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Background: Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey of countries on 6 continents to define MT access (MTA), the disparities in MTA, and its determinants on a global scale. Methods: Our survey was conducted in 75 countries through the Mission Thrombectomy 2020+ global network between November 22, 2020, and February 28, 2021. The primary end points were the current annual MTA, MT operator availability, and MT center availability. MTA was defined as the estimated proportion of patients with LVO receiving MT in a given region annually. The availability metrics were defined as ([current MT operators×50/current annual number of estimated thrombectomy-eligible LVOs]×100 = MT operator availability) and ([current MT centers×150/current annual number of estimated thrombectomy-eligible LVOs]×100= MT center availability). The metrics used optimal MT volume per operator as 50 and an optimal MT volume per center as 150. Multivariable-adjusted generalized linear models were used to evaluate factors associated with MTA. Results: We received 887 responses from 67 countries. The median global MTA was 2.79% (interquartile range, 0.70–11.74). MTA was Conclusions: Access to MT on a global level is extremely low, with enormous disparities between countries by income level. The significant determinants of MT access are the country’s per capita gross national income, prehospital LVO triage policy, and MT operator and center availability.

A 44-year-old female patient with a history of recurrent oral and genital ulcers presented with rapid gait disturbance, headaches, dysphonia, dysphagia, and diplopia evolving for 3 weeks. On examination, spastic tetraparesis, cerebellar ataxia, and nerves palsies were noted. Pseudofolliculitis of the lower limbs and active buccal ulcers were identified. Cerebral MRI demonstrated T2-Flair hyperintense capsulothalamic lesion with midbrain and latero-protuberantial extension. The international criteria for the diagnosis of definite Neuro-Behçet’s disease (NBD) were met in our patient. Evolution under cyclophosphamide and intravenous methylprednisolone was favorable. The radiological findings in NBD are broad and challenging. Clinicians should be particularly suspicious of NBD in brain MRI with extensive lesions, involving the brainstem.

The objective of our study was to investigate the impact of the mitochondrial polygenic score (MGS) and lifestyle/environmental data on age at onset in LRRK2 p.Gly2019Ser parkinsonism (LRRK2-PD) and idiopathic Parkinson’s disease (iPD).In this study, we included N=486 patients withLRRK2-PD and N=9259 patients with iPD from AMP-PD, Fox Insight, and a Tunisian Arab-Berber founder population. Genotyping data was utilized to perform the MGS analysis, using 14 Single Nucleotide Polymorphisms (SNPs) from genes causally associated with mitochondrial function and PD risk. Additionally, lifestyle and environmental data were obtained from the PD risk factor questionnaire (PD-RFQ). Correlation analyses and linear regression models were used to assess the relationship between MGS, lifestyle/environment, and AAO.We observed that higher MGS was associated with earlier AAO in patients withLRRK2-PD (p=4.0×10−4, β=-0.18) but not in patients with iPD. A correlation between MGS and AAO was visibly stronger in European ancestryLRRK2-PD patients (p=0.01, r=-0.16) than in Tunisian Arab-Berber patients (p=0.44, r=-0.05). We found that the MGS interacted with coffee (p=0.03, β=-0.38) and caffeinated soda consumption (p=0.03, β=-0.37) inLRRK2-PD and with caffeine soda consumption (p=0.047, β=-0.22) and pesticide exposure (p=0.02, β=-0.37) in iPD. Thus, patients with a high MGS had an earlier AAO only if they consumed caffeine or were exposed to pesticides.The MGS related to mitochondrial function was associated with AAO inLRRK2-PD but not iPD with an ethnic-specific effect. Caffeine consumption or pesticide exposure interacted with MGS to predict PD AAO. Our study suggests gene-environment interactions as modifiers of AAO inLRRK2-PD.

Pial arteriovenous fistulas (AVFs) are rare neurovascular malformations. They differ from arteriovenous malformations (AVMs) in that they involve single or multiple feeding arteries, draining directly into a dilated cortical vein with no intervening nidus. Pial and dural AVFs differ in blood supply, as the first originate from pial or cortical arteries and the latter from outside the dural leaflets. Unlike dural AVFs, most of the pial AVFs are supratentorial. The vast majority are congenital, manifesting during infancy. Acquired pial AVFs are significantly rarer and occur after vasculopathy, head trauma, brain surgery, or cerebral vein thrombosis. We describe a unique case of an acquired pial AVF in a 50-year-old man secondary to a cortical vein thrombosis manifesting as a focal-onset seizure with secondary generalization. A cerebral digital subtraction angiography revealed a low-flow pial AVF fed by a postcentral branch of the left middle cerebral artery draining to the superior sagittal sinus via a cortical vein. It also showed a collateral venous circulation adjacent to the previously thrombosed left parietal vein. There was no evidence of an associated dural AVF or venous varix. Endovascular treatment was scheduled three months later, but the angiogram preceding the embolization showed spontaneous and complete closure of the malformation. To our knowledge, this is the first case illustrating acquired pure pial AVF unaccompanied by a dural component following cortical vein thrombosis, eventually resulting in an unprompted closure.

Background : Sarcoidosis is a rare idiopathic systemic inflammatory disease that mainly affects the lymph nodes, lungs, skin and eyes. Nervous system involvement is only seen in 5% of cases of sarcoidosis. Cerebral vasculitis, is particularly uncommon in patients with sarcoidosis, with serious outcome. Case presentation : We reported the case of a 55 years-old female who developed a severe hemicranial headache with nausea and vomiting. She had a history of erythema nodosum. The clinical examination showed left arm weakness and central facial paralysis, along with brisk tendon reflexes and arthralgia. Brain MRI showed a moderate subarachnoid hemorrhage, multiple acute lacunar infracts, and a large ischemic stroke over the right superficial sylvian territory; and MR angiography revealed a Moya-Moya like vasculopathy pattern and the occlusion of intracranial internal carotid arteries. Extensive laboratory workup including infectious serologies and vasculitis screen was negative; and Angiotensin-converting enzyme levels were normal. Findings in the CT chest and abdomen scan, and Broncho alveolar lavage confirmed the diagnosis of sarcoidosis. Conclusions : Cerebrovascular manifestation are uncommon in sarcoidosis. Multiple factors seem to be involved in the pathogenesis of sarcoidosis related vasculopathy. The diagnosis should be considered when recurrent infracts and hemorrhage are encountered in a patient having systemic symptoms of sarcoidosis.

When the central nervous system (CNS) is the primary affected site in an initial attack of Behçet’s disease (BD), the differential diagnosis is particularly challenging. Some cases remain unclassified or qualified as probable neuro-Behçet’s disease (NBD). Several cytokines are involved in the immunopathogenesis of this disease; however, studies establishing the differential cytokine pattern between probable and definite NBD are scarce. Twenty-eight parenchymal NBD patients, diagnosed according to the International Consensus Recommendation (ICR) criteria and classified into definite (D-NBD; n = 17) and probable (P-NBD; n = 11), were sampled at their first neurological symptoms, and compared with healthy control subjects (n = 20). Oligoclonal bands (OCB) of IgG were detected by isoelectric focusing on agarose, and immunoblotting of matched serum and cerebrospinal fluid (CSF) sample pairs. T cell cytokines (INF-γ, IL-4, IL-17, and IL-10) and transcription factors related to Th1, Th2, Th17, and T regulatory populations (respectively T-bet, GATA-3, ROR-γt, and Foxp3) were studied by quantitative RT-PCR in peripheral blood mononuclear cells (PBMCs) and CSF cells. Inflammatory cytokines such as IL-6, TNF-α, and IL-1β were also analyzed. CSF OCB pattern 2 was present in only 1 out of 28 neuro-Behçet’s patients who belonged to the P-NBD group. Two D-NBD patients had OCB in CSF showing pattern 4. In the D-NBD CSF samples, IL-17 and IL-10 expressions were significantly elevated compared to P-NBD. Moreover, D-NBD patients had increased levels of T-bet/GATA-3 and ROR-γt/Foxp3 ratios compared to P-NBD. Furthermore, a significant increase of CSF IL-6 in D-NBD, compared to P-NBD and the controls, was found. In addition to the increased IL-6 level, the data obtained suggest the existence in D-NBD patients of a significantly disrupted balance between Th17 effector and T regulatory cells, as reflected by the enhanced ROR-γt/Foxp3 ratio. This could be considered as an additional criterion for definite neuro-Behçet’s disease.

Background: Iron plays an important role in maintaining cell survival, with normal iron trafficking known to be regulated by the ceruloplasmin-transferrin (Cp-Tf) antioxidant system. Disruption to this system is thought to be detrimental to normal brain function. Objective: To determine whether an imbalance of iron and the proteins involved in its metabolism (ceruloplasmin and transferrin) are linked to Alzheimer’s disease (AD) and to the expression of amyloid-beta (Aβ) peptide 1–42 (Aβ1–42), which is a major species of Aβ, and the most toxic. Methods: We evaluated the concentrations of iron, calcium, magnesium, and Aβ1–42 in the cerebrospinal fluid (CSF) of patients with AD and cognitively normal controls. Correlations between the components of the Cp-Tf antioxidant system in plasma were studied to determine the role of peripheral blood in the onset and/or development of AD. We used commercial ELISA immunoassays to measure Aβ1–42, immunoturbidimetry to quantify ceruloplasmin and transferrin, and colorimetry to quantify iron, calcium, and magnesium. Results: We found that the AD group had lower CSF concentrations of Aβ1–42 (p

At the beginning of the coronavirus virus (COVID-19) pandemic, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) was thought to cause mainly respiratory symptoms, largely sparing the brain and the rest of the nervous system. However, as the knowledge about COVID-19 infection progresses and the number of COVID19-related neurological manifestations reports increases, neurotropism and neuroinvasion were finally recognized as major features of the SARS-CoV-2. Neurological manifestations involving the central nervous system are sparse, ranging from headaches, drowsiness, and neurovascular attacks to seizures and encephalitis [1]. Thus far, several cases of non-epileptic myoclonus were reported in critical patients [2,3]. Here, we report the first case of myoclonus status as the inaugural and sole symptom of COVID-19 in a conscious patient.A 60-year-old man with unknown family history and no medical issues other than smoking one cigarette packet a day over the span of 25 years. The patient presented with 5 days of abnormal movements in bilateral arms following the COVID vaccination. They were described as brief, involuntary jerking, like in sleep starts, in the proximal part of their upper members, and his face with a regular tremor in his arms exacerbated by movements and emotion. His movement disorder worsened the second day, and he developed an abnormal gait with slurred speech, concomitantly with diarrhea. Seven days following the symptoms onset, the patient was alert. His neurological exam revealed multifocal myoclonic jerks affecting four limbs predominantly proximal, the face, and the trunk (video 1). The myoclonic jerks were sensitive to tactile and auditory stimuli, without enhanced startle response or hyperekplexia. His gait was unsteady due to severe myoclonus, without cerebellar ataxia (video 2) and he had mild dysarthria. No dysmetria at the finger-to-nose and heel-to-shin tests were found. Examination of eye movements revealed paralysis of Down-Gaze and no opsoclonus was detected. Physical exam was unremarkable, including lack of fever and meningitis signs. The electroencephalogram (EEG) did not show any abnormalities concomitant with myoclonic jerks (Fig.1). The cerebral Magnetic Resonance Imaging (MRI) was normal (Fig. 2). An extensive biological work-up including a complete blood count, a comprehensive metabolic panel, an arterial blood gas analysis, a urine drug screen, a thyroid function test, a vitamin B12, folate, and ammonia level, and HIV and syphilis serologies were inconclusive. Testing for autoimmune and paraneoplastic antineuronal antibodies including anti-NMDA-R was negative. The cerebrospinal fluid (CSF) study was unremarkable (0.3 g/l of proteinorachia, 1 white blood cell). Polymerase chain reaction (PCR) for herpes simplex virus, varicella-zoster virus, and SARS-CoV-2 in CSF was negative. However, the patient tested positive for COVID-19 through PCR for viral RNA from the nasopharyngeal swab. After the administration of 12mg/day of Dexamethasone for 3 days, along with clonazepam and levetiracetam, the patient's symptoms started improving on day 3 and he displayed a very slow but progressive recovery.Our patient presented with acute isolated multifocal myoclonus status without cognitive impairment. These movements were prominent, spontaneous, worsened by action, and sensitive to touch and sound. The anatomical source of this myoclonus could be cortical or subcortical despite the absence of evident EEG discharges. Several diseases can cause acute myoclonus such as severe hypoxia, metabolic disturbances, and paraneoplastic syndromes. these diagnoses were ruled out in our patient. Post-vaccinal origin was also suggested, but its accountability was not proven. Thus, the two hypothetic etiologies raised were either para-infectious or infectious mechanisms in relation to SARS-Cov 2 infection. HIV, VZV, HSV, and syphilis infections were eliminated and the patient tested positive for SARS-Cov2 infection. In the literature, COVID-19-related myoclonus was reported as a complication of an already-known SARS-CoV-2 infection in about 50 patients so far. It generally occurs between 6 days and 26 days following the SARS-CoV-2 infection [2-5], and affects critical illness patients with cognitive decline, mainly from the intensive care unit [3,4]. Yet, our patient did not display any symptoms of COVID-19 infection before the occurrence of these abnormal movements. Furthermore, he had a relatively good general condition and no cognitive impairment. Several pathophysiological mechanisms were suggested regarding the COVID-19-related myoclonus. Either central nervous invasion by SARS-Cov 2 after transneuronal spread and/or auto-immune cross-reactivity reaction, are likely incriminated in the pathophysiology of most of the cases [6]. We believe that there is an inflammatory process involved with increased levels of proinflammatory cytokines and systemic inflammation, including cytokine storm or cytokine release syndrome targeting the brain and more specifically the cortex and basal ganglia [6]. Data collection in clinical registries is needed to increase our knowledge of the prevalence of neurological symptoms in patients with COVID-19 and will hopefully clarify the causal relationship between SARS-CoV-2 infection and post-COVID-19 myoclonic syndrome.

When the central nervous system (CNS) is the primary affected site in an initial attack of Behçet’s disease (BD), the differential diagnosis is particularly challenging. Some cases remain unclassified or qualified as probable neuro-Behçet’s disease (NBD). Several cytokines are involved in the immunopathogenesis of this disease; however, studies establishing the differential cytokine pattern between probable and definite NBD are scarce. Twenty-eight parenchymal NBD patients, diagnosed according to the International Consensus Recommendation (ICR) criteria and classified into definite (D-NBD; n = 17) and probable (P-NBD; n = 11), were sampled at their first neurological symptoms, and compared with healthy control subjects (n = 20). Oligoclonal bands (OCB) of IgG were detected by isoelectric focusing on agarose, and immunoblotting of matched serum and cerebrospinal fluid (CSF) sample pairs. T cell cytokines (INF-γ, IL-4, IL-17, and IL-10) and transcription factors related to Th1, Th2, Th17, and T regulatory populations (respectively T-bet, GATA-3, ROR-γt, and Foxp3) were studied by quantitative RT-PCR in peripheral blood mononuclear cells (PBMCs) and CSF cells. Inflammatory cytokines such as IL-6, TNF-α, and IL-1β were also analyzed. CSF OCB pattern 2 was present in only 1 out of 28 neuro-Behçet’s patients who belonged to the P-NBD group. Two D-NBD patients had OCB in CSF showing pattern 4. In the D-NBD CSF samples, IL-17 and IL-10 expressions were significantly elevated compared to P-NBD. Moreover, D-NBD patients had increased levels of T-bet/GATA-3 and ROR-γt/Foxp3 ratios compared to P-NBD. Furthermore, a significant increase of CSF IL-6 in D-NBD, compared to P-NBD and the controls, was found. In addition to the increased IL-6 level, the data obtained suggest the existence in D-NBD patients of a significantly disrupted balance between Th17 effector and T regulatory cells, as reflected by the enhanced ROR-γt/Foxp3 ratio. This could be considered as an additional criterion for definite neuro-Behçet’s disease.

Remitting-RelapsingMultiple Sclerosis (RRMS) and Neuro-Behçet Disease (NBD) are two chronic neuroinflammatory disorders leading to neurological damage. Herein, we investigated in these patients the IL-10-producing cells during the early stages of these disorders. Cellular and molecular investigations were carried out on treatment naive patients suffering from RRMS and NBD recruited at the first episode of clinical relapse. Our findings demonstrate that CSF-B cells from NBD patients, but not RRMS, are the major source of intrathecal IL-10 as compared to T-CD4 cells. Moreover, we showed a lower expression of TGF-β and IL35, in the CSF cells of NBD patients as compared to the control group. Specific in vitro CpG stimulation of peripheral blood B cells from NBD patients resulted in a concomitant early mRNA expression of IL6 and IL10 but was limited to IL10 for RRMS patients. Furthermore, mRNA expression of IL-6 and IL-10 receptors was assessed and intriguingly IL6ST receptor subunit was significantly lower in NBD CSF, but not RRMS while IL10RB was increased in both. Deciphering the role of increased IL-10-producing B cells and IL10RB despite relapsing disease as well as the discordant expression of IL6 and IL6ST may pave the way for a better understanding of the pathophysiology of these neuro-inflammatory disorders.

Background Concomitant diagnosis of neuromyelitis optica spectrum disease and pulmonary tuberculosis has rarely been reported. Case report We report a case involving a young Tunisian male patient who developed dry cough followed, 2 months later, by weakness in the lower limbs. The findings of central nervous system imaging and anti-aquaporin-4 antibody positivity were compatible with the diagnosis of neuromyelitis optica spectrum disease. Constellation of the clinical and the typical radiological pulmonary findings in our patient, coming from an endemic region, allowed the diagnosis of pulmonary tuberculosis, although sputum smear examination for acid-fast bacilli and cultures was negative. The patient received anti-tuberculous polytherapy associated with immunomodulation, consisting of methylprednisolone and intravenous immunoglobulins. Pulmonary infection symptoms initially improved but with no motor recovery. The patient suddenly died at home 4 months after the onset of the first symptoms. Current data regarding the clinical presentation of this underreported concomitant or associated condition, the possible pathophysiological mechanisms, and the therapeutic options were reviewed. Conclusions This case underscores the necessity to understand the exact mechanism of these coincident entities and to clarify the best immunomodulatory choice since immunosuppression targeting neuromyelitis optica spectrum disease can lead to dissemination of pulmonary tuberculosis.

We describe the case of a 32-year-old-woman, who developed psychomotor agitation and memory disorders.The Clinical, biological and radiological findings initially showed an infectious etiology.The presence of Anti-N-Methyl-D-aspartate receptor (NMDA) antibodies allowed the diagnosis of a dysimmune etiology of the disease

Background and methods Stroke incidence and mortality are reported to have increased in the Middle-East and North African (MENA) countries during the last decade. This was a prospective observational study to examine the baseline characteristics of stroke patients in the MENA region and to compare the MENA vs. the non-MENA stroke cohort in the Safe Implementation of Treatments in Stroke (SITS) International Registry. Results Of the 13,822 patients with ischemic and hemorrhagic stroke enrolled in the SITS-All Patients Protocol between June 2014 and May 2016, 5897 patients (43%) were recruited in MENA. The median onset-to-door time was 5 h (IQR: 2:20–13:00), National Institutes of Health Stroke Scale (NIHSS) score was 8 (4–13) and age was 65 years (56–76). Hypertension (66%) and diabetes (38%) were the prevailing risk factors; large artery stenosis > 50% (25.3%) and lacunar strokes (24.1%) were the most common ischemic stroke etiologies. In comparison, non-MENA countries displayed an onset-to-door time of 5:50 h (2:00–18:45), a median of NIHSS 6 (3–14), and a median age of 66 (56–76), with other large vessel disease and cardiac embolism as the main ischemic stroke etiologies. Hemorrhagic strokes (10%) were less common compared to non-MENA countries (13.9%). In MENA, only a low proportion of patients (21%) was admitted to stroke units. Conclusions MENA patients are slightly younger, have a higher prevalence of diabetes and slightly more severe ischemic strokes, commonly of atherosclerotic or microvascular etiology. Admission into stroke units and long-term follow-up need to be improved. It is suspected that cardiac embolism and atrial fibrillation are currently underdiagnosed in MENA countries.

Background The growing burden of Parkinson's disease (PD) in Africa necessitates the identification of available therapies and services to improve patient care. Objective To investigate the availability, affordability, frequency of usage, and insurance coverage of PD therapies (pharmacological, surgical, physical, and speech therapies) and services including specialized clinics, specialists, and nurses across Africa. Methods A comprehensive web-based survey was constructed and distributed to neurologists/physicians with a special interest in PD across Africa. The survey instrument includes components that address availability, affordability, frequency of use, and insurance coverage of different therapies and services. Results Responses were received from 28 (of 43 contacted) countries. Levodopa-based oral preparations were always available in 13 countries (46.4%) with variable affordability and "partial or no" insurance coverage in 60% of countries. Bromocriptine was the most available (50%) and affordable ergot dopamine agonists (DA), whereas non-ergot DA was always available in only six countries (21.4%). Trihexyphenidyl was the most available and affordable anticholinergic drug (46.4%). Tricyclic antidepressants and selective serotonin reuptake inhibitors were available in most countries (89.3% and 85.7% respectively), with variable affordability. Quetiapine and clozapine were less available. Specialized clinics and nurses were available in 25% and 7.1% of countries surveyed, respectively. Other services were largely unavailable in the countries surveyed. Conclusion PD-specific therapies and services are largely unavailable and unaffordable in most African countries. The data provide a platform for organizing strategies to initiate or scale up existing services and drive policies aimed at improving access to care and tailoring education programs in Africa. © 2021 International Parkinson and Movement Disorder Society.

OBJECTIVE: To describe presenting symptoms, clinical outcomes, and therapeutic management of concurrent Coronavirus disease 2019 (COVID-19) infections in patients with a pre-existing myasthenia gravis (MG). METHODS: We conducted a retrospective study in patients with preexisting MG presenting with concurrent COVID-19 between September 21st and November 4th, 2020 when attending the emergency department or routine neurology consultation at the National Institute Mongi Ben Hamida of Neurology of Tunis, Tunisia. RESULTS: Five patients were identified. The Myasthenia Gravis Foundation of America scores (MGFA) prior to COVID-19 infection were class I in one patient, class II (IIa, IIb) in two patients, and class IIIb in one patient. Four patients had mild to moderate courses of COVID-19 infection. One patient presented a critical infection with acute respiratory disease syndrome (ARDS) requiring mechanical ventilation. Two of them also demonstrated signs of MG exacerbation requiring the use of intravenous immunoglobulin in one case. We maintained immunosuppressant therapy to MG in all our patients. All our patients received Azithromycin (AZM) as a part of specific drug treatment of COVID-19 infection. Outcome was favorable in 4 patients and rapidly fatal evolution was observed in the patient with ADRS. DISCUSSIONS AND CONCLUSION: The results from our study suggest that prior MG activity could partially influence the subsequent clinical outcomes. It emerged also that ongoing long-term immunosuppressive immunotherapy to MG should be maintained during the COVID-19 pandemic and that AZM can be used safely in MG patients and concurrent COVID-19 infection.

Diagnosis of spinal hydatidosis should be kept in mind in front of spinal cord compression.

Data regarding multiple sclerosis (MS) course in North Africans are scarce and mainly retrospective. To prospectively assess disability progression of multiple sclerosis in Tunisia. Analysis was performed in 600 patients from the MS database of the Mongi Ben Hmida National Institute of Neurology (Tunis, Tunisia), prospectively recorded over a 10-year period. Two MS phases were defined: phase 1, from MS clinical onset to Disability Status Scale (DSS) 3; and phase 2, from DSS 3 to DSS 6. Median durations of both phases and median ages at DSS 3 and DSS 6 were estimated using the Kaplan-Meier method. Median ages at DSS scores 3 and 6 were 48 years (95% confidence interval (CI), 45-50) and 53 years (95% CI, 52-55), respectively. Median time from onset to DSS 3 (phase 1 duration) was 9 years (95% CI, 7-11) and median time to DSS 6 was 12 years (95% CI, 10-15). Median phase 2 duration was 3 years (95% CI, 2.4-3.6). Males and progressive-onset patients had faster disability worsening during the first phase of the disease. Conversely, disability progression during the second phase was independent of gender and MS phenotype at onset. Our study showed that disability progression followed a two-stage process in Tunisian MS patients with however a more aggressive course compared to that in Westerners.

Introduction La thrombose veineuse cerebrale (TVC) est une maladie potentiellement severe. Les cephalees sont des manifestations frequentes. Cependant, l’ataxie est rarement revelatrice. Nous rapportons 2 cas de TVC revelee par une ataxie aigue. Observation Ce sont 2 femmes (A1 et A2) âgees respectivement de 83 ans et 60 ans, aux antecedents d’hypertension arterielle. Elles ont consulte aux urgences pour des troubles de la marche installes brutalement. Elles n’avaient ni fievre, ni cephalees, ni troubles visuels. A l’examen, la patiente A1 avait un syndrome cerebelleux stato-cinetique predominant a gauche et une dysarthrie cerebelleuse. Alors que la patiente A2 avait une ataxie cerebelleuse isolee. Un scanner cerebral a ete effectue pour les 2 patientes, montrant une hypodensite cerebelleuse gauche avec un effet de masse sur le vermis chez A1 ; et un infarctus cerebelleux gauche avec une transformation hemorragique chez A2. L’IRM cerebrale et l’angio-MR veineuse a revele une TVC du sinus lateral gauche chez A1 et une TVC du sinus droit et du sinus lateral gauche chez A2. Les deux etaient compliquees d’un infarctus hemorragique veineux. Le bilan etiologique etait negatif pour A2 et a montre une hyperhomocysteinemie chez A1. Les 2 patientes etaient traitees effectivement par une heparinotherapie. Discussion La TVC est caracterisee par une presentation clinique variable qui touche particulierement les sujets jeunes. Les formes du sujet âge sont peu frequentes et souvent trompeuses. Les TVC compliquees d’infarctus cerebelleux sont rares, celles-ci sont dues, comme nos cas, a des thromboses du sinus droit, du sinus lateral et du sinus sigmoide parfois en association avec les veines cerebelleuses. Conclusion Ces deux cas illustrent qu’une TVC doit etre evoquee devant des lesions vasculaires touchant le cervelet surtout si elles sont compliquees d’une hemorragie.

Introduction L’atteinte des racines lombaires pose un probleme diagnostique courant. Bien que les hernies compressives sont souvent en cause d’autres etiologies plus rares sont frequemment discutees. Observation Nous rapportons le cas d’une patiente âgee de 25 ans, sans antecedents pathologiques notables, qui a presente une faiblesse des deux membres inferieurs d’aggravation progressive depuis 3 mois. L’examen neurologique a objective un syndrome neurogene peripherique avec un deficit predominant en proximal et une abolition des reflexes au niveau des membres inferieurs, associe a des troubles de la deglutition a de type dysphagie. Le bilan biologique etait sans anomalie. L’EMG etait en faveur d’atteinte pluriradicualaire. L’IRM medullaire a mis en evidence une compression des racines nerveuses lombaires secondaire a une dilatation des veines epidurales autour des racines. Le scanner thoraco-abdomino-pelvien fait dans le cadre du bilan etiologique, a objective une interruption de la veine cave inferieure avec une dilatation compensatrice du reseau collaterale dont les veines epidurales et la veine azygos qui compriment respectivement les racines lombaires et l’œsophage. Discussion Les douleurs radiculaires peuvent etre d’origines multiples, ils posent un probleme diagnostique et therapeutique. Notre patiente illustre un cas exceptionnel d’une radiculopathie secondaire a une interruption congenitale de la veine cave inferieure. La dilatation du systeme veineux epidural compensatrice peut comprimer les racines nerveuses donnant lieu a des symptomes mimant ceux d’une hernie discale ou d’une stenose spinale. Ces manifestations sont rarement rapportees dans la litterature. Conclusion Les radiculopathies secondaires a une malformation vasculaire de la veine cave inferieure sont rares. Ce cas illustre l’importance de la rechercher comme etiologie en particulier chez le sujet jeune.

Introduction Le syndrome myasthenique de Lambert-Eaton (SMLE) est un trouble presynaptique rare de la transmission neuromusculaire. La presentation clinique est atypique et le diagnostic est parfois difficile. Observation Patiente 1 : Une femme de 39 ans a presente une fatigabilite musculaire progressive et non fluctuante associee a des douleurs des membres inferieurs. Patiente 2 a presente une fatigabilite matinale qui s’aggrave en fin de journee ; les deux patientes n’avaient pas de diplopie ni symptomatologie bulbaires. L’examen clinique a montre une faiblesse musculaire proximale avec areflexie des membres inferieurs chez nos deux patientes. L’EMG a montre un aspect myogene. Le diagnostic de myosite a ete initialement evoque chez nos deux patientes. La biopsie musculaire n’a montre aucune inflammation, et a revele une atrophie des fibres de type 2 dans la coloration ATPase. Les anticorps anti-VGCC etaient positifs. Un depistage neoplasique exhaustif a ete realise, s’est avere negatif chez les deux patientes. Le diagnostic de SMLE idiopathique a finalement ete retenu. Les patientes ont ete traitees par plasmapherese, steroides, 3-4 diamino-pyridine et agents immunosuppresseurs avec une amelioration progressive. Discussion Cliniquement, la faiblesse proximale des jambes est le principal symptome du SMLE. Nos patientes presentaient une fatigabilite sans autres symptomes. Les tests electrodiagnostiques sont le meilleur support pour le diagnostic de SMLE a condition d’effectuer les stimulations repetitives aux frequences appropriees. L’atrophie des fibres rapides de type 2 est connue caracteristique des SM a la biopsie musculaire. Cette constatation peut etre due a la diminution de leurs activites conduisant a cette atrophie. Conclusion Nous soulignons l’utilite de la biopsie musculaire dans le diagnostic du SMLE.

Summary Background Leucine-rich repeat kinase 2 ( LRRK2 ) mutation 6055G→A (Gly2019Ser) accounts for roughly 1% of patients with Parkinson's disease in white populations, 13–30% in Ashkenazi Jewish populations, and 30–40% in North African Arab-Berber populations, although age of onset is variable. Some carriers have early-onset parkinsonism, whereas others remain asymptomatic despite advanced age. We aimed to use a genome-wide approach to identify genetic variability that directly affects LRRK2 Gly2019Ser penetrance. Methods Between 2006 and 2012, we recruited Arab-Berber patients with Parkinson's disease and their family members (aged 18 years or older) at the Mongi Ben Hamida National Institute of Neurology (Tunis, Tunisia). Patients with Parkinson's disease were diagnosed by movement disorder specialists in accordance with the UK Parkinson's Disease Society Brain Bank criteria, without exclusion of familial parkinsonism. LRRK2 carrier status was confirmed by Sanger sequencing or TaqMan SNP assays-on-demand. We did genome-wide linkage analysis using data from multi-incident Arab-Berber families with Parkinson's disease and LRRK2 Gly2019Ser (with both affected and unaffected family members). We assessed Parkinson's disease age of onset both as a categorical variable (dichotomised by median onset) and as a quantitative trait. We used data from another cohort of unrelated Tunisian LRRK2 Gly2019Ser carriers for subsequent locus-specific genotyping and association analyses. Whole-genome sequencing in a subset of 14 unrelated Arab-Berber individuals who were LRRK2 Gly2019Ser carriers (seven with early-onset disease and seven elderly unaffected individuals) subsequently informed imputation and haplotype analyses. We replicated the findings in separate series of LRRK2 Gly2019Ser carriers originating from Algeria, France, Norway, and North America. We also investigated associations between genotype, gene, and protein expression in human striatal tissues and murine LRRK2 Gly2019Ser cortical neurons. Findings Using data from 41 multi-incident Arab-Berber families with Parkinson's disease and LRRK2 Gly2019Ser (150 patients and 103 unaffected family members), we identified significant linkage on chromosome 1q23.3 to 1q24.3 (non-parametric logarithm of odds score 2·9, model-based logarithm of odds score 4·99, θ=0 at D1S2768). In a cohort of unrelated Arab-Berber LRRK2 Gly2019Ser carriers, subsequent association mapping within the linkage region suggested genetic variability within DNM3 as an age-of-onset modifier of disease (n=232; rs2421947; haplotype p=1·07 × 10 −7 ). We found that DNM3 rs2421947 was a haplotype tag for which the median onset of LRRK2 parkinsonism in GG carriers was 12·5 years younger than that of CC carriers (Arab-Berber cohort, hazard ratio [HR] 1·89, 95% CI 1·20–2·98). Replication analyses in separate series from Algeria, France, Norway, and North America (n=263) supported this finding (meta-analysis HR 1·61, 95% CI 1·15–2·27, p=0·02). In human striatum, DNM3 expression varied as a function of rs2421947 genotype, and dynamin-3 localisation was perturbed in murine LRRK2 Gly2019Ser cortical neurons. Interpretation Genetic variability in DNM3 modifies age of onset for LRRK2 Gly2019Ser parkinsonism and informs disease-relevant translational neuroscience. Our results could be useful in genetic counselling for carriers of this mutation and in clinical trial design. Funding The Canada Excellence Research Chairs (CERC), Leading Edge Endowment Fund (LEEF), Don Rix BC Leadership Chair in Genetic Medicine, National Institute on Aging, National Institute of Neurological Disorders and Stroke, the Michael J Fox Foundation, Mayo Foundation, the Roger de Spoelberch Foundation, and GlaxoSmithKline.

Introduction Le NMOSD est une astrocytopathie auto-immune et demyelinisante du systeme nerveux central(SNC) avec des caracteristiques cliniques et radiologiques propres. Il s’agit d’une pathologie rare avec une evolution parfois severe. Objectifs Le but de notre etude etait de decrire les particularites epidemiologiques, cliniques, radiologiques et evolutives d’une serie tunisienne de patients suivis pour NMOSD. Patients et methodes Il s’agit d’une etude retrospective effectuee a l’Institut National de Neurologie Mongi ben Hmida entre 2014–2018. Nous avons collige 30 cas suivis pour NMOSD diagnostiques selon les criteres de 2015. Les caracteristiques epidemiologiques, cliniques, radiologiques et evolutives ont ete analysees. Resultats L’âge moyen de debut etait de 35,86 ans. Le sex-ratio etait de 0,11. Les principales manifestations revelatrices etaient un syndrome medullaire(53 %) et une nevrite optique(47 %). L’imagerie objectivait des lesions cerebrales typiques et une myelite etendue chez 40 % et 47 % des cas. Le traitement des poussees par corticoide IV et/ou echanges plasmatiques permettait une amelioration dans 77 % des cas. L’association Azathioprine-corticoide per os permettait une stabilisation chez 60 % des patients. Discussion Dans notre etude, la predominance feminine et l’âge moyen de debut concordent avec la litterature. Les manifestations revelatrices sont dominees par le syndrome medullaire. Les lesions IRM typiques sont presentes chez presque la moitie des patients. Les associations corticosteroides- echanges plasmatiques, lors des poussees et Azathioprine-corticoide per os, au cours du traitement d’entretien, permettent une bonne recuperation. Conclusion La distinction du NMOSD des autres pathologies demyelinisantes et sa prise en charge precoce sont particulierement importantes en raison du pronostic souvent severe qu’il engage chez une population majoritairement jeune.

Treg-mediated immune suppression involves many molecular mechanisms including the cleavage of inflammatory extracellular ATP to adenosine by CD39 ectoenzyme. In the peripheral blood of Multiple Sclerosis (MS) patients, it has been suggested that CD39+ Treg cells have the potential to suppress pro-inflammatory IL-17 secreting cells. Herein, we studied cellular phenotype and mRNA expression of CD39 and CD73 ectoenzymes in the Cerebrospinal fluid (CSF) of MS patients and another neuro-inflammatory disease: the Neuro-behçet's disease (NBD). Using qRT-PCR, we assessed mRNA expression of CD39 and CD73 as well as anti-inflammatory (IL-10) and pro-inflammatory (IL-6, TNF-α, IL-1β) cytokines in patients Peripheral blood mononuclear cells (PBMCs) and CSF of 28 relapsing-remitting multiple sclerosis (RRMS), 20 NBD and 22 controls with non inflammatory neurological disorders (NIND). The most substantial result in the CSF was the higher expression of CD39 in both RRMS and NBD patients compared to NIND. While, the expression of CD73 in CSF samples of NBD was low. In RRMS samples, we detected a significant positive correlation of both CD39 and CD73 with IL-10 expression. Moreover, results by flow cytometry revealed a high percentage of CD39 Treg cells in RRMS CSF. CD39 was preferentially expressed on B cells of NBD. Regarding inflammatory response, we showed a significant increase of IL-6 mRNA expression in NBD patients CSF while in RRMS this increase concerned TNF-α. These results bring evidence that CD39 correlates positively with an anti-inflammatory IL-10 response in RRMS. In contrast, no such association was observed in CSF of NBD patients and CD39 was preferentially expressed on B cells.

Introduction Le syndrome de Dorfman–Chanarin est une maladie autosomique recessive rare, responsable d’une surcharge en lipides au niveau de differents tissus. Nous rapportons une observation d’un SDC 1 associant une ichtyose cutanee et une atteinte musculaire. Observation Patiente âgee de 32 ans suivie depuis l’adolescence pour ichtyose cutanee generalisee non bulleuse. Elle decrit depuis 2 ans une fatigabilite a la marche d’aggravation progressive ; a l’examen elle presente un syndrome myopathique avec ichtyose generalisee, une hepatomegalie moderee avec steatose hepatique a l’echographie, les CPK sont a 3000 UI/L. Le bilan immunologique etait negatif. Le frottis sanguin avait montre des leucocytes anormaux contenant des vacuoles remplies de liquide appelees corps de Jordan. La biopsie musculaire avait montre des fibres arrondies avec necroses et regenerations. L’etude genetique est en cours. Discussion Le syndrome de Dorfman–Chanarin est une maladie autosomique recessive rare, elle touche habituellement le nourrisson, mais les formes de l’adulte sont possibles. Dans ce cas le tableau peut etre incomplet comme chez notre patiente. Le diagnostic repose sur la mise en evidence d’une surcharge lipidique au niveau des leucocytes et du muscle. Il n’existe pas de traitement specifique a l’heure actuelle pour cette pathologie. Conclusion Le syndome de Dorfman–Chanarin est une cause tres rare de myopathie. Il s’agit d’une pathologie le plus souvent benigne. Bien connaitre cette pathologie permet d’eviter des enquetes exhaustives inutiles.

Introduction Les mouvements anormaux secondaires aux atteintes medullaires representent une entite rare. Nous rapportons le cas d’un patient qui a ete diagnostique d’une myelopathie cervico-arthrosique (MCA) revelee par des mouvements pseudo-athetosiques. Observation Mr B.A., âge de 58, sans antecedents pathologiques notables, presente depuis quelques mois, des mouvements involontaires lents et sinueux des membres superieurs predominants a droite avec installation recente de lourdeur du membre inferieur gauche. L’examen neurologique a mis en evidence un syndrome quadripyramidal avec discret fauchage a gauche, des troubles de la sensibilite profonde bilateraux predominants a droite avec des mouvements pseudo-athetosiques des 2 mains plus marques a droite non aggraves par la fermeture des yeux. La numeration formule sanguine ainsi que le dosage de la Vit B12 etaient normaux, la serologie syphilis etait negative. L’IRM cerebro-medullaire n’a pas montre d’anomalies a l’etage encephalique, mais une MCA en regard de C3-C4 en rapport avec une hernie discale compressive. Le patient a ete opere avec des suites simples. L’evolution a un mois a montre une legere diminution des mouvements pseudo-athetosiques. Discussion Les mouvements athetosiques sont souvent associes a une atteinte des noyaux gris de la base. L’origine medullaire a ete etablie (lesions demyelinisantes, inflammatoires, syringomyelie et protrusions discales). La physiopathologie incrimine l’atteinte de la proprioception. L’implication du striatum par defaut d’integration est possible. L’evolution apres traitement est variable, la regression de ces mouvements n’est pas la regle. Conclusion L’atteinte de la proprioception au niveau medullaire peut se manifester par des mouvements pseudo-athetosiques qui sont importants a reconnaitre vu le caractere curable.

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) were found to be a significant cause of late-onset autosomal dominant forms of Parkinson's disease (PD). To determine the motor characteristics of LRRK2-related disease, we conducted a longitudinal study of 58 G2019S LRRK2-associated PD patients and compared them with genetically undefined (GU) PD patients. Fifty-eight patients diagnosed with PD-related LRRK2 G2019S mutation were included in the study and compared with 54 sporadic PD patients with negative tests for LRRK2 G2019S, PINK1, SNCA, PRKN, and DJ1 mutations. Patients were assessed at baseline and after a follow-up period of 6 years. The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the Hoehn and Yahr, and the Schwab and England scores were determined. Logistic regression was used to examine associations of G2019S mutation status with motor phenotype and rate of motor decline. The LRRK2-associated PD patients had a mean age of onset of 56.25 ± 12.05 years and in most cases (58.6%) a postural instability gait difficulty (PIGD) phenotype. The mean annual decline in the MDS-UDRS III motor score and the Hoehn and Yahr staging was of 1.3% and 2%, respectively. The PIGD phenotype predicted a more rapid progression of motor impairment. The PD motor phenotype and motor scores were similar in the LRRK2-associated PD group and in the GU PD group, with no significant differences in the progression rate of motor impairment. Motor phenotype seems to be similar in LRRK2-related PD and idiopathic PD.

Introduction Le deficit en vitamine B12 represente une affection potentiellement grave du fait de son retentissement sur le systeme nerveux et les organes hematopoietiques. Il est frequent chez l’adulte notamment chez les sujets âges. Objectifs Le but de notre travail est de determiner le profil epidemiologique, les aspects cliniques et paracliniques et les modalites evolutives sous traitement des atteintes neurologiques par carence en vitamine B12. Patients et methodes Nous proposons une etude retrospective de 17 observations des patients presentant une atteinte neurologique en rapport avec une carence en vitamine B12 colligees dans le service de neurologie a l’institut National de neurologie Mongi Ben Hamida. Resultats L’âge moyen est de 50 ans (38–78 ans). L’atteinte neurologique etait polymorphe et relativement severe representee par un tableau de sclerose combinee de la moelle dans 10 cas, une neuropathie optique dans 07 cas, une neuropathie peripherique dans 06 cas, un syndrome anxieux-depressif dans 03 cas, un syndrome cordonal posterieur dans 02 cas. Les signes neurologiques ont revele la carence en vitamine B12 dans tous les cas. Discussion La maladie de Biermer a domine les etiologies de la carence en vitamine B12, aucune etiologie n’a ete retenue dans 04 cas. Tous nos patients ont ete mis sous vitaminotherapie B12 sous forme d’hydroxocobalamine par voie injectable. Concernant l’evolution clinique, une amelioration a ete notee chez la majorite de nos patients. L’evolution paraclinique a ete marquee par une normalisation de l’hemogramme. Conclusion Cette etude menee par 17 patients presentant des manifestations neurologiques par carence en vitamine B12 montre le polymorphisme et la gravite du tableau neurologique reversible sous traitement d’ou la precosite du diagnostic et de la prise en charge.

Background Cognitive impairment and dementia are frequent and debilitating features associated with idiopathic Parkinson’s disease (PD). However the prevalence and the pattern of these complications are lacking for LRRK2 (leucine-rich kinase 2)-associated PD patients. Purpose The purpose of this study was to assess cognitive function in LRRK2- associated PD patients. Material and methods 55 patients diagnosed with PD-related LRRK2 G2019S mutation were included in the study and compared to the same number of G2019S non-carriers PD patients. Age, sex, disease duration, the movement disorder society-unified Parkinson’s Disease rating scale (MDS-UPDRS), Hoehn and Yahr stage, Schwab and England scale and the 30-item geriatric depression scale (GDS) scores were noted. Cognitive assessment included MMSE (Mini-Mental Examination), MOCA (Montreal Cognitive Assessment) and FAB (Frontal Assessment Battery). Results MMSE, MOCA and FAB performance in G2019S carriers PD patients was similar to that of non-carriers. In both groups, performance was primarily impaired on visuospatial and executive tasks. Cognitive impairment was associated with older age, lower educational level and increased severity of motor impairment. Conclusion Cognitive functions were similarly affected in PD patients with and without LRRK2 G2019S mutation with mainly impaired visuospatial and executive abilities. However, these results need to be confirmed by further large and prospective studies.

Background The frequency and type of central nervous system involvement in primary Sjogren's syndrome (pSS) remain controversial. Brain magnetic resonance imaging (MRI) abnormalities in pSS are usually discrete hyperintense areas in the white matter. Tumefactive brain lesions have been rarely reported. Case report We describe a 31-year-old woman who exhibited transcortical motor aphasia, hemiparesis and partial motor seizures as the initial manifestation of pSS. Brain MRI revealed a large frontoparietal lesion extending into the corpus callosum. The patient had spontaneous recovery and developed sicca symptoms 6 months after onset. Primary SS was diagnosed on the basis of clinical features, abnormal Schirmer test findings, high levels of anti-La/SSB antibodies and positive salivary gland biopsy results. Conclusion The present case suggests that a pseudotumoral brain lesion can occur as an initial symptom of pSS.