Clinical Neuroscience

[Experience with natalizumab-treatment at Semmelweis University]

GOMBOS Barbara, ILJICSOV Anna, BARSI Péter, HEGEDÛS Katalin, SIMÓ Magdolna

MAY 30, 2017

Clinical Neuroscience - 2017;70(05-06)

DOI: https://doi.org/10.18071/isz.70.0185

[Multiple sclerosis is an autoimmune demyelinating disorder of the central nervous system. During the last two decades, numerous disease modifying drugs have been introduced for the treatment of the relapsing-remitting form of the disease. Since 2010, natalizumab (NTZ) treatment has been used as a second-line therapy for patients with breakthrough disease. In comparison to conventional immunomodulant drugs, NTZ has a more specific effect in that it prevents the entry of immune cells into the central nervous system without interfering with systemic immune response. The efficacy and the safety of NTZ have been confirmed by several studies. The most severe side-effect of NTZ is progressive multifocal leukoencephalopathy, which has been associated with an increased incidence in patients with anti-JCV antibody positivity, and in those who have been undergoing NTZ treatment for over two years and who have received prior immunosuppressive therapy. In the present study, our experience with natalizumab treatment of 37 patients at the Department of Neurology of Semmelweis University during the last 6 years is presented. We have observed a significant decrease of disease activity in our patients; in many cases the disease has become inactive both clinically (36/37) and radiologically (34/37). The patients’ quality of life has improved significantly during the treatment. In accordance with the literature, we confirm that NTZ is a highly effective treatment in a carefully selected patient group, and can be administered without significant inconvenience to the patient. ]

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Clinical Neuroscience

[Prevention of invasive meningococcal infection, recognition and first treatment of the disease in primary care]

KOVÁCS Ákos, KULCSÁR Andrea, KALABAY László, TORZSA Péter

[Neisseria meningitidis, the meningococcus, is a Gram-negative diplococcal bacterium that is only found naturally in humans. The meningococcus is part of the normal microbiota of the human nasopharynx and is commonly carried in healthy individuals. In some cases systemic invasion occurs, which can lead to meningitis and/or septicemia. Invasive disease caused by Neisseria meningitidis is potentially devastating, with a high case fatality rate and high rates of significant sequelae among survivors after septicaemia or meningitis. Between 2006-2015 every year between 34 and 70 were the numbers of the registered invasive disease because of Neisseria meningitis, the morbidity rate was 0.2-0.7⁰⁄₀₀₀₀. Half of the diseases (50.7%) were caused by B serotype N. meningitidis, 23.2% were C serotype. In this article the authors summarise what you must do and must not do as primary care physician when suddenly meeting a young patients suspected of having meningococcus infection. ]

Clinical Neuroscience

[EEG-based cerebral networks in 14 neurological disorders]

DÖMÖTÖR Johanna, CLEMENS Béla, CSÉPÁNY Tünde, EMRI Miklós, FOGARASI András, HOLLÓDY Katalin, PUSKÁS Szilvia, FEKETE Klára, KOVÁCS Attila, FEKETE István

[Background - Brain networks have not been systematically investigated yet in most neurological disorders. Purpose - To investigate EEG functional connectivity (EEGfC) networks in 14 neurological disorders. Patients - Potentially eligible patients were collected from clinical and EEG databases. All the available clinical data and EEG records were critically revised. All the patients who suffered of a single neurological disorder (out of the 14) and had a good quality EEG recording entered the study. Confoundig factors as comorbidity and CNS-active drug effects were eliminated as far as possible. EEG analysis - Three minutes of resting-state, waking EEG activity were selected for analysis. Current source density (CSD) values were computed for 2394 cortical voxels by Low Resolution Electromagnetic Tomography (LORETA). Thereafter, Pearson correlation coefficients were computed between all pairs of 23 cortical regions of interest (ROI) in each hemisphere (LORETA Source Correlation, LSC software). Computation was carried out for conventional EEG broad bands and very narrow bands (1 Hz bandwidth) between 1 and 25 Hz as well. Correlation coefficients of each group were statistically compared to our normative EEG (LSC) database by two-talied t-tests. Bonferroni-corrected p<0.05 values were accepted as statistically significant, and were graphically displayed as topographical networks. Results and conclusion - Group-specific networks were demonstrated. However, non-specific networks, charasteristic for most groups, were detected as well. Common finding were: decreased connectivity in the alpha band and increased connectivity in the delta, theta bands and upper-beta band. Decreased alpha-band connectivity presumably reflected primary lesional effects and on the other hand, non-specific vulnerability of “rich club connections”. Increased connectivity in the slow bands presumably indicated adaptive-compensatory activity of brain homeostasis. ]

Clinical Neuroscience

[Relationship between the number of hours of sunshine and the number of (violent) suicides in Hungary]

BOZSONYI Károly, ZONDA Tamás, FÜLÖP Andrea, BÁLINT Lajos

[Aim - Studying the impact of the sunshine on the numbers of suicides. The number of suicides is highest in the late spring and early summer months, while it is lowest in the cold, gloomy winter. Although the exact causes are still un-known, there are some theories about this phenomenon. A number of studies conducted in recent years have conclud-ed that the rise in suicide rate during the warm months might be due to an increased exposure to sunlight, especially in the cases of the violent method. We studied the validity of this hypothesis on a large Hungarian database. Methods and subjects - We analyzed the number of monthly hours of sunshine and the number of suicides by sex and by violent vs. non-violent method over a 360-month period. Our sample consisted of 127 877 committed suicides between 1971 and 2000. The parabolic trend of seasonality had to be removed from the suicide time series, then regression analysis was conducted on the seasonally adjusted data. Results - Our analysis revealed that in Hungary there was no statistically significant direct relationship between the number of hours of sunshine and the number of suicides. Moreover, there was no correlation between the hours of sunshine and the number of violent suicides either. Conclusion - If the above claim were confirmed in subsequent research, it would mean that our current therapeutic regime should be reconsidered during the spring-summer seasons.]

Clinical Neuroscience

Independent validation of the Quality of Life in Essential Tremor Questionnaire (QUEST)

KOVÁCS Márton, MAKKOS Attila, JANSZKY József, KOVÁCS Norbert

Quality of Life in Essential Tremor Questionnaire (QUEST) was specially developed for essential tremor population to measure the health-related quality of life. Besides the development of the Hungarian version, we performed an independent testing of the scale adding further information on its clinimetric properties. In this study 133 ET patients treated at University of Pécs, Hungary, were enrolled. Besides QUEST, we assessed Patient’s Global Impression-Severity (PGI-S) and Fahn-Tolosa-Marin Tremor Rating Scales. After the independent validation in accordance to the Classic Theory of Tests, we evaluated cut-off values for detecting clinically meaningful ET-related disabilities based on receiver operating characteristics analysis. Cronbach’s a was 0.897. QUEST demonstrated high convergent validity with PGI and divergent validity with disease-duration, positive family history, need for deep brain stimulation surgery, and the presence of depression and anxiety. Presence of moderate ET-related disabilities was identified by scores > 11.25 points on QUEST-SI (sensitivity: 77.4%, specificity: 83.3%); whereas scores > 20.35 points indicated severe ET-related disabilities (sensitivity: 83.3%, specificity: 59.1%). We demonstrated that the fundamental clinimetric properties of the QUEST are satisfactory.

Clinical Neuroscience

The role of the insula in the parieto-frontomedial epileptic network. Clues from successful surgical treatment

BALOGH Attila, AIMEN Anwar, KELEMEN Anna, ERÕSS Loránd, FABÓ Dániel

We present a case of MRI negative SMA seizure with the seizure onset zone in the secondary leg area on the superior bank of the Sylvian fissure, localized with multiscale electro-clinical and neuroradiological examinations. The 34-year-old female patient’s intractable epilepsy started at age 14. She had diffuse pain aura in her left leg followed by tonic posturing with fully preserved consciousness suggesting parieto-fronto-medial seizure propagation. Her daily nocturnal SMA seizures became drug-resistant. Multiple 3T MRI images and neuropsychological evaluations were normal. Interictal PET detected a right parietal and insular FDG hypometabolism. The seizure onset zone and the symptomatogenic zone were localized by invasive electrophysiology. The insular deep electrode showed the propagation of ictal activity with an onset in the secondary sensory leg area through the insula to the fronto-medial surface. Eighteen spontaneous seizures, electrical cortical stimulation and cortical mapping confirmed the designated area of the resection, which was later proved macroscopically abnormal during surgery. The histological and immunohistological workup confirmed focal cortical dysplasia (IIb type). Postoperative postprocessing morphometry of the preoperative MRI study confirmed the lesion in the right inferior parietal lobe. The patient remained seizure free after surgery for more than 4 years, and medication free for the last two years. Our results concluded that the insula has a „relay” or „node” function in the parieto-opercular-fronto-medial epileptic network. The insular functional connectivity predisposed frontal propagation of the epileptic activity in the connectome of her epilepsy. The three-way insular structural connectivity has determining function on the seizure propagation.

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[Immunomodulatory treatment in multiple sclerosis ]

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Clinical Neuroscience

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[Multiple sclerosis (MS) is the most common chronic disease of the central nervous system in young adults. No curative therapy is known. Currently, six drugs are available that can reduce the activity of MS. The first-line drugs can completely reduce the activity of the disease in nearly two-thirds of the patients. In the remainder, who suffer from breakthrough disease, the condition of the patient worsens, and secondline therapies must be used. The second-line drug natalizumab exhibits almost double efficacy of the first-line drugs, but also have less favourable adverse effects. As a severe side-effect for instance, natalizumab carries the risk of the development of progressive multifocal leucoencephalopathy (PML), caused by a polyoma virus, the JC virus. There are three major risk factors for PML: an anti-JCV antibody status, a long duration of natalizumab treatment and prior immunosuppressant therapy. The lowest-risk group (1:14 286) comprises of patients who are anti-JCV antibody-negative, in whom the prior immunosuppressant use and duration of natalizumab therapy do not influence the risk of PML. With no prior immunosuppressant treatment, the incidence of PML increases to 1 in 192 patients after 2 years among those who are anti-JCV antibody-positive. These data may lead the physician to decide to discontinue natalizumab treatment. The half-life of natalizumab is three months; during this time other therapies can not be administered and the patients encounter the rebound effect: as the patients receiving natalizumab therapy displayed a high disease activity before treatment, the rebound effect can lead to relapses. After the termination of natalizumab secondline disease-modifying therapy with fingolimod may be introduce; no PML cases occur in response to fingolimod treatment. In the large majority of patients taking natalizumab who do not develop PML, this drug is highly effective and can prevent the progression of MS. The benefit of therapy and the risk of PML must be considered on an individual basis, with regard to the disease activity, the progression and the MRI activity, before natalizumab therapy is implemented.]

Clinical Neuroscience

[Extending therapeutic possibilities in relapsing-remitting multiple sclerosis: dimethyl fumarate]

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Lege Artis Medicinae

[IMMUNE-MEDIATED NEUROLOGICAL DISORDERS]

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Clinical Neuroscience

[Is second-line immunomodulatory treatment effective in multiple sclerosis?]

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