Biomedical subjects
Anthony Schapira
Publications and source records attributed to Anthony Schapira.
Diagnosing restless legs syndrome (RLS) in primary care.
This paper represents a review of current opinion and information on the effective diagnosis of restless legs syndrome (RLS) in a primary care setting. RLS can be a distressing condition--it can cause serious sleep disturbance and has a significant impact on quality of life comparable to that of depression or type 2 diabetes. The prevalence of adults whose RLS is severe enough to warrant medical advice has been estimated to be approximately 3%, but only a small proportion of these patients currently report having been diagnosed in primary care, despite stating that they have presented to their GP. The benefits of increased understanding of the symptoms of RLS and how patients present in primary care are discussed, with emphasis on how this will help GPs more effectively diagnose and manage the patients affected. Guidelines on how to diagnose RLS in a primary care setting are given--when a patient presents with sleep disturbance, RLS should be routinely considered and, where existing, be readily diagnosed in a primary care setting on the basis of the patient's clinical history, a physical examination and with the aid of four questions based on the International RLS Study Group (IRLSSG) four essential diagnostic criteria.
Assessment of in vitro and in vivo mitochondrial function in Friedreich's ataxia and Huntington's disease.
Huntington's disease (HD) and Friedreich's ataxia (FRDA) are associated with defects of respiratory-chain enzyme activities. In the respective disorders, these can be identified in tissue samples from postmortem brain and also during life from skeletal or cardiac muscle samples. The mitochondrial abnormalities are robust and reproducible. In the case of HD, it is uncertain how these mitochondrial defects fit in the pathogenetic cascade. Studies are ongoing to identify whether the respiratory-chain defect present in the brain is expressed in skeletal muscle at the spectrophotometric level. The presence of a bioenergetic defect as identified by 31P magnetic resonance spectroscopy (MRS) suggests that in HD expression of the mutant protein can exert an influence on mitochondrial function in tissues outside the central nervous system (CNS). It would appear that frataxin deficiency has a direct effect on mitochondrial function, either through iron-sulfur cluster construction or through the generation of free radicals. The identification these bioenergetic abnormalities in these neurodegenerative disorders has opened up the prospect for the development of disease-modifying therapies directed to the biochemical abnormalities demonstrated. 31P-MRS studies have detected a deficit of in vivo oxidative phosphorylation in the skeletal muscle of FRDA and HD patients and in the myocardium of FRDA patients. In both FRDA and HD patients, a relationship between the triplet repeat expansion and the extent of in vivo energy metabolism deficit has been shown. The total safety of MRS scans makes them an ideal tool for repeated assessments to monitor disease progression as well as the effect of new therapies. This chapter describes useful methods for assessment of mitochondrial function in vitro and in vivo.
End-of-dose wearing off in Parkinson disease: a 9-question survey assessment.
We have previously reported that the use of a 32-symptom Wearing-off Questionnaire (WOQ-32) identified wearing off more frequently than a clinician's evaluation or the complications subscale of the Unified Parkinson Disease Rating Scale (UPDRS). However, this prototype tool was not designed for clinical practice and required simplification for daily use. Although wearing off is a commonly understood concept among neurologists caring for Parkinson disease patients, there are a number of definitions in the literature. For the purpose of this study and to include both motor and nonmotor parkinsonian symptoms, wearing off was defined as a generally predictable recurrence of motor and nonmotor symptoms that precedes scheduled doses of anti-parkinsonian medication and usually improves after those doses. Using this definition, retrospective analysis and expert opinion were used to identify the 9 most predictive and relevant of the symptoms previously identified as part of the WOQ-32. The resulting 9-symptom questionnaire (WOQ-9) identified 158 (95.8%) of the 165 subjects captured by the 32-Symptom Wearing-off Questionnaire as having wearing off, excluding 7 subjects reporting only balance difficulty (n = 3), numbness (n = 2), difficulty standing (n = 1), and abdominal discomfort (n = 1). Subjects reporting wearing off with the WOQ-9 were significantly younger, had been longer diagnosed with Parkinson disease, experienced a longer duration of levodopa therapy, exhibited a higher UPDRS total score, had higher levodopa equivalent dosages, and increased dyskinesia compared with patients not identified as wearing off with the WOQ-9. No statistical differences were noted with respect to sex, UPDRS subsection scores, Schwab & England Scale, or Hoehn & Yahr Scale.