Elisa Visani

Intra- and extra-cranial effects of transient blood pressure changes on brain near-infrared spectroscopy (NIRS) measurements

Highlights ► We recorded NIRS from the visual cortex during pattern-reversal stimulation. ► Transient blood pressure changes were induced by arm-raising. ► Blood pressure changes significantly altered deep and shallow NIRS recordings. ► The effect appears to originate from both intra- and extra-cranial regions. ► Blood pressure must be considered as a potential confound in NIRS studies.

Movement-activated myoclonus in genetically defined progressive myoclonic epilepsies: EEG–EMG relationship estimated using autoregressive models

OBJECTIVE To study electroencephalography-electromyography (EEG-EMG) relationships in patients with different forms of progressive myoclonic epilepsies (PME). METHODS EEG-EMG auto-spectra, coherence and phase functions were estimated by means of bivariate and time varying autoregressive (AR) models in 15 patients: 8 with Unverricht-Lundborg, 4 with Lafora body disease, and 3 with sialidosis. RESULTS The coherence spectra of the EMG epochs including action myoclonus and contralateral frontocentral EEG derivations showed a main beta peak (average coherence: 0.60-0.79) in all patients, regardless of the type of PME. The time lag from cortex to muscle was 13.0-21.3 ms. Significantly, coherent gamma activity was consistently found only in the 3 patients with sialidosis; the most heterogeneous results were obtained in the patients with Lafora disease, who showed a more complex coherence profile. Periods of normal muscle contractions, which could be recorded in patients with Unverricht-Lundborg PME, were characterised by the presence of an EEG-EMG beta coherence peak on the same frequency as in the case of action myoclonus, but with a lower coherence value. CONCLUSIONS AR models were capable of describing EEG-EMG relationships in patients with PME, and indicated that coherent cortical and EMG beta oscillations are crucially involved in the generation of myoclonus. Moreover, they could detect the uneven spectral profiles characterising the different forms of PME.

Sensorimotor cortex excitability in Unverricht-Lundborg disease and Lafora body disease.

Objective: To investigate whether Unverricht–Lundborg disease (ULD) and Lafora body disease (LBD) can be differentiated on the basis of their neurophysiologic profiles. Methods: Somatosensory evoked potentials (SSEPs), long-loop reflexes (LLRs), and the influence of conditioning nerve stimulation on the motor potentials evoked by transcranial stimulation in 8 patients with LBD and 10 patients with ULD were investigated. Results: Both groups showed sensorimotor cortex hyperexcitability, but their electrophysiologic profiles were different. Enlarged P25 to N33 SSEP components and enhanced LLRs were common in the ULD patients, whereas medium-latency “giant” SSEP components and less consistently enhanced LLRs were more frequently found in the patients with LBD. Cortical relay time was extremely brief in ULD but varied in LBD. Conditioning somatosensory stimuli differently affected motor cortex excitability, leading to early facilitation in ULD and delayed and prolonged facilitation in LBD. Conclusions: Patients with Unverricht–Lundborg disease (ULD) and Lafora body disease (LBD) have different electrophysiologic profiles. The ULD findings point to an aberrant subcortical or cortical loop (possibly short-cutting the somatosensory cortex) that is involved in generating the prominent action myoclonus characterizing the disorder. The LBD findings highlight sustained hyperexcitability of the sensorimotor cortex in response to afferent stimuli, which fit with a more severe impairment of inhibitory mechanisms.

Progressive myoclonic epilepsies Definitive and still undetermined causes

Objective: To define the clinical spectrum and etiology of progressive myoclonic epilepsies (PMEs) in Italy using a database developed by the Genetics Commission of the Italian League against Epilepsy. Methods: We collected clinical and laboratory data from patients referred to 25 Italian epilepsy centers regardless of whether a positive causative factor was identified. PMEs of undetermined origins were grouped using 2-step cluster analysis. Results: We collected clinical data from 204 patients, including 77 with a diagnosis of Unverricht-Lundborg disease and 37 with a diagnosis of Lafora body disease; 31 patients had PMEs due to rarer genetic causes, mainly neuronal ceroid lipofuscinoses. Two more patients had celiac disease. Despite extensive investigation, we found no definitive etiology for 57 patients. Cluster analysis indicated that these patients could be grouped into 2 clusters defined by age at disease onset, age at myoclonus onset, previous psychomotor delay, seizure characteristics, photosensitivity, associated signs other than those included in the cardinal definition of PME, and pathologic MRI findings. Conclusions: Information concerning the distribution of different genetic causes of PMEs may provide a framework for an updated diagnostic workup. Phenotypes of the patients with PME of undetermined cause varied widely. The presence of separate clusters suggests that novel forms of PME are yet to be clinically and genetically characterized.

A neurophysiological study of myoclonus in patients with DYT11 myoclonus-dystonia syndrome

Mutations in the ϵ‐sarcoglycan (SGCE) gene have been associated with DYT11 myoclonus‐dystonia syndrome (MDS). The aim of this study was to characterize myoclonus in 9 patients with DYT11‐MDS presenting with predominant myoclonus and mild dystonia by means of neurophysiological techniques. Variously severe multifocal myoclonus occurred in all of the patients, and included short (mean 89.1 ± 13.3 milliseconds) electromyographic bursts without any electroencephalographic correlate, sometimes presenting a pseudo‐rhythmic course. Massive jerks could be evoked by sudden stimuli in 5 patients, showing a “startle‐like” muscle spreading and latencies consistent with a brainstem origin. Somatosensory evoked potentials and long‐loop reflexes were normal, as was silent period and long‐term intracortical inhibition evaluated by means of transcranial magnetic stimulation; however, short‐term intracortical inhibition revealed subtle impairment, and event‐related synchronization (ERS) in the beta band was delayed. Blink reflex recovery was strongly enhanced. Myoclonus in DYT11‐MDS seems to be generated at subcortical level, and possibly involves basal ganglia and brainstem circuitries. Cortical impairment may depend from subcortical dysfunction, but it can also have a role in influencing the myoclonic presentation. The wide distribution of the defective SCGE in DYT11‐MDS may justify the involvement of different brain areas.

Enhanced frontocentral EEG connectivity in photosensitive generalized epilepsies: a partial directed coherence study.

Purpose:  Photosensitive epilepsy (PSE) is the most common form of reflex epilepsy presenting with electroencephalography (EEG) paroxysms elicited by intermittent photic stimulation (IPS). To investigate whether the neuronal network undergoes dynamic changes before and during the transition to an EEG epileptic discharge, we estimated EEG connectivity patterns in photosensitive (PS) patients with idiopathic generalized epilepsy.

Short and long interval cortical inhibition in patients with Unverricht-Lundborg and Lafora body disease.

Myoclonus has different clinical and neurophysiological features in patients with Unverricht-Lundborg (ULD) and Lafora body disease (LBD), probably because of a different cortical hyperexcitability profile. To investigate the role of intracortical inhibition in such different presentations, we used paired-pulse transcranial magnetic stimulation (TMS) in ten ULD and five LBD patients, all with a positive molecular diagnosis. All of the patients were treated with antiepileptic drugs (AEDs). In comparison with healthy subjects, both patient groups had significantly defective short intracortical inhibition (SICI), however LBD patients, but not ULD and healthy subjects, had a clear inhibition at ISI 6 ms and ISI 10 ms. Moreover, defective long interval cortical inhibition (LICI) was found in LBD but not ULD patients. The substantial reduction in SICI suggests that both ULD and LBD patients have impaired inhibitory interneuron pools which are involved in the generation of cortical reflex myoclonus, whereas the inhibition found in LBD patients at ISI 6 and 10 ms, as well the reduced inhibition found at long intervals, suggest a more complex circuitry dysfunction possibly involving both excitatory and inhibitory systems. These findings are probably related to the high epileptogenic propensity characterizing LBD with respect to ULD and to the more severely distorted neuronal network resulting from the pathogenesis of LBD.

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.

Myoclonus in Creutzfeldt-Jakob disease: polygraphic and video-electroencephalography assessment of 109 patients.

We used electroencephalography (EEG)‐polygraphic recordings to classify myoclonus in 109 patients with Creutzfeldt‐Jakob disease (CJD) on the basis of its electromyography (EMG) pattern, time course, distribution, and EEG correlates. We recorded myoclonic jerks in 55 patients (50.4%), and we classified them as periodic myoclonus in 28, rhythmic in 13, and irregular in 20 (6 patients showed two types of myoclonus). Myoclonus occurred as a prominently negative event (interrupting the EMG discharge) in 10. Periodic sharp‐wave complexes (PSWCs) were present in all but one patient with myoclonic jerks but were time‐locked with EMG‐bursts only in case of periodic myoclonus. Jerk‐locked back averaging revealed a variable EEG‐EMG transfer‐time commonly exceeding that characterizing cortical myoclonus. Myoclonus was frequently associated with Met/Met polymorphism at codon 129 of the prion protein gene, but it was also observed in association with Met/Val or Val/Val polymorphisms provided that the EEG showed the presence of the PSWC pattern. The presence of enlarged somatosensory evoked potentials significantly correlated with the myoclonic presentation, as did MR signal hyperintensity involving the cortical mantle. Our observations on the basis of standard polygraphic criteria suggest that CJD associates with a remarkable variety of myoclonic jerks, and therefore different brain structures are probably involved as generators. The significant association between the presence of all myoclonus types with PSWCs suggests that hyperexcitable corticosubcortical loops are always required to generate (or allow) both myoclonus and the EEG complexes, either they are time locked or not.

Rhythmic cortical myoclonus in a case of HIV-related encephalopathy.

We describe a 66‐year‐old, HIV‐seropositive patient presenting with ataxia and upper limb rhythmic myoclonus activated by postural maintenance. Electromyograph (EMG) recordings of the forearm muscles showed 50‐msec bursts, with a frequency of 10 Hz, concurring with frontocentral electroencephalograph (EEG) rhythmic activity. Autoregressive spectral analysis applied to the EEG–EMG traces made it possible to detect significant coherence between the rhythmic EEG discharges and EMG bursts. The amplitude of the middle‐latency somatosensory evoked potentials was increased. Long‐latency reflexes were enhanced. On the basis of the electrophysiological findings, the movement disorder should be considered a rhythmic variant of cortical myoclonus. In our patient, HIV infection may have caused a dysfunction in the central nervous system pathways involving the cerebellum and sensorimotor cortex, similar to that occurring in genetically determined conditions characterised by cortical myoclonus.