Isabella Gilioli

Focal epilepsies in adult patients attending two epilepsy centers: classification of drug-resistance, assessment of risk factors, and usefulness of "new" antiepileptic drugs

Purpose:  To classify the grade of antiepileptic drug (AED) resistance in a cohort of patients with focal epilepsies, to recognize the risk factors for AED resistance, and to estimate the helpfulness of “new‐generation” AEDs.

Abnormal ERD/ERS but unaffected BOLD response in patients with Unverricht-Lundborg disease during index extension: a simultaneous EEG-fMRI study.

Electrophysiological studies indicate that Unverricht–Lundborg’s disease (ULD), the most common form of progressive myoclonus epilepsy in Europe, is characterized by the involvement of multiple cortical regions in degenerative changes that lead to enhanced excitation and deficient inhibition. We searched for the haemodynamic correlates of these effects using functional MRI (fMRI) of self-paced index extensions, a well-accepted task highlighting significant differences. EEG and fMRI were simultaneously acquired in 11 ULD patients and 16 controls, performing the index extensions individually (event-related task) as well as repetitively (block task). ERD/ERS analysis was performed for the EEG data in the alpha and beta bands. fMRI time-series were analyzed using the traditional general linear model, as well as with an assumption-free approach, and by means of cross-region correlations representing functional connectivity. In line with the existing literature, ULD patients had enhanced desynchronization in the alpha band and reduced post-movement synchronization in the beta band. By contrast, fMRI did not reveal any difference between the two groups; there were no activation intensity, latency or extent effects, no significant engagement of additional regions, and no changes to functional connectivity. We conclude that, so long as the patients are executing a task which does not induce obvious action myoclonus, the hypothesized abnormalities in pyramidal neuron and interneuron dynamics are relatively subtle, embodied in processes which are not metabolically-demanding and take place at a time-scale invisible to fMRI.

Cortical myoclonus in childhood and juvenile onset Huntington's disease.

OBJECTIVE Huntingtons disease (HD) appearing before the age of 20 years gives rise to a distinct phenotype with respect to the classical adult-onset disease. Here we describe three patients with childhood or juvenile HD onset presenting with action myoclonus. METHODS We performed jerk-locked back-averaging (JLBA), EEG-EMG coherence and phase analysis, long-loop reflexes (LLRs) and somatosensory evoked potentials (SSEPs). In one patient, we also performed transcranial magnetic stimulation (TMS) using single and paired pulses. RESULTS In all patients, the EMG features revealed movement activated quasi-rhythmic repetitive jerks; the JLBA and EEG-EMG spectral and coherence profiles indicated a cortical generator of the myoclonus. All patients had enhanced LLRs during muscle contraction, while none showed giant SSEPs. The evaluation of intracortical inhibition by means of TMS revealed reduced inhibition at short and long interstimulus intervals. CONCLUSIONS The rhythmic course of the action myoclonus and the characteristics of the LLRs suggest that myoclonus is due to a reverberant circuit involving the motor cortex, possibly because of an imbalance between excitatory and inhibitory cortical neuronal systems. SIGNIFICANCE Our findings suggest a similar cortical dysfunction in childhood and juvenile onset HD, which probably results from a specific circuitry impairment.

Electroclinical spectrum of the neuronal ceroid lipofuscinoses associated with CLN6 mutations

Objectives: To describe the clinical and neurophysiologic patterns of patients with neuronal ceroid lipofuscinoses associated with CLN6 mutations. Methods: We reviewed the features of 11 patients with different ages at onset. Results: Clinical disease onset occurred within the first decade of life in 8 patients and in the second and third decades in 3. All children presented with progressive cognitive regression associated with ataxia and pyramidal and extrapyramidal signs. Recurrent seizures, visual loss, and myoclonus were mostly reported after a delay from onset; 7 children were chairbound and had severe dementia less than 4 years from onset. One child, with onset at 8 years, had a milder course. Three patients with a teenage/adult onset presented with a classic progressive myoclonic epilepsy phenotype that was preceded by learning disability in one. The EEG background was slow close to disease onset in 7 children, and later showed severe attenuation; a photoparoxysmal response (PPR) was present in all. The 3 teenage/adult patients had normal EEG background and an intense PPR. Early attenuation of the electroretinogram was seen only in children with onset younger than 5.5 years. Somatosensory evoked potentials were extremely enlarged in all patients. Conclusions: In all patients, multifocal myoclonic jerks and seizures were a key feature, but myoclonic seizures were an early and prominent sign in the teenage/adult form only. Conversely, the childhood-onset form was characterized by initial and severe cognitive impairment coupled with electroretinogram and EEG attenuation. Cortical hyperexcitability, shown by the PPR and enlarged somatosensory evoked potentials, was a universal feature.

Hemodynamic and EEG Time-Courses During Unilateral Hand Movement in Patients with Cortical Myoclonus. An EEG-fMRI and EEG-TD-fNIRS Study

Multimodal human brain mapping has been proposed as an integrated approach capable of improving the recognition of the cortical correlates of specific neurological functions. We used simultaneous EEG-fMRI (functional magnetic resonance imaging) and EEG-TD-fNIRS (time domain functional near-infrared spectroscopy) recordings to compare different hemodynamic methods with changes in EEG in ten patients with progressive myoclonic epilepsy and 12 healthy controls. We evaluated O2Hb, HHb and Blood oxygen level-dependent (BOLD) changes and event-related desynchronization/synchronization (ERD/ERS) in the α and β bands of all of the subjects while they performed a simple motor task. The general linear model was used to obtain comparable fMRI and TD-fNIRS activation maps. We also analyzed cortical thickness in order to evaluate any structural changes. In the patients, the TD-NIRS and fMRI data significantly correlated and showed a significant lessening of the increase in O2Hb and the decrease in BOLD. The post-movement β rebound was minimal or absent in patients. Cortical thickness was moderately reduced in the motor area of the patients and correlated with the reduction in the hemodynamic signals. The fMRI and TD-NIRS results were consistent, significantly correlated and showed smaller hemodynamic changes in the patients. This finding may be partially attributable to mild cortical thickening. However, cortical hyperexcitability, which is known to generate myoclonic jerks and probably accounts for the lack of EEG β-ERS, did not reflect any increased energy requirement. We hypothesize that this is due to a loss of inhibitory neuronal components that typically fire at high frequencies.

EEG-informed fMRI analysis during a hand grip task: estimating the relationship between EEG rhythms and the BOLD signal

In the last decade, an increasing interest has arisen in investigating the relationship between the electrophysiological and hemodynamic measurements of brain activity, such as EEG and (BOLD) fMRI. In particular, changes in BOLD have been shown to be associated with changes in the spectral profile of neuronal activity, rather than with absolute neural power. On the other hand, though, recent findings showed that different EEG rhythms are independently related to changes in the BOLD signal: therefore, it would be important to distinguish between the contributions of the different EEG rhythms to BOLD fluctuations when modeling the relationship between EEG and BOLD. Here we proposed a novel method to perform EEG-informed fMRI analysis, so that the EEG regressors take into account both the changes in the spectral profile and the rhythms distinction. We applied it to EEG-fMRI data during a bimanual motor task in healthy subjects, and compared the results with those obtained by regressing fMRI data onto a single regressor covering the entire range of frequencies, ignoring the distinction between different EEG rhythms. Our results showed that the proposed method better captures the correlations between BOLD signal and EEG rhythms modulations, identifying task-related well localized activated volumes.

Simultaneous EEG-fMRI in patients with unverricht-lundborg disease: event-related desynchronization/synchronization and hemodynamic response analysis

We performed simultaneous acquisition of EEG-fMRI in seven patients with Unverricht-Lundborg disease (ULD) and in six healthy controls using self-paced finger extension as a motor task. The event-related desynchronization/synchronization (ERD/ERS) analysis showed a greater and more diffuse alpha desynchronization in central regions and a strongly reduced post-movement beta-ERS in patients compared with controls, suggesting a significant dysfunction of the mechanisms regulating active movement and movement end. The event-related hemodynamic response obtained from fMRI showed delayed BOLD peak latency in the contralateral primary motor area suggesting a less efficient activity of the neuronal populations driving fine movements, which are specifically impaired in ULD.

EEG-informed fMRI analysis during a hand grip task

In the last decade, an increasing interest has arisen in investigating the relationship between the electrophysiological and hemodynamic measurements of brain activity, such as EEG and (BOLD) fMRI. In particular, changes in BOLD have been shown to be associated with changes in the spectral profile of neuronal activity, rather than with absolute neural power. On the other hand, though, recent findings showed that different EEG rhythms are independently related to changes in the BOLD signal: therefore, it would be important to distinguish between the contributions of the different EEG rhythms to BOLD fluctuations when modeling the relationship between EEG and BOLD. Here we proposed a novel method to perform EEG-informed fMRI analysis, so that the EEG regressors take into account both the changes in the spectral profile and the rhythms distinction. We applied it to EEG-fMRI data during a bimanual motor task in healthy subjects, and compared the results with those obtained by regressing fMRI data onto a single regressor covering the entire range of frequencies, ignoring the distinction between different EEG rhythms. Our results showed that the proposed method better captures the correlations between BOLD signal and EEG rhythms modulations, identifying task-related well localized activated volumes.

Multimodality fNIRS-EEG, fMRI-EEG and TMS Clinical Study on Cortical Response During Motor Task in Adult Volunteers and Epileptic Patients with Movement Disorders

A multimodality fNIRS-EEG, fMRI-EEG and TMS clinical study was performed on adult volunteers and epileptic patients with movement disorders to assess cortical response during motor tasks

Electroencephalographic (EEG) Photoparoxysmal Responses Under 5 Years of Age: Diagnostic Implications and Peculiarities.

Electroencephalographic (EEG) photoparoxysmal response has been little investigated in very young patients. We studied 5055 patients aged less than 5 years with no acquired brain damage, who underwent EEG recording. We determined the prevalence and significance of photoparoxysmal response induced by 1 to 20 Hz photic stimulation. Fifty-three showed photoparoxysmal response and were diagnosed as having Dravet syndrome (11), epileptic encephalopathy with myoclonic seizures (8), neurodegenerative disorders (8), benign idiopathic epilepsies (9), and static disorders with a known or suspected genetic origin (17). Photoparoxysmal response occurred in response to 1 to 5 Hz trains in 41.5% subjects. In most patients with epileptic encephalopathies, photoparoxysmal response was a transient finding: in 53.2%, it failed to be replicated in the recordings performed more than 6 months after initial evaluation. Photoparoxysmal response is rare in patients aged less than 5 years and has some peculiarities such as occurrence with low-frequency stimuli. Its distribution in specific conditions indicates that photoparoxysmal response may be useful in diagnostic workup.