Phenotype and imaging features associated with APP duplications.

BACKGROUND: APP duplication is a rare genetic cause of Alzheimer disease and cerebral amyloid angiopathy (CAA). We aimed to evaluate the phenotypes of APP duplications carriers. METHODS: Clinical, radiological, and neuropathological features of 43 APP duplication carriers from 24 French families were retrospectively analyzed, and MRI features and cerebrospinal fluid (CSF) biomarkers were compared to 40 APP-negative CAA controls. RESULTS: Major neurocognitive disorders were found in 90.2% symptomatic APP duplication carriers, with prominent behavioral impairment in 9.7%. Symptomatic intracerebral hemorrhages were reported in 29.2% and seizures in 51.2%. CSF Aß42 levels were abnormal in 18/19 patients and 14/19 patients fulfilled MRI radiological criteria for CAA, while only 5 displayed no hemorrhagic features. We found no correlation between CAA radiological signs and duplication size. Compared to CAA controls, APP duplication carriers showed less disseminated cortical superficial siderosis (0% vs 37.5%, p = 0.004 adjusted for the delay between symptoms onset and MRI). Deep microbleeds were found in two APP duplication carriers. In addition to neurofibrillary tangles and senile plaques, CAA was diffuse and severe with thickening of leptomeningeal vessels in all 9 autopsies. Lewy bodies were found in substantia nigra, locus coeruleus, and cortical structures of 2/9 patients, and one presented vascular amyloid deposits in basal ganglia. DISCUSSION: Phenotypes associated with APP duplications were heterogeneous with different clinical presentations including dementia, hemorrhage, and seizure and different radiological presentations, even within families. No apparent correlation with duplication size was found. Amyloid burden was severe and widely extended to cerebral vessels as suggested by hemorrhagic features on MRI and neuropathological data, making APP duplication an interesting model of CAA.

C-reactive protein and D-dimer in cerebral vein thrombosis: Relation to clinical and imaging characteristics as well as outcomes in a French cohort study.

Introduction: Cerebral venous sinus thrombosis (CVST) is a rare disease with highly variable clinical presentation and outcomes. Clinical studies suggest a role of inflammation and coagulation in CVST outcomes. The aim of this study was to investigate the association of inflammation and hypercoagulability biomarkers with CVST clinical manifestations and prognosis. Methods: This prospective multicenter study was conducted from July 2011 to September 2016. Consecutive patients referred to 21 French stroke units and who had a diagnosis of symptomatic CVST were included. High-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), D-dimer, and thrombin generation using calibrated automated thrombogram system were measured at different time points until 1 month after anticoagulant therapy discontinuation. Results: Two hundred thirty-one patients were included. Eight patients died, of whom 5 during hospitalization. The day 0 hs-CRP levels, NLR, and D-dimer were higher in patients with initial consciousness disturbance than in those without (hs-CRP: 10.2 mg/L [3.6-25.5] vs 23.7 mg/L [4.8-60.0], respectively; NLR: 3.51 [2.15-5.88] vs 4.78 [3.10-9.59], respectively; D-dimer: 950 µg/L [520-2075] vs 1220 µg/L [950-2445], respectively). Patients with ischemic parenchymal lesions (n = 31) had a higher endogenous thrombin potential5pM than those with hemorrhagic parenchymal lesions (n = 31): 2025 nM min (1646-2441) vs 1629 nM min (1371-2090), respectively (P = .0082). Using unadjusted logistic regression with values >75th percentile, day 0 hs-CRP levels of >29.7 mg/L (odds ratio, 10.76 [1.55-140.4]; P = .037) and day 5 D-dimer levels of >1060 mg/L (odds ratio, 14.63 [2.28-179.9]; P = .010) were associated with death occurrence. Conclusion: Two widely available biomarkers measured upon admission, especially hs-CRP, could help predict bad prognosis in CVST in addition to patient characteristics. These results need to be validated in other cohorts.

Cerebral Venous Thrombosis: Clinical, Radiological, Biological, and Etiological Characteristics of a French Prospective Cohort (FPCCVT)-Comparison With ISCVT Cohort.

Introduction: Cerebral venous thrombosis (CVT) is a rare disease with highly variable clinical presentation and outcome. Etiological assessment may be negative. The clinical and radiological presentation and evolution can be highly variable. The mechanisms involved in this variability remain unknown. Objective: The aim of this multicenter French study registered on ClinicalTrials.gov (NCT02013635) was therefore to prospectively recruit a cohort of patients with cerebral venous thrombosis (FPCCVT) in order to study thrombin generation and clot degradation, and to evaluate their influence on clinical radiological characteristics. The first part of the study was to compare our cohort with a reference cohort. Methods: This prospective, multicenter, French study was conducted from July 2011 to September 2016. Consecutive patients (aged >15 years) referred to the stroke units of 21 French centers and who had a diagnosis of symptomatic CVT were included. All patients gave their written informed consent. The diagnosis of CVT had to be confirmed by imaging. Clinical, radiological, biological, and etiological characteristics were recorded at baseline, at acute phase, at 3 months and at last follow-up visit. Thrombophilia screening and the choice of treatment were performed by the attending physician. All data were compared with data from the International Study on CVT published by Ferro et al. Results: Two hundred thirty-one patients were included: 117 (50.6%) had isolated intracranial hypertension, 96 (41.5%) had focal syndrome. During hospitalization, 229 (99.1%) patients received anticoagulant treatment. Median length of hospital stay was 10 days. Five patients died during hospitalization (2.2%). At 3 months, 216 patients (97.0%) had follow-up with neurological data based on an outpatient visit. The mean duration of antithrombotic treatment was 9 months, and the mean time to last follow-up was 10.5 months. At the end of follow-up, eight patients had died, and 26 patients were lost to follow-up. At least one risk factor was identified in 200 patients. Conclusions: We demonstrated that the FPCCVT cohort had radiological, biological, and etiological characteristics similar to the historical ISCVT cohort. Nevertheless, the initial clinical presentation was less severe in our study probably due to an improvement in diagnostic methods between the two studies.

Management of acute central retinal artery occlusion: Intravenous thrombolysis is feasible and safe.

Background Although acute central retinal artery occlusion is as a stroke in the carotid territory (retinal artery), its management remains controversial. The aim of this study was to assess the feasibility and safety of intravenous thrombolysis delivered within 6 h of central retinal artery occlusion in French stroke units. Methods We performed a retrospective analysis of patients treated with intravenous alteplase (recombinant tissue-plasminogen activator), based on stroke units thrombolysis registers from June 2005 to June 2015, and we selected those who had acute central retinal artery occlusion. The feasibility was assessed by the ratio of patients that had received intravenous alteplase within 6 h after central retinal artery occlusion onset among those who had been admitted to the same hospital for acute central retinal artery occlusion. All adverse events were documented. Results Thirty patients were included. Visual acuity before treatment was limited to "hand motion", or worse, in 90% of the cases. The mean onset-to-needle time was 273 min. The individuals treated with intravenous alteplase for central retinal artery occlusion represented 10.2% of all of the patients hospitalized for central retinal artery occlusion in 2013 and 2014. We observed one occurrence of major bleeding, a symptomatic intracerebral hemorrhage. Conclusion When applied early on, intravenous thrombolysis appears to be feasible and safe, provided that contraindications are given due consideration. Whether intravenous thrombolysis is more effective than conservative therapy remains to be determined. In order to conduct a well-designed prospective randomized control trial, an organized network should be in place.

Long-term outcome of basilar stenosis in Erdheim-Chester disease: A case report.

BACKGROUND: Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis. This inflammatory myeloid neoplasm is frequently complicated by neurological symptoms, but stroke is an exceptional manifestation of this disease. METHODS: We report the case of a 59-year-old woman who presented a vertebrobasilar stroke secondary to infiltration and severe stenosis of the basilar artery, improved after interferon-alpha therapy. We performed a review of the relevant literature and reported the few other cases described. RESULTS: With our patient, we have found only 7 observations of cerebrovascular disorder in ECD. Most of them had supravascular arteries involvement. CONCLUSION: Stroke is a rare treatable and potentially reversible complication of ECD. The pathophysiological processes explaining stroke in this disease are uncertain, but periarterial stenosis of cerebral arteries may be a mechanism.

Neurodermatology.

Since the skin and the central and/or peripheral nervous system share a common source (the ectoderm), numerous genetic and acquired diseases (infectious, tumoral or autoimmune disorders) equally affect both. Neurologic diseases or symptoms such as stroke, cerebral or medullary vascular malformations, peripheral, brain or medullary tumors, epilepsy, ataxia, neurologic infections, or cognitive disorders (dementia, mental retardation) may be associated with specific cutaneous manifestations of which the discovery can facilitate the final diagnosis, thereby leading to specific treatment and/or genetic investigations. Careful examination of the skin, hair, and nails by the neurologist is consequently of the utmost importance; when unusual abnormalities of the skin are discovered or when greater expertise is required, consultation with a dermatologist is frequently advisable.

Obstetrical outcome of young women with a past history of cerebral venous thrombosis.

BACKGROUND: This study was designed to review the obstetrical outcome of a consecutive series of cerebral venous thrombosis (CVT) affecting fertile women over a long period of time. METHODS: From a computerized database of four hospitals of a French region (Poitou-Charentes), we selected patients admitted to hospital for CVT between January 1995 and February 2012. All the case notes were re-examined by two neurologists to confirm the initial diagnosis of CVT. The criterion of inclusion in our study was the occurrence of CVT in a woman ≤ 40 years of age. All the patients were recontacted by telephone in September 2012 and could be seen in an outpatient clinic. The data of interest were: occurrence of subsequent pregnancies, outcome of these pregnancies, their possible complications, their management with respect to preventive medication, details on the birth and the neonate. RESULTS: Out of 190 consecutive patients hospitalized for CVT, 62 women aged ≤ 40 years were included (mean age 27.2 ± 6.7 years at the time of their cerebrovascular event). The mean duration of follow-up was 89.5 ± 60.6 months (median: 76 months). There were 45 pregnancies in 24 of the women. Among these 45 pregnancies, 1 was in progress, 24 were completed resulting in normal children, whereas 20 were terminated (5 voluntary abortions, 14 miscarriages and 1 medical abortion). During the pregnancies recorded, there was one recurrence of CVT and no extra-CVT. Various management strategies were adopted, depending on the identified cause(s) for CVT and the medical history of the patient. CONCLUSIONS: Our study confirms that the occurrence of a CVT in young women is not a contraindication for subsequent pregnancy. However, it points to a high incidence of miscarriage. Apart from this fact, there is no increase in materno-fetal complications during pregnancy and childbirth, and the neonates are healthy. The risk of recurrence of a CVT or extra-CVT during subsequent pregnancy is low but most of patients were on preventive antithrombotic medication.

Sleep disorders and multiple sclerosis: a clinical and polysomnography study.

BACKGROUND: Patients with multiple sclerosis (MS) report sleep disturbances (SD) and excessive daytime sleepiness (EDS) more frequently than the general population. Our objectives were to evaluate SD and EDS in MS patients and to test the reliability of subjective sleep questionnaires. METHODS: Demographic and clinical characteristics of unselected consecutive patients with MS were collected. Different questionnaires were used to assess quality of sleep, daytime sleepiness, fatigue, anxiety, depression and quality of life (QoL). Nocturnal polysomnography and Multiple Sleep Latency Test (MSLT) were performed in 25 selected MS patients with fatigue and with or without EDS. RESULTS: 205 MS patients were enrolled. More than half of the MS patients were classified as 'poor sleepers'. In multivariate analysis, SD were correlated with disability, fatigue, depression, QoL, and pain, but not with EDS. Subjective sleepiness evaluated with the Epworth Sleepiness Scale and SD with the Pittsburgh Sleep Quality Index were not correlated with the results of the objective assessments of vigilance (MSLT) and sleep. CONCLUSIONS: SD and EDS are frequent among MS patients. Objective assessment of vigilance and sleep can be challenging but MS patients who are poor sleepers should receive immediate assessment and treatment in order to improve QoL.

Bilateral femoral neuropathy after massive toxic ingestion in a suicide attempt.

INTRODUCTION: Bilateral femoral nerve injury can occur after various surgical and nonsurgical processes, but has rarely been reported. CASE REPORT: We describe a case of bilateral femoral neuropathy after a suicide attempt in a 41-year-old woman. We suggest a stretch mechanism to explain this observation. We also discuss the other causes of bilateral nerve palsy, usually secondary to a compressive injury, with a review of the medical literature. CONCLUSIONS: The patient reported is the first in the literature to have suffered from bilateral femoral nerve palsy after a suicide attempt. Half of the reported cases are secondary to a surgical process (particularly abdominopelvic surgery). If a compressive origin is most frequent, a stretch mechanism may at times explain a bilateral femoral neuropathy.

Cerebral abscesses in hereditary haemorrhagic telangiectasia: a clinical and microbiological evaluation.

OBJECTIVES: Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder that can lead to neurological manifestations including strokes and cerebral abscesses. Our objectives were to describe clinical, radiological, bacteriological, and outcome characteristics of patients with cerebral abscess and HHT, and to concurrently compare this group with a control group with cerebral abscess, but without HHT. PATIENTS AND METHODS: Patients with HHT and cerebral abscess in 5 French medical centers were included. Their clinical, radiological, biological data and prognosis were compared to the data of unselected patients with cerebral abscesses but without HHT included during the same period of time. RESULTS: Twenty-six patients (13 men and 13 women; 44.7±17.2; range 12-79 years), with HHT and cerebral abscess were included. A pulmonary arteriovenous malformation (AVM) was present in all cases. Cerebral abscesses were solitary, supratentorial, and mostly lobar. In all cases, pathogens were anaerobic or facultative anaerobic germs (particularly streptococcus). No death was observed, but various sequels were present in up to two-thirds of the patients. We observed a recurrence of the cerebral abscess in 4 patients with a mean delay of 81 months. In comparison with the control group, cerebral abscesses were generally of later recurrence and significantly more often unique and less often due to staphylococcus. CONCLUSION: HHT cerebral abscesses are particularly linked to pulmonary arteriovenous malformations and anaerobic germs. Their clinical, radiological and bacteriological characteristics are quite different than in a control group with more solitary brain localizations, no staphylococcus infection and a significantly longer interval to recurrence.

Restless legs syndrome and pregnancy: follow-up of pregnant women before and after delivery.

AIMS: To describe the frequency of restless legs syndrome (RLS) in a French population of randomly selected women during their third trimester of pregnancy and its evolution up to 3 months after delivery and to identify potential factors associated with the improvement of RLS after delivery. METHODS: A cross-sectional questionnaire survey. RESULTS: 186 pregnant women living in a French town were included. 32% of women were affected by RLS during the third trimester of their pregnancy. Multiple pregnancies and iron intake during pregnancy were significantly associated with RLS during the third trimester. RLS disappeared after delivery among 64.8% of the women, and by less than 2 weeks after delivery in half of them. This improvement after delivery was not associated with the number of previous pregnancies, the RLS severity and iron intake during pregnancy, peridural anaesthesia, caesarean section, delivery complications, newborn weight, breastfeeding, dopaminergic agent intake after delivery, and with the absence of RLS before pregnancy. CONCLUSIONS: RLS affects one third of pregnant women during their third trimester and usually improves after delivery. Although there is no allowed treatment, most of the time only counselling and iron status assessment should be provided.

Restless legs syndrome and pregnancy: a questionnaire study in the Poitiers District, France.

AIMS: To perform a large and detailed epidemiologic study on restless legs syndrome (RLS) during pregnancy in a European country. METHODS: A cross-sectional questionnaire survey. The questionnaire was distributed by the medical staff in different outpatient waiting rooms (obstetrics and gynecology department of the university hospital, obstetrics and gynecology department of a private clinic, private midwives, private obstetrician-gynecologists, radiological centers before fetal ultrasound examination and general practitioners) in a French town and its surrounding area (200,000 inhabitants): A woman was considered affected if she met the International RLS Study Group criteria for RLS diagnosis. RESULTS: 1,022 pregnant women living in a French town were included. 24% of women were affected by RLS during their pregnancy. The disease was strongly related to the third trimester of pregnancy and had a significant impact on sleep leading to severe nocturnal and diurnal consequences with a high consumption of sleep medication. CONCLUSIONS: RLS affects one quarter of pregnant women, essentially during the third trimester and represents an important public health issue with sleep medication intake.

Cerebral, facial, and orbital involvement in Erdheim-Chester disease: CT and MR imaging findings.

PURPOSE: To retrospectively review the brain magnetic resonance (MR) imaging and computed tomographic (CT) findings in patients with Erdheim-Chester disease (ECD). MATERIALS AND METHODS: The ethics committee required neither institutional review board approval nor informed patient consent for retrospective analyses of the patients' medical records and imaging data. The patients' medical files were retrospectively reviewed in accordance with human subject research protocols. Three neuroradiologists in consensus analyzed the signal intensity, location, size, number, and gadolinium uptake of lesions detected on brain MR images obtained in 33 patients with biopsy-proved ECD. RESULTS: Thirty patients had intracranial, facial bone, and/or orbital involvement, and three had normal neurologic imaging findings. The hypothalamic-pituitary axis was involved in 16 (53%) of the 30 patients, with six (20%) cases of micronodular or nodular masses of the infundibular stalk. Meningeal lesions were observed in seven (23%) patients. Three (10%) patients had bilateral symmetric T2 high signal intensity in the dentate nucleus areas, and five (17%) had multiple intraaxial enhancing masses. Striking intracranial periarterial infiltration was observed in three (10%) patients. Another patient (3%) had a lesion in the lumen of the superior sagittal sinus. Nine (30%) patients had orbital involvement. Twenty-four (80%) patients had osteosclerosis of the facial and/or skull bones. At least two anatomic sites were involved in two-thirds (n = 20) of the patients. Osteosclerosis of the facial bones associated with orbital masses and either meningeal or infundibular stalk masses was seen in eight (27%) patients. CONCLUSION: Lesions of the brain, meninges, facial bones, and orbits are frequently observed and should be systematically sought on the brain MR and CT images obtained in patients with ECD, even if these patients are asymptomatic. Careful attention should be directed to the periarterial environment.

Awareness within the French population concerning stroke signs, symptoms, and risk factors.

BACKGROUND: Effective implementation of early treatment strategies for stroke requires prompt admission to hospital which could be delayed for several reasons such as poor awareness of population. OBJECTIVE: To assess current public knowledge of stroke. METHODS: We randomly selected 411 persons living in Poitou-Charentes (area of nearly 1,700,000 persons in France) and performed an open-ended questionnaire regarding stroke risk factors, stroke warning signs, source of information, and stroke attitude. RESULTS: Most of the patients (62.3%) were able to name three risk factors but not to report the most important and less than half of the respondents were able to recognize one or more stroke warning sign. Predictors of adequate knowledge of both stroke risk factors and warning signs were similar and included age and sources of information (books, magazines and newspapers or family members or relatives who have suffered from a stroke or general practitioner). CONCLUSIONS: This study emphasizes that knowledge of stroke risk factors and warning signs was moderate at best. Improvements can only result from using a broad range of sustained educational efforts through simple and understandable school education or public media.