Incident neuropathy in HIV-infected patients on HAART.

We determined the incidence of and risk factors for distal sensory polyneuropathy (DSP) in individuals on HAART. Sixty-one HIV-positive subjects on HAART for at least 6 months and neuropathy free were retrospectively selected. The study included subjects who had previously tolerated d-drugs without developing DSP. Neuropathy incidence over 4 years was calculated. Cox proportional hazards models were used to determine risk factors associated with incident DSP. Nineteen subjects developed DSP over a mean follow-up of 2.4 years. Subjects never treated with a d-drug developed DSP at a rate of 21 cases per 100 person-years (95% CI, 8.9-33.7). Subjects with a history of d-drug treatment but not on a d-drug at enrollment developed DSP at a rate of 17 cases per 100 person-years (95% CI, 2.1-31.8). Those on d-drug treatment developed DSP at a rate of 25 cases per 100 person-years (95% CI, 8.7-41.6). Multivariable analysis identified age [hazard ratio (HR) = 1.09; p < 0.01] and low CD4(+) nadir [hazard ratio (HR) = 0.79; p = 0.03] as significant risk factors. Current or prior history of treatment with d-drug was not a significant risk factor for incident DSP in subjects who had previously tolerated d-drug treatment without developing a toxic DSP. Age and low CD4(+) are risk factors for incident DSP. However, current or prior history of d-drug treatment is not a significant risk factor for incident DSP in subjects who had previously tolerated d-drug treatment without developing a toxic DSP.

Aging exacerbates extrapyramidal motor signs in the era of highly active antiretroviral therapy.

The phenotype of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) in the developed world has changed with the broad institution of highly active antiretroviral therapy (HAART) and with aging of the HIV+ population. Extrapyramidal motor signs were a prominent feature of HAND as defined in the early stages of the epidemic but has not been reevaluated in the era of HAART. Moreover, the contribution of aging to extrapyramidal motor signs in the context of HIV remains undefined. We examined these questions among the 229 HIV+ participants in the Hawaii Aging with HIV Cohort compared to age-, gender-, and ethnicity-matched HIV-negative controls. Extrapyramidal motor signs were quantified using the motor exam of the Unified Parkinson's Disease Rating Scale (UPDRSmotor) and compared to concurrent neuropsychological and clinical cognitive diagnostic categorization. The mean UPDRSmotor score increased with older age (1.68 versus 3.35; P<.001) and with HIV status (1.18 versus 3.56; P<.001). Age group (P=.024), HIV status (P<.001), and the interaction between age and HIV (P=.026) were significantly associated with UPDRSmotor score. Among HIV+ patients, the mean UPDRSmotor score increased with worsening cognitive diagnostic category (P<.001) where it was 2.06 (2.31) in normal cognition (n=110), 3.21 (3.48) in minor cognitive motor disorder (MCMD) (n=84), and 5.72 (5.01) in HIV-associated dementia (HAD) (n=37). We conclude that extrapyramidal motor signs are increased in HIV in the era of HAART and that the impact of HIV on extrapyramidal motor signs is exacerbated by aging. These results highlight the importance of a careful neurological examination in the evaluation of HIV patients.

Solitary brain lesions enhancing at MR imaging: evaluation with fluorine 18 fluorocholine PET.

PURPOSE: To prospectively determine whether differences between benign and malignant brain lesions can be depicted with fluorine 18 ((18)F) fluorocholine positron emission tomography (PET). MATERIALS AND METHODS: Thirty consecutive patients (14 women, 16 men; age range, 26-79 years) with solitary brain lesions that were enhanced at magnetic resonance (MR) imaging underwent whole-brain (18)F-fluorocholine PET after giving informed consent in this institutional review board-approved, HIPAA-compliant study. Histopathologic diagnoses were made in 24 cases (13 high-grade gliomas, eight metastases to the brain, and three benign lesions). In six cases, benign lesions were diagnosed on the basis of longitudinal follow-up MR findings. The maximum standardized uptake value (SUV(max)) for lesion and peritumoral regions was measured on PET images, and a lesion-to-normal tissue uptake ratio (LNR) was calculated. Differences were assessed with one-way analysis of variance, Fisher exact, and Student t tests. RESULTS: Differences in SUV(max) between high-grade gliomas (1.89 +/- 0.78 [mean +/- standard deviation]), metastases (4.11 +/- 1.68), and benign lesions (0.59 +/- 0.31) were significant (P < .0001). LNRs also differed significantly (5.15 +/- 2.51, 10.91 +/- 2.14, and 1.28 +/- 0.32, respectively; P < .0001). These differences were also significant at pairwise analysis. The peritumoral LNR exceeded 2.0 in seven high-grade gliomas and no metastases (P = .02). In 14 radiation-treated patients, the lesions classified as benign demonstrated significantly less uptake compared with the recurrent tumors (SUV(max): 0.72 +/- 0.38 vs 2.27 +/- 1.24, P < .01; LNR: 1.36 +/- 0.43 vs 5.88 +/- 3.66, P < .01). CONCLUSION: High-grade gliomas, metastases, and benign lesions can be distinguished on the basis of measured fluorocholine uptake. Increased peritumoral fluorocholine uptake is a distinguishing characteristic of high-grade gliomas.

Insulin resistance is associated with cognition among HIV-1-infected patients: the Hawaii Aging With HIV cohort.

OBJECTIVE: To determine if insulin resistance (IR) is associated with lower cognitive performance among HIV-1-infected adults and to determine if advanced age magnifies risk. DESIGN: Cross-sectional analysis within the Hawaii Aging With HIV Cohort. METHODS: We calculated the homeostasis model assessment of insulin resistance (HOMA-IR) among 145 cohort participants. Values were compared to concurrent neuropsychological test performance and cognitive diagnoses. RESULTS: Hypertension, body mass index (BMI), and non-Caucasian self-identity were directly related to insulin resistance (IR); however, age, CD4 lymphocyte count, and rates of treatment with HAART were not. In logistic regression analyses and stratifying cognition status on a 3-tiered scale (normal, minor cognitive motor disorder (MCMD), and HIV-associated dementia (HAD)), we identified an increased risk of meeting a higher diagnostic category as HOMA-IR increased (OR, 1.12; 95% CI: 1.003 to 1.242 per unit of HOMA-IR, P = 0.044). In linear regression models and among nondiabetic participants, an increasing degree of IR was associated with lower performance on neuropsychological summary scores. CONCLUSIONS: IR is associated with cognitive dysfunction in this contemporary HIV-1 cohort enriched with older individuals. Metabolic dysfunction may contribute to the multifactorial pathogenesis of cognitive impairment in the era of HAART.

Tropical marine neurotoxins: venoms to drugs.

Neurotoxic venoms are common among tropical marine creatures, which have specialized apparatuses for delivery of the venoms. These include jellyfish and anemones, venomous cone snails, venomous fish, stingrays, sea snakes, and venomous octopuses. Numerous toxic neuropeptides are found within these venoms, and some can discriminate between closely related intracellular targets, a characteristic that makes them useful to define cation channels and attractive for drug development. A synthetic derivative of an omega-conotoxin is now available, representing a new class of analgesics. In general, toxic marine venoms contain proteins that are heat labile, providing opportunity for therapeutic intervention following envenomation, while ingestible seafood toxins are thermostable toxins. Ingestible toxins found in the tropics include those associated with reef fish, pufferfish, and some shellfish, which serve as food-chain vectors for toxins produced by marine microorganisms.

Diabetes, insulin resistance, and dementia among HIV-1-infected patients.

OBJECTIVES: Metabolic complications have been associated with HIV-1 infection and with long-term use of antiretroviral (ARV) medications. In some studies, such complications have been linked to cardiovascular events, yet limited data exist concerning metabolic complications and dementia. The objective of this study was to examine the relationship between HIV-associated dementia (HAD) and diabetes among patients with HIV-1 infection. DESIGN: Cross-sectional analysis of entry data for a longitudinal cohort study. METHODS: A total of 203 participants who were enrolled in the Hawaii Aging with HIV Cohort between October 2001 and November 2003 served as the study population. Research case definitions of HAD were determined in consensus conferences by a panel that included neurologists, neuropsychologists, and a geriatrician. Diabetes was determined by self-report or a fasting glucose level > 125 mg/dL. RESULTS: Participants' ages ranged between 20-76 years at enrollment with approximately one-half aged >/=50 years. After adjustment for important covariates including age, education, ethnicity, CD4 lymphocyte count, duration of HIV infection, and protease inhibitor-based ARV therapy, we found a statistically significant association of diabetes with HAD (odds ratio 5.43, 1.66-17.70). A significant association remained after adjustment for other vascular risk factors. Among participants without diabetes, fasting glucose levels were higher with increasing impairment category. CONCLUSIONS: Within the Hawaii Aging with HIV Cohort, a longitudinal study enriched with older HIV-1-infected individuals, diabetes is associated with prevalent dementia. This finding is not fully explained by age or coexisting vascular risk factors. Evaluation of underlying mechanisms is warranted.

Cognitive impairment in older HIV-1-seropositive individuals: prevalence and potential mechanisms.

Individuals over 50 years of age comprise 11% of AIDS cases reported to the Centers for Disease Control and Prevention. A higher prevalence of AIDS in older individuals has been reported in certain states including Hawaii (20%) and Florida (13%). Although life expectancy in individuals with AIDS has increased with advances in antiretroviral therapy, it is likely that there are health consequences both of long-term infection and chronic antiretroviral therapy. Given the general increase in neurological disorders with age and the relatively high prevalence of cognitive dysfunction associated with HIV itself, the risk of HIV-associated dementia (HAD) in this aging HIV-seropositive subgroup is of particular concern. Existing data suggest, but have not conclusively demonstrated, increased rates of HAD in older compared with younger seropositive individuals. Preliminary data from the Hawaii Aging with HIV Cohort, a prospective cohort study designed to address this issue definitively, are presented. Factors underlying this hypothesized susceptibility in older individuals are discussed, including a synergy among HAD and other dementias, the role of vascular co-pathology, HIV and age-related immunological changes, and detrimental neuroglial changes that limit the compensatory ability of the aging brain.

Marine Neurotoxins: Ingestible Toxins.

Fish and shellfish account for a significant portion of food-borne illnesses throughout the world. In general, three classes of diseases result from seafood consumption--intoxication, allergies, and infections. In this review, the authors discuss several seafood-borne toxins, including domoic acid, which acts on the central nervous system. In addition, the authors discuss ciguatoxin-, brevetoxin-, saxitoxin-, tetrodotoxin-, and scombroid-related histamine toxicity, all of which act primarily on the peripheral nervous system. Fish has become a very popular food in the US mostly related to its potential health benefits. Fish is consumed to such a degree that fishing stocks are reportedly at an all time low from what seemed like an endless supply even 30 years ago. One of the most significant threats to human intoxication is the recreational harvest of shellfish, often times located in remote locations where the harvesters are subsistent on fishery resources and have no monitoring in place. The hazard to intoxication is not as common in purchased seafood, which is more stringently regulated, yet still is a serious problem. Most ingestible toxins are thermo-stable and therefore unaffected by cooking, freezing, or salting. Air transport of consumable products throughout the world makes it easy to obtain exotic edibles from far away countries. A seemingly unusual toxin can be more commonly encountered than previously thought and it is important to consider this when evaluating patients. Recognition and treatment of various neurologic symptoms related to seafood ingestion is paramount in today's mobile, gastronomic world. Specific treatments vary with each individual toxin and with the individual's specific reaction to the toxin. Generally, some degree of medical care is required with all ingestible toxin exposure, ranging from simple administration of medication and hydration to ventilatory and cardiovascular support.

Marine Neurotoxins: Envenomations and Contact Toxins.

Familiarity with the appearance and habitat of venomous sea creatures, the location of their stinging apparatus, and surveillance of population concentrations within recreational waters are essential in avoiding envenomations. Compared with the thermo-stable low molecular weighted ingestible seafood toxins, venomous toxins are often large molecular weight proteins and many are heat labile, which provides opportunity for therapeutic intervention. Heat therapy may denature the toxins, and provide immediate relief of pain in coelenterate and venomous fish envenomations. Injections of local anesthetic agents may also be used. First aid measures at the seashore may limit the spread of venom, and include immobilization of the affected sites, compression bandaging, and venous-lymphatic occlusive bandages. Measures to limit continued envenomation by attached stinging cells include topical vinegar for jellyfish tentacles and irrigation with debridment for spines of venomous fish. Antivenins are of limited availability and may be used for envenomations with sea snakes, Chironex box jellyfish, and some venomous fish. Sea snakes bites may be treated with antivenin from land snakes or with hemodialysis when antivenin is not available. Neuromuscular paralysis occurs with bites by sea snakes, cone snails, blue octopuses, and some jellyfish. Supportive treatment includes attention to cardiopulmonary resuscitation and intubation. Exposure to Pfeisteria may result in cognitive and behavioral abnormalities. Treatment with cholestyramine may be helpful in binding the toxin and improve recovery.