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.

Novel WFS1 Variants in Two Moroccan Families with Wolfram Syndrome.

Background: Wolfram syndrome (WFS) is an autosomal recessive disorder that often leads to diabetes, optic atrophy, and sensorineural hearing loss. The aim of this study was to determine the clinical characteristics and the genetic cause of the first two Moroccan families presenting with WFS. Methods: The clinical features of five members of two WFS families were evaluated. Whole-exome sequencing was conducted to explore the underlying genetic cause in the affected patients. Results: Two homozygous variants in the WFS1 gene were identified, each in one of the two families studied: a missense c.1329C>G variant (p.Ser443Arg) and a nonsense mutation c.1113G>A (p.Trp371Ter). These variants affected conserved amino acid residues, segregated well in the two families, and are absent from genetic databases and in controls of Moroccan origin. Bioinformatics analysis classified the two variants as pathogenic by in silico tools and molecular modeling. Conclusion: Our study identified for the first time two variants in Moroccan patients with WFS that extends the mutational spectrum associated with the disease.

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.

Trends in the consumption and cost of antiepileptics in Morocco between 2008 and 2018.

INTRODUCTION: Epilepsy is one of the most common chronic neurological diseases. In Morocco, it is the second most common reason for consulting a neurologist. Its prevalence was estimated in Casablanca in 1998 at 1.1%. This study was carried out with the aim of evaluating, on the one hand, the consumption of antiepileptics and, on the other hand, the impact of their generic drugs on the pharmaceutical market between 2008 and 2018 in Morocco. MATERIALS AND METHODS: We used sales data for antiepileptic drugs collected from the Moroccan subsidiary of IQVIA, a multinational healthcare data science company, and we converted them into a defined daily dose (DDD/1000 inhabitants). RESULTS: The consumption of antiepileptic drugs increased from 442 to 641 DDD/1000 inhabitants between 2008 and 2018, all molecules combined, recording a 45% increase in the period studied. From an economic point of view, the calculation of the average cost of DDD, all molecules combined, gives an average cost of 2.42 dollars/DDD in 2018 versus 3.53 dollars/DDD in 2008 (1 dirham = 0.11 dollar), which corresponds to a decrease of -30%. This is due mainly to the introduction of generic drugs. CONCLUSION: These results show that while the average cost of a DDD has decreased, the consumption of antiepileptics has increased in Morocco over the years. Several events that have marked the drug market in Morocco have contributed to this trend, including the arrival on the market of several new molecules indicated for the treatment of epilepsy, the decrease in drug prices in 2014 and the policy of promoting generic drugs.

Gene Panel Sequencing Identifies Novel Pathogenic Mutations in Moroccan Patients with Familial Parkinson Disease.

In the past two decades, genetic studies of familial forms of Parkinson's disease (PD) have shown evidence that PD has a significant genetic component. Indeed, 12 genes are strongly involved in PD causality, three of them having dominant inheritance and 9 causing early-onset autosomal recessive forms, including 3 with a typical PD and 6 with an atypical parkinsonism. The aim of this study was to determine the genetic basis of familial PD in Moroccan patients. We selected 18 Moroccan index case with familial forms of PD. Patients were first screened for exon-rearrangements by MLPA kit. They were then analyzed by gene panel next-generation sequencing (NGS). Functional variants with minor allele frequencies < 0.5% in public databases were considered potential candidate variants to PD. In the 18 PD patients with a positive family history that were analyzed, MLPA assays identified PRKN deletions in two patients: a homozygous exon 3-5 deletion and a heterozygous exon 4 deletion. Sixteen rare SNV were identified by NGS, four of them were novel. Seven mutations were categorized as pathogenic, five as likely pathogenic, two to be of uncertain significance, and 3 were predicted to be likely benign but may give a weaker pathogenic effect and could contribute to PD since they were found in late-onset PD patients. Rare or novel mutations that could be related to the disease were identified in 72% of these patients (13/18), including nine with bi-allelic pathogenic/likely pathogenic variants in genes causing recessive PD, particularly PRKN and PINK1. Mutations in genes with dominant inheritance were found in 4/18 patients (22%).

[Current antiplatelet agents, new inhibitors and therapeutic targets]. / Antiplaquettaires actuels, en cours de développement et cibles thérapeutiques.

Cardiovascular diseases are the leading cause of deaths in the world. Platelets play a major role in the occurrence of these diseases and the development of antiplatelet drugs is a priority in the fight against cardiovascular diseases-associated mortality. Aspirin and thienopyridine-based P2Y12 inhibitors are the main drugs currently used. These molecules target the initiation of platelets activation and are responsible for a moderate inhibitory action. Other antiplatelet agents, as glycoprotein (GP) IIb/IIIa antagonists, inhibit platelet aggregation independently of initial activation-associated pathways, but are responsible for increased hemorrhagic events. Regarding each antiplatelet agent's specific characteristics, the prescription of these drugs must take into account the type of cardiovascular event, the age of the patient, the past medical history, and the potential hemorrhagic adverse events. Thus, there is a need for the development of new molecules with a more targeted effect, maintaining optimal efficiency but with a reduction of the hemorrhagic risk, which is the principal limitation of these treatments.

TITLE: Antiplaquettaires actuels, en cours de développement et cibles thérapeutiques. ABSTRACT: Les maladies cardiovasculaires (MCV) sont la première cause de mortalité dans le monde. Les plaquettes jouent un rôle majeur dans le développement de ces maladies et la mise au point d'antiplaquettaires efficaces constitue une priorité dans le cadre de la lutte contre la mortalité liée aux MCV. L'aspirine et les médicaments de la famille des thiénopyridines sont les agents antiplaquettaires les plus utilisés actuellement. Ces médicaments ciblent des voies de signalisation impliquées dans l'initiation de l'agrégation, exerçant ainsi un effet antiplaquettaire modéré. D'autres médicaments aux effets plus importants, comme les molécules dirigées contre le récepteur GPIIb/IIIa, inhibent l'agrégation plaquettaire indépendamment de la voie de signalisation initiant l'activation plaquettaire, mais ils sont associés à des complications hémorragiques majorées. Étant données les caractéristiques spécifiques de chacun de ces agents antiplaquettaires, leur prescription nécessite de prendre en compte le type d'évènement cardio-vasculaire, l'âge et les comorbidités du patient traité et, bien sûr, les effets secondaires hémorragiques potentiels de la molécule qui est prescrite. Apparaît donc la nécessité de mettre au point de nouvelles molécules ayant un effet plus ciblé, gardant une efficacité optimale, mais permettant une réduction du risque hémorragique qui constitue la principale limite des médicaments antiplaquettaires.

A case of bilateral thalamic infarct complicating tuberculous meningoencephalitis.

Ischemic stroke can result from multiple etiologies. It can also be a complication of tuberculous meningoencephalitis and determine its outcome. stroke secondary to tuberculous meningoencephalitis, occurs in 30% cases in the basal ganglia region, unusually in the thalamus. The mechanism of stroke in this condition is vasculitis. We report an unusual case of bilateral thalamic infarcts complicating tuberculous meningoencephalitis. Ischemic stroke in tuberculous meningoencephalitis is unpredictable with poor prognosis despite antituberculous drug treatment, emphasising the importance of primary prevention, particularly in tuberculosis endemic areas.

Contribution of fibrin glue in the surgery of cyanogenic and non-cyanogenic congenital cardiopathies: retrospective cohort study.

BACKGROUND: Postoperative bleeding in cardiovascular surgery is a frequent and complicated situation for the surgical team, and may also be responsible for significant hospital expenditures. Fibrin glue are indicated in surgery to improve hemostasis when conventional techniques such as compression, sutures or electrocoagulation are insufficient. Through this study, we tried to study the contribution of fibrin glue to the improvement of the clinical parameters (volume of postoperative bleeding, length of stay in intensive care, volume of blood transfusion ...) in two populations having undergone cardiac surgery, one in which we used the fibrin glue and one without fibrin glue. METHODS: This was a retrospective cohort study conducted in the cardiovascular surgery department of our Hospital in Rabat between June 2012 and June 2015. Fibrin glue (Tissucol® of BAXTER) was used in one group with an haemostatic aim. The pre and post-operative clinical data of the patients were analyzed and compared with data from patients who were operated without the use of fibrin glue because it was not yet available in the hospital. The clinical parameters were collected analyzed using the SPSS 13.0 software. RESULTS: One hundred ten patients were included in this study. The fibrin glue was used intraoperatively in 55 patients and not used in 55 patients. 43 (39.1%) had cyanogenic diseases and 67 (60.9%) had non-cyanogenic pathologies. The volume of transfused red blood cells was lower in patients in whom we used biological glue (p = 0.005), as well as the number of days spent in intensive care (p = 0.02). However, the difference was not significant between the two groups for other parameters such as bleeding volume per kg, the number of units of fresh frozen plasma and the platelet units count transfused. CONCLUSIONS: The results we found show that fibrin glue reduces the duration of hospitalization in resuscitation and reduces the number of units of transfused red blood cells to patients after surgery. However, it does not reduce significantly the total postoperative bleeding volume per weight, the number of fresh frozen plasma units or platelets units transfused. The fibrin glue could therefore be of moderate benefit in pediatric cardiac surgery.

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.

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.

A Novel Homozygous p.L539F Mutation Identified in PINK1 Gene in a Moroccan Patient with Parkinsonism.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Ten of fifteen causative genes linked to familial forms of PD have been reported to cause autosomal recessive forms. Among them, mutations in the PTEN-induced kinase 1 (PINK1) gene were shown to be responsible for a phenotype characterized by early onset, good response to levodopa, and a benign course. Using chromosomal microarray analysis and Sanger sequencing, we identified a homozygous G/C substitution in a 58-year-old Moroccan man diagnosed with recessive inherited Parkinson's disease. This G-to-C transition occurred at position 1617 leading to an amino acid change L/F at position 539 located in highly conserved motif in the C terminal sequence of PINK1. Interestingly, the c.1617G>C substitution is absent in 192 ethnically matched control chromosomes. Our findings have shown that the p.L539F is a novel mutation located in the C terminal sequence of the PINK1 protein that could be pathogenic and responsible for a clinical phenotype resembling idiopathic Parkinson's disease with rapid progression and early cognitive impairment.

Mutations in CAPN1 Cause Autosomal-Recessive Hereditary Spastic Paraplegia.

Hereditary spastic paraplegia (HSP) is a genetically and clinically heterogeneous disease characterized by spasticity and weakness of the lower limbs with or without additional neurological symptoms. Although more than 70 genes and genetic loci have been implicated in HSP, many families remain genetically undiagnosed, suggesting that other genetic causes of HSP are still to be identified. HSP can be inherited in an autosomal-dominant, autosomal-recessive, or X-linked manner. In the current study, we performed whole-exome sequencing to analyze a total of nine affected individuals in three families with autosomal-recessive HSP. Rare homozygous and compound-heterozygous nonsense, missense, frameshift, and splice-site mutations in CAPN1 were identified in all affected individuals, and sequencing in additional family members confirmed the segregation of these mutations with the disease (spastic paraplegia 76 [SPG76]). CAPN1 encodes calpain 1, a protease that is widely present in the CNS. Calpain 1 is involved in synaptic plasticity, synaptic restructuring, and axon maturation and maintenance. Three models of calpain 1 deficiency were further studied. In Caenorhabditis elegans, loss of calpain 1 function resulted in neuronal and axonal dysfunction and degeneration. Similarly, loss-of-function of the Drosophila melanogaster ortholog calpain B caused locomotor defects and axonal anomalies. Knockdown of calpain 1a, a CAPN1 ortholog in Danio rerio, resulted in abnormal branchiomotor neuron migration and disorganized acetylated-tubulin axonal networks in the brain. The identification of mutations in CAPN1 in HSP expands our understanding of the disease causes and potential mechanisms.

[Clinical and environmental aspects of amyotrophic lateral sclerosis in moroccan population: a study of 60 cases]. / Aspects cliniques et environnementaux de la sclérose latérale amyotrophique chez une population morocaine: etude de 60 cas.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is the most common disease of the motor neuron disease. Its etiology remains unknown but several studies incriminate the environmental factors in its genesis. THE AIM: of this study was to describe the epidemiological, clinical and environmental aspects of ALS in Moroccan population. METHODS: 60 ALS patients were recruited over a period of 5 years from January 2008 to September 2012. Patients were evaluated by detailed record of exploitation. Statistical analysis was performed using SPSS 13.0. RESULTS: The average age of the population was 52.1 ± 11.2 years with a sex ratio of M/F = 1.5. The average age of onset was 50 ± 11.7 years. In the group of patients exposed to toxic a significantly higher proportion of solvent exposure was found (p = 0.02). However there was no significant association with exposure to heavy metals, pesticides, or with toxic and eating habits. ALS is more frequent in the west region of Morocco (p = 0.03). CONCLUSIONS: The positive association between exposure to solvents and ALS found in our population has been reported in the literature. The frequency of the ALS early west region suggests may be environmental or genetic origin. These results are preliminary and require a multicenter study to have more data and better highlight the environmental characteristics of ALS in the Moroccan population.

[Pathological and clinical correlations in renal AA amyloidosis: A Moroccan series of 30 cases]. / Amyloses rénales AA : corrélations anatomocliniques dans une série marocaine de 30 cas.

OBJECTIVE: Study of histological and clinical correlations of 30 cases of renal amyloidosis AA diagnosed between November 2010 and December 2012. RESULTS: The main causes associated with amyloidosis AA were represented by chronic infectious diseases (60%). Nephrotic syndrome and renal failure were observed in 94% and 73% respectively. The distribution of amyloid deposits: 90% of patients had a glomerular form and 10% had a vascular form. Inflammatory reaction associated with AA renal amyloidosis was present in 50% of cases. This inflammation was observed near amyloid deposits associated with a deposition of immunoglobulin chains and/or complement factors. CONCLUSION: Our study confirms the predominance of AA amyloidosis complicating chronic infectious diseases, especially tuberculosis. Our data point out a relationship between the morphology of renal AA amyloidosis, its clinical presentation and prognosis.