Background and Purpose—Embolic stroke of undetermined source (ESUS) designates patients with nonlacunar cryptogenic ischemic strokes in whom embolism is the likely stroke mechanism. It has been hyp...

Embolic Stroke of Undetermined Source: A Systematic Review and Clinical Update.

Background: Non-motor symptoms (NMSs) are a real burden in Parkinson's disease (PD). They may appear in early pre-symptomatic stage as well as throughout the disease course. However, their relationship with the deterioration of the patient's quality of life (QoL) is still under debate. The present study aimed to investigate the prevalence of NMSs and their impact on the QoL in a cohort of Moroccan patients. Methods: We carried out a cross-transactional study where a total of 117 patients were submitted to a structured clinical interview and examination investigating motor and NMSs based on common and conventional scales. Motor symptoms were assessed by the UPDRS I to VI during ON condition. The NMSs were evaluated with common scales and their relationship with the QoL was investigated. Results: The mean patient's age was 60.77±11.36 years-old, and the median disease duration was 6 years [2.5-9.5]. Motor's phenotype subtypes were the mixed form in 40.2% of patients, akinetic-rigid in 20.5% and a tremor-dominant form in 39.3%. The median Hoehn and Yahr staging was 2 [1-2.5]. Regarding NMSs, the most common were urinary dysfunctions (82.6%), sleep (80.6%) and gastrointestinal (80%) disorders. Other autonomic dysfunctions were also frequent: thermoregulatory dysfunctions 58.6%, cardiovascular troubles 50.9% and sexual dysfunctions 47.9%. Depression was present in 47.9% and fatigue symptoms in 23.1%. The median score of SCOPA-AUT was 14 [7.75-21.80]. The median PD questionnaire 39-Score index (PDQ39-SI) was 23.22% and the most affected dimension was "mobility". Univariate and multivariate analyses showed that the SCOPA-AUT score impacted the QoL (p=0.001), especially the gastrointestinal (p=0.007), and cardiovascular (p=0.049) dimensions. Conclusion: Our data show that all patients have presented at least one NMS. Autonomic and sleep disorders were the most frequent, and in contrast to other studies, digestive and cardiovascular disorders were rather the factors influencing negatively the QoL of patients. Understanding the pathophysiology of these NMSs should be placed at the forefront in order to develop new therapeutic approaches improving the QoL of PD patients.

/pdf/non-motor-symptoms-of-parkinson-s-disease-and-their-impact-u74p1tw7qm.pdf

Non-Motor Symptoms of Parkinson’s Disease and Their Impact on Quality of Life in a Cohort of Moroccan Patients

Motor symptoms in Parkinson’s disease (PD) are tightly linked to the degeneration of substantia nigra dopaminergic neurons and their projections into the striatum. Moreover, a broad range of non-motor symptoms like anxiety and depression frequently occur in PD, most likely related to the loss of serotonergic neurons and their projections into corresponding targets. Strikingly, nigral dopaminergic neurons and raphe serotonergic neurons are severely affected in PD showing characteristic hallmarks of PD neuropathology, in particular alpha-synuclein containing Lewy bodies and Lewy neurites. So far, the initial events underlying neurodegenerative processes in PD are not well understood. Several observations, however, indicate that neurites and synapses of diseased neurons may be the first subcellular compartments compromised by alpha-synuclein associated pathology. In particular axonal pathology and deficits in axonal transport may be leading to the onset of synucleinopathies such as PD. This review will highlight current findings derived from imaging and neuropathological studies in PD patients, as well as cellular and animal PD models, which define the initial underlying structural and molecular events within dopaminergic and serotonergic circuits leading to the ‘dying back’ degeneration of axonal projections in PD.

/pdf/early-degeneration-of-both-dopaminergic-and-serotonergic-56t1n82hyj.pdf

Early Degeneration of Both Dopaminergic and Serotonergic Axons - A Common Mechanism in Parkinson's Disease.

Background The objective of this study was to investigate 24-month of effects of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on nonmotor symptoms in Parkinson's disease (PD). Methods In this prospective, observational, multicenter, international study including 67 PD patients undergoing bilateral STN-DBS, we examined the Non-motor Symptom Scale, Non-Motor Symptoms Questionnaire, Parkinson's Disease Questionnaire-8, Scales for Outcomes in Parkinson's Disease-motor examination, -activities of daily living, and -complications, and levodopa-equivalent daily dose preoperatively and at 5 and 24-month of follow-up. After checking distribution normality, longitudinal outcome changes were investigated with Friedman tests or repeated-measures analysis of variance and Bonferroni correction for multiple comparisons using multiple tests. Post hoc, Wilcoxon signed rank t tests were computed to compare visits. The strength of clinical responses was analyzed using effect size. Explorative Spearman correlations of change scores from baseline to 24-month follow-up were calculated for all outcomes. Results The Non-motor Symptom Scale and all other outcome parameters significantly improved from baseline to the 5-month follow-up. From 5 to 24-month, partial decrements in these gains were found. Nonetheless, comparing baseline with 24-month follow-up, significant improvements were observed for the Non-motor Symptom Scale (small effect), Scales for Outcomes in PD-motor examination showed a moderate effect, and Scales for Outcomes in Parkinson's Disease-complications and levodopa-equivalent daily dose showed large effects. Non-motor Symptom Scale change scores from baseline to 24-month follow-up correlated significantly with Parkinson's Disease Questionnaire-8, Scales for Outcomes in Parkinson's Disease-activities of daily living, and -motor complications change scores. Conclusions This study provides evidence of beneficial effects of bilateral STN-DBS on nonmotor symptoms at 24-month follow-up. The extent of nonmotor symptom improvement was directly proportionate to improvements in quality of life, activities of daily living, and motor complications. This study underlines the importance of nonmotor symptoms for holistic assessments of DBS outcomes. © 2018 International Parkinson and Movement Disorder Society.

Nonmotor symptoms evolution during 24 months of bilateral subthalamic stimulation in Parkinson's disease.

An ever-expanding number of disease-modifying drugs for multiple sclerosis have become available in recent years, after demonstrating efficacy in clinical trials. In the real-world setting, however, disease-modifying drugs are prescribed in patient populations that differ from those included in pivotal studies, where extreme age patients are usually excluded or under-represented. In this multicentre, observational, retrospective Italian cohort study, we evaluated treatment exposure in three cohorts of patients with relapsing-remitting multiple sclerosis defined by age at onset: paediatric-onset (≤18 years), adult-onset (18-49 years) and late-onset multiple sclerosis (≥50 years). We included patients with a relapsing-remitting phenotype, ≥5 years follow-up, ≥3 Expanded Disability Status Scale (EDSS) evaluations and a first neurological evaluation within 3 years from the first demyelinating event. Multivariate Cox regression models (adjusted hazard ratio with 95% conﬁdence intervals) were used to assess the risk of reaching a first 12-month confirmed disability worsening and the risk of reaching a sustained EDSS of 4.0. The effect of disease-modifying drugs was assessed as quartiles of time exposure. We found that disease-modifying drugs reduced the risk of 12-month confirmed disability worsening, with a progressive risk reduction in different quartiles of exposure in paediatric-onset and adult-onset patients [adjusted hazard ratios in non-exposed versus exposed >62% of the follow-up time: 8.0 (3.5-17.9) for paediatric-onset and 6.3 (4.9-8.0) for adult-onset, P < 0.0001] showing a trend in late-onset patients [adjusted hazard ratio = 1.9 (0.9-4.1), P = 0.07]. These results were confirmed for a sustained EDSS score of 4.0. We also found that relapses were a risk factor for 12-month confirmed disability worsening in all three cohorts, and female sex exerted a protective role in the late-onset cohort. This study provides evidence that sustained exposure to disease-modifying drugs decreases the risk of disability accumulation, seemingly in a dose-dependent manner. It confirms that the effectiveness of disease-modifying drugs is lower in late-onset patients, although still detectable.

/pdf/disease-modifying-drugs-can-reduce-disability-progression-in-40anoyzfxx.pdf

Disease-modifying drugs can reduce disability progression in relapsing multiple sclerosis.

The Cryptogenic Stroke International Working Group defined a new subgroup of cryptogenic stroke – embolic stroke of undetermined source (ESUS), based on clinical and imaging findings. Minor cardioembolic and atheroembolic sources were putatively implicated, and it was hypothesized that anticoagulant therapy might be warranted (1). We aimed to assess the role of minor embolic sources in ESUS in young stroke patients by comparing the prevalence of minor embolic sources in patients with ESUS and in patients with stroke of determined origin. Etiology was defined according to the TOAST criteria. ESUS and minor cardioembolic/atheroembolic stroke were defined according to the proposed criteria (1). We studied 100 consecutive ischemic stroke patients (see Table 1) aged between 18 and 55 years admitted in a Neurology department between January 2010 and August 2014 (mean age 46 years, range 22–55; 56% male; mean NIHSS at admission 4). The overall prevalence of minor cardioembolic sources was 53%, and of atheroembolic sources was 32%. Cryptogenic stroke was diagnosed in 51 patients. Among these, 42 patients were ESUS (mean age 45 years, range 26–55; 50% male; mean NIHSS at admission 4). The ESUS group neither have a higher prevalence of minor cardioembolic, 50% (21/42) vs. 50% (27/54), nor a higher prevalence of minor atheroembolic, 38·1% (16/42) vs. 30·8% (15/47), P = 0·641, sources, when compared with all strokes with a determined cause other than cardioembolic and other than large vessel disease, respectively. Although most young patients with cryptogenic stroke fulfill ESUS criteria, minor embolic sources do not seem to be more prevalent in ESUS than in strokes of determined cause; therefore, further explanations should be sought in this group.

Embolic stroke of unknown source (ESUS) in young patients.

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.

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

We used video-polysomnography to characterize motor events (ME) in 14 Parkinson’s disease (PD-RBD) and 18 idiopathic (iRBD) REM sleep behavior disorder cases. ME occurred predominantly in the upper limbs and were mostly simple, non-emotional, distal and focal. There were no significant differences in ME features between PD-RBD and iRBD groups. Our data suggests that RBD ME are mostly non violent. Similarity between PD-RBD and iRBD groups suggests that motor dysfunction does not affect ME features.

Characterization of motor events in REM sleep behavior disorder.

Headaches are a large group of neurological disorders, with a high personal and social burden (1). Evidence on temporal changes in headache prevalence remains conflicting, with some studies reporting an increase while others report relative stability (2). Google Trends is a web-based facility that analyses unbiased samples of Google search queries. It calculates the amount of searches for a given term relative to the total number of searches entered on the Google search engine. Search volume for medical subjects has been pointed out as a valuable epidemiological indicator of disease prevalence over time. There is a high correlation between Google search volume and laboratorysupported epidemiological data of seasonal disorders such as influenza (3). To analyse the evolution of the search for migraine and other headaches, we extracted Google Trends world data since its inception (January 2004) to September 2016. We used migraine and headache as keywords and compared search trends with other high burden neurological disorders. We also included asthma, a non-neurological condition that has a similar prevalence to migraine in children and young adults. The Google Trends algorithm excludes queries made by very few people or the same person over a short period of time. It normalises data against total search volume, scaling results from 0 to 100 (details on support.google.com/trends). The Matlab polyfit function was used to fit the data with a second-degree polynomial (Figure 1). We observed an increase in online headache searches since September 2004. The relative number of online headache searches increased by 158% between January 2004 and January 2016, and a 15% increase was also observed for migraine. During this time period, searches for stroke (6%), multiple sclerosis (MS) (40%) and asthma (28%) decreased. In January 2016, the volume of headache searches was 266% higher than for MS, 141% higher than for stroke and 227% higher than for asthma. Migraine

"Dr Google" will see you now - time trends in online searches on headache.

Advancing age is a well-known risk factor for Parkinson’s disease (PD). With population ageing it is expected that the total number of patients with PD onset at oldage increases. Information on the motor but particularly on non-motor phenotype of this late-onset population is lacking. We recruited 24 patients with PD onset at or over 75 years. Each patient was matched with 1 control patient with PD onset between the ages of 40 and 65 and matched for disease duration. Both groups were assessed with the UPDRS, the Non-motor symptoms scale (NMSS) and other scales to assess non-motor symptoms. Groups were compared with conditional logistic regression analysis. Old-age onset PD was, on average, 80 years at the time of PD onset while middle-age onset were 59. Disease duration was approximately 5 years in both groups. While no difference was observed in the total UPDRS-III scores, old-age onset PD was associated with higher axial symptoms (7.42 vs. 4.63, p = 0.011) and a higher frequency of dementia (7/24 vs. 0/24, p = 0.009). While no difference in the total number of non-motor symptoms was observed (6.79 vs. 6.22, p = 0.310), old-age onset patients had a higher prevalence of gastrointestinal symptoms (20/24 vs. 12/24, p = 0.037). For the same disease duration, older age onset is associated with worse axial motor dysfunction and dementia in PD patients. Beside gastrointestinal symptoms, non-motor symptoms are not associated with age.

Motor and non-motor symptoms in old-age onset Parkinson’s disease patients

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