Evidence for a novel subcortical mechanism for posterior cingulate cortex atrophy in HIV peripheral neuropathy.

We previously reported that neuropathic pain was associated with smaller posterior cingulate cortical (PCC) volumes, suggesting that a smaller/dysfunctional PCC may contribute to development of pain via impaired mind wandering. A gap in our previous report was lack of evidence for a mechanism for the genesis of PCC atrophy in HIV peripheral neuropathy. Here we investigate if volumetric differences in the subcortex for those with neuropathic paresthesia may contribute to smaller PCC volumes, potentially through deafferentation of ascending white matter tracts resulting from peripheral nerve damage in HIV neuropathy. Since neuropathic pain and paresthesia are highly correlated, statistical decomposition was used to separate pain and paresthesia symptoms to determine which regions of brain atrophy are associated with both pain and paresthesia and which are associated separately with pain or paresthesia. HIV+ individuals (N = 233) with and without paresthesia in a multisite study underwent structural brain magnetic resonance imaging. Voxel-based morphometry and a segmentation/registration tool were used to investigate regional brain volume changes associated with paresthesia. Analysis of decomposed variables found that smaller midbrain and thalamus volumes were associated with paresthesia rather than pain. However, atrophy in the PCC was related to both pain and paresthesia. Peak thalamic atrophy (p = 0.004; MNI x = - 14, y = - 24, z = - 2) for more severe paresthesia was in a region with reciprocal connections with the PCC. This provides initial evidence that smaller PCC volumes in HIV peripheral neuropathy are related to ascending white matter deafferentation caused by small fiber damage observed in HIV peripheral neuropathy.

Treatment of human immunodeficiency virus-related peripheral neuropathy with Scrambler Therapy: a case report.

Peripheral neuropathy is one of the most common neurological complications of HIV infection with a 30-60% lifetime prevalence. Newer HIV drugs cause less peripheral neuropathy, but patients are now living long enough to develop concomitant diabetes-related, vascular-related, and chemotherapy-related neuropathy so it continues as a major debilitating issue. Recent national CDC guidelines have stressed the importance of non-opioid therapies, especially in this population that may have had drug abuse problems. We treated a 52-year-old man who had severe disabling classic peripheral neuropathy since 1998 with Scrambler Therapy (Calmare), an FDA-cleared peripheral non-invasive neuromodulation device. His pain rapidly improved, as did his motor and sensory function, with just four 45-min treatments, and he was able to come off opioids for the first time in years. When his pain returned six months later, only two treatments were needed to resolve it. This represents the first published use of this novel, inexpensive, and non-invasive pain modality in HIV peripheral neuropathy, and should engender further trials.

Medical marijuana for HIV-associated sensory neuropathy: legal and ethical issues.

The number of states legalizing medical marijuana is increasing. Medical marijuana is possibly effective therapy for HIV-associated sensory neuropathy. Despite legalization at the state level, however, the current and contradictory federal drug enforcement policy creates the risk that physicians who recommend medical marijuana to their patients will lose their ability to prescribe medications. The federal-state tension has legal and ethical implications for neurologists who receive a request for medical marijuana from their patients since neurologists must strive to both relieve suffering and obey relevant laws. Recommendation of medical marijuana by neurologists to their patients is ethically permissible but is not ethically mandatory.

Peripheral neuropathy in HIV: an analysis of evidence-based approaches.

Peripheral neuropathy is a common and vexing symptom for people living with HIV infection (PLWH). Neuropathy occurs in several different syndromes and is identified in the literature as distal sensory polyneuropathy or distal sensory peripheral neuropathy. More recently, the HIV literature has focused on the syndrome as painful HIV-associated sensory neuropathy, addressing the symptom rather than the underlying pathophysiology. Assessment of neuropathy in PLWH is critical and must be incorporated into nursing practice for each visit. Neuropathy has been attributed to the direct effects of HIV, exposure to antiretroviral medications (particularly the nucleoside reverse transcriptase inhibitors), advanced immune suppression, and comorbid tuberculosis infection and exposure to antituberculosis medications. Evidence supports the importance of addressing neuropathy in PLWH with pharmacologic treatment regimens and complementary/alternative approaches. This paper examines the pathophysiology, evidence, and approaches to managing peripheral neuropathy. A case study has been included to illustrate a patient's experience with neuropathy symptoms.

Cultural resources for health participation: examining biomedicine, acupuncture, and massage therapy for HIV-related peripheral neuropathy.

In this article we use a culture-centered approach to understand people's experiences of treatment options for human immunodeficiency virus (HIV)-related peripheral neuropathy. We present from often unheard and marginalized voices the stories of how people live with this chronic illness and negotiate treatment options. Based on individual and group interviews, participants reported that biomedical pills were an important context for understanding decision making regarding neuropathy treatment. While most people spoke of the necessity of these drugs for their survival, they also expressed deep resentment and frustration with biomedically prescribed pills. Complaints about the pills worked to frame the holistic alternatives of acupuncture and massage therapy as better options for neuropathy and to establish a foundation for understanding how participants made particular health treatment decisions. Through strategically refusing certain drugs and choosing holistic treatments instead, participants asserted agency and control over their health decision making. By choosing holistic therapies, these clients were able to make choices about their neuropathy treatment in light of the many issues surrounding drug toxicity and treatment efficacy.

Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial.

OBJECTIVE: To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model. METHODS: Prospective randomized placebo-controlled trial conducted in the inpatient General Clinical Research Center between May 2003 and May 2005 involving adults with painful HIV-associated sensory neuropathy. Patients were randomly assigned to smoke either cannabis (3.56% tetrahydrocannabinol) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days. Primary outcome measures included ratings of chronic pain and the percentage achieving >30% reduction in pain intensity. Acute analgesic and anti-hyperalgesic effects of smoked cannabis were assessed using a cutaneous heat stimulation procedure and the heat/capsaicin sensitization model. RESULTS: Fifty patients completed the entire trial. Smoked cannabis reduced daily pain by 34% (median reduction; IQR = -71, -16) vs 17% (IQR = -29, 8) with placebo (p = 0.03). Greater than 30% reduction in pain was reported by 52% in the cannabis group and by 24% in the placebo group (p = 0.04). The first cannabis cigarette reduced chronic pain by a median of 72% vs 15% with placebo (p < 0.001). Cannabis reduced experimentally induced hyperalgesia to both brush and von Frey hair stimuli (p < or = 0.05) but appeared to have little effect on the painfulness of noxious heat stimulation. No serious adverse events were reported. CONCLUSION: Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy. The findings are comparable to oral drugs used for chronic neuropathic pain.

Effect of acupuncture administered in a group setting on pain and subjective peripheral neuropathy in persons with human immunodeficiency virus disease.

OBJECTIVES: The present study was performed to determine the effect of 5 weeks of acupuncture treatment in a group setting on pain and symptoms of peripheral neuropathy in human immunodeficiency virus (HIV)infected individuals. DESIGN: Twenty-one (21) subjects completed the study that consisted of a pretreatment and post-treatment case series design. The subjects completed the Pain Rating Scale and the Subjective Peripheral Neuropathy Screen (SPNS) before and after 5 weeks of acupuncture. The acupuncture treatments occurred two evenings per week. Each of the 10 sessions consisted of participants receiving 10-15 needle insertions in acupoints that addressed the individual's changing pattern of pain, sleep problems, or other health issues. The treatment utilized only main or common points located below the elbows and knees, and on the head, neck, and ears. Only reactive points were used in the acupuncture treatments. Needles were left in situ for 30-45 minutes. RESULTS: Comparison of the pretreatment and post-treatment Pain Rating Scale results indicated a significant reduction in present pain (p = 0.0002), least and most pain in the last 24 hours (p < 0.0001 and p = 0.0004, respectively) and the total pain summary score (p < 0.0001). Symptoms reported in the SPNS were reduced during the 5 weeks of acupuncture. Scores for pain/aching/burning, pins and needles, and numbness in the hands and feet were reduced (all significant at less than p = 0.0065), as well as the total summary score (p = 0.0001). CONCLUSION: The results of this study indicate that subjective pain and symptoms of peripheral neuropathy were reduced during the period of individual acupuncture therapy delivered in a group setting. While the study design did not allow for control of nonspecific placebo factors, the data support the hypothesis that acupuncture in a group setting can reduce pain and neuropathic symptoms in HIV-infected individuals.

Self-care management for neuropathy in HIV disease.

Peripheral neuropathy is the most common neurological complication in HIV and is often associated with antiretroviral therapy. As part of a larger study on self-care for symptoms in HIV disease, this study analyzed the prevalence and characteristics of peripheral neuropathy in HIV disease, the self-care strategies, and sources of information for self-care utilized by the sample. A convenience sample of 422 respondents was recruited from an Internet web-based site developed by the University of California, San Francisco International HIV/AIDS Research Network and from five geographic data collection sites (Boston, New York City, San Francisco and Paterson in the USA, and Oslo, Norway). Results of the study indicated that respondents with peripheral neuropathy identified 77 self-care behaviours including complementary therapies, use of medications, exercise and rest and/or elevation of extremities. Sources of information included health care providers, informal networks and media sources.

Viral isolation from cases of epidemic neuropathy in Cuba.

OBJECTIVE: To investigate the possibility of a viral agent in the central nervous system of patients with epidemic neuropathy. DESIGN: Virus isolation attempts, in cell cultures and suckling mice, from cerebrospinal fluid (CSF) of neuropathy patients and controls undergoing lumbar puncture for unrelated reasons. Serologic studies in patients, contacts, and controls. SETTING: An epidemic of optic and peripheral neuropathy affected more than 50,000 people in Cuba in 1991 through 1993. Illness was associated with dietary limitations and increased physical demands accompanying the shortages of food and fuel experienced in Cuba since 1989. Most patients responded to parenteral vitamin therapy, and the epidemic began to subside when oral vitamin supplementation was begun for the entire Cuban population. RESULTS: Coxsackievirus A9 (five isolates) and a similar, less cytopathic virus (100 isolates) were recovered from 105 (84%) of 125 CSF specimens from neuropathy patients. The strains with light cytopathic effect were antigenically related to Coxsackieviruses A9 and B4 by cross-neutralization and immunoblotting assays. Virus persisted in CSF of some patients for 1 to 12 months. Cerebrospinal fluid from patients and both types of virus from cell culture produced illness, including complete posterior flaccid paralysis, in newborn mice, and virus was reisolated from the mice. Mouse tissues and sural nerve biopsy specimens from patients were stained by immunoperoxidase and colloidal gold techniques using hyperimmune rabbit antisera against the virus with light cytopathic effect. CONCLUSIONS: Coxsackievirus A9 or an antigenically related agent with a light cytopathic effect was present in CSF of 84% of 125 patients with epidemic neuropathy. The role of these agents, probably in combination with nutritional factors, in the pathophysiology of the disease requires further investigation.