Headache and Status Epilepticus Reveal Paget's Disease of the Bone.

Paget's disease of the bone (PDB) is a benign osteodystrophy of the elderly characterized by excessive remodeling of bone tissue, mainly in the pelvis, femur, and skull. Its neurological manifestations are numerous and affect both the central and peripheral nervous systems. As headaches are often reported, epileptic seizures remain exceptional. We report the case of a 75-year-old female patient with a history of chronic worsening headache who was admitted to the emergency department for the first episode of a seizure. Brain imaging revealed heterogeneous bone thickening and circumscribed skull osteoporosis. Bone scintigraphy showed pagetoid lesions restricted to the skull and face. Alkaline phosphatases increased. The rest of the biological work-up and the cerebrospinal fluid study ruled out other metabolic causes or central nervous system infections. The patient was treated with bisphosphonates and anti-convulsive treatment. The evolution was satisfactory, with progressive improvement in headache and seizure control, even several months after discontinuation of anti-seizure medication. Our case report highlights the importance of exploring chronic headaches in the elderly, not only in search of lesions of the cerebral parenchyma but also of the structures containing them, in this case, the skull.

Interplay between subthalamic nucleus and spinal cord controls parkinsonian nociceptive disorders.

BACKGROUND: Pain is a non-motor symptom that impairs quality of life in Parkinson's patients. Pathological nociceptive hypersensitivity in patients could be due to changes in the processing of somatosensory information at the level of the basal ganglia, including the subthalamic nucleus (STN), but the underlying mechanisms are not yet defined. Here, we investigated the interaction between the STN and the dorsal horn of the spinal cord (DHSC), by first examining the nature of STN neurons that respond to peripheral nociceptive stimulation and the nature of their responses under normal and pathological conditions. Next, we studied the consequences of deep brain stimulation (DBS) of the STN on the electrical activity of DHSC neurons. Then, we investigated whether the therapeutic effect of STN-DBS would be mediated by the brainstem descending pathway involving the rostral ventromedial medulla (RVM). Finally, to better understand how the STN modulates allodynia, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) expressed in the STN. METHODS: The study was carried out on the 6-OHDA rodent model of Parkinson's disease, obtained by stereotactic injection of the neurotoxin into the medial forebrain bundle of rats and mice. In these animals, we used motor and nociceptive behavioral tests, in vivo electrophysiology of STN and wide dynamic range (WDR) DHSC neurons in response to peripheral stimulation, deep brain stimulation of the STN and the selective DREADD approach. Vglut2-ires-cre mice were used to specifically target and inhibit STN glutamatergic neurons. RESULTS: STN neurons are able to detect nociceptive stimuli, encode their intensity and generate windup-like plasticity, like WDR neurons in the DHSC. These phenomena are impaired in dopamine-depleted animals, as the intensity response is altered in both spinal and subthalamic neurons. Furthermore, As with L-Dopa, STN-DBS in rats ameliorated 6-OHDA-induced allodynia, and this effect is mediated by descending brainstem projections leading to normalization of nociceptive integration in DHSC neurons. Furthermore, this therapeutic effect was reproduced by selective inhibition of STN glutamatergic neurons in Vglut2-ires-cre mice. CONCLUSION: Our study highlights the centrality of the STN in nociceptive circuits, its interaction with the DHSC and its key involvement in pain sensation in Parkinson's disease. Furthermore, our results provide for the first-time evidence that subthalamic DBS produces analgesia by normalizing the responses of spinal WDR neurons via descending brainstem pathways. These effects are due to direct inhibition, rather than activation of glutamatergic neurons in the STN or passage fibers, as shown in the DREADDs experiment.

Predictors and Pathophysiology of Axial Postural Abnormalities in Parkinsonism: A Scoping Review.

Background: Postural abnormalities involving the trunk are referred to as axial postural abnormalities and can be observed in over 20% of patients with Parkinson's disease (PD) and in atypical parkinsonism. These symptoms are highly disabling and frequently associated with back pain and a worse quality of life in PD. Despite their frequency, little is known about the pathophysiology of these symptoms and scant data are reported about their clinical predictors, making it difficult to prompt prevention strategies. Objectives: We conducted a scoping literature review of clinical predictors and pathophysiology of axial postural abnormalities in patients with parkinsonism to identify key concepts, theories and evidence on this topic. Methods: We applied a systematic approach to identify studies, appraise quality of evidence, summarize main findings, and highlight knowledge gaps. Results: Ninety-two articles were reviewed: 25% reported on clinical predictors and 75% on pathophysiology. Most studies identified advanced disease stage and greater motor symptoms severity as independent clinical predictors in both PD and multiple system atrophy. Discrepant pathophysiology data suggested different potential central and peripheral pathogenic mechanisms. Conclusions: The recognition of clinical predictors and pathophysiology of axial postural abnormalities in parkinsonism is far from being elucidated due to literature bias, encompassing different inclusion criteria and measurement tools and heterogeneity of patient samples. Most studies identified advanced disease stage and higher burden of motor symptoms as possible clinical predictors. Pathophysiology data point toward many different (possibly non-mutually exclusive) mechanisms, including dystonia, rigidity, proprioceptive and vestibular impairment, and higher cognitive deficits.

Gene Panel Sequencing Analysis Revealed a Strong Contribution of Rare Coding Variants to the Risk of Parkinson's Disease in Sporadic Moroccan Patients.

Parkinson's disease (PD) is a neurodegenerative movement disorder which can be either familial or sporadic. While it is well known that monogenic mutations are not a very common cause of PD, GWAS studies have shown that an additional fraction of the PD heritability could be explained by rare or common variants. To identify the rare variants that could influence the risk of PD in the Moroccan population, a cohort of 94 sporadic PD patients negative for the LRRK2 G2019S mutation was subjected to NGS gene panel sequencing, and gene dosage using the MLPA method. Mean age of onset at enrollment was 51.7 ± 11.51 years, and 60% of patients were men. We identified 70 rare variants under 0.5% of frequency in 16 of the 20 genes analyzed, of which 7 were novel. Biallelic disease-causing variants in genes with recessive inheritance were found in 5 PD cases (5.31%), whereas 13 patients (13.8%) carried likely pathogenic variants in genes with dominant inheritance. Moreover, 8 patients (8.5%) carried a single variant in MAPT or POLG, whereas co-occurrence of rare variants involving more than one gene was observed in 28 patients (30%). PD patients with variants in recessive genes had a younger mean age at onset than patients with dominant ones (33.40 (12.77) vs. 53.15 (6.63), p < 0.001), while their clinical features were similar. However, patients with rare variants in the risk factor genes or in more than one gene tended to have less resting tremor (p < 0.04), but more dystonia (p < 0.006) and dementia (p < 0.002) than those without any rare variants in known PD-associated genes. Our results showed a significant enrichment of rare variants particularly in LRRK2, VPS13C, POLG, and MAPT and underline their impact on the risk of sporadic form of the disease.

Management of rare movement diseases in different world regions.

To evaluate the management of rare movement disorders (RMD) at the international level and identify care needs to be addressed, the Rare Movement Disorders Study Group of the International Parkinson and Movement Disorders Society (MDS) has conducted an exploratory survey. We sent an online survey to experts in Africa, Asia, Oceania and American continents following the classification of the MDS Regional Sections: Africa, Asia and Oceania (A&O), and Pan-America. We did not include Europe as the European Reference Network for Rare Neurological Diseases recently performed a similar care needs survey across European countries. We obtained responses from experts from 20 African, 26 A&O and 19 Pan-American countries. According to the respondents, only 55% of African countries had movement disorders experts, while these were present in 96% of A&O and 91% of Pan-American. Access to care for patients with RMD was stated difficult in 70% of African, 54% of A&O, and 65% of Pan-American countries. Africa was the region with greatest difficulties in accessing diagnostic tests. However, in Pan-America and A&O, large inequalities were observed between countries with quite variable access to therapeutic options such as deep brain stimulation. The survey results reflect wide variability in the management of RMD and provide evidence that a worldwide care-focused network is highly warranted. Scientific and medical organisations should raise awareness of deficits in managing RMD and care disparities among regions. The goals should be to facilitate the training of professionals, establish improvement strategies, and increase support and budgeting for these diseases.

Task Force Consensus on Nosology and Cut-Off Values for Axial Postural Abnormalities in Parkinsonism.

Background: There is no consensus with regard to the nosology and cut-off values for postural abnormalities in parkinsonism. Objective: To reach a consensus regarding the nosology and cut-off values. Methods: Using a modified Delphi panel method, multiple rounds of questionnaires were conducted by movement disorder experts to define nosology and cut-offs of postural abnormalities. Results: After separating axial from appendicular postural deformities, a full agreement was found for the following terms and cut-offs: camptocormia, with thoracic fulcrum (>45°) or lumbar fulcrum (>30°), Pisa syndrome (>10°), and antecollis (>45°). "Anterior trunk flexion," with thoracic (≥25° to ≤45°) or lumbar fulcrum (>15° to ≤30°), "lateral trunk flexion" (≥5° to ≤10°), and "anterior neck flexion" (>35° to ≤45°) were chosen for milder postural abnormalities. Conclusions: For axial postural abnormalities, we recommend the use of proposed cut-offs and six unique terms, namely camptocormia, Pisa syndrome, antecollis, anterior trunk flexion, lateral trunk flexion, anterior neck flexion, to harmonize clinical practice and future research.

How Does the Immune System Enter the Brain?

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.

Availability of Therapies and Services for Parkinson's Disease in Africa: A Continent-Wide Survey.

BACKGROUND: The growing burden of Parkinson's disease (PD) in Africa necessitates the identification of available therapies and services to improve patient care. OBJECTIVE: To investigate the availability, affordability, frequency of usage, and insurance coverage of PD therapies (pharmacological, surgical, physical, and speech therapies) and services including specialized clinics, specialists, and nurses across Africa. METHODS: A comprehensive web-based survey was constructed and distributed to neurologists/physicians with a special interest in PD across Africa. The survey instrument includes components that address availability, affordability, frequency of use, and insurance coverage of different therapies and services. RESULTS: Responses were received from 28 (of 43 contacted) countries. Levodopa-based oral preparations were always available in 13 countries (46.4%) with variable affordability and "partial or no" insurance coverage in 60% of countries. Bromocriptine was the most available (50%) and affordable ergot dopamine agonists (DA), whereas non-ergot DA was always available in only six countries (21.4%). Trihexyphenidyl was the most available and affordable anticholinergic drug (46.4%). Tricyclic antidepressants and selective serotonin reuptake inhibitors were available in most countries (89.3% and 85.7% respectively), with variable affordability. Quetiapine and clozapine were less available. Specialized clinics and nurses were available in 25% and 7.1% of countries surveyed, respectively. Other services were largely unavailable in the countries surveyed. CONCLUSION: PD-specific therapies and services are largely unavailable and unaffordable in most African countries. The data provide a platform for organizing strategies to initiate or scale up existing services and drive policies aimed at improving access to care and tailoring education programs in Africa. © 2021 International Parkinson and Movement Disorder Society.

A Specific Diplotype H1j/H2 of the MAPT Gene Could Be Responsible for Parkinson's Disease with Dementia.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease. Five to ten percent of patients have monogenic form of the disease, while most of sporadic PD cases are caused by the combination of genetic and environmental factors. Microtubule-associated protein tau (MAPT) has been appointed as one of the most important risk factors for several neurodegenerative diseases including PD. MAPT is characterized by an inversion in chromosome 17 resulting in two distinct haplotypes H1 and H2. Studies described a significant association of MAPT H1j subhaplotype with PD risk, while H2 haplotype was associated with Parkinsonism, particularly to its bradykinetic component. We report here an isolated case displaying an akinetic-rigid form of PD, with age of onset of 41 years and a good response to levodopa, who developed dementia gradually during the seven years of disease progression. The patient does not carry the LRRK2 G2019S mutation, copy number variations, nor pathogenic and rare variants in known genes associated with PD. MAPT subhaplotype genotyping revealed that the patient has the H1j/H2 diplotype, his mother H1j/H1j, his two healthy brothers H1j/H1v and his deceased father was by deduction H1v/H2. The H1j/H2 diplotype was shown in a total of 3 PD patients among 80, who also did not have known PD-causing mutation and in 1 out of 92 healthy individual controls. The three patients with this diplotype all have a similar clinical phenotype. Our results suggest that haplotypes H1j and H2 are strong risk factor alleles, and their combination could be responsible for early onset of PD with dementia.

In vivo validation of a new portable stimulator for chronic deep brain stimulation in freely moving rats.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is considered as a gold standard therapy for the alleviation of motor symptoms in Parkinson's disease (PD). This success paved the way to its application for other neurological and psychiatric disorders. In this context, we aimed to develop a rodent-specific stimulator with characteristics similar to those used in patients. NEW METHOD: We designed a stimulator that can be connected to an electrode container with options for bilateral or unilateral stimulation selection and offers a wide range of frequencies, pulse widths and intensities, constant current, biphasic current-control and charge balancing. Dedicated software was developed to program these parameters and the device was tested on a bilateral 6-hydroxydopamine (6-OHDA) rat model of PD. RESULTS: The equipment was well tolerated by the animals with a good general welfare. STN stimulation (130 Hz frequency, 0.06 ms pulse width, 150 µA average intensity) improved the motor deficits induced by 6-OHDA as it significantly increased the number of movements compared to the values obtained in the same animals without STN stimulation. Furthermore, it restored motor coordination by significantly increasing the time spent on the rotarod bar. CONCLUSION: We successfully developed and validated a new portable and programmable stimulator for freely moving rats that delivers a large range of stimulation parameters using bilateral biphasic current-control and charge balancing to maximize tissue safety. This device can be used to test deep brain stimulation in different animal models of human brain diseases.

Genetic Analysis of Undiagnosed Juvenile GM1-Gangliosidosis by Microarray and Exome Sequencing.

GM1 gangliosidosis is an autosomal recessive lysosomal storage disorder due to mutations in the lysosomal acid 3-galactosidase gene, GLB1. It is usually classified into three forms, infantile, juvenile, or adult, based on age at onset and severity of central nervous system involvement. Because of their broad clinical spectrum and their similarity to many other aetiologies, including inherited neurodegenerative and metabolic diseases, it is often difficult to diagnose such diseases. Recently, whole exome sequencing (WES) has become increasingly used when a strong hypothesis cannot be formulated based on the clinical phenotype. Here, we present three patients belonging to a consanguineous Moroccan family with a GM1-gangliosidosis with unusual clinical onset and atypical radiological presentation that had eluded diagnosis for over a decade. To identify the disease-causing mutation, we performed a whole exome sequencing and a chromosomal microarray genotyping in order to reduce the number of genetic variants to be interpreted, by focusing the data analysis only on the linked loci. The already known pathogenic missense mutation c.601G>A in GLB1 (p.R201C) was found at homozygous state in the proband V.1 and at heterozygous state in his father IV.1. The mutation was validated by Sanger sequencing and segregated in all the family members according to a recessive mode of inheritance. Outside of the linked loci, we found the EXOSC8 p.Ser272Thr mutation at heterozygous state in all the patients and their mother IV.2. This mutation was reported to cause pontocerebellar hypoplasia type 1C and could act as a modifying factor that exacerbates the brain atrophy of patients. Our study identified the first GLB1 mutation in North Africa in patients with unexpected brain-MRI outcomes extending the clinical spectrum of the GM1-gangliosidosis.

Deep Brain Stimulation in Moroccan Patients With Parkinson's Disease: The Experience of Neurology Department of Rabat.

Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is known as a therapy of choice of advanced Parkinson's disease. The present study aimed to assess the beneficial and side effects of STN DBS in Moroccan Parkinsonian patients. Material and Methods: Thirty five patients underwent bilateral STN DBS from 2008 to 2016 in the Rabat University Hospital. Patients were assessed preoperatively and followed up for 6 to 12 months using the Unified Parkinson's Disease Rating Scale in four conditions (stimulation OFF and ON and medication OFF and ON), the levodopa-equivalent daily dose (LEDD), dyskinesia and fluctuation scores and PDQ39 scale for quality of life (QOL). Postoperative side effects were also recorded. Results: The mean age at disease onset was 42.31 ± 7.29 years [28-58] and the mean age at surgery was 54.66 ± 8.51 years [34-70]. The median disease duration was 11.95 ± 4.28 years [5-22]. Sixty-three percentage of patients were male. 11.4% of patients were tremor dominant while 45.71 showed akinetic-rigid form and 42.90 were classified as mixed phenotype. The LEDD before surgery was 1200 mg/day [800-1500]. All patients had motor fluctuations whereas non-motor fluctuations were present in 61.80% of cases. STN DBS decreased the LEDD by 51.72%, as the mean LEDD post-surgery was 450 [188-800]. The UPDRS-III was improved by 52.27%, dyskinesia score by 66.70% and motor fluctuations by 50%, whereas QOL improved by 27.12%. Post-operative side effects were hypophonia (2 cases), infection (3 cases), and pneumocephalus (2 cases). Conclusion: Our results showed that STN DBS is an effective treatment in Moroccan Parkinsonian patients leading to a major improvement of the most disabling symptoms (dyskinesia, motor fluctuation) and a better QOL.

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

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. This 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-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 by improving the QoL of PD patients.

Mutation Analysis of Consanguineous Moroccan Patients with Parkinson's Disease Combining Microarray and Gene Panel.

During the last two decades, 15 different genes have been reported to be responsible for the monogenic form of Parkinson's disease (PD), representing a worldwide frequency of 5-10%. Among them, 10 genes have been associated with autosomal recessive PD, with PRKN and PINK1 being the most frequent. In a cohort of 145 unrelated Moroccan PD patients enrolled since 2013, 19 patients were born from a consanguineous marriage, of which 15 were isolated cases and 4 familial. One patient was homozygous for the common LRRK2 G2019S mutation and the 18 others who did not carry this mutation were screened for exon rearrangements in the PRKN gene using Affymetrix Cytoscan HD microarray. Two patients were determined homozygous for PRKN exon-deletions, while another patient presented with compound heterozygous inheritance (3/18, 17%). Two other patients showed a region of homozygosity covering the 1p36.12 locus and were sequenced for the candidate PINK1 gene, which revealed two homozygous point mutations: the known Q456X mutation in exon 7 and a novel L539F variation in exon 8. The 13 remaining patients were subjected to next-generation sequencing (NGS) that targeted a panel of 22 PD-causing genes and overlapping phenotypes. NGS data showed that two unrelated consanguineous patients with juvenile-onset PD (12 and 13 years) carried the same homozygous stop mutation W258X in the ATP13A2 gene, possibly resulting from a founder effect; and one patient with late onset (76 years) carried a novel heterozygous frameshift mutation in SYNJ1. Clinical analysis showed that patients with the ATP13A2 mutation developed juvenile-onset PD with a severe phenotype, whereas patients having either PRKN or PINK1 mutations displayed early-onset PD with a relatively mild phenotype. By identifying pathogenic mutations in 45% (8/18) of our consanguineous Moroccan PD series, we demonstrate that the combination of chromosomal microarray analysis and NGS is a powerful approach to pinpoint the genetic bases of autosomal recessive PD, particularly in countries with a high rate of consanguinity.

Erratum to: Severe Paraneoplastic Parkinsonism: A Rare Cause Revealing Breast Cancer.

This corrects the article on p. 310 in vol. 13, PMID: 28748681.

Evidence for prehistoric origins of the G2019S mutation in the North African Berber population.

The most common cause of the monogenic form of Parkinson's disease known so far is the G2019S mutation of the leucine-rich repeat kinase 2 (LRRK2) gene. Its frequency varies greatly among ethnic groups and geographic regions ranging from less than 0.1% in Asia to 40% in North Africa. This mutation has three distinct haplotypes; haplotype 1 being the oldest and most common. Recent studies have dated haplotype 1 of the G2019S mutation to about 4000 years ago, but it remains controversial whether the mutation has a Near-Eastern or Moroccan-Berber ancestral origin. To decipher this evolutionary history, we genotyped 10 microsatellite markers spanning a region of 11.27 Mb in a total of 57 unrelated Moroccan PD patients carrying the G2019S mutation for which the Berber or Arab origin was established over 3 generations based on spoken language. We estimated the age of the most recent common ancestor for the 36 Arab-speaking and the 15 Berber-speaking G2019S carriers using the likelihood-based method with a mutation rate of 10-4. Data analysis suggests that the shortest haplotype originated in a patient of Berber ethnicity. The common founder was estimated to have lived 159 generations ago (95% CI 116-224) for Arab patients, and 200 generations ago (95% CI 123-348) for Berber patients. Then, 29 native North African males carrying the mutation were assessed for specific uniparental markers by sequencing the Y-chromosome (E-M81, E-M78, and M-267) and mitochondrial DNA (mtDNA) hypervariable regions (HV1 and HV2) to examine paternal and maternal contributions, respectively. Results showed that the autochthonous genetic component reached 76% for mtDNA (Eurasian and north African haplogroups) and 59% for the Y-chromosome (E-M81 and E-M78), suggesting that the G2019S mutation may have arisen in an autochthonous DNA pool. Therefore, we conclude that LRRK2 G2019S mutation most likely originated in a Berber founder who lived at least 5000 years ago (95% CI 3075-8700).

LRRK2 G2019S Mutation: Prevalence and Clinical Features in Moroccans with Parkinson's Disease.

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.

Severe Paraneoplastic Parkinsonism: A Rare Cause Revealing Breast Cancer

No abstract available.