Insight into epileptic and physiological déjà vu: from a multicentric cohort study.

BACKGROUND AND PURPOSE: The presence of a continuum between physiological déjà vu (DV) and epileptic DV is still not known as well as epidemiological data in the Italian population. The aim was to identify the epidemiological distribution of DV in Italy, and secondly to look for specific features of DV able to discriminate between epileptic and non-epileptic DV. METHODS: In all, 1000 individuals, 543 healthy controls (C) (313 women; age 40 ± 15 years) and 457 patients with epilepsy (E) (260 women; age 39 ± 14 years), were prospectively recruited from 10 outpatient neurological clinics throughout Italy. All populations were screened using the Italian Inventory for Déjà Vu Experiences Assessment (I-IDEA) test and E and pairwise C underwent a comprehensive epilepsy interview. RESULTS: Of E, 69% stated that they experienced 'recognition' and 13.2% reported that this feeling occurred from a few times a month to at least weekly (versus 7.7% of the control group). Furthermore, a greater percentage of E (6.8% vs. 2.2%) reported that from a few times a month to at least weekly they felt that it seemed as though everything around was not real. In E, the feeling of recognition raised fright (22.3% vs. 13.2%) and a sense of oppression (19.4% vs. 9.4%). A fifth of E felt recognition during epileptic seizures. CONCLUSION: Only E regardless of aetiology firmly answered that they had the feeling of recognition during an epileptic seizure; thus question 14 of the I-IDEA test part 2 discriminated E from C. Paranormal activity, remembering dreams and travel frequency were mostly correlated to DV in E suggesting that the visual-memory network might be involved in epileptic DV.

Neuropsychiatric adverse events of antiepileptic drugs in brain tumour-related epilepsy: an Italian multicentre prospective observational study.

BACKGROUND AND PURPOSE: We assessed the prevalence and magnitude of neuropsychiatric adverse events (NPAEs) associated with antiepileptic drugs (AEDs) among patients with brain tumour-related epilepsy (BTRE). METHODS: This observational, prospective, multicentre study enrolled 259 patients with BTRE after neurosurgery. All patients received AED monotherapy. Efficacy was assessed through clinical diaries, whereas NPAEs were collected using the Neuropsychiatric Inventory Test-12 questionnaire at baseline and after 5 months. RESULTS: Tumour localization in the frontal lobe was associated with a higher prevalence of NPAEs (odds ratio, 7.73; P < 0.001). Independent of tumour localization, levetiracetam (LVT) treatment was associated with higher prevalence and magnitude of NPAEs (odds ratio, 7.94; P < 0.01) compared with other AEDs. Patients with oligodendroglioma reported more NPAEs than patients with other tumour types. NPAEs were not influenced by chemotherapy, radiotherapy or steroid treatment. Evaluating non-neurobehavioural adverse events of AEDs, no significant differences were found among AEDs, although patients treated with old AEDs had a higher prevalence of adverse events than those treated with new AEDs. CONCLUSIONS: Both tumour localization in the frontal lobe and LVT treatment are associated with a higher risk of NPAEs in patients with BTRE. LVT is regarded as a first-line option in patients with BTRE because of easy titration and few significant drug-to-drug interactions. Thus, as NPAEs lead to poor compliance and a high dropout rate, clinicians need to accurately monitor NPAEs after AED prescription, especially in patients with frontal lobe tumours receiving LVT.

The Photoparoxysmal Response Reflects Abnormal Early Visuomotor Integration in the Human Motor Cortex.

BACKGROUND: Visual-paired associative stimulation (V-PAS) is a transcranial magnetic stimulation (TMS) technique able to investigate long-term potentiation (LTP) and depression (LTD)-like plasticity in the primary motor cortex (M1) arising through early visuomotor integration. OBJECTIVE/HYPOTHESIS: Abnormal early visuomotor integration might contribute to the pathophysiology of intermittent photic stimulation (IPS)-induced photoparoxysmal response (PPR). METHODS: We applied V-PAS in 25 healthy subjects (HS), 25 PPR-positive patients, with and without idiopathic generalized epilepsy (IGE), and 8 PPR-negative patients with IGE. V-PAS consisted of primary visual area activation achieved by visual evoked potentials coupled with TMS-induced M1 activation at 100 ms interstimulus interval (ISI) (V-PAS100). Before and after V-PAS, we measured changes in motor evoked potentials (MEPs). We compared MEPs after 1 Hz repetitive TMS (rTMS) and 0.25 Hz-V-PAS100. To examine possible V-PAS-induced after-effects at other ISIs, we delivered V-PAS at 40 (V-PAS40) and 140 ms ISIs (V-PAS140). To clarify whether V-PAS100 increases parieto-/premotor-to-M1 connectivity, before and after V-PAS100, we examined MEPs evoked by paired-pulse techniques. RESULTS: V-PAS100 increased MEPs more in PPR-positive patients than in HS. PPR-negative patients had normal response to V-PAS100. 1 Hz-rTMS, 0.25 Hz-V-PAS100 and V-PAS40 elicited similar responses in HS and PPR-positive patients, whereas V-PAS140 induced stronger after-effects in PPR-positive patients than HS. After V-PAS, MEPs elicited by facilitatory paired-pulse protocols decreased similarly in HS and PPR-positive patients. Conversely, MEPs elicited by inhibitory protocols decreased in HS, whereas in PPR-positive patients, they turned from inhibition to facilitation. CONCLUSION: We suggest that abnormal early visuomotor integration contributes to the pathophysiology of PPR.

Epilepsy, unawareness of seizures and driving license: the potential role of 24-hour ambulatory EEG in defining seizure freedom.

INTRODUCTION: Seizures represent a potential source of accidents/death. Permission to drive may, therefore, be granted in a seizure-free period. Laws and regulations regarding this issue vary widely, and the onus of reporting seizures ultimately rests on the individual. Unfortunately, as some patients are unaware of their seizures, their reports may be unreliable. METHODS: In this retrospective study, we selected, from a group of 1100 consecutive patients, 57 cases (26 males/31 females; mean age: 42.5 years) in whom the AEEG documented ictal events (UIEs) not reported in a self-kept diary. By means of a simple questionnaire, we interviewed all these patients to collect information on driving licenses. We, thus, assessed how many of these patients (both drug resistant and seizure free) drove regularly. RESULTS: Our study shows a relatively large number of patients with epilepsy and UIEs. Fifteen patients suffered from idiopathic generalized epilepsy (IGE) while 42 had partial epilepsy (PE). The patients were seizure free in 21 cases and 36 had drug-resistant seizures. Many patients in both these subgroups had a driving license and drove normally (active driving in 12/36 drug-resistant patients and in 18/21 seizure-free patients). Worthy of note is the finding that an "apparently" seizure-free group of patients drove regularly. CONCLUSIONS: This study revealed a large number of patients (both drug resistant and seizure free) with AEEG-documented UIEs. This finding highlights the usefulness of AEEG in clinical practice as a means of more accurately ascertaining seizure freedom and supporting decisions involving the renewal or granting of a driving license.

Recurrent partial seizures with ictal yawning as atypical presentation of Hashimoto's encephalopathy (steroid-responsive encephalopathy associated with autoimmune thyroiditis).

Hashimoto's encephalopathy (HE), also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), is a rare condition whose pathogenesis is unknown, though autoimmune-mediated mechanisms are thought to be involved. The prevalent neurological manifestations of this disorder are epileptic seizures and psychocognitive disorders associated with EEG alterations. High anti-thyroid antibody titers (particularly in cerebrospinal fluid) and the effectiveness of steroid therapy are usually considered to be crucial elements in the diagnostic process. We describe a 19-year-old female patient who had been referred to the psychiatric unit because of behavioral disorders characterized predominantly by delirium with sexual content. She developed recurrent focal seizures characterized by atypical ictal semiology (repetitive forceful yawning) and a rare EEG pattern (recurrent seizures arising from the left temporal region without evident "encephalopathic" activity). The presence of anti-thyroperoxidase antibodies in her cerebrospinal fluid and a good response to steroids confirmed the diagnosis of HE. The atypical presentation in the case we describe appears to widen the electroclinical spectrum of HE and highlights its importance for differential diagnosis purposes in the neuropsychiatric setting.

An unusual cause of delayed awakening following coronary artery surgery.

Neurological deficits are a frequent complication of adult cardiac surgery. Dandy-Walker malformation (DWM) is a rare posterior fossa malformation defined by hypoplasia and upward rotation of the cerebellar vermis, cystic dilation of the fourth ventricle and, on occasion, hydrocephalus. We report an incidental diagnosis of DWM in an adult following coronary artery surgery complicated by delayed awakening.

Intravenous Levetiracetam as first-line treatment of status epilepticus in the elderly.

BACKGROUND: Status epilepticus is a condition of prolonged/repetitive seizures that often occurs in the elderly. Treatment in the elderly can be complicated by serious side effects associated with traditional drugs. OBJECTIVE: The aim of this pilot study was to evaluate the short-term efficacy/safety of intravenously administered LEV (IVLEV) as the treatment of choice for SE in the elderly. METHODS: We enrolled nine elderly patients (five female/four male; median age 78 years) with SE. Two patients had a previous diagnosis of epilepsy; in the remaining seven, SE was symptomatic. SE was convulsive in five and non-convulsive in four. All the patients presented concomitant medical conditions (arrhythmias/respiratory distress/hepatic diseases). As the traditional therapy for SE was considered unsafe, IVLEV was used as first-line therapy (loading dose of 1500 mg/100 ml/15 min, mean maintenance daily dose of 2500 mg/24 h) administered during video-EEG monitoring. RESULTS/CONCLUSIONS: In all the patients but one, IVLEV was effective in the treatment of SE and determined either the disappearance of (7/8), or significant reduction in (1/8), epileptic activity; no patient relapsed in the subsequent 24 h. No adverse events or changes in the ECG/laboratory parameters were observed. These data suggest that IVLEV may be an effective/safe treatment for SE in the elderly.

Status epilepticus in epileptic patients. Related syndromes, precipitating factors, treatment and outcome in a video-EEG population-based study.

INTRODUCTION: Status epilepticus (SE) is frequently observed in epileptic patients. We reviewed a series of video-EEG documented SE to define the characteristics of SE in this population. MATERIALS AND METHODS: Retrospective evaluation of 50 epileptic patients with SE, revision of the electro-clinical data and therapies, and definition of the semeiological subtypes, aetiology, outcome and related epileptic syndromes. RESULTS: We identified 28 convulsive (19 focal and 9 generalized) and 22 non-convulsive (8 focal and 14 generalized) SE patients. In 13 patients, SE was situation-related (poor compliance, AED reduction, worsening seizures). In the remaining 37 patients, SE was related to the natural history of epilepsy (progression of underlying pathologies or intrinsic expression of epileptic syndromes); in these last cases, our results show a higher occurrence in cryptogenic frontal epilepsy (p=0.01). We identified two subgroups according to the duration of the event, i.e. SE lasting <12h and SE lasting >12h. Our results showed a worse response to therapy in SE lasting >12h (p=0.01), a better response to therapy in non-convulsive SE than in convulsive SE (p<0.05) and a relationship at statistical significance limit between a poor response to therapy/worse outcome and symptomatic epileptic syndromes (p=0.06). CONCLUSION: SE in epileptic patients has a wide spectrum of electro-clinical features. It may be related to the withdrawal or reduction of AEDs, or may even be the expression of the evolution of epileptic syndromes. Response to therapy is dependent on early diagnosis and therapy.

Use of levetiracetam in treating epilepsy associated with other medical conditions.

OBJECTIVE: This prospective, open-label study was conducted to evaluate the effectiveness, tolerability, and safety of levetiracetam in patients with epilepsy in whom unfavorable metabolism, complex drug interactions, or direct toxic effects of antiepileptic drugs (AEDs) had caused a worsening of comorbid conditions. METHODS: Study design included the introduction of levetiracetam, discontinuation of other AEDs, and a serial assessment comprising electroencephalograms and blood tests at baseline and 2, 6, and 12 months. Of 21 patients, 16 had partial and five generalized epilepsy. Concomitant pathologies were gastroenterological (six), vascular (four), endocrinological (four), or complex conditions including hematological (four) or dermatological (three) disease. A change of regimen was necessitated by drug-drug interactions in four patients, direct real or potential toxic effects of previous AEDs in 13, and a combination of interactions/toxic effects in four. RESULTS: After 12 months, 12 patients were seizure-free, nine had reductions in seizure frequency of 50-75%, and improvement in concomitant medical conditions was observed. No side effects were reported. CONCLUSION: Levetiracetam appears to be effective, well tolerated, and safe in patients with epilepsy and other medical conditions that are difficult to manage because of drug interactions or AED-related side effects.

LGI1 gene mutation screening in sporadic partial epilepsy with auditory features.

Partial epilepsy with auditory features occasionally segregates in families as an autosomal dominant trait. In some families mutations in the leucine-rich glioma inactivated (LGI1) gene have been identified. Sporadic cases might harbour either denovo or low-penetrant LGI1 mutations, which will substantially alter the family risk for epilepsy. We selected sixteen sporadic patients with cryptogenic temporal lobe epilepsy and partial seizures with auditory features. We compared clinical features of these patients with those of published autosomal dominant family cases. We screened these patients for LGI1 mutations. Comparing the sporadic patients with the published familial cases no difference in either the primary auditory features or in the other associated epileptic manifestations was identified. Sequence analysis of the whole LGI1 gene coding regions in sporadic patients did not reveal changes in the LGI1 gene. The genetic analysis demonstrates that LGI1 is not a major gene for sporadic cases of partial epilepsy with auditory features at least in the Italian population. Screening of sporadic patients for LGI1 mutations appears not useful in genetic counselling of these patients.

fMRI/EEG in paroxysmal activity elicited by elimination of central vision and fixation.

Using functional MRI (fMRI) with concurrent EEG monitoring the authors studied cortical activation associated with epileptiform discharges in three patients with fixation-off sensitivity. The EEG paroxysmal activity elicited by eliminating central vision correlated significantly with an increased blood oxygen level-dependent signal in the extrastriate cortex (Brodmann areas 19 and 37). fMRI provides a unique opportunity for localizing precisely the cortical areas generating paroxysmal activity in patients with fixation-off sensitivity.