Evaluation of morning bradykinesia in Parkinson's disease in a United States cohort using continuous objective monitoring.

Introduction: Bradykinesia in Parkinson's disease is a marker for clinical levodopa responsiveness, with persistent bradykinesia reflecting suboptimal response. We objectively measured prevalence and severity of morning bradykinesia using the Personal KinetiGraph® (PKG®). Methods: Retrospective evaluation of a large global database of de-identified PKG assessments from individuals (N=12,840) in routine clinical care in the United States (US; n=3288). Median bradykinesia scores (mBKS) and median dyskinesia scores (mDKS) were calculated using a validated algorithm and previously established targets to evaluate percent time in bradykinesia, levodopa responsiveness, and prevalence and severity (0-5; 5=highest severity) of morning bradykinesia. Results: mBKS was above target (≥26) in 65% of all individuals, and mDKS was above target (≥7) in 3%. Elevated percent time in bradykinesia occurred in 79%. Among individuals where levodopa responsiveness could be evaluated (n=1933), 31% had a significant response (≥1.15 postdose decrease in severity). Morning bradykinesia was identified in 85% of individuals with available morning data (1298/1524), and 64% (954/1501) experienced continued bradykinesia after the first daily levodopa dose. Morning bradykinesia was severe (4.0-4.7) in levodopa-responsive individuals regardless of percent time spent in bradykinesia. Conclusion: Elevated mBKS was very common in the US. Most individuals taking levodopa had morning bradykinesia that persisted even after the first daily dose, and severity was high, indicating a need for additional treatment options.

Widespread, restricted low-level measles virus infection of brain in a case of subacute sclerosing panencephalitis.

In situ reverse transcriptase-polymerase chain reaction amplification with labeled-probe hybridization (in situ RT-PCR/LPH) was used to detect measles virus RNA within formalin-fixed, paraffin-embedded brain tissue sections from a patient who died with subacute sclerosing panencephalitis (SSPE). Many more infected neurons and oligodendrocytes were detected by in situ RT-PCR/LPH than by immunohistochemistry or by in situ hybridization alone. In addition, infection of vascular endothelial cells was demonstrated only by in situ RT-PCR/LPH. The observation that many cells contained only a few copies of viral RNA without detectable antigen is consistent with a persistent viral infection of the central nervous system. In situ RT-PCR/LPH, combining the sensitivity of PCR with the tissue localization of in situ hybridization, should prove useful in further studies to detect nucleic acids in situ in the central nervous system.

Exons 16 and 17 of the amyloid precursor protein gene in familial inclusion body myopathy.

Accumulation of beta-amyloid protein (A beta) occurs in some muscle fibers of patients with inclusion body myopathy and resembles the type of amyloid deposits seen in the affected tissues of patients with Alzheimer's disease and cerebrovascular amyloidosis. Because mutations in exons 16 and 17 of the beta-amyloid precursor protein (beta APP) gene on chromosome 21 have been identified in patients with early-onset familial Alzheimer's disease and Dutch-type cerebrovascular amyloidosis, we searched for mutations of the same region in patients with familial inclusion body myopathy. Sequencing of both alleles in 8 patients from four unrelated families did not reveal any mutations in these exons. The amyloid deposition in familial forms of inclusion body myopathy may be either due to errors in other gene loci, or it is secondary reflecting altered beta APP metabolism or myocyte degeneration and cell membrane degradation.