Peripheral neuropathies in human immunodeficiency virus infection. A prospective study of 56 patients

Neurologic disorders are common in patients infected with HIV1. Judging from reported cases, the central nervous system would be more frequently involved than the peripheral nervous system (PNS). The purpose of the present prospective study was to ascertain the incidence and the nature of PNS disorders in patients infected with HIV1. Fifty-six patients [asymptomatic carriers: 5; persistent generalized lymphadenopathy (PGL): 13; AIDS related complex (ARC): 9 and acquired immunodeficiency syndrome (AIDS): 29] were submitted to clinical and laboratory investigations and 52 underwent electromyogram and nerve conduction velocity tests. CSF was examined in 29 and nerve biopsies in 28. Our findings showed that a PNS impairment was present in 50/56 patients i.e. 89 p. 100. It was mainly a moderate sensory polyneuropathy, more often at the subclinical (29/50: 58 p. 100) than at the clinical (21/50: 42 p. 100) level. It concerned asymptomatic carriers (2/5) as well as PGL (11/13), ARC (8/9) and AIDS (29/29) patients. These data show that peripheral nerves are a target for HIV1.     

Morphological findings on peripheral nerve biopsies in 15 patients with human immunodeficiency virus infection

Summary A peripheral nerve biopsy was performed in 15 patients with human immunodeficiency virus (HIV) infection and polyneuropathy. Two cases [1 asymptomatic, 1 AIDS-related complex (ARC)] presented with chronic inflammatory demyelinating polyneuropathy; there was 1 case (asymptomatic) of mononeuropathy multiplex and 12 cases (1 asymptomatic, 1 ARC, 10 AIDS) with distal symmetrical polyneuropathy. Epi- or endoneurial microvasculitis was observed in 6 cases. Electron microscopy showed that nerve fiber lesions were mainly axonal. Severe segmental demyelination was also present in both cases of chronic inflammatory demyelinating polyneuropathy, with characteristic features of active demyelination in one. Numerous plasmacytoid cells were found in the endoneurium in 4 patients. Tubuloreticular inclusions were present in endothelial cells in the 10 cases with AIDS but absent in the other patients. Direct immunopathological examination with anti-immunoglobulin sera was negative in all cases. HIV was evidenced by in situ hybridization in 2 AIDS patients; no Epstein-Barr virus or cytomegalovirus was detected.     

Prognostic value of the nervous system involvement in HIV patients

About 30-40% of AIDS patients present CNS and/or PNS involvement, due to direct action of HIV virus or opportunistic infections. Nervous system involvement in the HIV correlated syndromes is not a rare occurrence; nevertheless no studies about prognosis of AIDS related syndromes have been published yet. We tested 38 HIV positive patients for the assessment of neurological complications by means of clinical and instrumental evaluations: multimodal evoked potentials, EMG/ENG studies, nerve and muscle biopsy. At the baseline evaluation, 26/38 patients had neurological complications: 14 of CNS, 9 of PNS, 3 of both CNS and PNS. At follow-up, 16/37 patients had developed AIDS and 10/16 patients with AIDS died. Of these 16 patients, 14 had clinical and neurophysiological alterations at the baseline evaluation. Our results suggest that the presence of clinical and/or neurophysiological nervous system involvement in patients with HIV-related syndromes constitutes a negative prognostic factor for developing AIDS.     

The spectrum of changes on 20 nerve biopsies in patients with HIV infection

Nerve and muscle biopsies were performed on 20 patients with HIV infection and peripheral neuropathy. Nine patients had distal symmetrical peripheral neuropathy (DSPN) (six ARC and three AIDS), six had inflammatory demyelinating polyneuropathy (IDP) (three ARC, one AIDS, and two otherwise asymptomatic patients), one had mononeuropathy multiplex (MM) (AIDS), 1 had mononeuropathy (ARC), one had meningoradiculitis (AIDS), and two had areflexia-associated lymphocytic meningitides (ARC), DSPN exhibited axonal degeneration in four of nine cases and was associated with segmental demyelination in five of nine cases. IDP exhibited segmental demyelination associated with axonal degeneration in four of six cases. Demyelination was more frequent in asymptomatic patients (2 of 2 cases) and in ARC (7 of 12 cases), whereas axonal degeneration was predominant in AIDS (6 of 6 cases). Mononuclear cell infiltration was seen in 1 of 2 asymptomatic patients and in 11 of 12 ARC patients but was exceptionally found in AIDS (1 of 6 cases). Involvement of the walls of small vessels, mostly venules ("subacute microvasculitis"), was found in 1 of 2 asymptomatic patients, in 8 of 12 ARC patients, and never in AIDS. The polyclonal mononuclear cell population was composed mainly of Leu 2 (T8) positive cells in seven cases of ARC. No virions were seen in electron microscopy. HIV was isolated in two cases from the CSF or the nerve biopsy.     

Peripheral neuropathy in the acquired immunodeficiency syndrome

The histopathological and immunopathological features of peripheral neuropathy were investigated in 21 patients with the acquired immunopathological syndrome (AIDS) or AIDS-related complex (ARC). Clinical syndromes observed in the 11 (52%) symptomatic patients included distal symmetrical polyneuropathy (DSPN) and chronic inflammatory demyelinative polyneuropathy (CIDP). Specimens from 19 of 20 patients (95%), both symptomatic and asymptomatic, had histopathological evidence of moderate or severe demyelination (79%), axonal degeneration (36%), and mononuclear cell inflammation (37%). Nerves from patients with CIDP and DSPN showed similar degrees of demyelination and axonal degeneration, but inflammation was more intense in CIDP. Immunohistochemical staining identified the majority of inflammatory cells as T lymphocytes or macrophages, with a predominance of CD8+ cytotoxic/suppressor cells. Diffuse immunostaining for human leukocyte antigen (HLA)-DR was present on endothelial cells, mononuclear inflammatory cells, and Schwann cells, and variable patchy immunostaining for HLA-DR was present on nerve fibers. Control nerve specimens showed staining for HLA-DR limited to endothelial, and a few mononuclear cells. The patterns of immunostaining were similar for AIDS and ARC patients. Human immunodeficiency virus (HIV) was cultured from peripheral nerve in 3 patients, but HIV antigen was not detected by immunohistochemical staining of 8 specimens. The findings implicate HIV infection in nerve, with T cell- and macrophage-mediated tissue destruction as the pathogenetic mechanism of the AIDS/ARC neuropathy.     

The peripheral nervous system and HIV infection. 13 cases

Disorders of the peripheral nervous system occur at all stages of HIV infection. From 13 patients referred for a peripheral neuropathy, 9 were known to be HIV seropositive and 4 were found to be seropositive. All were Caucasian males aged 27 to 58. Ten were homosexual, 2 were drug-addicts. Patients fell into several groups: the first group was made of 5 patients, 4 asymptomatic and 1 AIDS-related-complex (ARC), with an inflammatory demyelinating polyneuropathy, acute in 1 case and subacute in 4; the CSF showed pleiocytosis in all cases. Motor conduction nerve velocities were markedly reduced and motor distal latencies prolonged. Three patients recovered spontaneously, 1 responded to corticosteroids, 1 to plasmapheresis. In the second group, 4 patients, 1 asymptomatic and 3 ARC, had a distal symmetrical polyneuropathy; CSF was normal in 2 cases. Electrophysiological studies and nerve biopsies indicated a mixed axonal-demyelinating polyneuropathy. Three patients recovered spontaneously, 1 is unchanged. Among both groups, an infiltration of mononuclear cells was found on nerve biopsies in 4 cases. The third group was made of 3 patients with AIDS who presented with a painful sensory polyneuropathy involving the distal lower limbs. Electrophysiological and pathological study of the nerve indicated axonal degeneration. No cell infiltration was found. The last patient with AIDS had a progressive meningoradiculopathy. These 4 patients died within 6 months after the onset of the neuropathy. These findings are close to those previously reported, and confirm the wide spectrum of disorders of the peripheral nervous system associated to HIV infection.     

The spectrum of polyneuropathies in patients infected with HIV.

Twenty five patients with peripheral neuropathy at different stages of human immunodeficiency virus (HIV) infection are reported. Cerebrospinal fluid (CSF) findings were available in 17 cases, electrophysiology in all and a neuromuscular biopsy in 11. Of six otherwise asymptomatic HIV+ patients, five had chronic inflammatory demyelinating polyneuropathy (CIDP) and one acute inflammatory demyelinating polyneuropathy (AIDP). CSF showed pleocytosis in all cases. Infiltration of the endoneurium and/or the epineurium by mononuclear cells was seen in biopsies from three cases. These six patients recovered either spontaneously, or with corticosteroids or plasmaphereses. Of five patients with AIDS related complex (ARC), three had distal predominantly sensory peripheral neuropathy (DSPN), one CIDP and one mixed neuropathy. Of 14 patients with AIDS, one had mononeuropathy multiplex and 13 painful DSPN. Electrophysiological studies were consistent with an axonopathy. Nerve biopsies in six cases showed axonal changes but surprisingly associated with marked segmental demyelination in two cases. Cell infiltration was present in nerve samples in two cases. Five patients died within six months after the onset of the neuropathy.     

Involvement of the peripheral nervous system in HIV infection: electromyographic study and nerve conduction velocity]

Disorders of the peripheral nervous system occur at all stages of HIV1 infection. Acute and subacute inflammatory demyelinating polyneuropathies are mainly observed in otherwise asymptomatic HIV+ patients and in patients with ARC (AIDS-related complex): clinical and electrophysiological features are similar to those observed in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), but CSF examination usually shows pleocytosis, and an infiltration of the endoneurium and/or the epineurium is commonly seen in nerve biopsies. Mononeuropathy multiplex is a rare complication occurring in ARC-patients: electrophysiological studies are consistent with an axonopathy and nerve biopsies may show vasculitis. Distal predominantly sensory polyneuropathies are the most frequent peripheral neuropathies in HIV1 infection and are usually reported in patients with AIDS and severe immunosuppression: electrophysiological features are of an axonopathy with signs of acute denervation. Meningoradiculitis is observed at the late stages of the disease and is mainly due to a cytomegalovirus infection. On the other hand, systematic electrophysiological studies in HIV+ cases reveal a high percentage of abnormalities concerning sensory and less frequently motor nerve conduction velocities. The severity of this asymptomatic involvement of the peripheral nervous system seems to be related to the degree of the immunodeficiency. The mechanism of these peripheral neuropathies remains hypothetical in most cases.     

Electroencephalography in AIDS and AIDS-related complex

EEG records from 47 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) were reviewed retrospectively to correlate EEG findings with neurologic abnormalities. Abnormal EEGs were found in 22 of 33 (67%) patients with AIDS and 5 of 14 (36%) patients with ARC. Among 27 patients with abnormal EEGs, there were 9 patients with dementia, 10 with opportunistic infections of the CNS, and 6 with no apparent neurologic disease. AIDS dementia was associated with intermittent or continuous slowing, often most prominent anteriorly. Focal slowing or sharp activity was usually found in patients who had focal CNS processes, such as cerebral toxoplasmosis and CNS lymphoma. These findings suggest the EEG can be a useful diagnostic test for evaluating patients with AIDS and ARC, particularly when these patients present with seizures, psychiatric symptoms, or cognitive dysfunction. The significance of abnormal EEGs in patients who are neurologically asymptomatic is unknown.     

Sensory testing in human immunodeficiency virus type 1-infected men. HIV Neurobehavioral Research Center Group.

Patients with acquired immunodeficiency syndrome frequently suffer peripheral neuropathy. We investigated its prevalence and relationship to clinical stage of human immunodeficiency virus (HIV) infection using quantitative sensory testing and nerve conduction testing. Vibratory threshold was determined in the right great toe and index finger of 179 men seropositive for HIV (28 with acquired immunodeficiency syndrome [AIDS] or AIDS-related complex [ARC], 151 asymptomatic) and 32 HIV-seronegative controls. None had clinical peripheral neuropathy. Abnormal threshold was control mean plus 2.5 SDs. In the toe, 10 (36%) of 28 subjects with AIDS or ARC had abnormal vibratory thresholds, compared with seven (5%) of 151 asymptomatic seropositive subjects and none of 32 controls. A subgroup of 168 seropositive subjects underwent nerve conduction testing. Abnormality rates were similar, but abnormalities of nerve conduction coincided with quantitative sensory testing abnormalities in only half the cases. Mean (+/-SD) vibratory threshold was significantly greater in subjects with AIDS or ARC (3.00 +/- 0.51 vibratory units) than in asymptomatic subjects (1.56 +/- 0.27 vibratory units) and controls (1.63 +/- 0.54 vibratory units). Finger abnormality rates did not differ, although subjects with AIDS or ARC had greater mean vibratory threshold. Subclinical peripheral neuropathy is thus related to stage of HIV infection and is present by quantitative sensory testing in 36% of patients with AIDS or ARC.     

获得性免疫缺陷综合征神经系统损害临床分析

目的 提高对获得性免疫缺陷综合征(艾滋病)合并神经系统损害临床特点的认识,以减少漏诊.方法 对28例人类获得性免疫缺陷病毒(HIV)感染和(或)艾滋病患者中的12例合并神经系统损害患者的临床资料和机会感染性疾病情况进行回顾,并结合文献分析总结.结果 12例患者分别诊断为艾滋病脑病(5例)、慢性脑膜炎(3例)、周围神经病...     

Serial MRI of the brain in asymptomatic patients infected with HIV: results from the UCMSM/Medical Research Council neurology cohort.

Seventy-six homosexual or bisexual men underwent two cranial MRI studies at a mean interval of 13 months; 23 were HIV seronegative, 41 seropositive but asymptomatic (Center for Disease Control (CDC) groups II/III), and 12 had AIDS related complex (ARC)/AIDS (CDC group IV). Agreement between two neuroradiologists was rated as very good for assessment of enlargement of ventricles and good for widening of cerebral sulci and the presence of focal lesions. For assessment of serial studies, the agreement was moderate. The prevalence of cerebral atrophy and focal white matter lesions was no higher in the asymptomatic patients (CDC group II/III) than in appropriate seronegative controls. Some patients with ARC/AIDS showed evidence of developing cerebral atrophy during the study period when serial scans were compared. The imaging evidence supports the other data obtained from this cohort, which suggest that no significant CNS involvement occurs in HIV infection before the development of ARC/AIDS.     

DEVELOPMENTAL ABNORMALITIES IN INFANTS AND CHILDREN WITH ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS) AND AIDS-RELATED COMPLEX

Children with acquired immune deficiency syndrome (AIDS) display two types of clinical picture: a full-blown AIDS characterized by the presence of opportunistic infections and/or Kaposi's sarcoma and a prodromal stage now identified as AIDS-related complex (ARC). Neurological complications have been identified in infants and children with the disease. This paper discusses the developmental abnormalities in 16 pediatric patients, seven with AIDS and nine with ARC, ranging in age from six months to six years. In all cases, the mothers of these children either had ARC, AIDS and/or used intravenous drugs. Developmental histories showed delayed acquisition of milestones in most children following the diagnosis of AIDS or ARC, with delayed motor milestones consistently noted in both groups. Several children with AIDS actually lost milestones as their illness progressed; this has not occurred in the ARC group. Psychometric testing revealed more severe cognitive dysfunction in the group with AIDS. Involvement of the central nervous system was documented clinically, radiologically, and/or electrophysiologically in all patients with AIDS. In the ARC group the course of the illness has shown greater variability. Medical and social factors that may contribute to the developmental abnormalities are discussed.     

获得性免疫缺陷综合征神经系统损害临床分析

目的提高对获得性免疫缺陷综合征（艾滋病）合并神经系统损害临床特点的认识,以减少漏诊。方法对28例人类获得性免疫缺陷病毒（HIV）感染和（或）艾滋病患者中的12例合并神经系统损害患者的临床资料和机会感染性疾病情况进行回顾,并结合文献分析总结。结果12例患者分别诊断为艾滋病脑病（5例）、慢性脑膜炎（3例）、周围神经病（表现为四肢远端对称性多发性神经病和获得性脱髓鞘性神经病各1例）、脑梗死（1例）和肌肉病（1例）。艾滋病合并神经系统损害的发病率约为42．86％（t2／28）。至少合并1～2种以上机会性感染,以真菌最为多见,发病率为83．33％（10／12）;隐球菌性脑膜炎发病率为25％（7128）。结论HIV感染可累及神经系统多个部位及肌肉。艾滋病期患者常合并多系统混合感染,以真菌最为常见;临床以消瘦、间歇性发热、头痛、咳嗽、认知功能减退、脑膜刺激征阳性等症状与体征为主,表现复杂多样,容易误诊或漏诊。诊断与鉴别诊断需依靠脑脊液检查、肺部CT、头部CT和（或）MRI等辅助检查结果,临床工作中应注意筛查,尽早明确诊断。     

Multimodal evoked potentials in human immunodeficiency virus infection

We have studied 95 HIV seropositive patients (77 males and 18 females; mean age: 31 years): 67 had no neurological symptoms or signs, 28 had various neurological symptoms and signs. This study included a full multimodal evoked potentials (MEP) assessment: visual evoked potentials by flash and reversal checkerboard; brainstem auditory evoked potentials; somatosensory evoked potentials obtained by stimulation of the median nerve. Patient evaluation further included: electroencephalography, electromyography with measurement of conduction velocities and neuroimaging (brain CT scan and/or MRI). We found abnormal MEP for all modalities. The prevalence of abnormal results was high in neurological symptomatic patients; in non neurological ones, the changes tended to be more frequent with the progression of the HIV infection. Whatever the stage of the disease, the various modes were equally affected. MEP were abnormal in 54.7 p. 100 of the cases: in 41.8 p. 100 (28/67) of patient without neurological signs (in 4/12 of fully asymptomatic subjects, 11/34 ARC patients and 13/21 AIDS patients) vs 85.7 p. 100 of neurological symptomatic patients. In neurological asymptomatic patients, a similar proportion of abnormal MEP was found in asymptomatic and ARC patients, while the evolution into AIDS was associated with a higher prevalence of abnormal MEP. In the latter group, MEP changes were nearly as frequent as in neurological symptomatic patients. Comparison between MEP and other electrophysiological procedures (EEG, EMG) and with neuroimaging techniques (CT Scan, MRI) showed the high sensitivity of the MEP technique at all stages of the disease. EMG was a sensitive method and complementary to MEP. The EEG and neuroimaging techniques showed abnormalities principally at the neurological symptomatic stage. Previous studies could not be properly compared.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anxiety, depression and HIV related symptomatology across the spectrum of HIV disease.

Levels of anxiety and depression were assessed for 207 HIV seropositive homosexual/bisexual men (AIDS = 34, ARC = 72, asymptomatic HIV infection = 101), and 36 seronegative controls. Lymphocyte subset enumeration, history of opportunistic infections, and occurrence of HIV-related symptoms were recorded at the time of assessment. No differences between groups were found on age, educational level, state/trait anxiety or depression scores. Neither the number of symptoms reported, their duration, severity, frequency of occurrence, nor the proportion of patients who reported a specific symptom was different between the three HIV seropositive groups. Severity of anxiety and depression was related to the magnitude of symptomatology, but not associated with either degree of immunodeficiency, number of opportunistic infections or diagnostic group. Principal component analysis extracted five symptom factors (cognitive, affective, psychosocial, neurological and physical), none of which predicted state anxiety scores. However, affective and psychosocial symptom factors predicted trait anxiety and depression scores. The results indicate that ratings of anxiety and depression are independent of stage of HIV infection, may be in part mediated by constitutional and physical symptoms of HIV disease, but are primarily associated with the presence of psychological and psychosocial symptoms.     

Disorders of the nervous system associated with the acquired immunodeficiency syndrome (AIDS)-clinical approach

The acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV) and characterized by disorders of the nervous system in addition to opportunistic infection and cancer. Centers for Disease Control (CDC) recommend the classification system consisting of four major groups. Group I is patients with acute HIV infection, and Group II is asymptomatic carriers. Group III is those with persistent generalized lymphadenopathy (PGL). Group IV includes five subgroups: IVA with constitutional disease, IVB with neurologic disease, IVC with secondary infectious diseases, IVD with secondary cancers and IVE with other conditions. The nervous system disorders are classified into two types: one is produced by HIV itself and not directly related to immunodeficiency, and the other caused by opportunistic infectious agents and cancers. The former is further divided into two kinds: atypical aseptic meningitis and acute inflammatory demyelinating polyneuropathy (AIDP) occur mainly in Group I and II, whereas HIV encephalopathy, distal symmetric polyneuropathy (DSPN) and vacuolar myelopathy in Group III and IV. Group I or II patients have no apparent medical problems. Therefore, when neurologists see patients with risk factors for HIV infection presenting with atypical meningitis or AIDP, it is of utmost importance to have a high index of suspicion and to look for evidence of HIV infection.     

Soluble interleukin-2 receptor and soluble CD8 in serum and cerebrospinal fluid during human immunodeficiency virus-associated neurologic disease

We have measured levels of soluble interleukin-2 receptor (sIL-2R) and soluble CD8 (sCD8) in serum and cerebrospinal fluid (CSF) of 127 human immunodeficiency virus (HIV)-seropositive and 51 HIV-seronegative individuals. Serum levels of sIL-2R and sCD8 were higher in HIV+ than in HIV- individuals. HIV+ individuals were grouped by neurological status: asymptomatic, abnormal on neuropsychological screening, HIV-related meningitis, inflammatory demyelinating polyneuropathy, opportunistic central nervous system (CNS) infections and HIV-related dementia, myelopathy or sensory neuropathy. Serum levels of sIL-2R and sCD8 were higher in all HIV+ categories compared to HIV- individuals. Patients with HIV-related meningitis had higher levels of sIL-2R and sCD8 than asymptomatic HIV+ individuals, and inflammatory polyneuropathy patients had higher levels of sCD8. CSF levels of sCD8 were higher in all categories of HIV+ than in HIV- individuals. Patients with HIV-related meningitis, inflammatory neuropathy and opportunistic infections had higher levels than asymptomatic individuals. Examination of the time course showed that serum and CSF levels of sIL-2R and sCD8 increased to very high levels during acute HIV infections. Serum levels then declined over several months to relatively stable elevated levels. By 1-2 years after HIV infection sIL-2R was relatively low in CSF, while sCD8 remained elevated with a gradual decrease over the subsequent years of follow-up.     

Peripheral neuropathy in individuals with HIV infection in Zimbabwe

Peripheral neuropathy is associated with HIV infection. The prevalence and types of peripheral neuropathy encountered in a randomly-selected HIV infected African population at different stages of disease were investigated. HIV positive individuals were categorized into 1 of 3 groups: asymptomatic, symptomatic and AIDS. HIV negative individuals formed the control group. Nerve conduction data were obtained using standard electrophysiological procedures and CD4⁺ levels were measured. The type of neuropathy was determined from the history, clinical presentation and electrophysiological abnormalities. The prevalence of peripheral neuropathy was 44%: subclinical neuropathy (SCN) accounted for 56%, acute inflammatory demyelinating polyneuropathy (AIDP) for 15% and distal symmetrical polyneuropathy (DSPN) for 22% of cases of neuropathy. SCN was found in all categories whereas AIDP predominated in the symptomatic category and DSPN in individuals with AIDS. The pattern and frequency of neuropathies seen in our African population is similar to that reported from other continents.     

B-cell neurolymphomatosis confined to the peripheral nervous system

Patients with neurolymphomatosis show lymphoma cells within the peripheral nerves, nerve root/plexus, or cranial nerves. However, most neurolymphomatosis patients show lymphomatous infiltration not only in the peripheral nervous system (PNS), but also in the meninges, Virchow–Robin space, and brain parenchyma. Here, we report a 74-year-old woman with diffuse large B-cell lymphoma presenting with motor–sensory–autonomic polyneuropathy and multiple cranial neuropathies. A diagnosis of neurolymphomatosis was made by sural nerve biopsy. Postmortem examination indicated that lymphoma cell infiltration in the nervous system was confined to the PNS with no involvement of the central nervous system, including the meninges. This was a very rare case of B-cell neurolymphomatosis with lymphomatous infiltration confined to the PNS, suggesting specific affinity of the lymphoma cells for the PNS in this patient.