Abstract

Background

Distal symmetrical polyneuropathy (DSP) is one of the most common neurological disorders affecting people living with HIV/AIDS, and also a major cause of morbidity affecting quality of life and indirectly on adherence to their drugs, which is fast becoming a global issue.

Methods

The study period was June 2004 to December 2004. For convenience, the non probability purposive sampling method was used to include 100 HIV/AIDS drug naive patients and 100 appropriate controls that satisfied the inclusion criteria. A standard proforma based on Standardized clinical screening tool for sensory neuropathy instrument was used to screen for DSP.

Results

Clinically diagnosed DSP in Jos University Teaching Hospital (JUTH) occurred in 38% of drug naïve HIV/AIDS patient. Of these, twenty-seven (71.1%) were in stage 1 (only signs, no symptom) while eleven (28.9%) were in stage II and III. The result of this study showed that neither gender nor age affected the frequency of clinically diagnosed DSP. However among the controls increasing age significantly affected DSP.

Conclusion

The frequency of clinically diagnosed DSP in our environment is similar to that obtained in western world, and this frequency is likely to decrease if patients present early.

Keywords: AIDS, Polyneuropathy, HIV

Resume

Introduction

Les polyneuropathies distales (DSP) sont des affections neurologiques les plus connues affectant les personnes vivants avec le VIHSIDA. Elles représentent une des causes majeures de mortalité et affectent également la qualité de vie.

Methode

L’étude a été réalisée de Juin à Décembre 2004. La méthode de calcul de probabilité d’échantillon a été utilisée par souci de commodité incluant 100 patients au traitement VIH/SIDA et 100 patients contrôles satisfaisant aux critéres élaborés. Une norme réglementaire sur une base standard de dépistage clinique de l’instrument de mesure sensitif neuropathique a été a utilisé pour le dépistage de l’E.S.P.

Resultat

L’E.S.P. a été diagnostiqué au centre hospitalier universitaire de Jos (JUTH) chez 38% de patients VIH/SIDA. Vingt sept (71.1%) sont resté a l’étape 1 (quelques signes, pas de symptome). Onze patients (28.9%) sont restés à l’étape II et III. Le resultat de cette étude a montré que ni le genre et ni l’âge n’ont affecté la fréquence des E.S.P cliniquement diagnostiqué.

Conclusion

La fréquence des DSP médicalement diagnostiqués dans notre environnement est semblable à celle observée dans les pays occidentaux et cette fréquence est susceptible de diminuer si les patients se présentent tôt.

Mots cle: Neuropathie périphérique, HIV, SIDA

INTRODUCTION

The acquired immunodeficiency syndrome (AIDS) is currently one of the most important diseases worldwide including Nigeria 20, 11 and the incidence and prevalence of the disease have continued to rise. 13

Despite improvement in the diagnosis and “effective palliative treatment” of AIDS related disorders, the number of people infected with human immunodeficiency virus (HIV) continues to grow, requiring a greater proportion of limited financial, medical and human resources. 16

Distal symmetrical polyneuropathy with sensory or sensory more than motor involvement is the most common pattern of peripheral neuropathy in HIV disease. Distal symmetrical polyneuropathy (DSP) was initially described in AIDS patients by Snider et al 17 and numerous authors have further characterized its clinical and pathological features. 5,6,8,18

The mechanism of HIV-associated distal symmetrical polyneuropathy is uncertain. Several pathogenetic mechanisms have been proposed including advancing age, nutritional status, chronic disease, low haemoglobin level, HIV itself, neurotoxic cytokines, HIV glycoprotein and low CD4 counts.1, 19 The risk of DSP is increased with higher plasma HIV viral level, low CD4 cell counts, advanced disease and increased age.3, 19

The evaluation of DSP may seem daunting when one considers the long list of potential underlying causes and formidable number of available diagnostic tests.
Standardization of examination method has led to development of various instruments in peripheral neuropathy including Standardized clinical screening tool for sensory neuropathy.9

Although DSP is not a life-threatening condition, it markedly affects the quality of life of patients with AIDS and may limit the use of neurotoxic antiretroviral agents. 15 The prevalence of DSP in HIV infection has consistently been estimated at about 30%, 18 after other recognized causes of polyneuropathy are excluded. Schifitto et al showed in a 30-month study of HIV infected patients in the pre-HAART era (1994-1995) that 35% had symptomatic DSP. The HIV-associated DSP and DSP due to use of dideoxynucleoside reverse transcriptase inhibitors are phenotypically identical and form the commonest neurological disorder affecting people with HIV/AIDS. There is paucity of information on DSP in Nigeria hence this study was carried out to provide information on DSP among Nigerian patients with HIV/AIDS.

PATIENTS AND METHODS

This is a cross-sectional comparative study to determine the frequency of distal symmetrical polyneuropathy among 100 drug naïve patients with HIV/AIDS and 100 age and sex matched controls seen in Jos University Teaching Hospital (JUTH), Jos. The study period was June 2004 to December 2004.The Research and Ethics Committee of JUTH approved the study and informed consent from patients was obtained prior to data collection.

Patients with HIV/AIDS attending the HIV clinic (Clinic II) of the infectious diseases unit of JUTH, were screened and examined by the investigator for distal symmetrical polyneuropathy using Standardized clinical screening tool for sensory neuropathy 9. The Standardized clinical screening tools for sensory neuropathy have been validated by previous workers2. Grading of distal symmetrical polyneuropathy using SPNS9.
The subject were asked to rate the severity of each symptom listed below and choose a number from 01 (mild) to 10 (most severe) for right and left. Presence/severity Score of: 01 – 03 = Grade 1; 04 – 06 = Grade 2; 07 – 10 = Grade 3;

00 = Grade 0

Symptoms
Pain, aching, or burning in feet, legs
“Pins and needles” in feet, legs
Numbness (lack of feeling) in feet, legs

Distal symmetrical neuropathy was staged by the method of Dyck. 11

0 = no neuropathy

1 = 2 or more abnormal neurological tests.

2 = 2 or more abnormal tests plus symptoms

3 = 2 or more abnormal tests plus debilitating symptoms.

Neuropathy was defined by depressed or absent reflexes at the ankles relative to the knees after reinforcement, increased vibratory threshold at the toes and ankles, reduced pain and temperature sensation in a glove and stocking distribution.

HIV was diagnosed by Enzyme-linked Immunosorbent Assay (ELISA) and confirmed by Western blot according to WHO/CDC criteria and CD4 counts were evaluated using Cyflow technique.

Age and sex-matched controls were recruited from patients preparing for elective surgery and endoscopy. These patients were non-diabetic, tested negative for HIV, had normal renal function and were not on drugs causing distal symmetrical polyneuropathy or for treatment of HIV/AIDS. Results of the study were analyzed using EPI-INFO 2004 version 3.2.2 statistical programme and p-value less than 0.05 were considered statistically significant.

RESULTS

One hundred HIV patients comprising 42 male and 58 female whose ages ranged between 21 and 59 years (Mean = 34.68 ± 8.69 years), and 100 control subjects whose ages ranged between 23 and 59 years (Mean = 36.20 ± 9.30 years) were evaluated. Table I shows the age and sex distribution of patients and control, while table II shows the age and sex distribution of patients with DSP.

Table III shows the frequency of clinically diagnosed DSP. Of the 100 HIV positive drug naïve patients 38 had DSP. Twelve of the 100 controls had DSP. The difference was statistically significant.

Tables IV and V show the grading of DSP based on standardized clinical screening tool for sensory neuropathy and Dyck grading system. Using the subjective sensory neuropathy grade fourteen of those who are HIV positive had neuropathy compared to four of the control. The Dyck grading system however showed that thirty-eight of HIV positive patients and twelve of the control had neuropathy.

In table VI the median CD4 count for HIV drug naïve patients was 161.0 cells/µl Range: 5 and 839 cells/µl). The median CD4 count among those with DSP was 105.5 cells/µl with lowest the lowest CD4 5cells/µl and highest 482 cells/µl.

DISCUSSION

DSP is one of the most common neurological complications of HIV/AIDS and its treatment. The results of this study showed that clinically diagnosed DSP in JUTH occurred in 38% of patients with HIV/AIDS not on highly active antiretroviral therapy (HAART). Of these, twenty-seven (71.1%) were in stage 1 (only signs, no symptom) while eleven (28.9%) were in stage II and III. These frequencies compared well with the 35% prevalence rate documented by So et al 18 in a population based survey and 38% by Tagliati et al 19. In Zimbabwe, Parry et al 12 found a prevalence rate of 22%. Other workers have reported a prevalence of approximately 30%, after excluding other recognizable causes of DSP 6. However in the Dana cohort, an advanced preHAART group, Schifitto et al 14 found that 55% of baseline evaluation revealed DSP. Among these, 20% were in stage I, while 35% were in stages II and III. They also suggested that stage I DSP was not a predictor of progression to stages II and III. It is therefore, possible that these stages may not be part of a continuum.
The result of this study showed that gender did not affect the frequency of clinically diagnosed DSP. This study is in agreement with that of Schifitto et al 14 who also observed that gender was not a risk factor for developing DSP for drug naïve HIV patients. Age did not also affect the frequency of DSP among drug naïve HIV positive patient. However among the controls increasing age significantly affected DSP. Tagliati et al 19 found DSP to increase significantly with age and that nerve conduction abnormalities were associated with increased age in patients with HIV/AIDS. It is possible that the mean age of presentation may play a role as most of the previous works done had mean ages greater than 40.8,14,19
An important finding in this study was the lack of correlation between DSP and decreased CD4 count among drug naïve HIV patients. Although this finding appears paradoxical, it may suggest that increasing rates of DSP seen with advancing HIV disease suggest that the pathology develops gradually, and that subclinical or silent nerve damage may be present in many people with HIV who are not yet symptomatic for DSP. Fifty-six HIV positive drug naïve patients had CD4 count less than 200 cells/ml. Of these twenty-seven (48.2%) had DSP. Forty-four had CD4 greater than 200 cells/ml with eleven (25%) having DSP (X2 = 5.58 p = 0.01816). Indeed, the common finding among the various early studies is that DSP is primarily a complication of late stage HIV disease with advanced immunosuppression. Data from Multicentre AIDS Cohort study (MACS) revealed that, in addition to those with a lower CD4 cell count being at higher risk of neuropathy, individuals with HIV RNA >10 000 copies/ml had a 2.3 fold greater risk of DSP than those with <500 copies/ml.3 There is a need for improved methods of determining the degree of subclinical DSP and also for harmonization of instruments for screening individuals with HIV/AIDS prior to commencing potentially neurotoxic antiretroviral agents, and monitoring patients for early mitochondrial dysfunction once they commence therapy, in order to better describe the individual's risk of developing DSP. Although DSP is not usually life threatening, it produces significant disabling symptoms in affected individuals. It is important that clinicians caring for patients with HIV infection are familiar with the diagnosis and treatment of DSP, as this may provide significant improvement in the quality of life in these patients. TABLE 1: Age and sex distribution of the study cohorts.

TABLE II: Age and sex distribution of patients with distal symmetrical polyneuropathy

TABLE III: Frequency of DSP in HIV patients and control

(X2 = 17.94 p = 0.0000228)

TABLE IV: Grades of distal symmetrical polyneuropathy using Subjective Peripheral Neuropathy Screen.

TABLE V: Stages of distal symmetrical polyneuropathy using Dyck grading system.

TABLE VI: Distribution of DSP by CD4 class.

(X2 = 5.58 p = 0.01816)