Pain is a frequent, but poorly studied symptom of Parkinson's disease (PD). DoPaMiP survey aimed to assess the prevalence of chronic pain in PD, to describe PD patients with chronic pain, and to record analgesic consumption. About 450 parkinsonian patients underwent structured standardized clinical examination and completed self-reported questionnaires in a cross sectional survey. Pains related or unrelated to PD were identified according to predefined criteria. About 98 patients with other chronic disorders than PD were examined to assess if pain was more frequent in PD than in this population. Two thirds parkinsonian patients (278 of 450) had chronic pain. Twenty-five patients with non-chronic pain (<3-month duration) were excluded from subsequent analysis. Twenty six percent (111 of 425) parkinsonian patients had pain unrelated to PD ("non-PD-pain", caused mainly by osteoarthritis), while 39.3% (167 of 425) had chronic pain related to PD ("PD-pain"). In this last group, PD was the sole cause of pain in 103 and indirectly aggravated pain of another origin (mainly osteoarthritis) in 64. Parkinsonian patients with "PD-pain" were younger at PD onset, had more motor complications, more severe depressive symptoms than those without pain or with "non-PD pain." "PD-pain" was more intense (P = 0.03), but was less frequently reported to doctors (P = 0.02), and was associated with less frequent analgesic consumption than "non-PD-pain." Pain was twice more frequent in PD patients than in patients without PD after adjustment for osteo-articular comorbidities (OR = 1.9; 95% CI 1.2-3.2). Chronic pain is frequent but underreported in PD. Awareness of this problem should be increased and the assessment of analgesic strategies improved.

BackgroundNon-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. This study aimed to investigate the prevalence of NMSs and their impact on the QoL in a cohort of Moroccan patients.MethodsWe 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–VI during ON condition. The NMSs were evaluated with common scales and their relationship with the QoL was investigated.ResultsThe 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.ConclusionOur 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 by improving the QoL of PD patients.

Multiple Sclerosis (MS) is considered the most frequent inflammatory demyelinating disease of the central nervous system (CNS). It occurs with a variable prevalence across the world. A rich armamentarium of disease modifying therapies selectively targeting specific actions of the immune system is available for the treatment of MS. Understanding how and where immune cells are primed, how they access the CNS in MS and how immunomodulatory treatments affect neuroinflammation requires a proper knowledge on the mechanisms regulating immune cell trafficking and the special anatomy of the CNS. The brain barriers divide the CNS into different compartments that differ with respect to their accessibility to cells of the innate and adaptive immune system. In steady state, the blood-brain barrier (BBB) limits immune cell trafficking to activated T cells, which can reach the cerebrospinal fluid (CSF) filled compartments to ensure CNS immune surveillance. In MS immune cells breach a second barrier, the glia limitans to reach the CNS parenchyma. Here we will summarize the role of the endothelial, epithelial and glial brain barriers in regulating immune cell entry into the CNS and which immunomodulatory treatments for MS target the brain barriers. Finally, we will explore current knowledge on genetic and environmental factors that may influence immune cell entry into the CNS during neuroinflammation in Africa.

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Painful sensations are common in Parkinson's disease. In many patients, such sensations correspond to neuropathic pain and could be related to central alterations of pain processing. Subthalamic nuclei deep brain stimulation improves motor function in Parkinson's disease. Several structures of the basal ganglia are involved in nociceptive function, and deep brain stimulation could thus also modify pain perception in Parkinson's disease. To test this hypothesis, we compared subjective heat pain thresholds, in deep brain stimulation OFF and ON conditions in 2 groups of Parkinson's disease patients with or without neuropathic pain. We also compared pain-induced cerebral activations during experimental nociceptive stimulations using H(2)(15)O positron emission tomography in both deep brain stimulation OFF and ON conditions. Correlation analyses were performed between clinical and neuroimaging results. Deep brain stimulation significantly increased subjective heat pain threshold (from 40.3 ± 4.2 to 41.6 ± 4.3, P=.03) and reduced pain-induced cerebral activity in the somatosensory cortex (BA 40) in patients with pain, whereas it had no effect in pain-free patients. There was a significant negative correlation in the deep brain stimulation OFF condition between pain threshold and pain-induced activity in the insula of patients who were pain free but not in those who had pain. There was a significant positive correlation between deep brain stimulation-induced changes in pain threshold and in pain-induced cerebral activations in the primary somatosensory cortex and insula of painful patients only. These results suggest that subthalamic nuclei deep brain stimulation raised pain thresholds in Parkinson's disease patients with pain and restored better functioning of the lateral discriminative pain system.

Background. The LRRK2 G2019S mutation is the most common genetic determinant of Parkinson's disease (PD) identified to date. This mutation, reported in both familial and sporadic PD, occurs at elevated frequencies in Maghreb population. In the present study, we examined the prevalence of the G2019S mutation in the Moroccan population and we compared the motor and nonmotor phenotype of G2019S carriers to patients with idiopathic Parkinson's disease. Methods. 100 PD patients were assessed for motor and nonmotor symptoms, current medication, and motor complication including motor fluctuations and dyskinesia. The LRRK2 G2019S mutation was investigated by direct sequencing in patients and ethnically matched controls, all of Moroccan origin. Results. Among the 100 PD Moroccan patients, 41 (41%) were carriers of the G2019S mutation. The mutation frequency was higher among probands with autosomal dominant inheritance (76%) than among sporadic ones (28%). Interestingly, G2019S mutation was also found in 5% of control individuals. Clinically, patients carrying the G2019S mutation have more dystonia (OR = 4.6, p = 0.042) and more sleep disorders (OR = 2.4, p = 0.045) than noncarriers. Conclusions. The LRRK2 G2019S prevalence in Morocco is the highest in the world reported to date. Some clinical features in G2019S carriers such as dystonia and sleep disturbances are worth noting.

Patients with MSA and patients with PD recruited different motor networks. Patients with PD preferentially activated cerebellar pathways, possibly to compensate for basal ganglia dysfunction. This was not observed in patients with MSA, probably because of cerebellar dysfunction; other frontoparietal cortical areas were recruited.

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