Treatment of relapsing multiple sclerosis in Hungary - consensus recommendation from the Hungarian neuroimmunology society.

Multiple sclerosis (MS) may impact quality of life, careers and family plans of the affected individuals. The current treatments with disease modifying therapies aim to prevent people with MS (pwMS) from disability accumulation and progression. Different countries have different reimbursement policies resulting in inequalities in patient care among geographical regions. Access to anti-CD20 therapies for relapsing MS is restricted in Hungary because therapy of individual cases only is reimbursed. In the light of the latest research and national guidelines, 17 Hungarian MS experts agreed on 8 recommendations regarding relapsing pwMS using the Delphi round method. Strong agreement (> 80%) was achieved in all except one recommendation after three rounds, which generated a fourth Delphi round. The experts agreed on treatment initiation, switch, follow-up and discontinuation, as well as on special issues such as pregnancy, lactation, elderly population, and vaccination. Well-defined national consensus protocols may facilitate dialogue between policymakers and healthcare professionals and thus contribute to better patient care in the long run.

Investigation of oxidative stress in patients with multifocal motor neuropathy.

Background and purpose: Multifocal motor neuropathy (MMN) is a rare, immune-mediated illness attacking ex-clusively motor nerves. It is known that oxidative stress is present in peripheral neuropathies, but it has not been investigated MMN. Methods: We measured in our prospective study the L-arginine, symmetric and asymmetric dimethylarginine (SDMA, ADMA) serum concentrations of 10 patients and 10 controls before and after intravenous immunoglobulin treatment (IVIG), as markers of the L-arginine/NO pathway involved in chronic inflammation and oxidative stress. The functions of motor nerves were tested in all patients and the serum antiganglioside antibody levels were de-tec-ted, as well. Results: MMN patients showed significantly higher ADMA (p = 0.0048; 0.98 and 0.63, respectively) and SDMA le-vels (p = 0.001; 0.88 and 0.51, respectively) than healthy controls, while L-arginine was not different. Controlling for the covariant age, ADMA (B = -0.474; p = 0.041) or SDMA (B = -0.896; p < 0.0005) serum levels proved to be the significant predictors of the presence of MMN. IVIG therapy decreased significantly ADMA concentrations (p = 0.025; 0.98 and 0.84, respectively) and showed a trend to reduce SDMA levels (p = 0.1; 0.88 and 0.74, respectively). The dimethylamine levels did not correlate with the number of affected nerves, disease duration, or the presence of ganglioside antibodies. The conduction block-related peripheral motor dysfunction improved right after the IVIG treatment. Conclusion: Dimethylamine levels are elevated in the serum and are responsive to IVIG therapy in MMN. These findings support the presence of oxidative stress in MMN.

[Paradigm shift in management of patients with vertigo and imbalance]. / Szemléletváltás a szédüléssel és egyensúlyzavarral járó kórképek ellátásában.

Dizziness is one of the most common causes of medical visits. Management of the dizzy patient may be challenging both for the general practitioner, in emergency departments, and special clinics, as behind a seemingly homogeneous clinical presentation several very different etiologies may occur. Research of the last two century enriched our knowledge about physiology and pathophysiology of the vestibular system. Much knowledge is now available about the labyrinth being able to sense head motions and gravity, processing of afferent vestibular stimuli, reflectory oculomotor and postural control, or recovery of the vestibular system. Based on scientific results new beside tests have been introduced including provocation maneuvers for detecting ectopic otoliths in different semicircular canals, head impulse test to examine function of the vestibulo-ocular reflex, and the HINTS+ battery for differentiation of peripheral or central origin of an acute vestibular syndrome. Technical innovations like videooculography and vestibular evoked myogenic potentials enable us to selectively and side-specifically examine the function of all six semicircular canals and two otolith organs. Pathomechanism of disorders with vertigo and dizziness became more clear resulting in the development or amendment of diagnostic criteria of several vestibular disorders including vestibular migraine, Menière's disease, benign paroxysmal positional vertigo, persistent postural-perceptual dizziness, bilateral vestibulopathy. Broader knowledge about the pathomechanism promoted the development of new therapeutic methods like different repositioning maneuvers in benign paroxysmal positional vertigo, pharmaceutical therapies, vestibular rehabilitation, and psychotherapy. We aimed to summarize the novelties in the field of oto-neurology.

Changes to the septo-fornical area might play a role in the pathogenesis of anxiety in multiple sclerosis.

BACKGROUND: Reports on the relationships between white matter lesion load (WMLL) and fatigue and anxiety in multiple sclerosis (MS) are inconsistent. OBJECTIVE: To investigate the association of total and tract-specific WMLL with fatigue and anxiety. METHODS: Total and regional T2 WMLL was assessed for 19 tracts in 48 MS patients (30 females). ICBM-DTI-81 Atlas-based parcellation was combined with WMLL segmentation of T2-weighted magnetic resonance imaging (MRI). Fatigue, anxiety, and depression were assessed using Fatigue Impact Scale, State Trait Anxiety Inventory, and Beck Depression Inventory, respectively. RESULTS: Fatigue, anxiety, and depression showed significant inter-correlation. We found no association between fatigue and total or regional WMLLs, whereas anxiety was associated with total and regional WMLLs in nine tracts. After adjusting for total WMLL, age, and depression, only the column and body of the fornix (CBF) remained significantly associated with anxiety. Post hoc analyses showed no CBF lesions on T1-weighted MRI and suggested, but could not confirm, that the septum pellucidum might play a role in the pathogenesis of anxiety. CONCLUSION: Our results suggest that anxiety in MS patients may have a neuropathological substrate in the septo-fornical area, which requires further validation using larger sample size and ultra-high-field MRI in targeted prospective studies.

[Emergency diagnosis of the acute vestibular syndrome]. / Az akut vestibularis szindróma sürgosségi diagnosztikájával szerzett tapasztalatok.

INTRODUCTION AND AIM: To diagnose acute vestibular syndrome (AVS) in a prospective study by a new bedside test (providing 1A evidence) based on oculomotor analysis and assessment of hearing loss. To assess the frequency of central and peripheral causes of acute vestibular syndrome in the emergency room. To establish the diagnostic accuracy of acute cranial computed tomography as compared to oculomotor analysis done by video oculography goggles and audiometry. METHOD: Between 1st March 2016 and 1st March 2017 we documented 125 patients (62 women, 63 men, average age 53 years) in the emergency room of the Petz Aladár County Teaching Hospital using the above bedside and instrumental testing. Diagnosis was verified by cranial magnetic resonance imaging. RESULTS: According to the results of the instrumental examination in AVS in 67% we found a peripheral cause and in 33% a central pathology. In 62% isolated posterior circulation stroke manifested itself by isolated vertigo without additional focal signs and the acute cranial computed tomography showed negative results in 96%. The instrumental examination increased diagnostic accuracy by making the diagnosis of isolated inferior semicircular canal vestibular neuritis possible. CONCLUSIONS: The new bedside oculomotor test is suitable for the diagnosis of posterior circulation stroke manifesting with isolated vertigo in early cases, when the routine neuroradiologic methods have a lower sensitivity or are not available. Orv Hetil. 2017; 158(51): 2029-2040.

[Magnetic resonance imaging in the course of alemtuzumab and teriflunomide therapy]. / Mágnesesrezonancia-képalkotás alemtuzumabés teriflunomidkezelés során.

Our work aimed to review the published results of magnetic resonance imaging (MRI) obtained in the course of alemtuzumab and teriflunomide therapy in multiplex sclerosis. In multiplex sclerosis MRI sensitively detects subclinical pathological processes, which do not manifest clinically in the early course of the disease, however have substantial significance from the viewpoint of the long-term disease prognosis. MRI has an increasingly important role in the early monitoring of the therapeutic efficacy. In the last 15 years several clinical trials have been conducted with alemtuzumab and teriflunomide in multiple sclerosis providing evidence about the favourable clinical effect of these drugs. MRI images were acquired in these trials as well, and the results published recently in the scientific literature. These MRI results denote the suppression of the disease activity and the neurodegenerative processes, which may imply a favourable effect on the long-term prognosis of the disease.

[MENTALIZING DEFICIT IN NEUROLOGICAL DISORDERS: A REVIEW ARTICLE]. / MENTALIZÁCIÓS DEFICIT NEUROLÓGIAI BETEGSÉGEKBEN: ÖSSZEFOGLALÓ KÖZLEMÉNY.

INTRODUCTION: Mentalization is the ability to attribute mental states (intentions, desires, thoughts, emotions) to others, and hence to predict their behaviour. This ability fundamentally determines our participation in social relationships and adaptation to society. A significant proportion of the disorders of the central nervous system (CNS) affects those brain structures and neurotransmitter systems that play a role in the mentalizing processes. Accordingly, a number of CNS disorders may be associated with mentalizing deficits, which may affect the outcome of these diseases. Here, we review recent research on mentalizing abilities in neurological diseases. METHODS: An internet database search was performed to identify publications on the subject. RESULTS: Sixty-two publications in English corresponded to the search criteria. These publications reported impaired mentalization in several neurological disorders (e.g. epilepsy, Parkinson's disease, multiple sclerosis, dementias, traumatic brain injury). DISCUSSION: The results indicate that a number of neurological disorders associate with mentalizing deficit. This deficit is often present in the early stages of the diseases and has a prognostic value, which in turn emphasizes the importance of the early detection and adequate rehabilitation.

Motor function and respiratory capacity in patients with late-onset pompe disease.

INTRODUCTION: The relationship between skeletal muscle strength and respiratory dysfunction in Pompe disease has not been examined by quantitative methods. We investigated correlations among lower extremity proximal muscle strength, respiratory function, and motor performance. METHODS: Concentric strength of the knee extensor and flexor muscles was measured with a dynamometer, and pulmonary function was evaluated using spirometry in 7 adult patients. The 6-minute walk test and the 4-step stair-climb test were used for assessing aerobic endurance and anaerobic power, respectively. RESULTS: Anaerobic motor performance correlated with strength of both thigh muscles. Respiratory function did not correlate with either muscle strength or motor function performance. CONCLUSIONS: Respiratory and lower extremity proximal muscles could be affected differentially by the disease in individual patients. Motor performance is influenced by thigh muscle strength and is less dependent of respiratory capacity in our cohort of ambulatory patients.

Disconnection mechanism and regional cortical atrophy contribute to impaired processing of facial expressions and theory of mind in multiple sclerosis: a structural MRI study.

Successful socialization requires the ability of understanding of others' mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus). Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients.

Bi-exponential diffusion signal decay in normal appearing white matter of multiple sclerosis.

PURPOSE: Our aim was to characterize bi-exponential diffusion signal changes in normal appearing white matter of multiple sclerosis (MS) patients. METHODS: Diffusion parameters were measured using mono-exponential (0-1000 s/mm(2)) and bi-exponential (0-5000 s/mm(2)) approaches from 14 relapsing-remitting subtype of MS patients and 14 age- and sex-matched controls after acquiring diffusion-weighted images on a 3T MRI system. The results were analyzed using parametric or nonparametric tests and multiple linear regression models. RESULTS: Mono-exponential apparent diffusion coefficient (ADC) slightly increased in controls (P=.09), but decreased significantly in MS as a function of age, nonetheless an elevated ADC was observed with increasing lesion number in patients. Bi-exponential analyses showed that the increased ADC is the result of decreased relative volume fraction of slow diffusing component (f(s)). However, the fast and slow diffusion components (ADC(f), ADC(s)) did not change as a function of either age in controls or lesion number and age in MS patients. CONCLUSIONS: These data demonstrated that the myelin content of the white matter affects diffusion in relapsing-remitting subtype of multiple sclerosis that is possibly a consequence of the shift between different water fractions.

Saccular function less affected than canal function in bilateral vestibulopathy.

Bilateral vestibulopathy (BV) is characterized by impaired or lost function of both labyrinths or eighth nerves. The diagnosis is routinely established by the head-thrust test, caloric irrigation and rotational testing with electronystagmography to determine the high- and low-frequency deficit of the vestibulo-ocular reflex. All three methods evaluate semicircular canal function only. Vestibular-evoked myogenic potentials (VEMPs) provide a measure of saccular otolith function. The aim of this study was to evaluate the frequency and extent of saccular dysfunction in patients with BV and to correlate saccular with horizontal semicircular canal dysfunction. A total of 84 BV-patients (23 females, mean age 62 +/- 15 (SD) years at the time of diagnosis assessment) were examined with VEMPs, electronystagmography with caloric irrigation and a standardized neuro-ophthalmological and -otological examination; 47 healthy subjects (18 females, mean 56 +/- 19 years) served as controls. Amplitudes P1-N1 were significantly lower in patients with BV compared to controls (mean P1-N1 of all ears 82.1 +/- 50.7 microV in the patients vs. 130.8 +/- 85.9 microV in healthy volunteers). VEMPs were absent unilaterally in four patients with BV and in none bilaterally. In contrast, caloric responses were absent bilaterally in 40 patients. There was no correlation between amplitude P1-N1 and caloric-induced nystagmus. The latencies P1 and N1 were not significantly different between patients and controls. Thus, in our study population saccular function appeared to be less affected than horizontal semicircular canal function.

Morphometric changes of gray matter in Parkinson's disease with depression: a voxel-based morphometry study.

The origin of the high rate of depression in idiopathic Parkinson's disease (PD) is unknown. We applied voxel-based morphometry (VBM), as a sensitive tool in detection of gray matter MR density alterations, to find differences in depressed and nondepressed PD patients. Patients with idiopathic PD were classified into depressed (DPD) and nondepressed (NDPD) groups based on the Montgomery-Asberg Depression Rating Scale (MADRS). Subsequently, a group comparisons were performed between depressed PD (n = 23), nondepressed PD (n = 27) and normal healthy controls (NC, n = 16). There was no difference in gray matter density comparing healthy controls to any PD groups. However, when NDPD and DPD cohorts were compared, density alteration of the bilateral orbitofrontal, bilateral rectal gyrus, and also the right superior temporal pole was detected in the depressed subgroup. Exploratory analyses revealed an inverse correlation of MADRS scores and severity of VBM alteration in these regions beside the right medial temporal gyrus, anterior and medial cingular gyrus, and parahippocampal gyrus. These results suggest that depression in PD is related to gray matter decrease in the bilateral orbitofrontal and right temporal regions as well as the limbic system.

[Susac syndrome: neurologic, psychiatric, ophthalmologic otorhinolaryngologic and neuroradiologic features of a rare autoimmune disease]. / Susac-szindróma: egy ritka autoimmun kórkép neurológiai, pszichiátriai, szemészeti, fül-orr-gégészeti és neuroradiológiai vonatkozásai.

UNLABELLED: Encephalopathy, recurrent occlusion of retinal arteries and hearing loss comprise the clinical picture of Susac's syndrome. The correct diagnosis is frequently missed because of incomplete clinical signs or negligence of previous symptoms. Early diagnosis and treatment can halt the progression and prevent permanent disability. METHODS: Here, we describe a Hungarian case and review the clinical characteristics, diagnostic procedures and current concepts of therapy. RESULTS: A 30-year-old female was admitted to our neurology department because of change in her personality, apathy, and difficulty in concentration. Brain MRI indicated multiple hyperintense T2-weighted lesions including cerebellum and corpus callosum. Protein content of the CSF was markedly elevated. The recurrent bilateral loss of vision and hearing along with migraine in her previous 2,5-year-long medical history suggested Susac's syndrome. Fundoscopy and fluorescein angiography indicated multiple occlusions of the retinal arteries, audiography revealed bilateral hearing loss. Systemic autoimmune and connective tissue diseases and thrombophilia were excluded. The markedly elevated protein in the cerebrospinal fluid supported Susac's syndrome. Chronic treatment with methylprednisolone resulted in remission of clinical signs. DISCUSSION: Consideration of multiple clinical signs is an important key to the diagnosis of rare clinical entities like Susac's syndrome.