[Treatments for SARS-CoV-2 infection: A retrospective study of drug-drug interactions and safety]. / Médicaments utilisés dans la prise en charge de l'infection à SARS-CoV-2 : étude rétrospective des principales associations à risque d'interactions médicamenteuses et des effets indésirables médicamenteux.

OBJECTIVES: The aim of the study is to provide an overview of Drug-drug Interactions (DDIs) and adverse effects caused by drugs used in SARS-CoV-2 infection during the first epidemic wave. METHODS: We retrospectively analyzed patients treated by drugs used in SARS-CoV-2 infection (Azithromycin, Hydroxychloroquine and/or Lopinavir/ritonavir) between 15th March 2020 to 17th April 2020. A review of adverse events and DDI-risky drug association on medical record was conducted for each patient. Each adverse events was analyzed by the Centre régional de pharmacovigilance (CRPV) to assess causality of drugs used in SARS-CoV-2 infection. RESULTS: A total of 312 precriptions were analyzed during the period, of which 110 prescriptions had 157 drug association at risk of DDIs; 26 adverse events were reported. Causality assessment by CRPV concluded that 10 (35,7 %) adverse effects were possibly related to SARS-CoV-2 drugs with only 2 (7,1 %) related to DDIs. CONCLUSIONS: Despite risk of adverse drug reactions and DDIs related to drugs used in SARS-CoV-2 infection, few iatrogenics diseases were found.

Stroke and syphilis: A retrospective study of 53 patients.

OBJECTIVE: The aim of this study was to describe the clinical, biological and radiological characteristics of patients with syphilitic vasculitis, and to assess the outcome after treatment. METHODOLOGY: A retrospective review was carried out based on the records of patients with ischemic stroke, and reactive CSF TPHA and VDRL results. None of these patients showed symptoms of any other diseases or had received high doses of penicillin. RESULTS: A total of 53 patients with stroke met the diagnostic criteria for syphilitic arteritis. Their average age was 41±12 years. Nine patients had a history of genital ulcer (17%), and the median duration of illness after presenting a chancre was 8 [range: 1-14] years. A prodromal syndrome was seen in 27 patients (50.9%) and included changes in mental status in 14 patients (26.4%), seizures in 10 cases (18.9%), headache in eight (15.1%) and memory loss in seven (13.2%). Neurological events included focal motor deficits in 29 cases (54.7%), ataxia in 11 (20.8%) and movement disorders in 15 (28.3%). HIV serology was performed in 31 patients and proved negative in every case. Disease evolution was generally favorable: 12 patients (22.6%) were autonomous at the time of hospital discharge; 29 (54.7%) had partially recovered; and only seven (13.2%) still had signs of severe sequelae. CONCLUSION: A diagnosis of syphilitic stroke should be suspected in young patients as a manifestation of syphilis, and tests for neurosyphilis should be routine in neurology departments to make a prompt diagnosis, thereby preventing psychological sequelae.

Association of vitamin D status with multiple sclerosis in a case-control study from Morocco.

BACKGROUND: Growing evidence suggests that hypovitaminosis D contributes to the pathogenesis of multiple sclerosis (MS). OBJECTIVE: This study aimed to evaluate whether vitamin D levels are associated with having MS and some of its characteristics in the Moroccan population. METHODS: Using liquid chromatography-tandem mass spectrometry, the 25(OH)D3 metabolite was measured to quantify vitamin D serum levels (DSLs) in 113 patients with MS and 146 healthy controls matched for gender and age. DSLs were then compared between patients and controls, with correlations sought between DSLs and gender, age at onset, disease duration, MS type, degree of disability (EDSS score) and disease severity (MSSS) in patients. RESULTS: Hypovitaminosis D (DSL<30ng/mL) was observed in 97.3% of MS patients and in 98.6% of controls. Although the mean DSL was slightly lower in patients (11.69±6.97ng/mL) than in controls (12.98±6.58ng/mL), there was no significant association between DSL and MS status (P=0.131). Similarly, among patients, no apparent association was found between DSL and MS type (P=0.214), EDSS score (P=0.076) or MSSS (P=0.772). CONCLUSION: Our study suggests that DSL is not associated with having MS nor with MS type, degree of disability or disease severity in the Moroccan population. On the other hand, DSL was lower in women and decreased with age.

Vitamin D deficiency and its role in neurological conditions: A review.

This review exposes recent advances on the role of vitamin D, cholecalciferol, a secosteroid, in the central nervous system. In humans, vitamin D arises from cutaneous transformation of 7-dehydrocholesterol under the effect of UVB exposure or from food intake. Vitamin D has an immunomodulatory role through its anti-inflammatory and anti-autoimmune actions. In the nervous system, vitamin D is involved in the regulation of calcium-mediated neuronal excitotoxicity, in the reduction of oxidative stress, and in the induction of synaptic structural proteins, neurotrophic factors and deficient neurotransmitters. Reduced exposure to sunlight and low food intake can lead to vitamin D deficiency. Increasing evidence highlights the impact of vitamin D deficiency as a favoring factor in various central or peripheral neurological diseases, especially multiple sclerosis and several neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease. Recently, several clinical trials on vitamin D supplementation stressed the role of vitamin D as a protective and/or prognostic factor in the onset and progress of such neurological conditions.

A clinical study of non-parkinsonian tremor in Moroccan patients.

OBJECTIVE: To report the characteristics of the most frequent tremors in a population of Moroccan patients. BACKGROUND: Tremor is the most common movement disorder. It implies a wide variety of disorders with Parkinson's disease and essential tremor being the most frequent. METHODS: A retrospective study of 148 patients with tremor referred to our movement disorders outpatient clinic was performed. Clinical features and treatment regimens were analyzed. Patients with parkinsonian tremor were excluded. RESULTS: We included 62 patients with non-parkinsonian tremor. The etiologies were as follows: essential tremor (54.8%), dystonic tremor (19.4%), tremor associated with dystonia (14.5%), enhanced physiological tremor (3.2%), cerebellar tremor (3.2%), psychogenic tremor (3.2%) and Holmes' tremor (1.6%). The characteristics of essential tremor patients were analyzed. Female patients accounted for 67.6% of patients. Mean age at the onset of tremor was 52.2 ± 16.4 years. Family history of tremor was reported in 17.6% of cases. Tremor affected the arms (94.1%), head (52.9%), voice (35.3%) and legs (8.8%). Tremor was bilateral in 87.5% but was asymmetrical in 50% of patients. Patients had postural tremor (76.5%), kinetic tremor (79.4%) and rest tremor (associated in 11.8%). Treatment relied on propranolol (88.3%), primidone (14.7%), gabapentin (14.7%), clonazepam (14.7%), alprazolam (11.8%), topiramate (5.9%) and, in one patient, radiosurgery. CONCLUSIONS: Essential tremor was the predominant diagnosis, confirming its high prevalence. There was a predominance of female patients and a peak of age at onset in the fifth and sixth decades. Asymmetry of the disease was noted in half of patients.

The Management of Persistent Distal Occlusions after Mechanical Thrombectomy and Thrombolysis: An Inter- and Intrarater Agreement Study.

BACKGROUND AND PURPOSE: The best management of patients with persistent distal occlusion after mechanical thrombectomy with or without IV thrombolysis remains unknown. We sought to evaluate the variability and agreement in decision-making for persistent distal occlusions. MATERIALS AND METHODS: A portfolio of 60 cases was sent to clinicians with varying backgrounds and experience. Responders were asked whether they considered conservative management or rescue therapy (stent retriever, aspiration, or intra-arterial thrombolytics) a treatment option as well as their willingness to enroll patients in a randomized trial. Agreement was assessed using κ statistics. RESULTS: The electronic survey was answered by 31 physicians (8 vascular neurologists and 23 interventional neuroradiologists). Decisions for rescue therapies were more frequent (n = 1116/1860, 60%) than for conservative management (n = 744/1860, 40%; P < .001). Interrater agreement regarding the final management decision was "slight" (κ = 0.12; 95% CI, 0.09-0.14) and did not improve when subgroups of clinicians were studied according to background, experience, and specialty or when cases were grouped according to the level of occlusion. On delayed re-questioning, 23 of 29 respondents (79.3%) disagreed with themselves on at least 20% of cases. Respondents were willing to offer trial participation in 1295 of 1860 (69.6%) cases. CONCLUSIONS: Individuals did not agree regarding the best management of patients with persistent distal occlusion after mechanical thrombectomy and IV thrombolysis. There is sufficient uncertainty to justify a dedicated randomized trial.

Genetic factors and multiple sclerosis in the Moroccan population: a role for HLA class II.

BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system that mainly affects young adults. The association between susceptibility to MS and HLA class II genes, in particular the DRB1*15 allele, has been reported in diverse ethnic groups. The aim of our study was to investigate the distribution of HLA-DRB1* and -DQB1* alleles in Moroccan population and their implication in the susceptibility to the disease. METHODS: Fifty-seven MS patients were compared to 172 healthy controls unrelated to one another and matched by age, sex and ethnic origin. HLA class II (DRB1* and DQB1*) typing was performed by PCR-SSP and/or Luminex (PCR-SSO). Allelic and haplotypic frequencies, P-values, odds ratio (OR) and 95% confidence interval (CI) were calculated using the software SPSS. RESULTS: A significant increase of DRB1*15 allele frequency (17.6% vs 8.4%, OR=2.67, 95% CI=1.36-5.23, P=0.004) and HLA-DRB1*15-DQB1*06 haplotype (8.8% vs 4.08%, OR=2.78, 95% CI=1.41-5.48, P=0.002) were observed in Moroccan MS patients. No association of the DR15 allele with sex or age at onset was appreciated. Concerning HLA-DQB1* alleles, no significant difference between patients and controls was found. CONCLUSIONS: Our results reveal a role for HLA-DRB1*15 allele molecules in the predisposition of Moroccan patients to MS. Although this study should be confirmed on a larger sample size, it analyzes for the first time the possible role of a genetic marker for susceptibility to MS in Moroccan population.

The gene for autosomal dominant cerebellar ataxia with pigmentary macular dystrophy maps to chromosome 3p12-p21.1.

Autosomal dominant cerebellar ataxia with pigmentary macular dystrophy (ADCA type II) is a rare neurodegenerative disorder with marked anticipation. We have mapped the ADCA type II locus to chromosome 3 by linkage analysis in a genome-wide search and found no evidence for genetic heterogeneity among four families of different geographic origins. Haplotype reconstruction initially restricted the locus to the 33 cM interval flanked by D3S1300 and D3S1276 located at 3p12-p21.1. Combined multipoint analysis, using the Zmax-1 method, further reduced the candidate interval to an 8 cM region around D3S1285. Our results show that ADCA type II is a genetically homogenous disorder, independent of the heterogeneous group of type I cerebellar ataxias.

Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion.

The gene for spinocerebellar ataxia 7 (SCA7) has been mapped to chromosome 3p12-13. By positional cloning, we have identified a new gene of unknown function containing a CAG repeat that is expanded in SCA7 patients. On mutated alleles, CAG repeat size is highly variable, ranging from 38 to 130 repeats, whereas on normal alleles it ranges from 7 to 17 repeats. Gonadal instability in SCA7 is greater than that observed in any of the seven known neuro-degenerative diseases caused by translated CAG repeat expansions, and is markedly associated with paternal transmissions. SCA7 is the first such disorder in which the degenerative process also affects the retina.

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.

Research participants may not recall their participation but have a better understanding of alternative management options than patients in routine care.

BACKGROUND: Patient understanding of care interventions, of the clinical uncertainty, and of their participation in clinical research is often poor. We hypothesized that compared to routine care, patients would better understand the prevailing uncertainty when they participated in research. METHODS: A questionnaire was administered to patients at the time they attended a follow-up neurovascular clinic 4 to 52 weeks after a care episode where they did or did not participate in a clinical trial. Patients were not reminded whether they had previously participated in a clinical trial. Questions concerned their understanding of the risks/benefits of interventions, the availability of alternative options, whether their personal opinion was taken into consideration, the reason for the final decision, their confidence at having received the best management, and whether they had been research participants. RESULTS: Between June 2019 and June 2020, 167 patients were recruited; 71 had truly been research participants, while 96 had not. A greater proportion of research patients were aware of the existence of management alternatives (65% versus 44%; P=0.008). Patients of both groups believed their personal opinion counted in the final decision (76% versus 70%), and patients were equally confident that they had received the best management (94%). Research patients believed they had participated in research 46% of the time, compared to 12% of routine care patients (P=0.003). CONCLUSION: Many patients do not recall that they participated in a clinical trial, but they have a better understanding of the clinical uncertainty and of the availability of alternative management options.

[Multiple sclerosis associated with antiphospholipid syndrome: diagnostic and therapeutic difficulties]. / Sclérose en plaques associée à un syndrome des antiphospholipides : difficultés diagnostiques et thérapeutiques.

Strokes are the main neurological manifestation of antiphospholipid syndrome. Other clinical presentations are possible and may mimic classic symptoms of multiple sclerosis (MS). A 46-year-old woman, with a history of two miscarriages, presented four subacute neurological episodes (optic neuritis, right facial paralysis, paraparesis of the thigh, and right brachial monoparesis). Using McDonald criteria, the diagnosis of multiple sclerosis was retained. Because of the occurrence of thrombocytopenia during a final relapse, we reconsidered the diagnosis of MS. Search for antiphospholipid antibodies was positive. All clinical manifestations and complementary tests were compatible with the diagnosis of antiphospholipid syndrome associated with multiple sclerosis. Given the great similarity of clinical, radiological and biological findings in the two diseases, non-thrombotic neurological manifestations of antiphospholipid syndrome can be difficult to distinguish from MS associated with antiphospholipid syndrome.

[Quality of life and multiple sclerosis: Arabic language translation and transcultural adaptation of "MSQOL-54"]. / Qualité de vie et sclérose en plaques: traduction en langue arabe et adaptation transculturelle du "MSQOL-54".

INTRODUCTION: Quality of life assessment of multiple sclerosis patients in Morocco appears essential, considering the early age of onset and the significant functional, psychological and social impact of disease symptoms and disorders. Our goal was to translate the MSQOL-54 into Arabic followed by cross-cultural adaptation, and validation of the translated version. METHODS: Patients with multiple sclerosis were recruited over a period of 7 months, from February to August 2007. Sociodemographic data and a detailed clinical description (neurological examination, EDSS, MMS) were collected before administration of the questionnaire. The MSQOL-54 was translated and test validation techniques were applied: back translation, revision by a committee of experts, study of acceptability, multivariate analysis, reliability and clinical validity. RESULTS: Seventy-eight patients were included. There were 23 men and 55 women of various ages, various stages of disability (EDSS from 1 to 8.5) and various clinical forms. Evaluation of the 78 completed questionnaires revealed a satisfactory acceptability considering the limited number of missing answers and the average time to complete the test (24 minutes). The reliability and the multimultivariate analysis were excellent (coefficient of Cronbach ≥0.7 with a percentage of convergence and divergence validity around 100%). A very significant relationship was found between physical scores and EDSS. CONCLUSION: Measuring the quality of life is an approach that confirmed its usefulness through this study. We propose a valid Arabic version of MSQOL-54.

Neurological manifestations of Behçet's disease: evaluation of 40 patients treated by cyclophosphamide.

INTRODUCTION: Neurological manifestations in Behçet's disease represent between 4 to 49% of systemic manifestations and remain, in the long term, the leading cause of morbidity and mortality. METHODS: Retrospective series of 40 severe Neurobehçet cases fulfilling the International Study Group criteria for Behçet's disease were consecutively recruited over a period from June 2004 to December 2010. All patients had clinical and ophthalmologic examinations; they underwent laboratory and imaging investigations. They received corticosteroids and cyclophosphamide as initial bolus of 600 mg/m(2) of BSA in the 1st, 2nd, 4th, 6th and 8th day followed by a bolus of 600 mg/m(2) BSA every 2 months for 2 years. Antithrombotic therapy was given to patients with cerebral deep venous thrombosis. Patient follow-up and tolerance to treatment were analyzed. RESULTS: The average age at diagnosis was 34±13 years, with a sex-ratio of 1.78. The clinical presentation was dominated by the meningoencephalitis in 48.8% of cases, cerebral deep venous thrombosis in 43.6% of cases and myelopathy in 7.7% of cases. The 40 patients receiving cyclophosphamide bolus, despite two aggravated cases, evolved positively with clinical improvement and good tolerance. CONCLUSION: The demographic and clinical aspects of our series are similar to those reported in the literature. In contrast to previously reported cases of a poor prognosis in severe neurobehçet's disease, our study suggests that immediate and aggressive treatment by cyclophosphamide may ameliorate the prognosis. However, a multicenter study is needed to confirm the possible efficacy of cyclophosphamide and further assess the long-term tolerance.

Understanding the reliability of trial outcome measures: The example of angiographic results of surgical or endovascular treatments of aneurysms.

BACKGROUND: The reliability of outcome measures is of central importance in clinical research. Studies of reliability remain rare in the neurovascular field. METHODS: A narrative review of the history (1997-2021) of reporting angiographic results of the surgical or endovascular treatments of aneurysms serves to illustrate the importance of precisely defining outcome measures. We also review how the reliability of an angiographic classification system was studied. DISCUSSION: Outcome measures are commonly used without precise definitions. When definitions or classification systems exist, they are rarely verified for their reliability. Twenty-five years following its introduction, a classification of angiographic results of aneurysm treatments is still being studied and modified. CONCLUSION: The reliability of outcome measures should be made a research priority if we are to practice outcome-based medical or surgical care.

Inter-rater reliability of the simplified Modified Rankin Scale as an outcome measure for treated cerebral aneurysm patients.

BACKGROUND: The modified Rankin scale (mRS) is commonly used as a clinical outcome measure in aneurysm trials, but inter-observer reliability in treated patients has not been tested. METHODS: We reviewed the literature on inter-observer reliability studies of the mRS. Sixty patients with ruptured (n=47) or unruptured (n=13) aneurysms treated with endovascular methods (n=34) or surgical clipping (n=26) were independently evaluated by a neurosurgeon, a stroke neurologist, and a novice research assistant, and a simplified mRS score assigned. Results were analyzed using Gwet's AC1/2 reliability coefficients (KG). RESULTS: No previous reports validating the reliability of the mRS in treated aneurysm patients were identified. Using the mRS 0-5, inter-rater agreement was almost perfect (KG=0.89 [0.86-0.93]). Agreement between raters remained almost perfect regardless of the rater's expertise. Agreement was almost perfect (KG=0.87 [0.77-0.96] when the mRS was dichotomized 0-2 vs 3-5, but fell to moderate when dichotomized 0-1 vs 2-5 (KG=0.59 (0.42-0.75). Agreement using the 0-2 vs 3-5 dichotomized mRS remained almost perfect for coiled (KG=0.90), clipped (KG=0.82), ruptured (KG=0.84), and unruptured (KG=0.95) aneurysms. Dichotomization of results at 0-1 vs 2-5 would have resulted in an (undesirable) significant difference in good outcomes between raters (P=.003), but not at 0-2 vs 3-5 (P=.52). CONCLUSION: The simplified mRS appears to be a reliable clinical outcome measure for treated cerebral aneurysm patients. When needed, dichotomization is more reliable at mRS 0-2 vs 3-5 than at 0-1 vs 2-5. The simplified mRS is a promising tool in the functional assessment of aneurysm patients recruited in pragmatic care trials.

[Neuromarketing: When marketing meet neurosciences]. / Neuromarketing : lorsque neurosciences et marketing se rejoignent.

INTRODUCTION: The emergence of brain imaging in recent years has been accompanied by an alliance between neuroscientists and marketers. This collaboration gave birth to "neuromarketing", a new field that uses imaging techniques with the aim of resolving marketing issues. STATE OF THE ART: Several studies have shown that pleasure felt at the sight of a product or after its consumption, is activated by a reward system involving ventral striatum. Since then, marketers seeking exploit this data and have found that some marketing actions can generate added satisfaction in a placebo-like manner. However, neuromarketing suffer from many limits that are a barrier to its development and its scope is restricted. PERSPECTIVES: Through this article, we attempt to give an overview on neuromarketing and its neural correlates while provide a perspective toward the use of field for less commercial purposes. CONCLUSION: The neuromarketing is a new field which efficiency is not proven. Its results must be interpreted with caution.

[Stroke revealing granulomatosis]. / Accident vasculaire cérébral révélant une granulomatose.

INTRODUCTION: Central nervous system involvement is rare in Wegener granulomatosis. Stroke is the most common event suggestive of the disease. COMMENT: A 35-year-old woman, who was followed for rhinitis and mild asthma, described gradual decline of visual acuity in the right eye over two months, persistent nasal obstruction and fronto-orbital headache since a few weeks. She presented left hemiparesis due to a stroke, associated with exophthalmos and deficits of the optic nerve and abducens of the right eye. The otolaryngological examination found signs of crusty rhinitis and right nasal stenosis. The diagnosis of Wegener's granulomatosis was established on the basis of the clinical findings, radiological aspects and the presence of ANCA. The patient was treated by antiplatelet agents and high-dose corticosteroids associated with immunosuppressive drugs including cyclophosphamide in a monthly bolus. DISCUSSION: This case illustrates two of the three pathogenic mechanisms that may account for central nervous system involvement in Wegener granulomatosis: vasculitis, extension by contiguity of granulomatous tissue from the nasal cavity or sinuses, and in situ formation of a granuloma into the brain parenchyma or meninges.

Noninvasive Angiographic Results of Clipped or Coiled Intracranial Aneurysms: An Inter- and Intraobserver Reliability Study.

BACKGROUND AND PURPOSE: Noninvasive angiography is commonly used to assess the outcome of surgical or endovascular treatment of intracranial aneurysms in clinical series or randomized trials. We sought to assess whether a standardized 3-grade classification system could be reliably used to compare the CTA and MRA results of both treatments. MATERIALS AND METHODS: An electronic portfolio composed of CTAs of 30 clipped and MRAs of 30 coiled aneurysms was independently evaluated by 24 raters of diverse experience and training backgrounds. Twenty raters performed a second evaluation 1 month later. Raters were asked which angiographic grade and management decision (retreatment; close or long-term follow-up) would be most appropriate for each case. Agreement was analyzed using the Krippendorff α (αK) statistic, and the relationship between angiographic grade and clinical management choice, using the Fisher exact and Cramer V tests. RESULTS: Interrater agreement was substantial (αK = 0.63; 95% CI, 0.55-0.70); results were slightly better for MRA results of coiling (αK = 0.69; 95% CI, 0.56-0.76) than for CTA results of clipping (αK = 0.58; 95% CI, 0.44-0.69). Intrarater agreement was substantial to almost perfect. Interrater agreement regarding clinical management was moderate for both clipped (αK = 0.49; 95% CI, 0.32-0.61) and coiled subgroups (αK = 0.47; 95% CI, 0.34-0.54). The choice of clinical management was strongly associated with the size of the residuum (mean Cramer V = 0.77 [SD, 0.14]), but complete occlusions (grade 1) were followed more closely after coiling than after clipping (P = .01). CONCLUSIONS: A standardized 3-grade scale was found to be a reliable and clinically meaningful tool to compare the results of clipping and coiling of aneurysms using CTA or MRA.