Increased depressant effect of phenytoin sodium as compared to carbamazepine on cortical excitability: a transcranial magnetic evaluation

To evaluate the effect of monotherapy (phenytoin sodium (DPH) and carbamazepine (CBZ) on the threshold intensity (TI), cortical latency (CL), central conduction time (CCT), using transcranial magnetic stimulation (TMS). A single pulse transcranial magnetic stimulation was used for recording the motor-evoked potentials (MEP) from the thenar muscles of both hands, in 36 patients with well-controlled epilepsy on monotherapy, with normal EEG and imaging studies. The TI, CL, CCT and the MEP amplitude were recorded and compared with 20 healthy controls. The threshold intensity was significantly higher in patients on DPH, (P< 0.05) with a significant decrease in the MEP amplitude when compared with controls (P< 0.05). Anticonvulsants alter the excitability of human motor pathways in epileptic subjects. This effect differs among the drugs used; DPH had a greater depressant effect on the excitability than CBZ in the present study.     

Increased cortical excitability with longer duration of Parkinson's disease as evaluated by transcranial magnetic stimulation

Transcranial Magnetic Stimulation (TMS) was used to evaluate the cortical excitability and central motor pathways in Parkinson's disease (PD) and correlate with severity and duration of disease. 19 cases of PD and 13 controls were enrolled. The threshold intensity (TI), cortical latency (CL), central conduction time (CCT), motor evoked potential amplitude (MEP) obtained with TMS were correlated with Hoehn and Yahr and duration of disease. The threshold intensity (TI) was significantly lower in patients of PD than controls. The TI in patients with PD was 53.16-/+8.4% patients and 67.1-/+21.6% in controls (p<0.05). This strongly correlated with duration of disease, TI being lower in patients with disease duration more than 5 years. There was no difference in the other TMS parameters - CL, CCT, MEP between patients and controls. Our study revealed increased excitability in PD which was related to longer duration of disease.     

'Excitability changes of muscular responses to magnetic brain stimulation in patients with central motor disorders.

The 'excitability' and 'conductivity' of motor pathways during transcranial stimulation (TCS) have been investigated in 49 patients affected by multiple sclerosis (34), amyotrophic lateral sclerosis (7), spino-cerebellar ataxia (3), primary lateral sclerosis (4) and brain metastasis (1). Hyper-reflexia, spasticity and weakness were correlated with the central motor conduction time (CCT) and with the threshold intensity of TCS required to produce a motor evoked potential (MEP). MEPs to magnetic TCS were recorded from hand and foot muscles during relaxation, contraction and after tendon vibration. Thresholds and CCTs of the patients were compared with those of 30 healthy controls. Increased threshold was found in 37 out of 49 patients (75.5%). Prolongation of the CCT was found in 38 out of 63 clinically affected upper limbs (60.3%) and in 56 out of 77 clinically affected lower limbs (72.7%). Absent motor responses to maximal TCS were found in 20 out of 98 lower limbs (20.4%). Excluding ALS patients (in whom there was a lower threshold for MEP elicitation), a significant linear correlation was found between prolonged CCT and increased threshold. While MEPs with prolonged CCTs have elevated TCS threshold, it is important to note that an elevated threshold was found in 14 out of 49 patients (28.5%) despite unchanged CCT. Spasticity and/or hyper-reflexia were more frequently associated with increased threshold than with prolonged CCT, while weakness was correlated equally well with both these parameters. In this respect magnetic TCS proves to represent a new tool for the detection of abnormal 'excitability' of the central motor tracts.     

Cerebrospinal Fluid γ-Aminobutyric Acid Levels in Children with Different Types of Epilepsy: Effect of Anticonvulsant Treatment

The mean gamma-aminobutyric acid (GABA) level in lumbar CSF of 31 children with epilepsy was not significantly different from that of 41 age-matched controls. However, when the epileptic children were subdivided into untreated patients and patients treated with antiepileptic drugs, the medication-free subgroup had a significantly lower mean CSF GABA level than nonepileptic children. Patients controlled by anticonvulsant therapy had significantly higher CSF GABA levels than untreated epileptic patients. A more detailed analysis of the children taking antiepileptic medication indicated that the only drug that significantly increased GABA in CSF was valproic acid. Analysis of CSF data with respect to the seizure type of the patients showed that, compared with controls, significantly reduced average GABA levels were present in children with infantile spasms (mostly untreated) and unmedicated generalized tonic-clonic seizures, whereas treated children with generalized tonic-clonic seizures and patients with partial epilepsy (mostly treated) did not significantly differ from controls. The data provide further evidence that impairment of the central GABA system may be involved in human epilepsy.     

Transcranial electrical motor evoked potentials as a prognostic indicator for motor recovery in stroke patients.

Transcranial electrical motor evoked potentials (MEP) were examined in 33 patients within three days after stroke. Normal values for MEP and motor central conduction time (CCT) were obtained in 46 healthy controls whose MEPs were evaluated during slight voluntary muscle contraction and at rest. Two months later 23 patients were re-examined clinically and electrophysiologically. Motor function change was correlated with MEP results. Two months after stroke the patients with normal or prolonged CCT had an improved motor function compared with those with absent CCT. MEP may be a valuable prognostic indicator in the acute stage of paralytic stroke for recovery of motor function.     

Motor cortical thresholds and cortical silent periods in epilepsy.

We studied motor cortical thresholds (TIs) and cortical silent periods (SPs) evoked by transcranial magnetic stimulation (TMS) in 110 epileptic patients. Sixty-two had primary generalised, 48 had partial type seizures. Fifteen out 110 patients were analysed both before and after anticonvulsant medication. Our aims were to evaluate the TI levels and the duration of SPs in patients with epilepsy and to determine the reliability of TMS in patients with epilepsy. There was no negative effect of TMS on the clinical status and EEG findings in patients with epilepsy. TIs obtained from patients with partial epilepsy were higher than those obtained from both controls and primary epileptics. The duration of SP in patients with primary epileptics was more prolonged than those obtained from controls. There was no correlation between EEG lateralisation and both SP duration and TI values. In de novo patient group, SP duration was significantly prolonged after anticonvulsant medication. We concluded that TMS is a reliable electrophysiological investigation in patients with epilepsy. The analysis of SP duration may be an appropriate investigation in monitoring the effect of anticonvulsant medication on the cortical inhibitory activity.     

Computerized Analysis of EEG Background Activity in Epileptic Patients

Background activity was studied in 128 idiopathic epilepsy patients and 30 normal controls using EEG topography and t-statistic significance probability mapping (t-SPM). In epileptic patients, EEG background activity showed a marked increase in delta, theta, alpha 1, and beta 1, and a decrease in alpha 2 activity as compared with controls. Untreated epileptic patients had a significant increase in delta, theta, and alpha 1 as compared with controls. For epileptic patients treated with antiepileptic drugs (AEDs), the most marked slowing was observed in the polytherapy group, followed by the monotherapy group and then the untreated group. Among seizure types, patients with partial seizures (PS) tended to exhibit more slowing than patients with only generalized tonic-clonic seizures (GTC). Moreover, PS had a right-left asymmetry in alpha 2 and beta 1 activities. In a comparison of AEDs, patients receiving carbamazepine (CBZ) and phenobarbital (PB) showed no significant difference as compared with the untreated group. In contrast, patients receiving valproate (VPA) showed a decrease in slow and fast activities. EEG changes associated with each AED were different in GTC and PS. Patients receiving VPA for GTC showed a decrease in theta and beta 1 activities, but those with PS showed a decrease only in delta activity.     

Neurophysiological evaluation of the central nervous impulse propagation in patients with sensorimotor disturbances

Motor evoked potentials (MEPs) to transcranial stimulation (TCS) and somatosensory evoked potentials to median nerve stimulation (MN-SEPs) were examined in 74 patients affected by multiple sclerosis (MS = 49 cases), amyotrophic lateral sclerosis (ALS = 9 cases), cervical cord lesions (7 cases), Parkinson's disease (PD = 5 cases), Huntington's chorea (HC = 2 cases), Wilson's disease (WD = 1 case), subacute combined degeneration (SCD = 1 case). MN-SEPs were altered in 38% of arms in MS with a higher incidence in clinically affected than in clinically 'silent' arms (= 77.8% vs. 27.5%). MEP alterations were found in 54% of examined arms, mostly because of a prolongation of the motor CCT. This index was invariably altered in the affected arms, whilst it was involved in 40% of the 'silent' ones. Twelve out of 18 arms displayed abnormal MEPs in ALS. These were mainly due to an absent response, even if moderate motor CCT prolongation and 'giant' MEPs were also encountered. MN-SEPs were altered in 3/18 arms. By recording MEPs from proximal and distal upper limb muscles, cues on the level of abnormal propagation were obtained in patients suffering from 'focal' lesions of the spinal cord. Combining SEP records enhanced the diagnostic yield in this field. Both MEPs and SEPs were normal in patients with PD and HC, whilst abnormally prolonged CCTs were found in the case with WD. MEP and SEP recording revealed central propagation abnormalities coupled to a severe clinical picture of the peripheral nerve involvement (as in the case of SCD).     

The effects of carbamazepine, valproic acid and phenobarbital on the oxidative and antioxidative balance in epileptic children

BACKGROUND: Oxidative stress has been related in a wide variety of ways with nervous tissue. We studied the effect of antiepileptic monotherapy on serum level of total antioxidant capacity, lipid hydroperoxide, total peroxide, oxidative stress index, and individual serum antioxidants such as albumin, bilirubin and uric acid. PATIENTS AND METHODS: We studied 122 subjects including healthy controls, untreated epileptic patients and epileptic patients treated with valproic acid, carbamazepine or phenobarbital. Serum total antioxidant capacity was measured as an index of antioxidants, and total peroxide was measured as index of oxidative stress. The serum concentrations of uric acid, albumin, bilirubin and lipid hydroperoxide were monitored simultaneously. RESULTS: We found that serum total antioxidant capacity levels were significantly decreased in the untreated group compared with the controls. Serum total peroxide levels were markedly increased in the untreated and carbamazepine-treated groups compared to in the controls; and lipid hydroperoxide and oxidative stress index levels were significantly higher in the phenobarbital-treated group than in the controls. Uric acid concentrations were significantly lower in the valproic-acid-treated group than in the untreated group, and total bilirubin concentrations were higher in the untreated group than in the controls. CONCLUSION: Epileptic children exposed to oxidative stress and conventional antiepileptic drugs change the oxidative/antioxidative balance. The serum oxidant and antioxidant status of epileptic children with valproic acid monotherapy are better regulated compared with children with carbamazepine and phenobarbital monotherapy.     

Idiopathic Generalized Epilepsy: Magnetic Stimulation of Motor Cortex Time-Locked and Unlocked to 3–Hz Spike-and Wave Discharges

Summary: In 20 patients with idiopathic generalized epilepsy who showed typical 3-Hz spike-and-wave (SW) EEG complexes, we studied the corticospinal motor output with a transcranial electromagnetic stimulator. First we measured the corticospinal discharge threshold for both hemispheres in the patient group and compared it with that of 10 ageand sex-matched volunteers. Threshold was significantly higher in the patient group, regardless of whether subjects were treated with antiepileptic drugs (AEDs). In 4 patients with very frequent SW paroxysms, we were able to study motor evoked potential (MEP) changes time-locked to epileptic EEG transients. The EEG signal was recorded bipolarly (C3–P3, C4–P4) by scalp needle-electrodes. For a given stimulus intensity, we collected and measured MEPs occurring during the spike or the wave portion of the SW complexes. Data were compared with those of MEPs obtained time-locked to normal EEG segments. MEP size was significantly decreased when the cortical stimulus was time-locked to the wave component, and was decreased or unchanged when the stimulus was time-locked to the spike. Magnetic stimulation never produced remarkable side effects.     

Motor-evoked potentials in patients with diabetes mellitus type 1

BACKGROUND AND PURPOSE: The aim of the study was to assess the function of the central motor pathway in young patients with diabetes mellitus type 1 by use of transcranial and paravertebral magnetic stimulation. MATERIALS AND METHODS: MEPs were recorded in 68 young patients (25+/-5.69 years), with diabetes mellitus type 1, from muscles: abductor digiti minimi and abductor hallucis (AH). Central motor conduction time (CMCT) was calculated by subtracting cortical latency (CL) after transcranial stimulation from the motor nerve conduction time (MNCT) after paravertebral stimulation. The obtained results were compared with normative data from the group of 36 healthy volunteers, matched for age and height. Statistical comparison of CMCT between diabetic and control groups was performed. RESULTS: There were no significant differences between the diabetics and control means of CMCT. Also, we were unable to elicit the MEPs cortically from AH muscle in 19 (27.9%) of diabetic patients and only in 3 (8.3%) controls. CONCLUSION: CMCT is normal in patients below 40 years of age, in whom the MEPs after transcranial stimulation can be elicited. Lack of MEPs in lower limb muscles following transcranial stimulation in almost 30% of patients in the presence of MEPs in upper limbs may indirectly suggest the dysfunction of central motor conduction in those cases.     

Mutagenic Risk in Epileptic Patients Before and After Anticonvulsant Therapy

Therapy with anticonvulsant drugs has often been found to result in somatic chromosome aberrations in adult patients. There is also the possibility of epileptic fathers or mothers playing a role in the production of congenital malformations in their offspring. We have used the technique of sister chromatid exchange (SCE), a sensitive indicator of mutagenicity, to observe the mutagenic susceptibility in both male and female epileptic patients in different age groups prior to and after anticonvulsant therapy, and with respect to control. The frequency of SCE was significantly higher in all the age groups for treated and untreated cases compared with control. Between treated and untreated subjects in age group 26-50 years, a significantly higher SCE frequency was observed in the untreated patients (p less than 0.01). Similarly, untreated male patients showed a significantly higher SCE frequency (p less than 0.025) compared with treated male patients. Although the results of this study provide a general assessment of mutagenicity in epileptic patients that agrees with other studies and emphasizes the role of the disease in the higher occurrence of congenital malformation in their offspring, the importance of higher SCE frequency in untreated patients remains to be explained in further studies.     

Neuroleptic drug effects on cognitive function in schizophrenia

Neuropsychological test performance was compared in 37 neuroleptic treated DSM-III schizophrenic patients, 27 untreated schizophrenic patients, and 27 normal controls. Neuroleptic treated patients performed significantly less well than untreated patients at recalling a complex figure, at planning on a mazes test, and had poorer fine motor coordination. Controls and untreated patients performed equally well on these tests. The results were not altered in 16 neuroleptic treated patients who had been prescribed low doses of benztropine, nor 38 patients who reported prior substance abuse. Similar cognitive impairments are observed in Parkinson's disease and are associated with dopaminergic antagonist drugs in schizophrenics. Therefore, they do not comprise part of the Schizophrenic Deficit State. Two tests were better performed by controls than patients. Reaction time was slower and more variable in both treated and untreated patient groups than controls. The recall of paraphrased passages was significantly poorer in both patient groups than controls, a finding that is robust in subgroups matched for IQ. Neuroleptic treatment was associated with significantly better performance on this test.     

Neurophysiological evaluation of vigilance in epileptic patients on monotherapy with lamotrigine.

OBJECTIVE: Limited research has focused to date on daytime sleepiness in epileptic patients treated with either conventional or newer antiepileptic drugs. We evaluated the level of vigilance in 15 consecutive, newly diagnosed and never medicated adult epileptic patients, receiving initial monotherapy with lamotrigine (LTG). METHODS: Patients underwent the Multiple Sleep Latency Test (MSLT), visual reaction times (VRT) and Stanford Sleepiness Scale (SSS) on two separate occasions, i.e. before and 2 months after LTG treatment. A group of 15 age-matched healthy volunteers was taken as control. RESULTS: At baseline, mean sleep latencies on the MSLT were comparable in epileptic patients and in controls. In patients, 2 months after monotherapy with LTG 200 mg/day, MSLT scores did not significantly change as compared with pre-treatment values. Accordingly, subjective evaluation of vigilance by the SSS and psychomotor performance by VRT were superimposable in controls and in untreated patients, and did not change in patients after LTG treatment. CONCLUSIONS: These results suggest that in adult, newly diagnosed epileptic patients initial monotherapy with LTG does not impair vigilance.     

Cortico-motor excitability of the lower limb motor representation: a comparative study in Parkinson's disease and healthy controls.

OBJECTIVE: To compare indices of cortico-motor excitability derived from transcranial magnetic stimulation (TMS) of the lower limb motor representation in patients with Parkinson's diseases (PD) and healthy controls. METHODS: The cortico-motor excitability of the lower limb motor area was studied both at rest (motor threshold, amplitude of motor evoked potentials (MEPs)) and during active contraction of the quadriceps (Quad) muscle (MEPs facilitation and silent period) in 10 PD patients (11 legs) and 11 healthy controls using single pulse TMS. RESULTS: At rest, the motor threshold was found to be significantly lower and the amplitude of MEPs larger in patients than in controls. During active knee contraction, patients produced lower levels of MEP facilitation with respect to baseline values and the silent period was lengthened in comparison to controls. CONCLUSIONS: The present results provide further evidence from the lower limb motor area that enhanced cortico-spinal excitability is an important feature in the pathophysiology of PD.     

GABA levels in cerebrospinal fluid of patients with epilepsy

The lumbar cerebrospinal fluid (CSF) gamma-aminobutyric acid (GABA) levels were measured in 27 patients with epilepsy, another three epileptic patients with status epilepticus and three epileptic patients with chronic cerebellar ataxia. The mean lumbar CSF GABA levels of the 27 patients with epilepsy were not significantly different from those of normal controls. Six of these 27 patients who had daily partial complex and partial motor seizures showed significantly low CSF GABA levels as did the six other patients, three each with status epilepticus and chronic cerebellar ataxia. These findings suggest that some epileptic patients have impaired brain GABAergic neurons.     

抗癫痫药物对癫痫患者甲状腺激素水平影响的研究

目的 研究癫痫患者甲状腺激素水平和抗癫痫药物对其影响以及与疗效之间的关系。方法 测定已确诊的45例未服用过抗癫痫药物的癫痫患者血清甲状腺激素水平并与30例健康对照组进行比较。再经卡马西平、苯妥英钠、丙戊酸钠三种抗癫痫药物分组单药治疗3个月、6个月、年后观察甲状腺激素水平的变化及与疗效之间的关系。结果 未服用抗癫痫药物的新诊断癫痫患者游离甲状腺素（FT4）水平显著低于健康对照组,经苯妥英钠、卡马西平分别治疗3个月、6个月、1年后T4、FT4、FT3显著低于治疗前水平,TSH无显著性变化。经丙戊酸钠治疗后的不同时间段各甲状腺激素水平与治疗前比较无显著性差异（P＞0．05）。甲状腺激素水平的变化与化疗效之间似无相关性。结论 癫痫的反复发作虽未经抗癫痫药物治疗已存在FT4水平的降低。苯妥英钠、卡马西平可明显造成癫痫患者的亚临床甲状腺功能降低（T4、FT4、FT3下降）,丙戊酸钠对患者甲状腺激素水平无显著影响。甲状腺激素水平的变化与疗效之间无相关性。     

GABA Levels in Cerebrospinal Fluid of Patients with Epilepsy

Abstract: The lumbar cerebrospinal fluid (CSF) γ-aminobutyric acid (GABA) levels were measured in 27 patients with epilepsy, another three epileptic patients with status epilepticus and three epileptic patients with chronic cerebellar ataxia. The mean lumbar CSF GABA levels of the 27 patients with epilepsy were not significantly different from those of normal controls. Six of these 27 patients who had daily partial complex and partial motor seizures showed significantly low CSF GABA levels as did the six other patients, three each with status epilepticus and chronic cerebellar ataxia. These findings suggest that some epileptic patients have impaired brain GABAergic neurons.     

Dysfunction of transcallosally mediated motor inhibition and callosal morphology in patients with schizophrenia

OBJECTIVE: In order to assess the functional integrity of motor pathways through the corpus callosum (CC) in patients with schizophrenia transcallosally mediated inhibition (TI) of voluntary tonic EMG activity of first dorsal interosseus muscle following ipsilateral focal transcranial magnetic stimulation (fTMS) was investigated. In addition thickness and length of CC were calculated. METHOD: Twelve patients suffering from schizophrenia and 12 healthy controls were investigated. CC morphology was measured in mid-sagittal MRI-slices. Latency and duration of TI were calculated. RESULTS: In schizophrenics the duration of TI was significantly prolonged, whereas latencies were not. In addition, a lack of TI was found unilaterally in three patients. Measurements of CC revealed a significantly reduction of the length and thickness in the anterior part of CC in patients. CONCLUSION: These findings indicate that measurement of TI could be used to detect clinical silent affection of transcallosal motor pathways in schizophrenics. The effect of neuroleptic drugs has to be explored.     

Monoamine metabolites in the CSF of epileptic patients.

To assess the possible role of amine neurotransmitters in human epilepsy, we measured metabolites of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), dopamine (homovanillic acid [HVA]), and norepinephrine (3-methoxy-4-hydroxyphenylethylene glycol [MHPG]) in the lumbar cerebrospinal fluid (CSF) of patients with partial complex seizures and in neurologic controls. Untreated epileptic patients had lower concentrations of 5-HIAA and HVA in the lumbar CSF than the controls, but the differences were not statistically significant. Among epileptic patients receiving effective antiepileptic drug treatment, the HVA concentration was within the control range. Mean MHPG concentrations were similar in patients and controls. From the epileptic patients whose CSF was obtained at pneumoencephalography we obtained a second sample of CSF that was originally in the basal cisterns. No significant differences between treated and untreated patients were found for any of the three metabolites. The concentrations of HVA and 5-HIAA were higher in cisternal than in lumbar CSF, but there was no such gradient for MHPG.