remained seizure-free. Conclusions: Video-EEG monitoring using a heart rate- based seizure detection software can be helpful in diagnosti- cally differentiating ...
Epilepsicr, 41(S): 1039-1043, 2000 Lippincott William & Wilkins, Inc., Baltimore 0 Intcrnational Lcaguc Against Epilepsy
Brief Communication
Autonom c Seizures Versus Syncope in 18q- De etion Syndrome: A Case Report "Kerstin Sturm, "Susanne Knake, "Ulrich Schomburg, j-Jorg-P. Wakat, "Hajo M. Hamer, $Barbara Fritz, *Wolfgang H. Oertel, and *Felix Rosenow Departments of *Neurology, fNeuroradiology, and $Clinical Genetics, Philipps- University Marburg, Germany
Summary: Purpose: The 18q- deletion syndrome (1 8qDS) is frequently associated with cardiac anomalies. Patients with this syndrome may also have epilepsy, which presents certain diagnostic difficulties. This case report aims to illustrate these diagnostic problems, document the usefulness of heart ratebased seizure detection algorithms in this setting, and define the epilepsy syndrome associated with 18qDS. Methods: Closed-circuit video electroencephalogram (EEG) monitoring using a heart rate-based seizure detection software was used to identify the event in question and to establish the diagnosis of epilepsy. Chromosomal analysis and magnetic resonance imaging (MRI) were used to further define the epilepsy syndrome. Results: We report on a patient with an atrial septa1 defect, enlargement of the right heart, and incomplete right bundle branch block, who developed episodes of tachycardia, loss of consciousness, and pallor, for which he was amnesic. Chromo-
somal analysis demonstrated karyotype 4h,XY,del( 18)(q21.3). ish del(lX)(wcp18+,D18Zl+) with a loss of the gene for myelin basic protein. MRI revealed multifocal dysrnyelination. VideoEEG monitoring using an electrocardiogram (ECG)-triggered seizure detection software proved to be indispensable in detecting an autonomic seizure and establishing the correct diagnosis; the procedure also allowed for the definition of the epilepsy syndrome. The patient was treated with carbamaLepine and remained seizure-free. Conclusions: Video-EEG monitoring using a heart ratebased seizure detection software can be helpful in diagnostically differentiating autonomic seizures from syncope. Dysmyelination due to loss of the myelin basic protein gene on 1Xq and cortical dysgenesis may be of pathogenic relevance. Key Words: Chromosome 18-Myelin basic protein-Automated seizure detection-Ictal tachycardia-Dysmyelination.
The 18q- deletion syndrome (18qDS) was first described by de Grouchy in 1964 (1). This genetic imbalance syndrome is caused by variable deletions of parts of the long arm of chromosome 18 from 18q21.3 or 18q22.2 to the' q-terminal. This segment includes the gene for myelin basic protein. The size of the deletion can correlate with the severity of the highly variable phenotype (1-3). Patients with this syndrome often have a short stature, mental retardation, behavioral problems, poor coordination, midfacial hypoplasia, a "carp-shaped" mouth, cleft palate and lips, tapering fingers, and a short first metacarpal with proximal thumb and vertical talus with or without talipes equinovarus (2,3). Cardiac anomalies are frequent, and a substantial minority of the patients also have epilepsy (2).
Focal seizures are frequently associated with ictal tachycardia or rarely with bradycardia (4). Other autonomic features, such as a pale or flushed face, changes in blood pressure, or sweating, can be prominent (5,6). It has recently been suggested that such seizures be classified as autonomic, provided there is objective documentation of significant ictal autonomic changes (7). Cardiac anomalies, however, can cause syncopal events, and syncope can be associated with tachycardia, changes in facial color, sweating, and symmetric or even asymmetric convulsive movements; in such cases, these events are classified as convulsive syncope (8). Cardiogenic episodes of pallor and dizziness have also been described in 18qDS (9). Therefore, this differential diagnosis can be difficult, especially if the patient does not remember the seizures. We report a case with 18qDS where closed-circuit video electroencephalogram (EEG) monitoring with an electrocardiogram (ECG)-triggered seizure detection software proved indispensable in detecting the episodes in question and in proving their epileptic etiology.
Accepted March 10, 2000. Address correspondence and reprint requests to Dr. Felix Rosenow at Neurologische Klinik, Philipps-University Marburg, RudolfBultmannstr. 8, 35033 Marburg, Germany. E-mail: rosenow@mailer. uni-niarburg.de
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METHODS Continuous video-EEG monitoring using a system that includes spike and EEG seizure detection software and an ECG-based seizure detection algorithm (Vangard, Cleveland, OH, U.S.A.) was performed. The heart ratebased seizure detection algorithm has an extremely robust QRS identifier that can reliably determine heart rate by identifying and suppressing artifacts and premature ventricular contractions (1 0 , l l ) . A seizure is detected by a tachycardia that exceeds a rate threshold and a duration threshold. The rate threshold is a combination of the absolute rise and the rate of rise of the heart rate. The heart rate is then compared with a baseline that is exponentially weighted and focused on the preceding 30 seconds. If the rate exceeds a threshold, which is 2 SD higher than baseline for more than a user-specified duration (with a default duration of 30 seconds), the detector will be triggered.
CASE HISTORY A 36-year-old man had a 4-year history of increasingly frequent episodes of sudden loss of consciousness, tachycardia, pallor, cyanotic acres, and grimacing. He had experienced similar spells in infancy but had not required medication at that time. The patient was the product of a normal pregnancy and an on-term vaginal delivery. In the following years, his psychomotor development was delayed. He finished a school for mentally retarded children at the age of 20 years. Over the last years, several routine EEG recordings failed to show epileptiform discharges. A 24-hour ECG recorded a baseline heart rate of 65 to 80 beats per minute and an episode of supraventricular tachycardia up to 150 beats per minute and 90 seconds in duration (Fig. 1). No symptoms were reported at that time, and no treatment was recommended. The patient was admitted
to the Neurologische Klinik of the Philipps-University, Marburg, Germany, to establish or exclude an epileptic origin for his spells. On admission, we saw an adipose man with midfacial hypoplasia, gnathopalatoschisis, tapering fingers, an equinovarus deformity, and labyrinthine hearing loss. His blood pressure was 140/80 mm Hg, and his pulse rate was 72/min. A 2/6 systolic heart murmur was also present. The ECG showed regular sinus rhythm, right axis deviation, signs of right heart hypertrophy, and an incomplete right bundle branch block. The left ventricular and valvular function were normal. Transthoracic and transesophageal echocardiography showed a normal left ventricular ejection fraction, a normal valvular function, and an atrial septa1 defect with enlargement of the right heart (diameter 40 mm). Laboratory investigations revealed a hyperlipoproteinemia type IV and hyperuricemia. Chromosomal analysis of peripheral blood leukocytes demonstrated karyotype 46,XY,de1(18)(q21.3). ish del( 1 X)(wcpl8+,DlSZl+) (Fig. 2A). T,-weighted magnetic resonance imaging (MRI) of the head showed subcortical bilateral white matter lesions, especially in the right frontal periventricular and peritrigonal regions and in the temporal lobes; the MRI also showed mild occipital atrophy (Fig. 2B). These lesions were interpreted as dysmyelination. The mesial temporal structures appeared normal. Neuropsychological testing revealed severe cognitive deficits-three errors in the Benton Visual Retention Test, drawing form and seven points in the raw score of the Block Design, a subtest of the Wechsler Adult Intelligence Scale-Revised (WAlS-R). The Token Test showed aphasic signs. The patient was not able to perform 6 of 10 instructions in part V of the Token Test (e.g., “take the blue circle or the yellow square”). In testing for apraxia, the patient was not able to perform 6 of 15 tasks on verbal command, but he was able to per-
seconds FIG. 1 . A: An episode of intermittent supraventricular tachycardia recorded during long-term ECG recording is shown with an increase in heart rate from 75/min to 150/min. B: An identical increase in heart rate from a baseline of 72fmin to 155/min starting 4 seconds after the EEG seizure onset (arrow) and 3 seconds after clinical seizure onset was detected by the ECG-triggered seizure detection software during video-EEG monitoring and occurring during a typical epileptic seizure of the patient. Epilepsiu, Vol. 41, No. 8, 2000
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FIG. 2. A: The patient’s chromosomes 18 with deletion of the long arm of one chromosome 18 at location 21.3. B: Axial long-TR/ long-TE image (4,000/98) showing right frontal periventricular and peritrigonal lesions and additional lesions in the subcortical white matter at both sides, especially in the temporal lobe. Notice mild occipital atrophy.
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form them in imitation, which again demonstrated his verbal comprehension problems. In the Logical Memory subtest of the Wechsler Memory Scale-Revised, the patient recalled only 2 of 25 details in one story (2.3 SD below average performance). His performance was even worse in the Memo Test, a standardized 10-word list test, in which he could remember an average of only 2.4 words (4.8 SD below average performance). His performance on a subtest of the WAIS-R indicated an estimated IQ of 60. Closed-circuit video-EEG monitoring was performed for 3 days, using the international 10-20 system. The interictal EEG showed a low-voltage posterior background activity of normal frequency (9 Hz) (Fig. 3). Bitemporal, independent sharp waves (80% maximum FTlO and 20% maximum FT9) were recorded almost exclusively during sleep (Fig. 3). One typical seizure was detected by the ECG-triggered seizure detection system. The seizure had been missed by the EEG technician, who was sitting 3 meters away from the patient in front of the video and EEG screens, and by a board-certified epileptologist on a routine review of the EEG data. On review of the video, the patient showed behavioral arrest, an asymmetric tonic contraction of the face, which turned pale and later red, and a subtle tonic elevation of the right arm. During the last seconds of the seizure, a nystagmus was seen to the right. After 31 seconds, the patient’s behavior and expression returned to normal. He did not remember the seizure. The EEG showed a generalized electrodecrement followed by a generalized, rhythmical
alpha and, later, delta activity with a superimposed tonic muscle artifact starting after 1 second (clinical seizure onset). Four seconds after the EEG seizure onset, a marked increase in heart rate identical with the tachycardia recorded during the previous 24-hour ECG occurred (Fig. 1). The patient was treated with carbamazepine and has remained seizure-free since treatment began 18 months ago.
DISCUSSION The reported case illustrates how heart rate-based seizure detection algorithms can improve seizure identification and assist in detecting an epileptic event. The majority of focal seizures and almost all autonomic seizures are associated with significant changes in heart rate (4-6). Therefore, a major proportion of monitored patients could benefit from the use of such algorithms, especially if the seizures are difficult to detect clinically and the patients are amnesic or otherwise unable to report on them. ECG-based seizure identification is complicated by muscle and movement artifacts, which impair QRS detection, and by spontaneous or exercise-induced baseline shifts in heart rate, which disallow the use of a fixed heart rate as the detection threshold. These difficulties, however, can be overcome by the identification and suppression of artifacts, a moving baseline, and inclusion of the rate of rise in the algorithm.
The epilepsy syndrome in 18qDS The patient’s EEG seizure pattern was nonlocalizing. Clinically, his bilateral, asymmetric tonic seizure evolved Epilepsiu, Vol. 41, No. 8, 2000
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Fp 1-F7 50 UV
F7-FT9 FT9-T7 T7-P7 P7-01 Fp2-F8 F8-FT 10 FT 10-18 T8-P8 P8-02 FPI-F3 F3-C3 C3-P3 P3-0 1 FP2-F4 F4-C4 C4-P4 P4-02 FIG. 3. EEG samples of the patient showing (a) the low-voltage9-Hz posterior backgroundactivity, (b) a sharp wave arising from the left anterior temporal region, and (c) a sharp wave arising from the right anterior temporal region recorded during sleep.
into an autonomic one, suggesting insular involvement (4,5). Interictally bitemporal sharp waves were recorded. Therefore, insular or temporal lobe epilepsy was diagnosed and carbamazepine was prescribed. The patient's MRI showed multifocal T, hyperintensities sparing the mesial temporal structures. Similar MRI findings were common in other patients with 18qDS who had a variety of neurological disorders, such as segmental spinal muscular atrophy, dystonia, action tremor, chorea, nystagmus, and epilepsy (2,9,12). Abnormal gyration and myelination, heterotopic neurons in the molecular layer and white matter, and cerebellar atrophy were found in another case of 18qDS (9), while polymicrogyria was noted in another (3). These neuronal migration abnormalities can be highly epileptogenic and may cause epilepsy in some patients with 18qDS. However, the MRI in this patient did not reveal such abnormalities. As in this case, the deleted segment of chromosome 18q usually contains the gene for myelin basic protein (3,12). This gene's absence may be related to the multifocal dysmyelination seen in the majority of cases with CNS involvement (12,13) and could explain the diversity of clinically observed neurological symptoms and signs in patients with 18qDS. Even though they mainly affect Epilepsiu, Vol. 41, NO, 8, 2000
the white matter, disorders of myelination can cause symptomatic epilepsy. In patients with multiple sclerosis, for example, the presence of multiple, subcortical, hyperintensive lesions on MRI correlates with the occurrence of epilepsy. Therefore, it is likely that dysmyelination contributes to epileptogenesis in the majority of patients with 18qDS and epilepsy.
REFERENCES 1. Wertelecki G, Gerald PS. Clinical and chromosomal studies of the 18q- syndrome. J Pediatr 1971;78:44-52. 2. Miller G, Mowrey PN, Hopper KD, et al. Neurologic manifestations in 18q- syndrome. Am J Med Genet 1990;37:128-32. 3. Cody JD, Hale DE, Brkanac Z, et al. Growth hormone insufficiency associated with haploinsufficiency at 18q23. Am .I Med Genet 1997;71:420-5. 4. Galirnberti CA, Marchioni E, Barzizza F, et al. Partial epileptic seizures of different origin variably effect cardiac rhythm. Epilepsia 1996;37:742-7. 5. Van Buren JM. Some autonomic concomitants of ictal automatisms: a study of temporal lobe attacks. Bruin 1958;81:505-28. 6. Burgess RC. Autonomic signs associated with seizures. In: Luders HO, Noachtar S, eds. Epileptic seizures: pathophysiology and clinical semiology. London: Churchill Livingstone, October 2000 (in press). 7. Liiders H, Acharya J, Baumgartner C, et al. Semiological seizure classification. Epilepsia 1998;39: 1006-13.
AUTONOMIC SEIZURE IN 18q- DELETION SYNDROMES 8. Lempert T. Recognizing syncope: pitfalls and surprises. J R Soc Med 1996;89:372-5. 9. Vogel H, Urich H, Horoupian DS, et al. The brain in the 18qsyndrome. Dev Med Child Neurol 1990;32:732-7. 10. Burgess RC, Turnbull JP, Bartolo A, O’Donovan C. Heart rate signal artifact identification improves tachycardiograph seizure detection. Epilepsia 1996;37(suppl 5):63. I I . Burgess RC, Turnbull JP, Bartolo A, Rekhson MS. Combined EEG
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and EKG detection algorithms improve computerized seizure identification. Epilepsia 1997;38(suppl 3):155. 12. Loevner LA, Shapiro RM, Grossman R1, et al. White matter changes associated with deletions of the long arm of chromosome 18: a dysniyelinating disorder? Am J Neurorudiol I996;17: 1843-8. 13. Becker LE. MR findings in the central nervous system of patients with a deletion of the long arm of chromosome 18 (1 8q-). Am J Neurorudiol 1998;19:399.
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