Horner syndrome in ipsilateral lenticulostriate stroke: a novel localization for a classic stroke syndrome.

Horner's syndrome has important localizing and etiological value in acute ischemic stroke. In a prospective series of consecutive acute ischemic stroke patients, we identified three patients with Horner's syndrome and contralateral hemiparesis due to ipsilateral small deep infarction in the middle cerebral artery territory (lenticulostriate arteries). Lacunar stroke was the most likely stroke mechanism in all three patients. This observation might suggest the existence of an uncrossed cortico-hypothalamic sympathetic pathway passing through the basal ganglia and modulating oculosympathetic function.

[Neurology]. / Neurologie.

Aducanumab reduces the burden of amyloid plaques in Alzheimer's disease, with significant improvement of clinical scores. Endovascular thrombectomy is recommended in patients with acute stroke with proximal occlusion of the anterior circulation. CGRP antagonists and botulinum toxin are effective in migraine. ZIKA virus infection has been linked to the Guillain-Barré syndrome. Edaravone has been approved for amyotrophic lateral sclerosis. Two monoclonal antibodies (ocrelizumab and daclizumab) and siponimod show positive results in multiple sclerosis. Thalamotomy of ventral intermediate nucleus (by gamma-knife or by magnetic resonance-guided focused ultrasound) is effective in drug-resistant essential tremor. The dose-dependent risk of foetal malformations associated with valproate and topiramate is confirmed.

L'aducanumab réduit la présence de plaques amyloïdes dans la maladie d'Alzheimer, avec amélioration significative des scores cliniques. Dans l'AVC aigu, la thrombectomie endovasculaire est recommandée en présence d'une occlusion proximale de la circulation antérieure. La toxine botulinique est efficace dans la migraine chronique. L'infection à virus Zika est associée au syndrome de Guillain-Barré. L'édaravone a été approuvé pour la sclérose latérale amyotrophique. Deux anticorps monoclonaux (ocrélizumab et daclizumab) et le siponimod montrent des résultats positifs dans la sclérose en plaques. La thalamotomie du noyau ventral intermédiaire par gamma-knife et par ultrasons focalisés guidés par résonance magnétique est efficace dans le tremblement pharmaco-résistant. Le risque dose-dépendant de malformations fœtales liées au valproate et au topiramate est confirmé.

[Neurology]. / Neurologie.

In 2015, cerebral stimulation becomes increasingly established in the treatment of pharmacoresistant epilepsy. Efficacy of endovascular treatment has been demonstrated for acute ischemic stroke. Deep brain stimulation at low frequency improves dysphagia and freezing of gait in Parkinson patients. Bimagrumab seems to increase muscular volume and force in patients with inclusion body myositis. In cluster-type headache, a transcutaneous vagal nerve stimulator is efficient in stopping acute attacks and also reducing their frequency. Initial steps have been undertaken towards modulating memory by stimulation of the proximal fornix. Teriflunomide is the first oral immunomodulatory drug for which efficacy has been shown in preventing conversion from clinical isolated syndrome to multiple sclerosis.

Interobserver agreement and validity of bedside 'positive signs' for functional weakness, sensory and gait disorders in conversion disorder: a pilot study.

BACKGROUND: Conversion disorder (CD) is no longer a diagnosis of exclusion. The new DSM-V criteria highlight the importance of 'positive signs' on neurological examination. Only few signs have been validated, and little is known about their reliability. OBJECTIVE: The aim was to examine the clinical value of bedside positive signs in the diagnosis of CD presenting with weakness, gait or sensory symptoms by assessing their specificity, sensitivity and their inter-rater reliability. PATIENTS AND METHODS: Standardised video recorded neurological examinations were performed in 20 consecutive patients with CD and 20 'organic' controls. Ten previously validated sensory and motor signs were grouped in a scale. Thirteen additional motor/sensory 'positive signs', 14 gait patterns and 1 general sign were assessed in a pilot validation study. In addition, two blinded independent neurologists rated the video recordings to assess the inter-rater reliability (Cohen's κ) of each sign. RESULTS: A score of ≥ 4/14 on the sensory motor scale showed a 100% specificity (CI 85 to 100) and a 95% sensitivity (CI 85 to 100). Among the additional tested signs, 10 were significantly more frequent in CD than controls. The interobserver agreement was acceptable for 23/38 signs (2 excellent, 10 good, 11 moderate). CONCLUSIONS: Our study confirms that six bedside 'positive signs' are highly specific for CD with good-excellent inter-rater reliability; we propose to consider them as 'highly reliable signs'. In addition 13 signs could be considered as 'reliable signs' and six further signs as 'suggestive signs' while all others should be used with caution until further validation is available.

Bilateral deep brain stimulation: the placement of the second electrode is not necessarily less accurate than that of the first one.

BACKGROUND: Deep brain stimulation (DBS) is recognized as an effective treatment for movement disorders. We recently changed our technique, limiting the number of brain penetrations to three per side. OBJECTIVES: The first aim was to evaluate the electrode precision on both sides of surgery since we implemented this surgical technique. The second aim was to analyse whether or not the electrode placement was improved with microrecording and macrostimulation. METHODS: We retrospectively reviewed operation protocols and MRIs of 30 patients who underwent bilateral DBS. For microrecording and macrostimulation, we used three parallel channels of the 'Ben Gun' centred on the MRI-planned target. Pre- and post-operative MRIs were merged. The distance between the planned target and the centre of the implanted electrode artefact was measured. RESULTS: There was no significant difference in targeting precision on both sides of surgery. There was more intra-operative adjustment of the second electrode positioning based on microrecording and macrostimulation, which allowed to significantly approach the MRI-planned target on the medial-lateral axis. CONCLUSION: There was more electrode adjustment needed on the second side, possibly in relation with brain shift. We thus suggest performing a single central track with electrophysiological and clinical assessment, with multidirectional exploration on demand for suboptimal clinical responses.

[Deep brain stimulation: past, present time and future]. / Stimulation cérébrale profonde: passé, présent et avenir.

Recently awarded by the prestigious Lasker Foundation, high-frequency deep brain stimulation (DBS) has been used for the first time in 1987 in tremor and in 1993 in Parkinson's disease (PD) by the Grenoble group. So far, over 100 000 patients have been operated on worldwide. In PD, DBS induces an almost complete abatement of tremor, motor fluctuations and dyskinesias along with a reduction in levodopa dose. Although its mechanism of action is not fully understood, DBS would inhibit or modulate the expression of abnormal neuronal networks associated with given symptoms. It is therefore expected that DBS will extend to other severe neurological and psychiatric disorders. Furthermore, technological advances of the procedure are ongoing to optimize final outcomes.

[Deep brain stimulation for movement disorders: indications, results and complications]. / Stimulation cérébrale profonde lors de maladie de Parkinson et autres troubles du mouvement: indications, résultats et complications.

Movement disorders such as Parkinson's disease (PD), essential tremor (ET) and dystonia can benefit from deep brain stimulation (DBS). DBS is considered when symptoms are disabling despite optimal medical therapy. Contraindications include dementia, uncontrolled psychiatric disease and/or comorbid conditions with potential for evolution. Targets are the subthalamic nucleus for PD, the ventral intermediate nucleus for ET and the globus pallidus internus for dystonia. The beneficial effet of DBS has been well documented for symptom control. Optimal target localization of the electrodes reduces the occurrence of side-effects. Stimulation-induced adverse effects can usually be abolished by turning the stimulation off, changing the active contact or other stimulation parameters.

[News in neurology 2014]. / Neurologie.

In 2014, breastfeeding during maternal antiepileptic therapy seems to be safe for the children and can be recommended. Intravenous thrombolysis by Alteplase improves the outcome after a stroke if administered within 4.5 hours and it is also recommended in elderly population over 80 years. ProSavin genic therapy for Parkinson disease is under investigation. The Transcranial Magnetic Stimulation (TMS) has an analgesic effect in neuropathic pain as well as an antidepressant effect. Antagonists of calcitonin gene-related peptide can have a beneficial role in migraine prevention. Diagnostic biomarker panels for Alzheimer disease are under investigation. Oral teriflunomide and dimethyl fumarate (BG-12) for relapsing multiple sclerosis treatment are now available in Switzerland.

VPS35 mutations in Parkinson disease.

The identification of genetic causes for Mendelian disorders has been based on the collection of multi-incident families, linkage analysis, and sequencing of genes in candidate intervals. This study describes the application of next-generation sequencing technologies to a Swiss kindred presenting with autosomal-dominant, late-onset Parkinson disease (PD). The family has tremor-predominant dopa-responsive parkinsonism with a mean onset of 50.6 ± 7.3 years. Exome analysis suggests that an aspartic-acid-to-asparagine mutation within vacuolar protein sorting 35 (VPS35 c.1858G>A; p.Asp620Asn) is the genetic determinant of disease. VPS35 is a central component of the retromer cargo-recognition complex, is critical for endosome-trans-golgi trafficking and membrane-protein recycling, and is evolutionarily highly conserved. VPS35 c.1858G>A was found in all affected members of the Swiss kindred and in three more families and one patient with sporadic PD, but it was not observed in 3,309 controls. Further sequencing of familial affected probands revealed only one other missense variant, VPS35 c.946C>T; (p.Pro316Ser), in a pedigree with one unaffected and two affected carriers, and thus the pathogenicity of this mutation remains uncertain. Retromer-mediated sorting and transport is best characterized for acid hydrolase receptors. However, the complex has many types of cargo and is involved in a diverse array of biologic pathways from developmental Wnt signaling to lysosome biogenesis. Our study implicates disruption of VPS35 and retromer-mediated trans-membrane protein sorting, rescue, and recycling in the neurodegenerative process leading to PD.

[News in neurology 2013]. / Neurologie.

In 2013, perampanel is approved as an add-on treatment for generalised and focal seizures in pharmaco-resistant epilepsy. New anticoagulants are superior to antivitamin K in stroke secondary prevention in case of atrial fibrillation. DBS remains a valid therapeutic option for advanced Parkinson's disease. Intranasal ketamine seems to reduce the intensity of severe migraine aura. High concentrations of topic capsaicin improve post-herpetic neuralgia. In Alzheimer's disease, statins might deteriorate cognitive functions. Oral immuno-modifing treatments for relapsing remitting multiple sclerosis have shown to slow cerebral atrophy progression at two years.

[Resistance to treatment in movement disorders]. / Résistances thérapeutiques dans les mouvements anormaux.

Therapeutic strategies for essential tremor (ET) and Parkinson's disease (PD) can be divided into two successive steps, one based on oral medications and the other, more invasive, using pumps or functional neurosurgery. When ET becomes refractory to propranolol, primidone and other, second-choice compounds, deep brain stimulation of the VIM nucleus of the thalamus can be considered. When PD becomes resistant to dopamine replacement therapy using various combinations of dopaminergic agents, then three options can be discussed: first, a subcutaneous apomorphine mini-pump, second, a jejunal levodopa-delivery system by means of percutaneous gastrostomy, and third, bilateral deep brain stimulation of the subthalamic nucleus. The above interventions are successful in about 80% of cases.

[What's new in neurology]. / Neurologie.

This article summarize principal news about treatments in the different specialities in neurology. We don't pretend to be exhaustive and to make a detailed analyse of all treatments, and preferred to present pertinent therapeutic advances, with an evidence-based point of view. We also mentioned some negative studies, to balance our purpose.

Strong EBV-specific CD8+ T-cell response in patients with early multiple sclerosis.

Epstein-Barr virus (EBV) has been associated with multiple sclerosis (MS), however, most studies examining the relationship between the virus and the disease have been based on serologies, and if EBV is linked to MS, CD8+ T cells are likely to be involved as they are important both in MS pathogenesis and in controlling viruses. We hypothesized that valuable information on the link between MS and EBV would be ascertained from the study of frequency and activation levels of EBV-specific CD8+ T cells in different categories of MS patients and control subjects. We investigated EBV-specific cellular immune responses using proliferation and enzyme linked immunospot assays, and humoral immune responses by analysis of anti-EBV antibodies, in a cohort of 164 subjects, including 108 patients with different stages of MS, 35 with other neurological diseases and 21 healthy control subjects. Additionally, the cohort were all tested against cytomegalovirus (CMV), another neurotropic herpes virus not convincingly associated with MS, nor thought to be deleterious to the disease. We corrected all data for age using linear regression analysis over the total cohorts of EBV- and CMV-infected subjects. In the whole cohort, the rate of EBV and CMV infections were 99% and 51%, respectively. The frequency of IFN-gamma secreting EBV-specific CD8+ T cells in patients with clinically isolated syndrome (CIS) was significantly higher than that found in patients with relapsing-remitting MS (RR-MS), secondary-progressive MS, primary-progressive MS, patients with other neurological diseases and healthy controls. The shorter the interval between MS onset and our assays, the more intense was the EBV-specific CD8+ T-cell response. Confirming the above results, we found that EBV-specific CD8+ T-cell responses decreased in 12/13 patients with CIS followed prospectively for 1.0 +/- 0.2 years. In contrast, there was no difference between categories for EBV-specific CD4+ T cell, or for CMV-specific CD4+ and CD8+ T-cell responses. Anti-EBV-encoded nuclear antigen-1 (EBNA-1)-specific antibodies correlated with EBV-specific CD8+ T cells in patients with CIS and RR-MS. However, whereas EBV-specific CD8+ T cells were increased the most in early MS, EBNA-1-specific antibodies were increased in early as well as in progressive forms of MS. Our data show high levels of CD8+ T-cell activation against EBV--but not CMV--early in the course of MS, which support the hypothesis that EBV might be associated with the onset of this disease.

Rapid resolution of dopamine dysregulation syndrome (DDS) after subthalamic DBS for Parkinson disease (PD): a case report.

OBJECTIVE: To describe how subthalamic deep brain stimulation (STN-DBS) and reduction in dopamine replacement therapy (DRT) allowed rapid resolution of dopamine dysregulation syndrome (DDS) with severe behavioral disorder in a patient with late stage Parkinson disease (PD). BACKGROUND: DDS was recently defined as compulsive use of dopaminergic drugs, associated with severe behavioral symptoms, and impaired social functioning, occurring in about 4% of PD patients under DRT. STN-DBS is an effective treatment for late stage PD with treatment resistant motor fluctuations, which frequently allows also to reduce DRT. METHODS: A late stage PD patient referred to our center for STN-DBS, suffering from severe DDS necessitating in-ward psychiatric management, was comprehensively assessed preoperatively and postoperatively for motor, cognitive, and psychiatric status. RESULTS: Following subthalamic DBS procedure and medication reduction, we observed a rapid and dramatic resolution of DDS and associated psychiatric symptoms, allowing discharge from a 2-year stay in a psychiatric institution. CONCLUSIONS: DDS occurring in late stage PD patients may be dramatically improved by STN-DBS, possibly in relation with the reduction of dopaminergic medication. In contrast to other psychiatric symptoms, DDS should not be considered as an obstacle to DBS procedure in late stage PD patients.

[Dissociative disorders: neurologists and psychiatrists working together]. / Trouble dissociatif: une clinique à l'interface de la neurologie et de la psychiatrie.

Dissociative disorders often have an atypical neurological presentation requiring a complex diagnostic process at the interface between neurology and psychiatry. A strong interdisciplinary collaboration is needed for diagnosis restitution and patient treatment. Current knowledge is still scarce but recent studies in clinical neuroscience enrich this field. This article presents the main aspects of dissociative disorders and suggests a treatment framework.

Prevalence of functional (psychogenic) parkinsonism in two Swiss movement disorders clinics and review of the literature.

BACKGROUND: Functional parkinsonism (FP) is considered rare but no studies have looked at its frequency. Case series have described high rates of comorbidity with Parkinson's disease (PD), suggesting a possible association between these conditions. OBJECTIVES: To study the prevalence, epidemiology and clinical features of FP and its association with PD. METHODS: We conducted a cross-sectional population-based prevalence study as well as a chart review of cases who received a diagnosis of FP over a 10-year-period in two movement disorder clinics in Switzerland. Epidemiological data regarding FP features were collected. The co-occurrence of PD, psychiatric disorders and other functional disorders were recorded. Clinical differences between FP and FP+PD groups are presented and discussed in light of a literature review. RESULTS: The crude prevalence of FP was 0.64 per 100,000 in our population. FP represented 0.24% of patients with parkinsonism. Among 12 FP cases, female gender predominance (87%), mean age of onset of 45.5(±13.3 Standard deviation SD) years and prolonged diagnostic delay (mean 59±75 SD months) was found. Six patients had an additional diagnosis of PD, 83% of depression and 66% of other functional neurological disorder. In four patients with FP+PD, FP preceded PD by 6 to 56months. CONCLUSIONS: These results suggest that FP should be considered in the differential diagnosis of patients presenting with parkinsonism. The high rate of co-occurrence with PD emphasizes the importance of long-term follow up of these patients. The observation that FP often precedes PD should be verified in prospective studies.