BIOL PSYCHIATRY 1990;28:551-554
551
CORRESPONDENCE Letters qf 600 words or less, with minimal allowance for tables, figures, a,'ut references, will be considered for publication. Rules regarding prior publication, conflict of interest, etc., are the same as for fuU manuscripts. All letters are subject to editing and condensation. Proofs will not be distribe;ed.
EPS, NMS, and AIDS To the Editor: Psychosis may be a frequent and early complication of AIDS. Potential causes of psychosis in AIDS patients include central nervous sys.tem (CNS) infection with the human immunodeficlency virus (HIV) or opportunistic organisms, CNS e:~fects of systemic illness, and an autoimmune proccss "7:ith cerebral involvement (Hoffman 1984). Low dose high potency neuroleptics may help ameliorate psychotic symi3toms (Wolcott etal. 1989). However, such treatment may place patients at increased risk for extrapyramidal side effects (EPS), ~ , . . . . . ~,ted by the ~o,,,,wing case. The patient, a 34-year-old bisexual man, was diagnosed HIV positive in 1986. Three yeats later he began showing symptoms of AIDS: generalized malaise, filtigue, and lymphadenopathy. He developed cytomegalovirus retinitis, herpetic perianal lesions, oroph~xyngeal candidiasis, anemia, and neutropenia. His behavior became increasingly bizarre and .rr,_a~iclike. He was treated with haloperidoi! 2 mE p . o . q . 6 hr. Within 1 week he developed an acute dystonic reaction affecting his eyes (oculogyric crisis) and neck; the dystonia responded promptly to treaanent with intramuscular diphenhydramine 50 rag. However, because he also had a high £ever (103.2 ° F) an3 aj'ff:,.se rigidity, he was admi..+teO to the hospital. Neuroleptic malignant syndrome (NM$) and primary CNS infection were considered in the differential diagnosis. However, multiple cultures of blood, urine, sputum, and cerebrospinal fluid failed te detect the presence of any organism, including Toxoplasma .eondii and Crypt~ coccus neofoi7nans. Computerized brain tomo~raphy _._94 _magnetic resonance imaging of the brain showed mild-to-moderate cortical atrophy. The remainder of the physical and laboratory evaluation was unremarkable. Haloperidol was disco:Jtinued. The patient ~mproved with suppo',five care and treatment with AZI', © 19o0Societyof Biological F~ych~ll'y
antibiotics, and lorazeparn 0.5 nag b.i.d. He was discharged afebrile end without rigidity. The most parsimonious explanation for this patient's neurological symptoms would be neurolepfie-induced parkinsonism and dystonia superimposed on the immunodeficient state. ,Mthough the diagnosis of NMS wa:i considered, based on the presence of hypertherraia, rigidity, and change, in mental status, this constellation of symptoms may also be found in advanced AIDS patients never treated with neurolepfics (Burch and Mc)ntoya 1989). As Levinson end Simpson (1986) have pointed out, NM~ may be difficult to validate whet, other known causes of fever and EPS coincide with the administratioz; of neuroleptics. Neveaheless, there do appear to be several "true" cases of NMS !npe,tients with AIDS (Breitbart eta!. 1988; Butch and Montoya 1989). A variety of ~onormal movements and seve.re EPS have been rel~rted in AIDS patients doting therapy with i:euroleptic and nonneuroleptic dopamine blocking agents (He!!~nder et ~. 1965; Edelstein and Knight 1987: Nath et al. •~ o..o,j. Q ~ x NM3 has also occurred in other patients who were possibly predisposed on the basis of non-HIV viral illnesses (Chaimowitz et al. 1988; Price et ai. 1OSO). It is not clear why AIDS patients appear to be more susceptible to EPS, although it is believed that patients with organic brain syndromes in general are at increased risk for NMS (Lazarus etal. 1989). HIV is directly neurotoxic, affecting primarily the white matter and subcortical structures, with relative sparing Gf tbe codex (Navia et ai. i986). The early appearance of neuropsychiatric disturbances in AIDS patients suggests a particular vulnerability of dopaminergic systems in this condition. Arthur Lazarus Philadelphia Psychiatric Center Philadelphia, PA 1913 !
0096-3223/90/$03.50
552
BIOL PSYCHIATRY 1990;28:551-5:~4
References
Correspondence
Malignant Syndrome and Related Conditions. Washington DC: American Psychiatric Press.
Breitbart W, Marotta RF, Call P (!988): MDS and neuroleptic malignant syndrome. Lancet ii:1488-1489. Burch EA Jr, Montoya J (1989): Neuroleptic malignant syndrome in an AIDS patient. J Clin Psychopharmacol 9:228-229. Chaimowitz GA, Gomes U, Maze SS 0988): Neurc~leptic malignant syndrome. Can Med Assoc J 138:51-53. Edelstein H, Knight RT (1987): Severe parkinsonism in two AIDS patients taking prochlorpromazine. Lancet ii:341342. HoffmanRS (1984): Neuropsychiatriccomplicationsof AIDS. Psychosomatics 25:393-400. Hollander H, Golden J, Mendelson T, et al. (1985): Extrapyramidal symptoms in AIDS patients given low-dose metoclopramide or chlorpromazine. Lancet ii:1186. Lazarus A, Mann SC, Caroff SN (1989): The Neuroleptic
Levinson DF, Simpson GM (1986): Neuroleptic-induced extrapyramidal symptoms with fever: Heterogeneity of the "neuroleptic malignant syndrome." Arch Gen Psy. chiatry 43:839-848.
Excitato~ _Amino Acids and Schizophrenia
mission is ~ble to return to its previous level ,of functioning, and the process is completed. This psychotic episode is called a "schizop,hreniform reaction." In more severe cases, the dysfunction becomes progressive and c.hronic and results in the actual degeneration of the striatal and other neurons. Negative symptoms occth- when the degeneration becomes extensive and when the mesocortical dopamine system is involved. But then, how could this cessation of function and actual degeneration have ~curred? The recent studies on the NMDA receptors could provi0e the clues. The excitatory amino acids (EAA) are the most abundantly found neu~ransmi~ers in the brain. The EAA pathways have been delineated ~ d include the cortico-cortical, conico-fu~al, and sensory systems. .Activity o! the NMDA receptors of the EAA are found to be responsible for plasticity in the developing and matu~ CNS and long-term potentiation (LTP) in the hippocamlms. In the event of prolonged and excessive stimulation, excitotoxicity comes into play when there is too much glutamate and too much c.~cium. Whgn the neurons are briefly exposed to glma.'natc, the cells swell transiently and then go on to recover. But when influx of calcium also occurs, the cells slowly degenerate. The cortico-fugal pathways run from the cortex to the basal ganglia (caudate/putamen and nucleus accumbens), the hippocampus, and other pars of the
To the Editor: Dr. Olney (Biol Psychiatry 26:565-525) suggested a link between hypofunction ~f the glutamate transmitter system and psychotic process. I ~,ish to propose here that an interaction between the glutamate and dopamine systems might be involved in the pathogenesis of schizophrenia. There are positive and negative symptoms in schizophrenia. Current findings ~,uggest that positive symp!oms are related to the hyperactivity of the dopamine system. In chronic schizophrenia, when negative symptoms prevail, ventricular dilatation and degeneration m me basal ganglia and the medial temporal lobe structures are reported, based on ~hes~ findings, a unitary theory on the etiology of schizophrenia can be formulated as follows. Some individuals are genetically determined to have weak and ~uinerable dopan-,ine systems. When subjected to stress, some of the neurons on which dophminerg~c afferems make synaptic contact cease to function. To compensate for the loss, the dopamine fibers give off additional nerve terminals ~u~d for:n new D2 receptors~ This ove.rreaction gives rise to a relative increase :n dopaminergic activity and manifests itself as the positive symptoms of schizophrenia. In mild cases, th~ dy~function is self-limiting and the dopaminergic trans-
Nath A, Iankovic J, Pettigrew LC (1987): Movement disorders and AIDS. Neurology 37:37-41. Navia BA, Cho ES, Pefito CK, et al. (1986): The AIDS dementia complex. If: Neuropathology. Ann Neurol 19:525-535. Price DK, Tumhnli Gi, Gregory RP, et aL (1989): Neuroleptic malignant syndrome in a case of post-partum psychosis. Br J Psychiatry 155:849-852. Wolcott DL, Fawzy FI, Namir S (1989): Clinical management of psychiatric disorders in HIV spectrum disease. Psychiatr Med 7:107-127.
551
CORRESPONDENCE Letters qf 600 words or less, with minimal allowance for tables, figures, a,'ut references, will be considered for publication. Rules regarding prior publication, conflict of interest, etc., are the same as for fuU manuscripts. All letters are subject to editing and condensation. Proofs will not be distribe;ed.
EPS, NMS, and AIDS To the Editor: Psychosis may be a frequent and early complication of AIDS. Potential causes of psychosis in AIDS patients include central nervous sys.tem (CNS) infection with the human immunodeficlency virus (HIV) or opportunistic organisms, CNS e:~fects of systemic illness, and an autoimmune proccss "7:ith cerebral involvement (Hoffman 1984). Low dose high potency neuroleptics may help ameliorate psychotic symi3toms (Wolcott etal. 1989). However, such treatment may place patients at increased risk for extrapyramidal side effects (EPS), ~ , . . . . . ~,ted by the ~o,,,,wing case. The patient, a 34-year-old bisexual man, was diagnosed HIV positive in 1986. Three yeats later he began showing symptoms of AIDS: generalized malaise, filtigue, and lymphadenopathy. He developed cytomegalovirus retinitis, herpetic perianal lesions, oroph~xyngeal candidiasis, anemia, and neutropenia. His behavior became increasingly bizarre and .rr,_a~iclike. He was treated with haloperidoi! 2 mE p . o . q . 6 hr. Within 1 week he developed an acute dystonic reaction affecting his eyes (oculogyric crisis) and neck; the dystonia responded promptly to treaanent with intramuscular diphenhydramine 50 rag. However, because he also had a high £ever (103.2 ° F) an3 aj'ff:,.se rigidity, he was admi..+teO to the hospital. Neuroleptic malignant syndrome (NM$) and primary CNS infection were considered in the differential diagnosis. However, multiple cultures of blood, urine, sputum, and cerebrospinal fluid failed te detect the presence of any organism, including Toxoplasma .eondii and Crypt~ coccus neofoi7nans. Computerized brain tomo~raphy _._94 _magnetic resonance imaging of the brain showed mild-to-moderate cortical atrophy. The remainder of the physical and laboratory evaluation was unremarkable. Haloperidol was disco:Jtinued. The patient ~mproved with suppo',five care and treatment with AZI', © 19o0Societyof Biological F~ych~ll'y
antibiotics, and lorazeparn 0.5 nag b.i.d. He was discharged afebrile end without rigidity. The most parsimonious explanation for this patient's neurological symptoms would be neurolepfie-induced parkinsonism and dystonia superimposed on the immunodeficient state. ,Mthough the diagnosis of NMS wa:i considered, based on the presence of hypertherraia, rigidity, and change, in mental status, this constellation of symptoms may also be found in advanced AIDS patients never treated with neurolepfics (Burch and Mc)ntoya 1989). As Levinson end Simpson (1986) have pointed out, NM~ may be difficult to validate whet, other known causes of fever and EPS coincide with the administratioz; of neuroleptics. Neveaheless, there do appear to be several "true" cases of NMS !npe,tients with AIDS (Breitbart eta!. 1988; Butch and Montoya 1989). A variety of ~onormal movements and seve.re EPS have been rel~rted in AIDS patients doting therapy with i:euroleptic and nonneuroleptic dopamine blocking agents (He!!~nder et ~. 1965; Edelstein and Knight 1987: Nath et al. •~ o..o,j. Q ~ x NM3 has also occurred in other patients who were possibly predisposed on the basis of non-HIV viral illnesses (Chaimowitz et al. 1988; Price et ai. 1OSO). It is not clear why AIDS patients appear to be more susceptible to EPS, although it is believed that patients with organic brain syndromes in general are at increased risk for NMS (Lazarus etal. 1989). HIV is directly neurotoxic, affecting primarily the white matter and subcortical structures, with relative sparing Gf tbe codex (Navia et ai. i986). The early appearance of neuropsychiatric disturbances in AIDS patients suggests a particular vulnerability of dopaminergic systems in this condition. Arthur Lazarus Philadelphia Psychiatric Center Philadelphia, PA 1913 !
0096-3223/90/$03.50
552
BIOL PSYCHIATRY 1990;28:551-5:~4
References
Correspondence
Malignant Syndrome and Related Conditions. Washington DC: American Psychiatric Press.
Breitbart W, Marotta RF, Call P (!988): MDS and neuroleptic malignant syndrome. Lancet ii:1488-1489. Burch EA Jr, Montoya J (1989): Neuroleptic malignant syndrome in an AIDS patient. J Clin Psychopharmacol 9:228-229. Chaimowitz GA, Gomes U, Maze SS 0988): Neurc~leptic malignant syndrome. Can Med Assoc J 138:51-53. Edelstein H, Knight RT (1987): Severe parkinsonism in two AIDS patients taking prochlorpromazine. Lancet ii:341342. HoffmanRS (1984): Neuropsychiatriccomplicationsof AIDS. Psychosomatics 25:393-400. Hollander H, Golden J, Mendelson T, et al. (1985): Extrapyramidal symptoms in AIDS patients given low-dose metoclopramide or chlorpromazine. Lancet ii:1186. Lazarus A, Mann SC, Caroff SN (1989): The Neuroleptic
Levinson DF, Simpson GM (1986): Neuroleptic-induced extrapyramidal symptoms with fever: Heterogeneity of the "neuroleptic malignant syndrome." Arch Gen Psy. chiatry 43:839-848.
Excitato~ _Amino Acids and Schizophrenia
mission is ~ble to return to its previous level ,of functioning, and the process is completed. This psychotic episode is called a "schizop,hreniform reaction." In more severe cases, the dysfunction becomes progressive and c.hronic and results in the actual degeneration of the striatal and other neurons. Negative symptoms occth- when the degeneration becomes extensive and when the mesocortical dopamine system is involved. But then, how could this cessation of function and actual degeneration have ~curred? The recent studies on the NMDA receptors could provi0e the clues. The excitatory amino acids (EAA) are the most abundantly found neu~ransmi~ers in the brain. The EAA pathways have been delineated ~ d include the cortico-cortical, conico-fu~al, and sensory systems. .Activity o! the NMDA receptors of the EAA are found to be responsible for plasticity in the developing and matu~ CNS and long-term potentiation (LTP) in the hippocamlms. In the event of prolonged and excessive stimulation, excitotoxicity comes into play when there is too much glutamate and too much c.~cium. Whgn the neurons are briefly exposed to glma.'natc, the cells swell transiently and then go on to recover. But when influx of calcium also occurs, the cells slowly degenerate. The cortico-fugal pathways run from the cortex to the basal ganglia (caudate/putamen and nucleus accumbens), the hippocampus, and other pars of the
To the Editor: Dr. Olney (Biol Psychiatry 26:565-525) suggested a link between hypofunction ~f the glutamate transmitter system and psychotic process. I ~,ish to propose here that an interaction between the glutamate and dopamine systems might be involved in the pathogenesis of schizophrenia. There are positive and negative symptoms in schizophrenia. Current findings ~,uggest that positive symp!oms are related to the hyperactivity of the dopamine system. In chronic schizophrenia, when negative symptoms prevail, ventricular dilatation and degeneration m me basal ganglia and the medial temporal lobe structures are reported, based on ~hes~ findings, a unitary theory on the etiology of schizophrenia can be formulated as follows. Some individuals are genetically determined to have weak and ~uinerable dopan-,ine systems. When subjected to stress, some of the neurons on which dophminerg~c afferems make synaptic contact cease to function. To compensate for the loss, the dopamine fibers give off additional nerve terminals ~u~d for:n new D2 receptors~ This ove.rreaction gives rise to a relative increase :n dopaminergic activity and manifests itself as the positive symptoms of schizophrenia. In mild cases, th~ dy~function is self-limiting and the dopaminergic trans-
Nath A, Iankovic J, Pettigrew LC (1987): Movement disorders and AIDS. Neurology 37:37-41. Navia BA, Cho ES, Pefito CK, et al. (1986): The AIDS dementia complex. If: Neuropathology. Ann Neurol 19:525-535. Price DK, Tumhnli Gi, Gregory RP, et aL (1989): Neuroleptic malignant syndrome in a case of post-partum psychosis. Br J Psychiatry 155:849-852. Wolcott DL, Fawzy FI, Namir S (1989): Clinical management of psychiatric disorders in HIV spectrum disease. Psychiatr Med 7:107-127.
