Inter-relationships between DNA damage, ascorbic acid and glycaemic control in Type 2 diabetes mellitus.

AIMS: The onset of complications in Type 2 diabetes mellitus (DM) patients cannot be predicted in individuals. Evidence suggests a link between complications and hyperglycaemia, oxidative stress and antioxidants, but causality is unclear. This study investigated baseline (entry) fasting plasma ascorbic acid, lymphocytic DNA damage and glycaemic control in Type 2 DM as part of a long-term study, the aim of which is to explore a biomarker profiling approach to identify and improve outcome in high-risk subjects. METHODS: A cross-sectional study, in which DNA damage, glycated haemoglobin (HbA(1c)), fasting plasma glucose (FPG) and ascorbic acid (AA) were measured on fasting blood samples collected from 427 Type 2 DM subjects. RESULTS: DNA damage was significantly (P < 0.0001) and directly correlated to both FPG (r = 0.540) and HbA(1c) (r = 0.282), and was significantly (P < 0.0001), independently and inversely correlated to plasma AA (r = -0.449). In those subjects with both poor glycaemic control and low AA (< 48 microm, the overall mean value for the study group), DNA damage was significantly (P < 0.005) higher compared with those subjects with a similar degree of hyperglycaemia but with AA above the mean. CONCLUSIONS: The novel finding of a significant inverse relationship between plasma AA and DNA damage in Type 2 DM indicates that poorly controlled diabetic subjects might benefit from increased dietary vitamin C. The data also have important implications for biomarker profiling to identify those subjects who might benefit most from intensive therapy. Longer-term follow-up is underway.

Magnetoencephalographic yield of interictal spikes in temporal lobe epilepsy. Comparison with scalp EEG recordings.

To compare magnetoencephalography (MEG) with scalp electroencephalography (EEG) in the detection of interictal spikes in temporal lobe epilepsy (TLE), we simultaneously recorded MEG and scalp EEG with a whole-scalp neuromagnetometer in 46 TLE patients. We visually searched interictal spikes on MEG and EEG channels and classified them into three types according to their presentation on MEG alone (M-spikes), EEG alone (E-spikes), or concomitantly on both modalities (M/E-spikes). The M-spikes and M/E-spikes were localized with MEG equivalent current dipole modeling. We analyzed the relative contribution of MEG and EEG in the overall yield of spike detection and also compared M-spikes with M/E-spikes in terms of dipole locations and strengths. During the 30- to 40-min MEG recordings, interictal spikes were obtained in 36 (78.3%) of the 46 patients. Among the 36 patients, most spikes were M/E-spikes (68.3%), some were M-spikes (22.1%), and some were E-spikes (9.7%). In comparison with EEG, MEG gave better spike yield in patients with lateral TLE. Sources of M/E- and M-spikes were situated in the same anatomical regions, whereas the average dipole strength was larger for M/E- than M-spikes. In conclusion, some interictal spikes appeared selectively on either MEG or EEG channels in TLE patients although more spikes were simultaneously identified on both modalities. Thus, simultaneous MEG and EEG recordings help to enhance spike detection. Identification of M-spikes would offer important localization of irritative foci, especially in patients with lateral TLE.

Magnetoencephalographic study of rhythmic mid-temporal discharges in non-epileptic and epileptic patients.

To evaluate the source location and clinical significance of rhythmic mid-temporal theta discharges (RMTD) by MEG in non-epileptic and epileptic patients, we conducted simultaneous MEG and EEG recordings with a whole-scalp 306-channel neuromagnetometer in three patients: one with right temporal lobe epilepsy (TLE), one with right frontal lobe epilepsy (FLE), and one with tension headache. We visually detected the RMTD activity and interictal spikes, and then localised their generators by MEG source modelling. We repeated MEG measurement 3 months after right anterior temporal lobectomy (ATL) in the TLE patient; 3 months after anticonvulsant medication in the FLE patient. In epileptic patients, RMTD activities were found during drowsiness over the left temporal channels of both MEG and EEG recordings, and their generators were localised to the left posterior inferior temporal region. In the patient with tension headache, RMTD was localised in the right inferior temporal area. When the epileptic patients became seizure free with disappearance of epileptic spikes, RMTD was still found over the left temporal channels. Besides, some bursts of RMTD appeared also in the right temporal channels in our TLE patient after ATL. Our results indicate that the source of RMTD activity is located in the fissural cortex of the posterior inferior temporal region. As a physiologic rhythm related to dampened vigilance, RMTD has no direct relation to epileptogenic activity.

Lateralizing value of early head turning and ictal dystonia in temporal lobe seizures: a video-EEG study.

To investigate early head turning, we retrospectively studied videotapes of 262 seizures from 82 patients who were seizure free after temporal lobectomy. Early head movements were arbitrarily classified into non-tonic turning, tonic turning, and absence of turning. Among the 222 seizures which showed early head turning, 168 (75.7%) had non-tonic turning and 54 (24.3%) had tonic turning. The direction of the first head turning was ipsilateral to the epileptogenic foci in 132 (78.6%) seizures with non-tonic turning and in 35 (64.8%) seizures showing tonic head turning. The proportion of seizures with turning towards the ipsilateral side in the presence of tonic and non-tonic head turning were significantly different (P= 0.04). Seventy-four seizures (28.2%) evolved to secondary generalization, more frequently found in seizures with early head turning (P= 0.0015) and especially those showing tonic turning (P< 0.0001). The direction of head turning immediately preceding secondary generalization was contralateral to the lesion side in 53 seizures (82.8%). Dystonic upper limb posturing occurred in 86 seizures (32.8%), exclusively contralateral to the seizure focus, whereas 65 (75.6%) were associated with initial head turning ipsilateral to the focus. In summary, temporal lobe seizures with tonic head turning tends to secondarily generalize and the direction of head turning before secondarily generalized was contralateral to the seizure foci. Earlier in the seizures the direction of non-tonic head turning tends to be towards the epileptogenic hemisphere. In addition, dystonic posturing of the extremities is a significant lateralizing sign to the contralateral hemisphere in temporal lobe seizures.

Antiepileptic drug withdrawal in patients with temporal lobe epilepsy undergoing presurgical video-EEG monitoring.

PURPOSE: To investigate antiepileptic drug (AED) withdrawal during video-EEG monitoring in adult patients with temporal lobe epilepsy (TLE). METHODS: Between 1995 and 1997, 102 consecutive patients with refractory TLE were admitted to the epilepsy monitoring unit for presurgical evaluation. Patients were monitored with ongoing AEDs being rapidly decreased and discontinued in 4-6 days. The monitoring was continued until sufficient numbers of seizures were recorded. Serum AED levels were checked at admission and after the first complex partial seizure (CPS). RESULTS: In all, 89 patients had 429 CPSs (mean, 4.8 per patient), including 156 (36.4%) secondarily generalized. A mean of 153.8 h (16-451 h) was required for completing the monitoring in each patient. Forty-three (48.3%) patients experienced seizure clusters, and eight (9.0%) had generalized seizures that had never occurred or had been absent for years. However, none evolved to status epilepticus. Carbamazepine was the most commonly used AED in 71.9% of patients, followed by valproate and phenytoin. When the first CPS occurred, mean 77.2 h since the beginning of the monitoring, serum levels of these three AEDs were mostly subtherapeutic rather than minimal. CONCLUSIONS: Acute AED withdrawal effectively provoked seizures in TLE patients undergoing presurgical video-EEG monitoring. However, nearly 50% of patients had seizure clusters or secondarily generalized seizures. Serum AED levels were mostly subtherapeutic when the first CPS occurred.

Sequential MRI studies of a patient with complex partial status--a case report.

Complex partial status (CPS), the status epilepticus of complex partial seizure, is rarely seen in clinical practice. The clinical presentations of CPS are characterized by confusion, slowness in response, together with stereotypic or complex automatisms and occasional secondary generalization. The electroencephalographic findings of CPS reveal characteristic focal epileptiform activities of mesial temporal region. Magnetic resonance image (MRI) is the imaging method of choice for studying epilepsy, particularly when focus is in the temporal lobe. We report a 49-year-old female with diagnosis of viral encephalitis and clinical presentation of CPS. We present the sequential brain MRI findings at acute, subacute and chronic stages of this patient.

A double-blind, placebo-controlled study of topiramate in adult patients with refractory partial epilepsy.

PURPOSE: The efficacy and safety of topiramate (TPM) as adjunctive therapy in the treatment of adult Chinese patients with refractory partial epilepsy were investigated in a randomized, double-blind, placebo-controlled study. METHODS: A total of 46 patients who had four or more complex partial seizures with or without secondary generalization within an 8-week baseline phase were enrolled. Patients were assigned randomly to receive TPM (n = 23) or placebo (n = 23). TPM or placebo was titrated to target doses of 300 mg/d for 6 weeks and maintained at stabilized levels for another 8 weeks. Concomitant antiepileptic drugs remained at constant previous levels during the trial. RESULTS: In all, 41 patients completed the trial (TPM group, n = 20; placebo group, n = 21). The proportion of patients with a > or =50% reduction from baseline in complex partial seizures was 11 of 23 (47.8%) in the TPM group and 3 of 23 (13.0%) in the placebo group (p = 0.01). In addition, patients treated with TPM had significantly better investigator (p = 0.014) and patient (p = 0.0005) global assessment scores than patients in the placebo group. Adverse events were mostly mild and transient, with no significant differences between treatment groups. Two patients with TPM therapy complained of weight loss. Routine blood cell counts and other laboratory results showed no significant changes from baseline in either treatment group. CONCLUSIONS: TPM 300 mg/d is effective and well tolerated as treatment for refractory partial epilepsy in adults.

Epileptic seizures in a patient by immersing his right hand into hot water.

We report on a 22-year-old assistant cook, presenting with seizures evoked by immersing his right hand into hot water of 40-46 degrees C. His seizure pattern consisted of either simple partial seizures of a tingling sensation arising in the right hand and marching to the right shoulder or a similar attack evolving to a complex partial seizure. Video-EEG monitoring recorded habitual seizures originating from the left centro-temporo-parietal region, compatible with lesions seen on brain magnetic resonance imaging. He responded well to antiepileptic drug treatment and wearing gloves while working in the kitchen. In this patient, hot water of 40-46 degrees C could maximally stimulate skin warm thermoreceptors in the right hand whereby afferent impulses subsequently activated the epileptogenic focus, adjacent to or in the sensory cortex, and elicited seizures.

Ictal vomiting in partial seizures of temporal lobe origin.

We report 3 cases presenting ictal vomiting during partial seizures of temporal lobe origin. Two patients had complex partial seizures accompanying vomiting characteristics. Ictal vomiting occurred early in the course of the seizure when rhythmic discharges involved predominantly the left hemisphere, the language dominance hemisphere. The other patient had ictal vomiting in simple partial seizures which originated from the right temporal lobe or the language nondominant side. All 3 patients underwent anterior temporal lobectomy with promising outcomes. Pathologic diagnosis included hippocampal sclerosis in 2 patients and astrocytoma in 1 patient. In our patients, ictal vomiting does not lateralize temporal lobe epilepsy and is not specific to pathology.

Relationship between mesial temporal seizure focus and elevated serum prolactin in temporal lobe epilepsy.

We evaluated the relationship between mesial temporal seizure focus and serum prolactin (PRL) in patients before and after they underwent anterior temporal lobectomy (ATL) for medically intractable temporal lobe epilepsy (TLE). These patients had a confirmed unilateral epileptogenic focus in mesial temporal structures, a postictal rise in serum PRL 15 to 20 minutes after onset of complex partial seizures, and were refractory for more than 2 years to antiepileptic drugs. Presurgical interictal serum PRL levels were significantly elevated (16.47 +/- 0.85 ng/mL, n = 62) and declined after ATL to normal values (patients, 9.63 +/- 0.55 ng/mL, n = 54; normal subjects, 8.99 +/- 0.57 ng/mL, n = 52). Serial evaluations indicated that normalization was seen 3 months after surgery (9.42 +/- 1.22 ng/mL, n = 9). The postsurgical reduction in serum PRL was similar in men and women, in patients with epileptogenic focus on either side of mesial temporal structures, and was unaffected by antiepileptic medication. We conclude that PRL is elevated following seizures and that a seizure focus in mesial temporal structures may exert a sustained excitatory influence on PRL release in patients with medically intractable TLE.

Lamotrigine as add-on therapy in adult patients with refractory epilepsy.

BACKGROUND: Lamotrigine (LTG), one of the newly developed antiepileptic drugs, is efficacious in treating both partial and generalized seizure disorders including Lennox-Gastaut syndrome. Its effect as an add-on therapy was evaluated in 41 adult Chinese patients with refractory epilepsy. Five of the patients were Lennox-Gastaut syndrome and 36 patients had partial epilepsy. METHODS: We started LTG at 25 mg or 50 mg per day, respectively, depending on whether the patients were simultaneously taking valproate (VPA) or not. Then, LTG was increased in steps to maximal dosage (200 mg or 400 mg per day) within seven weeks and maintained for three months while pre-existing antiepileptic drugs remained unchanged. The efficacy of LTG therapy was assessed by the reduction in the overall seizure frequency. Hematological and biochemical parameters were checked before and after the trial in all patients. RESULTS: In all, 38 patients completed the trial. Twenty-two patients (57.9%) had > or = 50% reduction in seizure frequency, including four patients with Lennox-Gastaut syndrome and 18 patients with partial seizures. Among the patients with partial epilepsy, there was no significant difference in the efficacy of LTG whether the seizures were of temporal or extra-temporal origin (p = 0.577). In addition, the efficacy was not determined by the concomitant use of VPA (p = 0.189). Thirteen patients (31.7%) complained of adverse experiences, usually mild and dose-dependent. LTG had to be discontinued in only two patients (4.9%) due to severe side effects. The change in blood cell counts and biochemistry profiles was not significant in any of the patients. CONCLUSIONS: We conclude that LTG is an efficacious and safe antiepileptic drug for add-on therapy in adult patients with refractory epilepsy.

Unusual electroencephalographic findings in subacute sclerosing panencephalitis: a case report.

Subacute sclerosing panencephalitis (SSPE) is a rare infectious central nervous system (CNS) disease with a poor prognosis. We reported on the case of an adolescent girl with SSPE and characteristic periodic electroencephalographic (EEG) complexes. Her neurological deficits including generalized myoclonic seizures improved after intraventricular interferon (IFN) treatment. However, unusual EEG patterns consisting of bisynchronous occipital spikes preceding periodic complexes developed in follow-up EEGs.

Role of foramen ovale electrodes in presurgical evaluation of intractable complex partial seizures.

BACKGROUND: The value of intracranial electrodes such as depth electrodes and subdural grids for intracranial electroencephalographic (EEG) recording in patients with intractable epilepsies has been well recognized. A new technique, foramen ovale electrode (FOE) implantation, was first introduced by Wieser in 1984 for the lateralization of bilateral mesiotemporal lobe (MTL) onset of seizures. METHODS: Since October 1993, a multipolar, three-contact FOE has been used in 12 intractable epileptic patients for presurgical evaluation. The reasons for FOE implantation included bilateral MTL onset of seizures recorded by extracranial EEGs in nine patients, and extracranial EEG abnormalities inconsistent with the results of magnetic resonance imaging (MRI), positron emission tomogram (PET) or Wada test in three patients. Under general anesthesia, the FOEs were implanted according to the technique introduced by Kirschner, using Barters landmarks. RESULTS: After long-term telemetry recording with FOE, seven patients revealed clear onset of seizures originating from one side of the MTL and underwent anterior temporal lobectomy (ATL). Two patients had seizures of bilateral MTL onset. However, they received ATL due to predominantly unilateral interictal epileptiform discharges (EDs) and/or MRI and PET abnormalities. Seven (78%) of the nine operated patients became seizure-free after ATL. Three patients were considered not operable because two had multifocal onset of seizures and one had seizures with independent bilateral MTL onset. No serious complication resulted from implantation of FOE in this series. CONCLUSIONS: The semi-invasive technique of FOE is reliable for lateralization of bilateral MTL onset of seizures which are often not clearly recorded by extracranial EEGs. This procedure is safe and can be an alternative to invasive implantation of depth electrodes and subdural grids.

Ictal speech manifestations in temporal lobe epilepsy: a video-EEG study.

To evaluate ictal speech manifestations in complex partial seizures (C PS), we reviewed videotapes of 68 consecutive patients who underwent anterior temporal lobectomy (ATL) for treatment of intractable epilepsy in Taiwan. In all, 261 CPS were collected from their video-EEG (VEEG) recordings. Cerebral speech dominance was determined by intracarotid injection of sodium amobarbital (Wada test) in all cases. Ictal speech manifestations, classified as verbalization or vocalization, occurred in 32 patients (47.1%) with 96 seizures (36.8%). Ictal verbalization occurred in 10 patients (14.7%). Ictal vocalization was observed in 28 patients (41.2%); including 6 patients who also had ictal verbalization. Thirty-six patients (52.9%) had no seizure with ictal speech manifestations. Ictal verbalization had significant lateralization value: 90% of patients with this manifestation had seizure focus in the nondominant temporal lobe (p = 0.049). Seizures of patients with ictal vocalization were not more likely to arise from either temporal lobe. We also observed bilingual patients who exclusively spoke in their mother tongue (Taiwanese) rather than the acquired language (Mandarin) in 72.2% of seizures with verbalization. This finding is significant and contrary to a commonly held notion that the acquired language is used in seizures associated with speech behaviors.

Startle epilepsy presenting as drop attacks: a case report.

A case of startle epilepsy, induced by an unexpected touch on the left shoulder of a 3.5 year old boy, was investigated. The startle epilepsy manifested as an atonic drop attack. Neurological examination revealed a mild hemiparesis on the left side. Computed tomography (CT) scanning demonstrated an enhancement over the right parieto-frontal region, suggesting a hemangioma. Interictal electroencephalography (EEG) showed diffuse slowing and asymmetry of background activities with lower amplitude over the right centro-parieto-temporal region. The ictal EEG showed a paroxysmal bilaterally synchronized high amplitude single spike followed by a few slow waves lasting about one second over the bilateral centro-parieto-temporal regions. The seizure resisted anticonvulsant therapy and no significant responses were observed despite the use of combined therapy with valproic acid, phenytoin, primidone and clonazepam.

Hypothalamic hamartoma and gelastic epilepsy: a case report.

We studied a 6-year-old girl who presented with inappropriate and uncontrollable laughing episodes since age 3. Physical examination revealed a precocious puberty. The luteinizing hormone-releasing hormone (LH-RH) stimulation test showed an increased level of follicle-stimulating hormone (FSH). The interictal electroencephalogram (EEG) was normal. Several laughing fits were documented during video/EEG monitoring. During laughing, the ictal EEG showed a diffuse suppression of background rhythm, prominent over the left mesial temporal region. A mass lesion about 2 x 2 cm in size was found over the suprasellar cistern with a broad base attached to the hypothalamus, which was isodense on a computed tomography (CT) scan, isointense to gray matter on T1-weighted magnetic resonance (MR) imaging and hyperintense on T2-weighted MR imaging. The findings were suggestive of a hypothalamic hamartoma. A variety of anticonvulsants had been used with little or no response to the frequency or duration of the laughing seizures.

Frequency and characteristics of early seizures in Chinese acute stroke.

We retrospectively studied 1200 hospitalized acute strokes of all etiologies between July 1990 and August 1992. Ninety-six % of all strokes underwent computed tomography of the head. Fifty-eight percent of the 1200 strokes were brain infarction, 32% brain hemorrhage, 6% subarachnoid hemorrhage and 4% were other stroke subtypes. Thirty (2.5%) of all strokes suffered from early seizures. The incidences of early seizures were 2.8% in brain hemorrhage, 2.3% in brain infarction, 2.7% in subarachnoid hemorrhage and 2% in other stroke subtypes. Early seizures were documented in 6% of the patients with carotid territory cortical infarctions and 12% of the patients with lobar hemorrhage, whereas only 0.6% of the patients without carotid territory cortical infarctions and 0.6% of the patients without lobar hemorrhage were affected. Sixty-six percent of 30 early seizures were partial seizures, 24% generalized and status epilepticus were seen only in 10%. In conclusion, we found the early seizure incidence was 2.5% in Chinese patients hospitalized with acute strokes. There was no correlation between seizure occurrence and stroke subtypes. Early seizure developed significantly higher in acute stroke patients with lesions of the cortex than those patients without cortical involvement. The partial seizures were the most frequent type occurring in 66% of all acute stroke patients with early seizures.

Temporal lobectomy in adults with intractable epilepsy.

We report on 30 adult patients with intractable complex partial seizure (CPS) of the temporal lobe origin who received anterior temporal lobectomy. The average follow-up period was 41 months. The age of onset was younger and the duration of epilepsy was longer in the non-mass lesion group than in the mass lesion group. Postoperatively, 21 patients (70%) were seizure-free, four patients (13%) had only rare seizures (less than three attacks per year), three patients (10%) achieved a remarkable reduction (more than 50%) of seizure frequency, and two patients (7%) showed no worthwhile improvement. Based on our experience, anterior temporal lobectomy is an effective and safe procedure for adult patients with intractable CPS. For diagnosis, magnetic resonance imaging (MRI) yielded a higher sensitivity rate than computed tomography (CT), especially in the group without mass lesions. Positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) was superior to single photon emission computed tomography (SPECT) which had a relatively high false localization rate. With high resolution MRI and FDG-PET, localization of the epileptogenic zone was more accurate. A preresection electrocorticogram (ECoG) was used to confirm the epileptogenic focus during the operation. The residual spikes on the postresection ECoG did not necessarily predict a poor seizure control outcome after anterior temporal lobectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbamazepine drug interactions: the influence of concurrent drug therapy on serum concentrations of carbamazepine and its epoxide metabolite.

The influence of concurrent drug therapy (phenytoin, valproate, phenobarbital, primidone) on serum concentrations of total and free carbamazepine (CBZ) and its active metabolite carbamazepine-10, 11-epoxide (CBZ-E) in 135 epileptic patients was studied. Serum CBZ and CBZ-E levels were analyzed by high performance liquid chromatography, whereas serum levels of the anticonvulsants were determined by fluorescence polarization immunoassay. Ultrafiltration was used to separate the free drugs from the protein-bound drugs in serum. Patients were divided into five groups according to the medication they received. Linear regression analyses revealed that concurrent drug therapy affected the metabolic rate of CBZ and CBZ-E in various ways. In patients on CBZ monotherapy, 78.3% of CBZ and 52.4% of CBZ-E were bound to plasma proteins. The total serum CBZ and CBZ-E concentrations significantly correlated with their respective free levels in serum. Compared with the CBZ monotherapy group, patients receiving concurrent drug therapy showed higher CBZ clearance and had elevated CBZ-E/CBZ ratios. Although the decrease in the total CBZ concentration depended on the simultaneous phenytoin and valproate concentrations (p less than 0.05), the serum levels of phenobarbital and primidone appeared to have no significant influence on the CBZ concentration. Since great interindividual variations were found in the serum concentration after a given dose, routine monitoring of the CBZ and CBZ-E serum concentrations is essential in designing a safe and effective therapeutic regimen for epileptic patients, especially for those on polytherapy.