Use of perampanel oral suspension for the treatment of refractory and super-refractory status epilepticus.

INTRODUCTION: Status epilepticus (SE) is a medical emergency associated with a significant risk of disability and death. The treatment of SE follows a step-wise approach, with limited data on ideal antiseizure medications (ASMs) for refractory and super refractory SE (RSE/SRSE). Perampanel (PER), an AMPA receptor antagonist, has shown promise in animal models but still has limited data in humans. This study tried to evaluate optimal dosage and safety of PER in RSE and SRSE patients. MATERIALS AND METHODS: We retrospectively analysed 17 adult patients with RSE (1) or SRSE (16) treated with PER. Demographic and clinical data, including EEG patterns, ASMs administered, PER dosages, and PER plasma concentrations, were collected. For patients receiving a 24 mg PER loading dose (full dose group), the following treatment regimen was applied: 24 mg per day for 48 h following by 16 mg per day. The response to PER was assessed based on electroencephalographic (EEG) improvement from high to low epileptiform activity or from low to the absence of epileptiform activities. Safety was evaluated monitoring hepatic and renal function. RESULTS: A response rate of 58.82 % was observed, with significantly higher responses in the full dose group (81.82 %) compared to those receiving PER doses below 24 mg (low dose group) (16.67 %) (p-value = 0.004; OR 0.044, 95 % CI 0.003 to 0.621, p = 0.021). No other clinical factors significantly influenced treatment response. Hepatic enzymes become elevated in most patients (70.59 %) but spontaneously decreased. DISCUSSION: Our findings suggest that a 24 mg PER dose administered for 48 h may be more effective in managing RSE and SRSE compared to doses below 24 mg, potentially due to pharmacokinetic factors. CONCLUSION: More robust data on PER in RSE and SRSE, including standardized dosing procedures and plasma level monitoring are needed. PER's potential benefits should be explored further, particularly in patients with RSE and SRSE.

Lacosamide in monotherapy in BTRE (brain tumor-related epilepsy): results from an Italian multicenter retrospective study.

PURPOSE: Lacosamide (LCM) is a third-generation anti-seizure medication (ASM) approved for focal onset epilepsy in patients aged ≥ 4.378 Previous studies have reported an efficacy of LCM as add-on treatment in brain tumor-related epilepsy (BTRE). To date, there are no studies in the literature focusing on lacosamide used in monotherapy to treat BTRE. In our retrospective study we investigated efficacy and tolerability of LCM in monotherapy in a multicenter national cohort of primary brain tumor patients. METHODS: We collected from 12 Italian Centers 132 patients with primary brain tumors who were treated with LCM in monotherapy. For each patient we evaluated seizure freedom at 3 and 6 months (primary endpoints), side effects and drop-out rate (secondary endpoints). RESULTS: Overall, LCM led to seizure freedom in 64.4% of patients at 3 months and 55% at 6 months. Patients who used two or more ASMs before LCM had a worse seizure control than patients in monotherapy with LCM as first choice. In 14 patients, we observed seizure control despite tumor progression on magnetic resonance (MRI). Multivariate analysis showed that gross-total resection at diagnosis was significantly associated with higher seizure freedom rate at 6 months. Side effects were mainly mild (grade 1-2 according to CTCAE classification) and drop-out rate was low (1.5%). Main side effects were dizziness and somnolence. CONCLUSIONS: This is the first study showing a good efficacy and tolerability of LCM when used in monotherapy in BTRE. Further prospective studies are needed to confirm these preliminary data, investigating also quality of life and neurocognitive functions.

Cluster-like headache. A comprehensive reappraisal.

Among the primary headaches, cluster headache (CH) presents very particular features allowing a relatively easy diagnosis based on criteria listed in Chapter 3 of the International Classification of Headache Disorders (ICHD-II). However, as in all primary headaches, possible underlying causal conditions must be excluded to rule out a secondary cluster-like headache (CLH). The observation of some cases with clinical features mimicking primary CH, but of secondary origin, led us to perform an extended review of CLH reports in the literature. We identified 156 CLH cases published from 1975 to 2008. The more frequent pathologies in association with CLH were the vascular ones (38.5%, n = 57), followed by tumours (25.7%, n = 38) and inflammatory infectious diseases (13.5%, n = 20). Eighty were excluded from further analysis, because of inadequate information. The remaining 76 were divided into two groups: those that satisfied the ICHD-II diagnostic criteria for CH, 'fulfilling' group (F), n = 38; and those with a symptomatology in disagreement with one or more ICHD-II criteria, 'not fulfilling' group (NF), n = 38. Among the aims of this study was the possible identification of clinical features leading to the suspicion of a symptomatic origin. In the differential diagnosis with CH, red flags resulted both for F and NF, older age at onset; for NF, abnormal neurological/general examination (73.6%), duration (34.2%), frequency (15.8%) and localization (10.5%) of the attacks. We stress the fact that, on first observation, 50% of CLH presented as F cases, perfectly mimicking CH. Therefore, the importance of accurate, clinical evaluation and of neuroimaging cannot be overestimated.

Osmophobia in migraine and tension-type headache and its clinical features in patients with migraine.

Intolerance to smell is often reported by migraine patients. This study evaluates osmophobia in connection with the diagnosis of migraine and episodic tension-type headache (ETTH). The characteristics of this symptom are also investigated. We recruited from our Headache Centre 1005 patients (772 female, 233 male; age 37 +/- 11 years), of whom 677 were migraine without aura (MoA), 130 migraine with aura (MA) and 198 TTH. Patients with two or more forms of primary headache were excluded. Among migraine patients, 43.9% with MoA and 38.5% with MA reported osmophobia during the attacks; none of the 198 TTH patients suffered this symptom. Most frequently offending odours were scents (63.9%), food (55.2%) and cigarette smoke (54.8%). Osmophobia appears structurally integrated into the migraine history of the patient. It seems to be a peculiar symptom favouring the diagnosis of migraine (MoA and MA) in the differential diagnosis with ETTH.

[The ST/HR slope and coronary stenoses]. / ST/HR slope e stenosi coronariche.

BACKGROUND: The heart rate adjustment of ST depression (ST/HR Slope) has been shown by some authors to markedly improve the accuracy of treadmill exercise electrocardiogram for identifying and quantifying coronary artery disease. However, other authors have obtained different results. In the present study the results of our exercise electrocardiography laboratory are compared with the data obtained from the literature. METHODS: Fifty patients (46 males and 4 females, age range 60 +/- 7 years) with suspect or certain coronary artery disease were referred for a routine treadmill exercise electrocardiogram, and subsequently underwent cardiac catheterization and selective coronary cineangiography to assess the severity of coronary obstruction. All patients exercised according to a recently reported modification of the standard Bruce protocol, proposed by Kligfield et al, for a more accurate evaluation of the ST/HR Slope, which was calculated in real time by a computerized system. Patients with coexisting valvular heart disease, cardiomyopathy, left bundle-branch block on the resting ECG, myocardial infarction within 8 weeks, diabetes mellitus, hypertensive response during exercise testing (diastolic blood pressure > 95 mm Hg and/or systolic blood pressure > 190 mm Hg), abnormalities or variations of the coronary arteries, were excluded from this study. RESULTS: This method correctly identified 13 of 14 patients with multivessel coronary artery disease and 35 of 36 with less severe disease: one patient was false negative and another one false positive. Thus, in our exercise electrocardiography laboratory this approach shows a sensitivity of 93%, a specificity of 97%, a positive predictive value of 93% and a negative predictive value of 97% for the detection of severe coronary disease. CONCLUSIONS: These findings suggest that, in patients selected as in this study, the ST/HR slope is a good method which improves the clinical usefulness of the treadmill exercise electrocardiogram in coronary artery disease.

Spontaneous carotid artery dissection with cluster-like headache.

A case of carotid artery dissection in a 41-year-old-woman is described whose main symptom was cluster-like pain. The case is interesting for its atypical presentation with only two other like cases in the literature, and the site of dissection, localized in the intrapetrous curvature of the carotid artery. The case highlights the need for active co-operation between clinician and neuroradiologist during neuroimaging assessment which must be focused on the clinical evaluation of the individual patient so as to avoid error, particularly in atypical cases.

Possible role of a ventricular conduction disturbance in the electrogenesis of the ECG-VCG signs of myocardial infarction.

The typical QRS patterns of myocardial infarction (MI-QRS) are commonly attributed to myocardial cellular death. However, observation of a transient appearance of MI-QRS during coronary insufficiency, the disappearance of MI-QRS after coronary by-pass surgery and the appearance of MI-QRS after intracranial hemorrhage suggest that a different electrophysiological mechanism may be at work. There is a single convincing explanation for all these observations. It seems possible, at least theoretically, that a localized conduction disturbance can generate or contribute to the generation of the MI-QRS. The results obtained in nine out of 194 cases studied by means of premature right atrial stimulation (PRAS) in our laboratory seem to confirm this hypothesis. In five of them we observed typical MI-QRS in the aberrant beats which were absent in the basal tracings. In the other four cases, MI-QRS which were present in basal tracings disappeared in the aberrant beats. In three of these a reduction in the duration of QRS was also observed, while in the fourth the duration of QRS did not change. In no case could the alterations of QRS (induction or disappearance of MI-QRS) be explained by a classical conduction disturbance, preexcitation or by a premature ventricular beat. While the induction of MI-QRS was clearly due to an aberrant conduction in the supraventricular beats, the disappearance of basal MI-QRS changes in premature supraventricular beats is more difficult to explain. One possible electrophysiological mechanism could be a supernormal phase conduction. If this is the case, the basal MI-QRS could be due to a ventricular conduction disturbance. In conclusion, our results suggest that MI-QRS can be generated, at least in our cases, by a localized conduction disturbance.

The role of left ventricular conduction in the electrogenesis of left ventricular hypertrophy. An electrophysiologic study in man.

Various electrocardiographic and vectorcardiographic (ECG-VCG) patterns of ventricular conduction disturbances are inducible by premature right atrial stimulation (PRAS). These patterns are a consequence of different degrees of refractoriness in the specialized ventricular conduction system. We observed that the intermediate phase of left bundle branch block (LBBB) induced by PRAS in 20 subjects with normal basal QRS (complexes) were similar to those of left ventricular hypertrophy (LVH). In 18 patients with basal ECG-VCG signs of LVH, right bundle branch block (RBBB) induced by PRAS produced a progressive disappearance of these signs and the "normalization" of the tracings. The initial maximum QRS vector decreased, disappeared or remained absent in the patients with LBBB induced by PRAS, and appeared (when absent in the basal VCG) and remained unchanged (when present) in patients with RBBB induced by PRAS. In this paper we discuss the electrogenetic implications of these data. The ECG-VCG sings of LVH are probably dependent on a slowed conduction in the left bundle branch system, while anatomical hypertrophy per se probably plays a less important role.

[Accelerated idioventricular rhythm wih isorhythmic A-V dissociation. An electrophysiological study (author's transl)]. / Ritmo idioventricolare accelerato con dissociazione A-V isoritmica. Studio elettrofisiologico.

Three cases of accelerated idioventricular rhythm with isorhythmic A-V dissociation are presented. One case was affected by hypertrophic non obstructive myocardiopathy and two cases were affected by coronary heart disease with previous myocardial infarction. In all the cases of the arrhythmia persisted for days or months. By means of the electrophysiological study we could establish that 1) the focus was not protected by entrance block and 2) it was localized in the main branches of the conduction system. In the first case the focus was localized in the right bundle branch, in the second case, it was localized in the anterior fascicle of the left bundle branch and in the third case in the posterior fascicle of the left bundle branch. These electrophysiological characteristics suggest that the arrhythmia was due to increased firing of normal idioventricular pacemakers. On the basis of this electrogenetic interpretation we outline that in our cases the term of accelerated idioventricular rhythm should be preferred to others used in literature such as slow ventricular tachycardia.

[Clinical significance of corrected sinus node recovery time and natural and unnatural history of sinus node dysfunctions. A four-year prospective follow-up of 101 cases]. / Significato clinico del tempo di recupero sinusale corretto e storia naturale ed innaturale delle disfunzioni del nodo del seno. Follow-up prospettico di 4 anni relativo a 101 casi.

The clinical significance of corrected sinus node recovery time (CSNRT) and the natural and unnatural history of sinus node dysfunctions are not completely known. To gain some insight into this problem, 101 patients (pts) (54M, 47F, mean age +/- SD = 62.02 yrs +/- 14.42) with clinical and ECG signs of definite or suspected sick sinus syndrome (SSS) underwent an electrophysiologic study and then were prospectively followed for a mean period of 44.36 months +/- 18.96 (range: 2-78 months). The pts were divided into two groups: 1) Group A: 68 pts with prolonged CSNRT (greater than 500 msec); 2) Group B: 33 pts with normal CSNRT. Thirty-three pts of Group A (48.5%) and 2 pts of Group B (6.1%) received VVI pacemaker implantation (PM) immediately after the electrophysiologic study. The following results were obtained: 1) Pts of Group A showed a higher prevalence of organic heart disease and of ECG signs of definite SSS than pts of Group B. (p less than 0.05). Moreover, the higher the CSNRT in Group A pts, the more severe the ECG abnormalities of SSS. 2) Pts without PM, both of Group A and Group B, noted during the follow-up period a disappearance of neurological symptoms (syncopes and/or dizziness) and of ECG abnormalities of SSS in more than 50% of the cases. However, this was less evident in Group A pts compared with Group B pts (53.8% vs 78.6% regarding neurological symptoms and 54.3% vs 74.1% regarding ECG abnormalities of SSS) as well as in pts with organic heart disease in comparison with those with primitive SSS. Moreover, the number of pts who needed PM implantation during the follow-up period due to the worsening of clinical and ECG signs of SSS were higher in Group A than in Group B (20% vs 6.5%). The occurrence of cardiac death among the pts without PM was similar in pts of Group A (8.5%) and in those of Group B (9.7%). One pt of Group A without PM died suddenly (less than 1 hour). 3) Pts who required PM implantation were older (p less than 0.01) and showed a prevalence of organic heart disease higher (p less than 0.05) than those who did not require PM implantation. Pts with PM, both of Group A and Group B, showed a complete disappearance of syncopes and a clear-cut reduction of dizziness after implantation of it. On the contrary, dyspnea nearly always persisted and sometimes appeared when initially absent. Sudden and non-sudden cardiac death in PM pts (13.6%) was somewhat more frequent than in those without PM. 4) The incidence of stable atrial fibrillation was 12.1% in pts without PM and 27.2% in pts with PM. The occurrence of stable atrial fibrillation in pts without PM was generally not followed by clinical improvement. 5) The incidence of cerebrovascular accidents was approximately 8%. The accidents always occurred in pts with organic heart disease and often in the older pts (mean age: 75.1 yrs +/- 5.7) particularly in those with PM. A bradycardia-tachycardia syndrome was observed only in 3 pts who had a stroke...