Iatrogenic Exserohilum infection of the central nervous system: mycological identification and histopathological findings.

An outbreak of fungal infections has been identified in patients who received epidural injections of methylprednisolone acetate that was contaminated with environmental molds. In this report, we present the mycological and histopathological findings in an index case of Exserohilum meningitis and vasculitis in an immunocompetent patient, who received a cervical spine epidural steroid injection for chronic neck pain 1 week before the onset of fulminant meningitis with subsequent multiple brain and spinal cord infarcts. The fungus was recovered from two separate cerebrospinal fluid specimens collected before initiation of antifungal therapy and at autopsy on standard bacterial and fungal culture media. The mold was identified phenotypically as Exserohilum species. DNA sequencing targeting the internal transcribed spacer region and D1/D2 region of 28S ribosomal DNA enabled further speciation as E. rostratum. Gross examination at autopsy revealed moderate brain edema with bilateral uncal herniation and a ventriculostomy tract to the third ventricle. The brainstem, cerebellum, and right orbitofrontal cortex were soft and friable, along with hemorrhages in the cerebellar vermis and thalamus. Microscopic examination demonstrated numerous fungi with septate hyphae invading blood vessel walls and inducing acute necrotizing inflammation. The leptomeninges were diffusely infiltrated by mixed inflammatory cells along with scattered foci of fungal elements. This is the first report of iatrogenic E. rostratum meningitis in humans. This report describes the microbiological procedures and histopathological features for the identification of E. rostratum (a pigmented vascularly invasive fungi), the cause of a current nationwide outbreak of fatal fungal meningitis.

Screening for HIV-associated peripheral neuropathy in resource-limited settings.

INTRODUCTION: Peripheral neuropathy is the most common neurological complication of human immunodeficiency virus (HIV) infection but is widely under-diagnosed in resource-limited settings. We investigated the utility of screening tools administered by nonphysician healthcare workers (HCW) and quantitative sensory testing (QST) administered by trained individuals for identification of moderate/severe neuropathy. METHODS: We enrolled 240 HIV-infected outpatients using 2-stage cluster randomized sampling. HCWs administered the several screening tools. Trained study staff performed QST. Tools were validated against a clinical diagnosis of neuropathy. RESULTS: Participants were 65% women, mean age 36.4 years, median CD4 324 cells/µL. A total of 65% were taking antiretrovirals, and 18% had moderate/severe neuropathy. The screening tests were 76% sensitive in diagnosing moderate/severe neuropathy with negative predictive values of 84-92%. QST was less sensitive but more specific. CONCLUSIONS: Screening tests administered by HCW have excellent negative predictive values and are promising tools for scale-up in resource-limited settings. QST shows promise for research use.

Lessons learned developing a diagnostic tool for HIV-associated dementia feasible to implement in resource-limited settings: pilot testing in Kenya.

OBJECTIVE: To conduct a preliminary evaluation of the utility and reliability of a diagnostic tool for HIV-associated dementia (HAD) for use by primary health care workers (HCW) which would be feasible to implement in resource-limited settings. BACKGROUND: In resource-limited settings, HAD is an indication for anti-retroviral therapy regardless of CD4 T-cell count. Anti-retroviral therapy, the treatment for HAD, is now increasingly available in resource-limited settings. Nonetheless, HAD remains under-diagnosed likely because of limited clinical expertise and availability of diagnostic tests. Thus, a simple diagnostic tool which is practical to implement in resource-limited settings is an urgent need. METHODS: A convenience sample of 30 HIV-infected outpatients was enrolled in Western Kenya. We assessed the sensitivity and specificity of a diagnostic tool for HAD as administered by a primary HCW. This was compared to an expert clinical assessment which included examination by a physician, neuropsychological testing, and in selected cases, brain imaging. Agreement between HCW and an expert examiner on certain tool components was measured using Kappa statistic. RESULTS: The sample was 57% male, mean age was 38.6 years, mean CD4 T-cell count was 323 cells/µL, and 54% had less than a secondary school education. Six (20%) of the subjects were diagnosed with HAD by expert clinical assessment. The diagnostic tool was 63% sensitive and 67% specific for HAD. Agreement between HCW and expert examiners was poor for many individual items of the diagnostic tool (K = .03-.65). This diagnostic tool had moderate sensitivity and specificity for HAD. However, reliability was poor, suggesting that substantial training and formal evaluations of training adequacy will be critical to enable HCW to reliably administer a brief diagnostic tool for HAD.

Training needs and evaluation of a neuro-HIV training module for non-physician healthcare workers in western Kenya.

BACKGROUND: Recent efforts to improve neurological care in resource-limited settings have focused on providing training to non-physician healthcare workers. METHODS: A one-day neuro-HIV training module emphasizing HIV-associated dementia (HAD) and peripheral neuropathy was provided to 71 health care workers in western Kenya. Pre- and post-tests were administered to 55 participants. RESULTS: Mean age of participants was 29 years, 53% were clinical officers and 40% were nurses. Self-reported comfort was significantly higher for treating medical versus neurologic conditions (p<0.001). After training, participants identified more neuropathy etiologies (pre=5.6/9 possible correct etiologies; post=8.0/9; p<0.001). Only 4% of participants at baseline and 6% (p=0.31) post-training could correctly identify HAD diagnostic criteria, though there were fewer mis-identified criteria such as abnormal level of consciousness (pre=82%; post=43%; p<0.001) and hallucinations (pre=57%; post=15%; p<0.001). CONCLUSIONS: Healthcare workers were more comfortable treating medical than neurological conditions. This training significantly improved knowledge about etiologies of neuropathy and decreased some misconceptions about HAD.

A survey of rheumatologists' practice for prescribing pneumocystis prophylaxis.

OBJECTIVE: Pneumocystis pneumonia (PCP) occurs in immunocompromised hosts, in both the presence and absence of human immunodeficiency virus (HIV) infection, with substantial morbidity and a heightened mortality. We assessed practice patterns among rheumatologists for prescribing PCP prophylaxis. METHODS: Invitations to an online international survey were e-mailed to 3150 consecutive members of the American College of Rheumatology. RESULTS: Completed surveys were returned by 727 (23.1%) members. Among respondents, 505 (69.5%) reported prescribing prophylaxis. Factors associated with significantly higher frequency of prescribing PCP prophylaxis included female gender (OR 1.47, p = 0.03), US-based (OR 1.77, p = 0.004), academic-based (OR 2.75, p < 0.001), in practice less than 10 years (OR 4.08, p < 0.001), having previously treated PCP (OR 2.62, p < 0.001), and in a practice with a higher proportion of patients maintained on chronic glucocorticoids (OR 2.04, p < 0.001) or other immunosuppressant medications (OR 3.19, p = 0.003). In multivariate analysis, rheumatologists early in their careers and those with academic and US-based practices were more likely to prescribe prophylaxis. Among prescribers, the most important determinants for issuing prophylaxis were treatment regimen (68.6%), rheumatologic diagnosis (9.3%), and medication dosage (8.3%). CONCLUSION: Nearly one-third (30%) of the rheumatologists surveyed reported that they never prescribed PCP prophylaxis. While the patient characteristics for which prophylaxis was prescribed varied widely, physician demographics were strongly predictive of PCP prophylaxis use. These findings suggest that development of consensus guidelines might influence clinical decision-making regarding PCP prophylaxis in HIV-negative patients with rheumatologic diagnoses.

Utility of quantitative sensory testing and screening tools in identifying HIV-associated peripheral neuropathy in Western Kenya: pilot testing.

BACKGROUND/AIM: Neuropathy is the most common neurologic complication of HIV but is widely under-diagnosed in resource-constrained settings. We aimed to identify tools that accurately distinguish individuals with moderate/severe peripheral neuropathy and can be administered by non-physician healthcare workers (HCW) in resource-constrained settings. METHODS: We enrolled a convenience sample of 30 HIV-infected outpatients from a Kenyan HIV-care clinic. A HCW administered the Neuropathy Severity Score (NSS), Single Question Neuropathy Screen (Single-QNS), Subjective Peripheral Neuropathy Screen (Subjective-PNS), and Brief Peripheral Neuropathy Screen (Brief-PNS). Monofilament, graduated tuning fork, and two-point discrimination examinations were performed. Tools were validated against a neurologist's clinical assessment of moderate/severe neuropathy. RESULTS: The sample was 57% male, mean age 38.6 years, and mean CD4 count 324 cells/µL. Neurologist's assessment identified 20% (6/30) with moderate/severe neuropathy. Diagnostic utilities for moderate/severe neuropathy were: Single-QNS--83% sensitivity, 71% specificity; Subjective-PNS-total--83% sensitivity, 83% specificity; Subjective-PNS-max and NSS--67% sensitivity, 92% specificity; Brief-PNS--0% sensitivity, 92% specificity; monofilament--100% sensitivity, 88% specificity; graduated tuning fork--83% sensitivity, 88% specificity; two-point discrimination--75% sensitivity, 58% specificity. CONCLUSIONS: Pilot testing suggests Single-QNS, Subjective-PNS, and monofilament examination accurately identify HIV-infected patients with moderate/severe neuropathy and may be useful diagnostic tools in resource-constrained settings.

Mirtazapine use in human immunodeficiency virus-infected patients with progressive multifocal leukoencephalopathy.

BACKGROUND: An efficacious treatment is needed for human immunodeficiency virus (HIV)-infected and uninfected patients with progressive multifocal leukoencephalopathy (PML). OBJECTIVE: To report clinical and magnetic resonance imaging changes in response to mirtazapine treatment in HIV-positive patients with PML. DESIGN: Case series. SETTING: Outpatient neurology clinic. PATIENTS: Four HIV-positive patients with PML. INTERVENTIONS: Mirtazapine use, 15 mg nightly. MAIN OUTCOME MEASURES: Neurologic examinations and cranial magnetic resonance imaging. RESULTS: Three patients demonstrated objective clinical improvement, and 1 patient showed improvement on magnetic resonance imaging. The patient who experienced the most significant clinical improvement was the patient who received mirtazapine therapy closest to PML symptom onset. Mirtazapine use was safe and well tolerated. CONCLUSION: Mirtazapine use may offer some benefit as treatment or prophylaxis for PML in patients with HIV infection.

Reproducibility of optical coherence tomography in multiple sclerosis.

BACKGROUND: Optical coherence tomography (OCT) is a promising new method of quantifying axon thickness in the retinal nerve fiber layer (RNFL) that has been used predominantly by ophthalmologists to monitor glaucoma. Optical coherence tomography is being considered as a potential outcome measure in multiple sclerosis (MS) clinical trials, but no data exist on the reproducibility of this technique in MS centers. OBJECTIVE: To determine the reproducibility of OCT measurement of mean RNFL thickness in the undilated eyes of healthy control subjects and patients with MS. DESIGN: Prospective analysis of 4 healthy controls to determine interrater, intrarater, and longitudinal reproducibility. Cross-sectional analysis of 3 cohorts of patients with MS (n = 396) and healthy controls (n = 153). SETTING: Multiple sclerosis clinics at 3 academic medical centers. PATIENTS OR OTHER PARTICIPANTS: Healthy controls and patients with MS. Main Outcome Measure Thickness of RNFL. RESULTS: We found excellent agreement with respect to interrater (intraclass correlation [ICC], 0.89), intrarater (ICC, 0.98), and intervisit (ICC, 0.91) results. Mean RNFL thickness did not vary significantly among research centers for patients with MS (93, 92, and 90 microm) or among healthy controls (103, 105, and 104 microm) by site. CONCLUSIONS: We demonstrate that mean RNFL thickness can be reproducibly measured by trained technicians in an MS center using the OCT-3 model. The RNFL measures from cohorts of age-matched controls and patients with MS from 3 different research centers were remarkably similar.