The central vein sign in multiple sclerosis patients with vascular comorbidities.

BACKGROUND: The central vein sign (CVS) is an imaging biomarker able to differentiate multiple sclerosis (MS) from other conditions causing similar appearance lesions on magnetic resonance imaging (MRI), including cerebral small vessel disease (CSVD). However, the impact of vascular risk factors (VRFs) for CSVD on the percentage of CVS positive (CVS+) lesions in MS has never been evaluated. OBJECTIVE: To investigate the association between different VRFs and the percentage of CVS+ lesions in MS. METHODS: In 50 MS patients, 3T brain MRIs (including high-resolution 3-dimensional T2*-weighted images) were analyzed for the presence of the CVS and MRI markers of CSVD. A backward stepwise regression model was used to predict the combined predictive effect of VRF (i.e. age, hypertension, diabetes, obesity, ever-smoking, and hypercholesterolemia) and MRI markers of CSVD on the CVS. RESULTS: The median frequency of CVS+ lesions was 71% (range: 35%-100%). In univariate analysis, age (p < 0.0001), hypertension (p < 0.001), diabetes (p < 0.01), obesity (p < 0.01), smoking (p < 0.05), and the presence of enlarged-perivascular-spaces on MRI (p < 0.005) were all associated with a lower percentage of CVS+ lesions. The stepwise regression model showed that age and arterial hypertension were both associated with the percentage of CVS+ lesions in MS (adjusted R2 = 0.46; p < 0.0001 and p = 0.01, respectively). CONCLUSION: The proportion of CVS+ lesions significantly decreases in older and hypertensive MS patients. Although this study was conducted in patients with an already established MS diagnosis, the diagnostic yield of the previously proposed 35% CVS proportion-based diagnostic threshold appears to be not affected. Overall these results suggest that the presence of VRF for CSVD should be taken into account during the CVS assessment.

West Nile Virus Neuroinvasive Disease Accelerating Probable Dementia With Lewy Bodies.

We describe a case of dementia with Lewy bodies immediately following encephalitis due to West Nile virus (WNV). The patient had rapid eye movement-sleep behavior disorder and constipation before the onset of encephalitis, which suggests that he would have ultimately developed dementia with Lewy bodies even without WNV infection. Our case illustrates the interactions between α-synuclein and WNV, as observed in mouse models, wherein synuclein expression augments after WNV infection and protects neurons against the virus.

The "central vein sign" in patients with diagnostic "red flags" for multiple sclerosis: A prospective multicenter 3T study.

BACKGROUND: The central vein sign (CVS) has been shown to help in the differential diagnosis of multiple sclerosis (MS), but most prior studies are retrospective. OBJECTIVES: To prospectively assess the diagnostic predictive value of the CVS in diagnostically difficult cases. METHODS: In this prospective multicenter study, 51 patients with suspected MS who had clinical, imaging, or laboratory "red flags" (i.e. features atypical for MS) underwent 3T fluid-attenuated inversion recovery (FLAIR*) magnetic resonance imaging (MRI) for CVS assessment. After the diagnostic work-up, expert clinicians blinded to the results of the CVS assessment came to a clinical diagnosis. The value of the CVS to prospectively predict an MS diagnosis was assessed. RESULTS: Of the 39 patients who received a clinical diagnosis by the end of the study, 27 had MS and 12 received a non-MS diagnosis that included systemic lupus erythematosus, sarcoidosis, migraine, Sjögren disease, SPG4-spastic-paraparesis, neuromyelitis optica, and Susac syndrome. The percentage of perivenular lesions was higher in MS (median = 86%) compared to non-MS (median = 21%; p < 0.0001) patients. A 40% perivenular lesion cutoff was associated with 97% accuracy and a 96% positive/100% negative predictive value. CONCLUSION: The CVS detected on 3T FLAIR* images can accurately predict an MS diagnosis in patients suspected to have MS, but with atypical clinical, laboratory, and imaging features.

Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies.

OBJECTIVES: In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the "central vein sign") improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS). METHODS: In 31 patients with inflammatory CNS vasculopathies and 52 with relapsing-remitting MS, 3-dimensional T2*-weighted and T2-fluid-attenuated inversion recovery images were obtained during a single MRI acquisition after gadolinium injection. For each lesion, the central vein sign was evaluated according to consensus guidelines. For each patient, lesion count, volume, and brain location, as well as fulfillment of dissemination in space MRI criteria, were assessed. RESULTS: MS showed higher frequency of perivenular lesions (median = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies, Behçet disease showed the highest median frequency of perivenular lesions (34%), followed by PACNS (14%), antiphospholipid syndromes (12%), Sjögren syndrome (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%. INTERPRETATION: The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283-294.

Multiple Sclerosis Multidisciplinary Care: A National Survey and Lessons for the Global Community.

BACKGROUND: Access to, standardization and reimbursement of multidisciplinary care for people with MS (PwMS) is lacking in many countries. Therefore, this study aims to describe the current multidisciplinary care for people with MS (PwMS) in Belgium and identify benefits, needs and future perspectives METHODS: A survey for PwMS questioned various aspects of MS and viewpoints on care. For MS nurses (MSN) and neurologists, employment, education, job-content, care organization and perspectives were inquired. Descriptive and univariate statistics were performed RESULTS: The PwMS survey comprised 916 respondents with a mean age of 46±12.7 years and 75,4 % of the respondents being female. The majority of the participants had relapsing remitting MS (60.8 %) and the mean patient determined disease steps (PDDS) was 2.0 (IQR=3). 65.3 % and 60.4 % of the PwMS reported having access to a multidisciplinary team (MDT) or MSN. Access to an MSN was associated with more frequent disease modifying treatment (p=.015), spasticity (p=.042) and gait treatment (p=.035), but also more physiotherapy (p=.004), driver's license adjustment (p<.001) and a higher employment rate (p=.004). MDT access was associated with more frequent symptomatic bladder treatment (p=.047), higher physiotherapy rate (p<.001), higher work- (p=.002), insurance- (p<.001) and home support measures (p=.019). PwMS without an available MDT more often indicated that MS care needs improvement (p<.001). MSN's (n = 22) were mainly funded through various budgets, including hospital and neurology practice budgets. Finally, 69 % and 75 % neurologists (n = 62) working without an MSN or MDT stated a need of such support and 61 % agreed that MDT's should be organized at hospital-network level CONCLUSION: MDT and MSN availability may enhance medical and socio-economic support for PwMS. Guidelines, alignment and reimbursement are needed.

Diagnosis of dizziness in the emergency department: A 1-year prospective single-center study.

BACKGROUND: The management of dizziness and vertigo can be challenging in the emergency department (ED). It is important to rapidly diagnose vertebrobasilar stroke (VBS), as therapeutic options such as thrombolysis and anticoagulation require prompt decisions. OBJECTIVE: This study aims to assess the rate of misdiagnosis in patients with dizziness caused by VBS in the ED. METHODS AND RESULTS: The cohort was comprised of 66 patients with a mean age 56 years; 48% were women and 52% men. Among dizzy patients, 14% had VBS. We used Cohen's kappa test to quantify the agreement between two raters -namely, emergency physicians and neurologists -regarding the causes of dizziness in the ED. The Kappa value was 0.27 regarding the final diagnosis of central vertigo disorders and VBS, thus showing the low agreement. We used the χi2 test to show the association between the presence of two or more cardiovascular risk factors and admission to the stroke unit (p = 0.015). CONCLUSION: There is a substantial rate of misdiagnosis in patients with dizziness caused by VBS in the ED. To reduce the number of missing diagnoses of VBS in the future, there is a need to train emergency physicians in neurovestibular examinations, including the HINTS examination for acute vestibular syndrome (AVS) and the Dix-Hallpike (DH) maneuver for episodic vestibular syndrome. Using video head impulse test could help reduce the rate of misdiagnosis of VBS in the ED.

Occipital Epilepsy With Subcortical Atrophy in Celiac Disease: A Case Report.

We report a 50-year-old man with celiac disease who presented with occipital epilepsy. Brain MRI showed right occipital subcortical white matter hyperintensities, consistent with the posterior epileptic focus suggested by the clinical features of the seizures and documented on EEG. Shortly after the introduction of a gluten-free diet, the white matter abnormalities resolved. The patient went on to develop simultagnosia. Follow-up MRI showed right occipital lobe atrophy. This report emphasizes the importance of recognizing gluten-associated neurologic manifestations and usefulness of thegluten-free diet.

COVID-19: Post-vaccine Smell and Taste Disorders: Report of 6 Cases.

Post-vaccine olfactory and gustatory disorders are very rare and were reported in patients who received influenza vaccines. In this article, we report 6 cases of post-coronavirus disease 2019 (COVID-19) vaccine olfactory and gustatory disorders in patients with negative nasal swabs. Precisely, olfactory and gustatory dysfunctions were reported in 5 and 1 patients, respectively. Sense disorders occurred after the first injection of AstraZeneca (n = 4) or the second injection of Pfizer (n = 2) vaccines. In 4 cases, the olfactory or gustatory disorder was confirmed with psychophysical evaluations. The duration of chemosensory dysfunction ranged from 4 to 42 days. None of the patient reported mid- or long-term olfactory or gustatory disorder. The occurrence of olfactory and gustatory dysfunctions in adults benefiting from COVID-19 vaccines is still rare but has to be known by otolaryngologists.

Clonidine administration during intraoperative monitoring for pediatric scoliosis surgery: Effects on central and peripheral motor responses.

OBJECTIVE: To study the effect of clonidine administrated as a co-analgesic during scoliosis surgery, on the neuromonitoring of spinal motor pathways. METHODS: Using standardized intraoperative monitoring, we compared the time course of peripherally and transcranially electrically evoked motor potentials (TcEMEPs) before and after injection of a single bolus of clonidine in children under total intravenous anesthesia (TIVA). MEP data were obtained from 9 patients and somatosensory evoked potentials (SSEPs) were obtained from 2 patients. The potential effect of clonidine on mean blood pressure (BP) was controlled. RESULTS: TcEMEPs from upper and lower limbs rapidly showed significant drops in amplitude after the injection of clonidine. Amplitudes reached minimal values within five minutes and remained very weak for at least 10-20minutes during which monitoring of the central motor pathways was severely compromised. SSEPs were not altered during maximal amplitude depression of the TcEMEPS. CONCLUSIONS: This is the first report showing that clonidine severely interferes with neuromonitoring of the spinal cord motor pathways. The results are discussed in light of the literature describing the effects of dexmedetomidine, another α-2 adrenergic agonist. The experimental and literature data point to central mechanisms taking place at both the spinal and cerebral levels. Therefore, clonidine as well as other α-2 adrenergic agonists should be used with extreme caution in patients for whom neuromonitoring of the motor pathways is required during surgery.

Improvement of sleep architecture parameters in cirrhotic patients with recurrent hepatic encephalopathy with the use of rifaximin.

BACKGROUND AND AIM: Sleep disorders are frequently reported in patients with cirrhosis and hepatic encephalopathy (HE). This study assessed the effect of rifaximin on sleep architecture parameters in patients with recurrent HE. PATIENTS AND METHODS: This sequential, prospective, and exploratory study involved all patients with cirrhosis and recurrent HE admitted between June 2014 and September 2015. HE was assessed according to the West-Haven Classification. Patients underwent 24-h polysomnography (PSG) and 7-day actigraphy. Rapid eye movement (REM) sleep was considered to be an indicator of good sleep quality. Patients completed questionnaires assessing the quality of sleep and sleepiness. After a 28-day course of rifaximin, the same assessment was repeated. RESULTS: Fifteen patients were included (nine men, mean age: 57±11 years). Child-Pugh scores ranged from B7 to C15. Before rifaximin, the mean HE score was 2.7±0.7. Data from PSG analysis indicated long total sleep time (TST): 571±288 min, and limited REM sleep: 2.5% TST (0-19). Seven-day actigraphy showed an impaired number of steps: 1690/24 h (176-6945). Questionnaires indicated that patients experienced impaired sleep quality and excessive daytime sleepiness. After rifaximin, HE scores decreased to 1.7±0.6 (P<0.001). REM sleep increased to 8.5% TST (0-25) (P=0.003). No changes were observed for TST, number of steps, and on questionnaires. CONCLUSION: Patients with recurrent HE suffer from poor sleep quality and excessive daytime sleepiness. On 24-h PSG, rifaximin improves objective sleep architecture parameters with no changes in the subjective quality of sleep and sleepiness.

Electrophysiological assessment of the effect of intrathecal baclofen in dystonic children.

OBJECTIVE: To evaluate the effect of intrathecal baclofen in a group of dystonic children using electrophysiological procedures previously validated in spastic children. METHODS: Seven children (aged 2-16 years) with dystonia of various aetiologies (dyskinetic cerebral palsy, pantothenate kinase-associated neurodegeneration and Aicardi-Goutières syndrome) underwent transcranial magnetic stimulation, H-reflex and flexor reflex studies before and after intrathecal injection of baclofen. The Barry-Albright Dystonia Scale (BADS) was used for clinical evaluation of dystonia. RESULTS: Motor-evoked potentials, present in 2 of 5 patients before baclofen, were preserved after injection. Before baclofen, H reflex was present in 6 of 7 patients (mean H(max)/M(max:) 0.45+/-0.21). It was markedly reduced after the injection (mean H(max)/M(max:) 0.09+/-0.11) (P<0.001). Area of flexor reflex significantly decreased after baclofen (P=0.047), while threshold significantly increased (P=0.01). No significant clinical improvement of the BADS scores was observed (P=0.058). CONCLUSIONS: These electrophysiological procedures, previously demonstrated to quantify the action of intrathecal baclofen in spastic adults and children, also appear sensitive in dystonic children. The electrophysiological changes are consistent with primarily spinal sites of action of baclofen. They appear more sensitive than clinical evaluation.

Cervical myelitis from herpes simplex virus type 1.

Although subacute ascending paralysis without sensory involvement is typically evocative of Guillain-Barré syndrome, it can alternatively be due to infection or inflammation of the spinal cord. We describe a 16-month-old female who presented with ascending flaccid paresis after an upper respiratory tract infection. She then developed signs of upper motor neuron involvement of the lower limbs associated with upper motor neuron involvement of the upper limbs. Motor nerve conduction and electromyographic studies of upper limbs demonstrated anterior horn cell involvement. Neuroimaging was consistent with cervical myelitis, and cerebrospinal fluid polymerase chain reaction was positive for herpesvirus-1. Although association with the primary infection of the respiratory tract may be fortuitous, possible neurotropic or hematogenous spread of herpesvirus-1 to the cervical spinal cord cannot be excluded. She then developed signs of upper motor neuron involvement of the lower limbs associatred with lower motor neuron involvement of the upper limbs [corrected].

Benign intracranial hypertension: atypical presentation of Miller Fisher syndrome?

Acute ocular paresis, nausea, vomiting, and headaches associated with high intracranial pressure without obvious intracranial pathology are typical features of benign intracranial hypertension. We describe two young children whose presentation, initially suggestive of idiopathic or benign intracranial hypertension, evolved to comprise ophthalmoplegia, ataxia, and areflexia. This triad characterizes Miller Fisher syndrome, a clinical variant of Guillain-Barré syndrome that occurs rarely among children. In both patients, this diagnosis was supported by the clinical course and neurophysiologic findings. Plasma serology was positive for Campylobacter jejuni and anti-GQ1b antibodies in one patient and for antimyelin antibodies in the other. This report of two children with Miller Fisher syndrome presenting with intracranial hypertension adds to the findings for a similar patient treated previously, which raises the question concerning the possible role or contribution of benign intracranial hypertension in Miller Fisher syndrome.

Predictive value of electrophysiology in children with hypoxic coma.

Assessment of prognosis of children in hypoxic coma is difficult. The value of clinical evaluation is often limited. The usefulness of electrophysiologic tests has been documented mostly in adults and neonates and in cases of traumatic coma. We reviewed retrospectively 39 consecutive children with nontraumatic hypoxic coma to assess the prognostic value of EEG, visual, and auditory evoked potentials. Correlation between electrophysiology and neurologic outcome after mean follow-up period of 30 months was significant (r(s) = 0.6, P < 0.001). In contrast there was no correlation between Pediatric Risk of Mortality score (PRISM) and outcome (r(s) = -0.42, P = 0.8). Combining magnetic resonance imaging with electrophysiology further enhanced their prognostic value (r(s) = 0.69, P < 0.001). Neuroimaging was highly sensitive but less specific, and electrophysiologic tests were highly specific but less sensitive. We conclude that early electrophysiology can contribute to predicting outcome in pediatric hypoxic coma.

Involvement of peripheral and central nervous systems in a valosin-containing protein mutation.

BACKGROUND: Inclusion-body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD) is a rare, late-onset autosomal disorder arising from missense mutations in a gene coding for valosin-containing protein. CASE REPORT: We report the case of a man carrying the previously described p.Arg159His mutation, who had an unusual axonal sensorimotor neuropathy as the first clinical manifestation of IBMPFD, and for whom diagnosis only became clear 8 years later when the patient developed frontotemporal dementia. CONCLUSIONS: Peripheral neuropathy is a rare manifestation of IBMPFD. This underdiagnosed disorder should be considered when a patient develops dementia or has signs of Paget's disease.