Clinical Neuroscience

[IMPORTANCE OF THE ANALYSIS OF NEUTRALIZING ANTIBODIES TO IMMUNOMODULATORY THERAPY DURING TREATMENT OF MULTIPLE SCLEROSIS]

SERES Erika, VÉCSEI László

MAY 30, 2006

Clinical Neuroscience - 2006;59(05-06)

[Interferon-α, -β, and -γ have been used for the management of several diseases with varying clinical effects. Like many other proteins, all interferon species are potentially immunogenics especially those produced by recombinant gene technologies. A reliable screening assay for anti-interferon-β antibodies is suggested for patients with multiple sclerosis receiving interferon-β therapy. Natural interferon-β is a glycosylated 166 amino acid 25 kDa protein, recombinant interferon-β is available for therapy as 1a and 1b products. Both preparations induce anti-interferon-β antibodies, detectable in the serum of interferon-β-treated patients with multiple sclerosis. The question of wich assay is optimal for testing for antiinterferon- β antibodies in interferon-β-treated patients is unsettled. Two types of antibody assays are generally used: those measuring binding antibodies and those measuring neutralizing antibodies. The findings suggest that high titers of both binding and neutralizing antibodies reduce the clinical efficacy of interferon-β in relapsing-remitting multiple sclerosis, which is important for the long-term efficacy of these drugs. Treatment with glatiramer acetat has also been shown to induce the development of “reactive antibodies” in patients with multiple sclerosis. This article briefly describes some of the findings concerning anti-interferon binding and neutralizing antibodies.]

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Clinical Neuroscience

[EPILEPSY AND MALE SEXUAL DYSFUNCTION: ETIOLOGY, DIAGNOSIS AND THERAPY]

BÓNÉ Beáta, JANSZKY József

[While 10% of healthy men had sexual dysfunctions, male epilepsy patients experience sexual problems in 40-70%. The cause of sexual dysfunction in epilepsy is multifactorial, but there are three main factors: the epilepsy itself, antiepileptic treatment and psychiatrical/psychic problems. Antiepileptics with hepatic enzyme induction potential (carbamazepine, phenytoin) enhance the metabolism of sexual steroids. Valproic acid as an enzyme inhibitor and drug with high protein binding affinity elevates the free serum levels of androgenes. Certain antiepileptic drugs may have negative cognitive side effects, some of them can induce psychiatric disorders. These drugs can facilitate male sexual dysfunctions through these psychic side effects. The metabolic and endocrine alterations caused by carbamazepin may return to normal level after replacement of carbamazepin with oxcarbazepine. After an oxcarbazepin-carbamazepin replacement, carbamazepin-induced impotency can be cured. According some new data lamotrigine can also help in sexual dysfunction. The therapy of sexual dysfunction in epilepsy depends on its cause. In cases of hormonal alterations, the fist step is a change of antiepileptic regimen. Instead of enzymeinductor antiepileptics and valproate, new antiepileptic drugs should be prescribed. At present, the most investigated antiepileptic drug is the oxcarbazepine with positive effect on antiepileptic-induced male sexual dysfunction, however, lamotrigine seems to be also beneficial. If the hormonal and sexual dysfunctions cannot be eliminated by drug changes, androgenic therapy or bromocriptin may be required. Testosteron may not only be beneficial on sexual functions, but can reduce also the seizure frequency. Independent of etiology, erectile dysfunctions can be successfully treated by sildenafil.]

Clinical Neuroscience

[ABSTRACTS OF THE 8TH CONGRESS OF THE HUNGARIAN EPILEPSY LEAGUE Pécs, 25-27 May, 2006.]

Clinical Neuroscience

[COMPLEX GAZE DISTURBANCE CAUSED BY THALAMIC AND MESENCEPHALIC INFARCTS]

GULYÁS Szilvia, NAGY Ferenc, SZIRMAI Imre

[A 36 year-old male patient developed sudden double vision and gait imbalance. Neurological examination revealed gaze paresis upward and on the left side downward (vertical “oneand- a-half”-syndrome), horizontal gaze nystagmus on the left bulbus directed to left. The MRI revealed bilateral thalamic and left midbrain ischemic lesions. The brainstem auditory and visual evoked responses were normally configured. Optokinetic nystagmus test found rightward, upward and downward hypometric saccades, convergence-retraction nystagmus - which was not visible at physical neurological examination - saccadic smooth pursuit eye movement and pseudoabducent palsy on both sides. The complex gaze disturbance was attributed to the lesions in the intralaminar nuclei of the thalamus and in the pretectal and rostromedial tegmentum of the mesencephalon. Infarcts may have been due to a variant artery: i.e. the thalamoperforant and the superior paramedian mesencephalic arteries originate with common branch from one of the communicant basilar artery. The authors discuss the mechanism of complex gaze palsy and call attention to the diagnostic value of optokinetic nystagmus examination.]

Clinical Neuroscience

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Clinical Neuroscience

[Tünde Csépány-Zsolt Illés: Clinical neuroimmunology]

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[Health status and costs of ambulatory patients with multiple sclerosis in Hungary]

PÉNTEK Márta, GULÁCSI László, RÓZSA Csilla, SIMÓ Magdolna, ILJICSOV Anna, KOMOLY Sámuel, BRODSZKY Valentin

[Background and purpose - Data on disease burden of multiple sclerosis from Eastern-Central Europe are very limited. Our aim was to explore the quality of life, resource utilisation and costs of ambulating patients with multiple sclerosis in Hungary. Methods - Cross-sectional questionnaire survey was performed in two outpatient neurology centres in 2009. Clinical history, health care utilisation in the past 12 months were surveyed, the Expanded Disability Status Scale and the EQ-5D questionnaires were applied. Cost calculation was conducted from the societal perspective. Results - Sixty-eight patients (female 70.6%) aged 38.0 (SD 9.1) with disease duration of 7.8 (SD 6.7) years were involved. Fifty-five (80.9%) had relapsing-remitting form and 52 (76.5%) were taking immunomodulatory drug. The average scores were: Expanded Disability Status Scale 1.9 (SD 1.7), EQ-5D 0.67 (SD 0.28). Mean total cost amounted to 10 902 Euros/patient/year (direct medical 67%, direct nonmedical 13%, indirect costs 20%). Drugs, disability pension and informal care were the highest cost items. Costs of mild (Expanded Disability Status Scale 0-3.5) and moderate (Expanded Disability Status Scale 4.0-6.5) disease were 9 218 and 17 634 Euros/patient/year respectively (p<0.01), that is lower than results from Western European countries. Conclusion - Our study provides current inputs for policy making and contributes to understanding variation of costof- illness of multiple sclerosis in Europe.]

Clinical Neuroscience

[Family planning in multiple sclerosis: conception, pregnancy, breastfeeding]

RÓZSA Csilla

[Family planning is an exceptionally important question in multiple sclerosis, as women of childbearing age are the ones most often affected. Although it is proven that pregnancy does not worsen the long-term prognosis of relapsing-remitting multiple sclerosis, many patients are still doubtful about having children. This question is further complicated by the fact that patients – and often even doctors – are not sufficiently informed about how the ever-increasing number of available disease-modifying treatments affect pregnancies. Breastfeeding is an even less clear topic. Patients usually look to their neurologists first for answers concerning these matters. It falls to the neurologist to rationally evaluate the risks and benefits of contraception, pregnancy, assisted reproduction, childbirth, breastfeeding and disease modifying treatments, to inform patients about these, and then together come to a decision about the best possible therapeutic approach, taking the patients’ individual family plans into consideration. Here we present a review of relevant literature adhering to international guidelines on the topics of conception, pregnancy and breastfeeding, with a special focus on the applicability of approved disease modifying treatments during pregnancy and breastfeeding. The goal of this article is to provide clinicians involved in the care of MS patients with up-to-date information that they can utilize in their day-to-day clinical practice. ]

Clinical Neuroscience

[MR imaging of acute disseminated encephalomyelitis and multiple sclerosis in children. A review (in English language)]

PATAY Zoltán

[Inflammatory diseases of the central nervous system (CNS) are relatively rare in children, but their relevance to public health is considerable due to frequent and significant long term morbidity and even mortality. As in adults, acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) and their variants are the most common entities in this group of pathologies in the pediatric patient population. Recent efforts have focused on establishing standardized diagnostic criteria schemes to facilitate the diagnosis and differential diagnosis of these diseases, however especially with multiple sclerosis those have not been fully validated yet for disease occurring in children. In recent decades the role of MRI has been constantly increasing in the diagnostic work-up of suspected inflammatory diseases of the CNS as well as in the follow-up of patients with confirmed disease. Currently, MRI is the first-line diagnostic imaging modality in ADEM and MS and is fully integrated in the most widely used diagnostic criteria schemes, but it has a key role in clinical therapeutic research trials as well. This paper provides an update on the current concepts and strategies of MRI in inflammatory diseases of the CNS, as well as a review of the imaging semiology of the various disease entities and variants with emphasis on clinical and imaging particularities relevant to the pediatric patient population.]

Clinical Neuroscience

[Symptomatic trigeminal autonomic cephalalgia without headache]

RÓZSA Anikó, KOVÁCS Krisztina, GUBA Katalin, GÁCS Gyula

[We report the case of a 60-year-old man who exhibited trigeminal autonomic symptoms on his right side (numbness of the face, reddening of the eye, nasal congestion) occurring several times a day, for a maximum of 60 se­conds, without any pain. The complaints were similar to trigeminal autonomic cephalalgia, just without any headache. Our 60-year-old male patient underwent a craniocervical MRI as part of his neurological workup, which revealed lesions indicative of demyelination. Further testing was guided (ophthalmological examination, VEP, CSF test) by the presumptive diagnosis of multiple sclerosis. It is likely that in his case the cause of these trigeminal and autonomic paroxysms is MS. Here we present an overview of the few cases we found in the literature, although we did not find any similar case reports. Perhaps the most interesting among these is one in which the author describes a family: a 54-year-old female exhibiting the autonomic characteristics of an episodic cluster headache, only without actual headache, her son, who had typical episodic cluster headaches with autonomic symptoms, and the woman’s father, whose short-term periorbital headaches were present without autonomic symptoms. We had not previously encountered a case of trigeminal autonomic cephalalgia without headache in our practice, nor have we had an MS patient exhibiting similar neurologic symptoms. The significance of our case lies in its uniqueness. ]

Clinical Neuroscience

[Current questions of multiple sclerosis: the secunder progressive form of the disease]

VÉCSEI László

[Recent data suggest that long-term worsening is common in relapsing-remitting multiple sclerosis patients and is largely independent of relapses or new lesion formation on brain MRI. The current definition of secunder progressive multiple sclerosis is worsening of disability independent of relapses over at least 6-month interval. Early focal inflammatory disease activity and spinal cord lesion are predictors of very-long term disease outcomes in relapse - onset multiple sclerosis. The potential of PET imaging to visualize hidden inflammation in MS brain in vivo is an important contribution for better understanding the progression of the disease. Therefore, PET imaging is a promising tool in detecting the conversion from relapsing remitting multiple sclerosis to secunder progressive form of multiple sclerosis. Furthermore, neuro-axonal damage is the pathological substrate of permanent disability in different neurological disorders including multiple sclerosis. The neurofilament proteins have promise in this context because their levels rise upon neuro-axonal damage not only in the cerebrospinal fluid but also in blood. Patients with increased serum levels of neurofilament at baseline, independent of other clinical and MRI variables, experience significantly more brain and spinal cord volume loss over 2 years and 5 years of follow-up. The kynurenine-pathway abnormalities may be associated with the swich from early-mild stage multiple sclerosis to debilitating progressive forms of the disease. Analysis of these metabolites in serum may have application as multiple sclerosis disease biomarkers. Free radical action has been suggested as a causal factor in the illness. Increased free radical production and consumption of the scavenger molecules were found during the active phase of the disease. Based on the clinical findings (EXPAND Study) and pathomechanism of the disease siponimod is approved by the US Food and Drug Administration for the treatment of relapsing remitting forms of multiple sclerosis, to include secunder progressive multiple sclerosis with active disease, relapsing-remitting multiple sclerosis and clinically isolated syndrome.]