Neuropathology of JC virus infection in progressive multifocal leukoencephalopathy in remission.

AIM: To investigate the neuropathology of the brain in a rare case of remission following diagnosis of progressive multifocal leukoencephalopathy (PML). METHODS: Consent from the family for an autopsy was obtained, clinical records and radiograms were retrieved. A complete autopsy was performed, with brain examination after fixation and coronal sectioning at 1 cm intervals. Fourteen regions were collected for paraffin embedding and staining for microscopic analysis. Histologic sections were stained with Luxol blue, hematoxylin/eosin, and immunostained for myelin basic protein, neurofilament, SV40 T antigen and p53. The biopsy material was also retrieved and sections were stained with hematoxylin/eosin and immunostained for SV40 and p53. Sections were examined by American Board of Pathology certified pathologists and images captured digitally. RESULTS: Review of the clinical records was notable for a history of ulcerative colitis resulting in total colectomy in 1977 and a liver transplant in 1998 followed by immune-suppressive therapy. Neurological symptoms presented immediately, therefore a biopsy was obtained which was diagnosed as PML. Immunotherapy was adjusted and clinical improvement was noted. No subsequent progression was reported. Review of the biopsy demonstrated atypical astrocytes and enlarged hyperchromatic oligodendroglial cells consistent with JC virus infection. Strong SV40 and p53 staining was found in glial cells and regions of dense macrophage infiltration were present. On gross examination of the post-mortem brain, a lesion in the same site as the original biopsy in the cerebellum was identified but no other lesions in the brain were found. Microscopic analysis of this cerebellar lesion revealed a loss of myelin and axons, and evidence of axonal damage. This single burned-out lesion was equivocally positive for SV40 antigen with little p53 staining. Examination of thirteen other brain regions found no other occult sites. CONCLUSION: Our study reveals residual damage, rare macrophages or other inflammation and minimal evidence of persistent virus. This case demonstrates the possibility of complete remission of PML.

Safety of botulinum toxin for dysphagia in oculopharyngeal muscular dystrophy.

INTRODUCTION: Despite multiple studies reporting marked benefit of botulinum toxin (BTX) for treatment of cricopharyngeal dysphagia, little is known about its safety for this indication. We examined the safety of cricopharyngeal BTX for dysphagia in oculopharyngeal muscular dystrophy (OPMD). METHODS: We reviewed records of patients with OPMD who received cricopharyngeal BTX. RESULTS: Twenty-four patients underwent 66 procedures. Overall adverse event frequency was 44%. The most common adverse events were dysphonia (24%) and worsened dysphagia (14%). Logistic regression demonstrated that dose was a significant predictor of worsened dysphagia (P = 0.036) and of the composite event of dysphonia or worsened dysphagia (P = 0.009). There was a nonsignificant trend for dose as a predictor of dysphonia (P = 0.073). 59% of procedures were associated with symptomatic improvement. CONCLUSIONS: While BTX appears to be beneficial for treatment of dysphagia in OPMD, caution is warranted when injecting the cricopharyngeus muscle due to dose-related risk of dysphonia or worsened dysphagia.

Glycosylated hemoglobin for diagnosis of prediabetes in acute ischemic stroke patients.

BACKGROUND: Prediabetes (PD) is an independent risk factor for stroke. The American Diabetes Association (ADA) has recently published new guidelines recommending glycosylated hemoglobin A1c (HbA1c) as a marker to diagnose diabetes and PD. Diagnosis of diabetes Mellitus (DM) is often made at the time of hospitalization for stroke. Less is known about identifying PD in acute ischemic stroke (AIS) patients. We aim to investigate the frequency of new-onset PD in the hospitalized AIS patients using the new ADA guidelines. METHODS: We retrospectively studied 362 AIS patients from our local database. Stroke risk factors, type of stroke, and white matter hyperintensities (WMHs) were all collected. Based on the 2010 ADA guidelines, patients were classified as prediabetics, with HbA1c levels of 5.7%-6.4%; diabetics, with HbA1c levels more than 6.5%; and normoglycemic, HbA1c levels less than 5.7%. We used SAS 9.3 for analysis. RESULTS: On admission, 279 (78%) AIS patients had HbA1c values collected. Stratifying by HbA1c, 113 (31%) AIS patients were given the diagnosis of DM and 109 (30%) were given the diagnosis of PD. From the 166 patients with no DM history, 53% had PD and 15% had DM. Patients with DM and PD were more likely to have hypertension (P<.001) and hyperlipidemia (P=.05). The likelihood of new-onset PD increased with age (P<.01). No differences were found by the type of stroke or WMH. CONCLUSION: Diabetes and PD are highly prevalent in the hospitalized ischemic stroke (IS) patients. Our results suggest a need for routine HbA1c testing in all patients with IS. Further larger studies need to confirm these findings.