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Reevaluation of Serum Cortisol in Conversion Disorder With Seizure (Pseudoseizure)
Letters Reevaluation of Serum Cortisol in Conversion Disorder With Seizure (Pseudoseizure) TO THE EDITOR: The pathogenesis of psychogenic seizure is not well understood. The findings on serum cortisol levels with psychogenic seizure are contradictory.1–3 We reported previously that depressive symptoms supervening to conversion disorder contributed to disruption of hypothalamic-pituitary-adrenal (HPA) axis function.4 The patients in that study not only had seizures but also other pseudoneurologic findings, such as paralysis and aphonia. The present study investigates cortisol level during psychogenic seizures and its relationship to depression, anxiety, the impairment of consciousness, blood pressure, and pulse rate. Eighteen patients (16 women, 2 men; meanⳲSD age⳱27.2Ⳳ8.5) admitted to the emergency unit with seizures of complete or partial deficits of consciousness and/or convulsions were studied. Detailed medical and psychiatric histories were taken from family members; physical and neurological examinations were also performed. Routine laboratory tests, ECG, and EEG (and CT scan and CSF examinations if necessary) were normal. None of the patients had a history of brain injury, drug toxicity, or alcohol/substance dependence. None of the patients had body injury, tongue biting, or urinary incontinence during the seizure, and postictal confusion was not observed. Glasgow Coma Scale was scored during the seizures. Patients were interviewed by a psychiatrist when they had recovered clear consciousness and were diagnosed as conversion disorder with seizure and convulsions according to DSM-IV criteria.5 They were scored by Turkish ver152
sions of the 17-item Hamilton Rating Scale for Depression (Ham-D) and the Hamilton Rating Scale for Anxiety (Ham-A), which have been found to be reliable and valid. Eight volunteers, age and sex matched (5 women, 3 men), were recruited as control subjects. The serum cortisol of the 18 seizure patients was measured from blood samples obtained during the seizure. To investigate possible contribution of circadian rhythm on cortisol, the patients were divided into three groups according to their time of seizures (morning, afternoon, and evening). The seizures of 5 patients were between 11:00 A.M. and 12:00 A.M., 5 were between 1:00 P.M. and 2:00 P.M., and 6 were between 4:00 P.M. and 5:00 P.M.; this information was missing for 2 patients. Extra blood samples were obtained from 8 patients the following morning at 8:00 A.M., when they were symptom- and drugfree. Cortisol levels of control subjects were also obtained at 8:00 A.M. Cortisol measurements were done by radioimmunassay standard kit (Gamma BTC Cortisol, Immunodiagnostic System, UK). Intra- and interassay coefficient variations were 5.8% and 9.1%, respectively. The mean serum cortisol levels during seizure for these 18 patients were higher (22.5Ⳳ10.2 lg/dl) than levels for the healthy control subjects (11.8Ⳳ4.0 lg/dl) (Mann-Whitney U test: 118.00, P⳱0.01). The next morning, for patients with seizures, mean serum cortisol levels were lower (16.4Ⳳ9.5 lg/dl) than during seizures but were still higher than the levels of the control subjects (P⳱0.22; NS). The mean time period between seizure and the next morning at 8:00 A.M. was 18.1Ⳳ2.2 hours. Cortisol levels were higher in the afternoon and evening hours (24.6Ⳳ10.53 and 24.72Ⳳ8.06 lg/ dl, respectively) than the levels of control
subjects (Mann-Whitney U-test⳱20.5, P⳱0.016 and U⳱2.5, P⳱0.01, respectively), but not in the morning (18.32Ⳳ12.90 lg/dl) (Mann-Whitney U⳱20.0, P⳱0.3; NS) (Figure 1). Twelve patients had impairment of consciousness and 6 had both impaired consciousness and convulsions. Cortisol levels did not differ according to the types of seizures (21.12Ⳳ10.25 lg/dl and 25.17Ⳳ11.70 lg/dl, respectively, Mann-Whitney U⳱41.000, P⳱0.462; NS). The mean Glasgow Coma score was 11.0Ⳳ4.0, Ham-D soon after seizure was 20.7Ⳳ9.6 and Ham-A was 19.6Ⳳ5.8, and none of the patients fulfilled the criteria for the diagnosis of major depression according to DSM-IV. There was a weak, but not statistically significant, positive correlation between cortisol level and Glasgow Coma score, depression and anxiety scores, systolic/ diastolic blood pressures, and heart rates. Increased cortisol and escape from dexamethasone suppression in depression are documented.6 Cortisol secretion follows a circadian rhythm and peaks at 8:00 A.M., and this rhythm is impaired in depression and remains high in the evening.7 We found a tendency of cortisol to increase during the seizure in the evening hours, as observed in depression. Depression frequently accompanies conversion disorder.8 Cortisol increases in epileptic seizures.1,9,10 Rao et al.3 showed increased serum cortisol during epileptic seizures that decreased about 50% within 2 hours, whereas in patients with psychogenic seizures, cortisol levels fluctuated and dropped 90% compared to the interictal level. The apparent half-life of cortisol in epileptic patients is about 120 minutes. In our patients, cortisol dropped about 30% in 18 hours. Increased serum cortisol may be due to a nonspecific and protracted afPsychosomatics 41:2, March-April 2000
Letters fective arousal. In conclusion, HPA axis is moderately impaired in conversion disorder; therefore, it would be difficult and impractical to suggest serum cortisol level as a good predictor in differential diagnosis of epileptic and conversion disorder seizures. Zeliha Tunca, M.D. ¨ lku¨ Ergene, M.D. U Hu¨ray Fidaner, M.D. Can Cimilli, M.D. ¨ zerdem, M.D. Ays¸egu¨l O Tunc¸ Alkin, M.D. ¨ nal Aslan, M.D. Belgin U Departments of Psychiatry, Emergency Medicine, and Department of Public Health, Dokuz Eylu¨l University, Medical School, Balc¸ova, 35340, Izmir, Turkey
References
1. Abbott RJ, Browning MCK, Davidson DLW: Serum prolactine and cortisol concentrations after grand mal seizures. J Neurol Neurosurg Psychiatry 1980; 43:163– 167
2. Pritchard PB, Wannamaker BB, Sagel J, et al: Serum prolactine and cortisol levels in evaluation of pseudoepileptic seizures. Ann Neurol 1985; 18:87–89 3. Rao ML, Stefan H, Bauer J: Epileptic but not psychogenic seizures are accompanied by simultaneous elevation of serum pituitary hormones and cortisol levels. Neuroendocrinology 1989; 49:33–39 4. Tunca Z, Fidaner H, Cimilli C, et al: Is conversion disorder biologically related with depression? A DST study. Biol Psychiatry 1996; 39:216–219 5. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Washington, DC, American Psychiatric Association, 1994 6. Coulemans DL, Westenberg HG, van Praag HM: The effect of stress on the dexamethasone suppression test. Psychiatry Res 1985; 14:189–195 7. Kandel ER: Disorders of mood: depression, mania, and anxiety disorders, in Principles of Neural Science, 3rd Edition, edited by Kandel ER, Schwartz JH, Jessell TM. New York, Elsevier, 1985, pp. 869–886 8. Bowman ES: Etiology and clinical course of pseudoseizures: relation to trauma, depression and dissociation. Psychosomatics 1993; 34:333–342 9. Aminoff MJ, Simon RP, Wiedermann E: The hormonal responses to generalized tonic-clonic seizures. Brain 1984; 107:569– 578
FIGURE 1. Cortisol levels through the day for control subjects (䉱) and pseudoseizure patients during (•) and before (䡩) seizure episodes
Note: (䉱), n⳱8; (•), n⳱16; (䡩), n⳱8. Solid lines indicate the mean in each group. The dotted line indicates Ⳮ4 standard deviations (SD) in control subjects. Cortisol levels in 1 control (12.5%), 5 patients’ interictal (50%), and 11 patients during seizure (75%) exceed 4 SDs from control mean. P⬍0.01 (Mann-Whitney U test).
Psychosomatics 41:2, March-April 2000
10. Calabrese VP, Grueme HD, Tripathi H, et al: Serum cortisol and cerebrospinal fluid beta-endorphins in status epilepticus: their possible relation to prognosis. Arch Neurol 1993; 50:689–693
Use of Mirtazapine as Prophylactic Treatment for Migraine Headache TO THE EDITOR: Migraine headache is a common and often underrecognized problem that affects about 11 million adults in the United States.1,2 Headaches are one of the most common medical complaints faced by physicians.3 There are many therapeutic options that may relieve migraine sufferers, such as vasoconstrictors, antidepressants, analgesics, anticonvulsant medications, biofeedback, relaxation techniques, and spinal manipulation.2 We discuss a case in which Remeron威 (mirtazapine) assisted in reducing the number of migraine headaches suffered by a patient. Case Report The patient is a 60-year-old man who had worked as a preacher until 5 years ago, when his wife left him because of marital difficulty. Since that time, he has had depressed mood, anhedonia, erratic sleep, decreased energy and concentration, feelings of guilt, and a weight problem. However, he exhibited no suicidal or homicidal ideation or intent. The patient also reported that because of these problems, he had driven away his children, extended family, and friends, leaving him isolated and withdrawn from society. He did not meet criteria for substance abuse or dependence, mania or hypomania, posttraumatic stress disorder, obsessive-compulsive disorder, or panic disorder. However, he did report problems with muscle tension and anxiety. His medical history was significant for hypoglycemia, increased 153
sions of the 17-item Hamilton Rating Scale for Depression (Ham-D) and the Hamilton Rating Scale for Anxiety (Ham-A), which have been found to be reliable and valid. Eight volunteers, age and sex matched (5 women, 3 men), were recruited as control subjects. The serum cortisol of the 18 seizure patients was measured from blood samples obtained during the seizure. To investigate possible contribution of circadian rhythm on cortisol, the patients were divided into three groups according to their time of seizures (morning, afternoon, and evening). The seizures of 5 patients were between 11:00 A.M. and 12:00 A.M., 5 were between 1:00 P.M. and 2:00 P.M., and 6 were between 4:00 P.M. and 5:00 P.M.; this information was missing for 2 patients. Extra blood samples were obtained from 8 patients the following morning at 8:00 A.M., when they were symptom- and drugfree. Cortisol levels of control subjects were also obtained at 8:00 A.M. Cortisol measurements were done by radioimmunassay standard kit (Gamma BTC Cortisol, Immunodiagnostic System, UK). Intra- and interassay coefficient variations were 5.8% and 9.1%, respectively. The mean serum cortisol levels during seizure for these 18 patients were higher (22.5Ⳳ10.2 lg/dl) than levels for the healthy control subjects (11.8Ⳳ4.0 lg/dl) (Mann-Whitney U test: 118.00, P⳱0.01). The next morning, for patients with seizures, mean serum cortisol levels were lower (16.4Ⳳ9.5 lg/dl) than during seizures but were still higher than the levels of the control subjects (P⳱0.22; NS). The mean time period between seizure and the next morning at 8:00 A.M. was 18.1Ⳳ2.2 hours. Cortisol levels were higher in the afternoon and evening hours (24.6Ⳳ10.53 and 24.72Ⳳ8.06 lg/ dl, respectively) than the levels of control
subjects (Mann-Whitney U-test⳱20.5, P⳱0.016 and U⳱2.5, P⳱0.01, respectively), but not in the morning (18.32Ⳳ12.90 lg/dl) (Mann-Whitney U⳱20.0, P⳱0.3; NS) (Figure 1). Twelve patients had impairment of consciousness and 6 had both impaired consciousness and convulsions. Cortisol levels did not differ according to the types of seizures (21.12Ⳳ10.25 lg/dl and 25.17Ⳳ11.70 lg/dl, respectively, Mann-Whitney U⳱41.000, P⳱0.462; NS). The mean Glasgow Coma score was 11.0Ⳳ4.0, Ham-D soon after seizure was 20.7Ⳳ9.6 and Ham-A was 19.6Ⳳ5.8, and none of the patients fulfilled the criteria for the diagnosis of major depression according to DSM-IV. There was a weak, but not statistically significant, positive correlation between cortisol level and Glasgow Coma score, depression and anxiety scores, systolic/ diastolic blood pressures, and heart rates. Increased cortisol and escape from dexamethasone suppression in depression are documented.6 Cortisol secretion follows a circadian rhythm and peaks at 8:00 A.M., and this rhythm is impaired in depression and remains high in the evening.7 We found a tendency of cortisol to increase during the seizure in the evening hours, as observed in depression. Depression frequently accompanies conversion disorder.8 Cortisol increases in epileptic seizures.1,9,10 Rao et al.3 showed increased serum cortisol during epileptic seizures that decreased about 50% within 2 hours, whereas in patients with psychogenic seizures, cortisol levels fluctuated and dropped 90% compared to the interictal level. The apparent half-life of cortisol in epileptic patients is about 120 minutes. In our patients, cortisol dropped about 30% in 18 hours. Increased serum cortisol may be due to a nonspecific and protracted afPsychosomatics 41:2, March-April 2000
Letters fective arousal. In conclusion, HPA axis is moderately impaired in conversion disorder; therefore, it would be difficult and impractical to suggest serum cortisol level as a good predictor in differential diagnosis of epileptic and conversion disorder seizures. Zeliha Tunca, M.D. ¨ lku¨ Ergene, M.D. U Hu¨ray Fidaner, M.D. Can Cimilli, M.D. ¨ zerdem, M.D. Ays¸egu¨l O Tunc¸ Alkin, M.D. ¨ nal Aslan, M.D. Belgin U Departments of Psychiatry, Emergency Medicine, and Department of Public Health, Dokuz Eylu¨l University, Medical School, Balc¸ova, 35340, Izmir, Turkey
References
1. Abbott RJ, Browning MCK, Davidson DLW: Serum prolactine and cortisol concentrations after grand mal seizures. J Neurol Neurosurg Psychiatry 1980; 43:163– 167
2. Pritchard PB, Wannamaker BB, Sagel J, et al: Serum prolactine and cortisol levels in evaluation of pseudoepileptic seizures. Ann Neurol 1985; 18:87–89 3. Rao ML, Stefan H, Bauer J: Epileptic but not psychogenic seizures are accompanied by simultaneous elevation of serum pituitary hormones and cortisol levels. Neuroendocrinology 1989; 49:33–39 4. Tunca Z, Fidaner H, Cimilli C, et al: Is conversion disorder biologically related with depression? A DST study. Biol Psychiatry 1996; 39:216–219 5. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Washington, DC, American Psychiatric Association, 1994 6. Coulemans DL, Westenberg HG, van Praag HM: The effect of stress on the dexamethasone suppression test. Psychiatry Res 1985; 14:189–195 7. Kandel ER: Disorders of mood: depression, mania, and anxiety disorders, in Principles of Neural Science, 3rd Edition, edited by Kandel ER, Schwartz JH, Jessell TM. New York, Elsevier, 1985, pp. 869–886 8. Bowman ES: Etiology and clinical course of pseudoseizures: relation to trauma, depression and dissociation. Psychosomatics 1993; 34:333–342 9. Aminoff MJ, Simon RP, Wiedermann E: The hormonal responses to generalized tonic-clonic seizures. Brain 1984; 107:569– 578
FIGURE 1. Cortisol levels through the day for control subjects (䉱) and pseudoseizure patients during (•) and before (䡩) seizure episodes
Note: (䉱), n⳱8; (•), n⳱16; (䡩), n⳱8. Solid lines indicate the mean in each group. The dotted line indicates Ⳮ4 standard deviations (SD) in control subjects. Cortisol levels in 1 control (12.5%), 5 patients’ interictal (50%), and 11 patients during seizure (75%) exceed 4 SDs from control mean. P⬍0.01 (Mann-Whitney U test).
Psychosomatics 41:2, March-April 2000
10. Calabrese VP, Grueme HD, Tripathi H, et al: Serum cortisol and cerebrospinal fluid beta-endorphins in status epilepticus: their possible relation to prognosis. Arch Neurol 1993; 50:689–693
Use of Mirtazapine as Prophylactic Treatment for Migraine Headache TO THE EDITOR: Migraine headache is a common and often underrecognized problem that affects about 11 million adults in the United States.1,2 Headaches are one of the most common medical complaints faced by physicians.3 There are many therapeutic options that may relieve migraine sufferers, such as vasoconstrictors, antidepressants, analgesics, anticonvulsant medications, biofeedback, relaxation techniques, and spinal manipulation.2 We discuss a case in which Remeron威 (mirtazapine) assisted in reducing the number of migraine headaches suffered by a patient. Case Report The patient is a 60-year-old man who had worked as a preacher until 5 years ago, when his wife left him because of marital difficulty. Since that time, he has had depressed mood, anhedonia, erratic sleep, decreased energy and concentration, feelings of guilt, and a weight problem. However, he exhibited no suicidal or homicidal ideation or intent. The patient also reported that because of these problems, he had driven away his children, extended family, and friends, leaving him isolated and withdrawn from society. He did not meet criteria for substance abuse or dependence, mania or hypomania, posttraumatic stress disorder, obsessive-compulsive disorder, or panic disorder. However, he did report problems with muscle tension and anxiety. His medical history was significant for hypoglycemia, increased 153