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OBJECTIVE Mechanisms underlying immune activation and HIV-associated neurocognitive disorders (HAND) in untreated chronic infection remain unclear. The objective of this study was to identify phenotypic and transcriptional changes in blood monocytes and CD4 T cells in HIV-1-infected and uninfected individuals and elucidate processes associated with neurocognitive impairment. DESIGN A group of chronically HIV-1-infected Thai individuals (n = 19) were selected for comparison with healthy donor controls (n = 10). Infected participants were further classified as cognitively normal (n = 10) or with HAND (n = 9). Peripheral monocytes and CD4 T cells were phenotyped by flow cytometry and simultaneously isolated for multiplex qPCR-targeted gene expression profiling directly ex vivo. The frequency of HIV-1 RNA-positive cells was estimated by limiting dilution cell sorting. RESULTS Expression of genes and proteins involved in cellular activation and proinflammatory immune responses was increased in monocytes and CD4 T cells from HIV-1-infected relative to uninfected individuals. Gene expression profiles of both CD4 T cells and monocytes correlated with soluble markers of inflammation in the periphery (P

Objective A randomized, double-blinded, crossover, placebo controlled trial was conducted to evaluate the efficacy and safety of 0.075% capsaicin lotion for treating painful diabetic neuropathy (PDN). Patients and methods PDN subjects were randomized to receive 0.075% capsaicin/placebo for 8 weeks, then crossing over to the other treatment after a 4-weeks washout period. Primary endpoint was the change in visual analog scale score of pain severity. Secondary outcomes were score changes in Neuropathic Pain Scale, short-form McGill Pain Questionnaires, and proportions of patients with pain score reductions of 30% and 50%, and adverse events. Results A total of 42 subjects were enrolled, 27 completed at least an 8-week treatment period. Intention-to-treat analysis showed no significant improvement in pain control with capsaicin lotion compared with placebo for all pain measures and proportion of patients who had 30% or 50% pain relief, respectively. Per protocol analysis were consistent. Capsaicin lotion was well tolerated but local skin reactions were common. Conclusion In patients with PDN, the efficacy of 0.075% capsaicin lotion was similar to placebo but was well tolerated. More work is needed to assess different capsaicin formulations.

We aimed to determine (1) the frequency of high-risk sudden unexpected death in epilepsy (SUDEP) in patients with epilepsy who have had obstructive sleep apnea (OSA) in different stages of sleep using the revised SUDEP risk inventory (rSUDEP-7) score instrument and (2) the factors associated with high risk SUDEP in patients with epilepsy who have had OSA.We conducted a cross-sectional study of consecutive subjects who are more than 15 years old without known sleep disorders, recruited from a single epilepsy clinic in a tertiary care facility. Participants underwent polysomnography. Scoring was performed by two blinded board-certified sleep physicians. The relationships between rSUDEP-7 scores and OSA measures were evaluated using Wilcoxon rank-sum test, chi-squared test, and quantile regression.Our study population consisted of 95 participants. Overall median (IQR) apnea-hypopnea index (AHI) of our populations was 2.3 (0.7,7.5) events rate per hour; 12 (75%) patients had moderate OSA and 4 (25%) patients had severe OSA. Nine patients had a rSUDEP-7 score of 5 to 7. There was no significant difference between total rSUDEP-7 score or rSUDEP-7 score of5 or5 and total AHI, supine AHI, non-supine AHI, NREM AHI, or REM AHI; similarly, (2) there was no significant difference in total rSUDEP-7 score between AHI of15 or15.Our study reveals no association between AHI score, OSA, and total rSUDEP-7 score or rSUDEP-7 score of5. The pathophysiology underlying SUDEP appears complex. We need further studies on SUDEP to help elucidate the cardiorespiratory mechanisms and predisposing factors.

Background: We aimed to study the efficacy and safety of allopregnanolone which convert from oral micronized progesterone as an adjunctive treatment for Thai patients with refractory status epilepticus.Methods: Adults 18–80 years old who diagnosed with either convulsive or non-convulsive refractory status epilepticus receiving standard AED treatment, intravenous midazolam, for longer than 60 minutes were included. The intervention group received Utrogestran® (micronized progesterone, 200 mg/capsule) via enteric feeding every 8 h for five days. Treatments for RSE were continuing along the clinical trial period. Serum allopregnanolone levels were measured by radioimmunoassay (DetectX® Allopregnanolone Immunoassay Kit; Arbor Assays, Michigan, United States). Control patients were randomly selected from our hospital RSE cohort during 2015–2019. Continuous data were presented as the mean and standard deviation. Discrete data were assessed by number and percentage. The changes in laboratories were analyzed by paired t-test. The difference between groups were compared by independent sample t-test. The Mann-Whitney U test, Chi-square test or Fisher’s exact test were used for non-parametric parameters. A p-value < 0.05 indicated statistical significance. All analyses were performed using SPSS version 26 software (IBM Corp., Armonk, NY).Results: The average duration of refractory status epilepticus after treatment with midazolam plus progesterone (intervention group) and without progesterone until status epilepticus termination was 25.5 and 58.4 hours, (p = 0.004), indicated that allopregnanolone significantly shortens the refractory status epilepticus duration in vivo.Conclusions: Allopregnanolone, produced from oral micronized progesterone, demonstrates efficacy and safety in treating refractory status epilepticus as an adjunctive treatment.Trial registration: This trial was registered in Thai Clinical Trials Registry (TCTR) database. The trial registration number was “TCTR20200717002”, 16 July 2020, retrospectively registered.

HIV-associated neurocognitive disorder (HAND) remains a challenge despite antiretroviral therapy (ART), and has been linked to monocyte/macrophage (M/M) migration to the brain. Due to the potential impact of T cell effector mechanisms in eliminating activated/HIV-infected M/M, T cell activation may play a role in the development of HAND. We sought to investigate the relationship between cognition and both CD8+ T cell activation (HLA-DR+/CD38+) and HIV-specific CD8+ T cell responses at the time of HIV diagnosis and 12 months postinitiation of ART. CD8+ T cell activation was increased in HAND compared to cognitive normal (NL) individuals and correlated directly with plasma viral load and inversely with the cognitive status. In addition, Gag-specific cytolytic activity (CD107a/b+) was decreased in HAND compared with NL individuals and correlated with their neurological testing, suggesting a potential role of cytotoxic CD8+ T cells in the mechanism of HAND development.

BACKGROUND: Myeloid activation contributes to cognitive impairment in chronic human immunodeficiency virus (HIV) infection. We explored whether combination antiretroviral therapy (cART) initiation during acute HIV infection impacts CD163 shedding, a myeloid activation marker, and in turn, implications on the central nervous system (CNS). METHODS: We measured soluble CD163 (sCD163) levels in plasma and cerebrospinal fluid (CSF) by enzyme-linked immunosorbent assay in Thais who initiated cART during acute HIV infection (Fiebig stages I–IV). Examination of CNS involvement included neuropsychological testing and analysis of brain metabolites by magnetic resonance spectroscopy. Chronic HIV-infected or uninfected Thais served as controls. RESULTS: We examined 51 adults with acute HIV infection (Fiebig stages I–III; male sex, >90%; age, 31 years). sCD163 levels before and after cART in Fiebig stage I/II were comparable to those in uninfected controls (plasma levels, 97.9 and 93.6 ng/mL, respectively, vs 99.5 ng/mL; CSF levels, 6.7 and 6.4 ng/mL, respectively, vs 7.1 ng/mL). In Fiebig stage III, sCD163 levels were elevated before cART as compared to those in uninfected controls (plasma levels, 135 ng/mL; CSF levels, 10 ng/mL; P < .01 for both comparisons) before normalization after cART (plasma levels, 90.1 ng/mL; CSF levels, 6.5 ng/mL). Before cART, higher sCD163 levels during Fiebig stage III correlated with poor CNS measures (eg, decreased N-acetylaspartate levels), but paradoxically, during Fiebig stage I/II, this association was linked with favorable CNS outcomes (eg, higher neuropsychological test scores). After cART initiation, higher sCD163 levels during Fiebig stage III were associated with negative CNS indices (eg, worse neuropsychological test scores). CONCLUSION: Initiation of cART early during acute HIV infection (ie, during Fiebig stage I/II) may decrease inflammation, preventing shedding of CD163, which in turn might lower the risk of brain injury.

Monocytes play a vital role in HIV-associated neurocognitive disorder (HAND), postulated to transport HIV into the brain and secrete pro-inflammatory cytokines. We analyzed cytokines released by cultured peripheral blood mononuclear cells enriched with the CD14 marker isolated from HIV-infected individuals with HAND and normal cognition (NC) in combination antiretroviral therapy naive and after 1 year on treatment. Interleukin-8 and monocyte chemoattractant protein-1 levels were higher in HAND compared with NC at baseline (P = 0.002 and P < 0.0001). These cytokines remained higher in HAND patients 1 year after combination antiretroviral therapy and were significant when NC patients who were initially HAND were excluded (P = 0.012 and P = 0.002). Both correlated with baseline CD14 peripheral blood mononuclear cell HIV DNA levels supporting the role of HIV DNA reservoir size and monocyte cytokines in HAND persistence.

In May 2012, the Division of AIDS Research at the National Institute of Mental Health (NIMH) organized the "Global NeuroAIDS Roundtable" in conjunction with the 11th International Symposium on Neurovirology and the 2012 Conference on HIV in the Nervous System. The meeting was held in New York, NY, USA and brought together NIMH-funded investigators who are currently working on projects related to the neurological complications of AIDS (NeuroAIDS) in Africa, Asia, Eastern Europe, and Latin America in order to provide an opportunity to share their recent findings and discuss the challenges encountered within each country. The major goals of the roundtable were to evaluate HIV-associated neurocognitive impairment and determine if it may be directly attributable to distinct HIV subtypes or clades and to discuss the future priorities for global NeuroAIDS research. At the "Global NeuroAIDS Roundtable", presentations of preliminary research indicated that HIV-associated neurocognitive impairment is prevalent in all countries examined regardless of which HIV clade is present in the region. The only clear-cut difference between HIV-1 clades was in relation to subtypes A and D in Uganda. However, a key point that emerged from the discussions was that there is an urgent need to standardize neurocognitive assessment methodologies across the globe before definitive conclusions can be drawn regarding the relationship between HIV clade diversity and neuropathogenesis. Future research directions were also discussed at the roundtable with particular emphasis on the potential of viral and host factor molecular interactions to impact the pathophysiology of HIV-associated neurocognitive disorders (HAND) from a global perspective. © 2013 Journal of NeuroVirology, Inc. (outside the USA).

ObjectiveTo evaluate differences in soluble inflammatory markers between chronically HIV-infected men and women, with or without cognitive impairment, and in response to treatment.DesignSoluble biomarkers were measured in cryopreserved plasma and cerebrospinal fluid (CSF) of 60 treatment-naïve individuals (25 men and 35 women) with chronic HIV infection and 18 HIV-uninfected controls (9 men and 9 women) from Thailand. Following enrollment, participants began combination antiretroviral therapy and were evaluated for expression of these markers after 48 weeks.MethodsPlasma and CSF levels of 19 soluble biomarkers (IFN-γ, TNFα, TNF-RII, IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-15, MCP-1, t-Tau, IP-10, neopterin, IFNα, I-FABP, and sCD14) were measured using either a multiparameter or standard ELISA assay.ResultsPrior to combination antiretroviral therapy, women with impaired cognition had elevated levels of neopterin and TNF-RII compared with women with normal cognition in both the plasma and CSF; however, levels did not differ between cognitively impaired or normal men. In a secondary outcome-hypothesis generating analysis, sex differences were also pronounced in plasma levels of MCP-1, IL-10, I-FABP, and sCD14 in response to treatment. Neopterin, IP-10, TNFα, TNF-RII, IFNα, MCP-1, IL-8, I-FABP, and sCD14 plasma levels remained elevated following 48 weeks of therapy in both sexes compared with uninfected controls.ConclusionWe provide evidence of sustained immune activation after 48 weeks of treatment and identify possible sex differences in biomarkers previously linked to cognitive impairment, chronic inflammation, and gut integrity that may contribute to immunological differences between sexes in relationship to disease progression and response to therapy.

HIV can infect the brain and impair central nervous system (CNS) function. Combination antiretroviral therapy (cART) has not eradicated CNS complications. HIV-associated neurocognitive disorders (HAND) remain common despite cART, although attenuated in severity. This may result from a combination of factors including inadequate treatment of HIV reservoirs such as circulating monocytes and glia, decreased effectiveness of cART in CNS, concurrent illnesses, stimulant use, and factors associated with prescribed drugs, including antiretrovirals. This review highlights recent investigations of HIV-related CNS injury with emphasis on cART-era neuropathological mechanisms in the context of both US and international settings.

(Headache 2011;51:52-63) Objective.— To evaluate the efficacy, safety, and optimum dose of a highly purified Clostridium botulinum type A toxin-hemagglutinin complex (Dysport) for migraine prophylaxis. Background.— Botulinum toxin type-A has demonstrated good efficacy in several open-label studies of patients with migraine, involving either individualized or standardized protocols, although data from placebo-controlled trials have been conflicting. Methods.— A 12-week, double-blind, randomized trial of Dysport (120 or 240 units) vs placebo was conducted in 6 centers in Thailand to evaluate the efficacy, safety, and optimum dose of botulinum toxin type-A (Dysport) for migraine prophylaxis. A total of 128 patients with migraine without aura were enrolled. The primary end point was the change in the mean number of migraine attacks per 4-week period from the pre-treatment period to 8-12 weeks post injection. Secondary efficacy measures included the change in the mean total intensity score from the pre-treatment period to 8-12 weeks, the investigator and patient global assessments of change at each visit compared with pre-treatment, and Migraine Disability Assessment and Short Form-36 scores. Results.— Change in number of migraine attacks from pre-treatment to weeks 8-12 was not significantly different. There was a greater improvement in total intensity score at weeks 8-12 with Dysport-240 (not significant), and interim visit data showed that this was significant at weeks 0-4 (P = .03 Dysport-240 vs placebo). The mean duration of headache during weeks 0-4 was lower with Dysport-240 (P = .04 vs placebo). Improvements in patient and investigator global assessments of change between weeks 0-4 and 8-12 were significant for the Dysport-240 group (both P

In this study we describe the electrophysiological findings in botulism patients with neuromuscular respiratory failure from major botulism outbreaks in Thailand. High-rate repetitive nerve stimulation testing (RNST) of the abductor digiti minimi (ADM) muscle of 17 botulism patients with neuromuscular respiratory failure showed mostly incremental responses, especially in response to >20-HZ stimulation. In the most severe stage of neuromuscular respiratory failure, RNST failed to elicit a compound muscle action potential (CMAP) of the ADM muscle. In the moderately severe stage, the initial CMAPs were of very low amplitude, and a 3-HZ RNST elicited incremental or decremental responses. A 10-HZ RNST elicited mainly decremental responses. In the early recovery stage, the initial CMAP amplitudes of the ADM muscle improved, with initially low amplitudes and an incremental response to 3- and 10-HZ RNSTs. Improved electrophysiological patterns of the ADM muscle correlated with improved respiratory muscle function. Incremental responses to 20-HZ RNST were most useful for diagnosis. The initial electrodiagnostic sign of recovery following treatment of neuromuscular respiratory failure was an increased CMAP amplitude and an incremental response to 10-20-HZ RNST. Muscle Nerve 40: 271-278, 2009.

SCN1A is the most clinically relevant epilepsy gene and is associated with generalized epilepsy and febrile seizure plus (GEFS+) and Dravet syndrome. We postulated that earlier onset of febrile seizures in the febrile seizure (FS) and febrile seizure plus (FS+) phenotypes may occur in the presence of a SCN1A mutation. This was because of the age-related onset of Dravet syndrome, which typically begins in the first year of life. We found that patients with FS and FS+ with SCN1A mutations had earlier median onset of febrile seizures compared to the population median. Patients with GABRG2 mutations had a similar early onset in contrast to patients with SCN1B mutations where onset was later. This study is the first to demonstrate that a specific genetic abnormality directly influences the FS and FS+ phenotype in terms of age of onset. Refereed/Peer-reviewed

The extent to which highly active antiretroviral therapy (HAART) era cognitive disorders are due to active processes, incomplete clearance of reservoirs, or comorbidities is controversial. This study aimed to determine if immunologic and virologic factors influence cognition after first-time HAART in Thai individuals with HIV-associated dementia (HAD) and Thai individuals without HAD (non-HAD).Variables were captured longitudinally to determine factors predictive of degree of cognitive recovery after first-time HAART. Neuropsychological data were compared to those of 230 HIV-negative Thai controls.HIV RNA and CD4 lymphocyte counts were not predictive of HAD cross-sectionally or degree of cognitive improvement longitudinally. In contrast, baseline and longitudinal HIV DNA isolated from monocytes correlated to cognitive performance irrespective of plasma HIV RNA and CD4 lymphocyte counts pre-HAART (p0.001) and at 48 weeks post HAART (p0.001). Levels exceeding 3.5 log(10) copies HIV DNA/10(6) monocyte at baseline distinguished all HAD and non-HAD cases (p0.001). At 48 weeks, monocyte HIV DNA was below the level of detection of our assay (10 copies/10(6) cells) in 15/15 non-HAD compared to only 4/12 HAD cases, despite undetectable plasma HIV RNA in 26/27 cases. Baseline monocyte HIV DNA predicted 48-week cognitive performance on a composite score, independently of concurrent monocyte HIV DNA and CD4 count (p0.001).Monocyte HIV DNA level correlates to cognitive performance before highly active antiretroviral therapy (HAART) and 48 weeks after HAART in this cohort and baseline monocyte HIV DNA may predict 48-week cognitive performance. These findings raise the possibility that short-term incomplete cognitive recovery with HAART may represent an active process related to this peripheral reservoir.

Objective Combination antiretroviral therapy (cART) can suppress plasma HIV RNA to undetectable levels; yet reports indicate persistent HIV-associated neurocognitive disorders (HAND) among treated individuals. We sought to investigate imaging correlates of incomplete cognitive recovery among individuals with chronic HIV. Methods We used single voxel proton magnetic resonance spectroscopy in 4 regions of the brain to measure changes in neuronal and glia biomarkers in cART-naive subjects before (n = 59, 27 with HAND) and after 12 months of cART. Results At baseline, we observed elevated total choline (CHO) in the basal ganglia (BG, P = 0.002) and in the posterior cingulate gyrus (PCG, P = 0.022) associated with HIV infection. Myo-inositol (MI) was elevated in the frontal white matter (FWM, P = 0.040). N-acetylaspartate was elevated in the BG (P = 0.047). Using a mixed model approach among all HIV-infected individuals, at 6 months, we observed decreased n- acetylaspartate in FWM (P = 0.031), decreased creatine in PCG (P = 0.026) and increased MI in frontal gray matter (FGM, P = 0.023). At 12 months, we observed an increase in BG MI (P = 0.038) and in FGM (P = 0.021). Compared to those with normal cognition, HAND cases had higher FGM MI (P = 0.014) at baseline. At 12 months, individuals that remained cognitively impaired compared with those without HAND exhibited elevated CHO in the PCG (P = 0.018) and decreased glutamate in both FWM (P = 0.027) and BG (P = 0.013). Conclusions cART started during chronic HIV is associated with reduced neuronal-glia and inflammatory markers. Alterations in CHO are noted among individuals who remain impaired after 12 months of cART.

Background. It is unknown whether neuronal injury begins during acute human immunodeficiency virus (HIV) infection, and whether immediate initiation of combination antiretroviral therapy (cART) prevents neuronal injury. Methods. Cerebrospinal fluid (CSF) neurofilament light chain (NFL), a measure of axonal injury, was assessed before and after cART initiation in individuals starting treatment during acute or chronic HIV infection. Nonparametric statistics examined relationships between NFL and disease progression, neuroinflammation, and cognitive performance. Results. Before treatment, subjects with acute infection had lower CSF NFL levels, with elevations for their age in 1 of 32 subjects with acute infection (3.1%) and 10 of 32 with chronic infection (31%) (P = .006). This persisted after cART initiation, with 1 of 25 acute (4%) and 4 of 9 chronic subjects (44%) showing elevated NFL levels (P = .01). In acute infection, pre-cART NFL levels were inversely correlated with proton magnetic resonance spectroscopic findings of N-acetylaspartate/creatine in frontal gray matter (r = −0.40; P = .03), frontal white matter (r = −0.46; P = .01), and parietal gray matter (r = −0.47; P = .01); correlations persisted after treatment in the frontal white matter (r = −0.51; P = .02) and parietal gray matter (r = −0.46; P = .04). Conclusions. CSF NFL levels are not elevated in untreated acute HIV infection or after 6 months of immediately initiated cART but are abnormal in chronic HIV infection before and after treatment. In acute HIV infection, CSF NFL levels are inversely associated with neuroimaging markers of neuronal health.

Background Northern Thailand's biggest botulism outbreak to date occurred on 14 March 2006 and affected 209 people. Of these, 42 developed respiratory failure, and 25 of those who developed respiratory failure were referred to 9 high facility hospitals for treatment of severe respiratory failure and autonomic nervous system involvement. Among these patients, we aimed to assess the relationship between the rate of ventilator dependence and the occurrence of treatment by day 4 versus day 6 after exposure to bamboo shoots (the source of the botulism outbreak), as well as the relationship between ventilator dependence and negative inspiratory pressure. Methods We reviewed the circumstances and timing of symptoms following exposure. Mobile teams treated patients with botulinum antitoxin on day 4 or day 6 after exposure in Nan Hospital (Nan, Thailand). Eighteen patients (in 7 high facility hospitals) with severe respiratory failure received a low- and high-rate repetitive nerve stimulation test, and negative inspiratory pressure was measured. Results Within 1-65 h after exposure, 18 of the patients with severe respiratory failure had become ill. The typical clinical sequence was abdominal pain, nausea and/or vomiting, diarrhea, dysphagia and/or dysarthria, ptosis, diplopia, generalized weakness, urinary retention, and respiratory failure. Most patients exhibited fluctuating pulse and blood pressure. Repetitive nerve stimulation test showed no response in the most severe stage. In the moderately severe stage, there was a low-amplitude compound muscle action potential with a low-rate incremented/high-rate decremented response. In the early recovery phase, there was a low-amplitude compound muscle action potential with low- and high-rate incremented response. In the ventilator-weaning stage, there was a normal-amplitude compound muscle action potential. Negative inspiratory pressure variation among 14 patients undergoing weaning from mechanical ventilation was observed. Kaplan-Meier survival analysis identified a shorter period of ventilator dependency among patients receiving botulinum antitoxin on day 4 (P=.02). Conclusions Patients receiving botulinum antitoxin on day 4 had decreased ventilator dependency. In addition, for patients with foodborne botulism, an effective referral system and team of specialists are needed.

Background : There are limited data on HIV-associated neurocognitive disorders (HANDs) from resource-constraint region and few studies have firm documentation of duration of treatment and suppression of plasma virus. This study aimed to estimate the prevalence of HIV-related cognitive deterioration among HIV-infected patients who were on stable ART and to describe the pattern of neurocognitive impairment (NCI), daily life disturbance and associated factors. Methods: This was a cross-sectional evaluation of cognition in a sample of HIV adults at HIV-NAT, the Thai Red Cross AIDS Research Centre with data captured over a 6-month period. The Montreal Cognitive Assessment (MoCA), International HIV Dementia Scale (IHDS) and Activities of Daily Living Questionnaire (ADLQ) scale were administered. NCI was defined as a score of ≤10 on the IHDS or

To determine the clinical outcomes of an aggressive combined cooling technique for exertional heatstroke in Thailand.We analyzed patients who were diagnosed with exertional heatstroke between 1995 and 2007. Outcomes were assessed both in hospital and at 3 months follow-up.Twenty-eight cases of exertional heatstroke presented to Phramongkutklao Army Hospital over 12 years. All patients developed multiorgan dysfunction and encephalopathy. Twenty-four cases had acute renal failure, 7 of whom required dialysis. Disseminated intravascular coagulation (DIC) was detected in 9 patients (32.1%). In-hospital mortality was 7.1%. Most survivors recovered with nearly normal organ function. However, 9 exhibited prolonged neurologic dysfunction and 2 had chronic renal dysfunction requiring hemodialysis. At 3-month follow-up, neurologic and renal dysfunction in those patients persisted. Higher serum prothrombin time and DIC correlated to fatality. The patients whose core body temperature achieved 38 degrees C within 3 hours revealed a significantly lower DIC and twice as low in the frequency of poor outcome than the patients cooled longer than 3 hours to reduce core body temperature to 38 degrees C.Despite early recognition and aggressive combined cooling, exertional heatstroke remains associated with multiorgan dysfunction. However, our 7.1% in-hospital mortality rate was low compared to previous studies. Early diagnosis and prompt treatment are critical.

To the Editor: HIV-associated sensory neuropathy (HSN) encompasses distal sensory polyneuropathy and antiretroviral toxic neuropathy with clinical features between the two that are indistinguishable.1 In the absence of antiretroviral (ARV) medications, HSN is as frequent as 30% among patients with AIDS.2 Immunosuppression and higher plasma HIV RNA levels increase both risk and severity.3 Dideoxynucleoside reverse transcription inhibitors (dNRTIs) add additional risk that may induce or unmask underlying neuropathy.4 Although less frequently employed in developed countries, dNRTIs, particularly stavudine (d4T), are commonly used in developing countries due to low cost. Here, HSN rates after initiation of predominantly d4T-containing ARV therapy range from 6% to 20.7%, with one Thai study reporting 6.9% after 48 weeks of treatment.5–8 We present a cross-sectional study of HSN from an outpatient infectious diseases (ID) clinic at Phramongkutklao Medical Center in Bangkok, Thailand. Approved by the Phramongkutklao Medical Center Institutional Review Board, this study screened 118 cases and enrolled 100 subjects between January and July 2006 by approaching all outpatients attending the clinic in consecutive order on days when the neurology staff was available (approximately 2 days of each month). Subjects had to be 14 years and above with documented HIV. Exclusion criteria were inability to sign consent or the presence of confounding factors known to potentially influence neuropathy (eg, neurotoxic chemotherapeutic treatment, diabetes, alcoholism, and chronic renal failure). History of HIV, comorbid illnesses, opportunistic infections, illicit drug use, and medication profiles including ARV history were obtained from chart review and participant interview. When available within 3 months before entry, CD4 lymphocyte counts (85/100) and plasma HIV RNA (37/100) were recorded. The neurological evaluation utilized standardized methodology as applied in the AIDS Clinical Trials Group (ACTG) noting proximity of distal sensory impairments in pinprick, temperature, vibration, and joint position at the great toes, ankles, and knees, bilaterally providing categorical scores from 0 to 4 based on sensory levels.9 Symptoms (paresthesias, numbness, and neuropathic pain) were each rated on a similar 4-point scale. We defined possible HSN as decreased sensation of at least 1 modality in both lower extremities or a decrease or absence of ankle reflexes when compared with the patellar reflex and probable HSN more stringently as decreased sensation of at least 1 modality in both lower extremities and a decrease or absence of ankle reflexes. Subjects meeting criteria for HSN who had symptoms were categorized as symptomatic HSN. Differences between subjects with and without HSN were assessed by Mann-Whitney test for 2 independent samples for continuous variables and by χ2 test or Fisher exact test for dichotomous variables. Most subjects had advanced HIV disease with a median (interquartile range) CD4 count of 132 (24–320) cells per deciliter, and 37% had a past AIDS-defining opportunistic illness, most frequently tuberculosis (19%). Thirty-seven subjects (37%) were ARV-naive. Among those treated, 61 (97%) were on 3-drug combination potent ARV therapy with 94% on dNRTI-containing regimens. The ARV-experienced subgroup was slightly older (38 vs. 35 years, P = 0.04), and the median body mass index was slightly higher than in the ARV-naive subgroup (21 vs. 19.7, P = 0.04). The ARV-experienced subgroup, on average, had a higher CD4 count (217 vs. 44, P < 0.001), and among cases where data were available (22/63), 55% had undetectable plasma HIV RNA levels. Symptoms possibly suggestive of neuropathy were noted in 13 (35%) of 37 ARV-naive subjects and in 22 (35%) of 63 ARV-experienced subjects. Interestingly, neuropathic pain was a symptom found only in ARV-experienced subjects (7/63 ARV-experienced patients compared with 0/37 ARV-naive patients). Six (16%) of 37 ARV-naive subjects and 10 (16%) of 63 ARV-experienced subjects had 1 or more bilateral signs suggestive of neuropathy. Possible neuropathy criteria were met in 12 (32%) of 37 ARV-naive patients and in 16 (25%) of 63 ARV-experienced subjects for an overall rate of 28%. Only 10 subjects (10%) met the stringent study-defined criteria for probable HSN (Table 1). All were symptomatic. The rate of probable HSN did not differ between the ARV-naive (4/37 subjects, 10.6%) and ARV-experienced (6/63 subjects, 9.5%) subgroups. No differences in sex, age, or body mass index were noted between subjects with or without HSN in either the ARV-naive or ARV-experienced subgroups. A lower CD4 lymphocyte count was associated with higher risk of HSN in the cohort as a whole and specifically in the ARV-experienced subgroup with a similar trend in the ARV-naive subgroup. A trend toward lower HIV viral load as a risk factor for HSN was observed in the ARV-experienced cohort. We identified no difference in dNRTI exposure between those with and without HSN (P = 0.34); although 94% were on dNRTI-based treatment. TABLE 1 Demographic and HIV-Related Information Comparing Subjects With and Without Probable HSN for the Entire Cohort and Separately Among ARV-Naive and ARV-Experienced Subgroups In other reports, rates of HSN have varied widely, likely due to multiple factors including differences in HSN definitional criteria, variations in HIV stage, possible differences in host and viral clade parameters, and variation in rates, types, and duration of ARV treatments. Our protocol employed a strict definition determined by neurological evaluations conducted by neurologists and identifies an overall 10% frequency that does not differ by ARV status. The subjects were all Thai and were most likely infected with recombinant circulating form (CRF) 01_AE, the predominant HIV subtype found in Bangkok.10 The study is limited by the lack of statistical power due to its small sample size and by the incomplete immunovirologic information. However, it is interesting to note a lack of difference in probable HSN rates by ARV status. This finding is unexpected considering the high frequency of dNRTI use (94%), a factor expected to increase rates of antiretroviral toxic neuropathy. Although many studies have reported high rates of HSN up to 55% with dNRTI, other studies have reported a lower prevalence.4,11–13 Therefore, it is tempting to hypothesize that in our cohort, the tendency of dNRTI to induce neuropathy may have been outweighed by the favorable effects of immunologic benefit with potent ARV therapy, particularly because our cohort had severe immunosuppression. A careful prospective evaluation of HSN before and after use of both dideoxynucleoside-containing and nondideoxynucleoside-containing ARV regimens may be warranted. In terms of immunovirologic parameters, a trend for low CD4 count in association with HSN was found in the cohort as a whole and specifically among ARV-experienced subjects. This finding is similar to that reported in the HIV Outpatient Study and suggests that immunologic parameters continue to be important as a risk factor for HSN after use of potent ARV medications.14 The association of low HIV RNA levels with HSN in the ARV-experienced cohort may reflect better HIV medication adherence and increase exposure to the dideoxynucleoside medications; however, it is also notable that virological data were very limited. In summary, this study found an overall frequency of probable HSN at 10% and that of possible HSN at 28% among HIV-infected subjects attending an outpatient ID clinic in Bangkok, Thailand. Rates of HSN were comparable between ARV-naive and ARV-experienced subjects, despite the heavy use of dideoxynucleoside-containing medications in ARV-experienced subjects. Low CD4 count was a risk factor for HSN in general and specifically in ARV-experienced subjects. Further studies are warranted to prospectively evaluate the changes in rates of HSN after highly active antiretroviral therapy initiation with both dideoxynucleoside-containing and nondideoxynucleoside-containing regimens.

We compared cerebrospinal fluid (CSF) opening pressure measurements in the lumbar subarachnoid space between the flexed position (F-OP) and relaxed position (R-OP) in recumbent patients. We devised an equation for using F-OP to determine the existence of raised intracranial pressure (ICP). Patients (n = 83) underwent lumbar puncture while in the flexed lateral decubitus position and then were moved to the relaxed position. F-OP and R-OP were measured with a water manometer. R-OP > 180 mmH2O plus relevant clinical signs were taken as indicators of raised intracranial pressure. Mean pressures for F-OP and R-OP were 178.54 and 160.52 mmH2O respectively, p 180, raised ICP could be significantly over diagnosed. The authors recommend an equation [R-OP(calculated, mmH2O) = 0.885 × F-OP(measured, mmH2O)] or using 200 mmH2O as the threshold for increased ICP with flexed posture.

HIV-associated dementia (HAD) is not firmly established in patients with circulating recombinant form (CRF) 01_AE HIV-1. In this study, we compared neuropsychological performance among 15 Thai individuals with HAD, 15 Thai individuals without HAD, and 30 HIV-negative control subjects. HIV-1 participants were highly active anti-retroviral therapy naive and matched by age, education, and CD4 count. Neuropsychological testing abnormalities were identified in most cognitive domains among HAD vs HIV-negative participants, confirming the presence of HAD in CRF01_AE.

AIM: To determine the clinical presentations, survival and prognostic factors of hepatocellular carcinoma (HCC) in Southern Thailand. METHODS: Retrospective analysis was performed on the 336 hepatocellular carcinoma patients treated at Songklanagarind hospital between 1 January 1991 and 31 January 1999. RESULTS: Of these 336 patients, 276 were males and 60 were females. The mean age was 54.4 years. The common symptoms and signs were abdominal pain and hepatomegaly. The most common presentation of tumor was a dominant mass with daughter nodules. Portal vein involvement was found in 50% of total. Extra hepatic metastasis was found in 13%, and the lung was the most common site. There were 65.4% with evidence of cirrhosis and half of them were in Child's class B. HBsAg was positive in 72.6%. Regarding Okuda's tumor staging, 15%, 61% and 24% were stage I, II and III, respectively. Overall median survival was 2.1 months (11.5, 2.6 and 0.7 months for stage I, II and III respectively). Treatments of HCC improved patient survival (5.5 months vs 1.6 months for untreated patients). Most common causes of death were hepatic failure. Using multivariate analysis, the prognostic factors identified were tumor staging, alpha-fetoprotein level above 10000 μg·L-1, extrahepatic metastasis, portal vein thrombosis and treatment. CONCLUSION: HCC in Thailand is a fatal disease with poor outcome due to late presentation and high prevalence of liver cirrhosis. Early detection and proper management may improve outcome.

An 18-year-old man presented with symptoms that evolved over the course of three days and included fever, radicular back pain, vertigo, ataxia, headache, and left-sided hemiparesis. He reported that he had had skin swellings in a migratory pattern during the preceding month. His diet typically consisted of raw fish. A complete blood count showed 7100 white cells per cubic millimeter with 33 percent eosinophils. A computed tomographic scan of the brain showed diffuse swelling. A magnetic resonance image of the brain revealed multiple worm-like lesions in both hemispheres and the cerebellum (arrows, Panels A and B), which did not enhance . . .