Antonella Muroni

Combined EEG/fMRI recording in musicogenic epilepsy

Seizures induced by musical stimulation are usually correlated to temporal epilepsy, although the precise localization of their epileptogenic networks are not well characterized. Brain imaging studies show that regional cerebral blood flow (rCBF) recorded during musicogenic seizures is increased in putative epileptogenic foci, as well as in other brain regions not directly related to seizure activity. These studies, however, afford only a virtual temporal relation between ictal discharges and rCBF changes, given that brain images are correlated with off-line EEG recordings. To obviate this problem, the simultaneous multimodal recording of the episode of musicogenic epilepsy is mandatory. The present study describes the EEG-fMRI co-recording of musicogenic elicited seizures in a case of simple partial epilepsy. Our results show that EEG features recorded in epileptogenic areas are largely coupled with rCBF increase. Furthermore, rCBF modifications in other regions suggest that additional aspects of musical processing are also elicited during musicogenic seizures.

Levetiracetam attenuates spontaneous spike-and-wave discharges in DBA/2J mice

Recent evidence highlights levetiracetam (LEV) as an advantageous treatment of absence epilepsy (AE). Thus, we investigated the effects of this drug in DBA/2J mice, a murine model of AE. Similarly to ethosuximide (200 mg/kg, intraperitoneal, i.p.) and sodium valproate (250 mg/kg, i.p.), two classic antiabsence agents, LEV (50-200 mg/kg, i.p.) reduced the occurrence of spike-and-wave discharges, AEs typical electroencephalographic patterns. Our results confirm LEVs efficacy in AE treatment.

Cardiovascular modulation during vagus nerve stimulation therapy in patients with refractory epilepsy.

To evaluate the effects of permanent vagal stimulation on cardiovascular system, 10 patients, affected by drug-resistant epilepsy with no primitive cardiovascular pathologies, were assessed prior to VNS surgery. A complete echocardiographic study [conventional and tissue Doppler imaging (TDI)], 24-h blood pressure (BP) monitoring and HRV evaluation were performed. The above mentioned parameters were investigated without any substantial changes to drug treatment during a check-up subsequent to VNS activation [mean: 7.7 months]. The results obtained show that while the anthropometrical data and both conventional and TDI echocardiography were unvaried compared to baseline, BP showed a significant increase of both systodiastolic values. Moreover, a close scrutiny of the most affected period of the BP increase (zenith between 16:31 and 17:30 pm) (systolic BP 114.7 mmHg vs 95.3 mmHg, P < 0.0001; diastolic BP 70.9 mmHg vs 56.9 mmHg, P < 0.001) showed a significant increase of the high frequencies components (HF) (28.4 ± 2.7 vs 36 ± 5.3, P < 0.05) and a significant reduction in low frequency/HF ratio (2.3 ± 0.3 vs 1.7 ± 0.3, P < 0.0001). The present study confirms the intrinsic cardiovascular safety and reliability of VNS procedures on both BP and HF and LF profiles and suggests that a primitive VNS-mediated central impingement on vagal efferents, independently by the antiepileptic mechanism, correlated to an moderate increase of parasympathetic activity, which in turn might play a protective role in seizure-triggered alterations of cardiovascular dynamic.

Involvement of GABA in mirror focus: A case report

Mirror focus (MF) is a cortical epileptogenic lesion that is posited to develop in the contralateral site to a cortical primary focus (PF) by secondary epileptogenic mechanisms. Previous animal evidence supports the implication of gamma-aminobutyric acid (GABA) in this phenomenon, but this contention has not yet been substantiated by clinical findings. Here we report for the first time clinical evidence suggesting the involvement of GABAergic cortical transmission in MF pathogenesis, in a 37-year-old man affected by a lesional PF in the right frontal lobe and a homotopic MF in the contralateral hemisphere, triggered by hyperventilation. One year after surgical excision of the PF, the electric activity of the MF remained unchanged, but was accompanied by a significant increase in the density of GABA(A)/benzodiazepine receptor binding in the left frontal lobe, as measured by (123)I-Iomazenil SPECT. These results extend previous evidence on the involvement of GABAergic signaling in MF pathophysiology.

Capgras syndrome in Parkinson’s disease: two new cases and literature review

The Capgras syndrome (CS) is a rare psychiatric disorder. CS is classified as a delusional misidentification syndrome. Initially, CS was described in paranoid schizophrenia and schizoaffective disorders. CS has also been reported in neurodegenerative diseases such as Alzheimer’s disease and Lewy body dementia. To date, there are very few descriptions of the occurrence of CS in idiopathic Parkinson’s disease (PD), with or without dementia. Considering the recent observation of two new cases in PD patients, a systematic overview of the literature published between 1976 and 2016 reporting CS in PD was conducted. The purpose of this article is to examine the phenomenon in people with PD with and without dementia, the psychopathologic context in which it happened, the role played by the dopaminergic medications and to define useful therapeutic strategies. Our CS cases occurred in two elderly patients with advanced PD and cognitive impairment, respectively, after an acute stressor event and after an increase of the total daily dose of levodopa. In light of our observations and the cases reported in the literature, we argue that CS is an acute or subacute psychotic disorder occurring mostly in PD with dementia. Besides, the increase in brain dopamine levels induced by acute stressful events and/or dopamine-enhancing medications should be considered as a possible causal mechanism of CS in patients with advanced stages of PD and cognitive decline.

Metabolomics As a Tool for the Characterization of Drug-Resistant Epilepsy

Purpose Drug resistance is a critical issue in the treatment of epilepsy, contributing to clinical emergencies and increasing both serious social and economic burdens on the health system. The wide variety of potential drug combinations followed by often failed consecutive attempts to match drugs to an individual patient may mean that this treatment stage may last for years with suboptimal benefit to the patient. Given these challenges, it is valuable to explore the availability of new methodologies able to shorten the period of determining a rationale pharmacologic treatment. Metabolomics could provide such a tool to investigate possible markers of drug resistance in subjects with epilepsy. Methods Blood samples were collected from (1) controls (C) (n = 35), (2) patients with epilepsy “responder” (R) (n = 18), and (3) patients with epilepsy “non-responder” (NR) (n = 17) to the drug therapy. The samples were analyzed using nuclear magnetic resonance spectroscopy, followed by multivariate statistical analysis. Key findings A different metabolic profile based on metabolomics analysis of the serum was observed between C and patients with epilepsy and also between R and NR patients. It was possible to identify the discriminant metabolites for the three classes under investigation. Serum from patients with epilepsy were characterized by increased levels of 3-OH-butyrate, 2-OH-valerate, 2-OH-butyrate, acetoacetate, acetone, acetate, choline, alanine, glutamate, scyllo-inositol (C < R < NR), and decreased concentration of glucose, lactate, and citrate compared to C (C > R > NR). Significance In conclusion, metabolomics may represent an important tool for discovery of differences between subjects affected by epilepsy responding or resistant to therapies and for the study of its pathophysiology, optimizing the therapeutic resources and the quality of life of patients.

Treatment of benign essential blepharospasm with finasteride: a case report.

We report the case of a 75-year-old man with a 35-year history of benign essential blepharospasm, which was poorly responsive to botulinum toxin. The patient had also developed Parkinson disease over the past 2 years. After his condition was diagnosed as benign prostatic hypertrophy, he started finasteride (FIN, 5 mg/d) treatment. During the following month, he experienced a significant attenuation of the severity of his dystonic symptoms; this improvement remained stable for the course of the therapy, with no notable adverse effect and no alterations of the symptoms of Parkinson disease. Discontinuation of FIN led to an abrupt exacerbation of symptoms, which was promptly reversed by resumption of the therapy. This case highlights the possibility that FIN may represent a useful therapeutic option in the treatment of certain clusters of benign essential blepharospasm.

Pisa-Like Syndrome Under Baclofen in a Patient With Spastic Hemiparesis due to Ischemic Stroke

In its original description, Pisa syndrome was reported as an iatrogenic dystonia of the trunk caused by neuroleptic drugs. However, sometimes, not dystonic lateral flexion of the trunk is described as Pisa syndrome. These observations support the possibility of a drug-induced lateral flexion of the trunk with clinical presentation similar to Pisa syndrome, although with a different etiology and pathophysiology. Here, we describe the case of a male patient, with a previous ischemic stroke and residual spastic hemiparesis to the right side, who subacutely developed a dramatic lateral flexion of trunk (approximately 45° to the right) a few days after the introduction of Baclofen (5 mg 3 times per day). After the discontinuation of baclofen, a full recovery of the correct posture was obtained. In this respect, our case is paradigmatic: it is drug-induced but not clearly dystonic in its manifestation. Baclofen reduces the spasticity depressing the monosinaptic and polisinaptic reflex in the spinal cord by stimulating Gamma-aminobutyric acid B (GABA-B) receptors, which inhibit the release of excitatory amino acids, glutamate and aspartate. We believe that the definition of Pisa syndrome for these forms, not clearly dystonic, might be not completely appropriate, but they should be defined more correctly as Pisa-like syndromes.