Postgrad Med J: first published as 10.1136/pgmj.64.749.180 on 1 March 1988. Downloaded from Postgraduate Medical Journal (1988) 64, 180-187 Review Article Neurological complications of human immunodeficiency virus infection Peter G.E. Kennedy Glasgow University Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, UK. Summary: The protean neurological manifestations of human immunodeficiency virus (HIV) infection are reviewed. Both the central nervous system and peripheral nervous system may be affected and many of the complications may occur in individuals with acquired immunodeficiency syndrome (AIDS)-related complex, or who are seropositive for HIV alone as well as those with the established AIDS syndrome. Specific therapy is available for certain of these neurological conditions, but the clinical course in others is untreatable and progressive. Although it seems likely that the pathogenesis of some of these syndromes such as the AIDS-dementia complex are due to the direct effect of HIV on the nervous system, in others the neurological injury probably occurs as a consequence of the immunosuppression which HIV induces, or immune-mediated mechanisms. Introduction copyright. Human immunodeficiency virus (HIV) is the AIDS-dementia complex if only mildly affected causative retroviral agent of the acquired immuno- patients are included.7 Our own experience in deficiency syndrome (AIDS). Previously known as Glasgow (Kennedy et al., in preparation) is in lymphadenopathy-associated virus (LAV)1 or agreement with a high incidence of neurological human T-lymphotropic virus III (HTLV-III)2, the complications, and the picture will become clearer term HIV has now gained widespread acceptance. with time and when more autopsy examinations are Neurological involvement in AIDS is common. In carried out on patients dying with AIDS. early studies from New York and San Francisco it The spectrum of neurological disease occurring http://pmj.bmj.com/ appeared that 30-40% of patients with AIDS in AIDS patients is very wide. The CNS is most became neurologically symptomatic during their frequently affected but a number of peripheral illness,3'4 and approximately 10% of patients nervous system (PNS) syndromes have also been presented with neurological symptoms.4 However, recognized. There appear to be at least two general neuropathological evidence of involvement of the pathogenetic mechanisms of infectious disease of the central nervous system (CNS) has indicated that CNS in AIDS, namely, direct involvement of HIV 55-80% of patients dying with AIDS have in some conditions, and in others opportunistic on September 26, 2021 by guest. Protected pathological abnormalities in their CNS.4'5'6 More infections with organisms that do not usually cause recent clinical studies have indicated that neuro- disease in normal immunocompetent individuals logical involvement in AIDS is indeed more occur. These organisms appear to become patho- common than previously thought with two-thirds of genic in AIDS patients as a result of the immuno- patients having some kind of neurological suppressive state which the virus induces. HIV abnormality, in particular evidence of the AIDS- causes a severe defect in cell-mediated immune dementia complex.7 The estimated percentage of mechanisms through its selective infection of the T patients with CNS involvement depends also on the helper lymphocyte population8 which plays a severity of the symptoms. For example, as many as central role in the immune response. These two 90% of individuals probably have evidence of the mechanisms of neurological damage are not mutually exclusive and in some cases both HIV and Correspondence: Professor P.G.E. Kennedy, M.D., Ph.D., opportunistic organisms such as cytomegalovirus M.R.C.P. (CMV) may be pathogenic. In other cases more Accepted: 15 October 1987 than one opportunistic infection, e.g., CMV and © The Fellowship of Postgraduate Medicine, 1988 Postgrad Med J: first published as 10.1136/pgmj.64.749.180 on 1 March 1988. Downloaded from NEUROLOGICAL COMPLICATIONS OF HIV INFECTION 181 herpes simplex virus (HSV) may operate.9 An termed the 'AIDS-dementia complex'.'0 This is now additional factor which has emerged over the last recognized as being the commonest neurological few years is that CNS and PNS complications may manifestation of AIDS occurring in at least two occur not only in patients with full-blown AIDS thirds of affected patients,7 and, as has been but also in those with the AIDS-related complex indicated above, the true incidence may be very (ARC), or even asymptomatic individuals who are much greater if mild cases are included. Moreover, only seropositive for HIV.10'11 The long-term nearly 25% of cases with this condition occur in prognosis of such patients remains to be seen but patients with seropositivity for HIV alone or ARC both host and viral factors must almost certainly before the full-blown AIDS syndrome develops.10 interact to produce these heterogeneous patterns of The syndrome is usually progressive over a disease. period of months and the initial complaints are of The following account will provide an overview lethargy, difficulty with concentration and memory of the neurological complications seen in AIDS disturbance. A confusional state including organic patients and will not be limited to infections, psychosis may develop and personality change with although infectious agents including HIV acting general apathy may also be evident. Motor features directly by itself may well prove eventually to be may develop early or later in the illness. The latter implicated in virtually all of these nervous system include weakness, ataxia, tremor, impaired ocular manifestations. Emphasis will be placed on the motility and myoclonus;7 seizures may also occur. more common conditions such as the AIDS- A variety of signs may be detected, slurring of dementia complex. The complications will be motor and verbal responses, hyper-reflexia, frontal considered under four broad groups: (a) infections lobe release signs and the neuropsychological of the CNS, (b) neoplasms, (c) vascular disturbances features of a subcortical dementia being the typical and (d) PNS complications. findings.7 The clinical course is usually relentless, resulting in increasing dementia until the patient is bed-bound and incontinent. Some of the earlier Infections of the CNS (Table I) signs, e.g., frontal lobe abnormalities, may be subtle AIDS-dementia complex and only detected if specifically looked for copyright. (Kennedy et al., in preparation7). In children with Since the early AIDS cases were first encountered it AIDS the progressive encephalopathy may be had been recognized that affected patients were characterized by loss of motor milestones or frequently slow mentally and had difficulty concen- intellectual abilities, secondary microcephaly, trating. These symptoms usually heralded a seizures and myoclonus. 2, 3 progressive dementia which was initially called Neurological investigations may reveal a variety 'subacute encephalitis'4 but has recently been of abnormalities. The cerebrospinal fluid (CSF) usually shows non-specific features such as a mild http://pmj.bmj.com/ Table I Neurological complications of HIV infection- pleocytosis and raised protein. HIV has been CNS complications isolated from the CSF of both patients with the AIDS-dementia complex and those with other CNS (a) Infections syndromes,l4 and locally synthesized HIV-specific AIDS-dementia complex has been detected in CMV encephalitis IgG the CSF in such HSV and VZV encephalitis patients.15 Computed tomographic (CT) scanning Cerebral toxoplasmosis in the AIDS-dementia complex usually shows on September 26, 2021 by guest. Protected Progressive multifocal leukoencephalopathy cortical atrophy with consequent enlargement of Vacuolar myelopathy and myelitis the ventricles,10 sometimes associated with basal Aseptic meningitis ganglion calcification in children.12 In our own Fungal infections experience (Kennedy et al. in preparation) and that Mycobacterial infections of others7 the atrophic changes seen on CT Treponema infection scanning may occur at an early stage of the CMV retinitis dementia. Magnetic resonance imaging (MRI) (b) Neoplasms abnormalities consisting of white matter attenuation Primary CNS lymphoma have also been demonstrated in these patients.7 Systemic CNS lymphoma Characteristic pathological findings in patients Kaposi's sarcoma who have died with the AIDS-dementia complex (c) Vascular include diffuse small areas of focal perivascular Cerebral haemorrhage demyelination in white matter,3 diffuse microglial Cerebral infarction nodules in grey and white matter,4"6 reactive Postgrad Med J: first published as 10.1136/pgmj.64.749.180 on 1 March 1988. Downloaded from 182 P.G.E. KENNEDY astrocytosis,4 focal or diffuse white matter the AIDS-dementia complex although it is possible vacuolation7 and accumulation of perivascular that it may respond to drugs currently being macrophages.4"7 evaluated in AIDS patients such as azido- Earlier studies suggested that CMV may be the thymidine.23 causative agent of the syndrome in view of the characteristic histopathology,4.16 the isolation of Encephalitis due to herpesviruses CMV from some of the patients' brains4 and the demonstration of CMV antigens in brain tissue.13 Encephalitis due to both HSV and varicella-zoster Although it is possible that a true CMV virus (VZV) have been described in patients with encephalitis may indeed occur in AIDS,