Pre-treatment risk markers for hemorrhagic transformation in posterior circulation acute ischemic stroke treated with reperfusion therapy.

BACKGROUND: Hemorrhagic transformation (HT) is an uncommon complication of posterior circulation acute ischemic stroke (PCS) compared to anterior circulation stroke. Nevertheless, it remains a major concern especially following reperfusion therapy. This study aimed at identifying potential predictive factors associated with HT in PCS. METHODS: Consecutive patients, from a multicenter cohort, with PCS treated by IVT or EVT or the combination of both, were included from December 2015 to May 2019. The European Cooperative Acute Stroke Study criteria was used to identify HT. Potential risk factors were analyzed using univariate and multivariable testing models. RESULTS: A total of 96 patients were included in our study. Median age was 66 (57-83) years, 54 patients (56%) were male and median baseline NIHSS was 8 (4-14). 77 patients (80%) received IVT and 54 patients (56%) benefited from EVT. HT occurred in 19 patients (20%), while sHT occurred in 3 patients (3%). HT was found to be associated with poor functional status at 3 months in univariate analysis (p = 0.0084). Multivariable analysis confirmed that higher baseline NIHSS (OR 1.1008; 95% CI [1.0216-1.1862]; p = 0.0117) and lobar topography of ischemia (OR 4.4275; 95% CI [1.3732-14.2753]; p = 0.0127) were independent predictors of the occurrence of HT. DISCUSSION: HT is associated with increased morbidity in patients with PCS; higher NIHSS and lobar ischemia were independent predictors of HT in our population. Easy-to-use predictive markers may help to tailor therapeutic management of patients with PCS.

Psychiatric Symptoms and Cognitive Disorders in Behçet's Disease: A Single-Center, Cross-Sectional Study.

BACKGROUND: Behçet's disease (BD) is a rare form of vasculitis involving both veins and arteries of all calibers. Psychological symptoms and cognitive impairment appear to be frequent, but few data are available. METHODS: All consecutive patients in our center fulfilling the 2013 BD criteria underwent a psychometric evaluation with auto- (SCL-90-R and Modified Fatigue Index) and hetero-questionnaires (MINI). A standardized test battery assessed cognitive dysfunction. Data were correlated with BD activity as well as quality of life (SF-36). RESULTS: We included 20 consecutive patients (16 men, four women) with a median [IQR] age of 38 (30.0-45.5) and a median disease duration of 7 years (1.8-11.0). Five patients had an abnormal brain MRI. The SCL-90-R questionnaire highlighted eight psychopathological profiles (42.1%) that correlated with altered quality of life and more severe fatigue. The most frequent symptoms were anxiety (9/19, 47.4%), somatization (8/19, 42.1%) and phobia (5/19, 26.3%). Psychopathological symptoms appeared to be more severe, but not more frequent, in neuro-Behçet's patients. Based on standardized cognitive evaluation, nine patients had cognitive impairment defined by three or more altered tests. Notably, 6/9 patients did not have any complaint of memory loss and were thus considered ansognostic. CONCLUSION: Cognitive involvement was significantly associated with BD activity score (BSAS) but not with brain MRI abnormalities.

Acute-Onset Ataxia and Transient Cerebellar Diffusion Restriction Associated with a PRRT2 Mutation.

PRRT2 gene mutations cause paroxysmal kinesigenic dyskinesia (PKD), infantile convulsions, hemiplegic migraine, and episodic ataxia. A 21-year-old woman reported an episode of dizziness and ataxic gait occurring after swimming. Brain MRI showed a hyperintense cerebellar lesion on diffusion-weighted imaging (DWI) with decreased apparent diffusion coefficient. The clinical course was favorable. Both clinical and MRI abnormalities regressed. Her brother had presented PKD since adulthood. A C.649dupC PRRT2 truncating mutation was identified in both patients. To our knowledge, this is the first case of an acute cerebellar ataxia associated with heterozygous PRRT2 mutation and transient cerebellar hyperintensity on DWI. Among the clinical and genetic heterogeneities of familial paroxysmal disorders, PRRT2 mutation may be considered in patients with episodic cerebellar ataxia and diffusion restriction on neuroimaging.

Refractory T-Cell Anergy and Rapidly Fatal Progressive Multifocal Leukoencephalopathy After Prolonged CTLA4 Therapy.

Progressive multifocal leukoencephalopathy (PML) is a deadly demyelinating disease due to central nervous system replication of the human polyomavirus JC virus (JCV) in immunosuppressed patients. The only effective therapeutic approach is to restore anti-JCV T-cell responses. In this study, we describe a case of rapidly fatal PML with JCV T-cell anergy in a renal transplant patient treated with CTLA4-Ig (belatacept, a CD28-B7 costimulation blocker and T-cell anergy inducer). T-cell anergy could not be reversed despite several therapeutic approaches. Progressive multifocal leukoencephalopathy secondary to biotherapy-induced T-cell anergy may thus represent a subset of PML with major resistance to anti-JCV immune recovery.

Can developmental venous anomalies cause seizures?

Developmental venous anomalies (DVAs) are congenital anatomical variants of normal venous drainage of normal brain. Although DVAs are often discovered on the occasion of a seizure, their involvement in epilepsy is poorly studied. Our objective was to determine whether DVA can cause seizures, in the cases where there is no associated lesion, including no cavernoma or dysplasia. Based on clinical history, cerebral MRI, EEG recording, and 18F-FDG PET, we report 4 patients with DVA revealed by seizures. The first patient had a convulsive seizure caused by a hemorrhagic infarction due to thrombosis of her DVA. The second patient had a left temporo-parietal DVA next to a nonspecific lesion, possibly a sequelae of a venous infarction. The last two patients disclosed an isolated and uncomplicated DVA with a concordant epileptic focus confirmed on ictal video EEG recording. We reviewed literature and identified 21 other published cases of seizures caused by complications of a DVA and 9 patients that may have a direct link between epilepsy and an isolated and uncomplicated DVA. Seizures are linked to a DVA in two main situations: presence of an associated epileptogenic lesion, such as cavernoma or dysplasia, and occurrence of a complication of the DVA. Before concluding that a seizure is caused by a DVA, it is essential to perform full MRI protocols to search them. It remains rare and uncertain that isolated and uncomplicated DVA can cause seizures. In this last situation, physiopathological processes are probably different in each patient.

Hippocampal volume predicts antidepressant efficacy in depressed patients without incomplete hippocampal inversion.

BACKGROUND: Incomplete hippocampal inversion (IHI), also called malrotation, is a frequent atypical anatomical pattern of the hippocampus. Because of the crucial implication of the hippocampus in Major Depressive Disorder (MDD) and the neurodevelopmental hypothesis of MDD, we aimed to assess the prevalence of IHI in patients with MDD, the link of IHI with hippocampal volume (HV) and the impact of IHI on the predictive value of HV for response and remission after antidepressant treatment. METHODS: IHI (right and left, partial and total and IHI scores) and HV were assessed in 60 patients with a current Major Depressive Episode (MDE) in a context of MDD and 60 matched controls. Patients were prospectively assessed at baseline and after one, three and six months of antidepressant treatment for response and remission. RESULTS: The prevalence of IHI did not significantly differ between MDD patients (right = 23.3%; left = 38.3%) and controls (right = 16.7%; left = 33.3%). IHI was not significantly associated with MDD clinical characteristics. IHI alone did not predict response and remission after antidepressant treatment. However, an interaction between left HV and left IHI predicted six-month response (p = 0.04), HDRS score decrease (p = 0.02) and both three-month (p = 0.04) and six-month (p = 0.03) remission. A case-control design in 30 matched patients with or without left IHI confirmed that interaction. In patients without left IHI, left HV at baseline were smaller in six-month non-remitters as compared to remitters (2.2(± 0.43) cm3 vs 2.97(± 0.5) cm3 p = 0.02), and in six-month non-responders as compared to responders (2.18(± 0.42) cm3 vs 2.86(± 0.54) cm3, p = 0.03). In patients with left IHI, no association was found between left HV at baseline and antidepressant response and remission. CONCLUSION: IHI is not more frequent in MDD patients than in controls, is not associated with HV, but is a confounder that decreases the predictive value of hippocampal volume to predict response or remission after antidepressant treatment. IHI should be systematically assessed in future research studies assessing hippocampal volume in MDD.

Diffusion tensor magnetic resonance imaging of trigeminal nerves in relapsing herpetic keratouveitis.

BACKGROUND: Corneal hypoesthesia is the landmark of HSV and VZV keratitis and can lead to neurotrophic keratitis. Diffusion tensor imaging (DTI) is a new magnetic resonance imaging (MRI) derived technique, which offers possibilities to study axonal architecture. We aimed at assessing the potential impact of recurrent HSV or VZV-related keratitis on the axonal architecture of trigeminal nerves using DTI. DESIGN: Prospective non-interventional study. PARTICIPANTS: Twelve patients and 24 controls. METHODS: DTI using MRI of the trigeminal fibers and corneal esthesiometry using the Cochet-Bonnet esthesiometer were acquired for patients affected by unilateral and recurrent HSV or VZV-related keratitis (3 months after the last corneal inflammatory event), and control subjects with no history of ocular or neuronal disease affecting the trigeminal pathways. MAIN OUTCOME MEASURES: Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were compared between the 2 eyes of both patients and controls, and correlated with corneal esthesiometry. RESULTS: FA was lower in the trigeminal fibers ipsilateral to the affected eye compared to the non-affected side (0.39±0.02 versus 0.46±0.04, P=0.03). This difference was more important than the intra-individual variability observed in controls. Concomitantly, the asymmetry in ADC results was significantly correlated with the loss of corneal sensitivity in the affected eye. CONCLUSIONS: Corneal hypoesthesia related to HSV and VZV keratitis is associated with persistent modifications in the architecture and functionality of the trigeminal fibers. These results add further explanation to the pathogenesis of HSV and VZV-induced neurotrophic keratitis, which may occur despite an apparent quiescence of the disease.

Pituitary MRI characteristics in 297 acromegaly patients based on T2-weighted sequences.

Responses of GH-secreting adenomas to multimodal management of acromegaly vary widely between patients. Understanding the behavioral patterns of GH-secreting adenomas by identifying factors predictive of their evolution is a research priority. The aim of this study was to clarify the relationship between the T2-weighted adenoma signal on diagnostic magnetic resonance imaging (MRI) in acromegaly and clinical and biological features at diagnosis. An international, multicenter, retrospective analysis was performed using a large population of 297 acromegalic patients recently diagnosed with available diagnostic MRI evaluations. The study was conducted at ten endocrine tertiary referral centers. Clinical and biochemical characteristics, and MRI signal findings were evaluated. T2-hypointense adenomas represented 52.9% of the series, were smaller than their T2-hyperintense and isointense counterparts (P<0.0001), were associated with higher IGF1 levels (P=0.0001), invaded the cavernous sinus less frequently (P=0.0002), and rarely caused optic chiasm compression (P<0.0001). Acromegalic men tended to be younger at diagnosis than women (P=0.067) and presented higher IGF1 values (P=0.01). Although in total, adenomas had a predominantly inferior extension in 45.8% of cases, in men this was more frequent (P<0.0001), whereas in women optic chiasm compression of macroadenomas occurred more often (P=0.0067). Most adenomas (45.1%) measured between 11 and 20 mm in maximal diameter and bigger adenomas were diagnosed at younger ages (P=0.0001). The T2-weighted signal differentiates GH-secreting adenomas into subgroups with particular behaviors. This raises the question of whether the T2-weighted signal could represent a factor in the classification of acromegalic patients in future studies.

Familial acute necrotizing encephalopathy due to mutation in the RANBP2 gene.

BACKGROUND: Acute necrotizing encephalopathy (ANE) is a rare and severe parainfectious central nervous system disease in which previously healthy children develop rapidly progressive coma following viral illness. While most ANE are sporadic, familial autosomal dominant ANE due to mutations in the RANBP2 gene has been recently reported (ANE1 or infection-induced acute encephalopathy-3 (IIAE3)). To date, only few IIAE3 families with ADANE episodes have been described. OBJECTIVE: To report a new family with ADANE, describe clinical and radiological features and discuss differential diagnosis including Leigh syndrome or multiple sclerosis. OBSERVATION: The family included 3 symptomatic individuals and one 59 year-old asymptomatic obligate carrier. Patients presented acute episodes of encephalopathy few days after common viral infection. Ages of onset ranged from 6 months to 5 years. Episodes not only occurred in childhood but also recurred in adulthood. Initial neurological signs included coma, focal neurological deficits and seizures. MRI showed typical necrotizing lesions primarily in the thalamus and brainstem, and in the temporal lobes and insula. CSF cell count and cultures were normal during episodes. RANBP2 gene screening identified pathogenic heterozygous c.1754C>T mutation (p.Thr585Met). Episodes led to cognitive or physical handicap in 2 patients and were fatal in one child. CONCLUSION: IIAE3 or ADANE due to RANBP2 mutations has a large clinical heterogeneity. Our family illustrates the associated phenotypes from asymptomatic carrier to severe episodes of encephalopathy. Based on MRI features, the genetic IIAE3 diagnosis is important since prophylaxis and symptomatic management of infections may be beneficial, possibly in association with steroid or gammaglobulins.

Congenital vertebral duplication: a predisposing risk factor for dissection.

Spontaneous cervical-artery dissection (CAD) is a major cause of cerebral ischaemia in young adults. While their pathophysiology remains still poorly understood, CAD is considered today as a multifactorial disease determined by general and local predisposing factors; these predisposing factors being predominantly constitutional abnormalities of the arterial wall. Here, we report an MRI-confirmed dissection of a duplicated vertebral artery, in a patient with attacks of vertigo due to cerebellar infarction following a minor neck trauma. Knowing that another case of vertebrobasilar CAD on a duplicated vertebral artery has been reported, these rare anatomical variants probably predispose to vertebral CAD, via local histological defects or significant hemodynamics alterations, as reported for the classical local predisposing conditions for vertebral dissection, i.e.: fibromuscular dysplasias or carotid redundancies (including loops, kinks and coils).

MR diffusion tensor imaging, fiber tracking, and single-voxel spectroscopy findings in an unusual MELAS case.

A 23-year-old man was admitted to the intensive care unit for respiratory failure, global lower and upper limb palsy, and higher cognitive function deterioration. Imaging, performed with a combination of the MR diffusion tensor imaging, fiber tracking, and MR spectroscopy, suggested the diagnosis of an acute severe unusual mitochondrial encephalopathy, lactic acidosis, and strokelike event, which was confirmed by muscle biopsy, but fiber tracking showed unexpected unaltered white matter tracts.