Early seizures and risk of epilepsy and death after intracerebral haemorrhage: The MUCH Italy.

INTRODUCTION: It is unclear which patients with non-traumatic (spontaneous) intracerebral haemorrhage (ICH) are at risk of developing acute symptomatic seizures (provoked seizures occurring within the first week after stroke onset; early seizures, ES) and whether ES predispose to the occurrence of remote symptomatic seizures (unprovoked seizures occurring more than 1 week after stroke; post-stroke epilepsy, PSE) and long-term mortality. PATIENTS AND METHODS: In the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) we examined the risk of ES and whether they predict the occurrence of PSE and all-cause mortality in a cohort of patients with first-ever spontaneous ICH and no previous history of epilepsy, consecutively hospitalized in 12 Italian neurological centers from 2002 to 2014. RESULTS: Among 2570 patients (mean age, 73.4 ± 12.5 years; males, 55.4%) 228 (8.9%) had acute ES (183 (7.1%) short seizures and 45 (1.8%) status epilepticus (SE)). Lobar location of the hematoma (OR, 1.49; 95% CI, 1.06-2.08) was independently associated with the occurrence of ES. Of the 2,037 patients who were followed-up (median follow-up time, 68.0 months (25th-75th percentile, 77.0)), 155 (7.6%) developed PSE. ES (aHR, 2.34; 95% CI, 1.42-3.85), especially when presenting as short seizures (aHR, 2.35; 95% CI, 1.38-4.00) were associated to PSE occurrence. Unlike short seizures, SE was an independent predictor of all-cause mortality (aHR, 1.50; 95% CI, 1.005-2.26). DISCUSSION AND CONCLUSION: The long-term risk of PSE and death after an ICH vary according to ES subtype. This might have implications for the design of future clinical trials targeting post-ICH epileptic seizures.

Successful Treatment of Post COVID-19 Neurogenic Dysphagia with Botulinum Toxin.

Introduction: Dysphagia in post COVID-19 patients could be caused by several factors, including reduced pharyngolaryngeal coordination due to SARS-CoV-2 tropism to the central and/or peripheral nervous system. To our knowledge, this is the first reported case of COVID-19-related dysphagia successfully treated with botulinum toxin type A injection. Case description: We report the case of a patient with severe oropharyngeal dysphagia due to COVID-19 confirmed by fibre endoscopy. As a result, the patient required an enteral feeding tube. After two months of traditional swallowing therapies, there was only limited improvement. An electrophysiologic evaluation of the cricopharyngeal muscle was performed and showed a normal inhibition of the cricopharyngeal muscle, followed by a hypertonic rebound. Based on this result, we decided to perform a unilateral laryngeal injection of botulinum toxin type A. After the injection, the patient's swallowing function improved significantly, allowing him to return to oral feeding. Discussion: Newly diagnosed oropharyngeal dysphagia was found in 35.3% of hospitalised patients with COVID-19. There are several possible causes of COVID-19-associated dysphagia, including stroke, encephalitis, critical illness neuropathy, Guillain-Barré syndrome and skeletal muscle injury. In our case, since stroke was excluded by brain MRI, cranial nerve injury was a possible explanation for the difficult recovery of swallowing despite daily swallowing therapy. Conclusion: We suggest that electrophysiology is a valid tool for the diagnosis and follow-up of patients with oropharyngeal dysphagia. LEARNING POINTS: SARS-CoV-2 tropism to the central and/or peripheral nervous system can cause dysphagia in post COVID-19 patients.An electrophysiologic approach is useful for the diagnosis and follow-up of patients with oropharyngeal dysphagia.A single botulinum toxin type A injection is a valid treatment option to improve the swallowing function in patients with post COVID-19 dysphagia.

Effect of extracranial-intracranial bypass revascularization procedure in acute stroke after endovascular failure: the EIRASP study protocol.

BACKGROUND: Intravenous thrombolysis and endovascular reperfusion represent nowadays the standard treatment for acute ischemic stroke. However, ineffective reperfusion may occur, representing a major negative prognostic factor on clinical outcome. Extracranial-intracranial (EC-IC) bypass revascularization procedure in an acute setting appears as a promising tool to increase reperfusion rates and improve clinical outcome in a highly selected population refractory or ineligible for standard reperfusion therapies. METHODS: The Extracranial-Intracranial Revascularization for Acute Stroke - Parma (EIRASP) study is an observational, prospective, single-center, study (protocol 203/2020/OSS/AOUPR). Patients admitted for an acute ischemic anterior circulation stroke due to large vessels occlusion and refractory or ineligible for standard reperfusion therapies will be submitted to an extracranial-intracranial bypass revascularization procedure when fulfilling all clinical and radiological inclusion criteria. The primary outcome will be the functional outcome (modified Rankin Scale and NIHSS score) at 3 months after the surgical procedure. Secondary outcome will include the evaluation of clinical and surgical complications rates, quantitative monitoring of perfusion parameters, and further functional and survival rates. RESULTS: Despite promising data regarding the feasibility and the favorable outcome of urgent EC-IC bypass revascularization procedure in selected patients suffering an acute ischemic stroke are emerging in literature, no studies to date have prospectively explored the real potential of this technique. CONCLUSIONS: The EIRASP study aims to provide further and stronger methodological evidence of the benefit of urgent EC-IC bypass revascularization procedure in acute ischemic stroke.

A case of Huntington disease-like 2 in a patient of African ancestry: the everlasting support of clinical examination in the molecular era.

Chorea, cognitive decline, and psychiatric symptoms are shared by Huntington's disease (HD) and similar conditions called HD phenocopies. We describe the first case reported in Italy of Huntington disease-like 2 (HDL2), clinically and radiologically indistinguishable from HD, showing the importance of considering African ancestry in the diagnostic process.

Sex differences in outcome after thrombectomy for acute ischemic stroke. A propensity score-matched study.

Background and purpose: We sought to investigate whether there are gender differences in clinical outcome after stroke due to large vessel occlusion (LVO) after mechanical thrombectomy (EVT) in a large population of real-world patients. Methods: From the Italian Registry of Endovascular Thrombectomy, we extracted clinical and outcome data of patients treated for stroke due to large vessel occlusion. We compared clinical and safety outcomes in men and women who underwent EVT alone or in combination with intravenous thrombolysis (IVT) in the total population and in a Propensity Score matched set. Results: Among 3422 patients included in the study, 1801 (52.6%) were women. Despite older age at onset (mean 72.4 vs 68.7; p < 0.001), and higher rate of atrial fibrillation (41.7% vs 28.6%; p < 0.001), women had higher probability of 3-month functional independence (adjusted odds ratio-adjOR 1.19; 95% CI 1.02-1.38), of complete recanalization (adjOR 1.25; 95% CI 1.09-1.44) and lower probability of death (adjOR 0.75; 95% CI 0.62-0.90). After propensity-score matching, a well-balanced cohort comprising 1150 men and 1150 women was analyzed, confirming the same results regarding functional outcome (3-month functional independence: OR 1.25; 95% CI 1.04-1.51), and complete recanalization (OR 1.29; 95% CI 1.09-1.53). Conclusions: Subject to the limitations of a non-randomized comparison, women with stroke due to LVO treated with mechanical thrombectomy had a better chance to achieve complete recanalization, and 3-month functional independence than men. The results could be driven by women who underwent combined treatment.

Impact on Prehospital Delay of a Stroke Preparedness Campaign: A SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial).

BACKGROUND AND PURPOSE: Public campaigns to increase stroke preparedness have been tested in different contexts, showing contradictory results. We evaluated the effectiveness of a stroke campaign, designed specifically for the Italian population in reducing prehospital delay. METHODS: According to an SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial) design, the campaign was launched in 4 provinces in the northern part of the region Emilia Romagna at 3-month intervals in randomized sequence. The units of analysis were the patients admitted to hospital, with stroke and transient ischemic attack, over a time period of 15 months, beginning 3 months before the intervention was launched in the first province to allow for baseline data collection. The proportion of early arrivals (within 2 hours of symptom onset) was the primary outcome. Thrombolysis rate and some behavioral end points were the secondary outcomes. Data were analyzed using a fixed-effect model, adjusting for cluster and time trends. RESULTS: We enrolled 1622 patients, 912 exposed and 710 nonexposed to the campaign. The proportion of early access was nonsignificantly lower in exposed patients (354 [38.8%] versus 315 [44.4%]; adjusted odds ratio, 0.81; 95% confidence interval, 0.60-1.08; P=0.15). As for secondary end points, an increase was found for stroke recognition, which approximated but did not reach statistical significance (P=0.07). CONCLUSIONS: Our campaign was not effective in reducing prehospital delay. Even if some limitations of the intervention, mainly in terms of duration, are taken into account, our study demonstrates that new communication strategies should be tested before large-scale implementation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01881152.

Long-term outcomes of patients with cerebral vein thrombosis: a multicenter study.

BACKGROUND: Little information is available on the long-term clinical outcome of cerebral vein thrombosis (CVT). OBJECTIVES AND METHODS: In an international, retrospective cohort study, we assessed the long-term rates of mortality, residual disability and recurrent venous thromboembolism (VTE) in a cohort of patients with a first CVT episode. RESULTS: Seven hundred and six patients (73.7% females) with CVT were included. Patients were followed for a total of 3171 patient-years. Median follow-up was 40 months (range 6, 297 months). At the end of follow-up, 20 patients had died (2.8%). The outcome was generally good: 89.1% of patients had a complete recovery (modified Rankin Score [mRS] 0-1) and 3.8% had a partial recovery and were independent (mRS 2). Eighty-four per cent of patients were treated with oral anticoagulants and the mean treatment duration was 12 months. CVT recurred in 31 patients (4.4%), and 46 patients (6.5%) had a VTE in a different site, for an overall incidence of recurrence of 23.6 events per 1000 patient-years (95% confidence Interval [CI] 17.8, 28.7) and of 35.1 events/1000 patient-years (95% CI, 27.7, 44.4) after anticoagulant therapy withdrawal. A previous VTE was the only significant predictor of recurrence at multivariate analysis (hazard ratio [HR] 2.70; 95% CI 1.25, 5.83). CONCLUSIONS: The long-term risk of mortality and recurrent VTE appears to be low in patients who survived the acute phase of CVT. A previous VTE history independently predicts recurrent events.

The PACE study: past-year prevalence of migraine in Parma's adult general population.

BACKGROUND: In the literature there are few data about the prevalence of primary headaches, including migraine, in the Italian general population. The PACE study (PArma CEfalea, or 'Headache in Parma') is an observational study aimed at detecting the prevalence and clinical features of primary headaches in the city of Parma's adult general population. MATERIALS AND METHODS: A total of 904 subjects representative of Parma's adult general population were interviewed face-to-face by a physician from the Parma Headache Centre. They were given a specially designed and validated questionnaire for the diagnosis of primary headaches according to the ICHD-II criteria. RESULTS: Past-year adjusted prevalence of definite migraine, including migraine with and without aura and chronic migraine, was 24.7% (95% CI 21.9 to 27.5); 13% (95% CI 9.7 to 16.4) were men and 32.9% (95% CI 28.8 to 37.0) were women. Past-year prevalence of probable migraine was 5.1% (95% CI 3.6 to 6.5): 5.2% (95% CI 3.0 to 7.4) in men and 5% (95% CI 3.1 to 6.9) in women. CONCLUSIONS: The high prevalence of definite migraine is the major difference between our results and the literature data. Such a difference in results may be due to the use of a different investigational approach compared with the other epidemiological studies. However, an actual higher frequency of migraine in the Italian general population cannot be excluded given the lack of studies on this topic.

Description and validation of an Italian ICHD-II-based questionnaire for use in epidemiological research.

BACKGROUND: In the absence of biological markers, the diagnosis of primary headache in epidemiological studies rests on clinical findings, as reported through ad-hoc interviews. OBJECTIVES: The aim of this study was to validate a specially designed headache questionnaire to be administered by a physician for the diagnosis of primary headaches or of probable medication overuse headache in the general population according to the 2004 International Classification of Headache Disorders, 2nd edition (ICHD-II). METHODS: The questionnaire comprises 76 questions based on the ICHD-II diagnostic criteria for migraine (codes 1.1, 1.2.1, 1.2.2, 1.2.3, 1.5.1, and 1.6), tension-type headache (codes 2.1, 2.2, 2.3, and 2.4), primary stabbing headache (code 4.1), and probable medication-overuse headache (code 8.2.7), as well as on other clinical features (eg, age at onset, relation between headache and pregnancy, etc). The answers to each question could be of the following types: (1) numbers (ie, age at onset); (2) "Yes" or "No" (eg, as in reply to "Do you have nausea during headache?"); and (3) predefined answers (eg, quality of pain). We assessed the validity and reliability of the questionnaire and its sensitivity and specificity for migraine and tension-type headache. RESULTS: The study population consisted of 50 patients (37 women and 13 men) aged 18-76 years (mean, 40.7) seen for the first time on a consecutive basis at the University of Parma Headache Centre. The questionnaire was administered independently by 2 trained physicians (E1 and E2) prior to the visit performed by a headache specialist taken as the gold standard (GS). GS, E1, and E2 were blind to the diagnosis made by each others. If appropriate, more than 1 headache type were considered. When present, we defined the 2 different headache types in the same subject as Diagnosis 1 and Diagnosis 2. Questionnaire-based diagnosis was compared with the diagnosis established by GS. For Diagnosis 1 (n = 50), we found an agreement rate of 98% (K-value: 0.96; 95% confidence interval [CI]: 0.88-1.00) between E1 and GS and between E2 and GS, and of 96% (K-value: 0.91; 95% CI: 0.80-1.00) between E1 and E2. For Diagnosis 2 (n = 24), we found an agreement rate of 83.3% (K-value: 0.80; 95% CI: 0.63-0.98) between E1 and GS, of 62.5% (K-value: 0.62; 95% CI: 0.41-0.82) between E2 and GS, and of 70.8% (K-value: 0.66; 95% CI: 0.45-0.87) between E1 and E2. Sensitivity and specificity were 100% and 93.3%, respectively, for migraine without aura (code 1.1) and 100% for frequent episodic tension-type headache (code 2.2). CONCLUSION: Our findings support the use of this questionnaire as a valid and reliable tool for diagnosis of headaches in epidemiological studies.

Mode of occurrence of traumatic head injuries in male patients with cluster headache or migraine: Is there a connection with lifestyle?

INTRODUCTION: Our study objective was to investigate the mode of occurrence of traumatic head injury in episodic cluster headache and migraine patients. METHODS: We conducted a retrospective study on 400 male patients, 200 with cluster headache (cases) and 200 with migraine (controls). We investigated the frequency and mode of occurrence of traumatic head injury and some lifestyle habits. RESULTS: The number of traumatic head injuries was significantly higher in cases than in controls (adjusted odds ratio [OR] = 2.0; 95% confidence interval [CI] = 1.5-2.8). Cases were more often responsible for the head traumas (adjusted OR = 2.6; 95% CI = 1.3-4.9) and reported a significantly higher proportion of injuries during scuffles or brawls (OR = 6.5; 95% CI = 2.9-14.8). Compared with other cluster headache patients, cases responsible for traumatic head injuries were more frequently heavy alcohol (p = .000), heavy tobacco (p = .03) and heavy coffee consumers (p = .003). CONCLUSIONS: Cluster headache patients (a) had traumatic head injuries more frequently than migraineurs; and (b) were more often responsible for them, perhaps due to particular behaviours related to their lifestyles.

Post-traumatic cluster headache: from the periphery to the central nervous system?

A correlation between head trauma and cluster headache is believed to exist. We report a case of post-traumatic episodic cluster headache that fulfills the criteria of the International Classification of Headache Disorders, 2nd edition. The distinctive features of this case are: a close temporal relation between head trauma and headache onset; pain ipsilateral to the side of trauma; mild severity of trauma; episodic course well-responsive to low doses of verapamil. Given the close temporal relation between the 2 events, multiple hypotheses can be advanced about a possible role of head trauma in the pathogenesis of cluster headache.

Fasting headache: a review of the literature and new hypotheses.

Headache is a common disorder in the general population. It is often highly debilitating for the people affected and highly costly to society. Although we know much about primary headaches, little is known about secondary headaches which, however,are a frequent occurrence in the general population. A study conducted on Denmark's general population found a lifetime prevalence rate of 22% for headache forms attributed to disorder of homeostasis, including fasting headache.The purpose of this review was to analyze literature data on fasting headache, in order to evaluate its possible pathophysiological mechanisms and to suggest therapeutic strategies.We considered only English-language articles published in scientific journals and searched for these articles on PubMed using "headache," "fasting," "Yom Kippur," "Ramadan," "hypoglycemia,"and "caffeine withdrawal" as key words, with no limitations to the year of publication. In most cases, fasting headache has the same clinical features as tension-type headache and the probability of onset increases directly with the duration of fasting.Hypoglycemia and caffeine withdrawal have been especially implicated as causative factors, but much remains to be understood about this topic.

Atrial septal defect closure and migraine with aura: is there a correlation?

Recently, some authors detected increased frequency or new onset of migraine with aura (MA) after atrial septal defect (ASD) closure. We report the effects of ASD closure on the occurrence of MA in three patients of Parma Headache Centre. Two of them developed MA after the procedure one had a worsening of pre-existing MA. The increased frequency or the de novo onset of MA after ASD closure may be related to the alteration of some physiological variables that play a central role in the physiopathogenetic mechanisms of MA and may trigger attacks in predisposed individuals. In previous literature reports, the new pattern of MA appeared self-limiting within a few weeks or months. In our cases, it seemed to last longer, but the natural history of this headache subtype suggests that this finding could be related to the extended duration of our follow-up and to the prospective nature of our study.

Cardiac cephalgia.

The purpose of this review was to provide a critical evaluation of medical literature on so-called "cardiac cephalgia" or "cardiac cephalalgia". The 2004 International Classification of Headache Disorders codes cardiac cephalgia to 10.6 in the group of secondary headaches attributed to disorder of homoeostasis. This headache is hardly recognizable and is associated to an ischaemic cardiovascular event, of which it may be the only manifestation in 27% of cases. It usually occurs after exertion. Sometimes routine examinations, cardiac enzymes, ECG and even exercise stress test prove negative. In such cases, only a coronary angiogram can provide sufficient evidence for diagnosis. Cardiac cephalgia manifests itself without a specific pattern of clinical features: indeed, in this headache subtype there is a high variability of clinical manifestations between different patients and also within the same patient. It "mimics" sometimes a form of migraine either accompanied or not by autonomic symptoms, sometimes a form of tension-type headache; on other occasions, it exhibits characteristics that can hardly be interpreted as typical of primary headache. Pain location is highly variable. When the headache occurs as the only manifestation of an acute coronary event, the clues for suspicion are a) older age at onset, b) no past medical history of headache, c) presence of risk factors for vascular disorders and d) onset of headache under stress. Knowledge of cardiac cephalgia is scarce, due to its rare clinical occurrence and to the scant importance given to headache as a symptom concomitantly with an ischaemic cardiac event.

Evaluation of the patterns of diagnostic and therapeutic care for first referrals at the Parma Headache Centre.

BACKGROUND AND AIM OF THE WORK: To evaluate the patterns of care for patients referred for the first time to a Headache Centre. METHODS: A semistructured questionnaire was administered to all patients consecutively referred for the first visit to the Parma Headache Centre between 15 March and 28 September 2006. RESULTS: The study included 202 patients, 55 men (27.2%) and 147 women (72.8%), mean age 40.6 years (41.8 for men and 40.2 for women). In 146 patients (72.3%), no diagnosis was made before. In the 56 patients (27.7%) with a prior diagnosis, there was concordance only in 16 cases (28.6%). The most common reason to get treatment at the Centre was having a specialistic opinion(n = 81, 40.1%). Sixty-two patients (30.7%) came for worsening of headache and 50 pts. (24.8%) for recent headache onset. Nine patients (4.4%) came for other reasons. Only in 98 cases (48.5%) the physician's prescription was correct with an explicit "visit at Headache Centre" request. The average waiting time was 191.1 days (range, 0-270). The most prescribed tests were EEGs (33.5%, i.e. 47.2% for men and 44.2% for women) and brain CT-scans (28.7%, i.e. 49% for men and 34.6% for women). Out of the 27 patients already taking tryptans, 25 were found to have migraine and two cluster headache. The prescription of tryptan was correct. Most patients were already taking NSAIDs (n =174, 86.1%). Only one female patient was taking ergot derivatives and antiemetics. CONCLUSIONS: Management of care should be improved to reduce waiting lists and unnecessary tests.

Hemicrania continua evolving from cluster headache responsive to valproic acid.

Hemicrania continua (HC) is a rare type of primary headache characterized by a prompt and enduring response to indomethacin. We describe a patient who suffered from cluster headache evolving into ipsilateral HC, who does not tolerate a long-term indomethacin therapy. The case was complex in terms of diagnosis, associated comorbidity, and choice of treatment; after several trials with different therapeutic regimens, we started the patient on a therapy with valproic acid and obtained an improvement of her HC.

Human psyche and headache: tension-type headache.

The role of psychological factors related to headache, particularly tension-type headache (TTH), has long been a focus of investigation. The subject at issue is a complex one, with some aspects that are still being debated by experts. In episodic TTH, it is possible to hypothesise that headache is not only a "primary" headache that causes gratuitous pain to sufferers. In fact, it might represent an improper mode of communicating the sufferers' intimate discomfort, caused by an inadequate relationship between their personality profiles and events in their lives. As in migraine, in TTH, too, evidence has been found of comorbidity between headache and psychiatric disorders, including depression and anxiety disorder. Such evidence will have to be confirmed by further studies on the general population. As regards behaviour and personality traits, subjects with TTH had significantly higher scores than healthy controls on measures of automatic thoughts and alexithymia, and lower scores on assertiveness. Patients with chronic TTH had higher automatic thoughts scores than patients with episodic TTH. These findings suggest that people with TTH may have difficulty in expressing their emotions. Finally, psychological factors and emotional disturbances have been indicated as risk factors for TTH. Indeed, stress and mental tension are the most common factors that cause TTH.

Cluster headache prevalence: methodological considerations. A review of the literature.

Cluster headache (CH), also known as "suicide headache", is characterized by a distinctive periodic temporal pattern and by accompanying autonomic symptoms during the attacks. Epidemiological data for the general population are scarce: only five studies have been carried out until now on CH prevalence in the general population, with conflicting results (prevalence rates vary between 56 and 326 cases every 100,000 inhabitants). Recently, a study was performed to investigate a representative sample of the Italian general population aged over 14 years. Possible CH cases according to the diagnostic criteria of the 1988 International Headache Society (IHS) classification were screened out of a sample of 10,071 patients registered in the lists of seven general practitioners (GPs) in Parma, using a previously validated, specially designed self-administered questionnaire. The diagnosis of CH was confirmed in 21 subjects (nine women and 12 men). The estimated prevalence rate was 279/100,000 (95% CI: 173-427), 227/100,000 (95% CI: 104-431) in women and 338/100,000 (95% CI: 175-592) in men. Based on methodological considerations, we believe that a lifetime prevalence rate of 279/100,000 for a population aged over 14 years is a reliable figure and it is probably not much lower than in the whole general population, since some studies performed on large case series have shown that the onset of CH is not frequent under 14 years of age.