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Autonomic symptoms during epileptic seizures Volume 3, issue 3, September 2001

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  • Autonomic symptôme during epileptic seizures
  • Autonomic symptôme during epileptic seizures
  • Autonomic symptôme during epileptic seizures
  • Autonomic symptôme during epileptic seizures
  • Autonomic symptôme during epileptic seizures
  • Autonomic symptôme during epileptic seizures
  • Autonomic symptôme during epileptic seizures
  • Autonomic symptôme during epileptic seizures
  • Autonomic symptôme during epileptic seizures

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Autonomic symptoms during epileptic seizures can either represent the sole or predominant seizure, manifestation as in simple autonomic seizures, or accompany complex partial or generalized seizures [1-5]. Autonomic symptoms are of both clinical and scientific interest for several reasons. Firstly, a better understanding of autonomic changes during epileptic seizures could help to clarify the pathophysiology of serious complications of epilepsy such as sudden unexplained death (SUDEP), seizure-induced cardiac arrhythmias or neurogenic pulmonary edema. Secondly, autonomic phenomena can help us better understand the functional organization of the central representation of the autonomic nervous system, i.e. the central autonomic network. Thirdly, certain autonomic symptoms such as ictal vomiting, ictal urinary urge, ictal spitting, postictal nose-wiping, postictal coughing etc. provide important clinical information on the localization and lateralization of the seizure onset zone. Fourthly, simple autonomic seizures can pose problems of differential diagnosis of non-epileptic conditions.

Autonomic symptoms can be divided into cardiovascular changes, respiratory manifestations, gastrointestinal symptoms, cutaneous manifestations, pupillary symptoms, genital and sexual manifestations as well as urinary symptoms.

We present a short review of autonomic manifestations of epileptic seizures, with special emphasis on seizures predominated by autonomic symptoms including typical video examples.

The central autonomic network

Autonomic symptoms during epileptic seizures are mediated by a dysfunction of the central autonomic network (CAN) which comprises (1) the insular and medial prefrontal cortex, (2) the central nucleus of the amygdala and the bed nucleus of the stria terminalis, (3) the preoptic region and the hypothalamus, (4) the midbrain periaqueductal gray matter, (5) the pontine parabrachial Kölliker-Fuse region, (6) the nucleus of the solitary tract and (7) the intermediate reticular zone of the medulla (figure 1) [6]. Inputs to the CAN are multiple, including viscerosensory inputs relayed on the nucleus of the tractus solitarius and humoral inputs relayed through the circumventricular organs. The CAN in turn controls preganglionic sympathetic and parasympathetic, neuroendocrine, respiratory and sphincter motor neurons.

The insula, the medial prefrontal cortex, and other regions of the prefrontal cortex are involved in higher order autonomic control. The insula can be viewed as a primary viscerosensory area that receives viscerotopically organized inputs from the gustatory pathways, gastric mechanoreceptors, arterial chemoreceptors and baroreceptors. Electrical stimulation of the insula results in heart rate, blood pressure, respiratory, pilorector, pupillary, gastrointestinal, salivatory and adrenal responses [1]. While stimulation of the right anterior insular cortex elicits tachycardia and pressor responses, bradycardia and depressor responses occur after left anterior insula stimulation, suggesting a hemispheric-specific organization [7]. A recent paper based on depth electrode stimulation hypothesized a particular topographic organization of the insula. The authors suggested two different cortical networks, i.e. an anterior visceral network extending to the temporomesial structures and a posterior somesthetic network reaching the opercular cortex [8]. The medial prefrontal cortex with its extensive efferent connections to diencephalic and brainstem autonomic nuclei is considered as the "visceral motor cortex". Stimulation of the medial prefrontal cortex produces changes in blood pressure, heart rate and gastrointestinal motility [1]. Furthermore, the orbitofrontal cortex and mesiotemporal structures seem to be involved in cardiac and respiratory changes as well as in oesophago-gastrointestinal motility [9].

The amygdala and the bed nucleus of the stria terminalis together form an anatomofunctional unit called the "extended amygdala" which is responsible for integrated autonomic and motor responses to emotion [6]. The preoptic region and the hypothalamus integrate autonomic, endocrine and behavioral responses essential for homeostasis and reproduction. The midbrain periaqueductal gray matter, the parabrachial region of the pons, the nucleus of the solitary tract and the ventrolateral medulla contain a network of respiratory, cardiovagal and vasomotor neurons [6].

Cardiovascular changes

Changes in blood pressure and cardiac rhythm frequently accompany epileptic seizures [1]. Sinus tachycardia represents the most frequent cardiac concomitant of epileptic seizures and can occur during subclinical, simple partial, complex partial and secondarily generalized tonic clonic seizures. Heart rate progressively increases as more brain tissue becomes involved in epileptic discharges [10]. Sinus tachycardia of > 120 beats per minute (bpm) has been reported in 67% [11], 76% [12] and 89.1% [13] of seizures, and peak frequencies of up to 201 bpm have been observed [11]. Sinus tachycardia precedes clinical and EEG onset by several seconds in 10-57% of seizures [1, 3, 11, 13, 14], and thus reflects activation of the central autonomic network rather than being a consequence of other, especially motor, manifestations of the seizure. We found that sinus tachycardia preceded EEG seizure onset for an average of 18.7 sec in 76.1% of all seizures on surface-EEG, and for an average of 11.0 sec in 45.7% of seizures on invasive subdural EEG [13]. These early heart rate changes therefore are probably caused by epileptic discharges, restricted to either mesial temporal lobe structures such as the amygdala or parts of the hippocampus [15-17], which cannot be detected on surface-EEG or even subdural electrodes covering the parahippocampal gyrus [18] or the insular cortex [7] which also is not readily accessible to either surface or subdural EEG.

Cortical stimulation studies in humans demonstrated depressor responses and bradycardia on stimulation of the left insular cortex, whereas the converse applied for the right insular cortex [7], which suggests that lateralization of the seizure onset zone could exert different influences on heart rate changes, i.e. that right-sided seizures would cause an ictal tachycardia whereas left-sided seizures would result in an ictal bradycardia. So far, the studies investigating hemispheric-specific effects on peri-ictal heart rate changes have yielded controversial results. While most studies failed to demonstrate any significant differences in ictal heart rate changes between right and left-sided seizures [10, 13, 14], in a recent study only right temporal seizures were associated with a significant increase in heart rate whereas left temporal seizures did not cause significant heart rate changes [19].

Bradyarrhythmias occur much less frequently than tachyarrhythmias during epileptic seizures [1]. Ictal bradycardia can vary from mild asymptomatic sinus bradycardia to more severe symptomatic bradyarrhythmias (pronounced sinus bradycardia, sinus arrest, atrioventricular block) and prolonged asystole [3].

In previous studies, the incidence of sinus bradycardia ranged from 1.3 to 5.5% [11, 20]. In our own series, an asymptomatic heart rate deceleration of more than 10 bpm was observed in 3.3% of seizures [13]. In one study, a significantly higher proportion of seizures (25.5%) with an early heart rate decrease was observed, which was attributed to methodological differences of heart rate assessment by the authors [21], although these discrepancies are difficult to reconcile.

A pronounced slowing of heart rate leading to cardiogenic syncope has been referred to as "ictal bradycardia syndrome" [22-25]. The ictal bradycardia syndrome most frequently occurs in male patients (5:1 ratio of male to female patients) suffering from temporal lobe epilepsy (87% of all cases where a confident localization of the ictal onset zone was possible), according to a recent review article [22]. In rare cases, ictal bradycardia was observed in frontal and occipital lobe epilepsies [22] as well as in generalized epilepsy [3].

Finally, sinoatrial arrest [26-29] and ictal asystole [22, 30-37] were reported in several case studies.

The pathophysiology underlying ictal bradyarrhythmias remains unclear although activation of the amygdala and the insular cortex have been implicated. Amygdala inputs to the hypothalamus may result in increased vagal output and subsequent bradycardia [3], furthermore there are direct projections from the amygdala to cardiovascular control centers in the dorsal medulla [38]. Stimulation of the amygdala and the left anterior insular cortex [7], as well as application of penicillin to the anterior hypothalamus [39] may result in sinus bradycardia and sinuatrial arrest. Furthermore, the fact that ictal bradycardia may occur during seizures of various cortical origin may point to a dysfunction of a complex cortical network including the insulo-opercular region, the mesio-temporal lobe and the orbito-frontal cortex [40-42].

Other cardiac arrhythmias reported during epileptic seizures include atrial fibrillation [43, 44], sinus arrhythmia, supraventricular tachycardia, atrial premature depolarizations, ventricular premature depolarizations, bundle branch block and atrioventricular nodal escape rhythm [11, 45]. These arrhythmias were observed in 39-42% of patients [11, 45] with potentially serious abnormalities occurring in 14% [45]. In contrast to these studies, other authors did not find high risk abnormalities such as ventricular ectopia, conduction defects or bradycardia during epileptic seizures [12]. Moreover, the incidence of interictal high risk cardiac arrhythmias was similar to age-matched controls without epilepsy in several studies [14, 46].

Focal seizures may also induce changes in cardiac depolarization and repolarization including S-T segment elevation and depression as well as alterations in T-wave morphology including inverted or biphasic waves, although the clinical relevance of these changes remains to be elucidated [45, 47, 48].

Some patients report a "pounding heart" during their seizures although these episodes usually are not accompanied by significant changes in heart rate or rhythm. Whether this complaint is simply the result of an increased awareness of normal physiological sensations due to an altered central perception caused by the seizure discharges or an actual increased cardiac contractility is unclear [3].

On rare occasions epileptic seizures can mimic cardiovascular disease and present with chest pain associated with radiation of the pain to the jaw or left arm, diaphoresis, shortness of breath and nausea simulating angina pectoris which can cause erroneous admission to a coronary care unit or even cardiac catheterization [24]. These sensations are not caused by myocardial ischemia, but rather are generated by discharges in limbic structures without any peripheral cardiac changes [24]. Some authors have reported temporal lobe seizures characterized by headache, fear, tachycardia, hypertension, mydriasis, tremor and sweating suggestive of pheochromocytoma [24, 49, 50].

Usually, cardiac arrhythmias and anginal pain during epileptic seizures are associated with other symptoms more typical for partial seizures, including unresponsiveness, visual illusions and hallucinations, and other autonomic symptoms such as pallor, flushing, epigastric sensations, warmth, perspiration and nausea [1].

Respiratory manifestations

Respiratory manifestations during epileptic seizures comprise a wide spectrum of symptoms including subjective shortness of breath, hyperventilation, stridor, coughing, choking, apnea and potentially fatal neurogenic pulmonary edema [1].

Hyperventilation represents a standard activation method in the EEG laboratory and is the method of choice to activate not only 3 Hz spike-wave discharges in childhood absence epilepsy, but also focal epileptiform discharges, and focal slow waves [51]. Furthermore, hyperventilation can be used to induce non-epileptic seizures [52]. Conversely hyperventilation can represent a symptom during simple and complex partial seizures. Hyperventilation was seen more frequently in seizures originating in the mesial temporal lobe as compared to neocortical temporal lobe seizures, which was attributed to intimate connections between mesial temporal lobe structures, the hypothalamus and brain stem autonomic nuclei [53]. In patients with frontal lobe epilepsy, hyperventilation was reported in seizures arising from the frontopolar and the orbitofrontal regions [54]. Hyperventilation and/or shortness of breath in simple partial seizures characterized by ictal fear and panic have to be differentiated from panic attacks and acute hyperventilation [1, 55].

Nocturnal acute larnyngospasm can be an unusual, isolated epileptic seizure manifestation in children [56]. Nocturnal choking associated with abnormal motor activity and excessive daytime sleepiness can occur in nocturnal frontal lobe epilepsy and can be misdiagnosed as sleep apnea syndrome [57].

Postictal nosewiping performed with the hand ipsilateral to the seizure onset zone has been recognized as a frequent and easy to assess symptom of good lateralizing value in patients with temporal lobe epilepsy [58, 61]. This symptom which occurs more frequently after right temporal seizures can be interpreted as a purposeful reaction to increased upper airway secretion during seizures. The hand ipsilateral to the hemisphere of seizure onset is used, most probably because of discrete contralateral paresis/weakness or neglect [58]. A depth electrode study has pointed out that involvement of the amygdala is crucial for the induction of postictal nosewiping, while seizures restricted to the hippocampus did not result in nosewiping [59].

Postictal coughing is believed to indicate a temporal lobe seizure onset as well, and was observed in 9-40% of seizures [62, 63]. Postictal coughing seems to be associated with postictal nosewiping and is also considered as a reactive phenomenon in response to an excessive autonomic activation of respiratory secretions [64].

Whereas apnea with cyanosis usually occurs during generalized tonic clonic seizures as well as during generalized tonic seizures and many frontal lobe seizures, isolated apnea represents a rare clinical seizure manifestation. Isolated apneic seizures are well described in neonates, and have to be differentiated from breath-holding spells or infantile syncope, apnea or cyanosis from other causes [65-67]. A few cases of isolated apneic seizures have been reported in infants [68-70], children [71] and recently in an adult patient with seizure onset in the left posterior lateral temporal region documented by prolonged video-EEG monitoring and ictal SPECT [72]. Respiratory monitoring in patients with epileptic automatisms disclosed apnea, with the chest in an expiratory position as the most frequent ictal respiratory sign, furthermore decreased breathing rates with and without diminished tidal volumes were observed [73].

Postictal apnea lasting more than 10 seconds (mean 24 seconds) was observed in 20 out of 47 seizures during prolonged video-EEG monitoring in 10 out of 17 patients. 16 seizures were complex partial seizures without secondary generalization [74]. Recently, postictal central apnea was reported as a possible cause of SUDEP in a 20 year-old woman [75]. In a series of witnessed SUDEP cases, 12 deaths were associated with convulsive seizures and 12 out of 15 patients were reported to have experienced respiratory difficulties [76]. In a sheep model, central hypoventilation was found to play a central role in the pathogenesis of SUDEP [77]. These studies therefore suggest that central apnea is an early event that can induce postictal bradycardia and cardiac arrest due to an altered cardiorespiratory reflex [75].

Oxygen desaturation lasting more than 70 seconds with a nadir of 83% was reported during partial seizures without convulsive muscle activation, and thus further supports centrally mediated hypoventilation during epileptic seizures [78].

Neurogenic pulmonary edema is a potentially fatal complication of generalized seizures and especially of status epilepticus. The primary pathophysiological mechanism consists of a rise in the pulmonary vascular pressure, either due to sympathetic effects with pulmonary vasoconstriction or increased left atrial pressure following systemic hypertension [79, 80]. Repetitive seizures or status epilepticus are more likely to be followed by pulmonary edema than single seizures because intravascular pressure within the pulmonary capillaries progressively increases with the number of seizures, reaching values of up to 400-600% of control. This increased intravascular pressure in the pulmonary capillaries results in a doubling of pulmonary lymphatic drainage and an increase in transcapillary albumin conductance compatible with an alteration in pulmonary capillary permeability [81]. On pathological examination, a protein rich pulmonary edema with alveolar hemorrhages was observed [82]. Nonfatal postictal neurogenic pulmonary edema may be associated with altered pulmonary function up to 3 days following the seizure, consisting of shortness of breath and tachypnea which usually improve with supplemental oxygen [1, 83]. The hypothalamus and the ventrolateral nucleus tractus solitarius could play a role in the pathogenesis of neurogenic pulmonary edema [1].

The exact brain regions responsible for the manifestation of respiratory symptoms in epilepsy are not well defined. Respiratory arrest could be elicited by stimulation of a variety of temporal and extratemporal regions including the temporal pole, the insula and the hippocampus [84], the amygdala [85], as well as the anterior cingulate gyrus, the lower motor strip and the uncus [86]. The influence of at least temporal lobe discharges on respiration is further supported by a correlation between respiratory cycles and single unit discharges in amygdala and hippocampal neurons [87]. These findings suggest that a common downstream subcortical center (e.g. hypothalamus, medulla) may be affected by epileptic activity [78].

Gastrointestinal symptoms

Epigastric auras

Epigastric auras probably represent the most common visceral symptom in adult epilepsy patients. In Van Buren's classical study [88] on 100 patients with epigastric auras, the following sensations were reported: fear, nervousness, guilt (16%), nausea (14%), tenseness, knot, external weight or squeezing (9%), rolling, turning or whirling movement in the abdomen (9%), tickling, tingling or electric shock sensation (9%), pain (8%), vibrating, fluttering or butterflies sensation (8%), gas or pressure within the abdomen (6%), an empty, hungry feeling (6%), sensation of warmth (5%), sensation of sudden descent in an elevator (5%), burning or heartburn (2%). The sensation begins usually in the epigastrium (57%) or stomach (25%) in the midline and either remains localized there (54%) or exhibits a rising sensation to the chest, throat, head or face. Frequently, epigastric auras are associated with other sensory, psychic, emotional or autonomic phenomena. Epigastric auras are not secondary to altered gastroesophageal motility since recordings of gastric motor activity during abdominal auras showed no effect upon gastromotor function. Although epigastric auras are most frequently encountered in temporal lobe epilepsy, they can occur also in extratemporal epilepsy. Epigastric sensations closely resembling epigastric auras can be elicited by electrical stimulation of mesial temporal structures (amygdala, hippocampus), the insula, the basal ganglia, the supplementary motor area, the pallidum and the centrum medianum of the thalamus [88]. Concerning the insula it is worth mentioning a recent paper by Isnard et al. [89] showing a rather frequent involvement of the insula during seizures of mesio-temporal origin which further supports the hypothesis that at least some autonomic symptoms are the result of discharge spread. Studies on the lateralizing significance of epigastric auras yielded controversial results. While some authors reported epigastric auras significantly more often in patients with seizures arising from the non-dominant temporal lobe concordant with an asymmetric central autonomic representation [90, 91], other studies could not find a lateralizing value of epigastric auras [63, 92-94].

Abdominal epilepsy

Whereas epigastric auras frequently precede or are associated with complex partial seizures, abdominal sensations as the sole manifestation of epileptic seizures are rare. They are more common in children than in adults, and are generally referred to as abdominal epilepsy [95, 96]. Abdominal epilepsy is characterized by paroxysmal pain of abrupt onset and brief duration of a few minutes or less and is localized to the midline or upper abdomen. It may be accompanied by anorexia, nausea and vomiting, and is frequently associated with a change in consciousness, such as disorientation or confusion, but usually consciousness is not lost completely [97]. Abdominal epilepsy also was described in a limited number of adult patients and here consisted of paroxysmal abdominal pain, nausea, bloating and diarrhea, accompanied by dizziness, headache, confusion, syncope and transient blindness [98, 99]. However, these cases were not documented by video-EEG monitoring and thus conclusions on the underlying pathophysiology remained speculative. From a series of 858 patients, three temporal lobe epilepsy patients suffered from seizures characterized by recurrent abdominal pain [100]. Recently, a patient with bilateral perisylvian cortical malformations presenting with recurrent intense colicky periumbilical pain accompanied by pallor, dizziness, multicolored photopsias and an EEG seizure pattern arising in the left frontotemporal region was reported [101].

Ictal vomiting and ictal retching

Ictal vomiting and ictal retching represent rare clinical seizure manifestations during temporal lobe seizures in adults [102-106], indicating seizure activity within the non-dominant hemisphere [104-107]. In our own series of 178 patients with medically refractory temporal lobe epilepsy, we observed ictal vomiting in five patients (2.8%) [108]. Ictal vomiting can be preceded by an aura of nausea, and usually is associated with other symptoms typical of temporal lobe seizures such as behavioral arrest, staring, eye blinking, oral and bilateral hand automatisms and grimacing [103-105, 107, 108]. Whereas most patients are amnesic for ictal vomiting, some patients have preserved consciousness during these episodes [104, 105, 108].

The lateralization towards the non-dominant hemisphere can be explained by a functional hemispheric asymmetry for the control of gastrointestinal motility [6]. Concerning the specific anatomical structures responsible for ictal vomiting, activation of a complex cortical network including medial and lateral aspects of the temporal lobe and especially the lateral superior temporal cortex including the insula and maybe the occipital lobes, seems to be necessary for its generation [104, 105, 108]. The involvement of such a network is in accordance with results of cortical stimulation studies where abdominal sensations were elucidated from several distinct brain areas, which failed however to induce vomiting during stimulation of a single brain site [86, 88]. Furthermore, in patients evaluated with subdural grid electrodes the most epileptogenic activity was seen in medial temporal regions while ictal vomiting was associated with spread of the EEG seizure pattern to more lateral and superior parts of the temporal lobe [104]. On ictal SPECT performed in patients with ictal vomiting, a hyperperfusion of the medial and lateral aspects of the temporal lobe with concomitant involvement of the lateral superior temporal cortex suggesting involvement of the insular cortex was observed [108]. The potential role of the insula, which can be considered as the visceral sensory cortex [6], for the generation of ictal vomiting has been pointed out by several authors [103-105, 109] and is further supported by cortical stimulation studies in humans where nausea could be elucidated by stimulation of the insula [86], and abdominal sensations occurred on stimulation of medial temporal regions and the basal ganglia [88]. Epileptic activity involving these cortical structures would thus cause vomiting by activation of the vomiting center in the brain stem [110].

Whereas ictal vomiting is rare in adult temporal lobe epilepsy patients, various subgroups of benign childhood epilepsies with occipital spikes are commonly associated with seizures presenting with vomiting [111]. Thus, the early-onset variant of benign childhood epilepsy with occipital paroxysms typically consists of nocturnal seizures with lateral tonic eye deviation and vomiting [112-114]. Idiopathic photosensitive occipital lobe epilepsy is a recently described idiopathic localization-related epileptic syndrome with age-related onset, a specific mode of precipitation and seizures presenting with visual symptoms, cephalic pain, epigastric discomfort, vomiting and normal or only mildly impaired responsiveness [115]. The mechanism causing vomiting in these occipital lobe epilepsies was attributed to an infrasylvian spread of the epileptic discharges to the non-dominant temporal lobe [107]. Others suggested that both epileptic cortical manifestations and vomiting are the result of an age-related neurotransmitter-mediated process which is excitatory both for the brainstem vomiting center and/or the chemoreceptor triggering zone, as well as the cerebral cortex [111]. Finally, postictal migrainous phenomena triggered by an occipital discharge were suspected to be responsible for vomiting associated with occipital lobe seizures [116].

When ictal vomiting occurs without impairment of consciousness [102, 107], it has to be differentiated from non-epileptic gastrointestinal causes of recurrent vomiting [117]. Especially in children, gastrointestinal reflux which can be accompanied by vomiting, cyanosis and posturing has to be excluded [118]. The syndrome of cyclic vomiting which is characterized by recurrent attacks of vomiting with headache, abdominal pain and fever [110] is associated with migraine, but not with epilepsy [118]. However, the presence of other symptoms typical of temporal lobe seizures and the additional occurrence of seizures with impairment of consciousness should facilitate this differential diagnosis on clinical grounds, although documentation of seizures with intensive video-EEG-monitoring may be necessary in exceptional cases.

Ictal spitting

Ictal spitting is an infrequent seizure symptom and is considered to indicate a seizure onset in the non-dominant temporal lobe. In a recent paper, ictal spitting occurred in 5 out of 270 patients (2%) undergoing right temporal lobe resections, but in none of 290 undergoing left temporal resection. Ictal spitting can occur during simple and complex partial seizures. A case report of ictal spitting in a patient with left mesial temporal lobe epilepsy revealed right hemispheric dominance by Wada test further supporting the hypothesis that this symptom indicates a seizure onset in the non-dominant hemisphere [119]. Because patients do not usually report ictal gustatory hallucinations, ictal spitting can be considered a pure motor automatism rather than a provoked symptom in response to a gustatory aura. Ictal spitting was observed irrespective of the type of pathology or gender. This symptom most probably is generated by epileptic activity within the insula. Interestingly, ictal spitting does not occur in association with ictal vomiting, ictal coughing or ictal fear, suggesting different sites mediating these symptoms [120].

Cutaneous manifestations

Cutaneous autonomic seizure symptoms include flushing, pallor, sweating and piloerection, which may be accompanied by feelings of warmth, cold and pain [1, 2, 4]. These symptoms most often are symmetrical, however, lateralized or localized manifestations have also been reported in several cases. Cutaneous autonomic signs are usually associated with other autonomic and non-autonomic symptoms characteristic of simple and complex partial seizures [1].

Seizures with flushing have been reported by several authors [88, 121]. On rare occasions temporal lobe seizures are characterized by transient paroxysms of flushing, hypertension, tachycardia and increased plasma catecholamine levels at the peak of the spells [50]. Seizures with flushing have to be differentiated from pheochromocytoma, carcinoid syndrome, mastocytosis and finally "hot flushes" in postmenopausal women [122].

Ictal pallor originally described by Mulder et al. [121] and Van Buren [88] was recently reported as a cardinal feature in various epileptic conditions including temporal lobe epilepsy with ictal fear due to atrophy of the amygdala [123], bilateral perisylvian polymicrogyria associated with abdominal epilepsy [101] and early-onset benign childhood seizure susceptibility syndrome [114]. Non-epileptic paroxysmal pallor can occur in pheochromocytoma, as a prelude to syncope, and in hypoglycemia [122].

Ictal sweating was reported originally by Penfield and Kristiansen [124] and later by Mulder [121] and Van Buren [88]. Some patients had sweating in association with focal sensory or motor symptoms in an identical spatial distribution [124]. Furthermore, seizures with sweating were described in a patient with a basal forebrain malformation who experienced attacks of episodic sweating and shivering with reduced core temperature as a variant of Shapiro`s syndrome [125], in a patient with abdominal epilepsy where sweating occurred in conjunction with abdominal pain, headache and vertigo [126] and finally in a tumor patient who suffered from attacks of generalized coldness and sweating [127].

Seizures with piloerection characterized by gooseflesh or goosebumps sometimes associated with pain have been reported by several authors [124, 128-134]. The seizure onset zone most often was localized within the temporal lobe, but occasional pilomotor seizures originating in central [124] and orbitofrontal structures [135] were reported. Recently, several studies have indicated that pilomotor seizures occur ipsilaterally to the seizure onset zone [128, 129], and that in selected cases piloerection spreads in a "Jacksonian march" like pattern [128, 129]. Lesions in these patients included deep seated temporal lobe tumors [129], hippocampal sclerosis, meningeoma of the sphenoid wing [128, 129] and traumatic contusion of the temporal lobe [130]. In animal experiments, piloerection could be elicited by stimulation of the amygdala [136].

Pupillary symptoms

Bilateral mydriasis frequently occurs during generalized tonic clonic seizures [137], but also during complex partial seizures [86]. In a recent study, pupils were found to be dilated and unreactive to light during the time when consciousness was impaired, while they were reactive during the aura. The authors attributed this phenomenon to seizure effects on subcortical midline structures caused by contralateral seizure spread [138]. Bilateral mydriasis is also a characteristic sign of seizures with ictal fear due to amygdala atrophy [123]. Unilateral mydriasis, on the other hand, is far less common [139-141] and has been observed both ipsilateral [142] and contralateral [143] to the seizure focus.

Ictal miosis is a rare seizure manifestation. Bilateral ictal miosis accompanied by internal ophthalmoplegia was reported in a patient with a left temporo-occipital seizure focus [144]. Unilateral ictal miosis was observed in a patient with an occipital cavernoma and seizures characterized by additional homonymous hemianopia and visual hallucinations [145]. In temporal lobe epilepsy, paroxysmal unilateral miosis and ptosis were observed both ispi- and contralateral to the seizure onset zone [146].

Genital and sexual manifestations

Genital and sexual seizure manifestations represent rare clinical phenomenona during or after focal seizures and can be subdivided into (1) sexual auras, (2) genital auras, (3) sexual automatisms and (4) genital automatisms.

Sexual auras consist of erotic thoughts and feelings, sexual arousal and orgasm and may be accompanied by appropriate viscerosensory and autonomic changes of sexual excitement including vulvovaginal secretory activity as well as by olfactory hallucinations. Sexual auras are thought to result from epileptic discharges in the limbic portions of the temporal lobe and occur almost exclusively in women suggesting a gender-specific organization of sexual functions within the limbic system [147-150]. Whether sexual auras have lateralizing significance remains undetermined, although right temporal epileptic foci were more common in the patients reported so far [150].

Genital auras are characterized by unpleasant, sometimes painful, frightening or emotionally neutral somatosensory sensations in the genitals and can be accompanied by ictal orgasm. Genital auras are generated by epileptic discharges in the parasagittal postcentral gyrus where the cortical representation of genital sensation resides [151-154]. In addition, and mainly when these sensations are bilateral, the second somatosensory area of Penfield can be involved too.

Sexual automatisms are characterized by hypermotor movements consisting of writhing, thrusting and rhythmic movements of the pelvis, arms and legs, sometimes associated with picking and rhythmic manipulation of the groin or genitalia, exhibitionism and masturbation, and are considered as typical for frontal lobe seizures [155-157]. In a recent study, sexual automatisms were seen with seizure onsets from different subcompartments of the frontal lobe including the frontal convexity, the orbitofrontal region and the supplementary sensorimotor area [158].

Genital automatisms on the other hand are characterized by discrete genital automatisms such as grabbing or fondling the genitals which can be accompanied by masturbatory activity and exhibitionistic behavior. Genital automatisms are generally associated with temporal lobe seizures [147-149, 159]. We recently reported five patients with temporal lobe epilepsy whose seizures consisted of genital automatisms. Seizure onset within the temporal lobe was proven by good to excellent postoperative seizure control after selective amygdala-hippocampectomy in four patients and after removal of a ganglioglioma involving the hippocampus in one patient [160]. A possible role of the temporal lobe in sexual behavior was reported originally by Klüver and Bucy [161] who demonstrated that bilateral temporal lobectomy in monkeys produced hypersexuality, including exhibitionistic masturbatory activity. Similar findings were later obtained in humans [162, 163]. In a single case report automatisms during absence status in a patient with generalized epilepsy were manifested as compulsive masturbation, although sexual seizure symptoms in generalized epilepsy are exceptional [164]. We, and others, believe that a distinction between hypermotor sexual automatisms and discrete genital automatisms is helpful for differentiating frontal and temporal lobe seizures [160, 165].

Urinary symptoms

Urinary incontinence is a frequent accompaniment of generalized tonic clonic seizures. Although the intravesicular bladder pressure increases to 120 cm H2O during the tonic phase and then progressively decreases during the clonic phase to reach normal values after the last clonic jerk, voiding does not occur due to sphincter muscle contraction until the end of the clonic phase when the sphincter muscle relaxes. Thus, urine loss is not due to the increased intravesicular pressure during the seizure, but rather depends on the relaxing of the vesical sphincter during the phase of muscular recovery and occurs only if the bladder is full at the time of the attack [166]. Absence seizures can be accompanied by enuresis as well. Thus, intravesicular pressure increases 3 to 4 seconds after the onset of the spike wave discharges and subsequently reaches a maximum of 50 to 60 cm H2O. In children who actually pass urine, the pressure reaches or exceeds 120 cm H2O. Cortical inhibition freeing the subcortical centers which control the micturition reflex was considered as the mechanism responsible for the increase in intravesicular pressure [167].

Ictal urination without loss of consciousness may occur as a rare symptom of simple partial seizures [4, 121, 124]. In a recent article, we described ictal urinary urge as a rare symptom occurring in 6 patients with temporal lobe epilepsy [168]. Our patients expressed an intense urinary urge at the beginning of their seizures which was documented on video-EEG monitoring. While four patients remembered this symptom when interviewed postictally, the remaining two patients were amnesic for their aura including the urinary urge after their seizures. Three patients actually passed urine during the aura or the subsequent seizure, in one of them the aura lasted long enough that he could go to the toilet before the complex phase of his seizure began. In all patients the seizure onset could be lateralized to the non-dominant temporal lobe which can be explained by a hemispheric specific representation of central bladder control. Recent PET studies on brain activation during micturition in normal subjects suggested a predominance of the right brain in central bladder control [169, 170]. In patients suffering from stroke and brain tumors, incontinence correlated with right hemispheric lesions [171, 172]. In geriatric patients, urge incontinence with reduced bladder filling sensation was associated with hypoperfusion of the right frontal regions on interictal SPECT [173]. Concerning the specific brain areas responsible for the generation of ictal urinary urge, we proposed the involvement of the insular cortex because on ictal SPECT performed in two of our patients a hyperperfusion of the superior temporal gyrus containing the insular cortex could be observed. This hypothesis is further supported by PET studies in normal subjects where urination was associated with a significantly increased blood flow in the right dorsal pontine tegmentum and the right inferior frontal gyrus, whereas during the filled bladder condition the right frontal operculum and/or the right anterior insula were significantly activated [170]. Thus, epileptic activity within the insular cortex which can be regarded as the primary viscerosensory area could be responsible for a filled bladder sensation resulting in ictal urinary urge. Another possibility would be that ictal urinary urge was mediated by propagation of epileptic activity to frontal lobe structures, i.e. the right inferior frontal gyrus, which have been shown to be of critical importance in suprapontine bladder control [169, 170]. The role of the inferior frontal cortex and more specifically the orbitofrontal surface ­ which is closely connected with the insula ­ for the generation of ictal urinary symptoms has been discussed by Bancaud and Talairach [157].

  Received July 20, 2001 - Accepted August 26, 2001

Videosequence caption

Case 1: Postictal nosewiping

41 year-old patient with unilateral, right-sided mesial temporal epilepsy.

Clinical seizure semiology: 10:44:58 clinical seizure onset: patient experiences epigastric aura and looks at her watch; 10:45:08 patient says repeatedly "please help me"; 10:45:30 patient is asked by the technician for her first name; 10:45:35 patient says her first name; 10:45:36 patient is asked by the technician about where she is => patient hesitates; 10:45:45 patient names place correctly; 10:45:46 patient repositions herself => responsive and fully oriented; 10:45:56 scratches her head with her right hand; 10:46:01 postictal nosewiping with right hand; 10:46:05 reads sentence correctly.

EEG: 10:45:11 EEG seizure onset with non-lateralized rhythmic theta activity; 10:45:14 right temporal rhythmic delta activity; 10:45:45 EEG seizure end.

Case 2: Postictal coughing

59 year-old patient with unilateral, right-sided mesial temporal lobe epilepsy.

Clinical seizure semiology: patient is lying asleep on her stomach; 5:33:01 clinical seizure onset with patient elevating her head and looking around; 5:33:08 patient looks to the right; 5:33:33 dystonic posturing left upper extremity; 5:34:13 unilateral automatisms right upper extremity; 5:34:38 postictal nosewiping with right hand and postictal coughing; 5:34:41 postictal automatisms with right upper extremity; 5:34:55 postictal bilateral automatisms with upper and then lower extremities.

EEG: 5:33:03 EEG seizure onset with right temporal rhythmic theta activity; 5:34:14 contralateral spread to the left temporal lobe; 5:34:06 EEG seizure end.

Case 3: Postictal coughing associated with postictal nosewiping

47 year-old patient with bitemporal epilepsy (seizures were originating independently from the left and the right temporal lobe) and left-sided hippocampal atrophy on MRI.

Clinical seizure semiology: 8:52:30 clinical seizure onset with staring, slight oral automatisms, swallowing, automatisms of the left upper extremity and both legs; 8:52:41 hyperventilation and vocalization; 8:52:54 patient is non-responsive; 8:52:55 dystonic posturing right upper extremity; 8:53:00 unilateral automatisms left hand, word is given to remember; 8:53:21 patient does not follow command to elevate her arms; 8:53:33-8:54:06 postictal nosewiping with left hand and postictal coughing; 8:54:10 postictal oral and hand automatisms, postictal testing reveals postictal confusion.

EEG: 8:52:28 EEG seizure onset with left temporal rhythmic theta activity; 8:52:48 contralateral spread to the right temporal lobe; 8:53:33 EEG seizure end.

Case 4: Hyperventilation

28 year-old patient with multifocal epilepsy and moderate mental retardation.

Clinical seizure semiology: 16:33:44 clinical seizure onset: patients says that he is feeling nauseous; 16:33:48 hyperventilation; 16:33:55 patient waves purposefully with his right hand in response to a question; 16:33:57 unilateral automatisms right hand; 16:34:01 hypermotor automatisms with vocalization, rocking movements of the pelvis and beating of the left upper extremity; 16:34:08 elevation of both upper extremities; 16:34:10 hypermotor automatisms with right upper extremity; 16:34:14 dystonic posturing with left upper extremity, head turning to the right and unilateral automatisms of the right upper extremity; 16:34:22 tonic contraction of right hand.

EEG: 16:33:53 EEG seizure onset with non-lateralized rhythmic theta activity; EEG thereafter obscured by movement artifact.

Case 5: Ictal vomiting

30 year-old patient with unilateral, left-sided mesial temporal epilepsy and right hemispheric language representation documented by the Wada test.

Clinical seizure semiology: Patient is lying on her left side, 1:46:45 turns to the back and opens her eyes; 1:47:07 clinical seizure onset: patient presses seizure alarm button with her left hand; 1:47:15 sits up, takes the kidney dish followed by retching and vomiting; 1:47:28 unilateral right upper extremity automatisms; 1:47:31 preserved ictal speech, speech is slightly dysarthric, patient is fully responsive during the entire seizure.

EEG: 1:47:12 EEG seizure onset with left temporal rhythmic theta activity; 1:49:45 EEG seizure end (not shown on video).

Case 6: Ictal retching

41 year-old patient with unilateral, right-sided mesial temporal epilepsy.

Clinical seizure semiology: 11:38:41 clinical seizure onset with grimacing, swallowing and staring; 11:38:48 moaning; 11:38:51 ictal retching; 11:39:04 clinical seizure end; 11:39:10 hypersalivation manifesting in drooling; 11:39:15 and later repeated postictal nosewiping with right hand.

EEG: 11:38:40 EEG seizure onset with right temporal rhythmic theta activity; 11:39:03 EEG seizure end.

Case 7: Genital automatisms

44 year-old patient with unilateral, right-sided mesial temporal epilepsy.

Clinical seizure semiology: 12:45:11 clinical seizure onset with alteration of facial expression and staring, 12:45:29 head turning to the left and tonic posturing of left upper extremity => posturing and automatisms of both upper extremities, retching; 12:45:56 tonic, followed by clonic contraction of left face, tonic posturing left upper extremity => tonic elevation of right upper extremity; 12:46:06 patient non-responsive, automatisms with right upper extremity; 12:46:19 gential automatisms with right upper extremity; 12:46:28 postictal coughing; 12:46:30 postictal automatisms of both legs.

EEG: 12:45:09 EEG seizure onset with right temporal rhythmic theta activity; 12:46:05 EEG seizure end.

Case 8: Ictal urinary urge

30 year-old patient with unilateral right-sided mesial temporal epilepsy.

Clinical seizure semiology: 17:56:51 clinical seizure onset: patient puts away newspaper because of aura, brief tonic posturing of left upper extremity; 17:56:02 reports that she is experiencing an aura, slight hyperventilation; 17:56:36 says that she is feeling nauseous; 17:56:49 reports that she is experiencing an intense urinary urge; 17:58:14 says that she has to go to the toilet; 17:58:21 interview by the nurse, patient says that she feels nauseous; 17:58:44 interview by the physician starts; 17:58:55 reports that she is experiencing an intense urinary urge; 17:59:14 says that she is going to urinate; 17:59:19 staring, stiffening of the body, turns slightly to the left, hand automatisms concealed by blanket; 17:59:33 turns on her back, stares; 17:59:45 says that she has passed urine; 18:00:09 elevates both arms on command, responsive and fully oriented; 18:00:34 postictal nosewiping with right upper extremity.

EEG: 17:56:09 EEG seizure onset with right temporal rhythmic theta activity; 17:59:52 EEG seizure end.

Case 9: Pilomotor seizure

53 year-old patient with bitemporal epilepsy; independent right and left temporal EEG seizure patterns were recorded; seizures with goosebumps were not accompanied by ictal EEG changes. MRI showed right-sided hippocampal sclerosis.

Clinical seizure semiology: 16:00:11 ictal goosebumps right arm, patient fully responsive with preserved speech; 16:00:30 goosebumps fade away.

EEG: no significant change.

CONCLUSION

Autonomic symptoms frequently occur during epileptic seizures either accompanying other seizure symptoms or as the predominant seizure manifestation. Autonomic symptoms do not represent simple reactions to motor manifestations of seizures, but are mediated by an activation of the central autonomic network and thus open a unique window on its functional organization. Due to a hemispheric-specific representation of the central autonomic network, certain autonomic symptoms provide lateralizing and sometimes localizing information on the seizure onset zone. Autonomic symptoms range from subtle seizure manifestations, which become apparent only during meticulous seizure analysis, to severe, sometimes life-threatening events. Cardiovascular and respiratory autonomic symptoms are discussed as the mechanisms underlying sudden unexplained death in epilepsy. When autonomic symptoms represent the sole seizure manifestation they can pose problems for the differential diagnosis of various non-epileptic conditions. This underlines the importance of their careful analysis and correct interpretation.

Acknowledgements: We thank Dr Philippe Kahane for valuable comments on the manuscript.

Grant support: This work was supported by the Jubiläumsfond der Österreichischen Nationalbank (project 8135).