Allen J. Aksamit

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.

Quantitation of 14-3-3 and neuron-specific enolase proteins in CSF in Creutzfeldt–Jakob disease

CSF 14-3-3 and neuron-specific enolase (NSE) proteins were quantitated from patients who had Creutzfeldt–Jakob disease (CJD) or other rapidly dementing disorders initially considered to be CJD. Thirty-one patients were diagnosed as having CJD among 152 studied. CSF 14-3-3 values more than 8 ng/mL correlated with CJD. CSF NSE values less than 30 ng/mL and 14-3-3 values less than 8 ng/mL made a diagnosis of CJD unlikely, but did not exclude it.

Diagnosis of progressive multifocal leukoencephalopathy by brain biopsy with biotin labeled DNA:DNA in situ hybridization.

DNA:DNA in situ hybridization using a cloned JC virus (JCV) DNA probe labeled with biotin confirmed the presence of JCV DNA in formalin-fixed, paraffin-embedded brain biopsies from four cases of progressive multifocal leukoencephalopathy (PML). Only small pieces of tissue were available in each case. Detection of the JC DNA:DNA hybrids was carried out by affinity cytochemistry. JCV DNA was identified predominantly in the nuclei of interfascicular oligodendrocytes in demyelinated areas of the biopsies. JC virus was isolated from one case, and the diagnosis of PML was substantiated in all cases by electron microscopic identification or immunocytochemical labeling of JC viral antigen. In situ hybridization using a biotin labeled JCV DNA probe is a specific, sensitive and convenient method for confirming the diagnosis of PML in suspected cases evaluated by brain biopsy.

Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis

To evaluate the incidence and prevalence of autoimmune encephalitis and compare it to that of infectious encephalitis.

IN SITU HYBRIDIZATION FOR DETECTION OF VIRAL NUCLEIC ACID IN CELL CULTURES AND TISSUES

In situ hybridization to isolated cells and tissue sections is an important technique for the localization of mammalian and viral mRNA and DNA. This report describes advances in tissue fixation allowing superior preservation of specimen morphology, concurrent immunohistochemistry and in situ hybridization, and enhanced sensitivity of mRNA detection. In addition, strategies for isotopic and non-isotopic DNA and RNA labeling and assays for mRNA quantitation are described in measles, visna, AIDS and papovavirus infections.

An 85-year-old man with chronic lymphocytic leukemia and altered mental status

An 85-year-old man presented to Mayo Clinic in late summer 2003 with a 1-week history of increased shortness of breath on exertion. Two weeks prior to presentation, he had been on a canoeing trip in Montana. He had no known animal, insect, or tic exposure while there and had no significant rash. The patient had observed that his exercise tolerance had decreased prior to this presentation from walking 2 miles daily to only 3 to 4 blocks, mainly due to dyspnea. He had been hospitalized 6 months prior to presentation with community-acquired pneumonia. On that admission, he was diagnosed with chronic lymphocytic leukemia (CLL) B-cell type. He had not undergone pharmacologic treatment for CLL. His medications on presentation were doxazosin mesylate 4 mg daily, atenolol 50 mg daily, amlodipine 10 mg, and sertraline 50 mg daily. On presentation, he denied cough, weight loss, chest pain, or sputum production. He had chills and was found to have a fever of 38.9 °C. He was admitted to the medical service at St. Marys Hospital. His blood pressure was 144 mm Hg systolic and 76 mm Hg diastolic, his respiratory rate was 24 with 94% oxygen saturation on room air, and he appeared in mild respiratory distress with increased rate and work of breathing. He had bilateral crackles and reduced breath sounds on lung auscultation. He was alert and his cranial nerves were normal, as was his muscle strength. His muscle stretch reflexes were normal and symmetric. He had a wide-based, unsteady gait. He had no myoclonus, asterixis, or tremor. A chest x-ray showed bibasilar infiltrates or atelectasis. A CT angiogram of the chest showed lymphadenopathy and atelectasis or infiltrate in the right base, but was negative for pulmonary embolus. He was started on cefepime and doxycycline and later levofloxacin was added. His …