The role of stress as a trigger for epileptic seizures: A narrative review of evidence from human and animal studies

Stress is one of the most frequently self‐identified seizure triggers in patients with epilepsy; however, most previous publications on stress and epilepsy have focused on the role of stress in the initial development of epilepsy. This narrative review explores the causal role of stress in triggering seizures in patients with existing epilepsy. Findings from human studies of psychological stress, as well as of physiologic stress responses in humans and animals, and evidence from nonpharmacologic interventions for epilepsy are considered. The evidence from human studies for stress as a trigger of epileptic seizures is inconclusive. Although retrospective self‐report studies show that stress is the most common patient‐perceived seizure precipitant, prospective studies have yielded mixed results and studies of life events suggest that stressful experiences only trigger seizures in certain individuals. There is limited evidence suggesting that autonomic arousal can precede seizures. Interventions designed to improve coping with stress reduce seizures in some individuals. Studies of physiologic stress using animal epilepsy models provide more convincing evidence. Exposure to exogenous and endogenous stress mediators has been found to increase epileptic activity in the brain and trigger overt seizures, especially after repeated exposure. In conclusion, stress is likely to exacerbate the susceptibility to epileptic seizures in a subgroup of individuals with epilepsy and may play a role in triggering “spontaneous” seizures. However, there is currently no strong evidence for a close link between stress and seizures in the majority of people with epilepsy, although animal research suggests that such links are likely. Further research is needed into the relationship between stress and seizures and into interventions designed to reduce perceived stress and improve quality of life with epilepsy.     

Comparison of heart rate variability parameters during complex partial seizures and psychogenic nonepileptic seizures

Purpose: Psychogenic nonepileptic seizures (PNES) superficially resemble epileptic seizures. Little is known about ictal autonomic nervous system (ANS) activity changes in epilepsy and PNES. This study compares ictal heart rate variability (HRV) parameters as a reflection of ANS tone in epileptic seizures and PNES, and explores differences between interictal and ictal ANS tone in both patient groups. Methods: Ictal HRV parameters were extracted from single‐lead electrocardiography (ECG) data collected during video–electroencephalography (EEG) recordings of 26 patients with medically refractory temporal lobe epilepsy and 24 age‐ and sex‐matched patients with PNES. One seizure per patient in a resting, wake, supine state was analyzed. Interictal ECG data were available for comparison from 14 patients in both groups. HRV parameters in time and frequency domains were analyzed (low frequency [LF], high frequency [HF], standard deviation of all consecutive normal R wave intervals [SDNN], square root of the mean of the sum of the squares of differences between adjacent normal R wave intervals [RMSSD]). CVI (cardiovagal index), CSI (cardiosympathetic index), and ApEn (approximate entropy) were calculated from Lorenz plots. Key Findings: There were significant differences between ictal HRV measures during epileptic and nonepileptic seizures in the time and frequency domains. CSI (p < 0.001) was higher in epileptic seizures. Time interval between two consecutive R waves in the ECG (RR interval) (p = 0.002), LF (p = 0.02), HF (p = 0.003), and RMSSD (p = 0.003) were significantly lower during epileptic seizures. Binary logistic regression yielded a significant model based on the differences in CSI classifying 88% of patients with epilepsy and 73% of patients with PNES correctly. The comparison between resting and ictal states in both seizure disorders revealed significant differences in RR interval (epilepsy p < 0.001, PNES p = 0.01), CSI (epilepsy p < 0.001, PNES p = 0.02), HF (epilepsy p = 0.002, PNES p = 0.03), and RMSSD (epilepsy p = 0.004, PNES p = 0.04). In patients with epilepsy there were also significant differences in ictal versus interictal mean values of ApEn (p = 0.03) and LF (p = 0.04). Although CSI was significantly higher, the other parameters were lower during the seizures. Stepwise binary regression in the 14 patients with epilepsy produced a significant model differentiating resting state from seizures in 100% of cases. The same statistical approach did not yield a significant model in the PNES group. Significance: Our results show greater ANS activation in epileptic seizures than in PNES. The biggest ictal HRV changes associated with epileptic seizures (CSI, HF, and RMSSD) reflect high sympathetic system activation and reduced vagal tone. The reduced ApEn also reflects a high sympathetic tone. The observed ictal alterations of HRV patterns may be a more specific marker of epileptic seizures than heart rate changes alone. These altered HRV patterns could be used to detect seizures and also to differentiate epileptic seizures from PNES. Larger studies are justified with intergroup and intragroup comparisons between ictal and resting states.     

Examining a community model of epilepsy care for people with learning disabilities.

PURPOSE: To assess the use of specialised medical epilepsy services by people with learning disabilities (LD) and epilepsy in a community healthcare setting, to compare medical epilepsy care in this group to current management guidelines, and to contrast important outcomes with those achieved in different healthcare settings. METHODS: Postal survey with a carer completed questionnaire addressed to all adults with epilepsy registered on an LD register in Sheffield, UK (n=442). RESULTS: An analysis based on 225 returned questionnaires revealed that 22.7% of individuals with LD and epilepsy had been free of seizures for over 1 year. 95.1% were taking antiepileptic drugs (AEDs), 46.2% had had an EEG, and 41.3% a brain scan. 53.3% of diagnoses had been made by epilepsy experts, 38.7% of individuals with LD and epilepsy were under specialist review. Although patients with more severe epilepsy were more likely to be under specialist care, 60.6% of patients with ongoing seizures, 57.9% with major seizures and 68.7% of individuals taken to hospital with prolonged had no access to specialist advice. CONCLUSION: The proportion of people with LD who achieved seizure-control in the described population was lower than in all previously reported studies of LD patient groups. The poor outcome in terms of seizure-control, the lack of access to the epilepsy specialist service, and the apparent under-utilisation of investigations indicate that there are grounds for serious concern about this community model of medical epilepsy care for people with LD.     

Ultrastructure of liver tumors induced in F344 rats by methapyrilene

Liver tumors induced in F344 rats by methapyrilene were studied by electron microscopy. The tumor cells constituting hepatocellular carcinomas showed a pronounced increase in the number of mitochondria and conformational changes of these organelles while the content of lipid, glycogen and smooth endoplasmic reticulum was greatly reduced. The cholangiocarcinomas consisted of bile duct epithelia at varying stages of squamous metaplasia.     

Carcinogenicity of heptachlor and heptachlor epoxide

Heptachlor and its metabolite heptachlor epoxide are unequivocally carcinogenic in rats and mice. The chemicals induced carcinomas of the liver, which were highly significant. There were neoplasms at other sites in rats. Neoplasms at all sites, as well as malignant tumors, were increased in heptachlor-treated male rats. There were similar increases in benign and malignant neoplasms of endocrine organs, particularly in female rats. Neoplasms of the thyroid and pituitary were increased in male rats and neoplasms of the reproductive system, including the ovary and uterus, in female rats given heptachlor. Mice also developed hepatic vein thrombosis and thrombosis of the atria of the heart. Nephritis, myocarditis, encephalitis, hepatitis, polyarteritis and atrophy of the testes were observed in rats.     

The hermeneutics of symptoms

Medicine, Health Care and Philosophy - The clinical encounter begins with presentation of an illness experience; but throughout that encounter, something else is constructed from it – a...     

Carcinomas and other lesions of the liver in mice ingesting organochlorine pesticides.

Carcinomas of the liver were readily induced in male and female mice given organochlorine pesticides orally. The carcinomas were predominantly hepatocellular, with a few being cholangiocellular, and varied from well differentiated to poorly differentiated to undifferentiated. They are capable of invading, metastasizing, and killing the mice. Hemangiosarcomas, leimyosarcomas, and reticulum cell sarcomas were also occasionally seen in mice receiving these chemicals. Hepatic vein thrombosis and hepatic necrosis was observed in some mice.     

Stretch syncope: reflex vasodepressor faints easily mistaken for epilepsy

The pathophysiology of stretch syncope is demonstrated through the clinical, electrophysiological, and hemodynamic findings in three patients. Fifty-seven attacks were captured by video/EEG monitoring. Simultaneous EEG, transcranial (middle cerebral artery) doppler, and continuous arterial pressure measurements were obtained for at least one typical attack of each patient. They all experienced a compulsion to precipitate their attacks. Episodes started with a stereotyped phase of stretching associated with neck torsion and breath holding, followed by a variable degree of loss of consciousness and asymmetric, recurrent facial and upper limb jerks in the more prolonged episodes. Significant sinus tachycardia coincided with the phase of stretching and was followed within 9-16 seconds by rhythmic generalized slow wave abnormalities on the EEG in attacks with impairment of consciousness. Transcranial doppler studies showed a dramatic drop in cerebral perfusion in the middle cerebral arteries during the episodes. The combination of the stereotyped semiology of the attacks, the pseudofocal myoclonic jerking, and the rhythmic generalized slow wave EEG abnormalities with the tachycardia make differential diagnosis from epilepsy challenging.