Clinical Neuroscience

[Change of therapeutic algorithm in sclerosis multiplex based on two case reports]

BIERNACKI Tamás1, BENCSIK Krisztina1, KINCSES Zsigmond Tamás1, SANDI Dániel1, FRICSKA-NAGY Zsanett1, FARAGÓ Péter1, VÉCSEI László1,2

NOVEMBER 30, 2017

Clinical Neuroscience - 2017;70(11-12)

DOI: https://doi.org/10.18071/isz.70.0381

[The aim of our case reports is to demonstrate the therapeutic use and possibilities one has with alemtuzumab, should it be used either as a first or second line therapy. Our first patient's disease in the beginning seemed to be benign. It was not the case however, over several years the diesase showed high activity both radiologically and clinically, she was treated with alemtuzumab as part of an esclationbased therapeutic strategy. The second patient's disease on the other hand showed formidable activity since the very beginning both radiologically and clinically. Therefore we were facing a very disastrous prognosis on the long run, accordingly he received alemtuzumab treatment very early into his illness.]

AFFILIATIONS

  1. Szegedi Tudományegyetem, Általános Orvostudományi Kar, Szent-Györgyi Albert Klinikai Központ, Neurológiai Klinika, Szeged
  2. MTA-SZTE Idegtudományi Kutatócsoport, Szeged

COMMENTS

0 comments

Further articles in this publication

Clinical Neuroscience

[Role of peginterferon-β-1a in the therapy of multiplex sclerosis]

SIMÓ Magdolna, ILJICSOV Anna

[The subcutaneous peginterferon-b-1a is recently introduced in the therapy of relapsing-remitting multiplex sclerosis (RRMS) patients. Pegylation of IFN b-1a improved pharmacodynamic and pharmacokinetic properties, resulting in, increased biologic activity and a longer half-life. The efficacy of peginterferon-b-1a was proved by the ADVANCE study - a 2-year Phase 3, multicenter, randomized, double-blind study with a 1-year placebocontrolled period evaluating the efficacy and safety of subcutaneous peginterferon-b-1a administered every 2 or 4 weeks in patients with RRMS. Peginterferon-b-1a efficacy was maintained during the two years, with greater effects observed with every 2 week versus every 4 week dosing. Annualized relapse rate and confirmed disability progression was reduced comparing with patients on delayed treatment. Patients treated with continuous peginterferon-b-1a had fewer new or newly enlarging T2 lesions over 2 years than patients in the delayed treatment group. Adverse events were consistent with the known profiles of IFN b therapies in MS. The most commonly reported adverse events were injection site erythema, influenza-like illness. The less frequent administration is associated with fewer flu-like adverse events, which may improve patients’ compliance and adherence. Peginter-feron-b-1a could be an effective and safe treatment option for RRMS patients.]

Clinical Neuroscience

Posterior reversible encephalopathy syndrome as an initial manifestation of systemic lupus erythematosus

AYAS Özözen Zeynep, ÖCAL Öncel Ruhsen, GÜNDOGDU Aksoy Asli

Posterior reversible encephalopathy syndrome (PRES) is a disorder which is diagnosed with its characteristic clinical and radiological findings, typically resolves with treatment. The prevalence of PRES in systemic lupus erythematosus (SLE) patients is not exactly known. A systemic disorder frequently appears as a presenting symptom in SLE. However, in rare cases, the disease starts with a neurological manifestation. Here we report a 35-year-old woman presenting with a headache and blurred vision. She had neurologic symptoms and cerebral lesions on magnetic resonance imaging (MRI) suggesting PRES. The patient was diagnosed with SLE during the etiological investigation of PRES. In this article, we aimed to emphasize that PRES as an initial presentation of SLE.

Clinical Neuroscience

A case with reversible neurotoxicity induced by metronidazole

EREN Fulya, ALDAN Ali Mehmet, DOGAN Burcu Vasfiye, GUL Gunay, SELCUK Hatem Hakan, SOYSAL Aysun

Background - Metronidazole is a synthetic antibiotic, which has been commonly used for protozoal and anaerobic infections. It rarely causes dose - and duration - unrelated reversible neurotoxicity. It can induce hyperintense T2/FLAIR MRI lesions in several areas of the brain. Although the clinical status is catastrophic, it is completely reversible after discontinuation of the medicine. Case report - 36-year-old female patient who had recent brain abscess history was under treatment of metronidazole for 40 days. She admitted to Emergency Department with newly onset myalgia, nausea, vomiting, blurred vision and cerebellar signs. She had nystagmus in all directions of gaze, ataxia and incompetence in tandem walk. Bilateral hyperintense lesions in splenium of corpus callosum, mesencephalon and dentate nuclei were detected in T2/FLAIR MRI. Although lumbar puncture analysis was normal, her lesions were thought to be related to activation of the brain abscess and metronidazole was started to be given by intravenous way instead of oral. As lesions got bigger and clinical status got worse, metronidazole was stopped. After discontinuation of metronidazole, we detected a dramatic improvement in patient’s clinical status and MRI lesions reduced. Conclusion - Although metronidazole induced neurotoxicity is a very rare complication of the treatment, clinicians should be aware of this entity because its adverse effects are completely reversible after discontinuation of the treatment.

Clinical Neuroscience

[Tension-type headache in ulcerative colitis]

TAJTI Jr. János, LÁTOS Melinda, ÁBRAHÁM Szabolcs, SIMONKA Zsolt, PASZT Attila, LÁZÁR György

[Background and purpose - Tension-type headache is a very common disease with a high socio-economic impact as its lifetime prevalence is 30-78% in the general population. The incidence of inflammatory bowel diseases is continuously rising. Limited data are accessible on quality of life in patients with surgically treated ulcerative colitis. The aim of our study is to examine quality of life, concerning headache, among patients who had undergone surgery due to ulcerative colitis. Methods - Between 1 January 2005 and 1 March 2016, surgery was performed due to ulcerative colitis in 75 patients. During this retrospective analysis the average duration of the follow-up was 46 (1-124) months. The pre-sence of headache was evaluated by the use of Brief Illness Perception and Headache Questionnaires. Results - Among the primary headache disorders (n=27), tension-type headache occurred in 19 (70.4%) cases, and 8 (29.6%) patients had migraine (without aura). Among tension-type headache cases 17 (89.5%) patients experienced episodic form and 2 (10.5%) suffered from chronic form. Patients with headache had obtained a significantly higher score on Brief Illness Perception Questionnaire. Conclusions - According to our study tension-type headache is common among patients with ulcerative colitis. This observation raises the question whether stress plays role in the pathogenesis of both diseases, which influences and worsens considerably quality of life. Neurological examination, psychological and psychiatric guidance are worth considering in patients with ulcerative colitis.]

Clinical Neuroscience

[Alemtuzumab therapy 2017]

BIERNACKI Tamás, BENCSIK Krisztina, SANDI Dániel, VÉCSEI László

[Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system comprising of inflammation, demyelinisation and neurodegeneration. The natural history of MS is heterogenous. Owing to the vast range and severity of the symptoms MS can cause the effect of the disease on one’s cognitive and physical status is unpredictable. According to the new, phenotype based classification two subgroups can be distinguished; relapsing-remitting (RR) and progressive MS. Relapsing-remitting MS can be further divided into active and inactive disease. The activity of the disease can be proven either clinically and/or by radiological means. A patient’s disease is considered inactive, if it fulfills the criteriae set in the “no evidence of disease activity-3” (NEDA-3) concept, meaning that no progression can be seen on the MRI scans, the patient is relapse free and there is no worsening on any disability scale. Nowadays a paradigm shift can be seen in the treatment of MS. The aim of this shift is to provide each and every patient with the most potent medication best suiting his/her illness as soon as possible. Alemtuzumab offers a great option as either a first line treatment or as escalation therapy for patients with a highly active disease. The efficacy of alemtuzumab was proven in two phase III trials (CARE-MS I, II), where it was compared to subcutaneous interferon b-1a, administered three times weekly. In both studies alemtuzumab was superior to subcutaneous interferon b-1a in terms of relapse rate reduction, in all scouted MRI parameters. In the CARE-MS II trial it was found superior in terms of progression slowing. In the studies’ first 2 years 32% and 39% of the alemtuzumab treated patients managed to achieve the NEDA-3 state (data from CARE-MS II and I respectively). At the end of the 4 year extension of both studies these numbers have increased to 60% and 55% respectively. The aim of our synopsis is to suggest neurologists an evidence based guideline, a therapeutic algorithm to be used when they give their MS patients the very best, personalised treatment, and also to appoint the recently introduced alemtuzumab to its proper place in the algorithm.]

All articles in the issue

Related contents

Clinical Neuroscience

[Selective ultrastructural vulnerability in the cuprizone-induced experimental demyelination]

ÁCS Péter, KOMOLY Sámuel

[Background and purpose - It has been reported that multiple sclerosis has four different neuropathological subtypes, and two of them (type III and IV) are characterized by primary oligodendrocyte loss. However, the exact pathomechanism that lead to oligodendrocyte apoptosis in human demyelinating diseases is still elusive. The copper chelator cuprizone induces primary oligodendrocyte apoptosis and consequent demyelination in well defined areas of the mouse brain. Nevertheless, the precise subcellular events that result in oligodendrocyte cell death in the cuprizone model are still unknown. We aimed to study the ultrastructural alterations that might induce oligodendrocyte apoptosis in the cuprizone experimental demyelination model. Methods - C57BL/6 mice were given cuprizone for two, 21 and 35 days to induce demyelination to investigate early pathological events, and different stages of demyelination. In addition, mice were given cuprizone for 35 days and were allowed to recover for two or 14 days to study early and late remyelination. After the cuprizone treatment, mice were sacrificed and the corpus callosum, the superior cerebellar peduncle, the optic nerve and the sciatic nerve were studied by electron microscopy. Results - The ultrastructural analysis revealed that cuprizone induced oligodendrocyte apoptosis is accompanied by the formation of giant mitochondria in the affected cells in the corpus callosum and in the superior cerebellar peduncle. Apoptosis of the myelin producing cells was present through the whole cuprizone challenge. Severe demyelination occurred after three weeks of cuprizone administration associated with massive macrophage infiltration and astrocytosis of the demyelinated areas. Axons and neurons remained unaffected. Conclusion - The formation of giant mitochondria in myelin producing oligodendrocytes is the first pathological sign in the cuprizone experimental demyelination. Mitochondrium pathology in the cuprizone challenge might serve as a useful model to study the pathomechanism of multiple sclerosis subtypes (III and IV) characterized by primary oligodendrocyte degeneration.]

Clinical Neuroscience

[Benign-onset acute disseminated encephalomyelitis: A report on two cases]

DEGIRMENCI Eylem, ERDOGAN Cagdas, OGUZHANOGLU Attila, BIR Sinan Levent

[The signs and symptoms of acute disseminated encephalomyelitis are heterogeneous and dependent on the location and severity of the inflammatory process. The meningoencephalitic presentation may include meningism, impaired consciousness (occasionally leading to coma), seizures and confusion, or behavioral disturbances. Multifocal neurological features include a combination of optic neuritis, visual field defects, cranial neuropathy, sensorimotor impairment, ataxia, aphasia, and involuntary movements. One definition of acute disseminated encephalomyelitis is “an initial clinical event with a presumed inflammatory and demyelinating cause, with acute or sub-acute onset affecting multifocal areas of the central nervous system”. Patients with acute disseminated encephalomyelitis frequently suffer from seizures, disturbances of consciousness, fever, and headaches, and occasionally there are focal signs and symptoms. Here, we report on two cases who presented with different symptoms, but the clinical findings that the patients showed were benign.]

Clinical Neuroscience

[Alemtuzumab therapy 2017]

BIERNACKI Tamás, BENCSIK Krisztina, SANDI Dániel, VÉCSEI László

[Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system comprising of inflammation, demyelinisation and neurodegeneration. The natural history of MS is heterogenous. Owing to the vast range and severity of the symptoms MS can cause the effect of the disease on one’s cognitive and physical status is unpredictable. According to the new, phenotype based classification two subgroups can be distinguished; relapsing-remitting (RR) and progressive MS. Relapsing-remitting MS can be further divided into active and inactive disease. The activity of the disease can be proven either clinically and/or by radiological means. A patient’s disease is considered inactive, if it fulfills the criteriae set in the “no evidence of disease activity-3” (NEDA-3) concept, meaning that no progression can be seen on the MRI scans, the patient is relapse free and there is no worsening on any disability scale. Nowadays a paradigm shift can be seen in the treatment of MS. The aim of this shift is to provide each and every patient with the most potent medication best suiting his/her illness as soon as possible. Alemtuzumab offers a great option as either a first line treatment or as escalation therapy for patients with a highly active disease. The efficacy of alemtuzumab was proven in two phase III trials (CARE-MS I, II), where it was compared to subcutaneous interferon b-1a, administered three times weekly. In both studies alemtuzumab was superior to subcutaneous interferon b-1a in terms of relapse rate reduction, in all scouted MRI parameters. In the CARE-MS II trial it was found superior in terms of progression slowing. In the studies’ first 2 years 32% and 39% of the alemtuzumab treated patients managed to achieve the NEDA-3 state (data from CARE-MS II and I respectively). At the end of the 4 year extension of both studies these numbers have increased to 60% and 55% respectively. The aim of our synopsis is to suggest neurologists an evidence based guideline, a therapeutic algorithm to be used when they give their MS patients the very best, personalised treatment, and also to appoint the recently introduced alemtuzumab to its proper place in the algorithm.]

Clinical Neuroscience

[Clinical significance of the cardiovascular effects of fingolimod treatment in multiple sclerosis]

SZÉPLAKI Gábor, MERKELY Béla

[Fingolimod is a sphingosine-1 phosphate receptor modulator, which is effective in the treatment of severe relapsingremitting form of multiple sclerosis. Once daily oral use of fingolimod decreased the annualized relapse rate, inflammatory brain lesion activity and the rate of brain atrophy compared both to placebo and intramuscular administered interferon beta-1a. The drug targets the cardiovascular system as well via sphingosine- 1 phosphate receptors. After initiation of fingolimod therapy transient sinus bradycardia and slowing of the atrioventricular conduction develops. The onset of the effect is as early as 1 hour post administration, while heart rate and conduction normalized in 24 hours in most of the cases. According to the clinical trials symptomatic bradycardia developed in 0.5% of the cases, responding to the appropriate therapy. The incidence of Mobitz I type II atrioventricular blocks and blocks with 2:1 atrioventricular conduction was 0.2% and 0.1%, respectively. All of these cardiovascular events showed regression during observation and no higher degree atrioventricular blocks were detected at the approved therapeutic dose. Following the first dose effect, fingolimod had a moderate hypertensive effect on long-term. For the safety of fingolimod treatment detailed cardiovascular risk stratification of all patients, adequate patient monitoring after the first dose and competency in treating the possible side effects is necessary. In patients with increased cardiovascular risks, treatment should be considered only if anticipated benefits outweigh potential risks and extended monitoring is required.]

Clinical Neuroscience

[Magnetic resonance imaging in the course of alemtuzumab and teriflunomide therapy]

MIKE Andrea, KINCSES Zsigmond Tamás, VÉCSEI László

[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. ]