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Home arrow Environment arrow Inflammatory Disorders of the Nervous System: Pathogenesis, Immunology, and Clinical Management
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Treatment

Presently, AIDS and neuroAIDS remain incurable and existing therapeutic measures only contain the infection and improve patient’s clinical symptoms. Available antiretroviral therapies, if successful, can only decelerate the progression of the underlying disease and by altering its natural course, enhance patient’s lifespan. There has been a drop in the number of patients with HIV infection and moderate to severe dementia following the use of HAART as of 1996 [85]. Interestingly, the sustained presence of less severe forms of HAND, even in patients with sustained virologic control, fosters the idea that cognitive decline in certain patients may not be responsive to treatment. Multiple antiretroviral agents have been shown to have a better effect than monotherapy or no therapy at all in patient with HIV-related dementia. Another significant finding is that, even in the time of treatment with antiretroviral medications, a significant drop of the number of CD4+ T lymphocytes remains a strong risk factor for development of HAND. This also points to the fact that profound immunosuppression may lead to permanent neuropathology [86].

Improvements in psychomotor activities and speed have been shown in patients treated with HAART. MRI spectroscopy has shown the HAART regimen reverses abnormalities in brain metabolites seen in mild HIV dementia. HAART also has an effect in improving cognitive deficits compared to AZT or dual antiviral therapy. Some patients improve dramatically and may be able to return to employment. Neuropsychological evaluation shows improvement in the areas of attention, verbal fluency, and visuo-construction tasks. Of all FDA-approved antiretroviral medications, most have weak CSF-to-plasma ratios except for AZT, stavudine, abacavir, and nevirapine. Triple therapy is preferred. Viral load elevation following initiation of therapy may indicate resistance. Anti-inflammatory medications, antioxidants, and anti-excitotoxic agents may be utilized to circumvent neurodegeneration.

Psychiatric assessment and treatment of patients with neuroAIDS and HAD are necessary and useful since many of these patients suffer from agitation, anxiety, fatigue, and depression. Antidepressant, antipsychotics, or psychostimulants can help treat mania and psychosis. A multidisciplinary team should be available to these patients. Nutritional therapies can help with cognitive and motor symptoms particularly in those patients with wasting syndrome or toxic nutritional deficiencies. One particular medication, efavirenz, despite having good CNS penetration, may be associated with significant neuropsychiatric side effects (such as depression, anxiety, paranoia, and psychosis) and should be generally avoided in AIDS patients with psychiatric disorders.

Vacuolar myelopathy is incurable with very limited treatment options. The management of these patients significantly relies on physical therapy and symptomatic treatment of spasticity and its related complications. Gait difficulties as well as sphincter dysfunction require symptomatic therapy. There is no treatment for sensory polyneuropathy. However, neuropathy due to nucleoside analogue reverse transcriptase inhibitors may be treated with acetyl-L-carnitine. Supportive therapies such as pain management are also recommended for polyneuropathy.

Syndromes like AIDP and CIDP should be treated as with seronegative HIV patients. Some patient may improve with HAART. Patient with AZT myopathy can be helped with L-carnitine. Movement disorders in HIV patients are treated by treating the underlying opportunistic infection. They are not usually responsive to symptomatic treatment [87, 88]. One exception may be cases of hemiballismus, which may get better with the use of antipsychotics.

Except for eradication of secondary causes, treatment of headache in HIV is geared toward symptom improvement. General preventive and abortive headache treatments can be implemented. However, Sheikh and Cho [29] point out that there are important caveats to drug treatment in HIV patients due to their comorbidities and drug interactions with cART. Because HIV patients are at risk for vascular disease earlier in life, the practitioner must rule this out in each patient prior to using triptans. Triptans and preventives metabolized by the liver may also be contraindicated if the patient has hepatitis C, commonly seen with HIV. Ergots (rarely used for acute migraine anymore) and ergot derivatives such as dihydroergotamine are strictly contraindicated in the presence of protease inhibitors for HIV treatment because of reports of sometimes fatal ergotism. If nonsteroidal anti-inflammatory agents are used for headache, they should not be paired with proton pump inhibitors, which can interact with some cARTs causing decreased efficacy of the latter. Patients treated with corticosteroids to “break” a prolonged headache cycle must be monitored for signs of worsening immunosuppression. Beta-blockers for prevention are okay with the exception of metoprolol, which may act as a substrate for some cART medications. Divalproex sodium and topiramate are relatively safe in this population. Carbamazepine should be avoided due to induction of the CYP450 system leading to lower cART concentrations. Fluoxetine inhibits CYP450 and interferes with cART as well. On the other hand, tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors are used without problems for pain and headache syndromes in HIV. For chronic migraine, onabotulinum toxin A is the only FDA-approved preventive treatment and should not pose a problem for HIV patients. Injectors should take routine precautions to avoid HIV transmission through blood contact.

Conclusion

Over the past two decades and with widespread utilization of cART, the natural course of HIV infection has altered, and consequently neurologists encounter opportunistic CNS infections, CNS lymphoma, and HIV vacuolar myelopathy uncommonly. More chronic complications of AIDS such as cognitive decline, psychiatric disorders, peripheral neuropathy, and the side effects of antiretroviral therapy constitute most of the present day neurology consults. Proper and timely diagnosis of AIDS and its neurologic complications and early initiation of the therapy do carry a significant effect on the disease process and can potentially improve the quality of life of AIDS patients.

 
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