A case report of two Moroccan patients with hereditary neurological disorders and molecular modeling study on the S72L de novo PMP22 variant.

Hereditary neurological disorders represent a wild group of hereditary illnesses affecting mainly the nervous system, the majority of which have a Mendelian inheritance pattern. Here we present the case of two Moroccan patients each affected by a different hereditary neurological disorder. In the first patient WES analysis revealed the presence of the p.Ser72Leu de novo mutation in the PMP22 gene reported for the first time in Africa, specifically in Morocco. This variant is predicted to be in a mutation "hot-spot" region causing Dejerine-Sottas syndrome called also Charcot-Marie-Tooth type 3. The molecular modeling study suggests an important alteration of hydrogen and hydrophobic interactions between the residue in position 72 of the PMP22 protein and its surrounding amino acids. On the other hand, the p.Ala177Thr mutation on the RNASEH2B gene, responsible of Aicardi-Goutières syndrome 2, was carried in a homozygous state by the second patient descending from a consanguineous family. This mutation is common among the Moroccan population as well as in other North African countries. The present results contributed to a better follow-up of both cases allowing better symptom management with convenient treatments.

Retroperitoneal desmoid-type fibromatosis: a case report.

Desmoid-type fibromatosis (DF) is a rare subtype of soft tissue sarcomas that most commonly occurs in the anterior abdominal wall. When occurring in the retroperitoneum, DF is usually part of familial syndromes while only rarely sporadic. This makes it imperative to report any instance of experience with DF and the oncological outcomes of the different approaches to management. We report two cases of sporadic and severe DF occurring in the retroperitoneum at our institution. Case presentation: The first case is a male that presented with urinary obstruction symptoms and underwent surgical resection of the tumor that extended into the left kidney. The second case is a female with a history of recurrent desmoid tumors of the thigh and was incidentally diagnosed with retroperitoneal DF on imaging. She underwent tumor resection and radiotherapy; however, the tumor recurred with urinary obstruction symptoms that required another surgical resection. Histopathological characteristics and radiological imaging of both cases are described below. Clinical discussion: Desmoid tumors often recur, thus significantly influencing the quality of life which is reflected in one of our cases. Surgery remains a mainstay treatment, and both cases presented in this report required surgical resection of the tumors as symptomatic and curative measures. Conclusion: Retroperitoneal DF is a rare entity, and our cases add to the scarce literature available on the topic, which may well contribute to the formulation of practice-changing recommendations and guidelines focused on this rare variant of DF.

A regional strategy to decrease the time to thrombectomy in patients with low probability of treatment by thrombolysis.

BACKGROUND AND PURPOSE: The best transportation strategy for patients with suspected large vessel occlusion (LVO) is unknown. Here, we evaluated a new regional strategy of direct transportation to a Comprehensive Stroke Center (CSC) for patients with suspected LVO and low probability of receiving intravenous thrombolysis (IVT) at the nearest Primary Stroke Center (PSC). METHODS: Patients could be directly transported to the CSC (bypass group) if they met our pre-hospital bypass criteria: high LVO probability (i.e., severe hemiplegia) with low IVT probability (contraindications) and/or travel time difference between CSC and PSC<15 minutes. The other patients were transported to the PSC according to a "drip-and-ship" strategy. Treatment time metrics were compared in patients with pre-hospital bypass criteria and confirmed LVO in the bypass and drip-and-ship groups. RESULTS: In the bypass group (n=79), 54/79 (68.3%) patients met the bypass criteria and 29 (36.7%) had confirmed LVO. The positive predictive value of the hemiplegia criterion for LVO detection was 0.49. In the drip-and-ship group (n=457), 92/457 (20.1%) patients with confirmed LVO met our bypass criteria. Among the 121 patients with bypass criteria and confirmed LVO, direct routing decreased the time between symptom discovery and groin puncture by 55 minutes compared with the drip-and-ship strategy (325 vs. 229 minutes, P<0.001), without significantly increasing the time to IVT (P=0.19). CONCLUSIONS: Our regional strategy led to the correct identification of LVO and a significant decrease of the time to mechanical thrombectomy, without increasing the time to IVT, and could be easily implemented in other territories.

Cognitive Impairment and Basal Ganglia Functional Connectivity in Vascular Parkinsonism.

BACKGROUND AND PURPOSE: Patients with vascular parkinsonism have higher cognitive decline and more basal ganglia lesions. We aimed to evaluate the relationship of cognitive impairment with functional connectivity between the basal ganglia and cingulate cortex in vascular parkinsonism. MATERIALS AND METHODS: Thirty patients (8 with vascular parkinsonism and 22 with Parkinson disease) and 23 controls were enrolled. The Mattis Dementia Rating Scale and the Stroop Task were used to assess cognitive decline. MR imaging examinations included T1-MPRAGE, FLAIR, and resting-state fMRI sequences. MPRAGE was segmented to obtain basal ganglia and cingulate cortex volumes. FLAIR was segmented to obtain white matter hyperintensity lesion volume. Resting-state fMRI sequences were used to compare basal ganglia functional connectivity with the cingulate cortex between patients and controls. RESULTS: Patients with vascular parkinsonism exhibited impaired attention, resistance to interference, and inhibitory control and an increased number of errors on the Stroop Task. They also had higher caudate nucleus and white matter hyperintensity lesion volumes, which were positively correlated (ρ = 0.75, P < .0001). Caudate nucleus functional connectivity with the perigenual anterior cingulate cortex was increased in patients with vascular parkinsonism compared with controls and patients with Parkinson disease, and it was positively correlated with the caudate nucleus volume (ρ = 0.44, P = .016). Caudate nucleus functional connectivity with the posterior cingulate cortex was decreased in patients with vascular parkinsonism compared with controls and negatively correlated with the number of errors on the Stroop test (ρ = -0.51, P = .0003). CONCLUSIONS: In patients with vascular parkinsonism, cognitive decline could be related to changes of caudate nucleus functional connectivity with the cingulate cortex at resting-state, which may be induced by ischemia-related remodelling.

[Natalizumab as induction therapy in multiple sclerosis]. / Traitement d'induction dans la sclérose en plaques: place du natalizumab.

BACKGROUND: Current treatment options for first-line immunotherapy in relapsing-remitting multiple sclerosis (MS) are recombinant interferon-ß and glatiramer acetate. However, these therapies are only partially effective and certain patients may fail to respond. For this reason, it is important to elaborate alternative treatment strategies. Induction therapy represents a more aggressive approach in which powerful drugs are used right from the beginning to tackle the disease process hard and early. Natalizumab is a powerful monoclonal antibody approved for the treatment of relapsing-remitting MS and is known to silence disease activity. METHODS: We describe here the early outcome at 1 month and at 6 months of three patients treated with natalizumab for relapsing-remitting MS. RESULTS: All three patients had a high disease activity before the initiation of natalizumab, with 4, 8 and 5 gadolinium-enhancing lesions on brain MRI respectively. On the MRI scans made at 1 month after the first infusion, and at 6 months, there was no more gadolinium-enhancement and no new T2-lesion. Clinically, they did not experience any relapse. DISCUSSION: In these three cases, natalizumab showed a dramatic efficacy: the patients became "disease activity free" right from the first infusion. To our knowledge, natalizumab is not classically used as an induction therapy, unlike mitoxantrone. However, this treatment has potential hematological and cardiac toxicity and its use can be limited. Thus, in JC virus negative patients, natalizumab could be an interesting alternative treatment. CONCLUSION: Our report suggests that induction strategy with natalizumab may be applicable in patients with aggressive multiple sclerosis. A study of more similar cases may be interesting to confirm these preliminary results.

[Anti-GAD antibodies in paraneoplastic cerebellar ataxia associated with limbic encephalitis and autonomic dysfunction]. / Ataxie cérébelleuse associée à une encéphalite limbique et à un syndrome dysautonomique paranéoplasiques avec anticorps anti-GAD.

INTRODUCTION: Cerebellar ataxia and stiff person-syndrome are the main neurological syndromes associated with antibodies to glutamic acid decarboxylase (GAD). CASE REPORT: A 59-year-old patient, with history of polymyalgia rheumatica and active smoking, was admitted for subacute cerebellar ataxia and memory dysfunction explained by limbic encephalitis on brain MRI. He also presented with orthostatic hypotension and erectile dysfunction revealing autonomic dysfunction. CSF was inflammatory and antibodies to GAD were positive. Onconeuronal antibodies including GABA(B) receptor antibodies were negative. Patient's condition quickly improved after intravenous immunoglobulins. A few months later, a small cell lung carcinoma was diagnosed and precociously treated. CONCLUSION: This case report underlines the importance of appropriate studies to confirm a primitive neoplasia, when confronted with limbic encephalitis and cerebellar ataxia, even if anti-GAD antibodies rarely define paraneoplastic syndromes.

Susac's syndrome, a rare, potentially severe or lethal neurological disease.

Susac's syndrome (SS) is a rare, immune-mediated endotheliopathy affecting the microvasculature of the brain, the inner ear and the retina. Clinical presentation is characterised by a triad: encephalopathy, hearing loss and branch retinal artery occlusion (BRAO). Given the rarity of this disease, its natural history still remains partially unknown, but lethal cases appear to be extremely rare since there has never been, to our knowledge, a report of SS leading to death. We report 2 cases of SS illustrating the multiplicity of neurological symptomatology and its unpredictable course. One case is particularly unusual due to its severe neurological evolution, leading to death despite treatments. This report presents clinical and paraclinical findings contributory to SS diagnosis and offers an innovative perspective on disease management. These cases represent the potential severity of this disease. Early, aggressive treatment strategies may be warranted for SS in order to avoid neurological deterioration and lethal evolution.

[Meningomyeloradiculitis in an immunocompetent patient]. / Méningomyéloradiculite àCandida albicans chez un sujet immunocompétent.

INTRODUCTION: Candida infection limited to the central nervous system is extremely rare, and may be confused with tuberculosis on the grounds of the clinical and cerebrospinal fluid findings. CASE REPORT: A 23-year-old immunocompetent drug addict presented with alternating sciatica over a period of several months, followed by multiple cranial nerve involvement in the setting of marked weight loss. The histopathologic examination of a leptomeningeal neurosurgical biopsy was required to establish the diagnosis of neuromeningeal infection with Candida albicans. CONCLUSION: This case report underlines diagnostic difficulties of candidal meningitis and reviews current therapeutic recommendations.

[Chemotherapy treatment for anti-Hu paraneoplastic syndrome without active malignancy]. / Traitement par chimiothérapie d'un syndrome neurologique paranéoplasique anti-Hu sans cancer actif associé

INTRODUCTION: Anti-Hu associated paraneoplastic neurological syndromes are rare and characterized by poor prognosis. The research and treatment of a related cancer, a small-cell lung cancer most of the time, remains the best therapeutic strategy. CASE REPORT: We describe the clinical course of a paraneoplastic subacute sensory neuronopathy associated with anti-Hu antibodies in a male smoker treated by an early chemotherapy active against a small-cell lung cancer although no tumor could be found at repeated evaluations. In spite of this treatment, the neurological state deteriorated with the appearance of a cerebellar degeneration, and limbic encephalitis which resulted in a loss of autonomy. A small-cell lung cancer was found and treated 65 months after the onset of the neurological symptoms. The treatment of the underlying malignancy, when it can be found, is still considered as the optimal treatment for paraneoplastic neurological syndromes. Although no tumor could be found, we treated our patient with an empirical chemotherapy active against the most frequent malignancy associated to anti-Hu syndrome in a smoker man, without any improvement. CONCLUSION: Active and repeated research for a cancer related to an anti-Hu neurological syndrome and its treatment are undispensable. For our patient without any identified cancer empirical chemotherapy treatment was unable to stop neurological worsening. When no tumor can be identified by conventional imaging techniques, an early FDG-PET scan should be considered and then repeated if normal.

[Should mechanical ventilation be used in ICU patients in developing countries?]. / Faut-il ventiler les patients de réanimation dans les pays en développement?

The purpose of this monocentric prospective cohort study was to assess mortality in intensive care unit (ICU) patients requiring more than 6 hours of mechanical ventilation (MV) in a developing country. The study setting was a 10-bed polyvalent ICU at the Centre Hospitalier Régiona1 in El Maarouf, Comoros Islands. The study population included a total of 106 patients requiring MV out of 633 consecutive patients admitted to the ICU over a 10-month period. Study parameters included demographic data, simplified acute physiology score version 2 (SAPS II), reason for admission, urgency of MV, duration of MV, complications of MV need for sedation and mortality in hospital and at one year. In-hospital mortality was 59%. Mortality was significantly higher in patients presenting elevated SAPS II and requiring myorelaxant drugs. Age, gender, reason of admission, emergency, sedation, complications of MV, duration of MV were not correlated with mortality. The best prognosis was associated with the following indications: severe malaria, meningitis, eclampsia and poisoning. All patients who left the ICU (41) were alive at one year. Mortality associated with use of MV for resuscitation in a developing country was similar to that observed in developed countries. The young age of patients, acute nature of manifestations and reversibility of diseases encountered may explain the favorable outcome observed in this study. The initial diagnosis and associated risk factors (using a severity score if necessary) must be taken into account in deciding the indication for starting and stopping MV. The results of this study show that MV is feasible and effective in a developing country, but requires experience, inventiveness and realism.

[Recurrent acute polyneuropathy and cutaneous vasculitis]. / Polyneuropathie aiguë récidivante et vasculite cutanée.

A patient with relapsing cutaneous vasculitis presented 3 times in 10 years with an acute extensive neuropathy and respiratory failure which fully recovered. The relationships between Guillain-Barré syndrome and vasculitis are discussed.

[Arterial thrombolysis and angioplasty in atheromatous basilar artery occlusion]. / Thrombolyse par voie artérielle et angioplastie dans l'occlusion athéromateuse du tronc basilaire.

Basilar occlusions treated with conventional therapy (anticoagulants or antiplatelets) have a poor outcome (80p. cent mortality). This unfavorable outcome may require a treatment within 6 hours by intra-arterial thrombolysis, sometimes followed by percutaneous transluminal angioplasty (PTA) in case of atherothrombotic occlusion due to a tight atherosclerotic stenosis. A 48 year-old patient, presented with left hemiparesis, left multimodal hypoesthesia, paralytic dysarthria. CT-scan showed a spontaneous hyperdensity of the basilar artery and arterial occclusion was confirmed by angiography, which showed an atherothrombotic occlusion involving the proximal part of the vessel. Intra-arterial thrombolysis began five hours after the onset with 0,25mg/kg of Rt-Pa (Actilyse((R))), given by bolus followed by 4 others bolus of 10mg. After a total dose of 60mg, arterial recanalization was obtained showing a tight atherosclerotic stenosis involving the proximal part of the basilar artery. PTA was performed 18 hours later with a ballon inflation at 6 atmospheres during 20 seconds. It allowed to decrease the stenosis from 80p. cent to 60p. cent. The patient recovered and MRI at D20 showed a small right lateral infarct involving the pons. Our study confirms the usefulness of intra-arterial thrombolysis in basilar artery occlusion. Consecutive PTA may be proposed in case of associated atherosclerotic stenosis, and the interest of PTA is further discussed.

Dural puncture and corticotherapy as risks factors for cerebral venous sinus thrombosis.

Dural puncture with corticosteroid could be a predisposing factor for cerebral venous thrombosis (CVT). A 35-year-old woman using oral contraception was treated with corticosteroid epidural infiltration for L5 radiculalgia. The following day a postural headache developed and accidental dural puncture was suspected. Four days later, she presented with fever and consciousness impairment requiring mechanical ventilation. Magnetic resonance angiography (MRA) confirmed thrombosis of the superior sagittal sinus. Recanalization was observed three weeks later and the patient fully recovered. Blood tests for thrombophilia showed a moderate decrease in the C protein level (chronometric activity 44%, N = 65-130). CVT has been reported after spinal anaesthesia or peridural anaesthesia with accidental puncture. After dural puncture the decrease of cerebrospinal fluid pressure induces a rostrocaudal sagging effect with traumatic damage to the fragile venous endothelial wall, and may trigger a venous vasodilatation with resultant stasis. CVT has also been described in patients after lumbar puncture and oral corticoid treatment for multiple sclerosis and after corticosteroid intrathecal infiltration. Therefore, corticosteroids can be considered as a potential additional procoagulant stimuli.

[POEMS syndrome disclosed by ophthalmological manifestation]. / Syndrome POEMS à révélation ophtalmologique.

POEMS syndrome is characterized by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes. Papilledema is a common finding but ophthalmological complaints are rare. We report a case of POEMS syndrome in a 42-year old man which was revealed by oscillopsia and blurred vision. An osteosclerotic myeloma of the fifth lef rib was found, but there was no improvement after removal of the rib. The patient died two months later from pulmonary embolism.

Immunophenotypic identification of Sezary cells in peripheral blood.

Despite anecdotal literature that Sezary cells express the CD4+ CD7- immunophenotype, no formal validation has been published establishing the use of this immunophenotype for clinical or experimental purposes. Consequently, the only method presently available for Sezary cell identification is nuclear contour analysis, a labor-intensive procedure not generally available at most major medical centers. In this study, the accuracy of CD4+ CD7- subset quantitation for the identification of Sezary cells was examined. The study found that the percentage of CD4+ CD7- cells is elevated in many Sezary syndrome/MF patients relative to normal, healthy individuals. In addition, CD4+ CD7- enumeration correlates with enumeration by nuclear contour analysis in most patients (11 of 15) with elevated CD4/CD8 ratios. The CD4+ CD7- subset also correlates with the expression of other aberrant immunophenotypes, such as CD3low or CD4low. Lastly, CD4+ CD7- subset quantitation correlates with the number of clonal T lymphocytes, as measured using V beta-specific T-cell receptor monoclonal antibodies. The study found this method to be exceptionally accurate, with two caveats: (1) the absence of an expanded CD4+ CD7- subset in patients with a normal CD4/CD8 ratio is uninformative; and (2) in approximately 25% of patients with an elevated CD4/CD8 ratio, the Sezary cells are CD7+.