Rasmussen Encephalitis: An Update.

Rasmussen encephalitis (RE) is a rare, devastating, progressive pediatric epilepsy. First described 60 years ago, RE continues to present challenges in diagnosis and management. RE causes a unilateral focal epilepsy in children that typically becomes medically refractory, results in significant hemiparesis, and causes progressive cognitive decline. The etiology is a cell-mediated immune attack on one cerebral hemisphere, though the inciting antigen remains unknown. While the underlying histopathology is unilateral and RE is described as "unihemispheric," studies have demonstrated (1) atrophy of the unaffected hemisphere, (2) electroencephalographic abnormalities (slowing and spikes) in the unaffected hemisphere, and (3) cognitive decline referable to the unaffected hemisphere. These secondary contralateral effects likely reflect the impact of uncontrolled epileptic activity (i.e., epileptic encephalopathy). Hemispheric disconnection (HD) renders 70 to 80% of patients seizure free. While it has the potential to limit the influence of seizures and abnormal electrical activity emanating from the pathological hemisphere, HD entails hemiparesis and hemianopia, as well as aphasia for patients with dominant HD. With the recent expansion of available immunomodulatory therapies, there has been interest in identifying an alternative to HD, though evidence for disease modification is limited to date. We review what is known and what remains unknown about RE.

Clinical Experience with Cerebrospinal Fluid Aß42, Total and Phosphorylated Tau in the Evaluation of 1,016 Individuals for Suspected Dementia.

BACKGROUND: Elevated total tau (tTau), 181-phosphorylated phosphorylated tau (pTau), and low amyloid-ß42 (Aß42) in cerebrospinal fluid (CSF) represent a diagnostic biomarker for Alzheimer's disease (AD). OBJECTIVE: The goal was to determine the overall accuracy of CSF Aß42, tTau, pTau, and the Aß42/total tau index (ATI) in a non-research, clinical setting for the diagnosis of AD. METHODS: From medical records in 1,016 patients that had CSF studies for dementia over a 12-year period (2005 to 2017), we calculated the sensitivity and specificity of CSF Aß42, tTau, and pTau and the ATI in relation to the final clinical diagnosis. RESULTS: Compared with non-demented patients and patients with other dementias or mild cognitive impairment (MCI), the sensitivity and specificity of the recommended ATI and pTau cut-offs (ATI < 1.0 and pTau >61 pg/ml) for the diagnosis of AD were 0.88 and 0.72, respectively. Similar results were obtained comparing AD with non-demented patients only (0.88, 0.82) and AD with other types of dementia (0.81, 0.77). A subgroup of patients with presumed normal pressure hydrocephalus (n = 154) were biopsied at the time of shunt placement. Using the pathological manifestations of AD as the standard, the sensitivity was 0.83 while the specificity was 0.72. CONCLUSIONS: In a non-research setting, CSF biomarkers for AD showed a high sensitivity in accordance with previous studies, but modest specificity differentiating AD from other types of dementia or MCI. This study of unselected patients provides a valid and realistic assessment of the diagnostic accuracy of these CSF biomarkers in clinical practice.

Isolation and characterization of human T-Cell lymphotropic virus type-1 from patients with tropical spastic paraparesis

Endemic tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM) is a slowly progressive chronic neurological disorder that is manifested clinically by spastic paraperesis frequently in association with bowel and bladder dysfunction. It is one of the most common chronic neurologic disorders in many endemic foci around the world. Human T-lymphotropic virus type-1 (HTVL-I) has been etiologically associated with TSP/HAM based primarily on the high prevalence of antibodies to HTLV-I in the serum and CSF of affected patients. We report here the isolation of HTLV-I from peripheral blood lymphocytes and cerebrospinal fluid derived mononuclear cells of TSP/HAM patients by stimulation with interleukin-2 and cocultivation with umbilical cord blood mononuclear cells. Established cell lines contained HTLV-I antigen as demonstrated by immunoflourescence and cell-associated virus particles as observed by electron microscopy; low level reverse transcriptase activity was detected in cultures expressing viral antigens. Virus infected cultures were transformed in vitro as determined by their loss of contact inhibition and their continuous growth in the absence of exogenous IL-2. Of particular significance was our location of HTLV-I from three family members with TSP/HAM of varying duration and clinical severity. This study resulted in the first isolation of virus from a cluster of TSP/HAM patients within the same family, the first isolation of virus from a childhood case of TSP/HAM, and the first in vitro transformed HTLV-I infected cells from TSP/HAM patients. In addition, the methodology applied in this investigation subsequently has been used to consistently isolate virus from HTLV-I infected persons from widely separated geographic locations. This work supports a causative role for HTLV-I in the pathogenesis of TSP/HAM and helps to extend the spectrum of disease that may result from HTLV-I infection. (AU)