Fulminant Central Plus Peripheral Nervous System Demyelination without Antibodies to Neurofascin.

BACKGROUND: Combined central and peripheral nervous system demyelination is a rare and poorly described phenomenon. Recently, anti-neurofascin antibodies were reported to be positive in 86% of these patients in a Japanese cohort. Yet, there seems to be a clinical, radiological, and serological heterogeneity among these patients. In this report, our aim is to describe characteristics of our patients with this entity and compare with others in the literature. METHODS: We report clinical, electrophysiological, radiological, and laboratory characteristics of five patients with both multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy from our institutional database containing 1890 MS patients. RESULTS: Three patients presented with extensive, active demyelination of both central nervous system and peripheral nervous system with hypertrophic peripheral nerves. Plexuses, trunks, division and cords were involved in the process. Oligoclonal band was negative. Conduction block was not detected. Corticosteroid treatment was not adequate. Others had a slowly progressive clinical course. Serum anti-neurofascin antibody was negative. Review of the literature revealed similar cases with active disease, early-onset hypertrophic peripheral nerves, and central demyelination, in addition to other cases with an insidious course. CONCLUSIONS: Patients with combined central and peripheral demyelination form a spectrum. Some patients may have an antibody-mediated syndrome with or without anti-neurofascin antibodies and others seem to represent a coincidence.

Assessment of the effect of cigarette smoking on regional brain volumes and lesion load in patients with clinically isolated syndrome.

PURPOSE: Smoking has been associated with an increased risk of developing multiple sclerosis, disease progression and clinical disability. We detected the effects of smoking on regional brain volumes and lesion load in patients with clinically isolated syndrome using quantitative magnetic resonance imaging. MATERIALS AND METHODS: Smoker patients (n = 16), smoker healthy controls (n = 13), non-smoker patients (n = 17) and non-smoker healthy controls (n = 14) underwent magnetic resonance imaging and neocortical volumes were measured. Lesion load was calculated in terms of number and volume of white matter hyperintensities. RESULTS: Smoking was associated with increased gray matter volumes in several regions of the brain. A tendency towards greater lesion load in smoker patients was found. Smoking duration was significantly negatively correlated with intracranial volume and left hemisphere cortical gray matter volume. There was no relationship between regional brain volumes and clinical disability scores, lesion load duration of the disease and degree of smoking exposure. CONCLUSIONS: Clinically isolated syndrome related regional brain atrophy might vary in extent and severity with smoking. Despite increased lesion load, less cortical and deep gray matter damage with a possible neuroprotective effect occurs in smoking.

White matter involvement beyond the optic nerves in CRION as assessed by diffusion tensor imaging.

BACKGROUND: Chronic relapsing inflammatory optic neuropathy (CRION) is an inflammatory optic neuropathy, characterized by relapses and remissions in patients with normal brain and spinal magnetic resonance imaging (MRI). Discrepancy from other demyelinating diseases is important, and it is still uncertain whether CRION is restricted to the optic pathways or it affects other brain white matter (WM) structures. OBJECTIVE: To assess WM structure in patients with CRION by using diffusion tensor imaging (DTI). METHODS: DTI was performed in six CRION patients and six age- and sex-matched healthy controls on a 3 T scanner. Tract-based spatial statistics (TBSS) was used for voxelwise statistical analysis of DTI data. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) measures were obtained. RESULTS: TBSS analysis revealed two different patterns of WM alterations in patients with CRION. The optic chiasm and connected structures had significantly higher FA and lower RD, AD and MD in the patients than in the healthy controls. On the other hand, anterior frontal bundles of inferior fronto-occipital tracts, left uncinate fascicule and internal capsule showed decreased FA and increased RD. No correlation was found between the clinical variables and diffusion measures. CONCLUSION: WM appearing normal on brain MRI shows widespread abnormalities in a cohort of CRION patients as assessed by DTI.

Progressive neurodegenerative syndrome in a patient with X-linked agammaglobulinemia receiving intravenous immunoglobulin therapy.

A progressive encephalopathy of unknown etiology has been described in patients with primary immunodeficiency disorders. In this report, we characterize the clinical features of this progressive neurodegenerative dementing disorder in a young man with Bruton agammaglobulinemia, through neuropsychological tests and a video sequence. The clinical course of the encephalopathy seems rather uniform: Cognition, especially frontal lobe function, is affected in the early stages, and some patients develop movement disorders. The syndrome causes severe cognitive and physical disability, and can eventually be fatal. The autoimmunity results from dysregulated immune responses, but the underlying mechanism has not yet been fully explained.

Progressive Onset Multiple Sclerosis: Demographic, Clinical and Laboratory Characteristics of Patients With and Without Relapses in the Course.

AMAÇ: Primer progresif multipl skleroz (PPMS) ve progresif relapsing multipl skleroz (PRMS) baslangiçtan beri olan progresyon ile karakterize MS tipleridir. Nadir görülmelerinden dolayi, literatürde diger MS formlarina göre daha az bilgi bulunmaktadir. Bu çalismanin amaci progresif baslangiçli MS (PBMS) hastalarinda klinik ve laboratuvar özelliklerini ortaya koymaktir. YÖNTEM: PBMS hastalari 2010-2014 yillari arasinda degerlendirilip demografik, klinik özellikleri ve beyin omurilik sivisi (BOS) bulgulari belirlendi. BULGULAR: Otuz iki PBMS hastasi ile ilgili veriler degerlendirildi. Hastalik seyri 24 hastada relaps olmadan (PPMS), sekiz hastada ise relapsli progresifti (PRMS). Kadin/erkek orani tüm grupta 1'di. Ortalama baslangiç yasi tüm grup için 40 (23-55) yasti. Gruplar arasinda hastalik baslangiç yasi ortancasi anlamli farkli bulunmadi (p=0,053). En sik prezantasyon belirtisi motor bozukluklardi. Relapslar tüm hastalarda hastaligin ilk 10 yilinda görüldü. BOS analizinde oligoklonal bant pozitifligi ve artmis IgG indeksi açisindan gruplar arasinda fark saptanmadi (p=0,938, p=0,058). Hastalik süresi her iki grupta da benzer oldugu halde, PPMS grubunda degerlendirme sirasinda ortanca EDSS skoru daha yüksek bulundu (p=0,020). SONUÇ: Çalismamiz Türk PBMS hastalarinin klinik seyir ve laboratuvar bulgularina odaklanmis ilk çalismadir. Iki grubun klinik ve laboratuvar bulgularinin karsilastirilmasi benzer sonuçlar göstermistir. Gruplar arasinda hastalik baslangiç yasi ve artmis IgG indeksi açisindan farklilik olup olmadigini netlestirmek için gelecekte daha genis örneklemli çalismalar yapilmasi gerekmektedir.

Acute Disseminated Encephalomyelitis after Oral Therapy with Herbal Extracts: A Case Report.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disease of the central nervous system, commonly attributed to infections or vaccinations. Toxic or allergenic compounds can also trigger a response in the immune system and may cause demyelination. We present a case with ADEM after using oral herbal medications. CASE REPORT: A 25 year-old male developed bilateral central facial palsy and severe quadriparesis after taking herbal drugs (containing echinacea and many other herbal ingredients) for two weeks. He had used the extract to increase his potency and reproductivity. He had no past history of recent immunization or viral infection. The clinical findings, cerebrospinal fluid (CSF) analysis and brain magnetic resonance imaging (MRI) were compatible with ADEM. The neurological findings were improved after seven doses of pulse methylprednisolone treatment. To our knowledge, this is the third report in the literature that links herbal therapy and demyelinating disease. CONCLUSION: Most of the ADEM cases related to herbal therapy in the literature similarly used echinacea. It is our opinion that other ingredients of the herbal extract used by our case, besides echinacea, could have the potential to cause a trigger in the immune system. Further studies are needed to clarify the immunological effects of different kinds of herbal compounds, as well as the effects of different parts of the plants and the results of various dosages. Moreover, ingredients should also be tested for toxicity, adverse effects and drug interactions.

Unfavorable outcome of pediatric onset multiple sclerosis: Follow-up in the pediatric and adult neurology departments of one referral center, in Turkey.

BACKGROUND: The prevalence of MS starting under 18 years of age ranges between 2-10% of the total MS population. OBJECTIVE: We aimed to examine the clinical and long term follow-up data of pediatric-onset cases in our institutional MS database. METHOD: We evaluated the clinical data from the MS database of the Departments of Neurology and Pediatric Neurology of Hacettepe University Hospital. RESULTS: The clinical features of 74 patients who had experienced the first attack before age 18 years comprised 3.9% of our MS population. Median age at onset was 15 (3, 5-17, IQR=3.63) years, and female: male ratio was 2.4. The most frequent symptom at onset was brainstem/cerebellar dysfunction (32.4%). Seventy two patients (97.3%) initially had relapsing remitting course and in the follow-up, 17 (23%) of them developed secondary progressive (SP) course. The median interval to develop SPMS course was 10 (5-21, IQR=8) years. At the last visit, median disease duration was 6.67 (0.83-25, IQR=9.06) years, 41 (55.4%) of them had EDSS of ≥4. CONCLUSION: These findings illustrate the profile of our pediatric MS patients: almost all are relapsing-remitting initially; about one fourth become secondarily progressive in 10 years, and about half acquire disability EDSS ≥4 in mean 8 years.

Promotion of experimental autoimmune encephalomyelitis upon neutrophil granulocytes' stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) peptide.

It has been acknowledged that neutrophil granulocytes, the common mediators of immune responses against extracellular bacteria, can also intercede autoimmune reactions such as experimental autoimmune encephalomyelitis (EAE). Formyl-methionyl-leucyl-phenylalanine (fMLP) is a microbial peptide that can be well-tolerated when intravenously administered and can directly lead to activation and accumulation of neutrophils into the blood circulation. Here, this antigenic peptide was injected to the mice at the induction of EAE, and the immunological and pathological outcomes were assessed. As a peripheral immune organ, spleen of the animals that received fMLP contained considerably high percentages of Gr-1(hi)Ly7/4(hi) mature neutrophils. In the sera samples, only a slight difference was determined in Th1/Th2/Th17-related cytokine levels. Expression of CXCR1 or CXCR2 chemokine receptors was not significantly modulated in EAE with or without fMLP which might indicate a direct role for this antigenic peptide on neutrophil accumulation. Even though fMLP administration did not propone the clinical (symptomatic) onset of the disease, the animals showed severe body conditions with higher EAE scores. Accordingly, the expression of TNF-α and CXCL1 inflammatory mediators in the brain was increased in fMLP-EAE group. In conclusion, with its potent capacity to mobilize neutrophils and to stimulate innate immune cells, fMLP peptide can be used to aggravate immune reactions in EAE. This observation may indicate that the strength of innate immune responses particularly at the induction phase of EAE might influence the clinical course of the disease.

Voltage gated calcium channel antibody-related neurological diseases.

Voltage gated calcium channel (VGCC) antibodies are generally associated with Lambert-Eaton myasthenic syndrome. However the presence of this antibody has been associated with paraneoplastic as well as non-paraneoplastic cerebellar degeneration. Most patients with VGCC-antibody-positivity have small cell lung cancer (SCLC). Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the presynaptic part of the neuromuscular junction. Its classical clinical triad is proximal muscle weakness, areflexia and autonomic dysfunction. Fifty to sixty percent of LEMS patients have a neoplasia, usually SCLC. The co-occurrence of SCLC and LEMS causes more severe and progressive disease and shorter survival than non-paraneoplastic LEMS. Treatment includes 3,4 diaminopyridine for symptomatic purposes and immunotherapy with prednisolone, azathioprine or intravenous immunoglobulin in patients unresponsive to 3,4 diaminopyridine. Paraneoplastic cerebellar degeneration (PCD) is a syndrome characterized with severe, subacute pancerebellar dysfunction. Serum is positive for VGCC antibody in 41%-44% of patients, usually with the co-occurrence of SCLC. Clinical and electrophysiological features of LEMS are also present in 20%-40% of these patients. Unfortunately, PCD symptoms do not improve with immunotherapy. The role of VGCC antibody in the immunopathogenesis of LEMS is well known whereas its role in PCD is still unclear. All patients presenting with LEMS or PCD must be investigated for SCLC.

Comparing routine neurorehabilitation program with trunk exercises based on Bobath concept in multiple sclerosis: pilot study.

This study compared trunk exercises based on the Bobath concept with routine neurorehabilitation approaches in multiple sclerosis (MS). Bobath and routine neurorehabilitation exercises groups were evaluated. MS cases were divided into two groups. Both groups joined a 3 d/wk rehabilitation program for 8 wk. The experimental group performed trunk exercises based on the Bobath concept, and the control group performed routine neurorehabilitation exercises. Additionally, both groups performed balance and coordination exercises. All patients were evaluated with the Trunk Impairment Scale (TIS), Berg Balance Scale (BBS), International Cooperative Ataxia Rating Scale (ICARS), and Multiple Sclerosis Functional Composite (MSFC) before and after the physiotherapy program. In group analysis, TIS, BBS, ICARS, and MSFC scores and strength of abdominal muscles were significantly different after treatment in both groups (p < 0.05). When the groups were compared, no significant differences were found in any parameters (p > 0.05). Although trunk exercises based on the Bobath concept are rarely applied in MS rehabilitation, the results of this study show that they are as effective as routine neurorehabilitation exercises. Therefore, trunk exercises based on the Bobath concept can be beneficial in MS rehabilitation programs.

Evaluation of Th17-related cytokines and receptors in multiple sclerosis patients under interferon ß-1 therapy.

Th17-related cytokines (IL-17, IL-23, and IL-26) and receptors (IL-17R and IL-23R) were evaluated in MS patients under immunomodulatory IFN-ß1 therapy during a 2year follow-up. Before the initiation of treatment, no significant difference was found in cytokine or receptor expression between controls and MS patients. Of the three cytokines evaluated, IL-26 was the highest in the patients' sera. The amount of IL-17 and CD13(+)IL-17R(+) cells was steadily decreased whereas IL-23 and IL-26 levels were gradually increased with IFN-ß1 therapy. The patients in progressive phase had very high levels of IL-17. Th17-associated parameters should be considered in the immunomodulatory IFN-ß1 therapy of MS.

Mass lesions in the brain: tumor or multiple sclerosis? Clinical and imaging characteristics and course from a single reference center.

AIM: In demyelinating disease spectrum, tumor-like (tumefactive) demyelinating lesions (TDL) are rarely seen. Atypical imaging and clinical features of these lesions may cause misdiagnosis of tumor or abscess. MATERIAL AND METHODS: 25 patients with TDL in our center were followed and clinical, magnetic resonance imaging (MRI), magnetic resonance spectroscopy, cerebrospinal fluid (CSF) findings and disease course were retrospectively evaluated. RESULTS: Mean age at symptom onset was 29 years. Motor and sensory deficits were most common symptoms and 18 of them were polysymptomatic. Mostly frontal and parietal regions were affected. 10/25 patients were initially misdiagnosed clinically as brain abscess, primary central nervous system tumor metastasis. T2-hypointense rim, incomplete ring enhancement of the lesions on post-gadolinium T1- weighted imaging on brain MRI enabled accurate diagnosis of TDLs. 13 of 21 patients with first-TDL presentation sustained a monophasic course, remaining 8 patients converted to multiple sclerosis (MS) at a mean 38.4 months follow-up. Clinical isolated syndrome (CIS) patients were older than patients who developed MS and Expanded Disability Status Scale was lower (0.96 vs 3.7). CONCLUSION: Although MRI, CSF and pathologic examination help in differential diagnosis of the mass lesions, close follow-up is still crucial for the definite diagnosis. A higher MS conversion rate was found in patients with a younger TDL onset age.