Michele Franca

Encephalopathy with electrical status epilepticus during slow sleep or ESES syndrome including the acquired aphasia

Encephalopathy with electrical status epilepticus during sleep or ESES is an age-dependent and self-limited syndrome whose distinctive features include a characteristic age of onset (with a peak around 4-5 years), heterogeneous seizures types (mostly partial motor or unilateral seizures during sleep and absences or falls while awake), a typical EEG pattern (with continuous and diffuse paroxysms occupying at least 85% of slow wave sleep) and a variable neuropsychological regression consisting of IQ decrease, reduction of language (as in acquired aphasia or Landau-Kleffner syndrome), disturbance of behaviour (psychotic states) and motor impairment (in the form of ataxia, dyspraxia, dystonia or unilateral deficit). Despite the long-term favourable outcome of epilepsy and status epilepticus during sleep (SES), the prognosis is guarded because of the persistence of severe neuropsychological and/or motor deficits in approximately half of the patients. No specific treatment has been advocated for this syndrome, but valproate sodium, benzodiazepines and ACTH have been shown to control the seizures and the SES pattern in many cases, although often only temporarily. Subpial transection is proposed in some instances as in non-regressive acquired aphasia. Recent data support the concept that ESES syndrome may include a large subset of developmental or acquired regressive conditions of infancy.

Time Course of Functional Connectivity between Dorsal Premotor and Contralateral Motor Cortex during Movement Selection

The left dorsal premotor cortex (PMd) is thought to play a dominant role in the selection of movements made by either hand. We used transcranial magnetic stimulation to study the functional connectivity of the left PMd and right primary motor cortex (M1) during an acoustic choice reaction time (RT) task involving contraction of the thumb and forefinger. The facilitatory and inhibitory pathways that can be demonstrated between left PMd and right M1 at rest were suppressed during most of the reaction period. However, they were activated briefly at the start of the reaction period, depending on whether the cue indicated that the forthcoming movement had to be made with the left or the right hand. The facilitatory pathway was active at 75 ms in those trials in which the subjects were required to move the left hand, whereas the inhibitory pathway was active at 100 ms in trials in which the subjects had to move the right hand. These changes in excitability did not occur in hand muscles not used in the task. There were no significant changes in the excitability of intracortical circuits [short intracortical inhibition (SICI) and intracortical facilitation (ICF)] in the right M1. Interhemispheric interactions between the right PMd and left M1 were mainly inhibitory at rest and showed the same temporal profile of interhemispheric inhibition as for left PMd–right M1, although no evidence was found for facilitatory interactions. The results illustrate the importance of PMd not only in facilitating cued movements but also in suppressing movements that have been prepared but are not used.

Interactions between pairs of transcranial magnetic stimuli over the human left dorsal premotor cortex differ from those seen in primary motor cortex

A single TMS pulse (110% resting motor threshold, RMT) to the left dorsal premotor cortex (PMd) (CS2) suppresses the amplitude of motor evoked potentials (MEPs) from a test pulse (TS) over the right motor cortex (M1), and facilitates MEPs from the left motor cortex. We probed how this interaction was changed by a prior conditioning pulse over PMd (CS1) using a paired pulse TMS design. In the main experiments, the intensity of CS1 was 80% RMT. Basal suppression of right M1 was removed when CS1–CS2 was 1 ms or 5 ms with a similar tendency at 15 ms. Basal facilitation of left M1 was suppressed at CS1–CS2 of 5 ms. A similar time course was seen if CS2 was increased to 100% RMT, but there was no significant effect if CS1 was 70% RMT. Preconditioning PMd with continuous or intermittent theta burst repetitive TMS (cTBS, iTBS) abolished the basal CS2–TS interaction between premotor and motor cortices. Finally, if very short interstimulus intervals between CS1 and CS2 were explored to detect interactions similar to I‐wave facilitation in M1, we found that the basal suppression of right M1 was abolished at CS1–CS2 intervals of 1.8 and 2.8 ms. We suggest that paired pulse TMS may be capable of investigating properties of intrinsic circuits in PMd and that their properties differ from those in the nearby M1. Paired TMS may be a useful method of studying the excitability of intrinsic circuits in non‐primary areas of the motor system.

Effects of theta burst stimulation protocols on phosphene threshold

OBJECTIVE We investigated the effects on occipital cortex, of two newly developed methods of repetitive transcranial magnetic stimulation (rTMS): continuous and intermittent theta burst stimulation (cTBS and iTBS), that lead to long lasting changes in excitability when applied over primary motor cortex. METHODS Phosphene threshold to a single TMS pulse was measured before and after application of either continuous or intermittent theta burst stimulation (cTBS/iTBS; 600 total pulses at 80% phosphene threshold). RESULTS In our cohort, cTBS increased phosphene threshold by an average of 10%. In contrast, iTBS, which transiently increases motor cortex excitability, had no effect on phosphene threshold. CONCLUSIONS cTBS can be applied successfully to non-motor areas of cortex, but iTBS may need modification to produce maximal effects. SIGNIFICANCE cTBS maybe a new useful tool in disorders characterized by an abnormal state of activity of the visual cortex.

Altered Dorsal Premotor-Motor Interhemispheric Pathway Activity in Focal Arm Dystonia

Given the possible role of dorsal premotor cortex (PMd) in the pathophysiology of dystonia, we used transcranial magnetic stimulation (TMS) methods to study PMd and PMd–primary motor cortex (M1) interactions in patients with focal arm dystonia. Here, we tested the connectivity between left PMd and right M1 as well as the intracortical excitability of PMd in 11 right‐handed patients with focal arm/hand dystonia and nine age‐matched healthy controls. The results showed that excitability of the inhibitory connection between PMd and M1 was reduced in patients, but there was no significant difference to healthy subjects in the excitability of the facilitatory connection. A triple stimulation technique in which pairs of TMS pulses are given over PMd and their interaction measured in terms of the effect on the baseline PMd‐M1 connection failed to reveal the usual pattern of interaction between the pairs of PMd stimuli. Indeed, the results in patients were similar to those seen in a group of young healthy subjects after the excitability of PMd had been changed by pretreatment with high‐frequency rTMS. We suggest that reduced transcallosal inhibition from the PMd may be involved in the altered pattern of abnormal muscle contractions of agonists and antagonists (overflow).

How repeatable are the physiological effects of TENS

OBJECTIVE Several studies suggest that transcutaneous electrical stimulation (TENS) can have a variety of effects on the central nervous system (CNS). In this study, we tried to replicate the physiological effects of TENS and to explore its effects on intracortical circuits. METHODS We used transcranial magnetic stimulation (TMS) and spinal reflex testing to examine excitability of intracortical and spinal cord circuits before and after a 30-min period of TENS over the flexor carpi radialis (FCR) muscle. We measured the amplitude of TMS-evoked muscle responses (MEP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical antagonist inhibition (CAI) in flexor and extensor carpial radialis (FCR, ECR) muscles as well as spinal reciprocal inhibition (RI) and presynaptic inhibition (PI) from ECR to FCR. RESULTS TENS had no significant effect on any of these measures apart from a reduction in median nerve induced facilitation of FCR when testing CAI. CONCLUSIONS When compared with previous studies, our results suggest that the effects of TENS are highly variable and unreliable, likely by the difficulty in defining precise parameters of stimulation in individual subjects. SIGNIFICANCE Care should be taken in assuming that effects after TENS observed in small populations of subjects will apply equally to a wider population.

Epileptic intermittent snoring

Snoring is an inspiratory noise, from airflow-induced vibration of the oropharyngeal soft tissues during sleep.1 This vibration results from a narrowing of the upper airways, caused by a disequilibrium between two forces: the inspiratory increment of the intrathoracic pressure and the phasic activation of oropharyngeal dilator muscles.1 Intermittent snoring (IS) is the result of interruptions due to apneas and hypopneas.1 We report two epileptic patients whose polysomnographic (PSG) monitoring suggested that their IS was of epileptic origin. Recording parameters included EEG, electromyogram (EMG) from the mylohyoideus and both deltoids, electro-oculogram, EKG, oronasal and thoracic respiration (monitored with a thermistor and a strain gauge, respectively), and microphone. Both patients had normal brain CT and MRI. Their seizures were incompletely controlled despite antiepileptic polytherapy. ### Case 1. An obese 46-year-old woman had experienced tonic-clonic seizures during sleep since age 11. At age 14, she developed complex partial seizures and epileptic falling seizures. Neurologic examination was unremarkable. Interictal …