS progress heterogeneously, BSS approach being more sensitive to change than NMSS. The multivariate analysis has shown that S&E and NMSS Domain 4: perception/hallucinations scores are the stronger predictors of HRQL and cognitive dysfunction variation, favoring NMSS over the BSS approach.

Objective sleep data as predictors of cognitive decline in dementia with Lewy Bodies and Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) prognosis depends on cognitive function evolution. Sleep disorders, as objectivated by polysomnography (PSG), are intimately connected with PD and DLB pathophysiology, but have seldomly been used to predict cognitive decline. METHODS: 20 DLB and 49 PD patients underwent one-night in-lab video-PSG. Sleep variables were defined, including REM sleep motor events, Tonic and phasic REM sleep muscular tone and RBD diagnosis. Cognitive state (assessed with the Global Deterioration Scale (GDS) was collected from case files for 6 months intervals, for a maximum period of 3.5 years or until death/drop-out.). The relation between PSG data at baseline and variation of GDS scores over time was tested with mixed linear regression analysis. RESULTS: GDS scores were higher in DLB, than in PD. We confirmed significant cognitive decline in both disorders, but no significant differences in progression between them. There were no significant interactions between PSG data and GDS variation for the entire group and DLB separately. In PD patients, there was a significant interaction between RBD diagnosis and tonic excessive muscular tone and GDS increase. CONCLUSION: Our data suggests that PSG data can be useful in predicting cognitive decline in PD but not in DLB patients. In PD patients, an RBD diagnosis is predictive of cognitive deterioration, confirming the notion that this non-motor symptom relates to a malignant sub-type. Tonic excessive muscular activity, but not other RBD features, had predictive value in this group, pointing to a specific relation with the disease pathophysiology.

REM sleep absence in patients referred to polysomnography for REM sleep behavior disorder.

Detection of REM sleep behavior disorder (RBD) with polysomnography (PSG) is relevant for the diagnosis of α-synucleinopathies. However, some patients referred for suspicion of RBD do not present REM sleep at PSG (NoREMSusRBD), rendering the study inconclusive. Our objective was to investigate disorders possibility associated with REM sleep absence in patients referred to PSG for investigation of RBD, in particular α-synucleinopathies. A sleep-lab database was revised to select NoREMSusRBD (n = 15) and patients: with no REM sleep referred for suspicion of other sleep disorder (NoREMSusOther, n = 28); referred for RBD suspicion with negative PSG (NegativeRBD, n = 24); α-synucleinopathies with no REM sleep (NoREMα, n = 23) and idiopathic RBD (iRBD, n = 26). NoREMSusRBD patients were compared with the other groups regarding PSG data and the emergence of prodromal features or established criteria for α-synucleinopathy. Severe Obstructive Sleep Apnea (OSA) was significantly more frequent in the NoREMsusRBD compared to the NoREMα and iRBD groups. No patient in the NoREMSusRBD developed a α-synucleinopathy (2 cases on the iRBD group). The prevalence of prodromal features in NoREMSusRBD (n = 7, 46.7%) was similar to that of iRBD (n = 18, 69.2%) and significantly higher than in the other groups. Apnea-Hypopnea Indices (AHI) were significantly higher in the NoREMSusRBD compared with iRBD and NoREMα. Our study suggests that the absence of REM sleep in NoREMSusRBD could be caused by OSA but does not exclude the possibility of underlying α- synucleinopathy, suggested by an increased prevalence of prodromal features. These data support the need for excluding OSA in patients suspected for RBD and recommends follow-up of NoREMSusRBD patients to uncover a possible α- synucleinopathy.

Polysomnographic predictors of sleep, motor and cognitive dysfunction progression in Parkinson's disease: a longitudinal study.

OBJECTIVE: To assess the predictive value of polysomnographic (PSG) data in the prospective assessment of cognitive, motor, daytime and nighttime sleep dysfunction in Parkinson's Disease (PD) patients. METHODS: PD patients were assessed at baseline with video-PSG and with cognitive (MoCA), Sleep (SCOPA-Sleep Nighttime and Daytime scores) and Motor (UPDRSIII) function scales at both baseline and four years later. Linear regression analysis was used to assess the relation between PSG variables at baseline and change in symptoms scores. RESULTS: We included a total of 25 patients, 12 with rapid eye movement (REM) sleep behavior disorder (RBD) (in 8 PSG was inconclusive, due to lack of REM sleep). MoCA scores decreased significantly at follow-up, while SCOPA-Sleep Daytime and SCOPA-Sleep Nighttime and UPDRSIII did not vary. Lower N3 percentage at baseline was significantly associated with MoCA decrease. Higher Periodic Limb Movements in Sleep index (PLMS) and the presence of RBD were significantly associated with SCOPA daytime score increase. Higher global severity of RBD, tonic RSWA and total number of motor events during REM sleep were associated with SCOPA Nighttime score increase. CONCLUSIONS: The present work suggests that PSG data could be useful for predicting PD cognitive and sleep dysfunction progression. Reduced SWS could predict deterioration of cognitive function, while baseline PLMS could be useful to predict worsening of daytime sleep dysfunction. Severity of RBD could be used for estimating nighttime sleep symptoms progression.

Do dreams tell the future? Dream content as a predictor of cognitive deterioration in Parkinson's disease.

Cross-sectional studies suggest a correlation between alterations in dream content reports and executive dysfunction tests in Parkinson's disease (PD), but this has not been assessed in longitudinal studies. Our objective was to assess the predictive value of dream content for progression of cognitive dysfunction in PD. We prospectively addressed all consecutive, non-demented patients with PD attending an outpatient clinic during a 1-year period. Dream reports were collected at baseline by means of a dream diary and analysed according to the Hall and Van de Castle system. Patients were assessed at baseline for rapid eye movement sleep behaviour disorder, motor stage, mood disorder and psychosis. The Montreal Cognitive Assessment (MoCA) was applied at baseline and 4 years later. Linear regression analysis was used to the test the relation between each dream index (predictors), demographic and other motor and non-motor variables (covariates), and change in MoCA scores (dependent variable). In all, 58 patients were assessed at both time points and 23 reported at least one dream (range 1-27, total 148). Aggression, physical activities, and negatively toned content predominated in dream reports. The MoCA scores decreased significantly from baseline to follow-up. In the multivariate model, negative emotion index was the strongest predictor of cognitive decline. We found a significant positive association between negative emotions in dreams at baseline and subsequent reduction in MoCA scores. These findings suggest that some dream content in patients with PD could be considered a predictor of cognitive decline, independent of other factors known to influence either dream content or cognitive deterioration.

REM sleep behaviour disorder in essential tremor: A polysomnographic study.

Our objectives were to assess the prevalence of REM sleep behaviour disorder in patients with Essential Tremor, using video-polysomnography and to compare REM sleep behaviour disorder features in essential tremor with those of patients with alpha-synucleinopathies. Forty-nine patients with essential tremor were screened with the REM Sleep Behaviour Disorder Screening Questionnaire. Patients scoring positive and those with spontaneous complaints of REM sleep behaviour disorder (n = 6) underwent video-polysomnography. The clinical features of essential tremor were compared between patients with and without REM sleep behaviour disorder. Video-polysomnography data were compared between patients who had essential tremor and Parkinson's disease with REM sleep behaviour disorder and those with idiopathic REM sleep behaviour disorder. Fourteen patients (23.5%) screened positive for REM sleep behaviour disorder, confirmed by video-polysomnography in five (11.6%). All patients with essential tremor and REM sleep behaviour disorder had rest tremor, compared with 13 (34.2%) in the group with essential tremor but without REM sleep behaviour disorder (p = .009). In video-polysomnography, patients with essential tremor and REM sleep behaviour disorder were similar to patients with Parkinson's disease with REM sleep behaviour disorder and presented worse sleep dysfunction and lower severity of REM sleep behaviour disorder compared to those with idiopathic REM sleep behaviour disorder. We found a high prevalence of REM sleep behaviour disorder in patients with essential tremor, associated with a predominance of rest tremor. Polysomnography data from patients with essential tremor and REM sleep behaviour disorder were similar to those in patients with Parkinson's disease. This suggests a relation between this subgroup of patients with essential tremor and the alpha-synucleinopathies.

Factors Influencing the Presentation of REM Sleep Behavior Disorder: The Relative Importance of Sex, Associated Neurological Disorder, and Context of Referral to Polysomnography.

STUDY OBJECTIVES: To identify the interrelation and relative influence of sex, associated neurological disorder, and polysomnography (PSG) context on the manifestations of rapid eye movement (REM) sleep behavior disorder (RBD). METHODS: Fifty-seven patients with RBD were assessed with video PSG regarding sleep structure, muscular activity, and motor events (ME) during REM sleep. Patients were categorized according to sex, associated neurological disorder (clinically isolated RBD [iRBD] versus RBD associated with an overt α-synucleinopathy [sRBD]) and motive for PSG (direct referral due to RBD symptoms [First, n = 14]; referred after screening procedures [Screening, n = 13]; referred during clinical follow-up for other disorders [Follow-up, n = 22]; referred for symptoms other than RBD [Incidental, n = 8]). RESULTS: Phasic muscular activity index and the relative number of myoclonic and trunk ME were significantly higher in males and segmental ME in female patients. sRBD was associated with Screening and iRBD with First categories. There was a higher severity of ME in patients with iRBD. Global motor severity of ME was significantly higher in the First category. In multivariate analysis, both motive for PSG and associated neurological disorder had a significant and independent influence in the global severity of ME. CONCLUSIONS: Associated neurological disorder and motive for PSG can significantly influence RBD presentation. Male sex is related with higher muscular phasic activity and a different pattern of ME, which could contribute to prevalence variations across studies. Having iRBD and being directly referred for a first consultation because of complaints compatible with RBD are interrelated and contribute independently to a higher severity of ME.

Motor and non-motor function predictors of mortality in Parkinson's disease.

Doubts persist regarding the influence of Parkinson's disease (PD) on mortality. Our objective was to assess mortality rates in a prospectively followed cohort of PD patients and the impact of motor and non-motor symptoms in survival. 130 consecutive PD patients were followed during a 4-year period or until death. Baseline assessment included motor function (UPDRSIII, Hoehn and Yahr-HY), incapacity (Schwab and England-S&E, UPDRS II), Health-Related quality of life (EuroQol), non-motor symptoms (Non-Motor Symptom Scale-NMSS, MoCA, REM sleep behavior disorder symptoms questionnaire) and comorbidity burden (Charlson Comorbidity Index-CCI). These were used as predictor variables. Standardized mortality rates (SMR) were calculated, comparing with the general population. The association between mortality and predictors was tested with univariate and multivariate Cox proportional hazard regression models. Overall and gender-related SMRs were similar to the general population. SMR for pneumonia was five times higher than in the general population. Age, disease duration, CCI, EuroQol, dementia, MoCA, S&E, NMSS Hallucinations, HY, and PIGD motor phenotype were significantly associated with mortality. Adjusting for age, gender and disease duration, S&E remained significantly associated with mortality. In multivariate logistic regression analysis, death was significantly associated with disease duration, CCI and NMSS-mood/cognition scores. PD was not associated with an excess of mortality, but conferred a higher probability of dying from pneumonia. Comorbidity was a major determinant, but disease duration, baseline incapacity, cognition, psychosis, mood complaints and HRQL also contributed significantly to mortality.

Cognitive complaints in Parkinson's disease patients: from subjective cognitive complaints to dementia and affective disorders.

Subjective cognitive complaints (SCC) are frequent in elderly populations. PD patients report SCC more often than healthy controls. The association between SCC, objective cognitive impairment and affective symptoms remains controversial. We assessed consecutive PD patients between March 2014 and March 2015. Presence of SCC was defined as a score ≥ 1 in the Non-Motor Symptom Assessment Scale for Parkinson's Disease (NMSS) Domain 5. MoCA was used for cognitive impairment assessment. Pill Questionnaire measured the impact in daily activities. PD with Dementia (PDD) and PD with Mild Cognitive Impairment (PDMCI) were defined as the presence of cognitive impairment with or without impact on daily activities. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scales. Significance was set at p < 0.05. From 134 patients, 128 were included. PDD was diagnosed in 21 (16.4%), PDMCI in 31 (24.2%), and 76 (59.4%) had normal cognition (PDCN). SCC were present in 85% of whole cohort and evenly distributed (p = 0.361), PDD (95.2%), PDMCI (83.9%) and PDCN (82.9%). Severity was significantly different between PDD (20.00 ± 10.81), PDMCI (6.54 ± 5.5) and PDCN (6.97 ± 6.98), p < 0.001. A score ≥ 19 had a specificity of 77.3% and a sensitivity of 78.8% for identifying PDD. In PDCN, SCC severity was found to be related to depression (OR 1.23, CI 95% 1.02-1.47, p = 0.026) more than with MoCA scores (OR: 0.86, CI 95% 0.69-1.05, p = 0.141). SCC are common in PD. Their severity can help distinguish PDD from non-demented PD patients. In PDCN, SCC should alert the clinician for an affective disorder.

Polysomnographic data in Dementia with Lewy Bodies: correlation with clinical symptoms and comparison with other α-synucleinopathies.

INTRODUCTION: Sleep dysfunction is frequent in Dementia with Lewy Bodies (DLB), but polysomnographic (PSG) data is scarce. Our objectives were to: (1) compare PSG data between DLB patients and age normative values (NV), Parkinson's Disease (PD) and idiopathic REM sleep behavior disorder (iRBD) patients; (2) evaluate the relation between of OSA, Fluctuations and Hypersomnolence and PSG data. METHODS: We selected all consecutive patients with DLB, PD and iRBD that underwent video-PSG during a two year period. Clinical data was collected by file review. Video-PSG data included sleep structure, Apnea-Hypopnea Index (AHI), REM sleep atonia indexes and video file inspection of motor events (ME) during REM sleep. RESULTS: Subjects: In this study, 19 DLB, 51 PD and 20 iRBD patients participated. Of those, nine DLB (DLB-RBD) and 23 PD (PD-RBD) patients had RBD. Compared to NV, DLB patients had significantly lower sleep efficiency, total sleep time, and REM sleep duration and higher sleep latency, wake after sleep onset and N2 duration. There were no significant relations between PSG data and OSA, hypersomnolence or fluctuations. Sleep latency and AHI were significantly higher and lower, respectively, in DLB compared to PD patients. ME frequency was higher in iRBD. CONCLUSION: DLB patients present significant sleep fragmentation and shortened total and REM sleep time. These changes were not related with OSA, fluctuations or hypersomnolence, suggesting a different pathophysiology. PSG data was similar in the three RBD groups, in accordance with a common neuropathological origin, except for an increase in RBD severity in patients with iRBD.

Heart rate variability in Parkinson disease and idiopathic REM sleep behavior disorder.

PURPOSE: Heart rate variability, a marker of autonomic function modulation, is known to be blunted in Parkinson disease, although data remains conflicting and a putative modifying role of REM sleep behavior disorder persists unclarified. METHODS: We assessed ten patients with idiopathic REM sleep behavior disorder patients, 18 patients with Parkinson disease and REM behavior disorder and eight patients with Parkinson disease without REM sleep behavior disorder. Heart rate variability analysis was performed in 5-min epochs selected from wake, Non-REM and REM polysomnography records. We compared heart rate variability measures by stage between two sets of groups: Parkinson disease vs. idiopathic RBD and patients with vs. without RBD, by using repeated measures ANOVA. RESULTS: There were no heart rate variability differences between Parkinson disease and idiopathic REM sleep behavior disorder groups. There were significant stage vs. group interactions (p = 0.045) regarding the high frequencies components when comparing patients with and without REM sleep behavior disorder, with the former presenting lower values and attenuation of sleep stage variations. CONCLUSION: Our study suggests that RBD is related with reduction in parasympathetic modulation of heart rate variability and blunting of sleep stage related variations.

Stuttering in Parkinson's disease after deep brain stimulation: A note on dystonia and low-frequency stimulation.

Stuttering, a speech fluency disorder, is a rare complication of Deep Brain Stimulation (DBS) in Parkinson's Disease (PD). We report a 61 years-old patient with PD, afflicted by severe On and Off dystonia, treated with Subthalamic Nucleus DBS that developed post-DBS stuttering while on 130 Hz stimulation. Stuttering reduction was noted when frequency was changed to 80 Hz, but the previously observed dystonia improvement was lost. There are no reports in literature on patients developing stuttering with low-frequency stimulation. We question if low-frequency stimulation could have a role for managing PD's post-DBS stuttering, and notice that stuttering improvement was associated with dystonia worsening suggesting that they are distinct phenomena.

Deep brain stimulation for lesion-related tremors: A systematic review and meta-analysis.

Deep brain stimulation (DBS) is an effective treatment for essential tremor or tremor in Parkinson's disease. The effectiveness of DBS in reducing tremors that develop after a structural lesion of the central nervous system (such as Holmes' tremor - HT) has only been addressed in case reports or series. We conducted a systematic review of all published original reports of DBS in central nervous system lesion-related tremor (excluding demyelinating disorders due to their non-static nature). Where available, we extracted data regarding each patient's demographic, tremor and surgical details. Improvement was calculated as a percentage of change in any objective tremor rating scale. We identified 35 publications reporting on 82 patients. The ventral intermedius nucleus(VIM) of the thalamus was the preferred target (63.6%) and 18.2% targeted globus pallidus pars interna(GPi). Median improvement was 77.5% and 71.4% for patients with post-stroke and post-traumatic tremor respectively. Seven subjects (13.5%) had less than 50% improvement. Therapeutic effectiveness was not associated with age, tremor duration, age of onset or follow-up time. A large range of stimulation parameters were used with median voltage, pulse width and frequency values higher for GPi (4.80 V, 105 us, 170 Hz) than for thalamic stimulation (3.0 V, 90 us, 140 Hz). DBS reports for Holmes' and lesional tremors treatment are scarce and highly heterogeneous limiting a proper summary analysis and comparisons. Even facing a probable report bias, a high number of subjects with good long-term tremor control were found. These results should promote the creation of tremor registries before clinical trials.