Neurologic disease is frequently associated with HIV infection. Both the central nervous system (CNS) and the peripheral nervous system (PNS) may be affected. The causes of neurological disease are various: autoimmune reactions due to immune disregulation, opportunistic infections (OIs), metabolic and nutritional derangement due to or associated with AIDS, the direct attack on nerve tissue by HIV, and the toxic effects of drugs used to treat HIV and OIs.
The most common neurologic problem in HIV infection is peripheral neuropathy (PN), which involves lesions of the PNS. The major form of PN in HIV disease is distal symmetric polyneuropathy (DSPN), which has been reported to occur in about a third of patients with AIDS.(1) Several other PN types are associated with HIV disease, mainly acute and chronic inflammatory demyelinating polyradiculoneuropathies (Guillain-Barre-like diseases), mononeuropathy multiplex, and multifocal motor neuropathy. These diseases may be quite serious and life threatening. It is important to recognize them, but they are rare and occur in about 1% of AIDS patients.
DSPN is a "pattern recognition" disease involving a distal and symmetric numbness and/or dysesthesia, the famous "stocking and glove" distribution. This pattern results from the presumed mechanism of polyneuropathy, in which there is believed to be a systemic attack upon the nerves. Nerve repair is under the direction of the nerve cell body, which contains the nucleus and cell machinery.
In theory, the clinical diagnosis of DSPN is straightforward for any competent examiner. A "directed" neurologic exam for suspected DSPN is simple and should be performed by the provider when the patient's complaints are consistent with DSPN, i.e., numbness and or pain (usually described as burning, tingling, or "pins and needles") involving the distal extremities. The toes and feet are usually affected first, and as the disease progresses the height of the "stocking" will rise. When the symptoms reach the upper portions of the legs, the fingers and hands may be affected. There may or may not be weakness of the distal extremities. DSPN seems to affect primarily sensory nerves, but there may be some weakness, most often described as "clumsiness." Patients may complain that they can no longer cross their toes, or that their fingers are clumsy when they try to perform fine manipulations, like buttoning a shirt.
The exam consists first of "subjective" sensory testing, where the examiner uses a safety pin, 128 Hz tuning fork, and cotton swabs to assess vibration, thermal, light touch, and pain sensation. The tuning fork is used to evaluate vibration and thermal sensation. In order to test the latter, the weighted end of the fork is touched to the skin and the patient is asked whether it feels hot or cold. In DSPN one would expect the patient to report a distal and symmetric loss of perception of the various modalities. It is important to check all four modalities.
Next, the "objective" portion of the exam consists of checking the reflex pattern and muscle bulk and strength. In DSPN, one would expect a diminution or loss of the ankle jerk reflexes. The most common muscle bulk abnormality in DSPN is a loss of the extensor digitalis brevis muscles and "high arches" (a pes cavus/talipes deformity), as assessed by physical inspection. Another objective sign of DSPN is atrophic skin change, particularly a significant loss of hair from the distal extremities. Hair is usually present over the great toe and the ankle area.
When necessary, the diagnosis of DSPN can be confirmed by electromyelography (EMG) and nerve conduction velocities (NCVs or NCSs). My screening protocol for DSPN consists of checking the sural sensory, posterior tibial motor, posterior tibial F-waves, and H-reflex waveforms. Needle EMG is performed if there is a suspicion of radiculopathy or axonopathy.
In my non-prison practice I have found that my clinical diagnosis of DSPN is supported by EMG/NCS testing 90% of the time. In my prison practice my clinical diagnosis is supported by the results of EMG/NCS only 33% of the time. In other words, about 2/3 of my prison patients who present with "classic" DSPN are normal on all tests.
I have wondered why the clinical impression should be so discordant with the electrophysiological results in my prison patients. One thing that impresses me is that there is a higher rate of Hepatitis C coinfection among HIV-positive patients in the prison than in the non-prison setting. It is possible that Hepatitis C coinfection contributes to the symptoms that mimic DSPN. Chronic hepatitis of all types is associated with pruritis and burning/tingling dysesthesiae of the extremities. Erythromelalgia is the specific term for these dysesthesiae. The discomfort of erythromelagia is due to the irritation of dermal nerve endings by circulating vasoactive substances and toxins, rather than due to actual nerve damage.
Additionally, one must consider the reality that incarcerated patients have a high rate of substance dependence and may be influenced by secondary gain, may be consciously or subconsciously fabricating and/or amplifying symptoms. A drug addict stuck in prison may be seeking narcotics or other drugs for purposes other than pain control.
In summary, DSPN is common in patients who have HIV infection. In the non-prison setting, this diagnosis can usually be confirmed by taking an appropriate history and performing a directed neurological examination. In correctional medicine, the diagnosis may be complicated by coinfections such as HCV which may cause symptoms that mimic DSPN and drug-seeking behaviors among a population who have a high rate of substance dependence. In correctional medicine, if the diagnosis of DSPN is to be made on purely clinical grounds, it must be based on objective abnormalities, such as muscle wasting, loss of deep tendon reflexes, and atrophic skin changes. If these abnormalities are not present, it may be necessary to confirm or exclude the diagnosis with the use of electrophysiologic testing. A good "screening protocol" for DSPN includes testing sural sensory, posterior tibial motor and F-wave studies, and the H-reflexes. If these are completely normal, one can exclude any significant polyneuropathy.
|Peripheral Neuropathy Treatment|
|Drug Treatments||Related Comments|
- Nortriptyline 10mg hs: increase dose by 10mg q 5 days to a maximum of 75mg hs or 10-20mg po tid.
- Neurotin (gabapentin): 300-800mg po tid.
- Ibuprofen 600-800mg tid.
- Topical: Capsaicin-containing ointments (Zostrix, etc.) For topical application; Lidocaine ointment 20-30% for topical use.
- Alternatives: Phenytoin 200-400mg/d and crabmazepine 200-400mg po bid.
- Other tricyclics commonly used: amitriptyline, desipramine, or imipramine.
- Capsaicin is often not well tolerated.
- Mexiletene: inferior to amitriptyline in ACTG 242 and appeared no better than a placebo. Capsaicin ointment treatment disappointing.
- One report of 2 patients suggests response to HAART (Lancet 1998; 352:1906).
- A controlled trial of acupuncture failed to show any benefit (JAMA 1998; 280: 1590).
- Nucleosides commonly implicated.
|Table adapted from Bartlett J.G., and Gallant J.E. 2000-2001 Medical Management of HIV Infection, p.134.|
* Nothing to disclose.
- So Y.T., Holtzman D.M., Abrams D.I., Olney R.K. Peripheral neuropathy associated with acquired immunodeficiency syndrome. Arch Neurol. 1988; 45: 945-948.
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