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PubMed2002

Dynamic susceptibility contrast (DSC) MRI and interictal epileptiform activity in cryptogenic partial epilepsy.

PURPOSE: To study the possible correlation between interictal EEG patterns and neuroradiologic data obtained by dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) in patients with partial epilepsy. METHODS: Seventeen subjects with cryptogenic partial epilepsy underwent long-term video-EEG monitoring and DSC-MRI in the same session. Ten patients had temporal lobe epilepsy (TLE) and seven, epilepsy of extratemporal origin (ExTE). MRI data were compared with EEG findings, and the accuracy of DSC-MRI was analyzed considering spiking rate (number of interictal epileptiform abnormalities, IEA/min) and type of epilepsy. RESULTS: DSC-MRI showed a relevant asymmetry in the frontal, temporal, and occipital regions in eight (47%) of 17 patients, consisting of a relative regional cerebral blood volume (rCBV) increase in these areas. Because this region corresponded to the interictal EEG focus (IEF) or to the hemisphere involved in the genesis of epileptic discharges in most patients showing a higher spiking rate, patients were classified in two groups: patients with high spiking rate (HSR, n = 9) and with low spiking rate (LSR, n = 8); the cutoff corresponded to the median value of IEA/min. The rCBV increase corresponded to the IEF or to the hemisphere involved in the genesis of epileptic discharges in seven (77.7%) of nine HSR patients. No patients with LSR showed significant asymmetries in rCBV pattern. In five of six patients with TLE-HSR (83.3%), DSC-MRI showed a relative rCBV increase concordant with IEF or hemisphere involved in the genesis of epileptic discharges; in patients with ExTE-HSR, the concordance was 66%. CONCLUSIONS: DSC-MRI is a noninvasive procedure that may provide useful additional information to lateralize and/or localize the IEF when interictal epileptiform activity is sufficiently elevated.

Adolescent↗
PubMed2003

Sexual dysfunction and sudden death in epileptic male EL mice: inheritance and prevention with the ketogenic diet.

PURPOSE: The EL mouse is an animal model for multifactorial idiopathic epilepsy. Although EL mice have been studied extensively for >45 years, the etiology of male sudden death and its relation to seizures have not been defined. Here we investigated the cause of EL male sudden death and its relation to epilepsy. METHODS: For histopathologic analysis, the terminally ill EL mice (n = 15) were killed, and the tissues were fixed. Blood chemical composition was compared between the terminally ill EL (n = 9) and the healthy age-matched EL (n = 17) and DDY (n = 11) males. To determine the effect of the ketogenic diet (KD) on sudden male death, young male EL mice (P30) were randomly separated into two groups that were fed ad libitum with either Agway lab chow (control n = 38) or with the KD (treated, n = 39) for 5 months. The genetic predisposition to sudden death was analyzed in the backcross generation (n = 106) of a cross between EL and the nonepileptic ABP strains. RESULTS: Sudden death coincided with the onset of seizures (70-80 days) and affected 94% of male EL mice by age 300 days. Urethral plugs were observed histologically in 13 of 15 longitudinally sectioned penises. Concentrations of blood urea nitrogen, creatinine, phosphorus, and calcium in the terminally ill mice were significantly elevated when compared with those of healthy animals. None of the mice treated with the KD experienced sudden death, whereas 15 (39%) of the untreated control mice died by age 5 months. The sudden death in male EL mice was inherited as an autosomal recessive sex-limited lethal trait. CONCLUSIONS: The cause of sudden death in male EL mice arises from abnormal ejaculation, which produces a urethral plug with consequent urinary retention and acute severe uremia. The coincident onset of seizures and sudden death in EL males suggests that a sexual dysfunction is associated with epilepsy in this model.

Animals↗
PubMed2003

Transient hypohidrosis induced by topiramate.

PURPOSE: Hypohidrosis during topiramate (TPM) treatment was recently reported in children. We describe an adult epilepsy patient who developed inability to sweat as well as heat intolerance while undergoing treatment with TPM. METHODS: To detect the site of the sweat block, patient underwent examination of sweat gland function, cardiovascular autonomic test, and body temperature rhythm determination. RESULTS: During TPM treatment, cardiovascular autonomic function and circadian rhythm of body core temperature were normal, whereas thermoregulatory sweat test (TST) showed anhydrosis. This adverse drug effect was quickly resolved after drug discontinuation. CONCLUSIONS: Because of normal cardiovascular autonomic function and central and peripheral thermoregulatory mechanisms, we hypothesize that hypohidrosis during TPM treatment could be due to a carbonic anhydrases (CA) block at the level of sweat gland.

Adult↗
PubMed2003

Effects of vagus nerve stimulation on sleep-related breathing in epilepsy patients.

PURPOSE: To describe the effects of vagus nerve stimulation (VNS) on sleep-related breathing in a sample of 16 epilepsy patients. METHODS: Sixteen adults with medically refractory epilepsy (nine men, seven women, ages 21-58 years) underwent baseline polysomnograms (PSGs). Three months after VNS therapy was initiated, PSGs were repeated. In addition, patient 7 had a study with esophageal pressure monitoring, and patient 1 had a continuous positive airway pressure (CPAP) trial. RESULTS: Baseline PSGs: One of 16 patients had an apnea-hypopnea index (AHI) >5 (6.8). Treatment PSGs: Five of 16 patients had treatment AHIs >5. Respiratory events were more frequent during periods with VNS activation (on-time) than without VNS activation (off-time; p = 0.016). Follow-up studies: Esophageal pressure monitoring in patient 7 showed crescendos in esophageal pressure during VNS activation, supporting an obstructive pattern. The CPAP trial of patient 1 showed that all respiratory events were associated with VNS stimulation at low CPAP levels. They were resolved at higher CPAP levels. CONCLUSIONS: Treatment with VNS affects respiration during sleep and should be used with care, particularly in patients with preexisting obstructive sleep apnea. The AHI after VNS treatment remained <5 in the majority of patients and was only mildly elevated (<12) in five patients. In one patient, CPAP resolved VNS-related respiratory events.

Adult↗
PubMed2001

Primary neonatal thalamic haemorrhage and epilepsy with continuous spike-wave during sleep: a longitudinal follow-up of a possible significant relation.

Epilepsy with continuous spike-waves during sleep was diagnosed in a child who suffered primary neonatal thalamic haemorrhage, and who was followed from birth to 17 years of age. Early cognitive development was normal. Acquired behavioural problems and cognitive stagnation could be directly related to the epilepsy and not to the initial lesion and posthaemorrhagic hydrocephalus. This case and long-term follow-up data on a few children who suffered primary neonatal thalamic haemorrhage suggest that epilepsy with continuous spike-waves during sleep can be a sequel. Disturbances of thalamocortical interactions could play a role in the still poorly understood syndrome of epilepsy with continuous spike-waves during sleep.

Adolescent↗
PubMed1999

Acute psychotic symptoms induced by topiramate.

The incidence of psychosis during clinical trials of topiramate was 0.8%, not significantly different from the rate for placebo or reported rates of psychosis in patients with refractory epilepsy. We observed psychotic symptoms in five patients soon after initiation of topiramate therapy. We performed a retrospective chart review of the first 80 patients who began on topiramate after approval for clinical use, between January and April 1997. Symptoms suggestive of psychosis, including hallucinations and delusions, were sought for analysis. Cognitive effects such as psychomotor slowing, confusion, and somnolence were not included. Five patients developed definite psychotic symptoms 2 to 46 days after beginning topiramate. Dosages at symptom onset were 50-400 mg/day. Symptoms included paranoid delusions in four patients and auditory hallucinations in three. Symptoms of psychosis and other psychiatric symptoms resolved quickly with discontinuation of topiramate in three patients, dose reduction from 300 to 200 mg/day in one and with inpatient treatment and neuroleptics in another. One patient had a history of auditory hallucinations, one of aggressive and suicidal thoughts, but three had no significant psychiatric history. Physicians should be aware of the possibility of psychotic symptoms, even in patients without a previous psychiatric history, when prescribing topiramate. Symptoms resolve quickly with discontinuation.

Adult↗
PubMed2000

A placebo-controlled, double-blind cross-over trial of adjunctive one month remacemide hydrochloride treatment in patients with refractory epilepsy.

The efficacy, safety and pharmacokinetics of adjunctive remacemide hydrochloride, a novel, low-affinity non-competitive NMDA receptor channel blocker, were investigated in 28 adult patients with refractory epilepsy. This was a randomized double-blind placebo-controlled cross-over study with five 4-week periods (baseline, treatment 1, washout, treatment 2, washout). Baseline median seizure frequency was reduced by 33% following adjunctive remacemide hydrochloride 150 mg q.i.d. for 4 weeks compared with placebo (P= 0.041). Seizure frequency was reduced by > or =50% in 30% of patients treated with remacemide hydrochloride compared with 9% on placebo. Mean plasma concentration of concomitant carbamazepine increased by approximately 15% following adjunctive remacemide hydrochloride. There was no correlation between increased plasma carbamazepine and reduced seizure frequency. Remacemide hydrochloride was well tolerated and only three patients withdrew due to adverse events (two remacemide hydrochloride, one placebo). Two patients died unexpectedly from their epilepsy during placebo treatment; both deaths were considered by the investigators to be unrelated to earlier remacemide hydrochloride treatment. This first specific efficacy investigation with adjunctive remacemide hydrochloride demonstrated anticonvulsant effects in patients with refractory epilepsy. More extensive clinical investigation is justified.

Acetamides↗
PubMed2000

Remacemide hydrochloride: a placebo-controlled, one month, double-blind assessment of its safety, tolerability and pharmacokinetics as adjunctive therapy in patients with epilepsy.

Forty patients (33 male, 7 female) with refractory epilepsy were randomized to receive ascending weekly doses of adjunctive remacemide hydrochloride in a b.i.d. or q.i.d. regimen, or placebo for up to 1 month. Assessments included routine physical examination and laboratory tests, recording of adverse events and seizure frequency, and neuropsychological tests. Trough plasma concentrations of concomitant AEDs were measured at weekly intervals. Trough plasma concentrations of remacemide and its desglycinyl metabolite were measured before each dose increment, and complete 24-hour profiles were measured at steady state following administration of 600 mg day(-1)and 1200 mg day(-1). A daily dose of 1200 mg was well tolerated in a q.i.d. regimen and up to 800 mg was well tolerated in a b.i.d. regimen. The most common adverse events were dizziness, diplopia, dyspepsia and abdominal pain. On some occasions, these were considered to be related to raised concentrations of concomitant AEDs. No adverse effects were observed on seizure frequency. Neuropsychology tests revealed no significant changes. Remacemide and the desglycinyl metabolite demonstrated dose proportional pharmacokinetics over the dose range tested.

Acetamides↗
PubMed2003

[Hemiatrophia faciei progressiva and tonic pupil].

BACKGROUND: A variety of infectious and autoimmune diseases are described in association with pupillotonia. To our knowledge there is only one report on pupillotonia associated with hemiatrophia faciei. We describe another patient with this rare association. The aim is to investigate possible associations between both diseases. PATIENT: A twenty five-year-old male patient with hemiatrophia faciei, epilepsy and pupillotonia of the right eye since his twelfth birthday was presented for the first time at the age of fourteen at our institution. The patient underwent a complete neurological and paediatric as well as otolaryngological investigation; there was also an investigation by the internist. The patient also underwent a complete serological investigation for infectious and autoimmune disorders as well as an investigation of the local and systemic vascular reactivity by the "Ocular cold pressor test". The follow-up time is 11 years. RESULTS: The clinical picture of our patient was an association of hemiatrophia faciei, epilepsy and pupillotonia. There was no evidence of a local hyperactivity of the sympathetic nervous system. The serological investigation showed an elevated value of antinuclear antibodies. CONCLUSIONS: We assume that in our case the pupillotonia as well as the hemiatrophia faciei and the epilepsy is caused by a common autoimmune factor. All other aetiologies for these three diseases were excluded. Furthermore, the occurrence of pupillotonia, hemiatrophia faciei and epilepsy was simultaneous.

Adolescent↗
PubMed2001

Suppressed kindling epileptogenesis in mice with ectopic overexpression of galanin.

The neuropeptide galanin has been shown to suppress epileptic seizures. In cortical and hippocampal areas, galanin is normally mainly expressed in noradrenergic afferents. We have generated a mouse overexpressing galanin in neurons under the platelet-derived growth factor B promoter. RIA and HPLC analysis revealed up to 8-fold higher levels of galanin in transgenic as compared with wild-type mice. Ectopic galanin overexpression was detected especially in dentate granule cells and hippocampal and cortical pyramidal neurons. Galanin-overexpressing mice showed retardation of seizure generalization during hippocampal kindling, a model for human complex partial epilepsy. The high levels of galanin in mossy fibers found in the transgenic mice were further increased after seizures. Frequency facilitation of field excitatory postsynaptic potentials, a form of short-term synaptic plasticity assessed in hippocampal slices, was reduced in mossy fiber-CA3 cell synapses of galanin-overexpressing mice, indicating suppressed glutamate release. This effect was reversed by application of the putative galanin receptor antagonist M35. These data provide evidence that ectopically overexpressed galanin can be released and dampen the development of epilepsy by means of receptor-mediated action, at least partly by reducing glutamate release from mossy fibers.

Animals↗
PubMed1993

Comparison and spacial correlation of interictal HMPAO-SPECT and FDG-PET in intractable temporal lobe epilepsy.

The respective contribution of interictal HMPAO-SPECT and FDG-PET to the imaging of the epileptogenic zone in intractable temporal lobe epilepsy is not known. Ten consecutive patients with drug resistant focal epilepsy of temporal lobe origin were studied with prolonged noninvasive video-EEG monitoring, magnetic resonance imaging, interictal FDG-PET and HMPAO-SPECT. Five patients demonstrated unitemporal and 5 patients bitemporal interictal and/or ictal EEG epileptiform abnormalities. We developed a 3-dimensional semiquantitative method for interpretation and comparison of FDG-PET and HMPAO-SPECT using a 15-compartment model of the temporal lobe. In all 5 patients with unilateral epileptogenicity, interictal hypometabolism and hypoperfusion were recorded on the side of the EEG abnormalities without discrepancy between PET and SPECT. The severity and the extent of focal abnormalities were consistently greater on PET than on SPECT, in agreement with previously well documented better 'sensitivity' of PET. Among the 5 patients with bitemporal epileptogenicity, results of SPECT and PET were convergent in only 2 cases. In this group, SPECT abnormalities appeared more profound but either SPECT or PET were not constantly correlated with the side of predominant EEG epileptogenicity. Abnormalities on PET and SPECT were more frequently limited to mesiobasal structures among cases with unilateral epileptogenicity and tended to involve neocortical structures in bitemporal cases. We conclude that interictal FDG-PET and HMPAO-SPECT provide the same type of information on the side of the epileptogenic zone in cases with clearly unilateral epileptogenicity, with abnormalities more intense and more extensive on PET.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1997

Human hippocampal AMPA and NMDA mRNA levels in temporal lobe epilepsy patients.

This study was designed to determine whether hippocampal neuronal AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and NMDA (N-methyl-D-aspartate) mRNA levels were differentially increased in temporal lobe epilepsy patients compared with those measured in control tissue from non-seizure autopsies. Hippocampi from hippocampal sclerosis patients (n = 28) and temporal mass lesion cases (n = 12) were compared with those from the autopsies (n = 4), and studied for AMPA GluR1-3 and NMDAR1-2 mRNAs using semi-quantitative in situ hybridization, along with fascia dentata and Ammon's horn neuron densities. Compared with the autopsies, and without correction for neuron counts, the mass lesion cases with neuron densities similar to autopsies showed: (i) significantly increased NMDAR2 hybridization densities for fascia dentata granule cells; (ii) increased AMPA GluR3 mRNA densities for Ammon's horn pyramids; and (iii) similar or numerically increased mRNAs for all other subunits and hippocampal subfields. Compared with the autopsies, hippocampal sclerosis cases with decreased neuron densities showed: (i) significantly decreased AMPA GluR1-2 and NMDAR1-2 hybridization densities for Ammon's horn pyramids and (ii) similar or numerically decreased mRNAs for all other subunits and subfields. However, correcting for changes in neuron densities showed that hippocampal sclerosis patients had increased AMPA and NMDA mRNA levels per neuron compared with autopsies, and in the CA2 resistant sector GluR2 mRNA levels were numerically greater than autopsies and mass lesion cases. Furthermore, relative to autopsies both sclerosis and mass lesion hippocampi showed that, in the stratum granulosum, the greatest mRNA increases were in AMPA GluR1 and NMDAR2 compared with the other mRNAs. In chronic temporal lobe seizure patients these results indicate that mass lesion and sclerosis cases show differential increases in hippocampal AMPA and NMDA mRNA levels per neuron compared with autopsies, especially for AMPA GluR1 and NMDAR2 in fascia dentata granule cells. These findings support the hypothesis that temporal lobe seizures are associated with increased ionotropic glutamate receptor mRNA levels and alterations in receptor subunit composition that probably contribute to neuronal hyperexcitability, synchronization and seizure generation.

Adult↗
PubMed1998

Influence of somatosensory input on paroxysmal activity in benign rolandic epilepsy with 'extreme somatosensory evoked potentials'.

We studied six patients suffering from benign rolandic epilepsy of childhood with central temporal spikes who presented so-called 'extreme somatosensory evoked potentials (SEPs)' following peripheral somatosensory stimulation. Stimuli were delivered to the fingers of one hand using both a triggered tendon hammer and low-intensity electrical stimulation. The electrical stimulation was delivered in sequences in different conditions (i.e. random order, 1, 3 and 10 Hz). Both tapping and electrical stimulation produced scalp evoked potentials in all subjects, characterized by a spike followed by a slow wave, similar in morphology and scalp distribution to the spontaneously occurring spikes. This paroxysmal activity was sensitive to stimulus rate; the number of evoked spikes was inversely related to the frequency of stimulation, being maximal at 1 Hz and disappearing at high frequencies (10 Hz). Spontaneous spikes disappeared during high-frequency stimulation but were present during low-frequency stimulation. Averaged SEPs at 3-Hz stimulation showed a late high-amplitude component, identical in morphology and distribution to the single evoked spike. We therefore conclude that, in these subjects, the so-called 'extreme SEPs' are evoked spikes and that evoked and spontaneous spikes share common cortical sensorimotor generators. The evidence that these generators can be influenced by afferent input provides important information regarding the functional mechanisms involved in modulating cortical excitability in benign rolandic epilepsy. Moreover, we suggest that peripheral electrical stimulation can be used as an additional activation test in this kind of epilepsy.

Age of Onset↗
PubMed1997

Seizures and schizophrenia.

Patients with epilepsy develop psychosis or schizophrenia at a rate exceeding that expected if the two disorders were independent. Similarly, patients with schizophrenia are more prone to seizures than the general population. This excess vulnerability may be conferred by the neuropathological substrate of schizophrenia itself or by the secondary effects of the illness, including exposure to psychotropic medications that lower the seizure threshold. Neuropathological investigations into the anatomic substrate of seizures in patients with psychosis or schizophrenia are consistent with the notion that there are neurodevelopmental abnormalities involving the mesial temporal lobe. Finally, clinical recommendations for the evaluation and pharmacological management of patients with schizophrenia who have one or more seizures are described.

Anticonvulsants↗
PubMed1991

Early and delayed I-123 IMP SPECT in epileptic patients with partial seizures and normal CT.

Forty-six epileptic patients with partial seizures and normal CT underwent 48 examinations of early and delayed SPECT using I-123 IMP in the interictal phase. One of them underwent a follow-up SPECT in a more stable state compared to the first SPECT. Another patient, with informed consent, underwent a follow-up SPECT in combination with pharmacologic activation with bemegride. Early SPECT was performed 30 minutes after an IMP injection and delayed SPECT 4 to 4 1/2 hours later. Temporal changes in uptake pattern were visually classified into six types and compared with known patterns of SPECT uptake in relation to ischemic, hyperemic, and other changes. These were also correlated with the amount of epileptic activity seen on the EEG.

Adolescent↗
PubMed1991

Quantitative assessment of cerebral blood flow in partial epilepsy using Xe-133 inhalation and SPECT.

The Xe-133 inhalation method was used to study rCBF in 12 patients with partial epilepsy during the interictal phase. SPECT images evidenced a focal CBF defect in 10 out of 12 patients, while quantitative analysis showed CBF abnormalities in all the patients. The focal CBF defect corresponded to the site of EEG abnormalities in nine patients. Additional low-flow areas beyond the EEG focus were found. Five patients presented a significant CBF decrease in the cerebellar hemisphere contralateral to the EEG focus. In five patients with unilateral EEG abnormalities, a CBF reduction was found in the contralateral cerebral hemisphere, mirror to the EEG focus. Finally, a widespread CBF decrease involving one or both cerebral hemispheres was observed in seven patients. Global and rCBF values were not correlated with age, duration of disease, frequency of seizures, secondary generalization, or specific therapy. SPECT may be useful in evaluating EEG epileptic foci, and quantitative SPECT allows the detection of functional effects of the epileptic focus on anatomically connected remote areas, probably due to the decrease of afferent inputs (diaschisis phenomenon).

Administration, Inhalation↗
PubMed1996

Redistribution on I-123 IMP SPECT in children and adolescents with partial seizures.

To evaluate the redistribution phenomenon on delayed I-123 IMP SPECT images of children and adolescents with partial seizures, 25 patients were selected and investigated in the interictal state. Early and delayed SPECT were performed 15-20 minutes and 5 hours, respectively, after I-123 IMP injection. Redistribution patterns were classified into three groups: 1) redistribution (RD) (-) group (n = 5), in which a low-uptake area on the early image persisted or was enlarged on the delayed image, 2) RD (+) group (n = 14), in which a low-uptake area on the early image changed to normal distribution on the delayed image, and 3) marked redistribution (MRD) (+) group (n = 6), In which a low-uptake area on the early image changed to a high uptake area on the delayed image. Among the patients who were followed for at least 12 months after the SPECT scans, the short-term clinical outcome tended to be good in the RD (+) group, intermediate in the MRD (+) group, and poor in the RD (-) group. These results of our preliminary comparative study indicate that the redistribution pattern of I-123 IMP may be related to the clinical aspects in patients with partial seizures and that it may play an important role in predicting their short-term clinical outcome.

Adolescent↗