An observational study on electrolyte disorders in the acute phase of ischemic stroke and their prognostic value.

Data on electrolyte disorders in neurological conditions and in acute stroke are somewhat scanty and not easily compared. In our Stroke Unit we studied patients hospitalized within six hours of the onset of an acute ischemic stroke and recorded their demographic and clinical data. Blood test results were recorded before any pharmacological therapy. A total of 475 individuals (256 M, 219 F; range: 14-96 years) treated over a period of 18 consecutive months, were selected. According to multiple logistic regression analysis, the baseline National Institute of Health Stroke Scale (NIHSS) score (odds ratio [OR]=1.33; 95% confidence interval [CI]: 1.22-1.44) and natremia alterations (OR=6.89; 95% CI=1.94-24.40) were associated with higher odds of death. Based on the ordinal logistic regression analysis, the baseline NIHSS score (OR=1.07; 95% CI=1.03-1.10) and baseline hypernatremia (OR=9.69; 95% CI=1.55-60.69) were related to early neurological worsening. Our work suggests an association between serum sodium alterations and mortality, and between high sodium levels and neurological clinical impairment, in the acute phase of an ischemic stroke.

Ictal epileptic headache as "subtle" symptom in generalized idiopathic epilepsy.

Epilepsy and migraine are common neurologic chronic disorders with episodic manifestations characterized by recurrent attacks and a return to baseline conditions between attacks. Epilepsy and migraine are frequently observed in comorbidity, with the occurrence of one disorder increasing the probability of the other: Migraine occurs in about one-fourth of patients with epilepsy, whereas epilepsy is present in 8-15% of patients with migraine. The link between headache and seizures is controversial and multifactorial. In epilepsy, headache can be seen as a preictal, ictal, or postictal phenomenon. In this report, we describe a case of a 37-year-old patient, affected by both drug-resistant generalized idiopathic epilepsy and headache, who displayed the sudden onset of a headache attack referred during a 24-h electroencephalography (EEG). The EEG tracing during this event revealed the activation of subcontinuous epileptic activity consisting of generalized spike-wave discharges (GSWDs) and generalized polyspike and wave discharges (GPSWDs) that persisted for 60 min, that is, until the disappearance of the headache. The case we describe appears to be original in that it represents one of the few EEG-documented ictal epileptic headaches in generalized idiopathic epilepsy.

Ictal haemodynamic changes in a patient affected by "subtle" Epilepsia Partialis Continua.

We report on a 64 year-old woman presenting with Epilepsia Partialis Continua (EPC) affecting the left hand since the age of 24 without neurological deficit. Structural MRI showed a region of focal cortical dysplasia (FCD) over the right central gyrus and lesions in the mesial frontal and occipital cortex secondary to perinatal hypoxic injury. Ictal spike haemodynamic mapping using simultaneous EEG-fMRI revealed significant BOLD signal changes prominent in the region of FCD (larger cluster), occipital cortex (global statistical maximum), prefrontal cortex and cerebellum. The cluster over FCD was in good agreement with the result of EEG source analysis. Our findings provide an interesting illustration of the ability of EEG-fMRI to reveal epileptogenic networks confirming the intrinsic epileptogenic properties of dysplastic neurons.

Feasibility and clinical utility of transesophageal echocardiography in the acute phase of cerebral ischemia.

We evaluated the feasibility and clinical utility of transesophageal echocardiography (TEE) in the early management of ischemic stroke. TEE was performed in consecutive patients with acute cerebral ischemia within 48 hours of symptoms onset. The data were analyzed by age (<55 vs ≥55 years), and the baseline stroke etiology was classified (determined vs undetermined). TEE was feasible in 660 (61%) of 1,080 patients. Left atrial abnormalities and complicated aortic plaques prevailed in older patients (p <0.05), irrespective of the stroke etiology. A patent foramen ovale prevailed in younger patients (p <0.05) but even in older patients was present in 13% of the determined and 31% of the undetermined stroke subgroups. Overall, high-risk and potentially high-risk cardioembolic sources were detected in 47% of the patients, and stroke etiology was consequently reviewed: 40% of the baseline undetermined strokes were reclassified as cardioembolic, and 29% of lacunar, 42% of large artery, and 30% of other determined-cause strokes were reclassified as concurrent etiology. Subsequently, according to the current guidelines, 12% of patients were reassigned from antiplatelet to anticoagulant therapy and 17% of patients were treated with high-dose statins; overall, secondary prevention treatment was modified in 26% of patients. In conclusion, TEE was feasible in about 2/3 of the patients investigated within 48 hours of the index event, contributed to stroke classification in 1/3 of cases, and guided secondary prevention therapy in 1/4 of patients. Therefore, TEE is useful for defining patients' risk profile for stroke recurrence.

Seizures in Alzheimer's disease: a retrospective study of a cohort of outpatients.

PURPOSE: The aim of our study was to define the frequency of seizures in a population of outpatients attending a cognitive function clinic in Italy and to identify risk factors for seizures in patients with Alzheimer's disease. METHODS: In this retrospective study, we analyzed our clinical records to gather information on patients' demographic, metabolic, cardiovascular and cognitive features. We sought to determine the significance of abnormal neuroimaging findings and the use of potentially epileptogenic drugs on the onset of seizures. From the records of 583 patients referred to the clinic for cognitive disturbances, we identified 145 patients with Alzheimer's disease. RESULTS: Of these 145 patients, 14 (9.7%) had a history of complex partial or generalised seizures, or both. Of the risk factors identified, onset of seizures was associated with male gender and none of the patients with seizures had diabetes. The risk of seizure onset was higher in Alzheimer's disease patients with hyperlipaemia and severe dementia. No other risk factors were identified, although hypertensive patients seemed to be protected. CONCLUSIONS: Seizures in Alzheimer's disease are frequent and often under-recognized. In elderly patients, especially those with Alzheimer's disease, correct diagnosis and treatment are important to prevent disease from worsening and disability from increasing. Patients with dementia should routinely undergo history-taking designed to elicit a history of seizures and define patients at high risk.

Focal epileptic seizure induced by transient hypoglycaemia in insulin-treated diabetes.

Hypoglycaemia, common in diabetic patients treated with insulin, can induce various neurological disturbances. Of these, seizures are the most common acute symptom, mainly of the generalised tonic-clonic type, with focal events only exceptionally being reported and documented. Hypoglycaemia can modify cortical excitability by determining an imbalance between excitation and inhibition; some brain structures, such as the temporal lobe and hippocampus, appear to be particularly susceptible to this insult. We describe a case of a 61-year-old diabetic patient in whom insulin-induced transient hypoglycaemia triggered a focal seizure of temporal origin that was well documented by EEG during 24-hour ambulatory monitoring. This is, to our knowledge, one of the few, well-documented cases of this type of seizure.

Drug resistant ADLTE and recurrent partial status epilepticus with dysphasic features in a family with a novel LGI1mutation: electroclinical, genetic, and EEG/fMRI findings.

PURPOSE: We characterized a family with autosomal dominant lateral temporal epilepsy (ADLTE) whose proband presented uncommon electroclinical findings such as drug-resistant seizures and recurrent episodes of status epilepticus with dysphasic features. METHODS: The electroclinical characteristics and LGI1 genotype were defined in the family. In the proband, the ictal pattern was documented during video-EEG monitoring and epileptic activity was mapped by EEG/fMRI. RESULTS: The affected members who were studied had drug-resistant seizures. In the proband, seizures with predominant dysphasic features often occurred as partial status epilepticus. The video-EEG-documented ictal activity and fMRI activation clearly indicated the elective involvement of the left posterior lateral temporal cortex. Sequencing of LGI1 exons revealed a heterozygous c.367G>A mutation in exon 4, resulting in a Glu123Lys substitution in the protein sequence. CONCLUSIONS: The uncommon clinical pattern (high seizure frequency, drug-resistance) highlights the variability of the ADLTE phenotype and extends our knowledge of the clinical spectrum associated with LGI1 mutations.

Diffusion-weighted magnetic resonance imaging in patients with partial status epilepticus.

PURPOSE: Diffusion-weighted magnetic resonance imaging (DWI) is used to detect changes in the distribution of water molecules in regions affected by various pathologies. Like other conditions, ictal epileptic activity, such as status epilepticus (SE), can cause regional vasogenic/cytotoxic edema that reflects hemodynamic and metabolic changes. This study describes the electroclinical and neuroimaging findings in 10 patients with partial SE whose DWI evaluation disclosed periictal changes related to sustained epileptic activity. PATIENTS AND METHODS: In this retrospective study we selected 10 patients with partial SE of different etiologies (six acute symptomatic SE; four with previous epilepsy and concomitant precipitating factors) who underwent video-EEG (electroencephalography) monitoring and a DWI study during the periictal phase. We analyzed ictal electroclinical features and DWI changes in the acute phase and during the follow-up period. RESULTS: DWI images revealed significant signal alterations in different brain regions depending on the location of ictal activity. DWI changes were highly concordant with the electroclinical findings in all 10 patients. As the SE resolved and the clinical conditions improved, DWI follow-up showed that the signal alterations gradually disappeared, thereby documenting their close relationship with ictal activity. CONCLUSIONS: This study confirms the usefulness of DWI imaging in clinical practice for a more accurate definition of the hemodynamic/metabolic changes occurring during sustained epileptic activity.

An emergency clinical pathway for stroke patients--results of a cluster randomised trial (isrctn41456865).

BACKGROUND: Emergency Clinical Pathways (ECP) for stroke have never been tested in randomized controlled trials (RCTs). OBJECTIVE: To evaluate the effectiveness of an ECP for stroke patients in Latium (Italy) emergency system. METHODS: cluster-RCT designed to compare stroke patient referrals by Emergency Medical Service (EMS) and Emergency Room (ER) health professionals trained in the ECP, with those of non-trained EMS and ER controls. Primary outcome measure was the proportion of eligible (aged

Asymmetric responses to repetitive transcranial magnetic stimulation (rTMS) over the left and right primary motor cortex in a patient with lateralized progressive limb-kinetic apraxia.

Repetitive transcranial magnetic stimulation (5 Hz-rTMS, 10 stimuli, 120% resting motor threshold intensity, RMT) produces in healthy subjects a progressive facilitation of motor-evoked potential (MEP) amplitude probably through a short-term enhancement of cortical excitatory interneurones. We had the opportunity to investigate the effect of 5 Hz-rTMS delivered over the right and left primary motor cortex (M1) in a patient with limb-kinetic apraxia of the left hand and fingers and reduced cerebral perfusion in the fronto-parietal cortex of the right hemisphere documented by single-photon emission computed tomography scans. Changes in the MEP size during the trains and the RMT were measured and compared between the hemispheres. 5 Hz-rTMS was also delivered in a group of healthy subjects over both hemispheres in order to compare changes in the MEP size from the right and left M1. In the patient, 5 Hz-rTMS delivered over the left hemisphere elicited normal MEPs that progressively increased in size during the trains whereas 5 Hz-rTMS delivered over the right affected hemisphere failed to facilitate the MEP size. RMT was similar in both hemispheres. In healthy subjects, 5 Hz-rTMS delivered over either hemisphere elicited a similar, significant MEP size facilitation. Despite the limitations of a single case, our findings suggest an altered response to 5 Hz-rTMS over the M1 of the affected hemisphere. This asymmetric response correlated with the altered perfusion in the right hemisphere and the patient's lateralized clinical manifestations of apraxia.

Influence of the corticospinal tract on the cutaneous silent period: a study in patients with pyramidal syndrome.

The cutaneous silent period (CSP) is a brief transient suppression of the voluntary muscle contraction that follows a noxious cutaneous nerve stimulation. In this study we investigated the influence of the corticospinal tract on this spinal inhibitory reflex. In patients with pyramidal syndrome and in a group of healthy subjects we delivered painful electrical finger stimulation during sustained contraction of the ipsilateral abductor digiti minimi muscle. The CSP latency and duration and the background electromyographic (EMG) activity were measured and compared between-groups. The compound motor action potential amplitude and F-wave latency were also measured after electrical stimulation of the ulnar nerve at the wrist. The CSP latency was significantly longer in patients than in healthy subjects. None of the other variables differed in patients and healthy subjects. Our findings suggest that corticospinal projections influence the CSP latency probably by modulating the balance of excitability in the underlying circuits.

Intravenous thrombolysis with rt-PA in acute ischemic stroke patients aged older than 80 years in Italy.

BACKGROUND: Intravenous (i.v.) thrombolysis with rt-PA within 3 h from symptom onset is the only approved treatment of pharmacological revascularization in acute ischemic stroke. However, little information exists on its use in elderly patients, in particular those aged >80 years, who at present are excluded from treatment. METHODS: In a multicenter Italian study on i.v. thrombolysis, patients aged >80 years (n = 41) were compared with those aged 80 years had a higher mortality (34.1%) as compared to those aged 80-year-old group. CONCLUSIONS: Acute ischemic stroke patients aged >80 years treated with i.v. rt-PA have a higher mortality than younger patients, but there are no differences for SICH nor for favorable outcome. Our data suggest that thrombolytic therapy should not be a priori denied for appropriately selected >80-year-old patients but randomized controlled clinical trials are necessary before definite recommendations can be given.

Screening of a microvascular endothelial cDNA library identifies rabaptin 5 as a novel autoantigen in Alzheimer's disease.

The pathogenesis of Alzheimer's disease (AD) includes the participation of the immune system. To identify antigenic targets in AD, we screened a human microvascular endothelial cell cDNA library with sera from patients with AD, and we identified rabaptin 5 (RABPT5). We detected serum IgG specific to RABPT5 in 65% of patients with AD and in 35% of patients with systemic lupus erythematosus, but in no healthy controls. Our results demonstrated a massive redistribution of this protein in the cytoplasm of endothelial and neuronal cells in apoptosis. In conclusion, we identified RABPT5 as a novel autoantigen in AD.

Determinants of plasma levels of brain natriuretic peptide after acute ischemic stroke or TIA.

Plasma levels of brain natriuretic peptide (BNP) are frequently elevated after an acute stroke and have been shown to be an independent predictor of mortality. However, the relationships between stroke and BNP concentrations have not yet been systematically investigated. Plasma BNP assay and echocardiography were performed in 48 patients with ischemic stroke or TIA with a mean delay of 12.7 h after onset. Median BNP concentration was 88.6 pg/mL (range 5-1270). Older age, chronic heart failure, atrial fibrillation, stroke severity, lower hemoglobin levels, lower left ventricular ejection fraction, and abnormalities of left atrium or appendage (LA/LAA) were univariately associated with increased BNP levels. At multivariable analysis, the presence of at least one LA/LAA abnormality (atrial dilatation, low flow velocity, spontaneous echocontrast or thrombus) had the strongest association with BNP, explaining 38.9% of the variance in the whole sample and 28.5% in patients without atrial fibrillation. In acute ischemic stroke patients, elevated plasma BNP levels have multiple determinants, among which left atrial disease appears to be the stronger, even in patients without atrial fibrillation. These results encourage further investigation of plasma BNP concentration as a potential marker of the presence of left atrial sources of emboli.

Over-interpretation of electroclinical and neuroimaging findings in syncopes misdiagnosed as epileptic seizures.

Syncope and epileptic seizures share some common clinical characteristics that may complicate the diagnostic process. In clinical practice, syncope is frequently misdiagnosed as an epileptic seizure and consequently treated with antiepileptic drugs. In this study, we identified 57 patients with syncope (diagnosis based on accepted criteria) who had come to our unit with a previous diagnosis of definite epilepsy in 30 cases (syncope misdiagnosed as epileptic seizures, SMS), or suspected epilepsy in the remaining 27 cases (unrecognized syncope, US). We attempted to identify factors underlying misdiagnosis by reviewing clinical findings, particularly potentially confounding features, and EEG/neuroimaging data. Finally, we compared these two groups of patients to search for crucial elements that had led to misdiagnosis. Although some clinical elements were found to be confounding in both groups, it was the interpretation of the EEG and MRI findings, particularly when combined with the confounding clinical features that constituted the main reasons for misdiagnosis.

Effects of repetitive transcranial magnetic stimulation on spike-and-wave discharges.

Aim of this study was to evaluate the effect of 5Hz-suprathreshold repetitive transcranial magnetic stimulation (rTMS) on the duration of the spike-and-wave discharges (SWDs) in a patient presenting idiopathic absence seizures. At the moment of the study the patient presented a mild blunting of consciousness due to the high frequency of absences and EEG recordings showed sub-continuous, generalized, symmetrical and synchronous 3c/s SWDs, petit mal status. Trains of 10 stimuli (120% resting motor threshold) were delivered at 5Hz frequency at the beginning of the SWDs. 5Hz-rTMS trains significantly changed the EEG activity by reducing the duration of SWDs without changing the intervals between two consecutive discharges. rTMS had not significant after-effects on the epileptic activity and patient's clinical status. Despite the limitations of a single case report, our neurophysiological findings suggest that 5Hz-suprathreshold rTMS delivered in short trains induces a transitory interference of the ongoing epileptic activity.