By definition, the ANS refers to the portion of the central and peripheral nervous systems that regulates autonomic function through the sympathetic and parasympathetic branches. The ANS is under the control of the CAN, whose anatomy and physiology have been extensively reviewed by Benarroch.⁶ Structurally, the CAN consists primarily of the insular cortex, medial prefrontal cortex, amygdala, hypothalamus, and ventrolateral medulla. These areas can be functionally divided into those areas that relay sensory information and those that have a motor or effector action. There are reciprocal connections among all the structures within the CAN that help to integrate autonomic responses. The insular cortex is involved with visceral sensory function, while the anterior cingulate and other medial frontal structures appear to have primarily effector roles in autonomic seizures. Stimulation of the cingulate gyrus in humans can lead to intense vagal effects, including bradycardia and even cardiac arrest.⁹¹ Deeper mesial temporal and limbic structures including the amygdala are also involved. Activation of the insular cortex and amygdala can produce cardiac arrhythmias, whether initiated by epileptic seizures or by other lesions such as stroke.^6,82 The amygdala is involved with the autonomic response to emotion. Stimulation of the amygdala can produce salivation and mydriasis in cats.⁵¹

In the diencephalon, the hypothalamus has a major role in visceral motor, neuroendocrine, and sexual function.³⁸ The hypothalamus controls both sympathetic and parasympathetic activity and is also involved in temperature regulation. There is evidence that subpopulations of neurons within the hypothal-amus can selectively activate subpopulations of preganglionic neurons.¹⁶

Finally, in the brainstem, the nucleus of the tractus solitarius (NTS) and the ventrolateral medulla are crucial. These medullary structures have major roles in regulating cardiovascular activity, respiration, and other autonomic motor phenomena. The NTS is important both in the afferent relay of viscerosensory information from the periphery to higher centers and in the efferent control of cardiovascular function.

Central control of autonomic function is mediated though the parasympathetic and sympathetic branches of the ANS.⁵ Cells bodies for the parasympathetic branch are located for the most part in the brainstem. Parasympathetic innervation through cranial nerves III, VII, and IX mediates pupillary constriction, salivation, and lacrimation. Cranial nerve X (the vagus nerve) supplies parasympathetic innervation from the medullary structures of the dorsal motor nucleus of the vagus and the nucleus ambiguous to areas throughout the cardiovascular and gastrointestinal systems. Parasympathetic fibers in the second through fourth sacral spinal nerves largely influence genitourinary function.

Sympathetic innervation descends from the brainstem, synapsing on neurons in the intermediolateral cell columns located from T1 to L2 of the spinal cord. Axons from these cells exit the spinal cord through spinal nerves synapsing on neurons in the paravertebral chain ganglia. These preganglionic neurons are organized into functional units such that different functions under sympathetic control can be selectively activated.⁴⁶ Postganglionic axons provide extensive innervation of the cardiopulmonary system and the smooth muscle of blood vessels throughout the body, playing a role in blood pressure maintenance and vasodilation.⁵

Tachycardia and hypertension are impressively common in all types of seizures. In one study, 96% of seizures included increased heart rate; none produced bradycardia.⁵⁴ A study that recorded ambulatory electroencephalograms (EEGs) and simultaneous cardiograms during temporal lobe seizures showed an increased heart rate in 92% of 74 seizures; 30% had heart rates above 140.¹² These arrhythmias, consisting of irregular bursts of increased heart rate, occurred in 42% of seizures, typically late in the seizure. In a series of 145 seizures in 58 patients, 87% included tachycardia, which correlated with a mesial temporal seizure onset.⁶⁸ Only two (1.4%) had bradycardia, both with a left hemisphere seizure onset. Heart rate changes preceded EEG changes in 110 seizures, were simultaneous in five, and followed the EEG change in 30. Tachycardia preceded epileptic activity by a mean of 14 seconds in patients with temporal seizures and was more likely with a right-sided origin. With implanted depth electrode recording, there was no predominant laterality of seizures causing tachycardia, and tachycardia did not ensue from amygdala stimulation alone.²⁵ Rather, spread of seizures was necessary to produce tachycardia; its likelihood correlated with the extent of cortex involved.²⁵

Bradycardia, generally considered to be mediated through the hypothalamus and vagus nerve, is far less common than tachycardia during seizures. However, it can be a more severe clinical problem, occasionally leading to sinus arrest⁵⁵ or asystole,⁴⁴ and in some cases necessitating placement of a cardiac pacemaker.²⁰ Bradycardia causing syncope often correlates with visceral symptoms and left hemisphere epileptogenic sites.²⁰ Antiepileptic drugs (AEDs) may treat the bradycardia by preventing seizures.²⁰ A literature review of ictal bradycardia in the setting of focal seizures indicated a modest but clear left-sided predominance for the epileptogenic site; seizures could originate in medial temporal or frontal areas.¹⁰⁴ Bradycardia is more likely to occur in temporal lobe seizures than in seizures of other origin.²⁹

Other cardiac arrhythmias associated with epileptiform discharges include supraventricular tachycardia,⁹² paroxysmal atrial tachycardia,⁹⁷ and sinoauricular heart block.⁹⁰ In one case report, paroxysmal atrial tachycardia occurred during seizures with a right frontal focus due to a tumor. The seizures and the arrhythmia ceased following tumor resection.⁹⁷ Sinoauricular heart block can accompany right temporal seizures, associated with an epigastric aura, diminished responsiveness, and syncope, presumed to represent a vagal effect.⁹⁰ This arrhythmia was treated successfully with anticholinergic agents, and with phenytoin.

Abnormal autonomic activity in patients with epilepsy is not restricted to the ictal state. Interictally, many patients with temporal lobe epilepsy have reduced heart rate variability, independent of AED use.^2,3 In another study, patients with complex partial seizures had large interictal fluctuations in heart rate that were not seen in controls.²⁸

A major alteration in the variability of autonomic nerve activity innervating cardiovascular structures may be a risk for potentially serious arrhythmias.⁶¹

Analysis of the R-R interval (RRI), the period of time separating successive heartbeats, revealed RRI fluctuations at the respiratory frequency that were parasympathetically mediated, and RRI fluctuations at higher frequencies that were mediated by the combined effects of sympathetic and parasympathetic inputs to the heart.⁸⁰ In this analysis, complex partial seizures produced a marked imbalance in parasympathetic and sympathetic drive to the heart. Parasympathetic activity fell rapidly 30 seconds before seizure onset, while sympathetic activity continued to rise, peaking at seizure onset. In a report of two patients with temporal lobe epilepsy, investigators observed that a period of acute deterioration of seizure control was accompanied by increased parasympathetic function and that bradycardia began up to 40 seconds before seizure onset.¹⁰⁵

Gastrointestinal symptoms are by far the most common epileptic seizure symptoms mediated by the ANS. While the most common gastrointestinal manifestation is the rising epigastric sensation initially described by Gowers,³⁴ other symptoms include vomiting, cramping, bloating, and diarrhea. Abnormal visceral sensations can arise from the normal perception of abnormal intestinal motor activity due to abnormal autonomic activity. However, most symptoms appear to remain restricted to altered sensory perception by the brain. Indeed, during complex partial seizures there is typically an inhibition of gastric motility.¹⁰⁹

Van Buren¹⁰⁸ reviewed the histories of 100 patients who had depth electrode monitoring for refractory epilepsy and had chest, abdominal, or pelvic symptoms considered epileptic in origin. Symptoms characteristically began as partial seizures (auras) leading to complex partial seizures, with half of the patients reporting the spreading or rising epigastric sensation. Viscerosensory auras in patients with refractory seizures were temporal in onset in 90% of cases, with 10% from frontal and other areas.⁸⁴ In a series of patients with visceral symptoms, Mulder et al.⁷⁸ also noted that abdominal pain could be a manifestation of a sensory seizure alone or could be due to spasm induced by epileptic motor activity. Two thirds of these patients had gastrointestinal symptoms, especially nausea, which could occur in isolation. Abdominal discomfort occurred in another one third. In nine patients evaluated for epilepsy surgery with temporal lobe seizures and ictal vomiting, Kramer et al.⁵⁸ found a right-sided predominance of interictal and ictal discharges. In another study of patients with focal-onset seizures, one third of auras that began in the right hemisphere were autonomic in nature versus only 8% from the left, and 84% of all autonomic auras originated on the right.³⁶ Almost all consisted of abnormal epigastric sensations.

Gastrointestinal manifestations of seizures can also include motor or effector autonomic phenomena such as vomiting, swallowing, and salivation, suggesting involvement of the hypothalamus and lower medullary structures that coordinate such motor activity through the nucleus of the tractus solitarius and dorsal motor nucleus of the vagus.^78,107 Vomiting is the most prominent autonomic motor manifestation of seizures, with cyclic vomiting a major symptom of partial seizures in children.⁷⁷ An anterior temporal focus can cause vomiting, accompanied by olfactory hallucinations followed by loss of consciousness or generalized convulsions. Especially in children, this has been labeled abdominal epilepsy. Many children have benign overlap syndromes including features of both epilepsy and migraine, often with occipital spike discharges.

Panayiotopoulos syndrome is a remarkably common “idiopathic susceptibility to early-onset benign childhood seizures” with primarily autonomic manifestations.⁵⁷ Patients (usually children aged 3 to 6) have recurrent gastrointestinal symptoms distinct from migraine.⁸⁵ Nausea and vomiting upon arousal from sleep are the primary clinical manifestations. Pallor and flushing are also common. Other epileptic manifestations include eye deviation and loss of consciousness, some with hemibody or generalized convulsions. Seizure-induced vomiting is presumed to represent epileptic activity transmitted from cortical areas through the hypothalamus and medulla. Epileptiform discharges are often occipital but may be multifocal, usually in posterior areas. Seizures may be prolonged to the point of status epilepticus,⁵⁷ but many children have just single episodes, and the prognosis is generally excellent. Most children recover without AED treatment. About 20% go on to have later epilepsy.

The sensation of fear (often localized by patients to intestinal sensations) has a strong correlation with seizures involving the amygdala,³¹ and amygdala stimulation can produce such feelings in conscious patients. Ictal fear is usually accompanied by gastrointestinal or epigastric symptoms.¹⁰⁸ In one series, fear correlated better with amygdala atrophy than with hippocampal structural abnormalities.¹⁷

Urinary incontinence is common, but not invariant, in generalized convulsions, often occurring after the clonic phase. It occurs far less frequently in partial seizures, and fecal incontinence occurs even less often. Focal seizures can prompt a sensation of urinary urgency. We were unable to find unambiguous reports of urination as the sole manifestation of epileptic seizures.

Normal sexual function is dependent on the sensory nervous system and on motor and behavioral effector autonomic function. Seizures can affect sexual function in many ways. Epileptogenic foci in parietal or temporolimbic structures subserving sensation from genital and pelvic regions can produce “pure” sensations in those areas, without autonomic involvement or a more extensive sexual perception or feeling.⁷⁸ Erickson reported one woman with ictal sensations of pelvic “hotness,” proceeding to left leg jerking, left abdominal sensations, and loss of speech, all resolving after resection of a right frontal parasagittal tumor.²⁶

More typical sexual sensations arise from epileptogenic areas in temporolimbic regions, more often in the right hemisphere.⁹³ Remillard et al.⁹³ reported a series of 12 women with such sensations—generally unpleasant at first but later pleasurable in many. Seven of the 10 localizable seizure foci were on the right side. They were able to produce such feelings (sometimes progressing to arousal or orgasm) with mesial temporal depth electrode stimulation in two. A female predominance of these phenomena (20 of the total 23 patients reviewed) suggested that limbic structure organization differs between the two genders and offered a partial explanation of the behavioral differences in men and women with temporolimbic seizures.⁹³