Thalamic and limbic involvement in the mechanism of action of vagus nerve stimulation, a SPECT study.

PURPOSE: To unravel the mechanism of action of neurostimulation as a treatment for seizures, functional neuroimaging tools allow minimally invasive research in humans. We performed single-photon emission computed tomography (SPECT) in patients with epilepsy, treated with vagus nerve stimulation (VNS). Changes in regional cerebral blood flow (rCBF) at the time of initial stimulation as well as after chronic treatment were correlated with long-term clinical efficacy. METHODS: In this pilot study, 27 patients (14 female and 13 male) who were treated with VNS at Ghent University Hospital for refractory epilepsy underwent a (99m)Tc-ECD (ethyl cystein dimer) SPECT activation study at the time the first stimulation train was administered. 12 patients underwent an additional (99m)Tc-ECD SPECT activation study 6 months later. Image acquisition was performed on a high-resolution triple-headed gamma camera. Significant rCBF changes were correlated with prospectively assessed clinical efficacy data. RESULTS: Significant rCBF changes were found in the thalamus, the hippocampus and the parahippocampal gyrus. Acute limbic hyper-perfusion and chronic thalamic hypo-perfusion correlate with positive clinical efficacy. CONCLUSIONS: Acute and chronic electrical stimulation of the vagus nerve induces rCBF changes that can be measured by SPECT on a group-basis. The thalamus and the limbic system are thought to play a key role in the mechanism of action of VNS.

Chronic levetiracetam treatment early in life decreases epileptiform events in young GAERS, but does not prevent the expression of spike and wave discharges during adulthood.

PURPOSE: In Genetic Absence Epilepsy Rats from Strasbourg (GAERS), age-related absence seizures start to appear from postnatal day (PN) 30 concomitant with 'spike and wave discharges' (SWDs) appearing on cortical EEG recordings. The aim of this study was to investigate the effect of early chronic levetiracetam (LEV) treatment on the development of SWDs in young and adult GAERS. METHODS: From PN 23 until PN 60, LEV (54 mg/kg, i.p.) was administered once daily to GAERS (n=8), while control GAERS (n=7) received saline (0.9% NaCl, i.p.). All animals were implanted with four epidural EEG electrodes at PN 51. EEG was recorded for 3h daily, during the last 4 days of the treatment (PN 57-PN 60) and during 4 additional days after treatment had been terminated (PN 61-PN 64). The animals were monitored again at the age of 4 months (PN 120-PN 124), about 2 months after the last administration of LEV. RESULTS: During treatment, epileptiform events in the LEV group were significantly reduced (62%, P<0.05) in comparison with the control group. During the following 4 days, epileptiform events were reduced in the LEV group, with an average difference of 53% (P=0.064). Once the animals had reached adult age, there was no difference in epileptiform events between the LEV group and controls. CONCLUSION: In this study, chronic LEV administration induced a reduction in epileptiform events in young GAERS. This effect persisted to some extent after treatment cessation (PN 61-PN 64), which might indicate a slowing down of epileptogenic processes. However, at the age of 4 months all animals revealed a similar expression of epileptiform discharges.

Migraine-related vertigo: towards a distinctive entity.

Both migraine and vertigo are common complaints. Although they may coincide by chance, there is growing evidence for a clinical entity of recurrent vestibular symptoms related to migraine. This syndrome implies a possible causal relationship although the pathophysiology of migraine-related vertigo has not been fully elucidated. A migrainous aseptic inflammation is thought to create a central sensitivity that spreads from the trigeminal to the vestibular system. Diagnostic criteria for migraine-related vertigo are proposed. Treatment is based on anti-vertiginous drugs for acute interventions and prophylactic measures as are taken for migraine headaches. Multicenter, prospective controlled studies are highly warranted.

Statistical parametric mapping of (99m)Tc-ECD SPECT in idiopathic Parkinson's disease and multiple system atrophy with predominant parkinsonian features: correlation with clinical parameters.

UNLABELLED: Statistical parametric mapping was performed to investigate differences in regional cerebral blood flow (rCBF) between patients with idiopathic Parkinson's disease (IPD), patients with multiple system atrophy (MSA), and healthy volunteers. In addition, a voxel-based covariance analysis was performed with disease-specific parameters and clinical patient data such as disease duration, medication, and clinical subscores. METHODS: For this purpose, (99m)Tc-ethylcysteine dimer (ECD) SPECT was performed on 81 IPD patients (50 men, 31 women; age, 62.6 +/- 10.2 y), 15 MSA patients (9 men, 6 women; age, 61.5 +/- 9.2 y), and 44 age- and sex-matched healthy volunteers (27 men, 17 women; age, 59.2 +/- 11.9 y). RESULTS: Significant hypoperfusion was observed in IPD compared with healthy subjects in a symmetric subcortical-cortical network including the basal ganglia, thalami, prefrontal and lateral frontal cortex, and parietooccipital cortex (voxel P value P(height) < 0.001, corrected for multiple comparisons). For MSA, only symmetric hypoperfusion was seen in the putamen and thalamus with respect to healthy subjects and to IPD (P(height) < 0.01, corrected). Prolonged disease duration or higher Hoehn and Yahr stage results in hypoperfusion of the posterior associative cortex. There is a negative correlation between perfusion of the caudate heads and limbic system and the standardized dosage of dopamine agonists in the patients with PD, whereas for MSA a bilateral decrease in putamen activity was noted (P(height) < 0.001, uncorrected). Cognitive performance was positively correlated with limbic perfusion and inversely correlated with posterior associative cortical areas, but not with prefrontal regions. CONCLUSION: Voxel-based analysis of (99m)Tc-ECD perfusion SPECT shows detailed differences between IPD and MSA, which may be of use in the differentiation of both disease entities, and is able to elucidate cerebral perfusion correlates of disease severity, dopamine agonist medication, and cognitive performance.

Enterocolitis: an adverse event in refractory epilepsy patients treated with levetiracetam?

INTRODUCTION: Levetiracetam (LEV) is a recently marketed novel anti-epileptic drug with a promising efficacy and safety profile. In this report we describe two patients who presented with enterocolitis and discuss the possible relationship with concurrent LEV intake. PATIENTS: In two patients. LEV was initiated to control refractory complex partial seizures (CPS). The first patient was treated with 1500 mg/day and complained of abdominal pain and weight loss 6 months later. Internal examination and colonoscopy revealed a punctate colitis. The second patient presented with bloody stool 1 month after LEV initiation. Colonoscopy showed punctate colitis. In both patients gastrointestinal symptoms disappeared following tapering of LEV. DISCUSSION: There are no reports in the literature describing colitis related to LEV intake. Three possible mechanisms of action are discussed. Colitis may be part of a hypersensitivity syndrome caused by LEV. Pharmacodynamic interactions with other anti-epileptic drugs, for example, carbamazepine may play a role. A haematological adverse event is another possibility since piracetam, a related molecule, has a known impact on erythrocytes and platelets. CONCLUSION: The close temporal relationship between initiation of LEV intake, symptomatic colitis and clinical improvement following LEV tapering, suggests that colitis may be a possible and previously undescribed adverse effect of LEV.

Anatomically standardised 99mTc-ECD brain perfusion SPET allows accurate differentiation between healthy volunteers, multiple system atrophy and idiopathic Parkinson's disease.

The clinical differentiation between typical idiopathic Parkinson's disease (IPD) and atypical parkinsonian disorders such as multiple system atrophy (MSA) is complicated by the presence of signs and symptoms common to both forms. The goal of this study was to re-evaluate the contribution of brain perfusion single-photon emission tomography (SPET) with anatomical standardisation and automated analysis in the differentiation of IPD and MSA. This was achieved by discriminant analysis in comparison with a large set of age- and gender-matched healthy volunteers. Technetium-99m ethyl cysteinate dimer SPET was performed on 140 subjects: 81 IPD patients (age 62.6+/-10.2 years; disease duration 11.0+/-6.4 years; 50 males/31 females), 15 MSA patients (61.5+/-9.2 years; disease duration 3.0+/-2.2 years; 9 males/6 females) and 44 age- and gender-matched healthy volunteers (age 59.2+/-11.9 years; 27 males/17 females). Patients were matched for severity (Hoehn and Yahr stage). Automated predefined volume of interest (VOI) analysis was carried out after anatomical standardisation. Stepwise discriminant analysis with cross-validation using the leave-one-out method was used to determine the subgroup of variables giving the highest accuracy for this differential diagnosis. Between MSA and IPD, the only regions with highly significant differences in uptake after Bonferroni correction were the putamen VOIs. Comparing MSA versus normals and IPD, with putamen VOI values as discriminating variables, cross-validated performance showed correct classification of MSA patients with a sensitivity of 73.3%, a specificity of 84% and an accuracy of 83.6%. Additional input from the right caudate head and the left prefrontal and left mesial temporal cortex allowed 100% discrimination even after cross-validation. Discrimination between the IPD group alone and healthy volunteers was accurate in 94% of the cases after cross-validation, with a sensitivity of 91.4% and a specificity of 100%. The three-group classification (MSA, IPD and healthy volunteers) resulted in an overall accuracy of 86% post hoc, with 98% of normals, 78% of IPD and 93% of MSA correctly classified. These values were slightly lower after cross-validation: 96% for healthy volunteers, 77% for IPD and 67% for MSA. In conclusion, using age- and gender-matched healthy volunteer data and anatomical standardisation, it is possible to differentiate between IPD and MSA with high discriminating power in clinically relevant circumstances.