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Prolonged Psychosis With First-Rank Symptoms Following Metrizamide Myelography
CASE REPORT
R. JEFFREY DAVIS, D.O. JEFFREY L. CUMMINGS, M.D. BARNETD. MALIN, M.D. THOMAS GARRICK, M.D.
Prolonged psychosis with first-rank symptoms following metrizamide myelography Since its introduction in 1969,' metrizamide has become a widely used radiographic contrast agent for intrathecal visualization of CNS structures. The incidence of major adverse side effects following its use is relatively low, but mental status changes are far more common than with earlier agents. U Confusion, diminished attention, disorientation, anxiety and depression, incoherent speech, and perceptual aberrations (including visual and auditory hallucinations) have been described. J.6 Typically, these side effects are short-lived, rarely lasting longer than a few days. This report describes an unusually prolonged change in mentation accompanied by hallucinations, delusions, and a choreiform movement disorder that began following a metrizamide myelogram. The organic psychosyndrome was unique in that it was dominated by Schneiderian first-rank symptoms. Case report A 66-year-old man was admitted to the hospital for evaluation of neck and back pain. He had a history of peptic ulcer disease and of intermittent alcohol abuse but had maintained sobriety for six months prior to admission. He had no From the department ofneurology. UCLA (Dr. Davis); the neurobehavior unit. West Los Angeles VAMC (Brentwood Division) and the department ofneurology. UCLA (Dr. Cummings); the department of psychiatry and biobehavioral sciences. UCLA. and the psychiatry service. West Los Angeles VAMC (Dr. Garrick. Wadsworth Division; Dr. Malin. Brentwood Division). Reprint requests to Dr. Cummings. Neurobehavior Unit (691 /Bl 11). West Los Angeles VAMC (Brentwood Division). 11301 Wilshire Blvd.. Los Angeles. CA 90073.
MAY 1986-VOL27-N05
history of psychiatric illness, and there was no family history of neurologic or psychiatric disorders. A metrizamide myelogram (8 mL, 250 mgl/mL) was performed through a lumbar puncture site. Twelve hours after the procedure, the patient developed a mild headache. became disoriented to time and place. and told the staff that colors seemed very bright. The next morning, he complained that his thinking seemed dominated by the number 3 and sequences of 3. Although he was able to walk without difficulty, he remarked that his legs would not move, a problem he attributed to poisoned food and water. He was treated with 5 mg of haloperidol twice daily, improved over the next two days, and was discharged from the hospital without medication. Six days later, his family brought him back to the hospital. At home he had gradually improved but had not returned to normal and had intermittently complained of hearing voices. He also had unusual persistent movements of his hands and feet. The day before admission he became agitated, complained of hearing voices, and believed that signals from the television set controlled his thoughts. When examined in the emergency room, he was disoriented to time and place and could follow only simple commands. He was preoccupied with "a flashing sign on the ceiling" that blocked his thoughts until he could trace the proper geometric sequence and locate a specific dot that allowed his thoughts to emerge. Neurologic examination and laboratory studies including a CT scan of the head and lumbar puncture were normal. An EEG revealed excessive a-range slowing. The patient was placed on 5 mg of haloperidol three times daily. The following day (nine days after the myelogram), he was noted to have asymmetric, uncontrolled choreiform movements of the hands. A repeat EEG revealed a normal 10 to 12 Hz a-rhythm with superimposed a-range slowing.
373
Case report
Mental status testing revealed that he was awake and alert. He knew the year and month. but not the exact date. His recent memory was impaired but remote memory was intact. He interpreted idioms and simple proverbs abstractly and performed simple calculations well. He had moderate difficulty copying complex constructions. Twenty-three days after the myelogram (while still receiving 5 mg of haloperidol daily). the patient continued to be delusional. At this time. mental status examination revealed that he was completely oriented, and his constructions and abstractions were improved. Twenty-nine days after the myelogram no paranoid or persecutory ideation was present: he had no difficulty remembering his previous psychotic misperceptions and ideas. Haloperidol was discontinued. At a clinic visit 50 days after the myelogram. no psychotic ideation was elicited. Mental status testing revealed no abnormalities, and an EEG was normal.
Discussion This patient had an unusually prolonged change in mentation accompanied by hallucinations and delusions following metrizamide myelography. In the initial phase of the reaction, he was in an acute confusional state with psychosis. During this period a prominent choreiform movement disorder was also observed. Schneiderian first-rank symptoms including thought interference and impulses attributed to outside influences dominated the mental state and persisted as the confusion cleared. Schneider's first-rank symptoms include hearing one's thoughts spoken aloud; hearing voices that comment on one's actions; thought interference; delusional interpretation of percepts; and the experience that feelings, drives, and volitions are imposed or influenced by others. 7 Schneider suggested that in the absence of organic disorders, these symptoms were pathognomonic of schizophrenia. Schneiderian first-rank symptoms are known to occur in mania and depression,' but in the absence of a major mood disorder they remain important in the diagnosis of schizophrenia and are included among the diagnostic criteria of DSM-III.· Schneider acknowledged that first-rank symptoms occur in organic psychosyndromes as well as schizophrenia, but there has been little investigation of the relationship between brain dysfunction and these delusional experiences. Neurologic disorders in which first-rank symptoms have been reported include idiopathic basal ganglia calcification; post-encephalitic parkinsonism; temporal lobe epilepsy; hydrocephalus; and a variety of infectious, traumatic, and cerebrovascular conditions. 10 Dopamine is a principal neurotransmitter in subcortical and limbic structures-areas 374
commonly involved by diseases producing first-rank symptoms. Likewise, dopamine is the transmitter currently implicated in the pathophysiology of idiopathic schizophrenia, and involvement of dopaminergic systems in schizophrenia as well as in neurologic disorders with schizophrenia-like symptoms may account for the occurrence of first-rank symptoms in both disorders. The choreiform movement disorder reported in the patient described here implicated involvement of basal ganglionic structures and supports an association between subcortical dysfunction and first-rank symptoms. After his metrizamide myelogram, the patient manifested a confusional state as well as the schizophrenia-like symptom complex. The resolution of these two components of the psychosyndrome differed substantially: the intellectual impairment had largely resolved by the second week, whereas the delusions persisted almost twice as long. The pattern of the Mini-Mental State Examination (MMSE)" and Brief Psychiatric Rating Scale (BPRS)12 scores at various points during the course of the illness is shown in the Table. This suggests that the psychotic and confusional aspects of this syndrome were mediated by different cerebral mechanisms. Metrizamide is an epileptogenic agent, and neuroleptic drugs lower the seizure threshold, suggesting that co-administration may have potentially adverse consequences. 13 However, when seizures have not occurred, when the EEG is normal, and when psychosis is prominent, neuroleptic agents may be successfully used, as is illustrated by this case and others reported in the literature." Factors implicated in the pathogenesis of metrizamide encephalopathies include age, prolonged contact with and penetration of metrizamide into eNS gray matter, subclinical seizure activity, history of premorbid mental and or-
Tabl~MSE and
BPRS Scores During the Course of the Illness Days after myelogram
Questionnaire
9
23
27
50
MMSE' score
10
27
27
29
BPRStscore
56
36
16
2
'Mini-MenIal State Examination' (a score above 24 is normat) Bnel Psychlatnc Rating Scale8 (Individuals functioning ,n the normal range could be expected to obtain a score of 10 or less)
PSYCHOSOMATICS
ganic illness, disturbances of glucose metabolism, and interference with putative neurotransmitter function.'3-18 In the present case, the patient's age and history of alcohol abuse may have contributed to heightened vulnerability to a drug reaction. The absence of epileptiform discharges on the three EEGs suggests that seizures were unlikely to have been a significant contributing factor. More likely, toxic neuronal disturbances led to a disruption of neuronal function and accounted for the symptoms observed. In summary, the brief duration of the confusional state, when compared with the prolonged delusional aspect of the psychosyndrome, suggests that different functional neuro-
REFERENCES 1 Almen T Contrast agent design: Some aspects on the synthesis of watersoluble contrast agents of low osmolality. J Theor BioI 24:216-226. 1969. 2 Gelmers HJ Adverse side effects of metrizamide in myelography. Neuroradlology 18:119-123,1979 3 Schmidt RC Mental disorders after myelography with metrizamide and other water-soluble contrast media. Neuroradiology 19: 153-157. 1980 4. Hauge 0, Falkenberg H: Neuropsychologic reactions and other side effects after metrizamide myelography Am J Roentgenol 139:357-360, 1982 5 Killebrew K, Whaley RA. Hayward IN, et al: Complications of metrizamide myelography Arch Neuro/40:78-80, 1983. 6 Elliot RL, Wild JH Jr, Snow WT Prolonged delirium after metrizamide myelography JAMA 252:2057-2058,1984 7. Schneider K Primare und sekundare Symptomen bei Schizophrenie. FortSChr Neurol Psychlatr 25:487-490, 1957. 8 Carpenter WT Jr, Strauss JS. Muleh S: Are there pathognomonic symptoms in schizophrenia? Arch Gen Psychiatry 28:847-852.1973. 9 Diagnostic and Statistical Manual of Mental Disorders. ed 3. Washington, DC, American Psychiatric Association, 1980
MAY 1986- VOL 27- N05
nal systems were disturbed, and that these systems manifested distinctive vulnerabilities, sustained different degrees of disturbance, recovered at different rates, and responded differently to drug treatment. The presence of a choreiform movement disorder as one manifestation of the encephalopathy suggests that a disturbance of subcortical function was produced by the metrizamide. Delusions have been found with increased frequency among other disorders with subcortical abnormalities. 0 This project was supported by the Veterans Administration. Ms. Norene Hiekel prepared the manuscript. 10. Cummings JL: Organic delusions Br J Psychiatry 146: 184-197. 1985. 11. Folstein MF. Folstein SE. McHugh PR: 'Mini-mental state': A practical method for grading the mental state of patients for the clinician. J PsychiatrRes 12:189-198, 1975 12. Overall JE. Gorham DR: The brief psychiatric rating scale Psychol Rep 10:799-812,1962 13. Hanus PM: Metrizamide: A review with emphasis on drug interactions. Am JHospPharm37:510-513,1980. 14. Drayer BP, Rosenbaum AE: Metrizamide brain penetrance Acta Radiol (suppl) 355:280-293, 1977 15. Gonselle RE: Biologic tolerance of the central nervous system to metrizamide. Acta Radiol (suppl) 335:25-44, 1973 16. Bertoni JM. Schwartzman RJ, Van Horn G, et al: Asterixis and encephalopathy fOllowing metrizamide myelography: Investigations into possible mechanisms and review of the literature Ann Neuro/9:366-370, 1981. 17. Junck L. Marshall WH: Neurotoxicity of radiological contrast agents. Ann Neuro/13:469-484,1983. 18. Polls DG, Gomez DG, Abboll GF: Possible causes of complications of myelography with water·soluble contrast medium. Acta Radiol (suppl) 355:390-402,1977
375
R. JEFFREY DAVIS, D.O. JEFFREY L. CUMMINGS, M.D. BARNETD. MALIN, M.D. THOMAS GARRICK, M.D.
Prolonged psychosis with first-rank symptoms following metrizamide myelography Since its introduction in 1969,' metrizamide has become a widely used radiographic contrast agent for intrathecal visualization of CNS structures. The incidence of major adverse side effects following its use is relatively low, but mental status changes are far more common than with earlier agents. U Confusion, diminished attention, disorientation, anxiety and depression, incoherent speech, and perceptual aberrations (including visual and auditory hallucinations) have been described. J.6 Typically, these side effects are short-lived, rarely lasting longer than a few days. This report describes an unusually prolonged change in mentation accompanied by hallucinations, delusions, and a choreiform movement disorder that began following a metrizamide myelogram. The organic psychosyndrome was unique in that it was dominated by Schneiderian first-rank symptoms. Case report A 66-year-old man was admitted to the hospital for evaluation of neck and back pain. He had a history of peptic ulcer disease and of intermittent alcohol abuse but had maintained sobriety for six months prior to admission. He had no From the department ofneurology. UCLA (Dr. Davis); the neurobehavior unit. West Los Angeles VAMC (Brentwood Division) and the department ofneurology. UCLA (Dr. Cummings); the department of psychiatry and biobehavioral sciences. UCLA. and the psychiatry service. West Los Angeles VAMC (Dr. Garrick. Wadsworth Division; Dr. Malin. Brentwood Division). Reprint requests to Dr. Cummings. Neurobehavior Unit (691 /Bl 11). West Los Angeles VAMC (Brentwood Division). 11301 Wilshire Blvd.. Los Angeles. CA 90073.
MAY 1986-VOL27-N05
history of psychiatric illness, and there was no family history of neurologic or psychiatric disorders. A metrizamide myelogram (8 mL, 250 mgl/mL) was performed through a lumbar puncture site. Twelve hours after the procedure, the patient developed a mild headache. became disoriented to time and place. and told the staff that colors seemed very bright. The next morning, he complained that his thinking seemed dominated by the number 3 and sequences of 3. Although he was able to walk without difficulty, he remarked that his legs would not move, a problem he attributed to poisoned food and water. He was treated with 5 mg of haloperidol twice daily, improved over the next two days, and was discharged from the hospital without medication. Six days later, his family brought him back to the hospital. At home he had gradually improved but had not returned to normal and had intermittently complained of hearing voices. He also had unusual persistent movements of his hands and feet. The day before admission he became agitated, complained of hearing voices, and believed that signals from the television set controlled his thoughts. When examined in the emergency room, he was disoriented to time and place and could follow only simple commands. He was preoccupied with "a flashing sign on the ceiling" that blocked his thoughts until he could trace the proper geometric sequence and locate a specific dot that allowed his thoughts to emerge. Neurologic examination and laboratory studies including a CT scan of the head and lumbar puncture were normal. An EEG revealed excessive a-range slowing. The patient was placed on 5 mg of haloperidol three times daily. The following day (nine days after the myelogram), he was noted to have asymmetric, uncontrolled choreiform movements of the hands. A repeat EEG revealed a normal 10 to 12 Hz a-rhythm with superimposed a-range slowing.
373
Case report
Mental status testing revealed that he was awake and alert. He knew the year and month. but not the exact date. His recent memory was impaired but remote memory was intact. He interpreted idioms and simple proverbs abstractly and performed simple calculations well. He had moderate difficulty copying complex constructions. Twenty-three days after the myelogram (while still receiving 5 mg of haloperidol daily). the patient continued to be delusional. At this time. mental status examination revealed that he was completely oriented, and his constructions and abstractions were improved. Twenty-nine days after the myelogram no paranoid or persecutory ideation was present: he had no difficulty remembering his previous psychotic misperceptions and ideas. Haloperidol was discontinued. At a clinic visit 50 days after the myelogram. no psychotic ideation was elicited. Mental status testing revealed no abnormalities, and an EEG was normal.
Discussion This patient had an unusually prolonged change in mentation accompanied by hallucinations and delusions following metrizamide myelography. In the initial phase of the reaction, he was in an acute confusional state with psychosis. During this period a prominent choreiform movement disorder was also observed. Schneiderian first-rank symptoms including thought interference and impulses attributed to outside influences dominated the mental state and persisted as the confusion cleared. Schneider's first-rank symptoms include hearing one's thoughts spoken aloud; hearing voices that comment on one's actions; thought interference; delusional interpretation of percepts; and the experience that feelings, drives, and volitions are imposed or influenced by others. 7 Schneider suggested that in the absence of organic disorders, these symptoms were pathognomonic of schizophrenia. Schneiderian first-rank symptoms are known to occur in mania and depression,' but in the absence of a major mood disorder they remain important in the diagnosis of schizophrenia and are included among the diagnostic criteria of DSM-III.· Schneider acknowledged that first-rank symptoms occur in organic psychosyndromes as well as schizophrenia, but there has been little investigation of the relationship between brain dysfunction and these delusional experiences. Neurologic disorders in which first-rank symptoms have been reported include idiopathic basal ganglia calcification; post-encephalitic parkinsonism; temporal lobe epilepsy; hydrocephalus; and a variety of infectious, traumatic, and cerebrovascular conditions. 10 Dopamine is a principal neurotransmitter in subcortical and limbic structures-areas 374
commonly involved by diseases producing first-rank symptoms. Likewise, dopamine is the transmitter currently implicated in the pathophysiology of idiopathic schizophrenia, and involvement of dopaminergic systems in schizophrenia as well as in neurologic disorders with schizophrenia-like symptoms may account for the occurrence of first-rank symptoms in both disorders. The choreiform movement disorder reported in the patient described here implicated involvement of basal ganglionic structures and supports an association between subcortical dysfunction and first-rank symptoms. After his metrizamide myelogram, the patient manifested a confusional state as well as the schizophrenia-like symptom complex. The resolution of these two components of the psychosyndrome differed substantially: the intellectual impairment had largely resolved by the second week, whereas the delusions persisted almost twice as long. The pattern of the Mini-Mental State Examination (MMSE)" and Brief Psychiatric Rating Scale (BPRS)12 scores at various points during the course of the illness is shown in the Table. This suggests that the psychotic and confusional aspects of this syndrome were mediated by different cerebral mechanisms. Metrizamide is an epileptogenic agent, and neuroleptic drugs lower the seizure threshold, suggesting that co-administration may have potentially adverse consequences. 13 However, when seizures have not occurred, when the EEG is normal, and when psychosis is prominent, neuroleptic agents may be successfully used, as is illustrated by this case and others reported in the literature." Factors implicated in the pathogenesis of metrizamide encephalopathies include age, prolonged contact with and penetration of metrizamide into eNS gray matter, subclinical seizure activity, history of premorbid mental and or-
Tabl~MSE and
BPRS Scores During the Course of the Illness Days after myelogram
Questionnaire
9
23
27
50
MMSE' score
10
27
27
29
BPRStscore
56
36
16
2
'Mini-MenIal State Examination' (a score above 24 is normat) Bnel Psychlatnc Rating Scale8 (Individuals functioning ,n the normal range could be expected to obtain a score of 10 or less)
PSYCHOSOMATICS
ganic illness, disturbances of glucose metabolism, and interference with putative neurotransmitter function.'3-18 In the present case, the patient's age and history of alcohol abuse may have contributed to heightened vulnerability to a drug reaction. The absence of epileptiform discharges on the three EEGs suggests that seizures were unlikely to have been a significant contributing factor. More likely, toxic neuronal disturbances led to a disruption of neuronal function and accounted for the symptoms observed. In summary, the brief duration of the confusional state, when compared with the prolonged delusional aspect of the psychosyndrome, suggests that different functional neuro-
REFERENCES 1 Almen T Contrast agent design: Some aspects on the synthesis of watersoluble contrast agents of low osmolality. J Theor BioI 24:216-226. 1969. 2 Gelmers HJ Adverse side effects of metrizamide in myelography. Neuroradlology 18:119-123,1979 3 Schmidt RC Mental disorders after myelography with metrizamide and other water-soluble contrast media. Neuroradiology 19: 153-157. 1980 4. Hauge 0, Falkenberg H: Neuropsychologic reactions and other side effects after metrizamide myelography Am J Roentgenol 139:357-360, 1982 5 Killebrew K, Whaley RA. Hayward IN, et al: Complications of metrizamide myelography Arch Neuro/40:78-80, 1983. 6 Elliot RL, Wild JH Jr, Snow WT Prolonged delirium after metrizamide myelography JAMA 252:2057-2058,1984 7. Schneider K Primare und sekundare Symptomen bei Schizophrenie. FortSChr Neurol Psychlatr 25:487-490, 1957. 8 Carpenter WT Jr, Strauss JS. Muleh S: Are there pathognomonic symptoms in schizophrenia? Arch Gen Psychiatry 28:847-852.1973. 9 Diagnostic and Statistical Manual of Mental Disorders. ed 3. Washington, DC, American Psychiatric Association, 1980
MAY 1986- VOL 27- N05
nal systems were disturbed, and that these systems manifested distinctive vulnerabilities, sustained different degrees of disturbance, recovered at different rates, and responded differently to drug treatment. The presence of a choreiform movement disorder as one manifestation of the encephalopathy suggests that a disturbance of subcortical function was produced by the metrizamide. Delusions have been found with increased frequency among other disorders with subcortical abnormalities. 0 This project was supported by the Veterans Administration. Ms. Norene Hiekel prepared the manuscript. 10. Cummings JL: Organic delusions Br J Psychiatry 146: 184-197. 1985. 11. Folstein MF. Folstein SE. McHugh PR: 'Mini-mental state': A practical method for grading the mental state of patients for the clinician. J PsychiatrRes 12:189-198, 1975 12. Overall JE. Gorham DR: The brief psychiatric rating scale Psychol Rep 10:799-812,1962 13. Hanus PM: Metrizamide: A review with emphasis on drug interactions. Am JHospPharm37:510-513,1980. 14. Drayer BP, Rosenbaum AE: Metrizamide brain penetrance Acta Radiol (suppl) 355:280-293, 1977 15. Gonselle RE: Biologic tolerance of the central nervous system to metrizamide. Acta Radiol (suppl) 335:25-44, 1973 16. Bertoni JM. Schwartzman RJ, Van Horn G, et al: Asterixis and encephalopathy fOllowing metrizamide myelography: Investigations into possible mechanisms and review of the literature Ann Neuro/9:366-370, 1981. 17. Junck L. Marshall WH: Neurotoxicity of radiological contrast agents. Ann Neuro/13:469-484,1983. 18. Polls DG, Gomez DG, Abboll GF: Possible causes of complications of myelography with water·soluble contrast medium. Acta Radiol (suppl) 355:390-402,1977
375