Itay Lotan

Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: an open-label observational study.

ObjectiveThe use of cannabis as a therapeutic agent for various medical conditions has been well documented. However, clinical trials in patients with Parkinson disease (PD) have yielded conflicting results. The aim of the present open-label observational study was to assess the clinical effect of cannabis on motor and non–motor symptoms of PD. MethodsTwenty-two patients with PD attending the motor disorder clinic of a tertiary medical center in 2011 to 2012 were evaluated at baseline and 30 minutes after smoking cannabis using the following battery: Unified Parkinson Disease Rating Scale, visual analog scale, present pain intensity scale, Short-Form McGill Pain Questionnaire, as well as Medical Cannabis Survey National Drug and Alcohol Research Center Questionnaire. ResultsMean (SD) total score on the motor Unified Parkinson Disease Rating Scale score improved significantly from 33.1 (13.8) at baseline to 23.2 (10.5) after cannabis consumption (t = 5.9; P < 0.001). Analysis of specific motor symptoms revealed significant improvement after treatment in tremor (P < 0.001), rigidity (P = 0.004), and bradykinesia (P < 0.001). ConclusionsThere was also significant improvement of sleep and pain scores. No significant adverse effects of the drug were observed. The study suggests that cannabis might have a place in the therapeutic armamentarium of PD. Larger, controlled studies are needed to verify the results.

DJ-1 knockout augments disease severity and shortens survival in a mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive, lethal, neurodegenerative disorder, characterized by the degeneration of motor neurons. Oxidative stress plays a central role in the disease progression, in concert with an enhanced glutamate excitotoxicity and neuroinflammation. DJ-1 mutations, leading to the loss of functional protein, cause familial Parkinson’s disease and motor neuron disease in several patients. DJ-1 responds to oxidative stress and plays an important role in the cellular defense mechanisms. We aimed to investigate whether loss of functional DJ-1 alters the disease course and severity in an ALS mouse model. To this end we used mice that express the human SOD1G93A mutation, the commonly used model of ALS and knockout of DJ-1 mice to generate SOD1 DJ-1 KO mice. We found that knocking out DJ-1in the ALS model led to an accelerated disease course and shortened survival time. DJ-1 deficiency was found to increase neuronal loss in the spinal cord associated with increased gliosis in the spinal cord and reduced antioxidant response that was regulated by the Nrf2 mechanism.The importance of DJ-1 in ALS was also illustrated in a motor neuron cell line that was exposed to glutamate toxicity and oxidative stress. Addition of the DJ-1 derived peptide, ND-13, enhanced the resistance to glutamate and SIN-1 induced toxicity. Thus, our results maintain that DJ-1 plays a role in the disease process and promotes the necessity of further investigation of DJ-1 as a therapeutic target for ALS.

Retinal Nerve Fiber Layer May Be Better Preserved in MOG-IgG versus AQP4-IgG Optic Neuritis: A Cohort Study

Background Optic neuritis (ON) in patients with anti-myelin oligodendrocyte glycoprotein (MOG)-IgG antibodies has been associated with a better clinical outcome than anti-aquaporin 4 (AQP4)- IgG ON. Average retinal nerve fiber layer thickness (RNFL) correlates with visual outcome after ON. Objectives The aim of this study was to examine whether anti-MOG-IgG ON is associated with better average RNFL compared to anti-AQP4-IgG ON, and whether this corresponds with a better visual outcome. Methods A retrospective study was done in a consecutive cohort of patients following anti-AQP4-IgG and anti-MOG-IgG ON. A generalized estimating equation (GEE) models analysis was used to compare average RNFL outcomes in ON eyes of patients with MOG-IgG to AQP4-IgG-positive patients, after adjusting for the number of ON events. The final mean visual field defect and visual acuity were compared between ON eyes of MOG-IgG and AQP4-IgG-positive patients. A correlation between average RNFL and visual function was performed in all study eyes. Results Sixteen patients were analyzed; ten AQP4-IgG-positive and six MOG-IgG-positive. The six patients with MOG-IgG had ten ON events with disc edema, five of which were bilateral. In the AQP4-IgG-positive ON events, 1/10 patients had disc edema. Final average RNFL was significantly better in eyes following MOG-IgG-ON (75.33μm), compared to 63.63μm in AQP4-IgG-ON, after adjusting for the number of ON attacks (GEE, p = 0.023). Mean visual field defects were significantly smaller (GEE, p = 0.046) among MOG-IgG positive ON eyes compared to AQP-IgG positive ON eyes, but last visual acuity did not differ between the groups (GEE, p = 0.153). Among all eyes, average RNFL positively correlated with mean visual field defect (GEE, p = 0.00015) and negatively correlated with final visual acuity (GEE, p = 0.00005). Conclusions Following ON, RNFL is better preserved in eyes of patients with MOG-IgG antibodies compared to those with AQP4-IgG antibodies, correlating with better visual outcomes.

Primary brain T-cell lymphoma in an HTLV-1 serologically positive male

Primary central nervous system lymphoma (PCNSL) is a subgroup of extranodal non-Hodgkin lymphoma usually due to B-cells. The incidence of T-cell PCNSL is 1-4% in Western countries. Human T-lymphotropic virus (HTLV-1) causes tropical spastic paraparesis/myelopathy and adult T-cell leukemia/lymphoma. We describe the extremely rare occurrence of T-cell PCNSL in a 29 year old HTLV-1 carrier. Additional unusual features of the case included the patients young age and normal cerebrospinal fluid cytological findings, without leptomeningeal spread. Given the long latency between HTLV-1 infection and disease manifestation, more such cases may be diagnosed in the future. We recommend that every patient with T-cell PCNSL be screened for HTLV-1.

Atypical case of Morvan's syndrome.

Morvans syndrome is a rare neurological condition characterized by the combination of neuromyotonia, autonomic instability and encephalopathy, associated with auto-antibodies against voltage-gated potassium channels. We report a patient with an initial presentation suggestive of typical Guillain-Barré syndrome (GBS), who later developed clinical and laboratory features compatible with Morvans syndrome. Several months after resolution of the neurological symptoms, as well as disappearance of the characteristic anti-leucine-rich, glioma inactivated 1 (anti-LGI1) antibodies, the patient presented with episodes of fever of unknown origin, during which the antibodies became positive again, suggesting the possibility of a relapse. In this case, both the GBS-like symptoms at presentation and the isolated episodes of fever of unknown origin during follow-up are atypical, and may suggest the presence of an additional, yet unknown antibody.

Psychiatric side effects of acute high-dose corticosteroid therapy in neurological conditions.

It has been implied that high-dose corticosteroids (CSs) commonly cause psychiatric side effects. Here, we examined the rate and risk factors of psychiatric side effects during high-dose CS treatment in patients with neurological disorders. Patients treated with high-dose intravenous CSs for neurological disorders were evaluated for depression, mania, and psychosis using the Beck Depression Inventory, the Geriatric Depression Scale, the Young Mania Rating Scale, and the Brief Psychiatric Rating Scale before CS treatment, immediately after, and 1 month following treatment. Forty-nine consecutive patients were monitored. There was a reduction in the Beck Depression Inventory and Geriatric Depression Scale scores as well as in the Brief Psychiatric Rating Scale scores throughout the study period and a transitory increase in the Young Mania Rating Scale score immediately after CS administration. Thus, a tendency to develop transient mild euphoria during high-dose CS treatment exists, but is reversible at 1 month, whereas a reduction in depressive symptoms tended to persist. Overall, our data indicate that high-dose CS treatment for neurological diseases is relatively safe with respect to psychiatric complications.

Giant cell arteritis following varicella zoster vaccination

BACKGROUND Giant cell arteritis (GCA) is a form of large-vessel vasculitis affecting patients older than 50years old. Recent reports have suggested that the condition is caused by reactivation of varicella zoster virus (VZV). If that is indeed the case, a vaccine that prevents VZV reactivation should reduce the incidence of GCA. To further test that hypothesis, we assessed the incidence of GCA among patients older than 50years of age who were vaccinated against VZV and compared it to GCA incidence in the general population. METHODS Using a centralized electronic medical database of the major medical insurer in Israel, Clalit Health Services (CHS), we have calculated the incidence of newly-diagnosed GCA patients in the general population, as well as the incidence of GCA among patients previously vaccinated against VZV between 1.1 2014-31.10.2016. RESULTS The mean incidence of newly-diagnosed GCA among non-vaccinated patients older than 50years of age was 41.6/100,000/year, while the mean incidence of GCA among patients previously vaccinated against VZV in the same time period was 75.2/100,000/year (P=0.07). CONCLUSIONS These findings do not support the hypothesis that GCA is due to VZV reactivation.

Prior damage to lower motor neuron triggering myasthenia gravis

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Neuromyelitis Optica Spectrum Disorder: Disease Course and Long-Term Visual Outcome.

Background:Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease that classically manifests as attacks of optic neuritis (ON) and transverse myelitis (TM). The prevalence, course, and severity of NMOSD vary considerably. Few studies report the neuro-ophthalmologic disease course and visual outcome. Objective:We sought to describe the course and long-term visual outcome in a cohort of NMOSD patients treated in a single tertiary referral center. Methods:The database was searched for all patients with NMOSD who were treated in our center from 2005 to 2014. Data collected included detailed visual outcome, grade of final visual disability, neuroimaging, and results of optical coherence tomography. Details on relapses, acute episodes, and maintenance therapies were recorded. Results:Of the 12 patients with NMOSD who were followed for a mean duration of 9.06 years, 10 (83%) were women. Mean age at presentation was 33.90 ± 16.94 years. Patients with acute attacks were treated with high-dose intravenous methylprednisolone and offered immunosuppressive maintenance. ON occurred in 18 eyes of 12 patients, with a cumulative total of 37 ON episodes. At the end of the follow-up period, no patient had become legally blind and only 1 patient had lost her drivers license. Pain associated with acute ON was common (83%), whereas optic disc edema was a rare finding in our patient cohort (6%). Conclusions:In this retrospective series of 12 patients with NMOSD, followed for a mean of 9.06 years, acute-phase treatment was given within 8 days of relapse, followed by maintenance therapy. Functional visual outcome, as measured by the World Health Organization/International Classification of Diseases, Tenth Revision visual disability scale was better than reported in previous studies and drivers license was preserved in 11 of 12 patients. Pain accompanied 83% of ON attacks and may not aid differentiating multiple sclerosis from NMOSD-related ON.

Recurrent optic neuritis – Different patterns in multiple sclerosis, neuromyelitis optica spectrum disorders and MOG-antibody disease

BACKGROUND Optic neuritis is a frequent finding in multiple sclerosis (MS) and in neuromyelitis optica spectrum disorder (NMOSD), as well as in Myelin-Oligodendrocyte Glycoprotein (MOG) -positive disease. While both NMOSD and MOG-antibody disease are known to be associated with a humoral, antibody-mediated attack against a specific antigen, much less is known about the etiology and pathogenesis of MS. The aim of this study was to determine if the localization of recurrent episodes of ON follows the same pattern in MS as in NMOSD and in MOG-positive recurrent ON. METHODS We retrospectively reviewed our database to identify patients with recurrent ON. The eye affected in each episode of ON was recorded, and the findings were analyzed. RESULTS Forty-seven patients met the inclusion criteria. In the MS group, all episodes of ON recurred on the same side in 15 of the 29 patients (51.7%), accounting for 32 of the total 78 episodes (41%).In the NMSOD group, all episodes of ON recurred on the same side in 2 of the 12 patients (16.6%), accounting for 6 of the total 49 episodes (12.5%).In the MOG-positive group, all episodes of ON recurred on the same side in 1 out of 6 patients (16.6%), accounting for 2 of 21 episodes (9.5%).The between-group difference in the rate of recurrences affecting the ipsilateral side was statistically significant (p = .0007 and p = .0085 for the MS-NMOSD and MS-MOG groups, respectively). CONCLUSIONS The pattern of recurrent ON differs significantly between MS and NMOSD and MOG-positive recurrent ON. This finding suggests that in MS recurrences may be provoked by previous tissue damage, disruption of the blood-brain barrier, and other local factors while in NMOSD and MOG-antibody disease attacks are indeed due to localization of the auto antigen.