The ROME (Retrospective Observational Multicenter study on Eslicarbazepine) study: Efficacy and behavioural effects of Eslicarbazepine acetate as adjunctive therapy for adults with partial onset seizures in real life.

PURPOSE: Eslicarbazepine acetate (ESL) is a third-generation member of the dibenzazepine family approved in 2009 by the European Medicines Agency with the indication of adjunctive therapy in adult people with partial-onset seizures (PPOS). We aimed at assessing the ESL impact on seizure frequency and quality of life in PPOS with a particular attention to sleepiness and depression. METHODS: We evaluated 50 adult PPOS (>18 years; 48 ±â€¯14 years-old; 23 males) treated with adjunctive ESL for ≥2months with a retrospective multi-centric design. Clinical files of the last 2 years were reviewed checking for monthly seizure frequency, treatment retention rate, adverse drug reactions (ADRs), concomitant anti-epileptic drugs and behavioural scales for sleepiness (Stanford Sleepiness Scale, SSS, and Epworth Sleepiness Scale, ESS), depression (Beck Depression Inventory-II, BDI) and overall quality of life (QOLIE-31). RESULTS: At the end of 96 ±â€¯28 days of ESL treatment, the mean seizure reduction was 56%; 60% of patients had seizure reduction above 50%, with a 31% of the whole population becoming seizure free. We reported 16 ADRs with 4 hyponatremia. Retention rate was 76%. Patient reported less sleepiness after ESL (SSS, p = 0.031; ESS, p = 0.0000002). Before ESL, 38% of patients had pathologic BDI scores, which normalized in most of them (73%) after ESL (BDI improvement, p = 0.000012). These scores resulted in an amelioration of quality of life (QOLIE-31, p = 0.000002). CONCLUSIONS: ESL is a safe and effective anti-epileptic drug in a real life scenario, with an excellent behavioural profile for the overall quality of life and, in particular, for sleepiness and depression.

Optic Nerve Sheath Diameter Ultrasound Evaluation in Intensive Care Unit: Possible Role and Clinical Aspects in Neurological Critical Patients' Daily Monitoring.

Background. The increase of the optic nerve sheath diameter (ONSD) is a reliable, noninvasive sonographic marker of intracranial hypertension. Aim of the study was to demonstrate the efficacy of ONSD evaluation, when monitoring neurocritical patients, to early identify malignant intracranial hypertension in patients with brain death (BD). Methods. Data from ultrasound ONSD evaluation have been retrospectively analyzed in 21 sedated critical patients with neurological diseases who, during their clinical course, developed BD. 31 nonneurological controls were used for standard ONSD reference. Results. Patients with neurological diseases, before BD, showed higher ONSD values than control group (CTRL: RT 0.45 ± 0.03 cm; LT 0.45 ± 0.02 cm; pre-BD: RT 0.54 ± 0.02 cm; LT 0.55 ± 0.02 cm; p < 0.000) even without intracranial hypertension, evaluated with invasive monitoring. ONSD was further significantly markedly increased in respect to the pre-BD evaluation in neurocritical patients after BD, with mean values above 0.7 cm (RT 0.7 ± 0.02 cm; LT 0.71 ± 0.02 cm; p < 0.000), with a corresponding dramatic raise in intracranial pressure. Logistic regression analysis showed a strong correlation between ONSD and ICP (R 0,895, p < 0.001). Conclusions. ONSD is a reliable marker of intracranial hypertension, easy to be performed with a minimal training. Routine ONSD daily monitoring could be of help in Intensive Care Units when invasive intracranial pressure monitoring is not available, to early recognize intracranial hypertension and to suspect BD in neurocritical patients.

A Novel MGC4607/CCM2 Gene Mutation Associated with Cerebral Spinal and Cutaneous Cavernous Angiomas.

Cerebral cavernous malformations (CCMs) are vascular abnormalities that may cause seizures, headaches, intracerebral hemorrhages, and focal neurological deficits; they can also be clinically silent and occur as a sporadic or an autosomal dominant condition. Three genes have been identified as causing familial CCM: KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3, mapping, respectively, on chromosomes 7q, 7p, and 3q. Here, we report an Italian family affected by CCM due to a MGC4607 gene mutation, on exon 4. All the affected subjects suffered from seizures, and some of them underwent surgery for removal of a cavernous angioma. Brain MRI showed multiple lesions consistent with CCMs in all patients. Spinal and cutaneous cavernous angiomas were present too. This report underlines the need for a careful interdisciplinarity among neurologists, neuroradiologists, neurosurgeons, geneticists, ophthalmologists, and dermatologists for a total evaluation of the different manifestations of familial CCM. This points out that only referral centers are organized to offer a multidisciplinary management of this disease.

Current practice of brain death determination and use of confirmatory tests in an Italian University hospital: a report of 66 cases.

BACKGROUND: Time to final brain death (BD) determination is fundamental to rapidly identify donors without organ deterioration. Guidelines for BD determination are different from country to country and, through years, they have been subjected to several revisions, to simplify the procedure. The aim of this study was to describe a one-year experience according to the latest Italian Guidelines for BD in our University hospital and to focus on timing of final BD declaration according to the ancillary tests executed. METHODS: Sixty-six consecutive inpatients with BD diagnosis were enrolled. Etiological factors, ancillary tests and timing to final declaration were analyzed. RESULTS: Electroencephalogram (EEG) could be performed without artifacts in all the patients. Time to BD procedure starting depended on whether the demonstration of cerebral circulatory arrest was required, being shorter with EEG only (40±17 min), longer with cerebral blood flow evaluation (175±95 min), minimal with transcranial Doppler (83±32 min), maximal with angiography (165±20 min). None of the patients who initiated BD procedure were found to recover cerebral or brainstem function at the second observation. CONCLUSIONS: In Italy, the same guidelines ensure the same approach in every hospital, with multi-specialist cooperation. The EEG is mandatory and prompt recognition of the first, flat EEG is fundamental to reduce time to the final procedure. A multimodal neurophysiological approach with trained specialists, neurosonologists and monitoring devices in intensive care units may represents a valid help to further reduce time for BD diagnosis.

Advantages and pitfalls of three-dimensional ultrasound imaging of carotid bifurcation.

OBJECTIVES: Several specialists use three-dimensional (3D) ultrasound as adjuvant imaging technique in their clinical practice. It has been applied to study carotid plaque morphology, surface and volume during atherosclerosis progression. Nonetheless, no papers have so far described the use of this technique in conditions different than carotid stenosis, such as bifurcation anatomy changes of the caliber and vessel course modifications. METHODS: Patients admitted to our ultrasound laboratory for vascular screening were submitted to standard carotid duplex and to 3D ultrasound reconstruction of the carotid bifurcation. RESULTS: Forty normal subjects, 7 patients with caliber alterations (4 carotid bulb ectasia and 3 internal carotid lumen narrowing), 45 patients with course variations (tortuosities and kinking) and 35 patients with internal carotid artery stenosis of various degrees have been investigated. CONCLUSIONS: 3D ultrasound is a feasible technique. It can improve carotid axis imaging through a better presentation of caliber variations and vessel course 'at a glance'. 3D ultrasound from the inward flow can provide imaging of the stenosis, but stenosis quantification should always take into account the assessment of plaque morphology and vessel wall.

Reversible encephalopathy induced by cefoperazone: a case report monitored with EEG.

In patients with an impaired state of consciousness, EEG is fundamental, a correct neurological work-up. Cephalosporins have been identified as a case of triphasic waves' (TW) reversible encephalopathy. We report a case of an acute reversible encephalopathy with TWs during treatment with cefoperazone. We report the occurrence and regression of a confusional state with TWs encephalopathy at EEG after the administration of cefoperazone for urinary tract infection in a patient admitted for syncope. In conclusion, cefoperazone should be considered as a cause of toxic encephalopathy with EEG TWs, when there is a temporal relationship with its administration; EEG monitoring is useful in the neurological follow-up.

EEG patterns and epileptic seizures in acute phase stroke.

BACKGROUND: The rate of early post-stroke epileptic seizures ranges from 2 to 33%. This wide range is likely due to differences in study design, patient selection and type of neurophysiological monitoring. Electroencephalography (EEG), which is not used in the routine work-up of acute stroke, is the best neurodiagnostic technique for detecting epileptic activity, especially in patients with non-convulsive post-stroke epileptic activity. The aim of this study was to analyze patterns on EEGs performed within 24 h of stroke onset, and to investigate correlations between these patterns and the occurrence of early epileptic seizures and status epilepticus (SE), vascular risk factors, stroke subtypes and short-term outcome. METHODS: We prospectively studied 232 patients (mean age 71 ± 12 years; 177 ischemic strokes and 55 hemorrhagic). EEG recording was performed within 24 h from hospitalization. The follow-up lasted 1 week. RESULTS: Fifteen patients (6.5%) had early seizures within 24 h; 10 of these patients had focal SE with or without secondary generalization. EEG revealed sporadic epileptiform focal abnormalities in 10% and periodic lateralized epileptiform discharges (PLEDs) in 6%. SE was recorded in 71.4% of patients with PLEDs. At the multivariate analysis, only early epileptic manifestations (p < 0.001) were independently associated with PLEDs. CONCLUSIONS: Our study confirms that seizures are not frequent in the early phase of acute stroke and occur prevalently as focal SE at onset. EEG may help to detect specific patterns, such as PLEDs, that are closely related to early seizures. EEG monitoring should be performed in order to detect purely electrographic seizures.

Transcranial Doppler for brain death in infants: the role of the fontanelles.

OBJECTIVE: Transcranial Doppler (TCD) is a sensitive technique for circulatory arrest diagnosis in brain death when patterns such as reverberant flow and short systolic spikes are observed. In infants, the nonossified fontanelles compensate for intracranial hypertension. We describe TCD patterns in infants with brain death, different from adults, with the hemodynamic modifications induced by anterior fontanelle compression. METHOD: TCD was performed in 2 infants with diagnosed brain death admitted to the neonatal intensive care unit. RESULTS: TCD showed a large peak 'reverberant' flow, with a high peak systolic velocity and a consistent retrograde component, away from the brain. Compression of the anterior fontanelle induced, at first, a reduction in systolic flow with the subsequent appearance of the characteristic short systolic spikes. Upon compression removal, a brief increase in the systolic flow was observed before the prompt reappearance of the reverberant flow. CONCLUSION: TCD for brain death diagnosis should be done cautiously in infants. In these cases, reverberating flow may be indicative of circulatory arrest even if with a large peak and with a high peak systolic velocity. Heavy fontanelle compression may reproduce the classical adult TCD patterns of brain death, thus supporting the diagnosis of cerebral circulatory arrest.

Combined transcranial Doppler and EEG recording in vasovagal syncope.

BACKGROUND: In neurally mediated syncope a 'typical' EEG pattern during hyperventilation (HV) may be observed. This study aimed to investigate transcranial Doppler (TCD) and EEG variations in response to hyper- and hypocapnia using simultaneous recording. METHODS: Syncope patients with a typical EEG pattern during HV (SEEG+, n = 15) and those without abnormalities (SEEG-, n = 16) were compared with healthy controls (n = 20). Simultaneous TCD and EEG recordings were performed at rest (baseline), during 2 apnea tests and during HV. Cerebrovascular vasoreactivity, index for hypocapnia, total vasomotor reserve and time to flow velocity normalization after HV (t-norm) were recorded. RESULTS: With TCD, a reduction in Vasomotor reserve was observed in SEEG+ compared with the other 2 groups (control: 67 +/- 8%; SEEG-: 67 +/- 10%; SEEG+: 57 +/- 8%; p < 0.0001). t-norm was longer in all syncopal patients and in particular in SEEG+ (control: 20.2 +/- 3 s; SEEG-: 40 +/- 7 s; SEEG+: 123 +/- 45s; p < 0.0001). Quantitative EEG showed an increase in slow bands in all subjects during HV, small and nonsignificant in controls and SEEG-, higher and significant in SEEG+, related with flow reduction. CONCLUSIONS: Changes in the sympathetic modulation of cerebral vasoconstriction may explain both the pathophysiology of vasovagal syncope and the typical paroxysmal EEG findings.

Observations on EEG patterns in neurally-mediated syncope: an inspective and quantitative study.

We performed an observational EEG study in 43 patients with neurally-mediated syncope in basal condition and during hyperventilation (HV), and compared it with 32 healthy controls. On blind analysis at rest, EEG was classified as normal in 47% of patients (vs. 94% of controls, P < 0.001). More abundant and pronounced delta-theta activities and alpha slowing were found in patients than in control subjects on both visual inspection and quantitative spectral analysis. During prolonged HV, the EEG remained normal in 21% of patients only. Slow activities became more evident in patients than in control subjects, and intermittent rhythmic delta activity appeared in 40% of syncopal patients. These "pseudoparoxysmal" EEG changes differed from the common slowings induced by HV in adult subjects and were not observed in our control subjects. Moreover, these distinctive EEG changes, a common finding in syncopal patients, could not be confused with epileptiform activity of any kind. Further studies will clarify the pathophysiology of these EEG modifications.

Clinical and electroencephalographic effects of topiramate in patients with epilepsy and healthy volunteers.

Although topiramate, one of the newer drugs used in treating epilepsy, is effective in reducing seizure frequency and has a wide spectrum of action, it often induces intolerable adverse effects, predominantly related to the central nervous system. Information that would help document adverse reactions early, thus allowing topiramate doses to be adjusted during the drug titration and maintenance phases, could be obtained from electroencephalogram (EEG) studies. We studied the clinical effects and EEG changes induced by topiramate in patients with refractory partial epilepsy receiving the drug as add-on therapy. To exclude effects related to the other drugs and to epilepsy itself, we compared data from patients and healthy volunteers. After receiving topiramate, 22.6% of patients became seizure free and 29% had their seizures reduced by 50% or more. Topiramate nevertheless induced noteworthy adverse reactions, the main problems being sedative and cognitive changes. Also, in healthy volunteers, a single 100-mg dose of topiramate induced mild adverse reactions, mainly affecting concentration and attention, with difficulties in speech and writing. In patients with epilepsy, the EEG changes induced by topiramate consisted of increased delta and theta activities and decreased activity in the rapid bands. This recognizable topiramate-induced EEG pattern was again evident in the healthy volunteers, in whom we also detected a significant reduction in the alpha frequency rhythm. Our results confirm that topiramate needs to be introduced gradually while patients undergo close neuropsychologic and neurophysiologic monitoring to detect adverse sedative and cognitive reactions early. The EEG correlate of these events seems to be increased activity in the slower frequency bands.