Russell E. Bartt

PML diagnostic criteria: Consensus statement from the AAN Neuroinfectious Disease Section

Objective: To establish criteria for the diagnosis of progressive multifocal leukoencephalopathy (PML). Methods: We reviewed available literature to identify various diagnostic criteria employed. Several search strategies employing the terms “progressive multifocal leukoencephalopathy” with or without “JC virus” were performed with PubMed, SCOPUS, and EMBASE search engines. The articles were reviewed by a committee of individuals with expertise in the disorder in order to determine the most useful applicable criteria. Results: A consensus statement was developed employing clinical, imaging, pathologic, and virologic evidence in support of the diagnosis of PML. Two separate pathways, histopathologic and clinical, for PML diagnosis are proposed. Diagnostic classification includes certain, probable, possible, and not PML. Conclusion: Definitive diagnosis of PML requires neuropathologic demonstration of the typical histopathologic triad (demyelination, bizarre astrocytes, and enlarged oligodendroglial nuclei) coupled with the techniques to show the presence of JC virus. The presence of clinical and imaging manifestations consistent with the diagnosis and not better explained by other disorders coupled with the demonstration of JC virus by PCR in CSF is also considered diagnostic. Algorithms for establishing the diagnosis have been recommended.

Lamotrigine for HIV-associated painful sensory neuropathies: A placebo-controlled trial

Objective: To evaluate the efficacy and tolerability of lamotrigine (LTG) for the treatment of pain in HIV-associated sensory neuropathies. Methods: In a randomized, double-blind study, patients with HIV-associated distal sensory polyneuropathy (DSP) received LTG or placebo during a 7-week dose escalation phase followed by a 4-week maintenance phase. Randomization was stratified according to whether or not patients were currently using neurotoxic antiretroviral therapy (ART). Results: The number of patients randomized was 92 (62 LTG, 30 placebo) in the stratum receiving neurotoxic ART and 135 (88 LTG, 47 placebo) in the stratum not receiving neurotoxic ART. Mean change from baseline in Gracely Pain Scale score for average pain was not different between LTG and placebo at the end of the maintenance phase in either stratum, but the slope of the change in Gracely Pain Scale score for average pain reflected greater improvement with LTG than with placebo in the stratum receiving neurotoxic ART (p = 0.004), as did the mean change from baseline scores on the Visual Analogue Scale for Pain Intensity and the McGill Pain Assessment Scale and patient and clinician ratings of global impression of change in pain (p ≤ 0.02). The incidence of adverse events, including rash, was similar between LTG and placebo. Conclusions: Lamotrigine was well-tolerated and effective for HIV-associated neuropathic pain in patients receiving neurotoxic antiretroviral therapy. Additional research is warranted to understand the differing response among patients receiving neurotoxic antiretroviral therapy compared with those not receiving neurotoxic antiretroviral therapy.

Statin-Associated Peripheral Neuropathy: Review of the Literature

Various pharmacologic agents are available for the treatment of hypercholesterolemia, including 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors, commonly referred to as statins, which offer favorable lipid‐lowering effects and reductions in morbidity and mortality. Statins are usually better tolerated than other lipid‐lowering agents and therefore have become a mainstay of treatment for hypercholesterolemia. However, recent case reports of peripheral neuropathy in patients treated with statins may have gone unnoticed by health care professionals. To evaluate the possible link between statins and peripheral neuropathy, literature searches using MEDLINE (January 1993–November 2003) and International Pharmaceutical Abstracts (January 1970–June 2002) were performed. Key search terms were statin, neuropathy, and HMG‐CoA reductase inhibitors. Based on epidemiologic studies as well as case reports, a risk of peripheral neuropathy associated with statin use may exist; however, the risk appears to be minimal. On the other hand, the benefits of statins are firmly established. These findings should alert prescribers to a potential risk of peripheral neuropathy in patients receiving any of the statins; that is, statins should be considered the cause of peripheral neuropathy when other etiologies have been excluded.

NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: Results of a 52-week open-label study

Objectives:To evaluate the efficacy, safety, and tolerability of repeated NGX-4010 treatments in the open-label extension phase of a 52-week study in patients with neuropathic pain due to HIV-associated distal sensory polyneuropathy (HIV-DSP). Methods:Patients completing the 12-week, randomized, double-blind phase of the study could enter a 40-week, open-label phase, and receive up to 3, 60-minute NGX-4010 treatments. Patients recorded their “average pain for the past 24 hours” daily using the Numeric Pain Rating Scale (NPRS). Efficacy assessment included the percentage NPRS score reduction from baseline to weeks 2 to 12 after the final treatment, and Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) questionnaires at study termination. Results:Of 307 patients randomized, 272 entered the open-label phase; 81, 90, 55, and 46 received 0, 1, 2, and 3 retreatments, respectively. The mean percentage decrease in NPRS score from baseline to weeks 2 to 12 after the final treatment was similar in patients receiving single or multiple NGX-4010 treatments (−25.8%, −27.1%, −24.6%, and −22.7% for 1, 2, 3, and 4 NGX-4010 treatments, respectively). PGIC and CGIC results demonstrated a benefit of NGX-4010 treatment through to the end of the study regardless of the number of treatments received. Transient local application site reactions were the most frequently reported adverse events, and were mainly mild to moderate, nonserious, and did not increase with repeated treatment. Discussion:Repeated NGX-4010 treatments were generally well tolerated and resulted in consistent reductions in HIV-DSP-associated pain and improvement in patient-reported outcomes.

Cranial epidural abscess and subdural empyema.

Publisher Summary This chapter discusses the epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management of cranial epidural abscess and subdural empyema. Cranial epidural abscess is classically the consequence of frontal sinusitis with osteomyelitis of the frontal bone producing a visible swelling known as Potts puffy tumor. Epidural abscess and subdural empyema develop as a logical consequence of the anatomic relationship of these spaces and the infectious organisms. There is a formidable barrier that prevents infections of the epidural or subdural space and its avascular nature makes these locations less than hospitable. Clinical infection requires a process and pathogen that is sufficiently invasive or disruptive of the barrier. Paranasal sinusitis and otomastoiditis are the most common sources of epidural and subdural infections. The clinical features, presentation, and outcome of cranial epidural abscess and subdural empyema mostly differ, despite the similar clinical microbiology and underlying conditions. Cranial epidural abscess, in most cases, is well contained by the intact dura and progresses slowly. The typical patient is an adolescent boy with an acute exacerbation of chronic sinus disease. Familiarity with intracranial epidural abscess and subdural empyema and the way in which they differ from more common infectious conditions is essential for proper timely recognition and management.

Peripheral Neuropathy Associated With Nucleoside Reverse Transcriptase Inhibitor Therapy

Peripheral neuropathies are the most common neurological syndromes associated with HIV infection. The spectrum of neuropathic syndromes is broad (xi238-1|Table 1), and neuropathies may be encountered during any stage of the infection. Some disorders of the peripheral nerves in patients with HIV infection are presumed to be caused by pathological factors resulting from the virus itself, whereas others may result from responses of a competent immune system to viral antigens, opportunistic processes unleashed when immune deficiency has occurred, or as adverse effects of therapies for AIDS-related diseases. To provide a context for understanding the toxic neuropathies, these other HIV-related neuropathies are briefly described in this first section.