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Clinical course of subacute HIV encephalitis
Journal of Neuroimmunology, 20 (1988) 145-147
145
Elsevier JNI 00671
Clinical course of subacute HIV encephalitis A.A. M~511er, T. Gasser, H. J~iger a n d A. H e d l Max-Planck-Institute of Psychiatry, D-8000 Munich 40, F.R.G.
(Received 29 June 1988) (Accepted 1 July 1988) Key words: Human immunodeficiencyvirus, infection; Encephalitis, clinical course, cofactors
Summary A subacute encephalitis is increasingly recognized to be the most frequent cerebral manifestation of human immunodeficiency virus (HIV) infection. Contradictory reports are given in the literature concerning its clinical course. In the present study, a group of 19 patients with subacute encephalitis was followed for an average of 210 days. A steady progression of the disease was documented using the Karnofsky index. An advanced disease, rated according to the Walther Reed staging classification, but not isolated immunological parameters such as the ratio of O K T 4 / 8 subsets are associated with more rapid progression of the encephalitis. Age, social status, duration of HIV positivity and antibody titers to cytomegalovirus could not be identified as contributing factors.
Introduction
Clinical and epidemiological studies indicate that the clinical course of patients with serologically confirmed human immunodeficiency virus (HIV) infection is highly variable. Even after progression of the disease to the full-blown syndrome of acquired immune deficiency (AIDS), prognosis varies and survival times of more than 5 years have recently been reported (Rothenberg et al., 1987). Polk et al. (1987) identified a decrease in T-helper cells, an increase in T-suppressor cells, a low titer of anti-HIV antibodies and a high titer of antibodies to cytomegalovirus as indicators of a poor prognosis with respect to the development of full-blown AIDS. A subacute encephalitis (SE)
Address for correspondence,A.A. Mt~ller, Max-Planck-Institute of Psychiatry, Kraepelinstr! 10, D-8000 Munich 40, F.R.G.
with a predominance of cognitive deficits and a paucity of neurological abnormalities is found in many patients, the course of which is also variable according to the literature. Snider et al. (1983) reported that 'deterioration progressed over weeks to months', Kesselring (1986) describes the clinical course as 'slowly progressive' and rarely 'remitting'. Navia and Price (1987) found a deterioration of neurological and psychopathological findings in the course of 2 months to more than one year. Results
In a prospective study, 45 patients were examined repeatedly over a period of 54-489 days (mean 210 days). In 19 patients, a subacute HIV encephalitis was diagnosed according to the fol; lowing criteria: - persistent complaints of headache, fatigue, disturbance of concentration or memory of at least 4 weeks duration;
0165-5728/88/$03.50 © 1988 ElsevierSciencePublishers B.V. (BiomedicalDivision)
146
- repeated documentation of generalized slowing of EEG recordings without focal changes; - d o c u m e n t a t i o n of unremarkable findings or cerebral atrophy on cranial computerized tomography without focal lesions; - lack of focal deficits on neurological examination at the time of entry into the study; - documentation of psychopathological changes including psychomotor slowing and disturbance of memory and concentration by clinical psychiatric examination. The age of patients with HIV encephalitis was 34.6 + 7.5 years, ranging from 23 to 47 years. All patients were male, 16 were homosexual, three admitted to i.v. drug abuse. All of them were seen on an out-patient basis at the time of diagnosis. Patients with opportunistic infections of the central nervous system during the follow-up period were excluded from the study. The clinical course of the disease was documented using the Karnofsky index, grading global disability on a 0-100 rating scale (0 represents death, 100 no complaints). Only neurological and psychopathological symptoms were included for evaluation of disability. On follow-up examination, a steady decline of the Karnofsky index was observed (Fig. 1). However, the rate of progression was highly variable, as indicated by the marked increase of the standard deviation on follow-up examination.
KI 100-
50-
;8_* 27,5
\
TABLE 1 POSSIBLE P R E D I C T O R S O F T H E C L I N I C A L C O U R S E O F S U B A C U T E HIV E N C E P H A L I T I S Patients were grouped according to the Karnofsky index (KI) on follow-up examination and possible predictive parameters obtained on the initial examination were assessed separately for patients with a more favorable (KI > ~) and unfavorable (KI < ~) outcome. KI>X Age(years) Social class (0-4) O K T 4 / 8 ratio W R a stage Duration of HIV positivity (months) C M V b IgG (median of reciprocal titer)
39.5 + 2.3 + 0.51+ 4.3 +
21
5000
KI<~ 7.8 1.2 0.33 1.5
± 14
34.1 + 2.6 + 0.22+ 5.6 ±
23
7.9 0.9 0.16 0.8 *
± 10
5000
a Walter Reed staging classification. b Cytomegalovirus. * Significant difference ( M a n n - W h i t n e y U-test).
In order to delineate possible parameters predicting the course of the disease, patients were separated into two groups of equal size according to the rate of clinical deterioration as measured by the Karnofsky index, at the time of follow-up examination. Age, duration of HIV seropositivity, T 4 / T 8 ratio, clinical staging according to the Walter Reed staging classification and titers of antibodies (IgG) to cytomegalovirus at the time of entry into the study were retrospectively assessed separately for both groups (Table 1). The group of patients with a more rapid decline of the Karnofsky index had, at the time of entry, more advanced disease as rated by the Walter Reed staging classification. Age, duration of HIV positivity and anti-cytomegalovirus titer were not found to differ significantly between groups. Cytomegalovirus titers were not found to differ significantly between groups.
21±19,8
Discussion 90 -'180 d
t80-360 d
t
Fig. 1. Clinical course of 19 patients with subacute HIV encephalitis documented by the Karnofsky index (KI). M e a n and standard deviation are given.
The role of various cofactors modifying the risk of HIV infection and the development of the full clinical picture of AIDS after seroconversion has
147 been discussed in the literature (Broder, 1987). Variations between different high risk groups, a difference in virulence between different strains of the virus, genetic factors or pre-existing chronic disease damaging the immune system have been implicated. Likewise, according to the literature, the course of the subacute HIV encephalitis, the most frequent cerebral manifestation of the disease, is highly variable. The present prospective study was conducted in cooperation with a medical out-patient unit. During the follow-up period, clinical deterioration was continuous as assessed by the Karnofsky index. N o remission of symptoms was observed. The rate of disease progression was variable, indicated by an increase in variance of Karnofsky index ratings later in the follow-up period. Age, duration of HIV positivity, antibody titers against cytomegalovirus and the ratio of helper/suppressor T-cell subsets could not be identified as predictors of the rate of clinical deterioration. However, advanced stages of the disease, as measured by a combined immunological and clinical rating scale, the Walter Reed staging classification, are associated with a poorer prognosis with respect to
the progression comparison of groups was not vast majority of
of the encephalitic symptoms. A members of different high risk possible in this study, since the our patients were homosexuals.
References Broder, S, (1987) AIDS. Marcel Dekker, New York - Basel. Fischer, P.-A. and Enzensberger, W. (1987) Neurological complications in AIDS. J. Neurol. 234, 269-279. Kesselring, J. (1986) Neurologische Manifestationen beim erworbenen Immundefektsyndrom. Dtsch. Med. Wschr. 111, 1068-1073. Navia, B.A. and Price, R.W. (1987) The acquired immunodeficiency syndrome dementia complex as the presenting or sole manifestation of HIV infection. Arch. Neurol. 44, 65-69. Polk, B.F., Fox, R. et al. (1987) Predictors of the acquired immunodeficiency'syndrome developing in a cohort of seropositive homosexual men. New Engl. J. Med. 316, 61-66. Rothenberg, R., Woelfel, M. et al. (1987) Survival with the acquired iramunodeficiency syndrome. New Engl. J. Med. 317, 1297-1302. Snider, W.D., Simpson, D.M. et al. (1983) Neurological eomphcations of acquired immune deficiency syndrome. Ann. Neurol. 14, 403-418.
145
Elsevier JNI 00671
Clinical course of subacute HIV encephalitis A.A. M~511er, T. Gasser, H. J~iger a n d A. H e d l Max-Planck-Institute of Psychiatry, D-8000 Munich 40, F.R.G.
(Received 29 June 1988) (Accepted 1 July 1988) Key words: Human immunodeficiencyvirus, infection; Encephalitis, clinical course, cofactors
Summary A subacute encephalitis is increasingly recognized to be the most frequent cerebral manifestation of human immunodeficiency virus (HIV) infection. Contradictory reports are given in the literature concerning its clinical course. In the present study, a group of 19 patients with subacute encephalitis was followed for an average of 210 days. A steady progression of the disease was documented using the Karnofsky index. An advanced disease, rated according to the Walther Reed staging classification, but not isolated immunological parameters such as the ratio of O K T 4 / 8 subsets are associated with more rapid progression of the encephalitis. Age, social status, duration of HIV positivity and antibody titers to cytomegalovirus could not be identified as contributing factors.
Introduction
Clinical and epidemiological studies indicate that the clinical course of patients with serologically confirmed human immunodeficiency virus (HIV) infection is highly variable. Even after progression of the disease to the full-blown syndrome of acquired immune deficiency (AIDS), prognosis varies and survival times of more than 5 years have recently been reported (Rothenberg et al., 1987). Polk et al. (1987) identified a decrease in T-helper cells, an increase in T-suppressor cells, a low titer of anti-HIV antibodies and a high titer of antibodies to cytomegalovirus as indicators of a poor prognosis with respect to the development of full-blown AIDS. A subacute encephalitis (SE)
Address for correspondence,A.A. Mt~ller, Max-Planck-Institute of Psychiatry, Kraepelinstr! 10, D-8000 Munich 40, F.R.G.
with a predominance of cognitive deficits and a paucity of neurological abnormalities is found in many patients, the course of which is also variable according to the literature. Snider et al. (1983) reported that 'deterioration progressed over weeks to months', Kesselring (1986) describes the clinical course as 'slowly progressive' and rarely 'remitting'. Navia and Price (1987) found a deterioration of neurological and psychopathological findings in the course of 2 months to more than one year. Results
In a prospective study, 45 patients were examined repeatedly over a period of 54-489 days (mean 210 days). In 19 patients, a subacute HIV encephalitis was diagnosed according to the fol; lowing criteria: - persistent complaints of headache, fatigue, disturbance of concentration or memory of at least 4 weeks duration;
0165-5728/88/$03.50 © 1988 ElsevierSciencePublishers B.V. (BiomedicalDivision)
146
- repeated documentation of generalized slowing of EEG recordings without focal changes; - d o c u m e n t a t i o n of unremarkable findings or cerebral atrophy on cranial computerized tomography without focal lesions; - lack of focal deficits on neurological examination at the time of entry into the study; - documentation of psychopathological changes including psychomotor slowing and disturbance of memory and concentration by clinical psychiatric examination. The age of patients with HIV encephalitis was 34.6 + 7.5 years, ranging from 23 to 47 years. All patients were male, 16 were homosexual, three admitted to i.v. drug abuse. All of them were seen on an out-patient basis at the time of diagnosis. Patients with opportunistic infections of the central nervous system during the follow-up period were excluded from the study. The clinical course of the disease was documented using the Karnofsky index, grading global disability on a 0-100 rating scale (0 represents death, 100 no complaints). Only neurological and psychopathological symptoms were included for evaluation of disability. On follow-up examination, a steady decline of the Karnofsky index was observed (Fig. 1). However, the rate of progression was highly variable, as indicated by the marked increase of the standard deviation on follow-up examination.
KI 100-
50-
;8_* 27,5
\
TABLE 1 POSSIBLE P R E D I C T O R S O F T H E C L I N I C A L C O U R S E O F S U B A C U T E HIV E N C E P H A L I T I S Patients were grouped according to the Karnofsky index (KI) on follow-up examination and possible predictive parameters obtained on the initial examination were assessed separately for patients with a more favorable (KI > ~) and unfavorable (KI < ~) outcome. KI>X Age(years) Social class (0-4) O K T 4 / 8 ratio W R a stage Duration of HIV positivity (months) C M V b IgG (median of reciprocal titer)
39.5 + 2.3 + 0.51+ 4.3 +
21
5000
KI<~ 7.8 1.2 0.33 1.5
± 14
34.1 + 2.6 + 0.22+ 5.6 ±
23
7.9 0.9 0.16 0.8 *
± 10
5000
a Walter Reed staging classification. b Cytomegalovirus. * Significant difference ( M a n n - W h i t n e y U-test).
In order to delineate possible parameters predicting the course of the disease, patients were separated into two groups of equal size according to the rate of clinical deterioration as measured by the Karnofsky index, at the time of follow-up examination. Age, duration of HIV seropositivity, T 4 / T 8 ratio, clinical staging according to the Walter Reed staging classification and titers of antibodies (IgG) to cytomegalovirus at the time of entry into the study were retrospectively assessed separately for both groups (Table 1). The group of patients with a more rapid decline of the Karnofsky index had, at the time of entry, more advanced disease as rated by the Walter Reed staging classification. Age, duration of HIV positivity and anti-cytomegalovirus titer were not found to differ significantly between groups. Cytomegalovirus titers were not found to differ significantly between groups.
21±19,8
Discussion 90 -'180 d
t80-360 d
t
Fig. 1. Clinical course of 19 patients with subacute HIV encephalitis documented by the Karnofsky index (KI). M e a n and standard deviation are given.
The role of various cofactors modifying the risk of HIV infection and the development of the full clinical picture of AIDS after seroconversion has
147 been discussed in the literature (Broder, 1987). Variations between different high risk groups, a difference in virulence between different strains of the virus, genetic factors or pre-existing chronic disease damaging the immune system have been implicated. Likewise, according to the literature, the course of the subacute HIV encephalitis, the most frequent cerebral manifestation of the disease, is highly variable. The present prospective study was conducted in cooperation with a medical out-patient unit. During the follow-up period, clinical deterioration was continuous as assessed by the Karnofsky index. N o remission of symptoms was observed. The rate of disease progression was variable, indicated by an increase in variance of Karnofsky index ratings later in the follow-up period. Age, duration of HIV positivity, antibody titers against cytomegalovirus and the ratio of helper/suppressor T-cell subsets could not be identified as predictors of the rate of clinical deterioration. However, advanced stages of the disease, as measured by a combined immunological and clinical rating scale, the Walter Reed staging classification, are associated with a poorer prognosis with respect to
the progression comparison of groups was not vast majority of
of the encephalitic symptoms. A members of different high risk possible in this study, since the our patients were homosexuals.
References Broder, S, (1987) AIDS. Marcel Dekker, New York - Basel. Fischer, P.-A. and Enzensberger, W. (1987) Neurological complications in AIDS. J. Neurol. 234, 269-279. Kesselring, J. (1986) Neurologische Manifestationen beim erworbenen Immundefektsyndrom. Dtsch. Med. Wschr. 111, 1068-1073. Navia, B.A. and Price, R.W. (1987) The acquired immunodeficiency syndrome dementia complex as the presenting or sole manifestation of HIV infection. Arch. Neurol. 44, 65-69. Polk, B.F., Fox, R. et al. (1987) Predictors of the acquired immunodeficiency'syndrome developing in a cohort of seropositive homosexual men. New Engl. J. Med. 316, 61-66. Rothenberg, R., Woelfel, M. et al. (1987) Survival with the acquired iramunodeficiency syndrome. New Engl. J. Med. 317, 1297-1302. Snider, W.D., Simpson, D.M. et al. (1983) Neurological eomphcations of acquired immune deficiency syndrome. Ann. Neurol. 14, 403-418.