The heart of epilepsy: Current views and future concepts.

Cardiovascular (CV) comorbidities are common in people with epilepsy. Several mechanisms explain why these conditions tend to co-exist including causal associations, shared risk factors and those resulting from epilepsy or its treatment. Various arrhythmias occurring during and after seizures have been described. Ictal asystole is the most common cause. The converse phenomenon, arrhythmias causing seizures, appears extremely rare and has only been reported in children following cardioinihibitory syncope. Arrhythmias in epilepsy may not only result from seizure activity but also from a shared genetic susceptibility. Various cardiac and epilepsy genes could be implicated but firm evidence is still lacking. Several antiepileptic drugs (AEDs) triggering conduction abnormalities can also explain the co-existence of arrhythmias in epilepsy. Epidemiological studies have consistently shown that people with epilepsy have a higher prevalence of structural cardiac disease and a poorer CV risk profile than those without epilepsy. Shared CV risk factors, genetics and etiological factors can account for a significant part of the relationship between epilepsy and structural cardiac disease. Seizure activity may cause transient myocardial ischaemia and the Takotsubo syndrome. Additionally, certain AEDs may themselves negatively affect CV risk profile in epilepsy. Here we discuss the fascinating borderland of epilepsy and cardiovascular conditions. The review focuses on epidemiology, clinical presentations and possible mechanisms for shared pathophysiology. It concludes with a discussion of future developments and a call for validated screening instruments and guidelines aiding the early identification and treatment of CV comorbidity in epilepsy.

Increased prevalence of ECG markers for sudden cardiac arrest in refractory epilepsy.

BACKGROUND AND AIM: People with epilepsy are at increased risk of sudden cardiac arrest (SCA) due to ECG-confirmed ventricular tachycardia/fibrillation, as seen in a community-based study. We aimed to determine whether ECG-risk markers of SCA are more prevalent in people with epilepsy. METHODS: In a cross-sectional, retrospective study, we analysed the ECG recordings of 185 people with refractory epilepsy and 178 controls without epilepsy. Data on epilepsy characteristics, cardiac comorbidity, and drug use were collected, and general ECG variables (heart rate (HR), PQ and QRS intervals) assessed. We analysed ECGs for three markers of SCA risk: severe QTc prolongation (male >450 ms, female >470 ms), Brugada ECG pattern, and early repolarisation pattern (ERP). Multivariate regression models were used to analyse differences between groups, and to identify associated clinical and epilepsy-related characteristics. RESULTS: People with epilepsy had higher HR (71 vs 62 bpm, p<0.001) and a longer PQ interval (162.8 vs 152.6 ms, p=0.001). Severe QTc prolongation and ERP were more prevalent in people with epilepsy (QTc prolongation: 5% vs 0%; p=0.002; ERP: 34% vs 13%, p<0.001), while the Brugada ECG pattern was equally frequent in both groups (2% vs 1%, p>0.999). After adjustment for covariates, epilepsy remained associated with ERP (ORadj 2.4, 95% CI 1.1 to 5.5) and severe QTc prolongation (ORadj 9.9, 95% CI 1.1 to 1317.7). CONCLUSIONS: ERP and severe QTc prolongation appear to be more prevalent in people with refractory epilepsy. Future studies must determine whether this contributes to increased SCA risk in people with epilepsy.

Postictal sleep: syncope or seizure?

A 6-year-old boy presented with prolonged periods of unconsciousness (>60 min) following nausea and dizziness while standing. The application of EEG electrodes provoked a similar episode. These apparently long periods of unconsciousness could be explained by sleep. In view of the triggers (pain, distress, and prolonged standing), the prodromal features, and the transient sinus bradycardia during the EEG examination a diagnosis of vasovagal syncope was made. Sleep is an alternative explanation for delayed recovery after syncope in young children. Prompt recognition might avoid unnecessary investigations, distress, and an incorrect diagnosis.

Gastrointestinal hemorrhage and the skin.

Cutaneous manifestations are often associated with disorders in which gastrointestinal hemorrhage is a major feature. These manifestations include vascular abnormalities, connective tissue disorders, gastrointestinal polyposis, vasculitis and its variants, Kaposi's sarcoma, and inflammatory bowel disease. Because such skin lesions often develop prior to gastrointestinal hemorrhage, they may prove helpful in making a definitive diagnosis before gastrointestinal blood loss becomes a major clinical problem.

Tumor promoters cause changes in the state of phosphorylation and apparent molecular weight of a tyrosine protein kinase in T lymphocytes.

The T cell lymphoma LSTRA contains an elevated level of a tyrosine protein kinase of molecular weight of 56,000 (pp56Tcell) that is present in normal T lymphocytes. Treatment of 32P-labeled LSTRA cells with the phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), followed by immunoprecipitation of pp56Tcell, revealed that PMA causes complex changes in the state of phosphorylation of pp56Tcell, and the appearance of several new forms of pp56Tcell with higher apparent molecular weights on sodium dodecyl sulfate-polyacrylamide gels. The 32P-labeled pp56Tcell from untreated LSTRA cells contains phosphotyrosine and phosphoserine in a ratio of 2:1. After treatment of LSTRA cells with PMA, the form of pp56Tcell that runs with a molecular weight of 56,000 has approximately equal amounts of phosphotyrosine and phosphoserine, while the higher molecular weight forms of pp56Tcell seen after PMA have 3-4 times more phosphoserine than phosphotyrosine. The induction by PMA of higher molecular weight forms of pp56Tcell could also be demonstrated in preparations of normal human T lymphocytes. The changes in the state of phosphorylation of pp56Tcell after treatment of cells with PMA are consistent with the possibility that pp56Tcell is an in vivo substrate for protein kinase C and provide documentation for a linkage between a mitogenic agent and pp56Tcell.

Nodular cutaneous mucinosis associated with lupus erythematosus.

Nodular mucin-containing skin lesions in a Mexican woman were present in conjunction with probable systemic lupus erythematosus (SLE). Histologically, the lesions contained features of both lupus erythematosus (LE) and of the mucin deposition diseases. The clinical subsets of LE and the mucinoses are briefly reviewed and the unique clinical nature of the skin lesions in this case are emphasized.

Isolated nodular cutaneous coccidioidomycosis. The initial manifestation of disseminated disease.

Cutaneous manifestations of coccidioidomycosis may be divided into primary and secondary lesions. Since such lesions may be the only evidence of infection, the distinction is important. Primary (inoculation) lesions are rare. Secondary lesions develop from primary pulmonary disease, commonly. An isolated nodule on the scalp was the presenting sign of disseminated coccidioidomycosis in our patient. Because of the rarity of primary cutaneous coccidioidomycosis, cutaneous lesions due to it should alert the physician to the presence of disseminated disease. The clinical spectrum of such lesions is wide. Our patient was an elderly man with a hyperkeratotic scalp nodule clinically felt to be an actinic keratosis or an early squamous cell carcinoma. We suggest that patients with a travel or resident history in endemic areas be viewed with a high index of suspicion for skin lesions of cutaneous coccidioidomycosis. The advent of orally administered imidazole antifungal agents makes early and aggressive diagnosis of these lesions even more important.