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Arquivos de Neuro-Psiquiatria

Print version ISSN 0004-282XOn-line version ISSN 1678-4227

Arq. Neuro-Psiquiatr. vol.62 no.2a São Paulo June 2004 

The frequency of peripheral neuropathy in a group of HIV positive patients in Brazil


Freqüência da neuropatia periférica no Brasil em um grupo de pacientes HIV positivo



Claudia Zanetti; Gilberto M. Manzano; Alberto A. Gabbai

Department of Neurology of Universidade Federal de São Paulo (UNIFESP), São Paulo SP, Brasil




Peripheral neuropathy is a common neurological complication occurring in asymptomatic and symptomatic stages of HIV infection. The most common syndromes are distal symmetric polyneuropathy, inflammatory demielinating polyneuropathy, poliradiculopathy, mononeuropathy, mononeuropathy multiplex and autonomic neuropathy.
PURPOSE: To evaluate the frequency of peripheral neuropathy in a group of HIV seropositive outpatients in São Paulo, Brazil.
METHOD: Over a period of 17 months, 49 HIV+ patients where evaluated clinically. Laboratory analysis and electroneuromyography were requested to all patients.
RESULTS: >Thirty four (69.4%) of the 49 patients had the diagnosis of peripheral neuropathy established on clinical grounds. The most common sign was impairment (97.1%) of sensibility. Thirteen (33.3%) of the 39 that were subjected to electroneuromyography had features of peripheral neuropathy, being a sensitive-motor axonal neuropathy the most common. No abnormalities were found in the laboratory analysis performed in 42 patients, except in four who had VDRL positive.
CONCLUSION: A peripheral neuropathy was frequently found upon clinical examination in our group of HIV positive individuals.

Key words: peripheral neuropathy, HIV, AIDS.


A neuropatia periférica é complicação neurológica comum, podendo ocorrer nas fases assintomáticas e sintomáticas da infecção pelo vírus da imunodeficiência humana (HIV). As síndromes mais comuns são a polineuropatia distal simétrica, polineuropatia desmielinizante inflamatória, polirradiculopatia, mononeuropatia, mononeuropatia múltipla e neuropatia autonômica.
OBJETIVO: Avaliar a freqüência da neuropatia periférica em um grupo de pacientes HIV positivo em São Paulo, Brasil.
MÉTODO: Em um período de 17 meses, foram avaliados clinicamente 49 pacientes HIV positivos. Foram solicitados exames laboratoriais e eletroneuromiografia (ENMG) para todos os pacientes.
RESULTADOS: Foi estabelecido o diagnóstico clínico de neuropatia periférica em 34 (69,4%) dos 49 pacientes. O sinal neurológico mais comum foi a alteração da sensibilidade (97,1%). Treze (33,3%) dos 39 pacientes que realizaram a ENMG tiveram o diagnóstico de neuropatia periférica, sendo a neuropatia sensitivo-motora axonal o achado mais comum. Não foram encontradas alterações significativas nos exames laboratoriais (42 pacientes realizaram os exames), com exceção de quatro pacientes em que o VDRL foi positivo.
CONCLUSÃO: A neuropatia periférica foi um achado freqüente no grupo de pacientes HIV positivo estudados clinicamente.

Palavras-chave: neuropatia periférica, HIV, SIDA.



The acquired immunodeficiency syndrome (AIDS) was first described in 1981. At that time it was reported the occurrence of an uncommon opportunistic infection caused by Pneumocystis carinni in a previously healthy young homosexual man1. Neurological disorders in HIV patients were first reported in 19822. Peripheral neuropathy is a common neurological complication associated with human immunodeficiency virus type 1 (HIV-1) infection, occurring in asymptomatic and symptomatic individuals3-5 and it can be the first manifestation of the disease6. The peripheral neuropathy syndromes are somewhat specific according to the stage of the disease (Table 1). This specificity reflects the distinct mechanisms of the various types of peripheral neuropathies in HIV seropositive individuals6-11.



The prevalence of peripheral neuropathy associated with HIV-1 is estimated at 15 to 50% of patients7,12-15. But it may be almost 100% when a pathological study is performed14,15. Distal symmetrical polyneuropathy (DSP) is the most common peripheral nerve involvement in HIV-positive individuals3,16. There are other forms of peripheral neuropathies in HIV-positive patients including inflammatory demyelinating polyneuropathy6,17; progressive polyradiculopathy6,9; mononeuropathy and mononeuropathy multiplex10,18; autonomic neuropathy8; and diffuse infiltrative lymphocytosis syndrome19 (Table 1).

The objective of this study was to evaluate the frequency of peripheral neuropathy in a group of HIV-seropositive outpatients in São Paulo, Brazil.



Over a period of 17 months, from July 1999 to May 2000, 49 HIV-positive patients where evaluated at the AIDS Outpatient Clinic of the Infectious Diseases Division of the UNIFESP - Escola Paulista de Medicina in São Paulo, Brazil.

Each patient arbitrarily recruited by the Coordinating Nurse had a history taken and neurological examination done by the same neurologist, mostly looking for the diagnosis of a peripheral neuropathy. Although highly suspicious of a peripheral neuropathy, symptoms of extremity pain, numbness, tingling and weakness were not enough to make the diagnosis. The diagnosis was established when we found any of the following, isolated or combined: sensory impairment, absent deep tendon reflexes, amyotrophy and weakness. We examined thermal, tactile, pain, vibration and position sense sensory modalities. Weakness was considered diagnostic if it had a pattern compatible with any form of peripheral neuropathy20. Laboratory analysis (glucose, CBC, BUN, creatinine, electrolytes, liver function, vitamin B12, VDRL, HTLV 1/2) and electroneuromyography21 were requested to all patients.

The present study was approved by the ethics committee of the UNIFESP - Escola Paulista de Medicina. Informed consent was obtained from all patients.



Of the 49 patients included, 32 were male and 17 female. The mean age was 36.88 years with a range of 21-53 years. None of the patients had history of familial peripheral neuropathy, diabetes mellitus or recent (less than 2 years) history of alcohol abuse. Thirty four of our 49 patients (69.4%) had diagnosis of a peripheral neuropathy. Twelve (35.3%) had both symptoms and signs and 22 had only signs. Decreased distal superficial sensibility was the common sign occurring in 73.5% of the patients, one (3%) had only absent ankle jerks and 8 (23.5%) had sensibility and tendon reflexes altered. Two patients had only symptoms and two had sub-clinical peripheral neuropathy with neither symptoms nor signs - the peripheral neuropathy was diagnosed by the neurophysiologic study. Thirty two (94.1%) patients were taking drugs supposed to be neurotoxic (d4T,ddI, ddC, isoniazid)22-25. Thirty nine patients had electroneuromyography performed. Thirteen (33.3%) of those had features of peripheral neuropathy. The types of peripheral neuropathy are shown in Table 2. Seventy five percent (six patients) of the patients who had a diagnosis of DSP on electrophysiologic grounds were taking drugs supposed to be neurotoxic (d4T, ddI, ddC isoniazid)22-25. Laboratory analysis did not show any significant abnormalities (42 patients were tested), except in four who had VDRL positive.




To our knowledge this is the first study of the frequency of peripheral neuropathy in HIV-positive individuals in Brazil. In accordance with others26 we found that 69.4% of our patients had a clinical diagnosis of peripheral neuropathy, Interestingly, 64.7% of those did not have any complaint suggesting the involvement of the peripheral nervous system. That subclinical peripheral nerve dysfunction has been described5,27 and may reach 71% of those examined28. The most common complaints are numbness, parethesias and painful dysestesias12,29. In our series the main symptom was mild distal dysestesia that neither interfered with the activities of daily living nor required specific therapy. The main neurological sign was distal symmetric sensory alteration (in 97.1% of the patients) in the four limbs but mainly in the feet.

Thirteen (33.3%) of our 39 patients that had eletrophysiologic testing, had features of nerve lesion. The main eletrophysiologic diagnosis was sensitive-motor axonal neuropathy. In the literature DSP is responsible for 90% of the peripheral neuropathies in HIV-infected individuals3,12,13,16,30. Its incidence increases with advanced immunosupression and with decreased CD4-cell counts31, and thus more frequent in the later stages of the disease. DSP is clinically present in 10 to 35% of AIDS patients without known causes for their neuropathy12,13,16,32. In advanced immunosupression (CD4<100 cells/µl) DSP has been described in 30-80% of patients5,12,13. Sensory symptoms predominate, and the patients complain of numbness and paresthesias. On neurological examination there is symmetric distal sensory loss with absent ankle reflexes12,29. Electrophysiological studies are most compatible with an axonal neuropathy12,30, the same as we found. There is a low incidence of DSP in pediatric HIV patients33.

We also found patients with mononeuropathy, mononeuropathy multiplex and demyelinating neuropathy (Table 2).

The etiology and pathogenesis of peripheral neuropathy associated with HIV infection is uncertain. It can be caused by the direct or indirect action of HIV and antibody production, or secondary to infections (CMV,MAC ), toxic effects of certain drugs (isoniazid, vincristine, d4T, ddi, ddC), or nutritional deficiencies (vitamin B12)4,7,22-26,34-36. In our study, almost all the patients that had diagnosis of peripheral neuropathy were taking drugs probably neurotoxic (ddi, d4t,ddC isoniazid).

Our electrophysiologic findings were much lower when compared to our clinical neurological evaluation. The discrepancy between our clinical and electrophysiologic findings is probably do to the well known poor evaluation of thin fiber system related to the routine nerve conduction tests37.

Peripheral neuropathy in HIV seropositive patients may be overlooked or misdiagnosed. A discerning clinical analysis may be helpful in the diagnosis of this common disease since the conventional electrophysiological study can underestimate some cases of peripheral nerve involvement.



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Received 3 September 2003.
Accepted 3 December 2003.



Dra. Claudia Zanetti - Neurologia UNIFESP - Rua Botucatu 740 - 04023-900 São Paulo SP - Brasil. E-mail:

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