Cryptogenic Focal Epilepsy Research Articles

Typical absence status epilepticus in older people: syndromic delineation.

Objective We describe the clinical, electroencephalograph^ and neuroimaging findings of older patients with typical absence status epilepticus (ASE). Methods This investigation was a retrospective analysis of prospectively collected consecutive patients between January 2011 and October 2021. All patients ≥60 years with impairment of awareness and continuous generalized, rhythmic, synchronous and symmetric epileptiform discharges and normal background on video-electroencephalogram (vEEG) were included. Results Six patients were identified with a diagnosis of typical ASE. The mean age was 67 years. Five could be classified as idiopathic generalized epilepsy (IGE) though two had been erroneously categorized as cryptogenic focal epilepsy (FE). In one, the episode of ASE was thought to represent the beginning of late-onset IGE (de novo late-onset typical ASE). In all cases, ASE was controlled within the first 24 hours. Significance Typical ASE is a rare cause of confusion in the elderly population requiring urgent vEEG evaluation. It most frequently represents reactivation of a previous IGE, in effect related to patients with epilepsy with onset in childhood or adolescence, not previously diagnosed or treated, representing rather the debut of (de novo) late-onset IGE.

Sulthiame impairs mitochondrial function in vitro and may trigger onset of visual loss in Leber hereditary optic neuropathy

BackgroundLeber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder and characterized by acute or subacute painless visual loss. Environmental factors reported to trigger visual loss in LHON mutation carriers include smoking, heavy intake of alcohol, raised intraocular pressure, and some drugs, including several carbonic anhydrase inhibitors. The antiepileptic drug sulthiame (STM) is effective especially in focal seizures, particularly in benign epilepsy of childhood with centrotemporal spikes, and widely used in pediatric epileptology. STM is a sulfonamide derivate and an inhibitor of mammalian carbonic anhydrase isoforms I–XIV.ResultsWe describe two unrelated patients, an 8-year-old girl and an 11-year-old boy, with cryptogenic focal epilepsy, who suffered binocular (subject #1) or monocular (subject #2) visual loss in close temporal connection with starting antiepileptic pharmacotherapy with STM. In both subjects, visual loss was due to LHON. We used real-time respirometry in fibroblasts derived from LHON patients carrying the same mitochondrial mutations as our two subjects to investigate the effect of STM on oxidative phosphorylation. Oxygen consumption rate in fibroblasts from a healthy control was not impaired by STM compared with a vehicle control. In contrast, fibroblasts carrying the m.14484T>C or the m.3460G>A LHON mutation displayed a drastic reduction of the respiration rate when treated with STM compared to vehicle control.ConclusionsOur observations point to a causal relationship between STM treatment and onset or worsening of visual failure in two subjects with LHON rather than pure coincidence. We conclude that antiepileptic medication with STM may pose a risk for visual loss in LHON mutation carriers and should be avoided in these patients.

Genetic Landscape of Common Epilepsies: Advancing towards Precision in Treatment.

Epilepsy, a neurological disease characterized by recurrent seizures, is highly heterogeneous in nature. Based on the prevalence, epilepsy is classified into two types: common and rare epilepsies. Common epilepsies affecting nearly 95% people with epilepsy, comprise generalized epilepsy which encompass idiopathic generalized epilepsy like childhood absence epilepsy, juvenile myoclonic epilepsy, juvenile absence epilepsy and epilepsy with generalized tonic-clonic seizure on awakening and focal epilepsy like temporal lobe epilepsy and cryptogenic focal epilepsy. In 70% of the epilepsy cases, genetic factors are responsible either as single genetic variant in rare epilepsies or multiple genetic variants acting along with different environmental factors as in common epilepsies. Genetic testing and precision treatment have been developed for a few rare epilepsies and is lacking for common epilepsies due to their complex nature of inheritance. Precision medicine for common epilepsies require a panoramic approach that incorporates polygenic background and other non-genetic factors like microbiome, diet, age at disease onset, optimal time for treatment and other lifestyle factors which influence seizure threshold. This review aims to comprehensively present a state-of-art review of all the genes and their genetic variants that are associated with all common epilepsy subtypes. It also encompasses the basis of these genes in the epileptogenesis. Here, we discussed the current status of the common epilepsy genetics and address the clinical application so far on evidence-based markers in prognosis, diagnosis, and treatment management. In addition, we assessed the diagnostic predictability of a few genetic markers used for disease risk prediction in individuals. A combination of deeper endo-phenotyping including pharmaco-response data, electro-clinical imaging, and other clinical measurements along with genetics may be used to diagnose common epilepsies and this marks a step ahead in precision medicine in common epilepsies management.

MOG-IgG-associated demyelination: focus on atypical features, brain histopathology and concomitant autoimmunity.

Antibodies to myelin oligodendrocyte glycoprotein (MOG) have been demonstrated in patients with optic neuritis (ON), encephalitis and myelitis. To describe the clinical and paraclinical features in patients with MOG-associated demyelination, focusing on unusual cases, brain biopsy and concomitant autoimmunity. A single centre retrospective observational case series, analysing demographic, clinical, laboratory, histopathology and radiological data from MOG- positive patients. We identified 20 adults. The male/female ratio was 1.5. Mean age at onset was 31.6 years and mean disease duration was 7.5 years. The most frequent presentation was myelitis (45%), followed by ON (30%). One case had simultaneous myelitis and ON. Two patients had a cortical syndrome, 1 patient had an encephalopathic presentation and 1 cryptogenic focal epilepsy. Anti-neutrophil cytoplasmic antibodies (ANCA) were found in 3 cases, while 1 patient had an antibody to glutamic acid decarboxylase (GAD). Brain biopsy was performed in 2 patients. Relapsing course was identified in 60% of patients. We also discuss 3 cases with atypical features, brain histopathology and concomitant autoimmunity. MOG- associated demyelination represents a new disease entity. Unusual cases are reported, expanding the disease spectrum. Elucidating this further should be the focus of prospective studies.

Additional options for non-pharmacological treatment of epilepsy

Objective: to study the effect of blue polarizing glasses on photosensitivity in patients with photosensitive epilepsy (PSE). Materials and methods. On the backdrop of red light stimulation, EEG and daytime video EEG recordings were performed in 19 patients with epilepsy (15 women, 4 men) aged from 14 to 41 years. Among those, 8 patients had juvenile myoclonic epilepsy (JME), 2 – eyelid myoclonus with absences, 6 – generalized epilepsy, 1 – juvenile absence epilepsy (JAA), and 2 patients had unspecified (cryptogenic) focal epilepsy. All patients underwent photo-stimulation (PS) with an increasing light frequency from 1 to 31 Hz (in 3 Hz steps). The PS procedure was carried out twice: without and with the use of blue polarizing glasses with a degree of darkness of 50%.Results. In 19 patients with PSE, we observed a photo-paroxysmal response at frequencies of 10, 13, 15, 16, 19, and 21 Hz. In the same individual, this photo-paroxysmal response could have manifested either in a burst of epileptic activity without clinical symptoms or in myoclonus / myoclonia with absences. In 8 (42.1%) patients, there was a decrease in epileptic activity upon photo-stimulation: a decrease in the duration of the acute peak-slow-wave activity or a zero epileptic activity at one frequency on the backdrop of a notable epileptic activity at other frequencies. In 3 (15.8%) patients, who were using the blue glasses, there were neither seizures nor epileptic activity at all. In one case (5.3%), there was no seizure but the PS-induced epileptiform activity did occur. The disappearance of subclinical epileptic activity was noted in 2 (10.5%) cases.Conclusion. Blue polarizing glasses can be used as an additional means of non-pharmacological therapy of PSE. The protective effect may be associated with a decrease in the melatonin content in the daytime.

Maturational Changes of Gamma-Aminobutyric Acid A Receptors Measured With Benzodiazepine Binding of Iodine 123 Iomazenil Single-Photon Emission Computed Tomography

BackgroundIodine 123 (I-123) iomazenil is a specific ligand of the central benzodiazepine receptor, which is a part of the postsynaptic gamma-aminobutyric acid A receptor complex. We performed statistical image processing of I-123 iomazenil single-photon emission computed tomography to elucidate maturational changes in the GABAergic system. MethodsThirty patients (18 boys and 12 girls, aged 17 days to 14 years) with cryptogenic focal epilepsy were enrolled and underwent I-123 iomazenil single-photon emission computed tomography. We used a semiquantitative analytical method consisting of brain surface extraction, anatomic normalization, and a three-parameter exponential model. We then assessed developmental changes in benzodiazepine receptor binding activity in 18 regions of interest in both hemispheres. ResultsThe highest benzodiazepine receptor binding activity was observed during early infancy in all regions of interest. Benzodiazepine receptor binding activity then decreased exponentially across development. Benzodiazepine receptor binding in the primary sensorimotor cortex, primary visual cortex, cerebellar vermis, and striatum declined more rapidly than that in the cerebellar hemispheres and the frontal cortex. The pons and the thalamus had the lowest benzodiazepine receptor binding activities during the neonatal period, and benzodiazepine receptor binding in these areas declined gradually after infancy toward adolescence. There were no differences in adjusted benzodiazepine receptor binding activity according to laterality or sex. ConclusionsBenzodiazepine receptor binding activity decreased exponentially during infancy in all regions of interest. Binding activity in the primary somatosensory and motor cortices (M1 and S1), the primary and association visual areas, the cerebellar vermis, and the striatum (caudate nucleus and putamen) tended to decline more rapidly than that in the cerebellar hemisphere and the frontal association cortex.

DIFFERENTIAL DIAGNOSIS OF EPILEPTIC SEIZURES IN CRYPTOGENIC FOCAL FRONTAL LOBE EPILEPSY VERSUS PSYCHOGENIC NON-EPILEPTIC PAROXYSMS (A CASE REPORT)

The report addresses the causes and diagnostic problems of cryptogenic focal frontal epilepsy. A clinical case of a patient with cryptogenic focal frontal epilepsy is presented. In this patient, epileptic seizures have long been considered as psychogenic non-epileptic paroxysms.

CLINICAL AND EPIDEMIOLOGICAL ASPECTS OF EPILEPSY IN CHILDREN AND ADOLESCENTS LIVING IN KRASNOYARSK REGION

The high prevalence of epilepsy in the pediatric population, significant cognitive, psychological and social consequences of this disease determine the problem urgency and the need for research. Previously there were no clinical-epidemiological study of epilepsy in the pediatric population in the Krasnoyarsk region (KR). This study estimates prevalence of epilepsy among children and adolescents in the KR, specifies gender and age variations of the disease onset, analyzes epileptic syndromes structure. The study included 1032 patients aged 0 to 17 years with epilepsy. General and primary morbidity in KR within the last 3 years was at the same level: in 2012 – 5,9 and 1,4, respectively, in 2013 – 5,65 and 1,3, in 2014 – 5,96 and 1,5 per 1000 children; in 2012 – 7,3 and 1,4, respectively, in 2013 – 7,3 and 1,5, in 2014 – 7,9 and 1,3 per 1000 adolescents. These parameters are greater than those in the Siberian Federal District and the Russian Federation; boys are more likely to suffer from epilepsy (54%) than girls (46%). The epilepsy onset occurs mainly at age from 0 to 1 year (26%) and 4–6 years (24%), significantly more rare manifestation occurs in adolescence (4%). In the structure of epilepsy syndromes prevail symptomatic focal (41%) and cryptogenic focal epilepsy (28%); third and fourth place take idiopathic focal epilepsy (18%) and idiopathic generalized epilepsy (10%) respectively; less numerous group is epileptic encephalopathy (3%). Study results allow to discuss the strategy of dispensary observation of patients with epilepsy, to plan surveys financing and drug supply and organization of medical and social care for patients with epilepsy and their families.

Epileptic syndromes in childhood associated with secondary generalized tonic-clonic seizures

To study a group of patients with secondary generalized tonic-clonic seizures (SGTCS) in view of nosology, medical history, clinical, electroencephalographic and neuroimaging features. The study included 471 patients, 244 (51.8%) men and 227 (48.2%) women. SGTCS were observed in many epileptic syndromes. The most frequent were symptomatic focal epilepsy (33.8%), cryptogenic focal epilepsy (23.8%), rolandic epilepsy (12.6%), FEBL-BEDC syndrome (12.3%). Other forms of epilepsy were less frequent. The onset of epilepsy ranged over a wide age range from the first month of life to 18 years. The average age of onset was 5.7±4.96 years. SGTCS as the only type of paroxysms were observed in 28.3% of cases. Two or more types of seizures were observed in 71.7% of patients, three or more types in 39.3%. Epileptiform activity on EEG during long VEM was detected in 91.3% of patients with SGTCS. In 37.2% of patients, benign epileptiform discharges of childhood were recorded. Treatment with antiepileptic drugs (AEP) led to complete remission in 57.1% of cases of epilepsy associated with SGTCS. A reduction of the frequency of seizures by 50% or more was found in 33.6% of patients treated with AEP. No effect was observed in 9.3% of patients. Significant differences in the prognosis and therapeutic approaches to specific epileptic syndromes associated with SGTCS necessitate the use of the entire spectrum of diagnostic measures, which should include careful history taking, clinical examination, video-EEG monitoring with the inclusion of sleep dynamics, MRI / CT brain, genetic testing.

GENERALIZED TONIC-CLONIC SEIZURES : CLASSIFICATION, ELECTRO-CLINICAL CHARACTERISTICS, AND EFFICACY OF ANTIEPILEPTIC THERAPY

Objective: to study patients with generalized tonic-clonic seizures (GTCS) with emphasis on their nosological, anamnestic, clinical, EEG, and neuroimaging characteristics, as well as their response to antiepileptic therapy. Materials and methods . A total of 1261 patients with various forms of epilepsy and the onset of seizures from the first day of life to 18 years of age were examined. Among those, a group of patients with confirmed GTCS was subjected to further analysis. Results. We identified 190 patients with GTCS, which comprised 15.1% of all epilepsy cases (1261). There was a slight predominance of male patients in the GTCS group: 99 (52.1%) versus 91 (47.9%) females. It is known that GTCS can be part of 13 different epileptic syndromes. Among the patients in the present study, the following syndromes prevailed: epilepsy with isolated generalized seizures (26.2%), juvenile absence epilepsy (23.7%), and juvenile myoclonic epilepsy (23.2%). Symptomatic / cryptogenic focal epilepsy (SFE / CFE) was diagnosed in 11.6% of patients. In these patients with GTCS, the debut of epilepsy varied from the first month of life to 18 years of age. The average age of the debut was 10.4±5.35 years. The highest incidence of epilepsy in these pediatric patients was observed between 13 and 15 years of age – 27.4% of all cases. Along with that, the onset of epilepsy with generalized seizures reached its maximum at the interval between 10 and 18 years of age (60.4% of all cases). GTCS as the only type of seizures for the entire period of the disease was observed in 27.4% of cases. In the remaining patients, GTCS were observed together with other types of seizures. Of those, myoclonic seizures (34.2% of cases) and typical absences (31.6%) were mostly common. It is shown that in most patients (75.8%), antiepileptic medications brought about a complete remission. In 18.9% of patients, this treatment resulted in a more than two-fold decrease in the occurrence of seizures. In 5.3% of cases, the antiepileptic therapy had no effect. In 35 patients (18.4% of cases) in remission, recurrent seizure attacks were observed. Conclusion. The variety of GTCS- associated syndromes, and the significant differences in the prognosis and the therapeutic approaches, necessitate using the full range of diagnostic measures.

The effects of computer-based rehabilitation on the cognitive functions of epilepsy patients

Objective: The aim of this study was to examine the effects of computerized cognitive rehabilitation programs conducted with the purpose of slowing down cognitive losses and developing coping strategies in patients diagnosed with cryptogenic and symptomatic focal epilepsy, with participants’ cognitive functions being evaluated through neuropsychological tests prior to and after rehabilitation. Methods: Of 32 patients who were receiving treatment at the Istanbul University, Cerrahpasa Faculty of Medicine Hospital, Department of Neurology Epilepsy Clinic, 9 patients who met the inclusion criteria underwent an 8-consecutive-week computer-assisted cognitive rehabilitation program conducted by a psychologist once a week. The effectiveness of the program was tested with a comprehensive neuropsychological assessment both before the rehabilitation program and 3 months after its completion. Results: Test scores of patients before and after the rehabilitation were found as follows: Stroop-1 12.22±2.72; 11.55±4.36, Stroop-2 14.55±4.95; 15.55±9.20, Stroop-3 34.11±15.59; 26.44±12.25, Spatial Recall Test-1 14.22±5.99; 15.88±6.79, Spatial Recall Test-2 4.22±2.94; 6.88±2.93, Selective Reminding Test-1 55.88±11.95; 56.0±7.0, Selective Reminding Test-2 8.77±3.83; 8.77±2.72, Digit Symbol Substitution Test 38.33±19.31; 37.66±24.35, Lexical Verbal Fluency Test 25.77±11.3; 33.66±14.47, Semantic Verbal Fluency Test 15.77±4.52; 17.88±5.88. The pre- and post-rehabilitation scores of Stroop-3, Spatial Recall Test (SRT)-2 and Lexical Verbal Fluency tests were significantly different (p

FV 4. U-Fiber Density Imaging identifies specific microstructural alterations in the epileptogenic zone in individual patients with cryptogenic focal epileps

Patients with cryptogenic focal epilepsy (cFE), where conventional MRI does not show any structural lesion represent the fastest growing number of epilepsy surgery candidates in most tertiary referral centers. The absence of a visible surgical target challenges presurgical evaluation and requires complementary diagnostic methods to guide further investigations, especially intracranial EEG recordings. Here we present a new diagnostic approach, based on the quantification of regional u-fiber density to identify specific microstructural abnormalities in the epileptogenic zone of patients with cFE. 55 patients with cFE and 60 healthy controls were investigated. Diffusion Tensor Imaging (DTI) data was acquired on a GE Signa HDx 3T MRI Scanner, using an acquisition scheme with 64 diffusion weighted directions, a b-value of 1000 s/mm[b] and 2.4 mm slice thickness. Whole brain tractography was performed, creating an average of 1.05 million fiber tracts per subject. From this dataset, we specifically selected u-fibers, based on length, curvature and shape criteria. Density images were created, specifying the number of u-fibers within any 1 mm[c] voxel of the brain. These u-fiber density images (UFDI) were spatially normalized to a template in MNI-space and smoothed with an 8 mm kernel. For every single patient the UDFI was statistically compared against the control population, using SPM software. Clusters of significant reductions in UFDI were determined, thresholding at a minimum size of 5 cm[c] and a p-value <0.001, correcting for multiple comparisons using the family wise error (FWE) method. Localization of UFDI reductions was compared with clinical data from the presurgical evaluation. All patients had normal conventional MRI, using a specific epilepsy protocol on a 3T scanner. In 43 patients, a conclusive hypothesis on the epileptogenic zone could be derived, based on ictal and interictal EEG, seizure semiology, FDG-PET and ictal SPECT imaging and neuropsychological assessment. Only those 43 patients were included in the final analysis. In the remaining 12, clinical data was inconclusive, preventing further analysis of their UDFI alterations. Clusters of significant UFDI reductions were found in 91% of the patients and 78% of these reductions were consistent with the clinically suspected epileptogenic zone. Twelve patients underwent intracranial EEG recording with depth electrodes, confirming seizure onset in 74% of the detected UFDI reductions. Eight patients had resective surgery and the most frequent histopathological finding was a mild architectural disturbance with blurred gray-white matter border and ectopic neurons in the white matter. Quantitative UFDI has proven sensitive and specific to detect microstructural alterations in patients with cFE, superior to other complementary diagnostic methods. Histopathology has shown mild malformations of cortical development (MCD), a well-known cause of cFE. MCD typically affect the gray-white matter border, and this is exactly where u-fibers are located, spanning between neighboring gyri, directly underneath the cortex. We hypothesize the ectopic neurons disrupt the microstructural order of subcortical white matter, thereby artificially reducing the number of u-fibers we could reconstruct in this region. UFDI has become a routine diagnostic method in our department for all patients with cFE and is now routinely used to guide implantation of intracranial electrodes.

Circadian phase typing in idiopathic generalized epilepsy: Dim light melatonin onset and patterns of melatonin secretion-Semicurve findings in adult patients.

It has been debated in the literature whether patients with idiopathic generalized epilepsy (IGE) have a distinctive, evening-oriented chronotype. The few questionnaire-based studies that are available in the literature have conflicting results. The aim of our study was to define chronotype in patients with IGE by determining dim light melatonin onset (DLMO). Twenty adults diagnosed with IGE (grand mal on awakening [GM] in 7 cases and juvenile myoclonic epilepsy in 13 cases) were investigated by means of a face-to-face semistructured sleep interview, Morningness-Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI) questionnaire, and a melatonin salivary test with DLMO determination. Eighteen healthy subjects (HC) and 28 patients affected with cryptogenic focal epilepsy (FE) served as controls. The mean MEQ score was significantly lower in patients with IGE than that in patients with FE (49.1±5.9 versus 56.1±8.7 P<0.01) but not significantly lower than that in HC (49.1±5.9 versus 49.3±8.6). Midsleep on free days corrected for sleep duration did not differ significantly between the three subject groups (04:59±01:21h, 04:37±01:17h, 04:29±00:52h). The mean DLMO time in patients with IGE (22:13±01:34h) occurred 49min later than that in HC (21.24±1h), and the melatonin surge within the 30-minute time interval after DLMO in patients with IGE was significantly lower than that in HC (1.51±2.7 versus 3.8±3.6pg/mL P=0.045). Subjective measures of chronotype do not indicate a definite evening-oriented chronotype in patients with IGE. However, the data concerning endogenous melatonin secretion indicate that patients with IGE tend to have a late circadian phase. Further studies are warranted in order to better define the late pattern of endogenous melatonin secretion in patients with IGE and to ascertain the role of this pattern in influencing behavioral chronotype in these subjects.

FOCAL CORTICAL DYSPLASIAS: CLINICAL AND ELECTRO-NEUROIMAGING CHARACTERISTICS

In spite of a notable advance made in epileptology, resistant epilepsies account for approximately 30 % of all forms of epilepsy particularly in patients with focal seizures. One of the main causes of therapy-resistant focal epilepsies is focal cortical dysplasias (FCD). This term was first introduced by D. Taylor et al. in 1971. FCD belongs to abnormal cortical development. Among all abnormalities of cortical development, FCD in surgically treated children amounts to 75 %. FCD is the most common cause of resistant epilepsy in children and the most frequent reason for diagnosing cryptogenic focal epilepsy with intractable seizures. The author gives a detailed literature review dedicated to FCD as a cause of resistant epilepsy, including the classification and histologic characteristics of FCD, its clinical manifestations and prognosis, and approaches to medical and surgical treatments.

COMPARATIVE EFFICАCY AND TOLERABILITY OF MONOTHERAPY WITH DEPAKINE CHRONOSPHERE, DRUGS OF CARBAMAZEPINE GROUP WITH EXTENDED RELEASE AND OXCARBAZEPINE IN SYMPTOMATIC AND CRYPTOGENIC FOCAL EPILEPSY (SVT. LUKA’S INSTITUTE OF CHILD NEUROLOGY AND EPILEPSY)

Research on comparative efficаcy and tolerability of monotherapy with Depakine chronosphere, drugs of Carbamazepine group with extended release and oxcarbazepine in symptomatic and cryptogenic focal epilepsy has been conducted at Svt. Luka’s Institute of Child Neurology and Epilepsy (ICNE) (Moscow). This retrospective study covers a random sample of patients treated in ICNE in the period from December 1, 2013 to September 1, 2014. The study included 131 patients aged 1 to 18 years with symptomatic and cryptogenic focal epilepsy receiving treatment with one of the study drugs in monotherapy: group 1 – monotherapy with Depakine chronosphere (n = 56); group 2 – monotherapy with drugs of carbamazepine group with extended release (n = 55); group 3 – monotherapy with oxcarbazepine (trileptal) (n = 20). The obtained results allow us to conclude that the effectiveness of Depakin chronosphere, carbamazepine with extended release and oxcarbazepine in monotherapy of symptomatic and cryptogenic focal epilepsy was comparable (statistically significant differences in efficacy were not found). However, carbamazepine was awarded the highest frequency of seizures aggravation. Drugs showed approximately same tolerability (statistically significant differences in tolerability were not found). However, withdrawal of the drug due to side effects was the rarest in Depakine (3.5 %), and withdrawal due to intolerance was higher in carbamazepine and oxcarbazepine (5 and 10 % respectively). Depakinum and oxcarbazepine had the best results in the blocking of pathological activity on the electroencephalogram, whereas carbamazepine was clearly inferior to them. In this regard, complete clinical-electroencephalographic remission (lasting 12 months or more) was achieved under treatment of Depakine chromosphere in 21.5 % of cases, oxcarbazepi on therapy for 12 months was similar in all study drugs. Considering that the objective of epilepsy treatment is to achieve complete control over seizures, or at least substantially reduce and weaken them in the absence of significant side effects that disturb the patient’s quality of life, it can be concluded that the best treatment results were obtained in group of depakine chronosphere therapy.

ZONISAMIDE (ZONEGRAN) IN THE TREATMENT OF EPILEPSY IN ADULTS AND CHILDREN (A REVIEW AND CLINICAL CASE)

Despite the significant progress made in epileptology, resistant epilepsies constitute approximately 30 % of all forms of epilepsy. An overview of recent literature is provided on the efficacy and safety of a new antiepileptic drug zonisamide (Zonegran) in the treatment of epilepsy with emphasis on monotherapy. The mode of action, pharmacokinetic characteristics, the effectiveness and tolerance of zonisamide in resistant focal epilepsy, as well as other types of seizures and forms of epilepsy are described. Indications for use of the drug are discussed. Also a wider potential for application of zonisamide are described: in the treatment of generalized seizures, in monotherapy as well as in children and adolescents. At present, Zonegran is registered for application in children from 6 years and older, with focal seizures, in additional therapy. The authors present their own observation of high efficacy of zonisamide in adjunctive therapy in a child of 9 years with cryptogenic focal epilepsy. Onset of epileptic seizures at the age of 5 months. Since the onset of the disease the child has received a lot of antiepileptic drugs in various combinations, with no significant effect. Zonisamide (Zonegran) was introduced in therapy 4 months ago in combination with the valproate acid drug (which the child received over the years), and since the release to the full dose epileptic seizures are absent up to present. It should be noted that there was not a single remission of four-month duration since the onset of the disease. Moreover, normalization of sleep has been noted. Tolerability of the therapy is good. No side effects were noted.

The surgically remediable syndrome of epilepsy associated with bottom-of-sulcus dysplasia.

To determine clinical and EEG features that might help identify patients with epilepsy harboring small, intrinsically epileptogenic, surgically treatable, bottom-of-sulcus dysplasias (BOSDs). Retrospective review of clinical records, EEG, MRI, and histopathology in 32 patients with drug-resistant epilepsy and MRI-positive (72% 3.0 tesla), pathologically proven (type 2B cortical dysplasia) BOSDs operated at our centers during 2005-2013. Localization of BOSDs was frontal in 19, insula in 5, parietal in 5, and temporal in 3, on the convexity or interhemispheric surfaces. BOSDs were missed on initial MRI at our centers in 22% of patients. Patients presented with focal seizures during infancy in 9, preschool years in 15, and school years in 8 (median age 5 years). Seizures were stereotyped, predominantly nocturnal, and typically nonconvulsive, with semiology referable to the fronto-central or perisylvian regions. Seizures occurred at high frequency during active periods, but often went into prolonged remission with carbamazepine or phenytoin. Intellect was normal or borderline, except in patients with seizure onset during infancy. Scalp EEG frequently revealed localized interictal epileptiform discharges and ictal rhythms. Patients underwent lesionectomy (median age 14 years) guided by electrocorticography and MRI, with prior intracranial EEG monitoring in only one patient. Twenty-eight patients (88%) became seizure-free, and 20 discontinued antiepileptic medication (median follow-up 4.1 years). In patients with cryptogenic focal epilepsy, this clinical presentation and course should prompt review of or repeat MRI, looking for a BOSD in the frontal, parietal, or insula cortex. If a BOSD is identified, the patient might be considered for single-stage lesionectomy.

Use of valproates in women of childbearing age and pregnant women with epilepsy

The paper considers the specificity of using valproic acid (VA) preparations in young childbearing-aged women with epilepsy and discusses the clinical situations of practical application of valproates during pregnancy in view of the baseline efficiency of therapy, the type of epileptic seizures, and the form of epilepsy. It provides a few scenarios of the course of pregnancy and possible treatment policy. Owing to its multiple mechanism of action, VA has been effectively used to treat idiopathic (generalized/focal) cryptogenic and symptomatic focal epilepsies in patients of different age groups, including in childbearing-aged women. It is also effectively used to treat manias in the pattern of bipolar disorders and to prevent migraine. The range of action (the efficiency against different types of seizures and forms of epilepsy), good tolerance, a minimal aggravation risk, high continuous therapy rates, various drug dosage forms, including long-acting or intravenous formulatons, and favorable pharmacokinetic and pharmacodynamics profiles make VA indispensable at the present developmental stage of epileptology. However, VA has definite limitations: the drug is contra-indicated in some forms of mitochondrial encephalopathies; its prescription to young women requires comprehensive assessment of possible therapy consequences, especially in pregnancy planning, the drug should be used with extreme caution in the first trimester of pregnancy. The ideal variant of VA prescription in young women of fertile age is monotherapy, by using its minimal effective daily dose and sustained-release formulations.

A retrospective evaluation of retigabine in patients with cognitive impairment with highly drug-resistant epilepsy

PurposeThe purpose of this study was to evaluate retrospectively the efficacy and tolerability of retigabine (RTG) in residential patients of an epilepsy center. MethodWe used an industry-independent noninterventional retrospective evaluation on the basis of paper and electronic records plus interrogation of the treating neurologists. All patients (N=20; 7 females; mean age: 31.8, range: 18–54years) started on RTG between May 2011 and March 2012 were included. Evaluation was carried out after 6, 12, and 24months. Changes in seizure frequency were measured as the number of seizures during three months on RTG compared with a three-month baseline period. The Clinical Global Impression scale was applied to include qualitative changes in seizure severity. All but one patient had symptomatic (structural; one patient: metabolic) or cryptogenic focal or multifocal epilepsy. All had grade III drug-resistant epilepsy and cognitive deficits of different degrees. ResultsThe retention rates were 60% after 6months, 35% after 12months, and 20% after 24months. At 12months, there were 2 responders (10%): one had a >90% seizure reduction and the other had a >50% seizure reduction. Another 5 patients were still on RTG because of minor improvements. The reasons for discontinuation in 13 patients were adverse effects (6), lack of effect (6), and both (1). Cognitive or emotional changes were the side effects that most frequently led to discontinuation. Beyond the 12-month evaluation, 3 patients were discontinued as a consequence of the FDA warning regarding retinal pigmentation and discoloration of skin and nails in patients exposed to RTG. One patient had a moderate blue–gray finger coloring. Ophthalmological changes were not discovered. ConclusionRetigabine proved to be useful only for a small minority of patients in a sample of patients with particularly difficult-to-treat epilepsy.

Evaluation of the effect of c.2946 + 1G > T mutation on splicing in the SCN1A gene

Mutations in the SCN1A gene have commonly been associated with a wide range of mild to severe epileptic syndromes. They generate a wide spectrum of phenotypes ranging from the relatively mild generalized epilepsy with febrile seizures plus (GEFS+) to other severe epileptic encephalopathies, including myoclonic epilepsy in infancy (SMEI), cryptogenic focal epilepsy (CFE), cryptogenic generalized epilepsy (CGE) and a distinctive subgroup termed as severe infantile multifocal epilepsy (SIMFE). The present study was undertaken to investigate the potential effects of a transition in the first nucleotide at the donor splice site of intron 15 of the SCN1A gene leading to CGES. Functional analyses using site-directed mutagenesis by PCR and subsequent ex-vivo splicing assays, revealed that the c.2946+1G>T mutation lead to a total skipping of exon 15. The exclusion of this exon did not alter the reading frame but induced the deletion of the amino acids (853 Leu −971 Val) which are a major part in the fourth, fifth and sixth transmembrane segments of the SCN1A protein. The theoretical implications of the splice site mutations predicted with the bioinformatic tool human splice finder were investigated and compared with the results obtained by the cellular assay.