Atypical Affective Disorder with Episodic Dyscontrol: A Case of von Economo's Disease (Encephalitis Lethargica)* JEREMICH D. DOLAN, M.B. 1 AND RIFAAT KAMIL, M.D. 2
Case Report
The case is described of a patient with atypical affective disorder, episodic behavioural dyscontrol and parkinsonism resulting from presumed encephalitis lethargica. EEG abnormalities were found which were compatible with a post-encephalitic state and suggestive ofepileptiform complications. Poor or deleterious response to neuroleptics, sleep disorder, and parkinsonism are features that may allow recognition of this illness in a psychiatric setting.
A 23 year old, right-handed man became acutely somnolent for a one week period and could be aroused only with great difficulty. He recovered but continued to be fatigued and continued to suffer from daytime somnolence and hocturnal wakefulness. Nine months later the patient became euphoric and sexually preoccupied. Bipolar affective disorder was suspected, and he was treated with thioridazine 10 mg tid. By the end of the year, he had developed a tremor in his left arm, for which anticholinergic medications produced no amelioration. His behaviour gradually deteriorated; he became affectively labile with rapid, almost daily, mood swings from euphoria to despondency. When his inappropriate sexual advances were rejected, he became childish. Neuroleptics and lithium provided little improvement, but he suffered from extreme extrapyramidal effects from high-potency medications. The patient's tremor worsened, spreading to his left leg, and persisted even when he was not taking medication. An EEG revealed mild, diffuse slow-wave changes. A gradual deterioration of his clinical state continued, and four years later, while off medication, he began manifesting paroxysmal episodes of abnormal behaviour. A brief period of fearfulness preceded auditory and visual hallucinations, causing him to scream in a high pitched voice and to become violence towards himself and others. He would develop a course body tremor with general hypertonicity, tongue protrusion and occulogyric crisis, profuse diaphoresis, drooling, and urinary incontinence. These attacks were invariably nocturnal and would last several hours. The patient was able to recall the attacks afterward. The severe tremor and increased tone would persist for several days before he gradually improved. Chlorpromazine and a single dose of pipotiazine (75 mg) increased the frequency and severity of his attacks. An EEG revealed diffuse cerebral disturbance, and he was transferred to our institute for further assessment. Neuroleptics were discontinued and treatment with carbamazepine 400 mg bid and lorazepam 2 mg qid was begun. The "attacks" were alleviated using bolus intravenous lorazepam 4 mg. They ceased altogether after three months of this treatment, but his parkinsonian tremor persisted. There was no residual psychosis or sustained mood change but he occasionally engaged in sexually inappropriate behaviour. Durihg a six month follow-up, he had two isolated similar
V
on .Economo first brought attention to the neuropsychiatnc aspects of encephalitis lethargica (I). This presumed viral illness, responsible to a significant degree for morbidity and mortality, occurred in epidemic form between 1916 and 1927. The first symptom was frequently a sudden onset of prolonged sleep. Acute manifestations were similar to those in other encephalitic illnesses, and rigidity and akinesia often developed. A mortality rate of 30% was reported (2). Chronic features included the development of post-encephalitic parkinsonism, occulogyric crises, consistent inversion of the sleep-wake cycle, and paroxysmal episodes of vasomotor and autonomic dyscontrol (3). Psychiatric complications were common but protean; psychosis, affective lability, and impulse control were frequently reported (1-3). The etiologic agent has not been determined. Reviews of case reports (4) attest to the fact that encephalitis lethargica causes psychiatric and neurological morbidity. We report a case of encephalitic lethargica of recent onset which presented diagnostic and management challenges.
'Manuscript received May 1991. 1Lecturer, Department of Psychiatry, University ofToronto; Lakeshore Community and Mental Health Clinic, division of Queen Street Mental Health Centre; Assessment and Treatment Division, Clarke Institute of Psychiatry, Toronto, Ontario, Canada. 2Formerly Psychiatric Resident, Clarke Institute ofPsychiatry; University of Toronto, Toronto, Ontario. Addressreprint requeststo: Dr. 1. Dolan, Lakeshore Community and Mental Health Clinic, Queen Street Mental Health Centre, 1001 Queen Street West, Toronto, Ontario M6J IH4
Can. J. Psychiatry Vol. 37, March 1992
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March,1992
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A CASE OF VON ECONOMO'S DISEASE
"attacks", both related to non compliance with his drug regimen. The patient's medical and family history were unremarkable and he reported no substance abuse. The findings of a general and neurological exam were normal except for the following parkinsonian features: akinetic facies, reduced blinking, resting tremor of left arm and leg with marked cogwheeling. No features of tardive dyskinesia were noted. The results of routine hematological, biochemical and thyroid tests were normal, as were ceruloplasmin and complement levels and titers of auto-antibodies. Serum convalescent titers were less than 1:8 for influence B and herpes simplex, 1:30 for influenza A, and 1:64for the measles virus. Serology in blood and CSF was negative for eastern equine, western-equine, St. Louis, Japanese, California and Powassan encephalitis viruses. CSF titers for the measles virus were insignificant. Routine CSF tests were unremarkable. Oligoclonal banding and viral culture studies were negative. Brain CT and MRI studies were normal. Nasopharyngeal EEG records revealed diffuse delta waves, and paroxysmal abnormal dysrhythmias in the right temporal region.
,
(8), and no doubt neuroleptic use exacerbated the disorder. Our patient meets contemporary diagnostic criteria (9), but suggestions that neuroleptic use preclude a diagnosis of encephalitis lethargic a are impractical, since patients with behavioural disorders often receive treatment before a definite diagnosis made (10). Conclusion Until recently, encephalitis lethargica was only of historical interest. The current incidence and etiology have not been determined, but it is probable that "functional" psychiatric diagnoses are given to some patients who suffer from postencephalitic complications. Patients who have an unusual history of affective disorder, do not respsond to lithium, or are extremely sensitive to neuroleptic-induced side-effects should be assessed for encephalitic illness. Initial hypersomnolence, chronic sleep disturbance or early onset of irreversible parkinsonism should lead the clinican to consider encephalitis lethargica. In addition, despite our technical advances, this case accentuates one of our best diagnostic tools - a thorough clinical history. Acknowledgements
Discussion This patient's somnolence, sleep-cycle inversion, parkinsonism and behavioural abnormalities follow classic descriptions of encephalitis lethargica (I). A re-examination of his history found little evidence that he suffered from true bipolar disorder; rather it suggested that he had an affective illness secondary to encephalitis. His acute illness was misinterpreted as depression, and abnormal EEG records were disregarded. Had a more careful history been obtained, an organic mental disorder would have been suspected much earlier. The episodic dyscontrol described in encephalitis lethargic a has features similar to limbic and temporal lobe epilepsy (3,5). The above mentioned suspicion that epileptiform disorders occur in conjunction with encephalitis lethargic a was strengthened by this patient's EEG abnormalities. Ballenger and Post (6) postulate that a kindling mechanism causes limbic neuronal sensitization in patients with affective disorder (analogous to the role of kindling in epilepsy). In our patient, encephalitic damage may have initiated a similar kindling, producing affective lability. Carbamazepine's effectiveness may reflect its specific limbic "antikindling" and anticonvulsant properties (6). The usefulness of lorzepam may reflect anticonvulsant properties or GABAergic modulation of dopamine pathways (7). The use ofneuroleptics and lithium confounds the diagnosis of encephalitic lethargica. Features of this patient's history - the appearance of parkinsonism on very low doses of thioridazine, its persistence while the patient was off medication, the subsequent onset of attacks while the patient was drug-free - make it unlikely that medications were responsible for the observed abnormalities. Encephalitis lethargica preferentially damages basal ganglia and the mesencephalon
We would like to thank the 9th floor nursing staff for their astute clinical observations of this patient. Also, we express our appreciation to Drs. Serge Gauthier, Gary Remington and Brenda Toner for critical evaluation of this manuscript, and to Professor D.K. O'Donovan for instilling the art of a thorough clinical history.
References I.
2.
3. 4.
5. 6.
7. 8. 9.
10.
von Economo C. Encephalitis lethargica: its sequelae and treatment. Translation by Newman KD. London: Oxford University Press, 1931. Timme W. Acute epidemic encephalitis: an investigation by the Association for Research in Nervous and Mental Diseases. New York: Paul B. Hoeber, 1921. Ward CD. Encephalitis lethargica and the development of neuro-psychiatry. Psychiatr Clin North Am 1986; 9(2): 215-224. Hoenig J, Abbey S. von Economo's disease (encephalitis lethargica). Lessons for psychiatry. Kurstak E, Lipowski ZT, Morozov PV, eds. In: Viruses, immunity and mental disorder. New York: Plenum Publishers, 1987. Monroe RR. Episodic behavioral disorders and limbic ictus. Compr Psychiatry 1985; 26(5): 446-479. Ballenger JG, Post RM. Carbamazepine in manic-depressive illness. A new treatment. Am J Psychiatry 1980; 137(7): 782790. Betz BJ. Some neurophysiological aspects of individual behavior. Am J Psychiatry 1979; 136(10): 1251-1256. Lishman WA. Organic psychiatry. Oxford: Blackwell Scientific Publications, 1978. Rail D, Scholtz C, Swash M. Post-encephalitic parkinsonism: current experience. J Neurol Neurosurg Psychiatry 1981; 44: 670-676. Johnson J, Lucey PA. Encephalitis lethargica, a contemporary cause of catatonic stupor. A report of two cases. Br J Psychiatry 1987; 151: 550-552.
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Resume Les auteurs parlent d' un malade qui presentait un trouble affectif atypique, un dysfonctionnement eptsodique du comportement et du parkinsonisme, peut-etre a la suite d' une encephalite lethargique. Ils ont note certaines anomalies a
Vol. 37, No.2
l' EEG, compatibles avec l' etat post-encephalitique. Ces anomalies suggerent des complications epileptiformes. Une pietre ou une mauvaise reaction aux neuroleptiques, des troubles du sommeil et le parkinsonisme sont autant de caracteristiques qui permettent d'identifier cette maladie en milieu psychiatrique.
Case Report
The case is described of a patient with atypical affective disorder, episodic behavioural dyscontrol and parkinsonism resulting from presumed encephalitis lethargica. EEG abnormalities were found which were compatible with a post-encephalitic state and suggestive ofepileptiform complications. Poor or deleterious response to neuroleptics, sleep disorder, and parkinsonism are features that may allow recognition of this illness in a psychiatric setting.
A 23 year old, right-handed man became acutely somnolent for a one week period and could be aroused only with great difficulty. He recovered but continued to be fatigued and continued to suffer from daytime somnolence and hocturnal wakefulness. Nine months later the patient became euphoric and sexually preoccupied. Bipolar affective disorder was suspected, and he was treated with thioridazine 10 mg tid. By the end of the year, he had developed a tremor in his left arm, for which anticholinergic medications produced no amelioration. His behaviour gradually deteriorated; he became affectively labile with rapid, almost daily, mood swings from euphoria to despondency. When his inappropriate sexual advances were rejected, he became childish. Neuroleptics and lithium provided little improvement, but he suffered from extreme extrapyramidal effects from high-potency medications. The patient's tremor worsened, spreading to his left leg, and persisted even when he was not taking medication. An EEG revealed mild, diffuse slow-wave changes. A gradual deterioration of his clinical state continued, and four years later, while off medication, he began manifesting paroxysmal episodes of abnormal behaviour. A brief period of fearfulness preceded auditory and visual hallucinations, causing him to scream in a high pitched voice and to become violence towards himself and others. He would develop a course body tremor with general hypertonicity, tongue protrusion and occulogyric crisis, profuse diaphoresis, drooling, and urinary incontinence. These attacks were invariably nocturnal and would last several hours. The patient was able to recall the attacks afterward. The severe tremor and increased tone would persist for several days before he gradually improved. Chlorpromazine and a single dose of pipotiazine (75 mg) increased the frequency and severity of his attacks. An EEG revealed diffuse cerebral disturbance, and he was transferred to our institute for further assessment. Neuroleptics were discontinued and treatment with carbamazepine 400 mg bid and lorazepam 2 mg qid was begun. The "attacks" were alleviated using bolus intravenous lorazepam 4 mg. They ceased altogether after three months of this treatment, but his parkinsonian tremor persisted. There was no residual psychosis or sustained mood change but he occasionally engaged in sexually inappropriate behaviour. Durihg a six month follow-up, he had two isolated similar
V
on .Economo first brought attention to the neuropsychiatnc aspects of encephalitis lethargica (I). This presumed viral illness, responsible to a significant degree for morbidity and mortality, occurred in epidemic form between 1916 and 1927. The first symptom was frequently a sudden onset of prolonged sleep. Acute manifestations were similar to those in other encephalitic illnesses, and rigidity and akinesia often developed. A mortality rate of 30% was reported (2). Chronic features included the development of post-encephalitic parkinsonism, occulogyric crises, consistent inversion of the sleep-wake cycle, and paroxysmal episodes of vasomotor and autonomic dyscontrol (3). Psychiatric complications were common but protean; psychosis, affective lability, and impulse control were frequently reported (1-3). The etiologic agent has not been determined. Reviews of case reports (4) attest to the fact that encephalitis lethargica causes psychiatric and neurological morbidity. We report a case of encephalitic lethargica of recent onset which presented diagnostic and management challenges.
'Manuscript received May 1991. 1Lecturer, Department of Psychiatry, University ofToronto; Lakeshore Community and Mental Health Clinic, division of Queen Street Mental Health Centre; Assessment and Treatment Division, Clarke Institute of Psychiatry, Toronto, Ontario, Canada. 2Formerly Psychiatric Resident, Clarke Institute ofPsychiatry; University of Toronto, Toronto, Ontario. Addressreprint requeststo: Dr. 1. Dolan, Lakeshore Community and Mental Health Clinic, Queen Street Mental Health Centre, 1001 Queen Street West, Toronto, Ontario M6J IH4
Can. J. Psychiatry Vol. 37, March 1992
140
March,1992
141
A CASE OF VON ECONOMO'S DISEASE
"attacks", both related to non compliance with his drug regimen. The patient's medical and family history were unremarkable and he reported no substance abuse. The findings of a general and neurological exam were normal except for the following parkinsonian features: akinetic facies, reduced blinking, resting tremor of left arm and leg with marked cogwheeling. No features of tardive dyskinesia were noted. The results of routine hematological, biochemical and thyroid tests were normal, as were ceruloplasmin and complement levels and titers of auto-antibodies. Serum convalescent titers were less than 1:8 for influence B and herpes simplex, 1:30 for influenza A, and 1:64for the measles virus. Serology in blood and CSF was negative for eastern equine, western-equine, St. Louis, Japanese, California and Powassan encephalitis viruses. CSF titers for the measles virus were insignificant. Routine CSF tests were unremarkable. Oligoclonal banding and viral culture studies were negative. Brain CT and MRI studies were normal. Nasopharyngeal EEG records revealed diffuse delta waves, and paroxysmal abnormal dysrhythmias in the right temporal region.
,
(8), and no doubt neuroleptic use exacerbated the disorder. Our patient meets contemporary diagnostic criteria (9), but suggestions that neuroleptic use preclude a diagnosis of encephalitis lethargic a are impractical, since patients with behavioural disorders often receive treatment before a definite diagnosis made (10). Conclusion Until recently, encephalitis lethargica was only of historical interest. The current incidence and etiology have not been determined, but it is probable that "functional" psychiatric diagnoses are given to some patients who suffer from postencephalitic complications. Patients who have an unusual history of affective disorder, do not respsond to lithium, or are extremely sensitive to neuroleptic-induced side-effects should be assessed for encephalitic illness. Initial hypersomnolence, chronic sleep disturbance or early onset of irreversible parkinsonism should lead the clinican to consider encephalitis lethargica. In addition, despite our technical advances, this case accentuates one of our best diagnostic tools - a thorough clinical history. Acknowledgements
Discussion This patient's somnolence, sleep-cycle inversion, parkinsonism and behavioural abnormalities follow classic descriptions of encephalitis lethargica (I). A re-examination of his history found little evidence that he suffered from true bipolar disorder; rather it suggested that he had an affective illness secondary to encephalitis. His acute illness was misinterpreted as depression, and abnormal EEG records were disregarded. Had a more careful history been obtained, an organic mental disorder would have been suspected much earlier. The episodic dyscontrol described in encephalitis lethargic a has features similar to limbic and temporal lobe epilepsy (3,5). The above mentioned suspicion that epileptiform disorders occur in conjunction with encephalitis lethargic a was strengthened by this patient's EEG abnormalities. Ballenger and Post (6) postulate that a kindling mechanism causes limbic neuronal sensitization in patients with affective disorder (analogous to the role of kindling in epilepsy). In our patient, encephalitic damage may have initiated a similar kindling, producing affective lability. Carbamazepine's effectiveness may reflect its specific limbic "antikindling" and anticonvulsant properties (6). The usefulness of lorzepam may reflect anticonvulsant properties or GABAergic modulation of dopamine pathways (7). The use ofneuroleptics and lithium confounds the diagnosis of encephalitic lethargica. Features of this patient's history - the appearance of parkinsonism on very low doses of thioridazine, its persistence while the patient was off medication, the subsequent onset of attacks while the patient was drug-free - make it unlikely that medications were responsible for the observed abnormalities. Encephalitis lethargica preferentially damages basal ganglia and the mesencephalon
We would like to thank the 9th floor nursing staff for their astute clinical observations of this patient. Also, we express our appreciation to Drs. Serge Gauthier, Gary Remington and Brenda Toner for critical evaluation of this manuscript, and to Professor D.K. O'Donovan for instilling the art of a thorough clinical history.
References I.
2.
3. 4.
5. 6.
7. 8. 9.
10.
von Economo C. Encephalitis lethargica: its sequelae and treatment. Translation by Newman KD. London: Oxford University Press, 1931. Timme W. Acute epidemic encephalitis: an investigation by the Association for Research in Nervous and Mental Diseases. New York: Paul B. Hoeber, 1921. Ward CD. Encephalitis lethargica and the development of neuro-psychiatry. Psychiatr Clin North Am 1986; 9(2): 215-224. Hoenig J, Abbey S. von Economo's disease (encephalitis lethargica). Lessons for psychiatry. Kurstak E, Lipowski ZT, Morozov PV, eds. In: Viruses, immunity and mental disorder. New York: Plenum Publishers, 1987. Monroe RR. Episodic behavioral disorders and limbic ictus. Compr Psychiatry 1985; 26(5): 446-479. Ballenger JG, Post RM. Carbamazepine in manic-depressive illness. A new treatment. Am J Psychiatry 1980; 137(7): 782790. Betz BJ. Some neurophysiological aspects of individual behavior. Am J Psychiatry 1979; 136(10): 1251-1256. Lishman WA. Organic psychiatry. Oxford: Blackwell Scientific Publications, 1978. Rail D, Scholtz C, Swash M. Post-encephalitic parkinsonism: current experience. J Neurol Neurosurg Psychiatry 1981; 44: 670-676. Johnson J, Lucey PA. Encephalitis lethargica, a contemporary cause of catatonic stupor. A report of two cases. Br J Psychiatry 1987; 151: 550-552.
142
CANADIAN JOURNAL OF PSYCHIATRY
Resume Les auteurs parlent d' un malade qui presentait un trouble affectif atypique, un dysfonctionnement eptsodique du comportement et du parkinsonisme, peut-etre a la suite d' une encephalite lethargique. Ils ont note certaines anomalies a
Vol. 37, No.2
l' EEG, compatibles avec l' etat post-encephalitique. Ces anomalies suggerent des complications epileptiformes. Une pietre ou une mauvaise reaction aux neuroleptiques, des troubles du sommeil et le parkinsonisme sont autant de caracteristiques qui permettent d'identifier cette maladie en milieu psychiatrique.
