Late-onset neutropenia after anti-CD20 therapy for multiple sclerosis, neuromyelitis optica spectrum disorders and MOG antibody-associated disease: A prospective study.

Late-onset neutropenia (LON) after anti-CD20 therapy is a poorly described side effect in inflammatory disorders of the CNS. In this prospective study, patients treated with Rituximab or Ocrelizumab for MS, neuromyelitis optica spectrum disorders or MOG antibody-associated disease (MOGAD) were asked to perform complete blood count (CBC) every two weeks for six months, with the aim of identifying LON. Out of 152 patients, two (1,32%) had an absolute neutrophil count <1,000/mm3: one patient with MOGAD had agranulocytosis and one patient with MS had grade 3 neutropenia. Both were asymptomatic. These results confirm that LON after anti-CD20 therapy in inflammatory disorders of the CNS is not exceptional. Nevertheless, this biological complication remains too infrequent to justify close systematic CBC follow-up.

Audiovestibular neuropathy in an immunocompetent man with cryptococcal meningitis.

INTRODUCTION: Cryptococcus spp. is a fungus responsible for 600,000 deaths per year worldwide, mainly in immunosuppressed subjects. However, 20% of cases occur in immunocompetent subjects. Neuropathic disorders involving the auditory nerve have been reported, but vestibular disorders have never been described in detail. We report the case of an immunocompetent man, who presented audiovestibular disorders leading to a diagnosis of cryptococcal meningitis. CASE REPORT: A 39-year-old man was referred for balance disorders and right sensorineural hearing loss. He presented right vestibulo-saccular impairment and bilateral absence of auditory brainstem responses. Brain MRI was suggestive of cryptococcal meningitis. A cystic lesion in the right flocculus compressed the vestibulocochlear nerve. During monthly follow-up, pure tone audiometry gradually improved and speech audiometry in silence returned to normal. Partial resynchronization of the auditory afferent pathways was observed only on the contralateral side to vestibulocochlear nerve compression, while complete recovery of saccular function was observed. DISCUSSION: Cryptococcal meningitis in immunocompetent subjects may be accompanied by lesions of the auditory and vestibular afferent pathways. Recovery of hearing and balance was observed in response to medical treatment and early vestibular rehabilitation.

Off-label use of tocilizumab in neuromyelitis optica spectrum disorders and MOG-antibody-associated diseases: A case-series.

BACKGROUND: The objective of the study was to evaluate the indication, efficacy and safety of tocilizumab, a humanized anti-interleukin-6 receptor antibody, in patients with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody associated diseases (MOGAD) encountered in current neurological practice. MATERIAL AND METHODS: We conducted a retrospective analysis of an exhaustive cohort of patients with inflammatory CNS disorders at Toulouse University Hospital, France, from 2014 to 2020. Efficacy was evaluated with clinical outcome by the Annual Relapse Rate, and radiological outcome with MRI data. The other outcomes were adverse events and effectiveness according to the form of injection (intravenous or subcutaneous). RESULTS: Seven patients were treated with tocilizumab: four patients had NMOSD with AQP4+ antibodies (57%) and three had MOGAD (43%). Tocilizumab was administered in the presence of persistent clinical activity and/or severe side effects with other immunosuppressant medications. The median follow-up on tocilizumab was 23 months (4-50 months). All patients started with monthly intravenous injection, then three switched to a subcutaneous form. All patients were relapse-free throughout the duration of treatment with tocilizumab, and one presented with a new cervical lesion on MRI. Four patients had no adverse effect, two had a significant increase in infection rate, and one had dyslipidemia. CONCLUSION: tocilizumab appears to be an effective therapy for patients with refractory NMOSD or MOGAD. Subcutaneous and intravenous injections appear to be equally effective.

Late-onset neutropenia after RITUXIMAB therapy for multiple sclerosis, neuromyelitis optica spectrum disorders and MOG-antibody-associated diseases.

Few cases of late onset neutropenia after RITUXIMAB treatment (LONART) have been reported in patients with neuroinflammatory disorders. We conducted a retrospective analysis of patients treated with RITUXIMAB for neuromyelitis optica spectrum disorders (NMOSD), MOG-antibody-associated disease (MOGAD) and multiple sclerosis (MS) at the Toulouse University Hospital from November 2007 to October 2019. Ten patients with LONART were identified in a total of 385 patients: 4/25 were MOGAD patients, 2/20 were NMOSD patients and only 4/340 were MS patients (p < 0,05). Six required intravenous antibiotics whereas four were asymptomatic. Eight patients received new infusions of RITUXIMAB after resolution of their neutropenia. Neutropenia recurred in one patient.

[Transient monocular blindness: Vascular causes and differential diagnoses]. / Cécité monoculaire transitoire : causes vasculaires et diagnostics différentiels.

Transient monocular blindness is an acute episode of ischemic origin in which one eye has profound visual loss, followed by full recovery within one hour. Transient monocular blindness most often occurs in the setting of retinal ischemia secondary to carotid embolism, but other mechanisms have been reported, including thrombosis (most often in the setting of giant cell arteritis), hemodynamic disorders (secondary to severe carotid stenosis) or vasospasm. Transient monocular blindness is considered a transient ischemic attack originating in the carotid arteries and must benefit from the same management as transient ischemic attack involving the brain, in order to prevent a subsequent stroke.

First-line therapy in relapsing remitting multiple sclerosis.

Today, first-line treatments for multiple sclerosis include injectable immunomodulators - some of which have been on the market for nearly 25 years - as well as teriflunomide and dimethyl fumarate, which are more recent, but have opened the way for oral treatments. These drugs are considered similar in effectiveness, and their safety and side-effect profiles are generally reassuring. These treatments have been associated with a reduction in radiological and clinical disease activity, and a positive effect on patient quality of life, especially when introduced early in the disease process. This article will discuss data on first-line treatments currently available in France, their effectiveness and safety, and their place in pediatric patients and in woman who plan to become pregnant.

Transient monocular blindness: Vascular causes and differential diagnoses.

Transient monocular blindness is an acute episode of ischemic origin in which one eye has profound visual loss, followed by full recovery within one hour. Transient monocular blindness most often occurs in the setting of retinal ischemia secondary to carotid embolism, but other mechanisms have been reported, including thrombosis (most often in the setting of giant cell arteritis), hemodynamic disorders (secondary to severe carotid stenosis), or vasospasm. Transient monocular blindness is considered a transient ischemic attack originating in the carotid arteries, and must be managed the same as transient ischemic attack involving the brain, in order to prevent a subsequent stroke.

[Migraine with visual aura]. / « Migraine ophtalmique ¼ ou migraine avec aura visuelle.

Migraine with visual aura is marked by recurrent episodes of transient visual disturbance, often followed by headaches. Its pathophysiology has not been fully understood, but visual auras might be related to a self-propagating wave of cortical depolarization called "cortical spreading depression", triggering a trigemino-vascular "storm" ultimately leading to headaches. The most specific visual symptom is the "fortification spectrum" consisting of glimmering jagged lines spreading from the center to the periphery, and leaving a transient scotoma in its wake. Other visual symptoms are numerous, ranging from elementary positive or negative visual phenomena to complex and elaborate hallucinations. The diagnosis can be made according to the International Classification of Headache Disorders revised in 2013. The main goal of the treatment is to relieve the patient's pain quickly and to decrease the frequency of the episodes.

Cerebrovascular events as presenting manifestations of Myeloproliferative Neoplasm.

AIM: To determine the incidence and main characteristics of cerebrovascular events as the presenting manifestations of myeloproliferative neoplasm (MPN). METHODS: The Hematology in Lyon (HEMILY) registry is a prospective database (763 patients) of all cases of MPN diagnosed since 2005 in the Rhône-Alpes district of France. The MPN cases were divided into four groups: polycythemia vera (PV); essential thrombocythemia (ET); myelofibrosis (MF); and atypical MPN. The ischemic stroke subtype was classified according to TOAST criteria. RESULTS: A stroke history revealed MPN in 35 (4.3%) patients: 22 (63%) had an ischemic stroke; eight (23%) had a transient ischemic attack; four (11%) had cerebral venous thrombosis; and one (3%) had hemorrhagic stroke. All patients had hemoglobin and/or platelet count abnormalities. In addition, 12 (34%) patients had PV, 21 (60%) had ET, one (3%) had MF and one (3%) had atypical/unclassified MPN. The JAK2 V617F mutation was found in 83% of patients. In 18 (51%) patients, an additional mechanism of stroke was present (atherosclerosis in 10 patients, atrial fibrillation in one patient and dissection in another). The median NIHSS score at entry was 2, and the median modified Rankin Scale score at 3 months was 0. Compared with the general MPN population, stroke-MPN patients presented with significantly higher levels of hemoglobin (P<0.001) and were more frequently positive for the JAK2 V617F mutation (P=0.044). CONCLUSION: Stroke revealing MPN is rare. However, careful attention should still be paid to blood counts even in patients with obvious stroke etiologies, as early diagnosis permits prompt treatment and decreases the risk of recurrence, thus limiting morbidity and mortality.

Peripheral late reactivation of a previously typical monofocal Baló's concentric sclerosis lesion.

We report a 41-year-old woman with rapidly progressive left hemiparesis, revealing an inflammatory reactivation of a previously known parietal Baló's concentric sclerosis lesion. The first attack occurred five years before. After a slow recovery following high-dose steroid infusions the patient stabilized. Because of recurrent ataxia and left hemiparesis a new magnetic resonance imaging was performed showing an extension of the initial lesion with a peripheral gadolinium enhancement on T1-weighted images. Such a reactivation pattern of an isolated Baló's concentric sclerosis lesion, occurring some years later, is described for the first time.

[Balint syndrome and spatial functions of the parietal lobe]. / Syndrome de Balint et fonctions spatiales du lobe pariétal.

Balint's syndrome corresponds to the combination of optic ataxia, simultanagnosia and gaze apraxia. It generally results from a bilateral dysfunction of the posterior parietal cortex. Since its early descriptions the syndrome has been subject to many interpretations and controversies. In this article we will reconsider the current concept of Balint's syndrome. A first part will develop the clinical aspects, causes, description of symptoms, examination techniques and neuroanatomical correlations. In a second part, we will discuss how this syndrome can be included in the background of visual neurosciences, particularly through a visual attentional aspect. We will discuss the phenomenon of remapping and some recent data that may contribute to explain the pathophysiology of manifestations as optic ataxia, simultanagnosia or gaze apraxia.

[Rupture of intracranial dermoid cyst with disseminated lipid droplets]. / Dissémination sous-arachnoïdienne de gouttelettes lipidiques par rupture d'un kyste dermoïde intracérébral.

INTRODUCTION: Dermoid cysts are rare slow-growing benign tumors of the central nervous system generally diagnosed in the third to fifth decade. They are formed from inclusion of ectodermal elements during neural tube closure, and are mostly located along the cranial or spinal midline axis. They cause many non specific symptoms such as headache and seizures, and may spontaneously rupture spreading fatty droplets into the ventricles and subarachnoid spaces. Rupture of dermoid cysts causes sequelae which may vary from no symptoms to death. In general, subtotal surgical removal is required for ruptured dermoid cysts. CASE REPORTS: We report two cases of ruptured intracranial dermoid tumor with non-specific clinical presentations. The first rupture was asymptomatic and discovered on brain magnetic resonance imaging (MRI) performed for other purposes. The second case was identified on brain imaging performed because of daily headache. These dermoid cysts were not surgically treated. Surveillance was advised because of the spontaneously favourable outcome observed in both cases. CONCLUSION: Surgical removal is not the only treatment of ruptured dermoid cyst. Monitoring with brain MRI can be sufficient if the rupture has no severe clinical impact.

[What has changed for stroke at the beginning of the 21st century]. / Les accidents vasculaires cérébraux : ce qui a changé au début du xxi(e) siècle.

INTRODUCTION: Striking developments in stroke epidemiology, initially based on the results of the Framingham study, have greatly improved our neuroepidemiological knowledge of the disease. STATE OF ART: The development of stroke registries has made it possible to evaluate the descriptive epidemiology of stroke and its evolution. With the increasing use of CT-scan, MRI, and either cardiac or vascular imaging, the diagnosis of stroke and its subtypes has been made easier. Over the last 20 years, a decrease in the incidence and mortality of stroke has been observed in Western countries. In contrast, in Dijon, which has the only population-based stroke registry in France, stable incidence rates have been reported. However, over the same period, age at stroke onset has risen by five years in men and eight years in women, which is probably related to both population aging and improvements in primary prevention and general health. The reported decrease in case-fatality rates suggests better acute management of stroke patients, and explains in part the increase in the prevalence of stroke. In addition, the assessment of vascular risk factors has demonstrated that high blood pressure remains the principal risk factor for both ischemic and hemorrhagic stroke, and that antihypertensive treatment is able to reduce stroke incidence. PERSPECTIVES: Epidemiology studies could make it possible to measure the impact of new therapeutic strategies applied in both primary and secondary prevention. CONCLUSION: Prevention, diagnosis, and acute treatment of stroke have considerably improved, but cerebrovascular diseases together with myocardial infarction remain the leading cause of death. Despite the absence of a rise in the incidence of stroke, its prevalence has increased. This is due to the decrease in case-fatality rates. As a consequence, there is an urgent need to organize health networks around stroke. Moreover, the rise in stroke-free life expectancy is a positive finding that reflects improvements in prevention.

[Neurogenic osteoarthropathy of the knee associated with spina bifida: a diagnosis not to be missed]. / Ostéoarthropathie neurogène du genou associée à un spina bifida : un diagnostic à ne pas méconnaître.

Neurogenic arthropathy is a severe complication of chronic sensitive deficits that occurred commonly in diabetic neuropathies. It is a destructive and painless osteoarthritis associated with a loss of the deep sensitivity and a defect of protective reactions against chronic articular microtraumatisms. We report a 55-year-old woman with neuroarthropathy of the knee resulting from a spina bifida. Bisphosphonate use is an effective but non-consensual treatment.