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Tic disorder associated with encephalopathy in advanced HIV disease
Letter to the Editor Letters to the Editor are invited for comment on a topic of current interest or on material published in GENERAL HOSPITAL PSYCHIATRY. Letters should be typed double-spaced and are subject to editing according to space limitations.
Tic Disorder Associated with EnceDhaloDathv in Advanced HIV Disease Increasingly, psychiatrists are being called upon to manage the neuropsychiatric sequelae of HIV infection. The discovery in 1985 that HIV is a neurotropic virus dramatically changed the way psychiatrists approached the differential diagnosis of their HIV seropositive patients [l]. Neuropsychiatric manifestations of HIV disease include encephalopathy and cognitive impairment, organic mood disorders, delirium, sleep disorders, and anxiety disorders [24]. * has been characterized HIV encephalopathy as a complex of affective, cognitive, motor, and behavioral abnormalities [6]. Though such motor components as tremor, dystonia, and ataxia are well known neuropsychiatric complications of HIV encephalopathy, tic disorders have not been previously reported. We present the case of an HIV seropositive male with HIV-related encephalopathy who developed transient vocal and motor tics during the advanced stage of his HIV disease.
Case Report Mr. L, a 40-year-old male with advanced HIV disease, was referred for evaluation of abnormal extremity movements. He had been HIV seropositive for 4 years and at the time of evaluation had a CD4 count of 41. His AIDS-related complications included disseminated Mycobacterium avium complex, Kaposi’s sarcoma, and bilateral peripheral neuropathy in his lower extremities. He had a previous history of presumed major depression and was being treated with imipramine 100 mg/day by * The term “HIV encephalopathy” replaces earlier more general terms such as “AIDS dementia complex” or “AIDS dementia” [5]. Address reprint requests to: J. Stephen McDaniel, M.D., The Emory Clinic-Psychiatry, 1365 Clifton Road, NE, Atlanta, Georgia 30322.
298 ISSN 0163~8343/94/$7.00
his medical doctor. His other medications included clarithromycin, ethambutol, rifampin, and flucon-
azole . Upon examination, Mr. L gave a 3-month history of jerking extremity movements and a 2-month history of involuntary vocalizations. He described his jerking movements as occurring primarily in his upper extremities, characterized by a sudden, involuntary, recurrent, stereotyped pattern. These movements also frequently involved his head and neck and were associated with involuntary vocalizations occurring lo-15 times per day. He described the vocalizations as a “barking sound’ and at times a “mooing sound.“ These movements and vocalizations caused significant embarrassment and subsequent avoidance of social situations. The patient’s partner corroborated the history and documented that the movements and vocalizations sometimes occurred in the patient’s sleep. Mr. L had been given a previous trial of haloperidol 0.5 mg/day, which was gradually increased to 5 mg/day, with no noted improvement in his motor or vocal tics. Other pertinent history revealed a progressive course of cognitive decline and social apathy. The patient reported difficulty articulating his thoughts, as well as difficulty remembering names and numbers. He had stopped driving in the past year secondary to two accidents (neither involved head injury), and he had stopped cooking on the stove because he frequently forgot to turn off the burners. He reported no previous or current history of alcohol or recreational drug use. He had no history of head injury, seizure disorder, or HIVrelated central nervous system opportunistic infections or tumors. He had no personal or family history of tic disorder and no previous amphetamine or psychostimulant use. On mental status examination, Mr. L was a diGeneral Hospitaf Psychiatry 16, 298-300, 1994 0 1994 Else&r Science Inc. 655 Avenue of the Americas, New York, NY 10010
Letter to the Editor sheveled gentleman appearing markedly anxious. He had occasional rhythmic, involuntary movements of his upper extremities and head. He reported mild dysphoria and complained of intense anxiety. He displayed a blunted affect. His thought processes revealed circumstantiality; however, his thought content revealed no evidence of Cognitive functioning was false perceptions. grossly impaired (Mini-Mental State Exam, 21/30; Trailmaking Part A, 110 seconds, z = -8.6; Trailmaking Part B, unable to complete). Laboratory examination revealed a normal serum chemistry profile. Lumbar puncture revealed an elevated protein (252 mg/dl), but otherwise normal. An electroencephalogram (EEG) (awake and sleeping) revealed mild, nonspecific slowing. Both magnetic resonance imaging (MRI) and computed tomography (CT) of the head were interpreted as normal. Neurology consultation concluded abnormal tics and vocalizations of uncertain etiology and a presumptive diagnosis of encephalopathy associated with HIV infection. Mr. L met diagnostic criteria for HIV-related encephalopathy with an associated tic disorder characterized by both a motor and vocal component. Normal radiographic examination and nonspecific EEG findings were not sufficient evidence, in view of this patient’s clinical exam, to rule out HIVrelated brain involvement. However, these findings coupled with his history, clinical presentation, and elevated cerebrospinal fluid (CSF) protein were consistent with general findings in HIV brain disease [3]. As this patient’s presentation was more consistent with apathy associated with encephalopathy rather than major depression, his imipramine was discontinued. Because he had failed previous trials of haloperidol and was reluctant to try other neuroleptics, he was begun on a trial of clonazepam 0.5 mg/day. Within 1 week he reported feeling less anxious and reported mild subjective improvement in his motor tics but no improvement in his vocal tics. Although a trial of clonidine, an alphaadrenergic blocking agent used to treat Tourette’s syndrome [8], was planned, it was not instituted due to frequent orthostasis. The patient rapidly became more physically and mentally impaired and is currently receiving hospice care.
presentation remains complex. The encephalopathy associated with HIV is primarily thought to be subcortical [4]. Although there remains some disagreement as to which specific neural regions serve as the primary sites for HIV-related neuropathology, neuroimaging procedures have documented significant subcortical involvement [7]. Positron emission tomography has specifically shown basal ganglion and thalamic glucose hypermetabolism in the initial stages of HIV infection [7]. Further, clinical presentations of advanced HIV encephalopathy have consisted of a variety of motor abnormalities resembling such subcortical dementias as Huntington’s and Parkinson’s disease. This patient’s presentation was most significant for his involuntary motor and vocal tics in the absence of other movement abnormalities or ataxia. Generally, tic disorders are diagnosed in childhood or adolescence and are not frequently seen in adult cases of neuropsychiatric abnormalities. Although a number of neurochemical systems have been implicated in tic disorders, the strongest evidence supports the role of dopaminerigic systems in the pathophysiology [8]. Therefore, conditions, like HIV infection, which primarily affect subcortical structures rich in dopamine pathways, could feasibly yield transient tics. Dopamine antagonists, primarily haloperidol, have been utilized in the treatment of tic disorders, especially Tourette’s syndrome. Unfortunately, this medication did not prove effective for this patient. Pimozide, another potent neuroleptic frequently used to treat Tourette’s syndrome [9], was not instituted because of previous neuroleptic failure. The patient initially was begun on clonazepam to alleviate his anxiety and monitor any effects on his tics. As tics are known to emerge in susceptible children during periods of increased anxiety, the improvement in this patient’s tics may be related to the anxiolytic effects of clonazepam. Although other medication trials such as pimozide or clonidine were not possible in this patient, they are clearly alternative therapies. Such therapies should be considered as psychiatrists see increasing numbers of HIV seropositive patients with central nervous system involvement.
This case suggests the need for psychiatrists to remain curious as we assume more responsibility in the management of HIV seropositive patients. Though HIV encephalopathy has long been a known complication of HIV infection, its clinical
J. Stephen McDaniel, M.D. Mary B. Summerville, Ph.D. Emory University School of Medicine, Grady Health System Infectious Disease Program, Department of Psychiatry and Behavioral Sciences, Atlanta, Georgia
Letter to the Editor
References 1. Ho DD, Rota TR, Schooley RT, et al: Isolation of
2. 3. 4. 5.
HTLV-III from cerebrospinal fluid and neural tissues in patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med 313:14781484, 1985 Grant I: The neuropsychiatry of human immunodeficiency virus. Semin Neurol 10(3):267-275, 1990 Perry SW: Organic mental disorders caused by HIV; update on early diagnosis and treatment. Am J Psychiatry 147~696710, 1990 Van Gorp WG, Satz P, Hinkin C, Evans G, Miller EN: The neuropsychological aspects of HIV-l spectrum disease. Psychiatr Med 7(2):59-78, 1990 Centers for Disease Control: Revision of the CDC sur-
300
veillance case definitions for acquired immunodeficiency syndrome. MMWR 36 (Suppl l):lS-15S, 1987 Navia BA, Jordan BD, Price RW: The AIDS dementia complex: I. clinical features. Ann Neurol 19:517-524, 1986 Rottenberg D, Moeller J, Strother S, et al: The metabolic pathology of the AIDS dementia complex. Ann Neurol22:700-706, 1987 Williams DT, Pleak R, Hanesian H: Neuropsychiatric disorders of childhood and adolescence. In Hales RE, Yudofsky SC (eds), The American Psychiatric Press Textbook of Neuropsychiatry. Washington, DC, American Psychiatric Press, Inc., 1987, pp 365-386 Leckman, JF, Cohen DJ: Tourette’s disorder and other stereotyped movement disorders. In Cavenar JO (ed), Psychiatry, Vol 238. Philadelphia, J.B. Lippincott, 1988, pp l-8
Tic Disorder Associated with EnceDhaloDathv in Advanced HIV Disease Increasingly, psychiatrists are being called upon to manage the neuropsychiatric sequelae of HIV infection. The discovery in 1985 that HIV is a neurotropic virus dramatically changed the way psychiatrists approached the differential diagnosis of their HIV seropositive patients [l]. Neuropsychiatric manifestations of HIV disease include encephalopathy and cognitive impairment, organic mood disorders, delirium, sleep disorders, and anxiety disorders [24]. * has been characterized HIV encephalopathy as a complex of affective, cognitive, motor, and behavioral abnormalities [6]. Though such motor components as tremor, dystonia, and ataxia are well known neuropsychiatric complications of HIV encephalopathy, tic disorders have not been previously reported. We present the case of an HIV seropositive male with HIV-related encephalopathy who developed transient vocal and motor tics during the advanced stage of his HIV disease.
Case Report Mr. L, a 40-year-old male with advanced HIV disease, was referred for evaluation of abnormal extremity movements. He had been HIV seropositive for 4 years and at the time of evaluation had a CD4 count of 41. His AIDS-related complications included disseminated Mycobacterium avium complex, Kaposi’s sarcoma, and bilateral peripheral neuropathy in his lower extremities. He had a previous history of presumed major depression and was being treated with imipramine 100 mg/day by * The term “HIV encephalopathy” replaces earlier more general terms such as “AIDS dementia complex” or “AIDS dementia” [5]. Address reprint requests to: J. Stephen McDaniel, M.D., The Emory Clinic-Psychiatry, 1365 Clifton Road, NE, Atlanta, Georgia 30322.
298 ISSN 0163~8343/94/$7.00
his medical doctor. His other medications included clarithromycin, ethambutol, rifampin, and flucon-
azole . Upon examination, Mr. L gave a 3-month history of jerking extremity movements and a 2-month history of involuntary vocalizations. He described his jerking movements as occurring primarily in his upper extremities, characterized by a sudden, involuntary, recurrent, stereotyped pattern. These movements also frequently involved his head and neck and were associated with involuntary vocalizations occurring lo-15 times per day. He described the vocalizations as a “barking sound’ and at times a “mooing sound.“ These movements and vocalizations caused significant embarrassment and subsequent avoidance of social situations. The patient’s partner corroborated the history and documented that the movements and vocalizations sometimes occurred in the patient’s sleep. Mr. L had been given a previous trial of haloperidol 0.5 mg/day, which was gradually increased to 5 mg/day, with no noted improvement in his motor or vocal tics. Other pertinent history revealed a progressive course of cognitive decline and social apathy. The patient reported difficulty articulating his thoughts, as well as difficulty remembering names and numbers. He had stopped driving in the past year secondary to two accidents (neither involved head injury), and he had stopped cooking on the stove because he frequently forgot to turn off the burners. He reported no previous or current history of alcohol or recreational drug use. He had no history of head injury, seizure disorder, or HIVrelated central nervous system opportunistic infections or tumors. He had no personal or family history of tic disorder and no previous amphetamine or psychostimulant use. On mental status examination, Mr. L was a diGeneral Hospitaf Psychiatry 16, 298-300, 1994 0 1994 Else&r Science Inc. 655 Avenue of the Americas, New York, NY 10010
Letter to the Editor sheveled gentleman appearing markedly anxious. He had occasional rhythmic, involuntary movements of his upper extremities and head. He reported mild dysphoria and complained of intense anxiety. He displayed a blunted affect. His thought processes revealed circumstantiality; however, his thought content revealed no evidence of Cognitive functioning was false perceptions. grossly impaired (Mini-Mental State Exam, 21/30; Trailmaking Part A, 110 seconds, z = -8.6; Trailmaking Part B, unable to complete). Laboratory examination revealed a normal serum chemistry profile. Lumbar puncture revealed an elevated protein (252 mg/dl), but otherwise normal. An electroencephalogram (EEG) (awake and sleeping) revealed mild, nonspecific slowing. Both magnetic resonance imaging (MRI) and computed tomography (CT) of the head were interpreted as normal. Neurology consultation concluded abnormal tics and vocalizations of uncertain etiology and a presumptive diagnosis of encephalopathy associated with HIV infection. Mr. L met diagnostic criteria for HIV-related encephalopathy with an associated tic disorder characterized by both a motor and vocal component. Normal radiographic examination and nonspecific EEG findings were not sufficient evidence, in view of this patient’s clinical exam, to rule out HIVrelated brain involvement. However, these findings coupled with his history, clinical presentation, and elevated cerebrospinal fluid (CSF) protein were consistent with general findings in HIV brain disease [3]. As this patient’s presentation was more consistent with apathy associated with encephalopathy rather than major depression, his imipramine was discontinued. Because he had failed previous trials of haloperidol and was reluctant to try other neuroleptics, he was begun on a trial of clonazepam 0.5 mg/day. Within 1 week he reported feeling less anxious and reported mild subjective improvement in his motor tics but no improvement in his vocal tics. Although a trial of clonidine, an alphaadrenergic blocking agent used to treat Tourette’s syndrome [8], was planned, it was not instituted due to frequent orthostasis. The patient rapidly became more physically and mentally impaired and is currently receiving hospice care.
presentation remains complex. The encephalopathy associated with HIV is primarily thought to be subcortical [4]. Although there remains some disagreement as to which specific neural regions serve as the primary sites for HIV-related neuropathology, neuroimaging procedures have documented significant subcortical involvement [7]. Positron emission tomography has specifically shown basal ganglion and thalamic glucose hypermetabolism in the initial stages of HIV infection [7]. Further, clinical presentations of advanced HIV encephalopathy have consisted of a variety of motor abnormalities resembling such subcortical dementias as Huntington’s and Parkinson’s disease. This patient’s presentation was most significant for his involuntary motor and vocal tics in the absence of other movement abnormalities or ataxia. Generally, tic disorders are diagnosed in childhood or adolescence and are not frequently seen in adult cases of neuropsychiatric abnormalities. Although a number of neurochemical systems have been implicated in tic disorders, the strongest evidence supports the role of dopaminerigic systems in the pathophysiology [8]. Therefore, conditions, like HIV infection, which primarily affect subcortical structures rich in dopamine pathways, could feasibly yield transient tics. Dopamine antagonists, primarily haloperidol, have been utilized in the treatment of tic disorders, especially Tourette’s syndrome. Unfortunately, this medication did not prove effective for this patient. Pimozide, another potent neuroleptic frequently used to treat Tourette’s syndrome [9], was not instituted because of previous neuroleptic failure. The patient initially was begun on clonazepam to alleviate his anxiety and monitor any effects on his tics. As tics are known to emerge in susceptible children during periods of increased anxiety, the improvement in this patient’s tics may be related to the anxiolytic effects of clonazepam. Although other medication trials such as pimozide or clonidine were not possible in this patient, they are clearly alternative therapies. Such therapies should be considered as psychiatrists see increasing numbers of HIV seropositive patients with central nervous system involvement.
This case suggests the need for psychiatrists to remain curious as we assume more responsibility in the management of HIV seropositive patients. Though HIV encephalopathy has long been a known complication of HIV infection, its clinical
J. Stephen McDaniel, M.D. Mary B. Summerville, Ph.D. Emory University School of Medicine, Grady Health System Infectious Disease Program, Department of Psychiatry and Behavioral Sciences, Atlanta, Georgia
Letter to the Editor
References 1. Ho DD, Rota TR, Schooley RT, et al: Isolation of
2. 3. 4. 5.
HTLV-III from cerebrospinal fluid and neural tissues in patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med 313:14781484, 1985 Grant I: The neuropsychiatry of human immunodeficiency virus. Semin Neurol 10(3):267-275, 1990 Perry SW: Organic mental disorders caused by HIV; update on early diagnosis and treatment. Am J Psychiatry 147~696710, 1990 Van Gorp WG, Satz P, Hinkin C, Evans G, Miller EN: The neuropsychological aspects of HIV-l spectrum disease. Psychiatr Med 7(2):59-78, 1990 Centers for Disease Control: Revision of the CDC sur-
300
veillance case definitions for acquired immunodeficiency syndrome. MMWR 36 (Suppl l):lS-15S, 1987 Navia BA, Jordan BD, Price RW: The AIDS dementia complex: I. clinical features. Ann Neurol 19:517-524, 1986 Rottenberg D, Moeller J, Strother S, et al: The metabolic pathology of the AIDS dementia complex. Ann Neurol22:700-706, 1987 Williams DT, Pleak R, Hanesian H: Neuropsychiatric disorders of childhood and adolescence. In Hales RE, Yudofsky SC (eds), The American Psychiatric Press Textbook of Neuropsychiatry. Washington, DC, American Psychiatric Press, Inc., 1987, pp 365-386 Leckman, JF, Cohen DJ: Tourette’s disorder and other stereotyped movement disorders. In Cavenar JO (ed), Psychiatry, Vol 238. Philadelphia, J.B. Lippincott, 1988, pp l-8