Deep Brain Stimulation for Dystonia: Experience of a Moroccan University Hospital.

BACKGROUND: Deep brain stimulation (DBS) is a well-established procedure that provides long-term symptom control of the third most common movement disorder: dystonia. In this study, we aim to report the experience of Ibn Rochd University Hospital in the treatment of dystonia using DBS of the globus pallidus internus, which represents an exceptional challenge for a developing country such as Morocco. METHODS: Since 2013, we selected five eligible candidates for DBS surgery at the university hospital Ibn Rochd. A genetic assessment had been performed in four cases. Their motor and mental states were prospectively monitored using several validated scales, including Burke-Fahn-Marsden Dystonia Rating Scale, Mini Mental State Examination, 36-Item Short Form Survey, and Zarit scale. RESULTS: Our sample had two clinical phenotypes of dystonia: isolated dystonia (in two patients) and combined dystonia (in three patients). Patients were aged 14 to 32 years, and their mean onset age ranged from 7 to 13 years with a mean progression duration of 9 years. Our results indicate successful treatment of patients with dystonia using DBS. Scores from the Burke-Fahn-Marsden Dystonia Rating Scale confirm improvements ranging from 40% to 95%. However, some potentially surgery-related complications could occur such as lead infection, which, in our experience, was reported in one case. CONCLUSION: The experience of the university hospital Ibn Rochd regarding the use of DBS in treating dystonia was largely positive. However, the procedure faces challenges due to its complexity, specifically concerning its multidisciplinary nature, its genetic test costs, and the reluctance of pediatricians to get involved.

Hemodialysis-related headache: Still a challenge in 2020? Effect of conventional versus online hemodiafiltration from a study in Casablanca, Morocco.

Hemodialysis-related headache (HRH) is a well-known clinical event. It is considered as one of the most commonly reported neurological symptoms among hemodialysis patients. Its epidemiological, physiological, clinical, and therapeutic data remain scarce and are poorly studied. Our aim was to determine the frequency of HRH in the region of Casablanca, Morocco, to describe its clinical characteristics and to explore the hypothesis that renal replacement techniques, such as conventional versus online hemodiafiltration may have an association on clinical adverse effects like HRH. A descriptive, cross-sectional, and multicentric study was carried out among 100 chronic hemodialysis patients for at least 6 months. HRH was defined according to criteria published by the International Classification of Headache Disorder third edition beta version (ICHD3ß) [1]. Two different HD-modalities (standard HD and OL-HDF) have been investigated in order to explore their impact on HRH. Headache was reported by 60% of the patients including 41.6% of hemodialysis-related headache. HRH had on average a duration of 7.4 hours, pulsatile among 38% of interviewed patients and of moderate intensity in 48% of cases. In total, 51.3% of patients undergoing conventional hemodialysis modality reported HRH compared to 12.5% undergoing online hemodiafiltration technique (OL-HDF) (P = .008). Hemodialysis-related headache remains a poorly studied clinical event despite its high prevalence. Its diagnosis, management, and especially its prevention remain a challenge for the neurologist and the nephrologist. Our results suggest that OL-HDF is a promising therapeutic and preventive tool to reduce the incidence of HRH.

SARS-CoV2 disease seen through the prism of acutely decompensated chronic kidney disease and ischemic stroke: What lesson we have learned from using prophylaxis therapy of vascular thromboembolism?

Our case underlines the tight management of antithrombotic therapy in the context of acutely decompensated chronic kidney disease, ischemic stroke, and SARS-CoV2 infection, the development of stroke as a SARS-CoV2 complication increase the chances of adverse outcomes that may be mitigated by a rapid recognition and institution of available treatments.

Immune Reconstitution Therapy or Continuous Immunosuppression for the Management of Active Relapsing-Remitting Multiple Sclerosis Patients? A Narrative Review.

The majority of disease-modifying drugs (DMDs) available for the management of active relapsing-remitting multiple sclerosis (RMS) depend on continuous drug intake for maintained efficacy, with escalation to a more active drug when an unacceptable level of disease activity returns. Among continuously applied regimens, interferons and glatiramer acetate act as immunomodulators, while dimethyl fumarate, fingolimod, ocrelizumab, natalizumab and teriflunomide are associated with continuous immunosuppression. By contrast, immune reconstitution therapy (IRT) provides efficacy that outlasts a short course of treatment. Autologous hemopoietic stem cell transplantation is perhaps the classic example of IRT, but this invasive and intensive therapy has challenging side-effects. A short treatment course of a pharmacologic agent hypothesized to act as an IRT, such as Cladribine Tablets 3.5 mg/kg or alemtuzumab, can provide long-term suppression of MS disease activity, without need for continuous treatment (the anti-CD20 mechanism of ocrelizumab has the potential to act as an IRT, but is administered continuously, at 6-monthly intervals). Cladribine Tablets 3.5 mg/kg shows some selectivity in targeting adaptive immunity with a lesser effect on innate immunity. The introduction of IRT-like disease-modifying drugs (DMDs) challenges the traditional maintenance/escalation mode of treatment and raises new questions about how disease activity is measured. In this review, we consider a modern classification of DMDs for MS and its implications for the care of patients in the IRT era.

Clinical course of neuromyelitis optica spectrum disorder in a moroccan cohort.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) was suggested to be more frequent and have specific features among populations from Africa or North Africa. However, we could not find any large study about NMOSD in an African population in the medical literature. OBJECTIVES: To describe the characteristics of NMOSD in a Moroccan monocenter population. PATIENTS AND METHODS: A retrospective study was conducted. Patients fromJanuary 1999 to December 2015 fulfilling the 2015 International Consensus Criteria for NMOSD were included. RESULTS: Sixty four patients fulfilled the criteria. Mean age at onset was 35.7 ±â€¯10.7 years, and the sex ratio was 1/3.57. First clinical event was represented by optic neuritis (38.1%), followed by myelitis (27.0%) and a Devic's syndrome (17.2%). Mean annualized relapse rate was 1.07 ± 1.23 and mean EDSS at last visit was 5.1 ±â€¯2.8. Aquaporine 4 antibodies were positive in 47.1%. Brain lesions were found in 71.2%. Most patients (76.6%) received disease-modifying therapy, mainly cyclophosphamide (86.0%) and 49% remained relapse-free after treatment initiation CONCLUSION: Data from our study suggest more similarities between North African NMOSD patients and non-Caucasian populations. More studies are needed to assess other pathological patterns and compare disease course to other populations.

Biomarkers for Alzheimer Disease: Classical and Novel Candidates' Review.

The biomarkers may be useful for predictive diagnosis of Alzheimer's disease (AD). The current challenge is to diagnose it in its preclinical phase. The combination of cerebrospinal fluid (CSF) biomarkers and imaging has been investigated extensively for a number of years. It can provide an increased diagnostic accuracy. This review discusses the contribution of classical biomarkers to predict AD and highlights novel candidates identified as potential markers for AD. We referred to the electronic databases PubMed/Medline and Web of Science to search for articles that were published until February 2016. Sixty-two records were included in qualitative synthesis. In the first section, the results show the contribution of biomarkers to predict and track AD considered as classical biomarkers. In the second section, the results highlight the involvement of novel candidates that should be considered for future evaluation in the characterization of the AD progression. Reported findings open prospect to define noninvasive biomarkers to predict AD before symptoms onset.

Assessment of GAPDH expression by quantitative real time PCR in blood of Moroccan AD cases.

INTRODUCTION: Neuroproteomics studies have showed the high affinity interactions between GAPDH - ß-amyloid in Alzheimer disease. The aim of our study is to complete our previous studies by assessing the mechanism responsible of decreased expression of GAPDH protein in the blood of Moroccan AD cases probably due to an alteration at the transcriptional level or at the post translational level. METHODS: The mRNA expression of GAPDH was assessed by quantitative real time PCR in AD cases and healthy controls. RESULTS: Our result revealed a significant difference of mRNA expression level of GAPDH in AD cases as compared to healthy controls (P<0.05). CONCLUSION: This data is consistent with several studies by showing the direct involvement of GAPDH in amyloid aggregation by undergoing several modifications, which influence its chemical structure and its biological activity.

Genetic Aspects of Myoclonus-Dystonia Syndrome (MDS).

Myoclonus-dystonia (M-D) is an autosomal-dominant movement disorder with onset in the first two decades of life. Mutations in the epsilon-sarcoglycan gene (SGCE, DYT11) on chromosome 7q21-q31 represent the major genetic cause of M-D in some populations. The syndrome was related with mutations in two other genes (DRD2 and DYT1). A second locus has been reported in one large M-D family (DYT15, 18p11), but no gene has been identified yet. In this review, we discuss genetic aspects of myoclonus-dystonia.

A novel mutation in the ABCD1 gene of a Moroccan patient with X-linked adrenoleukodystrophy: case report.

BACKGROUND: X-linked adrenoleukodystrophy (X-ALD; OMIM: 300100) is the most common peroxisomal disease caused by mutations in the ATP-binding cassette, sub-family D member 1 gene or ABCD1 (geneID: 215), the coding gene for the adrenoleukodystrophy protein (ALDP), which is an ATP-binding transport protein associated to an active transport of very long chain fatty acids (VLCFAs). Dysfunction of ALDP induces an accumulation of VLCFAs in all tissues leading to a neurodegenerative disorder that involves the nervous system white matter. CASE PRESENTATION: In our case report, magnetic resonance imaging (MRI) as well as the high levels of VLCFAs prompted the diagnosis the X-ALD. Molecular analysis of ABCD1 gene have shown a pathogenic homozygous nonsense mutation (c.1677C > G; p.(Tyr559*)) in exon 7. CONCLUSION: Thus, we identified here a novel mutation in the ABCD1 gene in a Moroccan patient causing X-linked adrenoleukodystrophy.

A proteomic approach for the involvement of the GAPDH in Alzheimer disease in the blood of Moroccan FAD cases.

Several articles have highlighted the potential involvement of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in neurodegeneration by showing a non-glycolytic activity of GAPDH specifically in the brains of subjects with Alzheimer's disease (AD). The novel aim of this study was to elucidate the critical role of GAPDH and its interaction with ß-amyloid in the blood of Moroccan patients with familial AD (FAD) carrying presenilin mutations and in sporadic late onset AD (LOAD). Our results show a significant decrease in the activity of GAPDH in blood samples from patients with FAD as compared to sporadic cases and healthy controls. The expression level of GAPDH in brain specimens from mutant tau transgenic mice and patients with FAD was unchanged as compared to healthy controls. In contrast, the expression level of GAPDH in blood samples from mutant tau transgenic mice and patients with FAD was decreased as compared to sporadic cases and healthy controls. Moreover, there is an accumulation of ß-amyloid aggregates in the blood samples of patients with FAD and an increase in amyloid fibrils in both the blood and brain samples of these patients. Our study adds new insight to previous ones by showing the involvement of GAPDH in AD, which may influence the pathogenesis of this neurodegenerative disease.

Novel mutations in the amyloid precursor protein gene within Moroccan patients with Alzheimer's disease.

In Morocco, Alzheimer's disease (AD) affects almost 30,000 individuals, and this number could increase to 75,000 by 2020. To our knowledge, the genes predisposing individuals to AD and predicting disease incidence remain elusive. In this study, we aimed to evaluate the genetic contribution of mutations in the amyloid precursor protein (APP) gene exons 16 and 17 to familial and sporadic AD cases. Seventeen sporadic cases and eight family cases were seen at the memory clinic of the University of Casablanca Neurology Department. These patients underwent standard somatic neurological examination, cognitive function assessment, brain imaging, and laboratory tests. Direct sequencing of exons 16 and 17 of the APP gene was performed on genomic DNA of AD patients. In this original Moroccan study, we identified seven novel frameshift mutations in exons 16 and 17 of the APP gene. Interestingly, only one novel splice mutation was detected in a family case. There is a strong correlation between clinical symptoms and genetic factors in Moroccan patients with a family history of AD. Therefore, mutations in APP gene exons 16 and 17 may eventually become genetic markers for AD predisposition.

G894T endothelial nitric oxide synthase polymorphism and ischemic stroke in Morocco.

Nitric oxide plays a major role in the regulation of cerebral blood flow and loss of its function leads to alteration of the vascular relaxation given its central role in the physiology of the vascular system. G894T eNOS polymorphism could have adverse effects on the expression and activity of endothelial nitric oxide synthase, which can result in functional impairment of the endothelium and contribute to the development of ischemic stroke in the different models of transmission. In this study, genotyping with PCR-RFLP and HRM (high resolution melting) methods were conducted on 165 ischemic stroke patients as well as 182 controls. The goal here was to compare genotyping with PCR-RLFP primer sequences of eNOS gene (size < 300 bp) to HRM. Our data suggests a statistically significant association between G894T eNOS polymorphism and ischemic stroke in recessive, dominant and additive models with P < 0.05 and odds ratio of 2.68 (1.08-6.70), 1.78 (1.16-2.73), and 1.71 (1.21-2.43) respectively. In sum, although the sample size is relatively small, it suggests that G894T eNOS polymorphism could be a potentially important genetic marker of ischemic stroke in the Moroccan population. Future studies should be conducted in this direction taking into consideration the functional activity of eNOS.

Chorea paralytica: a videotape case with rapid recovery and good long-term outcome.

Chorea paralytica (or chorea mollis) is a very rare variant of Sydenham's chorea, characterized by a profound hypotonia, resulting in severe disability. Given the rarity of this condition, data on its prognosis are lacking. Most reports suggest that the delay from onset to recover total autonomy is long, usually several weeks to months which strongly affects the quality of life of these children. We report a videotape case of a 14-year-old girl, who became rapidly bedridden because of severe generalized chorea paralytica. Her clinical picture was totally improved 7 days only after initiation of an "aggressive" treatment, combining steroid pulse, haloperidol and long-term penicillin G, with no relapse after 4-year follow-up. We believe that the best care of this rare and severe form of Sydenham's chorea, should combine pathophysiological treatment with corticosteroids, preferably by pulse-therapy, symptomatic antichoreic treatment by neuroleptics, associated with a long-term antibiotic use to reduce recurrence risk.

Evolution of molecular diagnosis of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is the commonest of the muscular dystrophies. The DMD gene (DMD) is the biggest human gene and the most common molecular defect in the DMD gene, accounting for approximately 65 % of cases of DMD, is the deletion of one or more exons. The most basic method still in regular use involves multiplex PCR of the exons, known to be most commonly deleted. The multiplex is relatively simple. Quantitative analysis of all exons of the gene and multiplex ligation-dependent probe amplification have brought about an improvement in mutation detection rate, as they will detect all exon scale deletions as well as duplications, widely used to detect exonic and intronic mutations. As a sensitive and discriminative tool, MLPA can be used for prenatal testing. A more recent development in quantitative analysis is the use of oligonucleotide-based array comparative genomic hybridization.