Clinical Neuroscience

[Theoretical and practical considerations of rational polytherapy in epilepsy]


NOVEMBER 30, 2011

Clinical Neuroscience - 2011;64(11-12)

[Author analyses the consideration of rational polytherapy for epilepsy. Among the theoretical aspects he points the different effect of seizure inhibitory drugs on the epilepsy models but didn’t find data enough for the basis of any successful combination. Combinations of compounds having different way of action are more promising. Rational polytherapy can serve also the epileptic patients’ tailored therapy in the daily routine. There have already been some proved synergisms concerning drug interactions. Based on detailed analysis of side effects a possibility occurs for neutralization of side effects when anticonvulsants with side effects of opposite nature are combined. Considering both the side effect profiles and the different (somatic and psychic) habits of the patients we can create a special list of favourable combinations. Co-morbid states and their treatments play a significant role in the application of rational polytherapy. Combination of anticonvulsants of lower potential but without drug-interactions can be the choice in these cases. The non-epileptic indications of the anticonvulsants can also be utilized in polymorbid patients. Based on the theoretical and practical considerations the author defines the ten-step-cognitive-preparation-process in planning the optimal (poly)therapy. On speculative basis he suggests eight beneficial versions of seizure inhibitory rational polytherapy.]



Further articles in this publication

Clinical Neuroscience

[The carrier model of neurology in Hungary: a proposal for the solution until 2020]

BERECZKI Dániel, CSIBA László, KOMOLY Sámuel, VÉCSEI László, AJTAY András

[Based on our previous survey on the capacities of neurological services and on the predictable changes in the neurologist workforce in Hungary, we present a proposal for the organization of the structure of neurological services in the future. We discuss the diagnostic groups treated by neurologists, the neurological services and their progressive organization. Using the current capacities as baseline, we propose patient groups to be treated by neurologists in the future, and the levels of services. Based on the tendencies seen in the last years we suggest to consider to allocate acute stroke services exclusively to stroke units in neurological departments, and we identify a few other diagnostic groups where neurology should have a larger share in patient care. We define three levels for inpatient care: university departments, regional/county hospitals, city hospitals. Instead of minimum criteria we assign outpatient and inpatient standards that are functional from the economic point of view as well. University departments cover all areas of neurological services, have a function in graduate and postgraduate training, and on a regional basis they participate in professional quality assurance activities at the county and city hospital levels, and would have a more independent role in residency training. As far as patient care is concerned, the task of the regional/county hospitals would be similar to that of university departments - without the exclusively university functions. A general neurological service would be offered at the city hospital level - the representation of all subspecialties of neurology is not required. Neurorehabilitation would be organized at special units of neurological wards at the city hospital level, at independent neurorehabilitation wards in regional/county hospitals, and also as an outpatient service offered at the patients’ home. The most significant organizational change would affect the outpatient neurological services. In addition to the special outpatient units associated with university departments and regional/county hospitals, the general neurological outpatient services would be organized as private practices, similarly to the current system of general practitioners, where the individual practices contract independently with the health insurance fund. Their task would be a general neurological service offered 30 hours per week, and also basic, screening neurophysiological and neurosonological examinations, with proper equipment and trained assistance. A transformation in residency training and a change in financing is needed for this plan to fulfill.]

Clinical Neuroscience

[Vascular or “lower body parkinsonism”. Rise and fall of one diagnosis]


[The “arteriosclerotic parkinsonism”, which is called vascular parkinsonism (VP), was first described by Critchley1. The broad based slow gait, reduced stride lenght, start hesitation, freezing and paratonia was mentioned as “lower body parkinsonism” (LBP) which can be associated by slow speech, dysexecutive syndrome, and hand tremor of predominantly postural character. In VP the DAT-scan proved normal dopamine content of the striatum in contrast with Parkinson’s disease (PD). Additionally, Lewy bodies of brainstem type were not found in VP. Probability of VP increases if central type pathologic gait is prominent; the hands are slightly involved, the MRI indicates transparent periventricular white substance and/or brain atrophy. In some cases differentiation of gait apraxia and parkinsonism could be challenging. There is no rigor of the lower limbs at rest in neither of them, the disturbance of movement is evoked by the gait itself. Three subtypes of “gait ignition failure” has been recently described: (1) ignition apraxia, (2) equilibrium apraxia and (3) mixed gait apraxia. The primary progressive freesing gait was considered as a Parkinson-plus syndrome. Freesing occurs more frequently in diseases with pakinsonism than in PD. The grade of ventricle dilatation and the frontal leukoaraiosis was similar in LBP and gait apraxia. In cases of normal pressure hydrocephalus the impaired gait may mimic PD. Pathologic gait in VP can be explained by the lesions of the senso-motor association pathways in dorsal paramedian white substance within the vulnerable borderzone region. These may be colocalized with the representation of the lower extremities in the posterior third of the supplementer motor area. Rektor2 proposed to change the name of LBP to “cerebrovascular gait disorder”. Notwithstandig central type gait disorder develops also in many degenerative diseases other than cerebro-vascular origin. The neuronal net controling the regulation of movement is widespread, therefore several cortical and subcortical lesions could elicit large variations of pathologic gait, ie.: ataxia, apraxia, ignition failure, akinesis etc. In conclusion: most of the central gait disorders regarding the pathology and their appearance can not be called “parkinsonism”; these are much closer related to the localization of lesions rather than to the diagnostic categories.]

Clinical Neuroscience

[Subarachnoid hemorrhage in Hungary. Analysis based on the reports of the hospitals to the National Health Insurance Fund in 2009]

KOZÁK Norbert, SZABÓ Sándor, AJTAY András, BERECZKI Dániel

[Background and purpose - We analyzed the statistical characteristics of subarachnoid hemorrhage (SAH) in Hungary in 2009. Methods - Using data supplied by the hospitals about their inpatient services to the National Health Insurance Fund with ICD-10 code I60. Results - 1403 SAH hospital cases were recorded in 1028 patients. That is much more than we expected from previous data. 63.6% were women, hospital case fatality was 12.2%. The average hospital stay was 6.47 days. 763 CT examinations were done (74.2% of the patients). Hypertension was recorded in 61.3% of the patients. The incidence was increasing with age till the age group of 51- 60 years, and decreased beyond that. In 531 patients the source of bleeding could be verified. Aneurysm of the anterior communicating artery was more frequent in men, aneurysm of the middle cerebral artery (MCA) and internal carotid artery in women. In total MCA aneurysm was the most frequent. Arteriovenous malformation was present in 7.6% of the patients. SAH was most frequent in January and February, rarest in April and August. Conclusion - SAH is more frequent in Hungary than previously thought.]

Clinical Neuroscience

[A8344G mutation of the mitochondrial DNA with typical mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes syndrome]

VASTAGH Ildikó, GÁL Anikó, REMÉNYI Viktória, SEMJÉN Judit, LUKÁCS Tímea

[We report an unusual case of juvenile ischaemic stroke syndrome associated with the A8344G mutation in tRNALys gene of mitochondrial DNA. The clinical phenotype of patient was typical for MELAS (mitochondrial ecephalomyopathy with lactate acidosis and stroke like episodes). The MELAS has been related to mutation A3243G in most cases, but some other mitochondrial DNA mutations were described in the background of this syndrome as well. A 22-years-old man and his family were investigated. Throughout clinical investigation as well as Doppler sonography, neuroradiological, and immunserological examinations were performed. Molecular studies included the analysis of the Leiden, prothrombin G20210A and the most common mitochondrial DNA mutations. The DNA analysis of the proband revealed a heteroplasmic A8344G substitution in the T-loop of the tRNALys gene. The mutation could not been detected in her mother blood. We can conclude that A8344G mutation of the mitochondrial DNA resulted in juvenile ischemic stroke, which is associated only rarely to this genetic alteration. In young age onset of a stroke-like episode with undetermined etiology the mtDNA alterations always have to be excluded.]

Clinical Neuroscience

[Common variable immunodeficiency with coexisting central nervous system sarcoidosis. Case report and literature review with implications for diagnosis and pathogenesis]


[We describe a patient with a history of longstanding primary generalised epilepsy, on anticonvulsant therapy, who presented with fever, headache, worsening seizures and hallucinations. Among various investigations, the patient had high CSF protein and ACE levels, leptomeningeal nodular enhancement on MRI brain and non-caseating granulomas in the brain and meninges on the biopsy. The patient was diagnosed with neurosarcoidosis. Subsequently, he was found to be panhypogammaglobulinaemic and was diagnosed with probable common variable immunodeficiency (CVID). The coexistence of common variable immunodeficiency and neurosarcoidosis is rare. Typically, non-caseating granulomas in CVID patients are localised in the lymphatic tissue and solid organs. To our knowledge, there are only five reports of the granulomas of the central nervous system (CNS) in CVID. We discuss the diagnostic difficulties in this case and review the literature.]

All articles in the issue

Related contents

Clinical Neuroscience

Effects of valproate, carbamazepine and levetiracetam on Tp-e interval, Tp-e/QT and Tp-e/QTc ratio


Aim - To evaluate P-wave dispersion before and after antiepileptic drug (AED) treatment as well as to investigate the risk of ventricular repolarization using the Tpeak-Tend (Tp-e) interval and Tp-e/QT ratio in patients with epileptic disorder. Methods - A total of 63 patients receiving AED therapy and 35 healthy adults were included. ECG recordings were obtained before and 3 months after anti-epileptic treatment among patients with epilepsy. For both groups, Tp-e and Tp-e/QT ratio were measured using a 12-lead ECG device. Results - Tp-e interval, Tpe/QT and Tp-e/QTc ratios were found to be higher in the patient group than in the control group (p<0.05, for all), while QTmax ratio was significantly lower in the patient group. After 3 months of AED therapy, significant increases in QT max, QTc max, QTcd, Tp-e, Tp-e/QT, and Tp-e/QTc were found among the patients (p<0.05). When the arrhythmic effects of the drugs before and after treatment were compared, especially in the valproic acid group, there were significant increases in Tp-e interval, Tp-e/QT and Tp-e/QTc values after three months of treatment (p<0.05). Carbamazepine and levetiracetam groups were not statistically significant in terms of pre- and post-treatment values. Conclusions - It was concluded that an arrhythmogenic environment may be associated with the disease, and patients who received AED monotherapy may need to be followed up more closely for arrhythmia.

Clinical Neuroscience

[Zonisamide: one of the first-line antiepileptic drugs in focal epilepsy ]


[Chronic administration of antiepileptic drugs without history of unprovoked epileptic seizures are not recommended for epilepsy prophylaxis. Conversely, if the patient suffered the first unprovoked seizure, then the presence of epileptiform discharges on the EEG, focal neurological signs, and the presence of epileptogenic lesion on the MRI are risk factors for a second seizure (such as for the development of epilepsy). Without these risk factors, the chance of a second seizure is about 25-30%, while the presence of these risk factors (for example signs of previous stroke, neurotrauma, or encephalitis on the MRI) can predict >70% seizure recurrence. Thus the International League Against Epilepsy (ILAE) re-defined the term ’epilepsy’ which can be diagnosed even after the first seizure, if the risk of seizure recurrence is high. According to this definition, we can start antiepileptic drug therapy after a single unprovoked seizure. There are four antiepileptic drugs which has the highest evidence (level „A”) as first-line initial monotherapy for treating newly diagnosed epilepsy. These are: carbamazepine, phenytoin, levetiracetam, and zonisamide (ZNS). The present review focuses on the ZNS. Beacuse ZNS can be administrated once a day, it is an optimal drug for maintaining patient’s compliance and for those patients who have a high risk for developing a non-compliance (for example teenagers and young adults). Due to the low interaction potential, ZNS treatment is safe and effective in treating epilepsy of elderly people. ZNS is an ideal drug in epilepsy accompanied by obesity, because ZNS has a weight loss effect, especially in obese patients.]

Clinical Neuroscience

[Decisional collisions between evidence and experience based medicine in care of people with epilepsy]


[Background – Based on the literature and his long-term clinical practice the author stresses the main collisions of evidence and experience based medicine in the care of people with epilepsy. Purpose – To see, what are the professional decisions of high responsibility in the epilepsy-care, in whose the relevant clinical research is still lacking or does not give a satisfactory basis. Methods – Following the structure of the Hungarian Guideline the author points the critical situations and decisions. He explains also the causes of the dilemmas: the lack or uncertainty of evidences or the difficulty of scientific investigation of the situation. Results – There are some priorities of experience based medicine in the following areas: definition of epilepsy, classification of seizures, etiology – including genetic background –, role of precipitating and provoking factors. These are able to influence the complex diagnosis. In the pharmacotherapy the choice of the first drug and the optimal algorithm as well as the tasks during the care are also depends on personal experiences sometimes contradictory to the official recommendations. Same can occur in the choice of the non-pharmacological treatments and rehabilitation. Discussion and conclusion – Personal professional experiences (and interests of patients) must be obligatory accessories of evidence based attitude, but for achieving the optimal results, in some situations they replace the official recommendations. Therefore it is very important that the problematic patients do meet experts having necessary experiences and also professional responsibility to help in these decisions. ]

Clinical Neuroscience

[LADA type diabetes, celiac diasease, cerebellar ataxia and stiff person syndrome. A rare association of autoimmune disorders]

SOÓS Zsuzsanna, SALAMON Mónika, ERDEI Katalin, KASZÁS Nóra, FOLYOVICH András, SZŰCS Anna, BARCS Gábor, ARÁNYI Zsuzsanna, SKALICZKI József, VADASDI Károly, WINKLER Gábor

[Celiac disease - in its typical form - is a chronic immunemediated enteropathy with typical clinical symptoms that develops against gliadin content of cereal grains, and is often associated with other autoimmune diseases. In cases of atypical manifestation classic symptoms may be absent or mild, and extra-intestinal symptoms or associated syndromes dominate clinical picture. The authors present a longitudinal follow-up of such a case. A 63-years old woman was diagnosed with epilepsy at the age of 19, and with progressive limb ataxia at the age of 36, which was initially thought to be caused by cerebellar atrophy, later probably by stiff person syndrome. At the age 59, her diabetes mellitus manifested with type 2 diabetic phenotype, but based on GAD positivity later was reclassified as type 1 diabetes. Only the last check-up discovered the celiac disease, retrospectively explaining the entire disease course and neurological symptoms. By presenting this case, the authors would like to draw attention to the fact that one should think of the possibility of celiac disease when cerebellar ataxia, progressive neurological symptoms and diabetes are present at the same time. An early diagnosis may help to delay the progression of disease and help better treatment.]

Clinical Neuroscience

Relationship between Status Epilepticus Severity Score and etiology in adult NCSE patients

GENC Fatma, ERDAL Abidin, AKCA Gizem, KARACAY Ertan, GÖKSU Özaydın Eylem, KUTLU Gülnihal, GÖMCELI Bicer Yasemin

Purpose - Nonconvulsive status epilepticus (NCSE) is a heterogeneous, severe neurological disorder of different etiologies. In this study, the outcomes of NCSE episodes was assessed in a large series of adult patients. Our objective was to evaluate relationship between Status Epilepticus Severity Score (STESS) and etiology and the role of etiological factors on predicting the outcomes. Method - In this retrospective study, the medical records of 95 patients over 18 years of age who were diagnosed with NCSE between June 2011 and December 2015 were reviewed. Their treatment and follow-up for NCSE was performed at the Epilepsy Unit in Department of Neurology, Antalya Research and Training Hospital. Etiological factors thought to be responsible for NCSE episodes as well as the prognostic data were retrieved. The etiological factors were classified into three groups as those with a known history of epilepsy (Group 1), primary neurological disorder (Group 2), or systemic/unknown etiology (Group 3). STESS was retrospectively applied to patients. Results - There were 95 participants, 59 of whom were female. Group 1, Group 2, and Group 3 consisted of 11 (7 female), 54 (33 female), and 30 (19 female) patients, respectively. Of the 18 total deaths, 12 occurred in Group 2, and 6 in Group 3. The negative predictive value for a STESS score of ≤ 2 was 93.88% (+LR 2.05 95% CI: 1.44-2.9 and -LR 0.3 95% CI 0.10-0.84 ) in the overall study group. While the corresponding values for Group 1 (patients with epilepsy), Group 2 (patients with primary neurological disorder), and group 3 (patients with systemic or unknown etiology) were 100%, 92.59% (+LR 2.06 95%CI: 1.32-3.21 and -LR 0.28 95% CI 0.08-1.02 ) 83.33% (+LR 1.14 95%CI: 0.59-2.9 and -LR 0.80 95% CI 0.23-2.73). Conclusions - This study included the one of the largest patients series ever reported in whom STESS, a clinical scoring system proposed for use in patients with status epilepticus, has been implemented. Although STESS appeared to be quite useful for predicting a favorable outcome in NCSE patients with epilepsy and primary neurological disorders, its predictive value in patients with systemic or unknown etiology was lower. Further prospective studies including larger NCSE samples are warranted.