HIV-related Neuropathy

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Original Editor - Melissa Coetsee
Top Contributors - Melissa Coetsee, Kim Jackson and Pacifique Dusabeyezu

Clinically Relevant Anatomy

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Mechanism of Injury / Pathological Process

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Clinical Presentation

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Symptoms:

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Diagnostic Procedures

Based on medical history, clinical examination and laboratory tests

EMG

Outcome Measures

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Types

DSN:

DSN is the most common occurring mostly during the symptomatic stage of HIV disease (WHO stages 3 & 4) and was reported early on in the HIV epidemic in Africa28,36. The main symptoms of DSN are a burning, stabbing pain and paresthesia or numbness in the soles of the feet ascending symmetrically and less commonly involving the hands. Notably the pain or discomfort is most apparent on touching the soles or palms. Sensory symptoms are reported to be present in about 75% (50–90%) of DSN patients in Africa148. Signs of DSN include reduced or absent ankle reflexes and/or impaired light touch and/or impaired vibration and joint position sense.

The prevalence of DSN depends on the criteria used to define it and include any two of three signs with or without symptoms (symptomatic and asymptomatic) or any one sign with symptoms (symptomatic)149,150. More recently a clinical tool using 4 items: pain, numbness, ankle reflexes and vibration has been validated for use in Africa151. The pathophysiology of DSN is a distal axonal neuropathy secondary to activated dorsal root inflammation most probably due to viral proteins, gp120. The estimated pooled frequency of DSN in the pre ART era in Africa was 27% (11–37%)149,152,153. A much lower frequency of 3.9% was reported in a single large study from SA154. The worldwide prevalence during the same period ranged between 20–57%149. A frequency of 50% was reported in HIV2 in one study in West Africa using just one sign+/- symptoms45. In the post ART era in Africa there was a significant increase in frequency of DSN with pooled frequencies of DSN of 52% (36–60%)149,150,152,153,155–159. This increase was attributed to the widespread use of dideoxynucleoside reverse transcriptase inhibitors as a first line ART, in particular stavudine with the neuropathy typically beginning 5–6 months post starting ART153,158,160. In a recent study from SA involving a cohort of patients 2 years after starting ART (60% on stavudine) a slight increase in the frequency of symptomatic DSN from baseline 16% to 18% was reported with a 50% decrease in significant pain161. The rate of symptomatic DSN decreased from 22 to 17% in another study in SA involving 2nd line ART patients with an almost 2 year follow up period, notably the rate of asymptomatic DSN in that study increased from 21% to 29%162. Some studies from West Africa report a decrease in the frequency of DSN at three months post starting ART which may have been too early to observe this side effect of stavudine163,164. The main risk factors for DSN are advanced HIV disease, lower CD4 count, high viral load, advancing age, and a history of prior TB or alcohol intake149,153,162. Up to a quarter of ART treated HIV persons in Africa may be affected with symptomatic DSN for life162–164.

The management of DSN involves pain control with available neuropathic specific medications including amitriptyline, gabapentin, pregabalin and lamotrigine and the use of opioids only if necessary, however most patients tolerate their symptoms without medications. Strategies aimed at decreasing the burden of DSN in Africa include an early test and treat HIV policy, avoiding dideoxynucleoside reverse transcriptase inhibitors, an increased awareness of other possible concurrent causes of neuropathy i.e. alcohol, diabetes mellitus and pyridoxine deficiency secondary to isoniazid.

Mononeuropathy

Mononeuropathies are common in HIV infection in Africa149. The most common are facial nerve palsy or Bell's palsy and neuropathy complicating reactivation of herpes zoster in dorsal root ganglia165–168. Facial nerve palsy occurs most frequently at or around the time of seroconversion after primary infection and during the asymptomatic phase of HIV infection. During the early epidemic in Africa >50% of patients presenting with facial nerve palsy tested seropositive for HIV169. Facial nerve palsy/HIV is characteristically unilateral but may infrequently be bilateral or occur as part of a generalized acute inflammatory demyelinating neuropathy. Investigation, management and response to treatment are similar to facial nerve palsy/non-HIV. Herpes zoster reactivation is one of the earliest and most recognizable clinical presentations of HIV with its characteristic locally aggressive multi dermatomal involvement, involvement of atypical sites including face, cranium and sacrum and subsequent marked scarring. It affects 5–10% of HIV infected patients in Africa with the mean survival time estimated in the pre-ART era to be around 42 months166,168. It most commonly involves the thoracic and trigeminal nerves. Complications include dissemination, myelitis and pain, post herpetic neuralgia. Acute management is with acyclovir and pain control as for non-HIV. Other neuropathies that occur in HIV include other cranial nerve palsies, optic neuritis and mononeuropathies149,170. These are mostly either autoimmune based or secondary to opportunistic processes e.g. TB/lymphoma resulting in entrapment/infiltration in advanced disease.

Management / Interventions

HIV infection control

Drug regime alteration if associated with ARVs

Anti-seizure medications/anti-depressants or analgesics

Differential Diagnosis

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Resources

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