Luigi Giuseppe Bongiovanni

Early and Late Intracortical Inhibition in Juvenile Myoclonic Epilepsy

Summary: Purpose: We investigated 15 patients with juvenile myoclonic epilepsy (JME) by subjecting them to single and paired transcranial magnetic stimulation to test the hypothesis that motor cortical inhibition may be abnormal in this form of benign epilepsy.

Eclamptic encephalopathy: imaging and pathogenetic considerations

Eclampsia is a rare condition peculiar to pregnant and puerperal women, characterized by clinical pre‐eclampsia (hypertension, proteinuria, edema) and generalized seizures. Three cases of eclamptic encephalopathy are reported: CT and MRI demonstrated transient abnormalities in the cortical and subcortical regions of the posterior areas of the brain ‐ namely, parietooccipital lobes ‐ associated with occasional involvement of basal ganglia and/or brainstem. Pathogenesis is still unclear. Strict similarity with the pathological findings characterizing hypertensive encephalopathy suggests that a focal impairment in cerebral autoregulation may be the cause of vasodilation and fluid extravasation leading to hydrostatic edema; selective involvement of posterior areas could be explained by their lesser degree of adrenergic innervation supporting circulatory autoregulation mechanisms.

Cortical excitability in patients after loading doses of lamotrigine: a study with magnetic brain stimulation.

Summary: Purpose: Transcranial magnetic stimulation (TMS) of the brain allows the pharmacologic effects of anti‐convulsant drugs (AEDs) on the excitability of motor cortico‐spinal pathways to be evaluated in patients with epilepsy and normal subjects. However, no study has yet documented the changes in motor excitability in patients treated with lamotrigine (LTG). We aimed to study the effects of loading doses of LTG on TMS recordings in patients with epilepsy at the beginning of their treatment.

Comparative Assessment of Peripheral Sympathetic Function by Postural Vasoconstriction Arteriolar Reflex and Sympathetic Skin Response in NIDDM Patients

PURPOSE The aim of the study was to compare peripheral sympathetic adrenergic and cholinergic nerve function in NIDDM (non-insulin-dependent diabetes mellitus) patients with various degrees of diabetic neuropathy and neuropathic foot ulceration. The parameters used were postural vasoconstriction arteriolar reflex (VAR) and sympathetic skin response (SSR), respectively. PATIENTS AND METHODS Forty-seven NIDDM patients were studied. No patients had clinically significant peripheral vascular disease. They were divided according to peripheral somatic neuropathy, assessed by clinical score and vibration perception threshold (VPT). Twenty-two patients showed no significant evidence of peripheral neuropathy and normal VPT (DN-); 15 had signs and symptoms of neuropathy and VPT alteration (DN+); 10 had diabetic neuropathy and foot ulceration (DNU). Twenty-two normal subjects were also examined as a control group. Resting arteriovenous shunt skin blood flow, measured using laser-Doppler flowmetry, and the VAR of the big toe on lowering the foot were studied. Sympathetic skin response was assessed by an EMG apparatus. Autonomic function was also investigated by using standard cardiovascular reflex tests. RESULTS Resting blood flow values were similar in the three NIDDM groups and in the control group. VAR to foot lowering was significantly impaired in all NIDDM groups by comparison with controls (72.8 +/- 2.1%, mean +/- SEM), this impairment being progressively more pronounced in DN- (58.8 +/- 2.3%, P < 0.001), DN+ (33.3 +/- 3.0%, P < 0.001 versus DN-) and DNU (8.6 +/- 2.7%, P < 0.001 versus DN+). Sympathetic skin response was assessed in 28 patients and was significantly impaired in DN-compared with the control group (2.53 +/- 0.04 versus 2.71 +/- 0.04 log mcV, P < 0.01). This impairment was severe in the DNU compared with the DN+ group (1.36 +/- 0.05 versus 2.26 +/- 0.04 log mcV, P < 0.005). A positive correlation was found between VAR values and SSR (P < 0.001), and these measurements were also closely correlated with several parameters of central autonomic and somatic neuropathy. CONCLUSION These results indicate that peripheral sympathetic adrenergic and cholinergic fibers simultaneously undergo early alterations in diabetic patients, even when there is no clinical neuropathy. Our data also show almost complete abolition of peripheral sympathetic activity in NIDDM patients with foot ulceration.

Motor Responses to Afferent Stimulation in Juvenile Myoclonic Epilepsy

Summary:  Purpose: To document whether the mechanisms responsible for myoclonic jerks in juvenile myoclonic epilepsy (JME) are similar to those causing other forms of myoclonus.

Cerebral perfusion alterations in epileptic patients during peri-ictal and post-ictal phase: PASL vs DSC-MRI

Non-invasive pulsed arterial spin labeling (PASL) MRI is a method to study brain perfusion that does not require the administration of a contrast agent, which makes it a valuable diagnostic tool as it reduces cost and side effects. The purpose of the present study was to establish the viability of PASL as an alternative to dynamic susceptibility contrast (DSC-MRI) and other perfusion imaging methods in characterizing changes in perfusion patterns caused by seizures in epileptic patients. We evaluated 19 patients with PASL. Of these, the 9 affected by high-frequency seizures were observed during the peri-ictal period (within 5hours since the last seizure), while the 10 patients affected by low-frequency seizures were observed in the post-ictal period. For comparison, 17/19 patients were also evaluated with DSC-MRI and CBF/CBV. PASL imaging showed focal vascular changes, which allowed the classification of patients in three categories: 8 patients characterized by increased perfusion, 4 patients with normal perfusion and 7 patients with decreased perfusion. PASL perfusion imaging findings were comparable to those obtained by DSC-MRI. Since PASL is a) sensitive to vascular alterations induced by epileptic seizures, b) comparable to DSC-MRI for detecting perfusion asymmetries, c) potentially capable of detecting time-related perfusion changes, it can be recommended for repeated evaluations, to identify the epileptic focus, and in follow-up and/or therapy-response assessment.

Sympathetic skin response asymmetry in early stage idiopathic Parkinson's disease

Simultaneous bilateral plantar sympathetic skin response (SSR) was studied in 25 patients with early stage idiopathic Parkinsons disease (IPD), characterized by monolateral motor involvement (Hoehn and Yahr, stage <2) and without clinical evidence of autonomic dysfunctions. Thirteen (mean age: 68.69 +/- 7.70, range 55-76) had extrapyramidal clinical signs only at the left body side, 12 (mean age 66.60 +/- 7.43, range 51-73) at the right body side. A group of 25 healthy, age-matched, subjects were also evaluated. To evoke the responses, trains of 10 electrical pulses were applied at different intensities and frequencies. Only intensities of stimulation > or = 5 times the sensory electrical threshold always assured bilateral plantar responses in all the examined subjects. Amplitude asymmetry between left and right responses was found only in the IPD patients (P < 0.05). The amplitude reduction corresponded to the motor affected side. No analogue latency variation was observed in any group. Independently from the peripheral or central origins of such phenomena, these findings suggest that simultaneous bilateral SSR amplitude evaluation could be useful, in early IPD patients, to demonstrate and to monitor the sympathetic cholinergic dysfunction, despite the lack of autonomic symptoms.

Continuous EEG–fMRI in patients with partial epilepsy and focal interictal slow-wave discharges on EEG.

PURPOSE To verify whether in patients with partial epilepsy and routine electroenecephalogram (EEG) showing focal interictal slow-wave discharges without spikes combined EEG-functional magnetic resonance imaging (fMRI) would localize the corresponding epileptogenic focus, thus providing reliable information on the epileptic source. METHODS Eight patients with partial epileptic seizures whose routine scalp EEG recordings on presentation showed focal interictal slow-wave activity underwent EEG-fMRI. EEG data were continuously recorded for 24 min (four concatenated sessions) from 18 scalp electrodes, while fMRI scans were simultaneously acquired with a 1.5-Tesla magnetic resonance imaging (MRI) scanner. After recording sessions and MRI artefact removal, EEG data were analyzed offline. We compared blood oxygen level-dependent (BOLD) signal changes on fMRI with EEG recordings obtained at rest and during activation (with and without focal interictal slow-wave discharges). RESULTS In all patients, when the EEG tracing showed the onset of focal slow-wave discharges on a few lateralized electrodes, BOLD-fMRI activation in the corresponding brain area significantly increased. We detected significant concordance between focal EEG interictal slow-wave discharges and focal BOLD activation on fMRI. In patients with lesional epilepsy, the epileptogenic area corresponded to the sites of increased focal BOLD signal. CONCLUSIONS Even in patients with partial epilepsy whose standard EEGs show focal interictal slow-wave discharges without spikes, EEG-fMRI can visualize related focal BOLD activation thus providing useful information for pre-surgical planning.

Value of tongue biting in the differential diagnosis between epileptic seizures and syncope

BACKGROUND Tongue biting (TB) may occur both in epileptic seizures and in syncope. A comprehensive search of the literature to determine the accuracy of this physical finding and its prevalence in epileptic seizures and syncope is still lacking. AIMS To undertake a systematic review and a meta-analysis of studies evaluating the prevalence of TB in patients with epileptic seizures and syncope, and to determine sensitivity, specificity and likelihood ratios (LR) of this physical finding. METHOD Studies comparing the prevalence of TB in epileptic seizures and syncope were systematically searched. Prevalence of TB was analyzed calculating odds ratio (OR) with 95% confidence intervals (CIs). Sensitivity, specificity, positive and negative likelihood ratio (pLR, nLR) of TB were determined for each study and for the pooled results. RESULTS Two studies (75 epilepsy patients and 98 subjects with syncope) were included. There was a significantly higher prevalence of TB in patients with epileptic seizures (OR 12.26; 95% CI 3.99-37.69). Pooled accuracy measures of TB for the diagnosis of epileptic seizures were: sensitivity 33%, specificity 96%, pLR 8.167 (95% CI 2.969-22.461) and nLR 0.695 (95% CI 0.589-0.82). CONCLUSIONS A pooled analysis of data from the literature shows that TB has great value in the differential diagnosis between epileptic seizures and syncope. Given a certain pre-test probability of seizures, the presence of TB greatly increases the chance that the patient had an epileptic seizure. Systematic reviews with pooled analyses (meta-analyses) of data from the literature allow an increase in statistical power and an improvement in precision, representing a useful tool to determine the accuracy of a certain physical finding in the differential diagnosis between seizures and other paroxysmal events.

A multimodal imaging approach to the evaluation of post-traumatic epilepsy

ObjectElectroencephalography-functional magnetic resonance imaging (EEG-fMRI) coregistration and high-density EEG (hdEEG) can be combined to map noninvasively abnormal brain activation elicited by epileptic processes. By combining noninvasive imaging techniques in a multimodal approach, we sought to investigate pathophysiological mechanisms underlying epileptic activity in seven patients with severe traumatic brain injury.Materials and methodsStandard EEG and fMRI data were acquired during a single scanning session. The EEG-fMRI data were analyzed using the general linear model and independent component analysis. Source localization of interictal epileptiform discharges (IEDs) was performed using 256-channel hdEEG. Blood oxygenation level dependent (BOLD) localizations were then compared to EEG source reconstruction.ResultsOn hdEEG, focal source localization was detected in all seven patients; in six out of seven it was concordant with the expected epileptic activity as defined by EEG data and clinical evaluation; and in four out of seven in whom IEDs were recorded, BOLD signal changes were observed. These activities were partially concordant with the source localization.ConclusionMultimodal integration of EEG-fMRI and hdEEG combining two different methods to localize the same epileptic foci appears to be a promising tool to noninvasively map abnormal brain activation in patients with post-traumatic brain injury.