Assessing the Role of Locus Coeruleus Degeneration in Essential Tremor and Parkinson's Disease with Sleep Disorders.

Background: Previous studies have demonstrated the importance of the locus coeruleus (LC) in sleep-wake regulation. Both essential tremor (ET) and Parkinson's disease (PD) share common sleep disorders, such as poor quality of sleep (QoS). LC pathology is a feature of both diseases. A question arises regarding the contribution of LC degeneration to the occurrence of poor QoS. Objective: To evaluate the association between LC impairment and sleep disorders in ET and PD patients. Methods: A total of 83 patients with ET, 124 with PD, and 83 healthy individuals were recruited and divided into ET/PD with/without poor QoS (Sle/NorET and Sle/NorPD) subgroups according to individual Pittsburgh Sleep Quality Index (PSQI) score. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and free-water imaging derived from diffusion MRI were performed. Subsequently, we evaluated the association between contrast-to-noise ratio of LC (CNRLC) and free-water value of LC (FWLC) with PSQI scores in ET and PD groups. Results: CNRLC was significantly lower in ET (p = 0.047) and PD (p = 0.018) than in healthy individuals, whereas no significant difference was found in FWLC among the groups. No significant differences were observed in CNR/FWLC between patients with/without sleep disorders after multiple comparison correction. No correlation was identified between CNR/FWLC and PSQI in ET and PD patients. Conclusions: LC degeneration was observed in both ET and PD patients, implicating its involvement in the pathophysiology of both diseases. Additionally, no significant association was observed between LC integrity and PSQI, suggesting that LC impairment might not directly relate to overall QoS.

Comparing Essential Tremor with and without Soft Dystonic Signs and Tremor Combined with Dystonia: The TITAN Study.

BACKGROUND: Tremor disorders remain as clinical diagnoses and the rate of misdiagnosis between the commonest non-parkinsonian tremors is relatively high. OBJECTIVES: To compare the clinical features of Essential Tremor without other features (pure ET), ET plus soft dystonic signs (ET + DS), and tremor combined with dystonia (TwD). METHODS: We compared the clinical features of patients with pure ET, ET + DS, and TwD enrolled in The ITAlian tremor Network (TITAN). Linear regression models were performed to determine factors associated with health status and quality of life. RESULTS: Three-hundred-eighty-three patients were included. Sex distribution was significantly different between the groups with males being more represented in pure ET and females in TwD. The initial site of tremor was different between the groups with about 40% of TwD having head tremor and ET + DS unilateral upper limb tremor at onset. This pattern mirrored the distribution of overt dystonia and soft dystonic signs at examination. Sensory trick, task-specificity, and position-dependence were more common, but not exclusive, to TwD. Pure ET patients showed the lowest degree of alcohol responsiveness and ET + DS the highest. Midline tremor was more commonly encountered and more severe in TwD than in the other groups. Regression analyses demonstrated that tremor severity, sex, age, and to a lesser degree the variable "group", independently predicted health status and quality of life, suggesting the existence of other determinants beyond tremor. CONCLUSIONS: Pure ET and TwD manifest with a phenotypic overlap, which calls for the identification of diagnostic biomarkers. ET + DS shared features with both syndromes, suggesting intra-group heterogeneity.

The association between motor and non-motor symptoms in essential tremor patients being evaluated for deep brain stimulation surgery.

BACKGROUND: Non-motor symptoms, including depression and cognitive impairment, are common in essential tremor (ET), but associations between these symptoms and tremor are poorly understood. METHODS: A retrospective, single-institution, cohort study evaluated 140 patients with ET undergoing evaluation for deep brain stimulation (DBS) surgery. The Fahn-Tolosa-Marin (FTM) or Washington Heights-Inwood Genetic Study of ET (WHIGET) scale was used to grade tremor. Tremor scores were divided into quartiles. Patients underwent clinical neuropsychological evaluations that included a comprehensive cognitive test battery and Beck Depression Inventory-II (BDI-II). Subgroup analysis was performed with groups who met criteria for depression (BDI-II > 14) or overall cognitive impairment (<9th percentile on at least two dissimilar cognitive tests). Independent samples t-tests were used for continuous variables and chi square tests for categorical variables. Univariable and multivariable regressions were used to determine relationships between tremor and non-motor scores. RESULTS: Tremor quartile was correlated with language domain performance (p = 0.044) but not depression scores. FTM score was associated with BDI-II (ß = 0.940, p = 0.010), language (ß = -0.936, p = 0.012), and visuospatial domain (ß = -0.836, p = 0.025) scores, such that worse tremor was associated with more depression and worse language and visuospatial function. WHIGET score was not associated with any neuropsychological scores on multivariable regression. CONCLUSION: FTM score was associated with language, visuospatial, and mood symptoms, suggesting a relationship between the severity of these symptom types. Different tremor scores capture different motor symptoms and relationships with nonmotor symptoms.

Sleep problems as predictors of cognitive decline in essential tremor: A prospective longitudinal cohort study.

BACKGROUND: There is growing evidence that essential tremor (ET) patients are at high risk of cognitive impairment. Predictors of cognitive impairment have not been studied extensively. There is evidence from cross-sectional studies that sleep dysregulation is associated with cognitive dysfunction in ET, but longitudinal studies of the impact of sleep disruption on cognitive change have not been conducted. We investigated the extent to which sleep problems predict cognitive change in patients with ET. METHODS: ET cases enrolled in a prospective, longitudinal study of cognitive performance. Sleep quality was assessed using the Pittsburg Sleep Quality Index (PSQI). Cognitive abilities across five domains (memory, executive function, attention, language, and visuospatial ability), and a global cognitive score (mean of the domains) were extracted from an extensive neuropsychological assessment. Generalized estimated equations were used to examine the association between baseline sleep problems and cognitive changes over three follow-up assessments each spaced 18 months apart. RESULTS: The 188 non-demented ET cases had a mean age of 77.7 ± 9.5 years. Longer sleep latency was associated with longitudinal decline in executive function (p = 0.038), and marginally with longitudinal decline in global cognitive performance (p = 0.075). After excluding 29 cases with mild cognitive impairment, results were similar. CONCLUSION: Cognitively healthy people with ET who have longer sleep latency had greater declines in executive function during prospective follow-up. Early detection of, and possibly intervention for, abnormal sleep latency may protect against certain aspects of cognitive decline in ET patients.

The cognitive profile of essential tremor on the Repeatable Battery for the Assessment of Neuropsychological Status.

Objective: Essential tremor (ET), while defined by progressive motor symptoms, is increasingly associated with cognitive impairments (e.g. attention, memory, and executive functions). This study characterizes the cognitive profile of individuals with ET on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a commonly-used neuropsychological screening measure. Method: Seventy-seven individuals (mean age: 70.6, 34% female) diagnosed with ET and being considered for surgical/procedural intervention were recruited from a Movement Disorders Clinic. All participants completed the RBANS, Grooved Pegboard Test (GPB), and Fahn, Tolosa, Marin Tremor Scale (FTMTS) in the clinical evaluation of their tremor. Results: One-sample t-tests found Immediate Memory, Language, Attention, and Total Scale Index scores to be significantly lower than the expected population mean (p < .05). List Learning, Semantic Fluency, Coding, and List Recall subtests were significantly lower and Picture Naming was significantly higher than the expected population mean (p < .05). GPB scores were correlated with the Attention Index as well as List Learning and Coding subtests. FTMTS Severity was correlated with the Coding subtest and FTMTS Disability was correlated with the Figure Recall subtest. Conclusions: Results support prior literature indicating cognitive weaknesses in those with ET. Individuals with ET had poorer global cognitive abilities, with specific decrements in Immediate Memory, Attention, and Language. Notably, the Attention Index and Coding subtest were most affected by motor functioning. Cognitive screening measures, like the RBANS, can efficiently identify strengths and weaknesses in individuals with ET seeking surgical/procedural interventions.

Perception of cognitive change by individuals with Parkinson's disease or essential tremor seeking deep brain stimulation: Utility of the cognitive change index.

OBJECTIVE: The Cognitive Change Index (CCI-20) is a validated questionnaire that assesses subjective cognitive complaints (SCCs) across memory, language, and executive domains. We aimed to: (a) examine the internal consistency and construct validity of the CCI-20 in patients with movement disorders and (b) learn how the CCI-20 corresponds to objective neuropsychological and mood performance in individuals with Parkinson's disease (PD) or essential tremor (ET) seeking deep brain stimulation (DBS). METHODS: 216 participants (N = 149 PD; N = 67 ET) underwent neuropsychological evaluation and received the CCI-20. The proposed domains of the CCI-20 were examined via confirmatory (CFA) and exploratory (EFA) factor analyses. Hierarchical regressions were used to assess the relationship among subjective cognitive complaints, neuropsychological performance and mood symptoms. RESULTS: PD and ET groups were similar across neuropsychological, mood, and CCI-20 scores and were combined into one group who was well educated (m = 15.01 ± 2.92), in their mid-60's (m = 67.72 ± 9.33), predominantly male (63%), and non-Hispanic White (93.6%). Previously proposed 3-domain CCI-20 model failed to achieve adequate fit. Subsequent EFA revealed two CCI-20 factors: memory and non-memory (p < 0.001; CFI = 0.924). Regressions indicated apathy and depressive symptoms were associated with greater memory and total cognitive complaints, while poor executive function and anxiety were associated with more non-memory complaints. CONCLUSION: Two distinct dimensions were identified in the CCI-20: memory and non-memory complaints. Non-memory complaints were indicative of worse executive function, consistent with PD and ET cognitive profiles. Mood significantly contributed to all CCI-20 dimensions. Future studies should explore the utility of SCCs in predicting cognitive decline in these populations.

The Spectrum of Non-Parkinsonian Tremor: A Registry at a Tertiary Care Teaching Institute.

Background: Tremors other than those associated with Parkinson's disease (non-parkinsonian tremor) are commonly observed in clinical settings. However, their frequency and clinical characteristics have rarely been reported. Objectives: To classify non-parkinsonian tremors based on the consensus statement on the classification of tremors, from the task force of the International Parkinson and Movement Disorder Society published in 2018. Methods: A prospective registry at a tertiary care teaching institute. Results: A total of 475 patients with non-parkinsonian tremors were recruited for the study. 67.57% (n = 321) of our patients were male and a family history of tremor was present in 20.84% (n = 99) of patients. Dystonic tremor (DT) was the most common non-parkinsonian tremor (33.26%). 27.78% of patients fulfilled the new classification criteria for essential tremor, with 13.47% classified as pure ET (ET) and 14.31% exhibiting neurological soft signs, leading to the classification of ET plus (ETP). Patients with ETP had more family history (57.35%) [vs DT (26.48%, p = 0.00004) and ET (10.93%, p = 0.00003], longer duration of disease [mean ± standard deviation (SD) = 9.53 ± 8.64 years] [vs DT (5.60 ± 5.93, p = 0.0003) and ET (6.38 ± 5.97, p = 0.01) years], and more severe tremor as measured by the essential tremor rating assessment scale total score [mean ± SD = 27.42 ± 11.70] [vs DT (23.50 ± 8.62, p = 0.007) and ET (22.12 ± 8.19, p = 0.007)] compared with patients with DT and ET. Conclusions: DT was the most common cause of non-parkinsonian tremor in our registry followed by essential tremor syndrome. ETP was more common than ET.

Comparison of core and process scores on the California Verbal Learning Test-3 for Parkinson's disease and essential tremor patients.

INTRODUCTION: Parkinson's disease (PD) and essential tremor (ET) are two disorders known to lead to executive dysfunction, presumably through distinct pathways to the frontal lobes via the striatum or cerebellum, respectively. Memory functioning in PD and ET patients has been previously suggested to be adversely impacted by executive dysfunction. The aims of this exploratory study were to compare memory performance between and within groups on the California Verbal Learning Test - 3 (CVLT-3) through the analysis of core and process scores and to understand the relationship of these scores with measures of executive functioning. METHOD: Seventy PD and 54 ET patients completed comprehensive neuropsychological testing. Independent sample t-tests or Mann-Whitney tests were used to compare between group core and process scores on the CVLT-3. Within-subjects analyses were conducted via Wilcoxon Signed Rank Test due to nonparametric data. Spearman's correlations were conducted to explore the relationship between memory process scores and measures of executive functioning. RESULTS: The ET and PD samples were similar with regard to age, education, gender, and general cognitive functioning. PD patients made more repetition errors (U = 2391.50, p = .01) than ET patients and Normal Memory PD patients made more repetition errors than Low Memory PD patients (U= 711.00, p= .00). Correlational analyses revealed repetition errors were negatively associated with tests of inhibition, set shifting, and working memory (rs = -.293, -.232). ET patients demonstrated a preference for a serial cluster learning strategy (T = 861.00, p = .005), similar to PD patients (T= 1633.00, p = <.001). CONCLUSIONS: The study revealed presence of higher repetition errors in the PD sample that was demonstrated to have a negative relationship with measures of executive functioning. Implications for investigating process ("qualitative") scores in memory performance to determine extent of executive involvement are discussed.

Risk of neurodegenerative diseases in patients with sleep disorders: A nationwide population-based case-control study.

OBJECTIVE: Our study aimed to explore the associative relationship between neurodegenerative diseases and sleep disorders. PATIENTS: This 15-year retrospective longitudinal nationwide population-based matched case-control study used data extracted from the National Health Insurance Research Database. We evaluated 25,589 patients diagnosed with neurodegenerative diseases between 2000 and 2015 and a matched control of 102,356 patients without neurodegenerative diseases. RESULTS: Sleep disorders were an independent risk factor for the development of neurodegenerative diseases (adjusted odds ratio (OR): 1.794, 95% confidence interval (CI): 1.235-2.268, P < 0.001), with a positive dose-effect relationship (adjusted OR (95% CI): <1 year: 1.638 (1.093-2.872), P < 0.001; 1-5 years: 1.897 (1.260-3.135), P < 0.001; >5 years: 2.381 (1.467-3.681), P < 0.001. Moreover, patients with sleep disorder and comorbid depression had a significantly higher risk of neurodegenerative disorders (adjusted OR: 5.874). Subgroup analysis showed that insomnia was associated with Alzheimer's disease, Pick's disease and essential tremor (adjusted OR (95% CI): 1.555 (1.069-1.965), 1.934 (1.331-2.445) and 2.089 (1.439-2.648), respectively). Obstructive sleep apnea was associated with Parkinson's disease, essential tremor, and primary dystonia (adjusted OR (95% CI): 1.801 (1.239-2.275), 5.523 (3.802-6.977), and 4.892 (3.365-6.178), respectively). Other specific sleep disorders were associated with Pick's disease, Parkinson's disease, essential tremor, and primary dystonia (adjusted OR (95% CI): 8.901 (6.101-11.010), 1.549 (1.075-1.986), 2.791 (1.924-3.531), and 9.114 (6.283-10.506), respectively). CONCLUSION: Sleep disorders are associated with the subsequent development of neurodegenerative disorders. Moreover, sleep disorder patients with comorbid depression have a higher risk of neurodegenerative diseases.

Associations between cognitive function and a range of significant life events in an elderly essential tremor cohort study.

BACKGROUND: Although essential tremor (ET) is associated with cognitive decline, we know little about how specific cognitive changes predict significant events in patients' lives. We examined the relations of attention, executive function, language, memory, and visuospatial performance to the occurrence of near falls, falls, walking aid use, home health aide use, non-independent living and hospitalizations within a prospective, longitudinal study of ET cases. We expected executive function and memory to be most strongly associated with these events. METHODS: 131 ET cases (mean age at baseline = 76.4 ± 9.4 years; 109 normal cognition; 17 mild cognitive impairment, 5 demented) completed questionnaires (clinical history and occurrence of life events) and a battery of neuropsychological tests at baseline and at 18, 36, and 54 months. We assessed associations between cognitive functioning and outcomes via regression equations. RESULTS: Cases with lower baseline levels of executive function reported more near falls, p < 0.006, and were more likely to use a walking aid, p < 0.03, odds ratio (OR) = 2.89 during the follow-up period, than were other cases. Decline in executive function was associated with home health aide use during follow-up, p < 0.04, OR = 3.34. Baseline visuospatial performance also bore a marginally significant association with non-independent living arrangements during follow-up, p < 0.06, OR = 2.13. These effects were independent of age and tremor severity. CONCLUSION: These data establish the important role that cognitive decline, and executive function specifically, play in the experiences of ET patients. Moreover, these associations are of sufficient magnitude to have significant clinical implications.

Skin-related complications following deep brain stimulation surgery: A single-center retrospective analysis of 525 patients who underwent DBS surgery.

BACKGROUND: Although Deep Brain Stimulation (DBS) is a safe and proven treatment modality for patients suffering from debilitating movement and neuropsychiatric disorders, it is not free from complications. Management of skin erosion and infection following DBS surgery constitutes a challenge in everyday clinical practice. OBJECTIVES: Skin-related complications were evaluated in patients who underwent DBS surgery due to Parkinson's disease (PD), dystonia, essential tremor (ET), and other indications including Tourette syndrome (TS), Obsessive-Compulsive Disorder (OCD), and epilepsy. METHODS: A retrospective analysis of clinical data was performed on patients who underwent DBS surgery between November 2008 and September 2021 at the Department of Neurosurgery, Institute of Psychiatry and Neurology, Warsaw. RESULTS: 525 patients who underwent 927 DBS leads implantations were included in the analysis. There were 398 patients with PD, 80 with dystonia, 26 with ET, 7 with drug-resistant epilepsy, 5 with Multiple Sclerosis, 4 with Holme's or cerebellar tremor, 3 with TS, and 2 with OCD. 42 patients (8,0%) had 78 skin infection episodes. The overall level of skin erosion was 3,8% (20/525 patients). The risk of developing infection episode was connected with younger age at diagnosis (p = 0.017) and at surgery (p = 0.023), whereas the development of skin erosion was connected with the dystonia diagnosis (p = 0.012). Patients with dystonia showed the highest rate of infections and erosions (11/70 and 7/70 patients retrospectively). DISCUSSION: Postoperative skin complications are a serious side effect of DBS surgery. CONCLUSION: Our study suggests that dystonic patients are at higher risk of developing skin-related complications after DBS surgery.

Can the Montreal Cognitive Assessment and Mini-Mental State Examination detect cognitive decline in elderly patients with essential tremor?

Objective Given the association between essential tremor (ET) and higher rates of cognitive decline, assessing this decline is an important element of research and clinical care. The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are two broad, brief measures that are widely used to monitor cognitive impairment in various neurological disorders. We sought to determine the relative ability of the MoCA and the MMSE to detect cognitive decline in elderly patients with ET. Methods We administered a neuropsychological battery to an ET cohort every 18 months over 4.5 years. We defined the gold standard for change in cognition as the change in neuropsychological test scores over consecutive evaluations and applied the Reliable Change Method to detect meaningful increases/decreases in test scores. We performed receiver operating characteristics (ROC) analysis to quantify the area under the curve (AUC) and compare the ability of the MoCA and the MMSE to detect cognitive decline. Results The AUCs for the MoCA and the MMSE did not differ significantly at any interval or when all intervals were pooled for analysis. Across all intervals, the ability of the MoCA and the MMSE to detect cognitive decline was consistently fair or poor. Conclusions We found that the ability of the MoCA and the MMSE to detect cognitive decline in ET patients over 18-month intervals is inadequate. Unchanged scores on the MoCA and the MMSE in ET over time should be approached with caution. We propose that these screening tools should be supplemented with additional neuropsychological tests.

Analyses of correct responses and errors on measures of verbal fluency among Parkinson's disease and essential tremor patients.

Objective: Parkinson's disease (PD) and essential tremor (ET) involve neuroanatomical circuitry that impact frontal lobe functioning, via the striatum and cerebellum, respectively. The aim of this exploratory study was to investigate quantitative and qualitative performance between and within these groups on measures of verbal fluency. Method: Sixty-three PD and 53 ET patients completed neuropsychological testing. Linear regression models with robust variance estimation compared verbal fluency performance between groups related to correct responses and errors. Paired t-tests investigated within group error rates. Results: PD patients gave more correct responses for phonological (ß̂ =5.3, p=.01) and category fluency (ß̂ =4.1, p=.01) than ET patients; however, when processing speed was added as a covariate, this attenuated performance on both measures and only phonological fluency remained significant (ß̂ =4.0, p=.04). There were no statistical differences in error scores between groups. Error rates within groups suggested that PD patients had higher error rates in total errors and perseveration errors on phonological fluency (M = 2.6, p=.00; M = 1.6, p=.00) and higher total errors and set-loss error rates on category switching (M = 5.1, p<.001; M = 4.1, p<.001). ET patients had higher error rate with relation to total errors and set-loss errors on phonological fluency (M = 2.5, p=.00; M = 1.5, p=.02) and category switching (M = 3.9, p=,00; M = 3.9, p<.001). Conclusions: PD patients performed better than ET patients on phonological fluency. PD patients appear to make more perseveration errors on phonological fluency, while ET patients made more set-loss errors. Implications for frontal lobe dysfunction and clinical impact are discussed.

Onset and mortality of Parkinson's disease in relation to type II diabetes.

OBJECTIVES: There is growing evidence that Parkinson's disease and diabetes are partially related diseases; however, the association between the two, and the impact of specific treatments, are still unclear. We evaluated the effect of T2D and antidiabetic treatment on age at PD onset and on all-cause mortality. RESEARCH DESIGN AND METHODS: The standardized rate of T2D was calculated for PD patients using the direct method and compared with subjects with essential tremor (ET) and the general Italian population. Age at onset and survival were also compared between patients without T2D (PD-noT2D), patients who developed T2D before PD onset (PD-preT2D) and patients who developed T2D after PD onset (PD-postT2D). RESULTS: We designed a retrospective and prospective study. The T2D standardized ratio of PD (N = 8380) and ET (N = 1032) patients was 3.8% and 6.1%, respectively, while in the Italian general population, the overall prevalence was 5.3%. In PD-preT2D patients, on antidiabetic treatment, the onset of PD was associated with a + 6.2 year delay (p < 0.001) while no difference was observed in PD-postT2D. Occurrence of T2D before PD onset negatively affected prognosis (adjusted hazard ratio = 1.64 [95% CI 1.33-2.02]; p < 0.001), while no effect on survival was found in PD-postT2D subjects (hazard ratio = 0.86, [95% CI 0.53-1.39]; p = 0.54). CONCLUSIONS: T2D, treated with any antidiabetic therapy before PD, is associated with a delay in its onset. Duration of diabetes increases mortality in PD-preT2D, but not in PD-postT2D. These findings prompt further studies on antidiabetic drugs as a potential disease-modifying therapy for PD.

Closed loop deep brain stimulation: A systematic scoping review.

BACKGROUND: At the turn of the 21st century, closed-loop deep brain stimulation (CL-DBS) systems have emerged as promising neuromodulatory treatment strategies, that integrate real-time feedback based on the brain's condition to fine-tune the stimulation being applied. CL-DBS promises numerous advantages over open-loop deep brain stimulation (OL-DBS) systems. However, no up-to-date review articles are available which characterise the clinical outcomes of CL-DBS therapy. METHODS: A systematic literature search was conducted in seven major databases with various keywords relating to CL-DBS, for non-randomised cohort studies, finalised clinical trials, case reports, and nonrandomised control trials published between 2011 and 2021. RESULTS: Seven studies satisfied our inclusion criteria. Six investigated the use of CL-DBS therapy for neurological disorders, while one investigated its use for psychiatric disorders. The average patient age was 61 years (range: 27 - 78), and the mean disease duration before CL-DBS therapy was 15 years (range: 4 - 47). Patients included with essential tremor (ET) (n = 11) were older than patients with freezing of gait (FoG) in Parkinson's disease (PD) (n = 6) (p = 0.009), albeit insignificantly longer disease duration (p = 0.199). Following CL-DBS intervention, patients with ET (n = 11), major depressive disorder (n = 1) and Tourette syndrome (n = 1) had improvements in clinical outcomes, while PD patients had heterogeneous outcomes (n = 7). CL-DBS systems utilised by the included studies demonstrated a mean of 51.94 % (range: 36.62 - 68) energy-saving capacity over OL-DBS systems. CONCLUSIONS: To date, there is insufficient evidence that CL-DBS offers significant superior clinical outcomes over OL-DBS. Our scoping review suggests that CL-DBS can improve symptoms of specific neurological and psychiatric disorders, whilst demonstrating improved energy-saving capacity which has the potential to decrease battery replacement surgeries. Real-time adjustment of patients' symptoms using CL-DBS may improve patients' overall quality of life. Further studies are required to validate our observations.

Aligning Dentato-Rubro-Thalamic Tract and Subthalamic Nucleus Targets in a Patient with Comorbid Essential Tremor and Parkinson's Disease: Case Report.

Deep brain stimulation is an established treatment option for both essential tremor (ET) and Parkinson's disease (PD), although typically targeting different brain structures. Some patients are diagnosed with comorbid ET and PD. Selecting the optimal stimulation target in these patients is challenging. We present a patient with comorbid ET and PD in whom we used bilaterally a single parietal trajectory to align the dentato-rubro-thalamic tract and the subthalamic nucleus. Although parietal trajectories are challenging, we reached satisfactory outcomes for both conditions without complications. Single-electrode deep brain stimulation of the dentato-rubro-thalamic tract and the subthalamic nucleus through a parietal approach may represent a feasible treatment option in this patient group.

Cluster analysis of clinical, biochemical and electrophysiological features of essential tremor patients. Exploratory study.

BACKGROUND: Essential tremor (ET) is one of the most common movement disorders. The clinical heterogeneity of ET has been studied for many years, however, there are practically no comprehensive studies dedicated to the assessment of biochemical and electrophysiological parameters associated with the severity of motor and non-motor disorders present in patients with ET and taking into account their heterogeneity. OBJECTIVES: The objective of this report is to differentiate subgroups of essential tremor using cluster analysis of clinical, biochemical and electrophysiological parameters. METHODS: The study enrolled 90 patients with ET. Clustering was perform on the demographic data, scores of scales FTMS, ADL, MoCA, Beka, surface electromyographic data, levels of serum IL-1ß, IL-6, IL-8, IL-10, TNFα, uric acid, ceruloplasmin, MDA. RESULTS: Based on the analysis of the severity of motor manifestations, the psychoemotional state, the adaptive potential of patients and the biochemical aspects of the pathogenesis, three relatively homogeneous clusters of ET were identified. CONCLUSIONS: Revealing the heterogeneity of essential tremor allows to expand understanding the pathogenesis of disease.

Non-motor features of essential tremor with midline distribution.

BACKGROUND: Midline essential tremor (Mid-ET) is a distinctive group of essential tremor (ET) in which tremor affects the neck, jaw, tongue, and/or voice. For long, it has been considered as an ultimate stage of the disease and a marker of its severity. However, recent studies pointed its complexity in terms of non-motor presentation. Thus, we aimed to investigate the non-motor signs (NMS) in Mid-ET. DESIGN: We conducted a cross-sectional study in a tertiary neurology referral center including ET patients classified into two groups based on the presence or not of midline tremor (Mid-ET vs. No-Mid-ET). We assessed NMS using the non-motor severity scale (NMSS), a large battery of cognitive tests, clinical and electrophysiological study of the autonomic nervous system along with the evaluation of sleep disturbances. RESULTS: A total of 163 patients were included: Mid-ET (n = 79) and No-Mid-ET (n = 84) matched in gender and age of onset. Mid-ET patients had higher proportion of late-onset ET (> 60 years old, p = 0.002) and more extrapyramidal signs (p = 0.005). For NMS, Mid-ET was marked with cognitive dysfunction (p = 0.008). The hallmarks of the neuropsychiatric profile of Mid-ET were executive dysfunction (p = 0.004), attention problems (p < 0.000), episodic memory impairment (p = 0.003), and greater depression (p = 0.010). The presence of RBD was a trait of Mid-ET (p = 0.039). In both Mid-ET and No-Mid-ET phenotypes, clinical and neurophysiological dysautonomia correlated with cognitive dysfunction. CONCLUSION: Mid-ET patients had greater cognitive dysfunction, depression, RBD, higher proportion of late-onset ET, and more extrapyramidal signs. Taken all together, these findings could provide a redesigned insight into the underlying physiopathology of Mid-ET indicative of a greater cerebellar dysfunction.

New horizons in late-onset essential tremor: a pre-cognitive biomarker of dementia?

Essential tremor (ET) is the most common cause of tremor in older adults. However, it is increasingly recognised that 30-50% of ET cases are misdiagnosed. Late-onset ET, when tremor begins after the age of 60, is particularly likely to be misdiagnosed and there is mounting evidence that it may be a distinct clinical entity, perhaps better termed 'ageing-related tremor'. Compared with older adults with early-onset ET, late-onset ET is associated with weak grip strength, cognitive decline, dementia and mortality. This raises questions around whether late-onset ET is a pre-cognitive biomarker of dementia and whether modification of dementia risk factors may be particularly important in this group. On the other hand, it is possible that the clinical manifestations of late-onset ET simply reflect markers of healthy ageing, or frailty, superimposed on typical ET. These issues are important to clarify, especially in the era of specialist neurosurgical treatments for ET being increasingly offered to older adults, and these may not be suitable in people at high risk of cognitive decline. There is a pressing need for clinicians to understand late-onset ET, but this is challenging when there are so few publications specifically focussed on this subject and no specific features to guide prognosis. More rigorous clinical follow-up and precise phenotyping of the clinical manifestations of late-onset ET using accessible computer technologies may help us delineate whether late-onset ET is a separate clinical entity and aid prognostication.

Spectrum of movement disorders: Experience of a one and half year of existence of the first specialized center in Senegal.

BACKGROUND: Movement disorders have different prevalence in different regions and they are little studied in Africa. OBJECTIVES: Evaluate the prevalence and determine the spectrum of movement disorders in the first specialized center in Senegal. METHODS: It was a prospective study over on 18 months in adult outpatient clinic. Demographic, clinical, paraclinical data, including genetic test in collaboration with the Queen Square Institute of Neurology at UCL were collected. RESULTS: One hundred and thirty four patients were followed up, representing a prevalence of 4.7%. Men represented 56% for a sex ratio of 1.3. The mean age of population was 47.7 ± 18 years with limits ranging from 16 to 81 years. Eighty-one patients (60.4%) had hyperkinetic and 53 patients (39.6%) had hypokinetic movements. Twenty-nine patients (21.6%) had tremors and 18 (13.4%) had dystonic movements. Ataxia and choreic movements were respectively in 11 (8.2%) and 10 patients (7.5%). Twenty-four patients (17.9%) were from a first-degree consanguineous. A genetic test on saliva samples was done in 16 patients (11.9%) and confirmed Huntington's disease in 8 patients of 6 families. Parkinson disease was the most frequent etiology (32.8%) followed by essential tremor (12.7%) and psychogenic tremor in 7.5%. Stroke accounted for 6% of the causes of MD (tremor, ballism, dystonia, ataxia and parkinsonism) and no etiology was found in 9%. CONCLUSION: The spectrum of movement disorders is very heterogeneous with a non-negligible frequency and diverse etiologies in neurological practice in Senegal.