Neurophysiological study of epileptogenic networks in epilepsy

To increase understanding into the specific networks involved in the pathophysiology of different types of epilepsy, we proposed extensive neurophysiological studies. First, we studied patients with photosensitive epilepsy since they represent a \u201cmodel\u201d of system epilepsy. Then, we focused on patients with focal (FE) and generalized epilepsies (GE) to unravel the neurophysiological basis of seizure generalization. Finally, we explored the motor cortex plasticity in juvenile myoclonic epilepsy (JME), the most common subtype of GE in adults. We used the paired transcranial magnetic stimulation (paired-TMS) to investigate the time related changes in functional connectivity between visual and primary motor cortex in healthy subjects and in patients with photosensitivity to study the visuomotor integration. We also studied the interhemispheric connection involved in seizure generalization in FE and GE; to explore the motor cortex synaptic plasticity in patients with JME we used the paired associative stimulation.The findings support a physiologically relevant visuomotor functional connectivity, which likely contributes to visuomotor integration. Substantial physiologic changes in this network underlie the photosensitivity, which may justify the origin of epileptic motor phenomena (i.e. myoclonus). We found significant differences in the interhemispheric connection of drug-treated patients with FE and those with IGE. Whilst interhemispheric inhibition changes would not be crucial for the IGE pathophysiology, they may represent one key factor for the contralateral spread of focal discharges, and seizure generalization. As to the patients with JME, we provided evidence of a defective long term potentiation-like plasticity, which may be primarily involved in the pathogenesis of myoclonus. In conclusion, we documented substantial changes in the epileptogenic networks involved in different types of epilepsy

A real‐world comparison among third‐generation antiseizure medications: Results from the COMPARE study

Objective: There are few comparative data on the third-generation antiseizure medications (ASMs). We aimed to assess and compare the effectiveness of brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) in people with epilepsy (PWE). Efficacy and tolerability were compared as secondary objectives.Methods: This multicenter, retrospective study collected data from 22 Italian neurology/epilepsy centers. All adult PWE who started add-on treatment with one of the studied ASMs between January 2018 and October 2021 were included. Retention rate was established as effectiveness measure and described using Kaplan-Meier curves and the best fitting survival model. The responder status and the occurrence of adverse events (AEs) were used to evaluate efficacy and safety, respectively. The odds of AEs and drug efficacy were estimated by two multilevel logistic models.Results: A total of 960 patients (52.92% females, median age = 43 years) met the inclusion criteria. They mainly suffered from structural epilepsy (52.29%) with monthly (46.2%) focal seizures (69.58%). Compared with LCM, all the studied ASMs had a higher dropout risk, statistically significant in the BRV levetiracetam (LEV)-na & iuml;ve (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17-3.29) and PER groups (HR = 1.64, 95% CI = 1.06-2.55). Women were at higher risk of discontinuing ESL (HR = 5.33, 95% CI = 1.71-16.61), as well as PER-treated patients with unknown epilepsy etiology versus those with structural etiology (HR = 1.74, 95% CI = 1.05-2.88). BRV with prior LEV therapy showed lower odds of efficacy (odds ratio [OR] = .08, 95% CI = .01-.48) versus LCM, whereas a higher efficacy was observed in women treated with BRV and LEV-na & iuml;ve (OR = 10.32, 95% CI = 1.55-68.78) versus men. PER (OR = 6.93, 95% CI = 3.32-14.44) and BRV in LEV-na & iuml;ve patients (OR = 6.80, 95% CI = 2.64-17.52) had a higher chance of AEs than LCM.Significance: Comparative evidence from real-world studies may help clinicians to tailor treatments according to patients' demographic and clinical characteristics

Brain mechanisms underlying the placebo effect in neurological disorders

The potential of placebo treatments to alleviate a variety of medical conditions has long been recognised. Although the placebo effect is widely known, the physiological mechanisms underlying this phenomenon are not well understood. This review focuses on the existing evidence for placebo responses in different neurological conditions, including pain, Parkinson’s disease, depression, sleep and immune-mediated disorders. Special attention is paid to the neural changes associated with placebo treatments, as revealed by in vivo neurophysiological and functional neuroimaging studies. Converging evidence suggests that placebo analgesia is linked to the activation of the endogenous opioid analgesia network, whilst dopaminergic pathways seem to play a central role in the placebo effect in movement disorders and neuroimmunomodulation. Further research on the placebo response is needed, both to improve the efficacy of its application in clinical practice and to shed more light on the complexity of mind-body interaction

Auditory seizures in autoimmune epilepsy: a case with anti-thyroid antibodies

In its classic presentation, Hashimoto's encephalopathy is an acute-subacute complex neuropsychiatric syndrome with cognitive impairment, hallucinations, myoclonus, tremor or ataxia, associated with elevated anti-thyroid antibodies. Corticoids and immunotherapy are dramatically effective. However, in some cases, not all the associated features are presented and this delays diagnosis and appropriate treatment. We describe a man with abrupt onset of recurrent auditory seizures resulting in refractory non-convulsive status epilepticus. The patient was diagnosed with an autoimmune encephalopathy with elevated serum and CSF anti-thyroid antibodies. None of the antiepileptic drugs were successful, however, following immune-modulating therapy, the refractory non-convulsive status epilepticus dramatically improved, as did the patient overall. We suggest that Hashimoto's encephalopathy should be suspected in otherwise healthy patients with unexplained new-onset focal recurrent auditory seizures which do not respond to antiepileptic drugs. The presence of anti-thyroid antibodies in the CSF supports this diagnosis