Haatem Reda

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 ≤ 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.

Natural history of cutaneous innervation following herpes zoster.

&NA; As part of a comprehensive study of the natural history of herpes zoster (HZ), 57 of 94 subjects in a cohort at elevated risk for post‐herpetic neuralgia (PHN) consented to collection of 3‐mm skin punch biopsies from affected, mirror‐image, and distant control skin at baseline and followup visits. As cutaneous innervation is reduced in longstanding severe PHN, we tested the hypothesis that development of PHN is correlated with severity of initial neural injury and/or a failure of neural recovery. Quantitative analysis using single‐label PGP9.5 immunofluorescence microscopy showed epidermal profiles were reduced in zoster skin by approximately 40% at study entry compared to control and mirror skin. The density of the subepidermal plexus was approximately 15% lower in zoster skin. Mirror skin was not denervated compared to control skin. Although not significant at all visits, correlations between epidermal nerve fiber density in HZ skin and thermal sensation, allodynia, capsaicin response, and average daily pain all associated more severe abnormalities with lower epidermal innervation. There was limited evidence that the initial neural injury was more severe in the 15 eventual PHN subjects. Overall, pain and pain‐related disability resolved the fastest. Sensory abnormalities and symptom aggravation by focal capsaicin application showed partial and selective recovery over 6 months. In contrast, cutaneous innervation showed no recovery at all by 6 months, conclusive evidence that resolution of pain and allodynia does not require cutaneous reinnervation. A much longer period of observation is needed to determine if zoster‐affected skin is ever reinnervated.

Natural history of herpes zoster: Late follow-up of 3.9 years (n = 43) and 7.7 years (n = 10)

Summary Subjects examined 3.9 and 7.7 years after onset of herpes zoster showed continued resolution of pain and sensory symptoms. Sensory function continued toward normalization, but there was no recovery of cutaneous innervation. Abstract Postherpetic neuralgia (PHN) is a common complication after herpes zoster (HZ). Subjects who completed a longitudinal observational 6‐month study (4 visits) of the natural history of HZ were recontacted for 2 additional follow‐up visits that included pain and sensory symptom assessment, quantitative sensory testing, capsaicin response test, and 3‐mm punch skin biopsies in HZ‐affected, mirror‐image, and control skin sites. Forty‐three subjects (14 with PHN at 6 months) of the original 94 subjects in the cohort were comprehensively assessed at a median 3.9 years after HZ onset (visit 5), and 10 subjects underwent a final assessment at a median 7.7 years after HZ onset (visit 6). At 3.9 years, none of the 29 subjects who had been pain free at 6 months had a recurrence of pain. Only 2 of the 14 subjects with PHN at 6 months still had pain at 3.9 years. One subject with PHN at 6 months was free of symptoms at 3.9 years but had very mild pain at 7.7 years. Sensory function continued on a path toward normalization, but was still abnormal in many subjects, especially those who met criteria for PHN at 6 months. Even at 7.7 years, reinnervation of HZ‐affected skin was not apparent.

Effect of a single dose of pregabalin on herpes zoster pain

BackgroundThe effect of pregabalin on acute herpes zoster pain has not been previously evaluated.MethodsIn a randomized, double-blind, placebo-controlled, two-session crossover study the effect of a single oral dose of pregabalin (150 mg) on pain and allodynia was evaluated in 8 subjects with herpes zoster.ResultsOver 6 hours of observation, pain decreased by a mean of 33% with pregabalin and 14% with placebo (p < 0.10). Effects on allodynia and SF-MPQ were not significant.ConclusionsCompared to an earlier study of gabapentin 900 mg for acute zoster pain and allodynia that followed a nearly identical protocol, pregabalin had a similar effect on pain and was well tolerated, with no difference from placebo on sleepiness. Common side effects of light-headedness, unsteady gait, and slowed thinking were almost identical to that observed in the earlier study of gabapentin. Subject recruitment proved difficult in part due to the widespread off-label use of gabapentin and pregabalin for acute zoster pain in our region of the USA.Trial RegistrationClinicalTrials.gov Identifier: NCT00352651

Safety, tolerability, pharmacokinetics, and effects on human experimental pain of the selective ionotropic glutamate receptor 5 (iGluR5) antagonist LY545694 in healthy volunteers

Summary In a 2‐part study in healthy volunteers, we first established a maximally tolerated multiple dose of LY545694 of 25 mg twice daily and subsequently demonstrated antihyperalgesic effect using effects in the brief thermal stimulation experimental pain model. The antihyperalgesic effect was similar to that of gabapentin. ABSTRACT The objective of this study was to establish in healthy volunteers the maximally tolerated multiple dose (MTMD) of the ionotropic glutamate receptor 5 antagonist LY545694 (part A), and to investigate whether that dose had analgesic or antihyperalgesic effects in the brief thermal stimulation (BTS) pain model (Part B). Part A was a double‐blind, placebo‐controlled study in 3 groups of 10 healthy men. To simulate an extended‐release formulation, study drug was administered orally over 6 hours (12 equally divided aliquots at 30‐minute intervals). Part B was a double‐blind, placebo‐controlled, double‐dummy, 3‐way crossover study in 27 healthy men. At each of the 3 study periods, subjects received either LY545694 (MTMD; as determined during part A) as a simulated, twice daily extended‐release formulation for 4 doses over 3 days, gabapentin (600 mg 8 hours apart; 6 doses over 3 days; positive control), or matching placebo. The BTS model was induced twice with a 1‐hour interval on each of the 2 study days, before drug administration and at the time of expected peak analgesia of LY545694. Plasma exposure for LY545694 was approximately linear over the 25‐ to 75‐mg dose range. The MTMD of LY545694 was 25 mg twice daily. Areas of secondary hyperalgesia were significantly smaller after administration of LY545694 and gabapentin compared with placebo (P < .0001 and P = .0004, respectively), but there was no difference between areas after administration of gabapentin and LY545694 (P = .400). Neither gabapentin nor LY545694 reduced the painfulness of skin heating during BTS model induction. The most common treatment‐emergent adverse event was dizziness. The results of this study suggest that LY545694 should be explored further as a potential treatment for chronic pain involving neuronal sensitization.

Standardized sign-out improves completeness and perceived accuracy of inpatient neurology handoffs

Objectives: As residency programs adjust to new duty hour restrictions, the use of cross-coverage systems requiring handoffs will rise. Handoffs are vulnerable to communication failures when unstructured. Accordingly, we implemented a standardized sign-out process on our inpatient neurology services and assessed its effect on completeness and perceived accuracy of handoffs. Methods: Residents spent the first half of their rotations utilizing unstructured sign-out. They transitioned to a structured sign-out system (using the situation-background-assessment-recommendation format) during the second half of their rotations. We analyzed survey responses before and after implementation to evaluate for an effect. Results: Residents utilizing structured sign-out were significantly more likely to share test results with patients/families prior to shift changes (p = 0.037), update our electronic service list (p = 0.045), and feel all important data were being transmitted (p = 0.041). Overall satisfaction (scale 1–10) increased from 6.2 ± 1.6 to 7.4 ± 1.3 (p = 0.002). Conclusions: Our findings demonstrate that standardized sign-out improves the completeness and perceived accuracy of handoffs. Such improvement has the potential to improve patient safety and quality of care.

Zoster-associated mononeuropathies (ZAMs): a retrospective series.

Zoster‐associated limb paresis is an uncommon complication of herpes zoster (HZ) and one whose precise pathophysiologic mechanism is poorly understood. Occasionally, the paresis results from a zoster‐associated mononeuropathy (ZAM).

A case of sensory ataxia as the presenting manifestation of neurosarcoidosis.

Sarcoidosis rarely selectively affects the cauda equina with characteristic motor and sensory impairments.Using imaging, we report a case of cauda equina polyradiculopathy presenting with progressive sensory ataxia without clinical or electrophysiological evidence of motor involvement. Neurosarcoidosis was diagnosed pathologically by proximal dorsal root biopsy after systemic investigations for inflammatory, infectious, and neoplastic etiologies were found to be negative. There was clinical and radiographic improvement with corticosteroids. In addition, we review previously reported cases of cauda equina sarcoidosis. Muscle Nerve, 2011

Peripheral neuropathies of rheumatologic disease and gluten-related disorders.

Peripheral nervous system disease is a common and often debilitating feature of many systemic rheumatologic disorders. Such involvement takes many forms, reflecting the variety of underlying pathophysiology, though most patients present with painful multifocal neuropathy (usually vasculitic) or a distal sensory more than motor peripheral neuropathy (sometimes vasculitic and nearly always axonal). The presence of peripheral nervous system involvement is often an early signal of the generalization of inflammatory disease in blood vessels or extravascular tissues, though peripheral neuropathy is not itself an independent predictor of mortality. Nonetheless, progressive multifocal neuropathy, motor neuropathy, small fiber neuropathy, and sensory neuronopathy should be treated early and aggressively with immunosuppression (or the gluten-free diet in appropriate situations) to limit morbidity. Given the rapidly evolving therapeutic landscape, partnership with a rheumatologist is essential. Treatment is usually sustained for 1 to 2 years, and remission is possible in many cases within 6 to 12 months, with variable rates of relapse and treatment resistance. Patients should be meticulously monitored for relapse with serial laboratory testing, electrodiagnostic studies, and clinical examination. Functional rating scores, such as the neuropathy impairment scale and the total neuropathy score are useful for longitudinal assessment.

Case 13-2017

A 41-year-old man with a history of headaches and hearing loss presented with seizures, weakness, and cognitive decline. A diagnosis of stroke had been made 1 year earlier. Diagnostic tests were performed.