Publications equipe de recherche en neurologie et en neuogénétique brain anoxia

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]).Brain anoxia 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.Brain anoxia

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.Brain anoxia 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.

Human genetics studies have implicated GALNT2, encoding galnac-T2, as a regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, but the mechanisms relating GALNT2 to HDL-C remain unclear. We investigated the impact of homozygous GALNT2 deficiency on HDL-C in humans and mammalian models. We identified two humans homozygous for loss-of-function mutations in GALNT2 who demonstrated low HDL-C. We also found that GALNT2 loss of function in mice, rats, and nonhuman primates decreased HDL-C. O-glycoproteomics studies of a human GALNT2-deficient subject validated ANGPTL3 and apoc-III as galnac-T2 targets.Brain anoxia additional glycoproteomics in rodents identified targets influencing HDL-C, including phospholipid transfer protein (PLTP). GALNT2 deficiency reduced plasma PLTP activity in humans and rodents, and in mice this was rescued by reconstitution of hepatic galnt2. We also found that GALNT2 GWAS snps associated with reduced HDL-C also correlate with lower hepatic GALNT2 expression. These results posit GALNT2 as a direct modulator of HDL metabolism across mammals.

Objective. This study aims to evaluate the incidence of pathological cerebral activity responses to intermittent rhythmic photic stimulation (IPS) after a single epileptic seizure. Patients and methods. One hundred and thirty-seven eegs were performed at the neurophysiology department of mohamed V teaching military hospital in rabat.Brain anoxia clinical and EEG data was collected. Results. 9.5% of our patients had photoparoxysmal discharges (PPD). Incidence was higher in males than in females, but p value was not significant (p = 0.34), and it was higher in children compared to adults with significant p value (p = 0.08). The most epileptogenic frequencies were within the range 15-20 hz. 63 patients had an EEG after 72 hours; among them 11 were photosensitive (p = 0.001). The frequency of the PPR was significantly higher in patients with generalized abnormalities than in focal abnormalities (p = 0.001). EEG confirmed a genetic generalized epilepsy in 8 cases among 13 photosensitive patients. Conclusion. PPR is age related. The frequencies within the range 15-20 hz should inevitably be included in EEG protocols.Brain anoxia the presence of PPR after a first seizure is probably more in favor of generalized seizure rather than the other type of seizure. PPR seems independent from the delay seizure-EEG. Our study did not show an association between sex and photosensitivity.

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.Brain anoxia 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.1617GC 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.

It is well established that the temporal lobe epilepsy (TLE) is linked to the autonomic nervous system dysfunctions. Seizures alter the function of different systems such as the respiratory, cardiovascular, gastrointestinal, and urogenital systems.Brain anoxia the aim of this work was to evaluate the possible factors which may be involved in interictal cardiovascular autonomic function in temporal lobe epilepsy with complex partial seizures, and with particular attention to hippocampal sclerosis. The study was conducted in 30 patients with intractable temporal lobe epilepsy (19 with left hippocampal sclerosis, 11 with right hippocampal sclerosis). All subjects underwent four tests of cardiac autonomic function: heart rate changes in response to deep breathing, heart rate, and blood pressure variations throughout resting activity and during hand grip, mental stress, and orthostatic tests. Our results show that the right cerebral hemisphere predominantly modulates sympathetic activity, while the left cerebral hemisphere mainly modulates parasympathetic activity, which mediated tachycardia and excessive bradycardia counterregulation, both of which might be involved as a mechanism of sudden unexpected death in epilepsy patients (SUDEP).Brain anoxia

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is characterized by marked dilatation of the bladder and microcolon and decreased intestinal peristalsis. Recent studies indicate that heterozygous variants in ACTG2, which codes for a smooth muscle actin, cause MMIHS. However, such variants do not explain MMIHS cases that show an autosomal recessive mode of inheritance. We performed exome sequencing in a newborn with MMIHS and prune belly phenotype whose parents are consanguineous and identified a homozygous variant (c.3598AT: p.Lys1200Ter) in MYH11, which codes for the smooth muscle myosin heavy chain. Previous studies showed that loss of myh11 function in mice causes a bladder and intestinal phenotype that is highly reminiscent of MMIHS.Brain anoxia all together, these observations strongly suggest that loss-of-function variants in MYH11 cause MMIHS. The documentation of variants in ACTG2 and MYH11 thus points to the involvement of the contractile apparatus of the smooth muscle in MMIHS. Interestingly, dominant-negative variants in MYH11 have previously been shown to cause thoracic aortic aneurism and dilatation. Different mechanisms of MYH11 disruption may thus lead to distinct patterns of smooth muscle dysfunction.

BACKGROUND: multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by focal inflammatory infiltrates, demyelinating lesions and axonal injury. The purpose of the study was to evaluate the retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in moroccan patients with MS and to assess the relationship between RNFL thickness and disease duration, expanded disability status scale (EDSS) score, visual acuity and automated visual field indices.Brain anoxia

MATERIALS AND METHODS: thirty-one patients with definite MS and thirty-one disease-free controls were enrolled in the study. After neurologic consultation, ophthalmologic examination including visual acuity, automated visual field testing and OCT were performed.

RESULTS: significant differences between both groups were observed in OCT parameters (total, temporal and macular ganglion cell layer) with lower thickness in the MS group. In patients without a history of optic neuritis, there were statistically significant inverse correlations between total RNFL thickness and disease duration, neurologic disability evaluated by the EDSS, logmar visual acuity and automated visual field indices.

CONCLUSIONS: OCT seems to be a reproducible test to detect axonal loss of ganglion cells in MS.Brain anoxia further and larger longitudinal prospective studies would be valuable to assess the evolution over time of the RNFL measurements in moroccan MS patients.

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.Brain anoxia 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.Brain anoxia

BACKGROUND: huntington’s disease (HD) occurs worldwide with prevalence varying from 0.1 to 10/100,000 depending of the ethnic origin. Since no data is available in the maghreb population, the aim of this study is to describe clinical and genetic characteristics of huntington patients of moroccan origin.

METHODS: clinical and genetics data of 21 consecutive patients recruited from 2009 to 2014 from the outpatient clinic of six medical centers were analyzed. Statistical analysis was performed using descriptive statistics.

RESULTS: twenty one patients from 17 families were diagnosed positive for the IT15 gene CAG expansion. Clinical symptoms were predominantly motor (19/21). Twelve patients had psychiatric and behavioral disorders, and 11 patients had cognitive disorders essentially of memory impairment.Brain anoxia analysis of genetic results showed that 5 patients had reduced penetrant (RP) alleles and 16 had fully penetrant (FP) alleles. The mean CAG repeat length in patients with RP alleles was 38.4 ± 0.54, and 45.37 ± 8.30 in FP alleles. The age of onset and the size of the CAG repeat length showed significant inverse correlation (p 0.001, r = -0.754).

CONCLUSION: clinical and genetic data of moroccan patients are similar to those of caucasian populations previously reported in the literature.