Matteo Pugnaghi

Increased cortical BOLD signal anticipates generalized spike and wave discharges in adolescents and adults with idiopathic generalized epilepsies

Purpose:  Electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) coregistration has recently revealed that several brain structures are involved in generalized spike and wave discharges (GSWDs) in idiopathic generalized epilepsies (IGEs). In particular, deactivations and activations have been observed within the so‐called brain default mode network (DMN) and thalamus, respectively. In the present study we analyzed the dynamic time course of blood oxygen level–dependent (BOLD) changes preceding and following 3 Hz GSWDs in a group of adolescent and adult patients with IGE who presented with absence seizures (AS). Our aim was to evaluate cortical BOLD changes before, during, and after GSWD onset.

Recognition of emotions from faces and voices in medial temporal lobe epilepsy

Patients with chronic medial temporal lobe epilepsy (MTLE) can be impaired in different tasks that evaluate emotional or social abilities. In particular, the recognition of facial emotions can be affected (Meletti S, Benuzzi F, Rubboli G, et al. Neurology 2003;60:426-31. Meletti S, Benuzzi F, Cantalupo G, Rubboli G, Tassinari CA, Nichelli P. Epilepsia 2009;50:1547-59). To better understand the nature of emotion recognition deficits in MTLE we investigated the decoding of basic emotions in the visual (facial expression) and auditory (emotional prosody) domains in 41 patients. Results showed deficits in the recognition of both facial and vocal expression of emotions, with a strong correlation between performances across the two tasks. No correlation between emotion recognition and measures of IQ, quality of life (QOLIE-31), and depression (Beck Depression Inventory) was significant, except for a weak correlation between prosody recognition and IQ. These data suggest that emotion recognition impairment in MTLE is not dependent on the sensory channel through which the emotional stimulus is transmitted. Moreover, these findings support the notion that emotional processing is at least partly independent of measures of cognitive intelligence.

Features of somatosensory manifestations induced by intracranial electrical stimulations of the human insula

OBJECTIVE To study the clinical manifestations induced by intracranial electrical stimulation of the insular cortex in epileptic patients submitted to invasive stereo-electroencephalography (SEEG) recordings. METHODS We retrospectively studied the clinical manifestations induced by intracerebral electrical stimulations of the insular cortex in 96 patients. In order to precisely localize the position of the electrodes a postoperative 3D CT scan or a 3D MRI was obtained and then the images were merged with the preoperative MRI in the same stereotactic referenced system. RESULTS A total of 341 electrical bipolar stimulations were performed. The most frequently induced symptom was a somatosensory manifestation (70%), mainly tingling and electric sensation involving the contralateral face and arm. Motor responses represented the 8% of the total amount, as well as auditory phenomena. Language dysfunction accounted for 2% of responses. Autonomic and gustatory phenomena represented respectively 1% of responses. CONCLUSIONS We found a great prevalence of somatosensory manifestations whereas other types of clinical modifications were extremely infrequent. SIGNIFICANCE Our data support a prominent somatosensory role of the human insular cortex and provide a precise characterization of the different types of sensory manifestations induced by intracranial electrical stimulation of the human insula.

Generalized Spike and Waves: Effect of Discharge Duration on Brain Networks as Revealed by BOLD fMRI

In the past decade, the possibility of combining recordings of EEG and functional MRI (EEG–fMRI), has brought a new insight into the brain network underlying generalized spike wave discharges (GSWD). Nevertheless, how GSWD duration influences this network is not fully understood. In this study we aim to investigate whether GSWD duration had a threshold (non-linear) and/or a linear effect on the amplitude of the associated BOLD changes in any brain regions. This could help in elucidating if there is an hemodynamic background supporting the differentiation between interictal and ictal events. We studied a population of 42 patients with idiopathic generalized epilepsies (IGE) who underwent resting-state EEG–fMRI recordings in three centres (London, UK; Modena, Italy; Rome, Italy), applying a parametric analysis of the GSWD duration. Patients were classified as having Childhood Absence epilepsy, Juvenile Absence Epilepsy, or Juvenile Myoclonic Epilepsy. At the population level linear GSWD duration-related BOLD signal changes were found in a network of brain regions: mainly BOLD increase in thalami and cerebral ventricles, and BOLD decrease in posterior cingulate, precuneus and bilateral parietal regions. No region of significant BOLD change was found in the group analysis for the non-linear effect of GSWD duration. To explore the possible effect of both the different IGE sub-syndromes and the different protocols and scanning equipment used in the study, a full-factorial ANOVA design was performed revealing no significant differences. These findings support the idea that the amplitude of the BOLD changes is linearly related to the GSWD duration with no universal threshold effect of spike and wave duration on the brain network supporting this activity.

Non-convulsive status epilepticus of frontal origin as the first manifestation of Hashimoto's encephalopathy

Hashimoto’s encephalopathy is an often misdiagnosed, life threatening, but treatable, condition which improves promptly with steroid therapy. Since clinical manifestations are heterogeneous and non-specific, the diagnosis is often difficult. Several case reports of Hashimoto’s encephalopathy presenting with partial or generalised seizures are described, but only a few have focused on status epilepticus as the first clinical manifestation. We report two patients presenting with repetitive and prolonged seizures characterised by progressive reduction in contact and reactivity associated with frontal/diffuse polyspike-and-wave activities. This condition, which can be interpreted as a formof non-convulsive status epilepticus (NCSE) of frontal origin, was refractory to antiepileptic drugs but responded promptly to high doses of intravenous steroid treatment. In cases of unexplained encephalopathy with EEG documentation of NCSE, the early recognition and treatment of Hashimoto’s encephalopathy may lead to a favourable prognosis.

Ictal involvement of the nigrostriatal system in subtle seizures of ring chromosome 20 epilepsy

Studies in animal models and patients with epilepsy have suggested that basal ganglia circuits may control epileptic seizures and that striatal dopaminergic transmission may play a role in seizure modulation and interruption. Chromosome 20 [r(20)] syndrome is a well‐defined chromosomal disorder characterized by epilepsy, mild‐to‐moderate mental retardation, and lack of recognizable dysmorphic features. Epilepsy is often the most important clinical manifestation of the syndrome, with prolonged episodes of nonconvulsive status epilepticus suggesting dysfunction in the seizure control system. We present the ictal blood oxygen level–dependent (BOLD) changes in brief seizures recorded by means of electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) coregistration in a patient with [r(20)] syndrome. We observed ictal BOLD increments in a cortical‐subcortical network involving substantia nigrastriatum and frontal cortex. At present, this is the first functional neuroimaging evidence of the involvement of the nigrostriatal system during ictal EEG discharges in [r(20)] syndrome supporting a role of the basal ganglia circuits in human epileptic seizures.

Neurosteroids and epileptogenesis.

Epileptogenesis is defined as the latent period at the end of which spontaneous recurrent seizures occur. This concept has been recently re‐evaluated to include exacerbation of clinically‐manifested epilepsy. Thus, in patients affected by pharmacoresistant seizures, the progression toward a worse condition may be viewed as the result of a durable epileptogenic process. However, the mechanism potentially responsible for this progression remains unclear. Neuroinflammation has been consistently detected both in the latent period and in the chronic phase of epilepsy, especially when brain damage is present. This phenomenon is accompanied by glial cell reaction, leading to gliosis. We have previously described rats presenting an increased expression of the cytochrome P450 cholesterol side‐chain cleavage (P450scc) enzyme, during the latent period, in glial cells of the hippocampus. The P450scc enzyme is critically involved in the synthesis of neurosteroids and its up‐regulation is associated with a delayed appearance of spontaneous recurrent seizures in rats that experienced status epilepticus induced by pilocarpine. Moreover, by decreasing the synthesis of neurosteroids able to promote inhibition, such as allopregnanolone, through the administration of the 5α‐reductase blocker finasteride, it is possible to terminate the latent period in pilocarpine‐treated rats. Finasteride was also found to promote seizures in the chronic period of epileptic rats, suggesting that neurosteroids are continuously produced to counteract seizures. In humans, exacerbation of epilepsy has been also described in patients occasionally exposed to finasteride. Overall, these findings suggest a major role of neurosteroids in the progression of epilepsy and a possible antiepileptogenic role of allopregnanolone and cognate molecules.

Temporal lobe epilepsy exacerbation during pharmacological inhibition of endogenous neurosteroid synthesis

We report the case of a woman who presented cryptogenic temporal lobe seizures from the age of 43 years. Antiepileptic drug (AED) treatment with carbamazepine was able to control seizures for 1 year, but seizures relapsed and an add-on treatment with lamotrigine was started without achieving seizures control. The patients medical history was unremarkable except for a mild hirsutism for which she was taking finasteride since 45 years of age. In view of the possible relationship between finasteride, a known inhibitor of neurosteroids synthesis, and patients seizures exacerbation, we stopped finasteride resulting in prompt recovery of seizures control. It is know that 5α-dihydrosteroids are precursors of powerful positive modulators of γ-aminobutyric acid-A inhibitory currents and exert antiseizure effects in animal epilepsy models. This case supports the hypothesis that endogenous neurosteroids can modulate seizure susceptibility and response to AEDs also in humans, suggesting their possible use as a new therapeutic option.

My sister's hand is in my bed: a case of somatoparaphrenia.

Somatoparaphrenia is a disorder of body representation, usually following right brain lesions, which consists in the delusional belief that the contralesional limbs belong to someone else [1, 2]. We report a new case of somatoparaphrenia in which the patient was remarkably aware of this symptom to the point that she wrote a short poem about it. An 82-year-old woman, without previous history of neurologic or psychiatric disorders, presented with sudden headache and left side weakness. CT scan showed a right thalamic hematoma extending to the posterior arm of the internal capsule and lenticular nucleus, with surrounding edema spreading into the white matter of the right parietal lobe (Fig. 1a). On admission, she had a decreased level of alertness, mild dysarthria, right gaze preference, and complete left hemiplegia. Language was fluent with intact comprehension. Visual fields were preserved, but there was extinction on the left to simultaneous visual bilateral stimulation. She showed anosognosia for left-sided hemiplegia and left spatial neglect. Past medical history included high blood pressure and hypo-thyroidism. Before admission, she had been independent and active, took complete care of her invalid husband, had several intellectual interests, including writing poetry and music lyrics. Two days after admission, when her general alertness had improved, she was still unaware of her left hemiplegia (Bisiach Score [3] of anosognosia was 3/3) and had a profound left spatial neglect, as shown by drawing, line bisection, and Albert’s cancellation test (Fig. 1c, d). She reported that her sister’s hand was in her bed and described it as hard, and unable to move. When shown her left arm, she said it was her sister’s arm. She was convinced that this had happened because the day before being admitted to the hospital she had visited her invalid sister (who indeed was in vegetative status) and had touched her unresponsive hand. She neither showed any emotional distress, nor personality or behavioral changes and was aware of the strangeness of the phenomenon. When asked to give a rational explanation, she admitted ‘‘strange things can happen to the subconscious mind’’. In line with her premorbid cheerful personality, she humorously said once ‘‘I should ask my sister to pay for the parking of her hand’’. Four days after admission, she reported that her sister’s hand was not in her bed anymore, but had been moved to her bed side-table by the nurses earlier in the morning (see video in supplementary material). She recognized the left hand in her bed as her own, but continued to say that her sister’s hand was somewhere in the room. The belief about her sister’s hand ‘‘coming to her’’ at nighttime persisted for another two nights, then resolved. Thereafter, she continued to report and recognize the ‘‘hands phenomenon’’ as real, to the point that she even wrote a short poem addressed to her ‘‘little hand’’ (Fig. 2). A follow-up CT scan performed 10 days after admission and following the Electronic supplementary material The online version of this article (doi:10.1007/s10072-011-0874-z) contains supplementary material, which is available to authorized users.

Focal sensory-motor status epilepticus in multiple sclerosis due to a new cortical lesion. An EEG–fMRI co-registration study

A case of focal inferior limb sensory-motor status epilepticus as the only manifestation of a multiple sclerosis (MS) relapse is described. To obtain evidence of the relationship between the seizures, the cortical plaque and the left foot motor area, an EEG-fMRI co-registration study was undertaken demonstrating that seizure-related BOLD signal substantially overlapped with the inflammatory lesion involving the foot sensory-motor cortex. Seizures did not respond to intravenous anti-epileptic drugs (AEDs) but were controlled by steroid therapy.