Biomarkers of Parkinson's disease and Dementia with Lewy bodies

Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are progressive and disabling neurodegenerative disorders, in which signs and symptoms overlap with each other and with other neurodegenerative conditions. Currently, diagnosis, measurement of progression, and response to therapeutic intervention rely upon clinical observation. However, there remains a critical need for validated biomarkers in each of these areas. A definitive diagnostic test would improve clinical management and enrollment into clinical trials. An objective measure of progression is vitally important in identifying neuroprotective interventions. Biomarkers may also provide insight into pathogenesis, and might therefore suggest possible novel targets for therapeutic intervention. In addition, certain biomarkers might be of use in monitoring the biochemical and physiological effects of therapeutic interventions. Development of diagnostic biomarkers has focused until recently upon imaging techniques based upon measuring loss of dopamine neurons. Additionally, advances in understanding the genetic contribution to neurodegenerative disorders, in particular in PD, have identified multiple causative genes and risk factors that in some cases may help estimate PD risk. However, recent availability of increasingly sophisticated bioinformatics technology has rendered development of fluid biomarkers feasible, opening the possibility of generally accessible blood or cerebrospinal fluid (CSF) tests that could impact upon diagnosis, management, and research in PD, PDD, and DLB.     

Minocycline 1‐year therapy in multiple‐system‐atrophy: Effect on clinical symptoms and [11C] (R)‐PK11195 PET (MEMSA‐trial)

The aim of the study was to investigate the efficacy of the antibiotic minocycline as a drug treatment in patients with Multiple‐System‐Atrophy Parkinson‐type (MSA‐P). Sixty‐three patients were randomized to minocycline 200 mg/d (n = 32) or a matching placebo (n = 31). The primary outcome variable was the change in the value of the motor score of the Unified Multiple‐System‐Atrophy Rating‐Scale (UMSARSII) from baseline to 48 weeks. Secondary outcome variables included subscores and individual Parkinsonian symptoms as determined by the UMSARS and the Unified‐Parkinson's‐Disease Rating‐Scale (UPDRS). Health‐related quality of life (HrQoL) was assessed using the EQ‐5D and SF‐12. “Progression rate” was assumed to be reflected in the change in motor function over 48 weeks. At 24 weeks and 48 weeks of follow‐up, there was a significant deterioration in motor scores in both groups, but neither the change in UMSARSII nor in UPDRSIII differed significantly between treatment groups, i.e. “progression rate” was considered to be similar in both treatment arms. HrQoL did not differ among the two treatment arms. In a small subgroup of patients (n = 8; minocycline = 3, placebo = 5)[¹¹C](R)‐PK11195‐PET was performed. The three patients in the minocycline group had an attenuated mean increase in microglial activation as compared to the placebo group (P = 0.07) and in two of them individually showed decreased [11C](R)‐PK11195 binding actually decreased. These preliminary PET‐data suggest that minocycline may interfere with microglial activation. The relevance of this observation requires further investigation. This prospective, 48 week, randomized, double‐blind, multinational study failed to show a clinical effect of minocycline on symptom severity as assessed by clinical motor function. © 2009 Movement Disorder Society     

Costs of treating dystonias and hemifacial spasm with botulinum toxin A

Botulinum toxin (BTX) has become a safe and effective therapeutic tool in the treatment of a variety of neurological disorders, especially dystonias. One major disadvantage, however, is the high cost of a single injection of BTX. In this study of 835 patients, we calculated the cost of treatment with BTX serotype A (BTX-A) for different dystonias and hemifacial spasm. The annual expenditure per patient for BTX-A injections in this cohort totalled (mean +/- standard deviation) 1030 Deutschmarks (DM) [1996 values] +/- DM610 [$US570 +/- $US340; 230 +/- 130 pounds sterling (Pound)] for blepharospasm (n = 158), DM1450 +/- DM1520 ($US800 +/- $US830; 310 Pounds +/- 280 Pounds) for craniocervical dystonia (n = 148), and DM1480 +/- DM780 ($US810 +/- $US430; 330 Pounds +/- 180 Pounds) for oromandibular dystonia (n = 16), while the treatment of cervical dystonia consumed DM4590 +/- DM2060 ($US2520 +/- $US1130; 960 Pounds +/- 420 Pounds) [n = 362] per patient. In order to alleviate symptoms in patients with hemifacial spasm (n = 151), DM510 +/- DM270 ($US280 +/- $US150; 110 Pounds +/- 60 Pounds) had to be spent annually. The expenses for surgical therapy for cervical dystonia were DM10,120 +/- DM1900 (n = 54). No major differences concerning expenditure could be found in this study between the 2 available preparations of BTX. However, there appeared to be a lower rate of adverse effects with the Botox formulation, compared with the Dysport formulation, of BTX-A (this difference was statistically significant, i.e. p < 0.001). Although the cost of an individual injection is high, other cost factors also substantially contribute to the societal costs of adult-onset dystonias. Some of these costs may be attenuated with the use of BTX. The subjective and objective relief of these socially devastating and sometimes painful conditions rewards the expenditure associated with the use of BTX-A.     

Re-admission to Level 2 unit after hip-fracture surgery – Risk factors,reasons and outcome

Introduction

Hip fractures are common geriatric fractures with increasing incidence. Treatment of these fractures is still associated with high rates of complications and poor outcome. Data concerning unexpected re-admission to a Level 2 unit after an initial inconspicuous postoperative course are limited. We aimed to identify causes and associated risk factors for admission as well as impact of re-admission on acute care and short-term outcome.

Patients and methods

Patients over 60 years of age with hip fractures were included in this prospective single-centre observational study. Patients with polytrauma or malignancy-associated fractures were excluded. Age, gender, fracture type, pre-fracture residential, physical and cognitive status, recording to the American Society of Anesthesiologists (ASA) score, Barthel Index (BI) and Mini-Mental State Examination (MMSE) were recorded on admission. Date, type of surgery and operation time were evaluated. Postoperatively, the prevalence of and reasons for unexpected re-admission to the Level 2 unit and patients’ outcome were measured. Parameters were hospital mortality, BI at discharge, length of stay in hospital and type of discharge. Univariate and multivariate analyses were performed to identify risk factors for admission to the Level 2 unit and influence on patients’ outcome.

Results

Out of 402 included patients, 48 (12%) were re-admitted to the Level 2 unit. The most frequent reasons were non-surgical (n = 38), such as respiratory failure (n = 12), cardiovascular diseases (n = 8) and acute renal failure (n = 5). Ten patients were re-admitted due to a revision surgery of the hip. We identified two independent risk factors for readmission: male gender (odds ratio (OR) = 2.38, confidence interval (95% CI) = 1.10–5.15, p = 0.027) and type of fracture, especially femoral neck fracture (OR = 7.40, 95% CI = 2.39–23.26, p = 0.001). Patients who were re-admitted to the Level 2 unit had a higher mortality (β = 2.09, OR = 8.07, 95% CI = 2.44–26.75, p = 0.001), an increase in hospital stay (β = 7.0, 95% CI 5.2–8.7, p < 0.001) and a lower functional outcome (BI, β = –17, 95% CI = −23 to −10, p < 0.001).

Conclusion

Unexpected admission to the Level 2 unit in the post-surgical period is a frequent phenomenon in geriatric hip-fracture patients. Males and femoral neck fracture patients seem to be especially endangered. Although the majority of reasons for admissions were not immediately life-threatening illnesses, they had a substantial negative impact on patients’ outcome. This emphasises the importance of careful handling of this frail patient population.