Hypersalivation in Temporal Lobe Epilepsy

Transcription

1 Epilepsia, 47(3): , 2006 Blackwell Publishing, Inc. C 2006 International League Against Epilepsy Hypersalivation in Temporal Lobe Epilepsy Jagdish Shah, Huifang Zhai, Darren Fuerst, and Craig Watson Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan, U.S.A. Summary: Purpose: We sought to determine whether hypersalivation helps ize seizure onset during complex partial seizures of temporal lobe origin. Several clinical signs, which help ize seizure onset, have been reported in temporal lobe epilepsy (TLE). Increased salivation only occasionally has been reported as a manifestation of partial epilepsy. Methods: Of 590 consecutive patients admitted for video-eeg monitoring, either as a part of a presurgical evaluation of medically intractable epilepsy or for diagnosis and clarification of their paroxysmal symptoms, we identified 10 patients with ictal hypersalivation as a prominent manifestation of complex partial seizures. We reviewed the clinical features, scalp-sphenoidal video-eeg monitoring, intracarotid amytal (Wada) testing, hippocampal volumetric magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography (FDG-PET) scans of these patients. Results: Of the 10 patients with ictal hypersalivation, seven patients had nondominant/right TLE, and three patients had dominant/left TLE. All patients had hippocampal atrophy on volumetric MRI. Eight of the 10 patients underwent standard temporal lobectomy with amygdalohippocampectomy (six right, two left). All of the operated-on patients had a seizure-free (Engel class I) outcome, and their increased salivation resolved. Two patients, who did not undergo surgical treatment, continue to have complex partial seizures with increased salivation. Conclusions: We conclude that increased salivation as a prominent ictal finding in complex partial seizures of temporal lobe origin is more likely to be of nondominant temporal lobe origin. Further studies with larger numbers of patients are needed to replicate this finding. Key Words: Temporal lobe epilepsy Complex partial seizure Hypersalivation Video-EEG monitoring. Autonomic and visceral manifestations are common during epileptic seizures and are usually associated with impaired consciousness. Autonomic nervous system involvement in partial seizures of temporal lobe origin manifests as change in blood pressure, heart rate, cardiac rhythm, chest pain, sudden death, respiratory changes, flushing, pallor, piloerection, diaphoresis, mydriasis, miosis, abdominal pain, epigastric rising sensation, nausea/vomiting, bloating, diarrhea, stridor, choking, and coughing (1). Salivary secretion is under neural control. Stimulation of the parasympathetic nerve supply of the salivary glands results in profuse secretion of watery saliva, with relatively low content of organic material; whereas stimulation of the sympathetic nerve supply causes secretion of a small amount of saliva rich in organic constituents. Food in the mouth, stimulation of vagal afferent fibers at the gastric end of the esophagus, sight, smell, and even the thought of food can cause salivary secretion (2). We describe the clinical features, scalp-sphenoidal video-eeg monitoring, magnetic resonance imaging Accepted December 8, Address correspondence and reprint requests to Dr. C. Watson at Department of Neurology, Wayne State University School of Medicine, 8D University Health Center, 4201 St. Antoine, Detroit, MI 48201, U.S.A. crwatson@med.wayne.edu (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET), and Wada test results of 10 patients with intractable epilepsy and increased salivation as a prominent ictal manifestation of their complex partial seizures. METHODS We reviewed 590 consecutive patients who were evaluated by using prolonged video-monitoring. Of these patients, 31% had temporal lobe epilepsy (TLE), 14% had extratemporal partial epilepsy, 4% had primary generalized epilepsy, 33% had nonepileptic seizures, and 18% were unable to be classified. We found 10 cases of hypersalivation during complex partial seizures. Ictal hypersalivation was directly observed on video-eeg by one of the authors (J.S.) and was defined as a dramatic increase in production of saliva leading to uncontrollable drooling. All 10 patients were known to have medically intractable partial epilepsy and were being monitored for possible surgical treatment. All patients had their antiepileptic medication (AED) tapered 2 days before admission and then discontinued on the day of admission. This was followed by 2 to 5 days of continuous inpatient scalp-sphenoidal video- EEG recording. All patients also underwent hippocampal volumetric MRI, FDG-PET scan, neuropsychological 644

2 HYPERSALIVATION IN TEMPORAL LOBE EPILEPSY 645 evaluation, and Wada testing (patient 2 did not have a Wada test.). RESULTS Clinical characteristics Table 1 presents clinical summaries of the patients. They ranged in age from 26 to 53 years. Age at seizure onset ranged from 2 to 42 years. All patients had a history of medically intractable complex partial seizures of temporal lobe origin. All patients showed increased salivation as a prominent ictal manifestation and had some ictal phenomena before the occurrence of hypersalivation (Table 2). For instance, all patients had staring and impaired awareness preceding the hypersalivation. Various other clinical features were seen: upper limb automatism (8), oral-alimentary automatism (8), spitting automatism (1), eyelid fluttering (1), and upper extremity dystonia (8). Abdominal aura (6), déjà vu (3), fear and anxiety (2), and flushing (2) were the most common simple partial seizures (auras) reported, whereas two patients did not report an aura. Seven patients had right TLE, and three had left TLE. All patients had ictal onsets involving the temporal head region, and all but one patient (patient 9) had interictal epileptiform activity involving the temporal head region (Fig. 1). All patients were found to have hippocampal sclerosis (HS) on hippocampal volumetric MRI, which was confirmed on pathological examination in the eight patients who had surgery. All but one patient (patient 2) underwent Wada testing for language dominance and memory performance. Wada testing revealed left hemisphere dominance for language function in all patients, and all but one patient (patient 9) had adequate memory function in the normal temporal lobe. Surgical outcome Eight patients underwent standard anterior temporal lobectomy including amygdalohippocampectomy (six right, two left), and all of the operated-on patients had a seizure-free outcome (Engel class I). Two patients (one right TLE, one left TLE) refused surgical treatment and continue to have medically refractory epilepsy associated with hypersalivation. DISCUSSION This series adds prominent ictal hypersalivation as another possible izing clinical sign in TLE. Seven of 10 patients with this sign had nondominant TLE, and three patients had dominant TLE. This suggests that hypersalivation may be seen predominantly, but not exclusively, in TLE originating in the nondominant hemisphere. Increased salivation has been reported rarely as a manifestation of partial seizures. John Hughlings Jackson (3) first referred to a case reported by Sander. This patient had a glioma of the left inferior frontal and anterior medial temporal region and seizures whose clinical manifestations included increased salivation and spitting automatism. Penfield and Jasper (4) described a patient with increased salivation as a prominent manifestation of partial epilepsy, who had a posttraumatic cyst in the right postcentral gyrus just above the sulcus and demonstrated increased salivation after electrical stimulation of the same region. After resection of the lesion, the patient became seizure free, and the increased salivation resolved. These authors mentioned another patient with complex partial seizures, accompanied by hypersalivation, presumably caused by a tumor of the pes hippocampus (side not mentioned). A recent report (5) described a patient with medically intractable, dominant medial TLE in whom ictal hypersalivation was a prominent clinical feature. Resection of the temporal lobe structures in this patient resulted in seizure freedom as well as resolution of hypersalivation. Reports of partial seizures in children with benign epilepsy with centrotemporal spikes (BECTS, rolandic epilepsy) have described increased salivation/drooling as a prominent clinical manifestation [for a review, see Shafrir and Prensky (6)]. Three of these reports described status epilepticus in benign rolandic epilepsy associated with increased salivation and drooling, and two reports described cases of prolonged, fluctuating drooling, which worsened in association with increased epileptiform activity on EEG. The authors thought that ictal drooling was a result of excitation in opercular areas subserving salivation. Of the six cases reported, two had seizures that originated predominantly from the right side, one from the left side, and three were bi. Another case report (7) described reflex seizures associated with ictal drooling caused by a cryptic vascular malformation in the right parietal operculum. Epileptic salivation also can occur in partial epilepsy originating in the orbitofrontal and dorso frontal regions (number of cases and ity not mentioned) (8). As can be seen from these studies, the precise anatomic localization and ization of ictal hypersalivation remains unclear. Case reports and review articles (3 8) point toward involvement of various anatomic regions in ictal hypersalivation. These include medial temporal lobe structures, orbitofrontal and dorso frontal cortex, postcentral gyrus, and parietal operculum. The link between increased salivation and TLE is supported by known neuroanatomic connections. Limbic efferent fibers to the hypothalamus via the fornix are relayed by the dorsal longitudinal fasciculus to the brainstem inferior and superior salivary nuclei, which in turn innervate the salivary glands. However, the studies cited indicate that areas remote from the medial temporal lobe also are implicated in ictal hypersalivation. In our patients, ictal hypersalivation occurred in the middle or latter part of the seizure and at a time when the

3 646 J. SHAH ET AL. TABLE 1. Clinical summaries of patients Sz Sz Surgical Pt. Ageonsetduration Risk Sz Aura CPS Interictal outcome no. (yr) (yr) (yr) factors types (SPS) semiology EEG Ictal EEG MRI FDG-PET Wada (follow-up) CHI at age 5 yr CPS, GTCS None Staring, impaired awareness, lip smacking, RUE automatism, LUE dystonia, salivation. Tachycardia throughout Sz Meningitis at age 2 yr. R frontal meningioma removal Stab injury to R parietooccipital region SPS, CPS, GTCS Fear, anxiety, disagreeable smell, déjà vu SPS, CPS AA, sees blue lights Staring, impaired automatism, RUE dystonia, salivation, lip smacking, head version to right before GTCS Facial grimace, staring, impaired awareness, increase in respiratory rate, right facial clonic activity, salivation, LUE clonic, BUE tonic FC at 8 yr. FHx of Sz SPS, CPS AA Staring, impaired automatism, RUE dystonia, swallowing, salivation FC at 2 yr. R parietal meningioma excision SPS, CPS, GTCS AA, body flushing, déjà vu Staring, impaired awareness, lip smacking, LUE dystonia, RUE automatism, eyelid fluttering, salivation, head version to left at beginning of GTCS R temporal spikes, sharp waves, slow waves L temporal spike wave complexes, R frontal slowing R>L temporal sharp waves, slow waves, R parietal slow waves L temporal spikes, rare R temporal spikes R temporal spikes, slow waves L temporal L AM atrophy, L HS, R frontal postop changes R temporal R occipital encephalomalacia, R posterior HS L temporal L AM atrophy, L HS L medial & R occipital, parietal, & medial L medial & 7.5/9, R = 1.5/9 Not done (Presumed left hemisphere dominance for language based on postictal aphasia) 8/9, R = 0/9 6.5/9, R = 7/9 6/9, R = 1/9 Class I (19 mo) N/A Class I (53 mo) Class I (43 mo) Class I (33 mo)

4 HYPERSALIVATION IN TEMPORAL LOBE EPILEPSY 647 TABLE 1. Continued. Sz Sz Surgical Pt. Age onset duration Risk Sz Aura CPS Interictal outcome no. (yr) (yr) (yr) factors types (SPS) semiology EEG Ictal EEG MRI FDG-PET Wada (follow-up) None SPS, CPS AA Staring, impaired awareness, RUE automatisms, spitting, salivation, swallowing CHI at ages 3, 11,&13yr Coma for 1 wk after childbirth at age 14 yr CHI with LOC at 10 yr CPS None Staring, impaired awareness, RUE automatism, LUE tonic, salivation, oral automatisms, tachycardia throughout Sz SPS, CPS Feeling nervous Staring, impaired awareness, lip smacking, RUE automatism, LUE dystonia, salivation, eyes deviate to right SPS, CPS AA, déjà vu, fear Staring, impaired awareness, increase in respiratory rate, bicycling, myoclonic jerks of LUE, moaning, salivation CHI at age 8 yr SPS, CPS, GTCS AA, flushing Staring, impaired dystonia, RUE automatism, salivation, lip smacking, swallowing, head version to left before GTCS R temporal spikes, slow waves R>L temporal spikes, sharp waves, slow waves R>L temporal spikes, sharp waves, spike wave complexes Normal L temporal L AM atrophy & LHS R temporal spikes, spike wave complexes R temporal R posterior 2/3 HS, R anterior HF malformation L medial & R>>L medial & 9/9, R = 5.5/9 8/9, R = 0/9 8/9, R = 0/9 9/9, R = 0/9 5.5/9, R = 0/9 Class I (59 mo) Class I (9 mo) N/A Class I (45 mo) Class I (53 mo) Pt. no., patient number; Sz, seizure; SPS, simple partial seizure; CPS, complex partial seizure; GTCS, generalized tonic clonic seizure; CHI, closed head injury; RUE, right upper extremity; LUE, left upper extremity; BUE, both upper extremities; R, right; L, left, HS, hippocampal sclerosis; AM, amygdala; HF, hippocampal formation; AA, abdominal aura; FC, febrile convulsions; FHx, family history; LOC, loss of consciousness; N/A, not applicable.

5 648 J. SHAH ET AL. TABLE 2. Features of the recorded ictal hypersalivation events Time EEG from seizure Main Contra EEG onset clinical State of Duration of Localization of Main EEG electrodes seizure Duration compared features awareness clinical EEG pattern involved onset to of EEG with clinical Pt. Sz (in order of during Lateralizing seizure seizure during during salivation seizure onset no. no. Baseline occurrence) salivation signs (s) onset salivation salivation (s) (s) (s) 1 3 Awake Staring, impaired awareness, lip smacking, RUE automatism, LUE dystonia, salivation, tachycardia throughout Sz 2 2 Awake Aura, staring, impaired automatism, RUE dystonia, salivation, lip smacking, head version to right before GTCS 3 5 Awake Aura, facial grimace, staring, impaired awareness, increase in respiratory rate, right facial clonic activity, salivation, LUE clonic, BUE tonic 4 4 Awake Aura, staring, impaired automatism, RUE dystonia, swallowing, salivation 5 4 Awake Aura, staring, impaired awareness, lip smacking, LUE dystonia, RUE automatism, eyelid fluttering, salivation, head version to left at beginning of GTCS Unresponsive LUE dystonia 80 Right temporal Diffuse delta Significant Unresponsive RUE dystonia, postictal aphasia 43 Left temporal Diffuse theta and delta Unresponsive None 93 Right hemisphere, maximal temporal Unresponsive RUE dystonia, postictal aphasia Unresponsive LUE dystonia, ictal speech Diffuse rhythmic theta Significant Significant Left temporal Diffuse theta Significant Right temporal Diffuse rhythmic theta Significant

6 HYPERSALIVATION IN TEMPORAL LOBE EPILEPSY 649 TABLE 2. Countinued Time EEG from seizure Main Contra EEG onset clinical State of Duration of Localization of Main EEG electrodes seizure Duration compared features awareness clinical EEG pattern involved onset to of EEG with clinical Pt. Sz (in order of during Lateralizing seizure seizure during during salivation seizure onset no. no. Baseline occurrence) salivation signs (s) onset salivation salivation (s) (s) (s) 6 5 Awake Aura, staring, impaired awareness, RUE automatisms, spitting (15 s), salivation, swallowing 7 5 Awake Staring, impaired awareness, RUE automatism, LUE tonic, salivation, oral automatisms, tachycardia throughout Sz 8 5 Sleep Arousal, staring, impaired awareness, lip smacking, RUE automatism, LUE dystonia, salivation, eyes deviate to right 9 5 Awake Aura, staring, impaired awareness, increase in respiratory rate, bicycling, myoclonic jerks of LUE, moaning, salivation 10 5 Awake Aura, staring, impaired dystonia, RUE automatism, salivation, lip smacking, swallowing, head version to left before GTCS Unresponsive Ictal speech 90 Right temporal Diffuse theta Significant Unresponsive LUE tonic, ictal speech Unresponsive LUE dystonia, ictal speech 77 Right temporal Diffuse rhythmic theta Significant Right temporal Diffuse theta Significant Unresponsive None 70 Left temporal Diffuse theta Significant Unresponsive LUE dystonia, immediate postictal speech 65 Right temporal Diffuse theta Significant Pt. no., patient number; Sz no., number of seizures with ictal hypersalivation; Sz, seizure; GTCS, generalized tonic clonic seizure; RUE, right upper extremity; LUE, left upper extremity; BUE, both upper extremities.

7 650 J. SHAH ET AL. FIG. 1. A: Interictal epileptiform activity over the right temporal lobe (patient 1). B: Ictal electrographic onset involving the right temporal region (patient 1). LFF, low-frequency filter; HFF, high-frequency filter; Sec, second. EEG showed diffuse, bi activity; although without depth-electrode recording, precise electroclinical correlation is not possible. Therefore we believe that epileptic hypersalivation is probably a function of a network or networks, perhaps including the central autonomic network, rather than the function of a single anatomic structure or region. Some authors suggest right hemisphere dominance for autonomic functions (9 12). Three types of autonomic and oral-alimentary ictal phenomena deserve special consideration because of their possible confusion with or relation to ictal hypersalivation: ictal vomiting, spitting automatism, and oral-alimentary automatisms. Several studies of patients experiencing ictal vomiting, with seizures originating in or propagating to the right temporal lobe, suggested that the nondominant hemisphere may dominate for gastrointestinal control [for reviews, see Kramer et al. (9), Devinsky et al. (10), Schauble et al. (11)]. Spitting automatism was initially mentioned by Jackson (3) in citing a case presented by Sander. Since then, spitting automatism has been reported infrequently in TLE, often as a sign of nondominant temporal lobe involvement [for reviews, see Kaplan et al. (12), Kellinghaus et al. (13)]. However, increased salivation has not been associated with spitting in these patients. The exceptions to this are the case reported by Sander, one of our patients (patient 6), and a patient reported in a recent series (13). Therefore the mechanisms of ictal spitting and increased salivation must be different. Ictal spitting appears to be an oral-alimentary automatism, whereas ictal hypersalivation is more likely an autonomic manifestation of the seizure (13). Oral-alimentary automatisms, such as swallowing, chewing, and lip smacking, have been observed with insular cortex epileptic discharges (14) and insular stimulation (15), but increased salivation was not observed in either of these studies. This suggests that oral-alimentary automatisms are not the indirect result of increased salivation. Our patients exhibited several autonomic signs and symptoms in addition to ictal hypersalivation, indicating that distinct autonomic manifestations may coexist in the same seizure, perhaps due to activation of parts of the same network(s). Oral-alimentary automatisms were also common manifestations in our patients seizures (Tables 1 and 2). However, we could always distinguish clearly between ictal hypersalivation and these other manifestations. The resolution of increased salivation and seizure freedom after anterior temporal lobectomy and amygdalohippocampectomy in our patients support the role of temporal lobe structures in salivation. This study further supports the nondominant hemisphere dominance for autonomic function. Studies involving larger numbers of patients are needed to verify and extend these findings. REFERENCES 1. Freeman R, Schachter SC. Autonomic epilepsy. Semin Neurol 1995;15: Ganong WF. Review of Medical Physiology. 15th ed. Norwalk, CT: Appleton & Lange, Jackson JH, Taylor J, eds. Selected Writings of John Hughlings Jackson. New York: Basic Books, 1958:1: , 463, Penfield W, Jasper H. Epilepsy and the Functional Anatomy of the Human Brain. Boston: Little, Brown, 1954: Morita M, Kurtia A, Inoue K, et al. A case with left mesial temporal lobe epilepsy characterized by abnormal massive salivation. Rinsho Shinkeigaku 2001;41:

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