Cutaneous drug reactions to antiepileptic drugs and relation with HLA alleles in the Turkish population.

Summary: Background and objective. Many studies have shown associations between HLAB*15:02, HLA-A*31:01 and carbamazepine (CBZ)-induced delayed cutaneous hypersensitivity reactions. The aim of this study is to evaluate a possible association between delayed cutaneous reactions to antiepileptic drugs (AEDs) and certain HLA-A and HLA-B alleles in the Turkish population. Methods. The study consisted of 3 groups: Group I (reactive group) included the patients who had documented delayed cutaneous reactions to any antiepileptic drug. Group II (non-reactive group) included the patients who have been on antiepileptic treatment at least for three months without any adverse reactions. Group III consisted of healthy subjects. The HLA-A and B alleles were analyzed in all groups. Results. Forty patients (29 female) had experienced different hypersensitivity reactions due to AEDs: maculopapular exanthema (26 patients), Stevens-Johnson syndrome (6 patients), drug rash with eosinophilia and systemic symptoms (7 patients), toxic epidermal necrolysis (1 patient). Lamotrigine (11) and CBZ (10) were the most common culprit drugs involved in the reactions. The HLA-B*15:02 was not present in any of the study groups. However, HLA-B*35:02 was found in 4 patients from the reactive group, while it was not observed in non-reactive patients and was detected in only one healthy subject (p = 0.021). Conclusion. Although our preliminary results did not indicate a strong allele association with AED hypersensitivity, HLA-B*35:02 appears to be a candidate allele for MPE / DRESS / DIHSS induced by AED's in Turkish population. Further studies with a larger sample size may result in more comprehensive data about the genetic tendency for AED hypersensitivity in the Turkish population.

Expression analysis and clinical correlation of aquaporin 1 and 4 genes in human hippocampal sclerosis.

Mesial temporal sclerosis (MTS) is the most frequent cause of drug resistant symptomatic partial epilepsy. The mechanism and genetic background of this unique pathology are not well understood. Aquaporins (AQP) are regulators of water homeostasis in the brain and are expressed in the human hippocampus. We explored the role of AQP genes in the pathogenetic mechanisms of MTS through an evaluation of gene expression in surgically removed human brain tissue. We analyzed AQP1 and 4 mRNA levels by quantitative real-time polymerase chain reaction and normalized to ABL and cyclophilin genes, followed by immunohistochemistry for AQP4. Relative expressions were calculated according to the delta Ct method and the results were compared using the Mann-Whitney U test. Brain specimens of 23 patients with epilepsy who had undergone surgery for MTS and seven control autopsy specimens were investigated. Clinical findings were concordant with previous studies and 61% of the patients were seizure-free in the postoperative period. AQP1 and 4 gene expression levels did not differ between MTS patients and control groups. Immunofluorescence analysis of AQP4 supported the expression results, showing no difference. Previous studies have reported contradictory results about the expression levels of AQP in MTS. To our knowledge, only one study has suggested upregulation whereas the other indicated downregulation of perivascular AQP4. Our study did not support these findings and may rule out the involvement of AQP in human MTS.

Sleep characteristics of patients with epilepsy with pure sleep-related seizures.

OBJECTIVE: Our aim was to investigate the clinical features and sleep characteristics of patients with pure sleep-related seizures. METHODS: Patients with pure sleep epilepsy were prospectively enrolled and their clinical, EEG, and MRI findings investigated. The Medical Outcomes Study Sleep Scale (MOS-SS) was administered after receiving consent. RESULTS: Thirty-nine of 1401 consecutive patients (2.7%) with pure sleep-related seizures were included. Of these, 30 (76.9%) had epilepsy of unknown cause and 7 had epilepsy with known structural etiologies. Twenty-seven patients reported less than one seizure per month and 19 had been seizure free for at least 1 year. Thirty-four patients participated in our MOS-SS study. Comparison of sleep problems between those with epilepsy and healthy controls and between the subgroups with frequent and rare seizures did not reveal significant differences. CONCLUSION: Patients with pure sleep seizures had mostly undetermined etiology usually with a good prognosis, and this rare condition did not seem to affect their sleep quality.

Myoclonic seizures subside in the fourth decade in juvenile myoclonic epilepsy.

OBJECTIVE: Our aim was to assess the long-term follow-up of juvenile myoclonic epilepsy (JME), with an emphasis on the course of the myoclonic seizures. METHODS: We enrolled 48 patients with JME (29 F, 19 M; aged 39.9 +/- 9.5 years) followed up for a mean of 19.6 +/- 5.7 years. The remission for 5 years and relapses were evaluated for all seizure types and the changes in severity/frequency of myoclonia were systematically questioned. The clinical and EEG features, antiepileptic drug (AED) treatment regimen, and systemic and psychiatric comorbid diseases were evaluated. RESULTS: We found a benign course in 66.6% whereas 16.7% had pseudo-resistance due to problems in treatment or lifestyle. The true-resistant course observed in the remaining 16.7% was significantly associated with psychiatric disorders and the presence of thyroid diseases. In 54.2% of the patients, myoclonia were in remission for a mean duration of 8.4 +/- 7.7 years, after an average age of 32.9 +/- 9.6. Of these patients, 6 were on a lower dose of AED in comparison to the dosage needed to control the seizures in the beginning, and 5 patients had stopped AED treatment. None of the latter 11 patients except one relapsed during the follow-up. Furthermore, 21 other patients (43.8%) described substantial alleviation after age 31.3 +/- 8.4 in the severity of myoclonia. CONCLUSION: Although a great majority of the patients with juvenile myoclonic epilepsy had continuing seizures after a follow-up of 20 years, almost all had either 5-year remission or a substantial alleviation of the myoclonic seizures.

A severe neurological sequela in acute intermittent porphyria: presentation of a case from encephalopathy to quadriparesis.

Porphyrias present themselves with autonomic or peripheral neuropathy or central nervous system dysfunction. They are a varied group of inborn errors of metabolism that are characterized by specific inherited enzyme defects in haem biosynthesis. A patient whose mother was diagnosed as having porphyria was admitted to hospital because of her abdominal pains and dysuria. She had three generalized convulsions and, in a few hours, she lost the vision in both of her eyes. As the seizures continued, she became quadriparetic and fell into a coma after gradually losing consciousness. She improved but with sequelae; her serial MRIs, including apparent diffusion coefficient map imaging, diffusion-weighted imaging and angiography, showed ischaemic lesions that were both unlike and more severe than the ones reported in the literature.

Self-induction behavior in patients with photosensitive and hot water epilepsy: a comparative study from a tertiary epilepsy center in Turkey.

PURPOSE: The goal of this study was to compare self-induction (SI) patterns in photosensitive epilepsy (PSE) and hot water epilepsy (HWE). METHODS: Among 7609 consecutive patients, 129 were diagnosed as having PSE, and 34, HWE. RESULTS: Thirteen patients with PSE (10 females, 3 males, age at onset: 8.6; 3 with mental retardation) and 9 patients with HWE (all males, age at onset: 13.1) reported experiencing SI. During the seizures, a pleasurable feeling was described by all patients with HWE, but only by 3 patients with PSE. Patients with PSE induced their seizures by going very close to the TV screen or by waving their hands and blinking in front of the light sources. In the patients with HWE, seizures were precipitated by increasing the temperature of the water poured over the head or body. CONCLUSIONS: Our results indicate that SI is more frequent in HWE, although this behavior was attributed mostly to PSE in previous studies.

Hot water epilepsy: clinical and electrophysiologic findings based on 21 cases.

PURPOSE: Our aim is to outline the clinical and electroencephalographic (EEG) features of patients with hot water epilepsy (HWE), a rare and unique form of reflex epilepsy. METHODS: Twenty-one patients with HWE, seen in our clinic until 1999, were studied. Male outnumbered female subjects in a ratio of 3:1. The age at the onset of seizures ranged from 19 months to 27 years (mean age at onset, 12 years). RESULTS: The main factors precipitating seizures were bathing with hot water and/or pouring water over the head. Six patients reported self-induction, either by increasing the heat or the amount of water and/or recalling earlier bathing experiences. Nine patients expressed feeling pleasure during the seizures. Twenty patients had partial seizures, eight of whom also had secondarily generalized seizures. One patient had apparent generalized seizures only. Spontaneous seizures were present in 62% of the cases. Interictal epileptogenic abnormalities were documented in the EEGs of eight patients; the other eight had normal EEGs. The major sites of epileptogenic activity were over the unilateral temporal regions (in 40% of patients). Neuroimaging studies available for 12 patients (four cranial computed tomography and eight cranial magnetic resonance imaging scans) revealed normal findings. Seizure control in patients who were followed up was achieved by reducing the temperature or the duration of the bath or shower; several of the patients required medication. CONCLUSIONS: The major findings of this study are that HWE has a male preponderance, can be self-induced, is often done for pleasure, has complex triggering factors, and shows temporally located abnormalities in the EEGs. Although HWE is generally known to be self-limited, antiepileptic drug treatment may sometimes be necessary to control seizures. Hot water epilepsy should be classified separately among the epileptic syndromes.

Perioral myoclonia with absence seizures: a rare epileptic syndrome.

We present the clinical and video-EEG data on an epileptic boy whose absence seizures with marked perioral movements had started at the age of 1.5 years. From age 12 years, he experienced frequent episodes of typical absence status epilepticus (ASE) lasting 1-2 hours with marked perioral myoclonia and moderate confusion. Initial therapy with carbamazepine was substituted by valproate because of worsening of the absence seizures. At the age of 17, the patient was admitted to our clinic with his usual, but long lasting ASE attack, accompanied by 2 generalized tonic-clonic convulsions. ASE was confirmed with the EEG which showed continuous 3 Hz spike and wave paroxysms with occasional normal intervals of 1-5 seconds. IV injection of clonazepam improved the clinical and EEG findings immediately. Video- EEG examination performed after a few weeks demonstrated typical absence seizures with perioral myoclonia. Based on the characteristics of seizure semiology, other clinical data and EEG findings, the patient was diagnosed as having the syndrome of "perioral myoclonia with absence seizures" described by Panayiotopoulos.

Correlation between clinical stages and EEG findings of subacute sclerosing panencephalitis.

In this retrospective study 67 patients with SSPE seen between the years 1980 and 1998 were reviewed. Using the criteria of SSPE diagnosis (clinical signs, characteristic EEG patterns, high titres of measles antibodies in the serum and CSF), the patients were divided into two groups. Group A fulfilled all criteria, however, due to the inability of measuring measles antibody before 1987, it was not possible to observe the third criterion in Group B. Among 67 patients, groups A and B consisted of 51 boys and 16 girls ranging in age between 1 to 23 years, mean age 13.1. The male/female ratio was 3.1. The periodic EEG complexes (PCs) were usually bilateral, synchronous and symmetrical. PC amplitude asymmetry was seen in 12 patients and 2 patients had no PC synchronization between the hemispheres. Six patients had more than one form of PC. Delta activity in anterior hemispheres after PC was seen in 40 patients, mostly in stage 2A. Thirty-two patients had focal epileptiform abnormalities in multiple locations at every stage but most frequently in frontal, central and temporal regions. One patient had PC over both hemispheres and periodic lateralized epileptiform discharges (PLEDs) over the right hemisphere. The EEG findings described and observed in our study do not seem to be specific to SSPE but these findings were not atypical or unusual.

Longterm follow-up of electroencephalographic and clinical findings of a case with Gaucher's disease type 3a.

Among three recognised clinical phenotypes, type 3a Gaucher's disease is characterised by mild to severe systemic disease, neurological manifestations and myoclonic seizures. We report the long term clinical and electrophysiological follow-up of a 27-year old man with a diagnosis of type 3a Gaucher's disease, which was confirmed by bone marrow biopsy examination and leukocyte glucocerebrosidase level measurement. His neurological examination was normal throughout the follow-up period. EEG examination, recorded five days after the first seizure, revealed generalised nonrhythmic paroxysmal rapid spikes with occipital predominance increased by photic stimulation and normal background activity. The frequency of seizures increased from 3-4/year to 1-2/month within a follow-up period of 12 years and a repeat EEG examination on the eight year of diagnosis revealed additional background slowing. A giant potential was obtained in somatosensory evoked potential (SEP) examination. EEG findings of this case demonstrate a specific pattern with rapid spike activity, photosensitivity, eye closure sensitivity and gradual background slowing.

Periodic lateralized epileptiform discharges: association with seizures.

The clinical features and EEGs of 45 consecutive patients (40 adults and 5 children) who had periodic lateralized epileptiform discharges (PLEDs) were reviewed to determine the relationship between seizures and PLEDs. Focal encephalitis and ischemic stroke were the most frequent underlying processes for adult patients. All of the children, but only six of the adults, had long-lasting cerebral disorders whereas the remaining adults had acute or subacute illness. There were 38 patients (84.4%) experiencing a seizure disorder. Twenty-six of them had their first seizure during their acute illness, as the pattern of PLED was encountered. Eight cases had status epilepticus, and seven of them had epilepsia partialis continua. Nineteen patients had a recent seizure in the day when PLEDs were observed but not during EEG recording; 12 patients had their seizures within 10 days before the observation of PLED. PLEDs were grouped into three categories with respect to their extensions: lateralized to one hemisphere (n = 22), localized in one region (n = 17) and being prominent over one side with contralateral spread (n = 6). The last group was found to be more closely associated with frequent seizures or status epilepticus than the other two groups. Our results showed that PLEDs were highly correlated with recent seizures in the majority of the patients. These EEG findings may be considered as a manifestation of an increased neuronal excitability caused by different etiologies; but not an ictal pattern.

Nose wiping: an unrecognized automatism in absence seizures.

Nose wiping is a well-known postictal automatism in complex partial seizures, considered very important for lateralization. We report a 24-year-old woman selected from 32 patients with video-EEG investigations of absence seizures. The patient, with normal examination and imaging findings, had typical absence seizures from the age of 5 years, which were controlled with either ethosuximide or valproate and worsened by carbamazepine. In two of her recorded typical absence seizures associated with generalized 3 Hz symmetric spike-wave discharges, she wiped her nose as an automatism in the ictal and post-ictal period. Our case showed that nose wiping could be associated with generalized seizures, in contrast to other recent reports.

Changes in bone turnover and deoxypyridinoline levels in epileptic patients.

In this study, we evaluated bone turnover in 52 epileptic patients receiving chronic anticonvulsant therapy and in 39 healthy volunteers whose ages matched those of the patients. We determined serum osteocalcin and total and bone alkaline phosphatase levels as markers of bone formation, and urinary deoxypyridinoline and urinary calcium levels as markers of bone resorption. Statistical comparison of the levels of these markers between sexes in epileptic patients and their control groups revealed that total alkaline phosphatase levels were significantly increased in patients from both sexes compared with those of their controls. Urinary deoxypyridinoline levels of male epileptic patients were significantly increased compared with those of their controls. On the other hand, 25-hydroxyvitamin D levels of the male patients were significantly reduced compared with those of their controls. Serum osteocalcin, bone alkaline phosphatase, and urinary calcium levels of epileptic patients were not statistically different from those of the controls. We found that urinary deoxypyridinoline levels of male epileptic patients were increased, however, we observed no difference in serum osteocalcin and bone alkaline phosphatase levels. The lack of difference may be attributed to the fact that only the resorption phase of bone turnover is affected during chronic anticonvulsant therapy.

Eye closure related spike and wave discharges: clinical and syndromic associations.

Precipitation of spike and wave (SW) discharges in some epileptic patients by eye closure (EC) has rarely been reported. To disclose the clinical characteristics and classification of syndromes of epileptic patients with SW discharges induced by EC, we investigated 10 patients (1 M, 9 F) showing this peculiar EEG feature. The patients aged between 9-39 years (mean 20.6 +/- 9.058), underwent short-term (1-3.5 hr) video-EEG investigations in order to document the appearance of the SW discharges within 3 seconds of the act of EC, in at least two occasions. Clinical analysis showed that 5 female patients who had the syndrome of juvenile myoclonic epilepsy (JME) had a later onset of epilepsy (13-15 years) than the 3 patients (3 girls) with eyelid myoclonia with absences (EMA) (3-8 years of age at onset). The remaining 2 patients who were diagnosed as childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE) according to the international classification, did not show photosensitivity on the video-EEG. All but one of the 5 JME patients had experienced myoclonic seizures in intermittent photic stimulation (IPS) at the time of EC, associated with multiple spike and wave discharges. Two of the 3 EMA patients exhibited typical absences with eyelid myoclonia during the act of EC. The high rate of family history of epilepsy in first degree relatives of our patients was an outstanding feature, which could have future implications in research of the genetic basis of epilepsy patients with ECS.

A clinically recognizable neuronal migration disorder: congenital bilateral perisylvian syndrome. Case report with long-term clinical and EEG follow-up.

Congenital bilateral perisylvian syndrome (CBPS) is a recently described, neuronal migration disorder, characterized by pseudobulbar palsy, epilepsy and mental retardation and bilateral perisylvian dysplasia. A 15-year-old boy was diagnosed with CBPS according to the typical clinical, and magnetic resonance imaging (MRI) features. The patient was suffering from atypical absence seizures, repeating daily in spite of antiepileptic drug therapy, since age 7 years. He had also experienced rare generalized tonic-clonic seizures and complex partial seizures. Neurological examination showed severe restriction of tongue movements, severe dysarthria, dysphagia, facial diplegia, mild pyramidal signs and moderate mental retardation. A computed tomographic (CT) scan demonstrated bilateral perisylvian enlargement. The diagnosis was corrected with MRI after six years. Frequent irregular generalized spike and wave abnormalities and focal sharp and slow waves over the posterior regions of both hemispheres were shown by electroencephalograms (EEG). The patient was treated with Na-Valproate, carbamazepine and lamotrigine but did now show any significant change in seizure frequency in the eight-year follow-up period. Intractable seizures, mental retardation and particularly congenital pseudobulbar palsy suggest this congenital entity. Those patients who exhibit these typically clinical features, must have MRI.

MRI in subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a progressive, slow virus infection of the brain, caused by the measles virus, attacking children and young adults. We investigated 15 patients with SSPE by MRI, with 5 normal and 10 pathological results. In the early period, lesions were in the grey matter and subcortical white matter. They were asymmetrical and had a predilection for the posterior parts of the hemispheres. Later, high-signal changes in deep white matter and severe cerebral atrophy were observed. Parenchymal lesions significantly correlated with the duration of disease. A significant relationship between MRI findings and clinical stage was observed in the 1st year of the disease.

Diffuse spike-wave status of 9-year duration without behavioral change or intellectual decline.

Continuous, generalized 2.5 to 3.5-Hz spike-wave (SW) discharges were evident in an EEG performed 13 h after a first seizure associated with a viral illness, in an 8-year-old girl. On eye opening, the EEG abnormality was suppressed and replaced by delta activity and brief spike-wave paroxysms. No alteration in consciousness and seizures or behavioral abnormalities accompanied the EEG findings. Based on the EEG, she was diagnosed as having "diffuse electrical status," the rare EEG phenomenon that occurs during wakefulness without associated behavioral changes. Although the child was completely normal clinically, the EEG findings persisted during a 9-year-follow-up period. Ethosuximide (ESM) 1 gr daily resulted in temporary disappearance of the bioelectrical status. During the last 2 years without medication the EEG finding tended to be restricted to the posterior regions.

Spontaneous dissection of the extracranial vertebral artery with spinal subarachnoid haemorrhage in a patient with Behçet's disease.

A 40-year-old man with known definite Behçet's disease (BD) was admitted with confusional state which had started 4 days before admission with an acute headache and vomiting. Neurological examination revealed confusion, stiff neck, right facial weakness, left hemiparesis, dysartria and truncal ataxia. CSF was haemorrhagic and xanthochromic. Cranial CT scans were negative, but MRI showed a right pontine hyperintense lesion on T2-weighted images. Bilateral carotid angiograms were normal. Right vertebral angiogram showed findings consistent with a dissection at the V2 segment of the artery. At the level of the fifth cervical vertebra, a radiculomedullary branch of the vertebral artery with an aneurysmal dilatation in its intradural portion was notable. This case shows that, in BD, aneurysm formation can also occur in a spinal artery and spontaneous vertebral artery dissection can be seen.

Electrical status epilepticus lasting for 17 months without behavioural changes.

In an 8-year-old girl a seizure occurred, lasting 45 min with loss of consciousness and deviation of the eyes, 2 days after the onset of mumps. Next day the EEG showed bilateral, synchronized, continuous 2.5-3.5 c/sec spike-wave discharges, more prominent over the posterior regions. The abnormality was suppressed on eye opening and replaced by delta activity and short duration spike-wave paroxysms. Mental activity, hyperventilation, and photic stimulation did not change the pattern. The same EEG pattern persisted during daytime sleep. This picture has lasted for 17 months without any associated epileptic manifestations or behavioural disturbances. Psychometric tests and CAT scan were normal.