Wafa Regragui

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 Parkinsons 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 Parkinsons 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.

Hypertension intracrânienne bénigne: Aspects cliniques et thérapeutiques

INTRODUCTION Benign intracranial hypertension (BIH) or pseudotumor cerebri is diagnosed on the basis of Dandys criteria. BIH creates an emergency situation because of the risk of lost vision. In this work, we studied retrospectively a series of 10 cases of BIH all meeting Dandys criteria. Our objective was to assess the benefit of the corticosteroid-acetazolamide combination on clinical course, especially on papiledema. METHODS Eighty-four patients were hospitalized at the neurology department (Hopital des Specialites, Rabat) over a period of 14 years (1988-2001). They were divided into three groups: forty cases of cerebral thromophlebitis, 10 cases of BIH. In the remaining 34 cases, the investigations were insufficient, so that Dandys criteria could not be verified. We studied only the 10 cases presenting with a diagnosis of BIH diagnosis complying with Dandys criteria. The patients underwent a physical examination, cerebral magnetic resonance imaging (MRI) if possible or CT scan with conventional angiography, and CSF examination with pressure measurement. We analyzed age, sex-ratio, clinical aspects and the outcome after treatment. The major criterion of outcome was the regression of papilledema. RESULTS There were 9 women and 1 man. The mean age was 24.6 8.4 years. Behcets disease was noted in 3/10 patients. The clinical features were those described in the literature. Patients were treated by corticosteroids combined with acetazolamide and CSF depletion in all cases. CSF derivation was performed in only 1 patient. Definitive blindness was noted in 2 patients at admission. A favorable course was noted in 8/10 cases, with regression of papilledema within approximately 1 month. DISCUSSION We suggest that the corticosteroid-acetazolamide combination can have a beneficial effect on papilledema in BIH. However, these results should be confirmed by a prospective, randomized, double blind controlled study.

Profile of idiopathic parkinson’s disease in Moroccan patients

Objective To characterize clinical aspects of Idiopathic Parkinson’s disease from a movement disorders consultation in University Hospital of Rabat. Methods Retrospective review of medical records of 117 patients with diagnosis of Idiopathic Parkinson’s disease seen in our outpatient clinic from 2006 to 2011. Results Mean age was 64 ± 10 years with predominance of men (61.5%). Mean age at disease onset was 57 ± 11 years. Early onset Parkinson’s Disease was recorded in 12.8%. The median duration of disease was 5 years. Initial symptom appeared on the right side in 56.5%. Tremor presentation was the most frequent (40.2%). Symptom severity was mild to moderate in 80% of cases (UPDRS < 30). Forty four per cent of patients were receiving both Dopamine Agonists and Levodopa and in 69% of cases Levodopa was introduced within the first year following onset. The mean Levodopa Equivalent Doses (LED) was 667 ± 446 mg/day. Motor complications were found in 42% with motor fluctuations in 28.7% and 2dyskinesias in 26.7%. Non motor complications are represented mainly by autonomic disorders (44%). There were no differences in the clinical presentation related to the age at onset. Age of onset < 45 and LED > 600 mg are identified as risk factors for motor fluctuations whereas duration of Levodopa treatment is a risk factor of dyskinesias. Conclusion Our patients are younger compared to most series with high prevalence of early onset forms. In the majority of cases, Levodopa was introduced within the first year following onset which expose patients to dyskinesias early in the course of the disease.

Profile of multiple system atrophy in Moroccan patients attending a movement disorders outpatient clinic in Rabat university hospital

INTRODUCTION Multiple system atrophy (MSA) is a sporadic and rapidly progressive neurodegenerative disorder of poor prognosis, characterised clinically by any combination of parkinsonian, autonomic, cerebellar, or pyramidal signs. We report our experience in movement disorders consultation concerning the clinical presentation and the course of MSA in Moroccan patients. METHODS A retrospective review of the medical records of 17 patients with diagnosis of MSA seen in our outpatient clinic from January 2007 to December 2010. RESULTS In our 17 patients, 76.5% were men and the mean age of onset was 52±9 years. MSA-P was the major clinical phenotype (82.4%). Eleven patients (64.7%) were classified as having probable MSA and six patients (35.3%) as possible MSA. Dysautonomic features were detected in all patients; urinary symptoms were found in 76.5% of cases and orthostatic hypotension in 64.7%. Treatment regimen included l-Dopa with a mean daily dose of 621.4±346.8mg/day and symptomatic treatment of dysautonomia. The mean duration of disease evolution was of 4.7±1.9 years. DISCUSSION Our results show a male predominance and an early age of disease onset. MSA-P was the predominant subtype. Our results are similar to the European MSA series. CONCLUSION Multicentre studies are needed to better characterise MSA in Morocco given the rarity of this disease.

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).

Multiple sclerosis: Clinical characteristics and disability progression in Moroccan children

BACKGROUND 5% of multiple sclerosis have their onset in childhood. OBJECTIVES We aim to show the clinical features and follow-up of Moroccan pediatric MS patients. METHODS 25 pediatric MS records were analyzed between 2005 and 2013 at the Neurology B department of Rabat Ibn sina University Hospital and Medical School Group of Neurogenetic Disorder of Rabat Mohammed V University Souissi. RESULTS The median duration of follow up was 4 years [1.56]. The median age at disease onset was 14 years. Clinical symptoms were described. At the last evaluation, the median EDSS score was 3.0 [0-7.5]. The median time between disease onset and diagnosis was 2 years [1-9] and the median time from MS onset to second neurological episode was 1 year [0.9-3] with an average of 2 relapses in the first 2 years. The median time to reach EDSS 3.0 was 4.5 years [2-17] and the median time to go from EDSS 3.0 to 6.0 was 4 years [2.5-6]. The majority of cases at the last follow-up were; relapsing-remitting (17 patients: 68%), although 8 patients (32%) developed secondary progressive MS after median disease duration of 5 years [4-19]. None of the patients had a primary progressive MS. CONCLUSION Time EDSS 3.0 and to secondary progression was shorter in our cohort than previously reported in other series.

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 Parkinsons 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 Parkinsons 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.