A longitudinal study on α-synuclein in blood plasma as a biomarker for Parkinson's disease.

There have been no longitudinal studies on α-synuclein as a potential biomarker for the progression of Parkinson's disease (PD). Here, blood plasma 'total α-synuclein' and 'Ser-129 phosphorylated α-synuclein' were assayed at 4-6 monthly intervals from a cohort of 189 newly-diagnosed patients with PD. For log-transformed data, plasma total α-synuclein levels increased with time for up to 20 yrs after the appearance of initial symptoms (p = 0.012), whereas phosphorylated α-synuclein remained constant over this same period. The mean level of phosphorylated α-synuclein, but not of total α-synuclein, was higher in the PD plasma samples taken at first visit than in single samples taken from a group of 91 healthy controls (p = 0.012). Overall, we conclude that the plasma level of phosphorylated α-synuclein has potential value as a diagnostic tool, whereas the level of total α-synuclein could act as a surrogate marker for the progression of PD.

The need for support services for family carers of people with motor neurone disease (MND): views of current and former family caregivers a qualitative study.

PURPOSE: Family carers provide the majority of home-based care for people with motor neurone disease (MND). Carers' need for, and use of, support services are not fully understood; this study aimed to explore, from a qualitative perspective, the views of current and former family carers of people with MND. METHODS: A qualitative study was undertaken in Northwest England, using narrative interviews with current (18) and former (10) carers of a family member with MND. An optional longitudinal element involving diary completion was offered to the current carers. Data were analyzed using a thematic framework approach. RESULTS: Carer's needs vary, but encompass the provision of information and training, availability of respite care, counselling, and access to trained paid-for carers. CONCLUSIONS: There is need for a range of support services to be made available from which carers can select those most appropriate for them. Some support services are not always available for carers of this client group. There is a need for carers to access greater manual handling and training for physical care. Without sufficient support, carer burden can be overwhelming which may impact on the place of care of the patient and ultimately has implications for health and social care services.

Social services homecare for people with motor neurone disease/amyotrophic lateral sclerosis: why are such services used or refused?

Many patients with the terminal condition motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) do not access social service homecare, which may have implications for the location of end-of-life care. We aimed to identify factors related to uptake of such care in MND/ALS. A case note review of patients at a UK MND/ALS clinic (N = 97) provided data concerning disease onset and severity, demographic variables and care received. Narrative interviews with people with MND/ALS (N = 24) and family carers (N = 18) explored their perspectives on social services homecare. Quantitative analyses highlighted the role of increasing disease severity and age for social services homecare uptake. However, qualitative findings revealed a number of barriers delaying the uptake of such care. 'Internal' issues focused on retaining control and normality within the home. 'External' issues arose from limited understanding of the disease amongst service providers and lack of awareness of service entitlement amongst patients and carers. Multiple factors are implicated in the uptake of social services homecare. Uncertainties surrounding service entitlement must be addressed, including the simplification of bureaucratic procedures and clarification of the roles of health and social care professionals. Service providers need a greater awareness of the nature of the disease and their role in its management.

Phosphorylated α-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson's disease.

Parkinson's disease (PD) is characterized by the presence of Lewy bodies containing phosphorylated and aggregated α-synuclein (α-syn). α-Syn is present in human body fluids, including blood plasma, and is a potential biomarker for PD. Immunoassays for total and oligomeric forms of both normal and phosphorylated (at Ser-129) α-syn have been used to assay plasma samples from a longitudinal cohort of 32 patients with PD (sampled at mo 0, 1, 2, 3), as well as single plasma samples from a group of 30 healthy control participants. The levels of α-syn in plasma varied greatly between individuals, but were remarkably consistent over time within the same individual with PD. The mean level of phospho-α-syn was found to be higher (P=0.053) in the PD samples than the controls, whereas this was not the case for total α-syn (P=0.244), oligo-α-syn (P=0.221), or oligo-phospho-α-syn (P=0.181). Immunoblots of plasma revealed bands (at 21, 24, and 50-60 kDa) corresponding to phosphorylated α-syn. Thus, phosphorylated α-syn can be detected in blood plasma and shows more promise as a diagnostic marker than the nonphosphorylated protein. Longitudinal studies undertaken over a more extended time period will be required to determine whether α-syn can act as a marker of disease progression.

Drug therapy for pain in amyotrophic lateral sclerosis or motor neuron disease.

BACKGROUND: Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is the most common neurodegenerative disorder of the motor system in adults. Pain in ALS is a frequent symptom especially in the later stages of disease and can have a pronounced influence on quality of life and suffering. Treatment of pain therefore should be recognised as an important aspect of palliative care in ALS. OBJECTIVES: To systematically review the evidence for the efficacy of drug therapy in relieving pain in ALS. We also aimed to evaluate possible adverse effects associated with the different drugs and their influence on survival and quality of life. SEARCH STRATEGY: The authors searched the following databases: the Cochrane Neuromuscular Disease Group Trials Register (October 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (January 1966 to October 2007), EMBASE (January 1980 to October 2007), CINAHL (January 1982 to October 2007), AMED (January 1985 to October 2007) and LILACS (January 1982 to October 2007). We checked the bibliographies of trials identified and contacted other disease experts to identify further published and unpublished trials. SELECTION CRITERIA: We searched for randomised or quasi-randomised controlled trials on drug therapy for pain in amyotrophic lateral sclerosis. DATA COLLECTION AND ANALYSIS: Data were collected using a specially designed form and analysed using the Cochrane Review Manager software. MAIN RESULTS: No randomised or quasi-randomised controlled trials on drug therapy for pain in ALS or MND were found. AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials about the management of pain in ALS. Further research on this important aspect of palliative care in ALS is needed. Randomised controlled trials should be initiated to determine the effectiveness of different analgesics for treatment of pain in ALS.

TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain, and a mechanistic role in neurodegeneration remains speculative. We identified neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBPM337V segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. Mutant forms of TDP-43 fragmented in vitro more readily than wild type and, in vivo, caused neural apoptosis and developmental delay in the chick embryo. Our evidence suggests a pathophysiological link between TDP-43 and ALS.

Audit of outcomes in motor neuron disease (MND) patients treated with riluzole.

A review of riluzole in MND by NICE concluded that riluzole was modestly effective. NICE however suggested that further studies were needed to gain further insights into its clinical effectiveness. As these studies have not been carried out we audited outcomes in our use of riluzole. Median survival of 148 MND patients receiving riluzole was 3.07 years (2.25 years for 327 patients not given riluzole), hazard ratio 1.66, 95% confidence interval (CI) 1.32-2.12; 3.61 years in 103 limb onset patients given riluzole (2.62 years for 124 limb onset patients not given riluzole), hazard ratio 1.50, 95% CI 1.09-2.05; 2.19 years in 43 bulbar onset patients receiving riluzole (1.84 years for 103 bulbar onset patients not given riluzole), hazard ratio 1.34, 95% CI 0.89-2.07 and 3.80 years in 87 patients with a PEG given riluzole (2.21 years for 261 patients with a PEG not given riluzole), hazard ratio 1.86, 95% CI 1.44-2.39. These findings are comparable with the results of similar analyses from other groups. The uncertainties they raise emphasize the importance of adequate randomized studies being completed prior to licensing of new drugs. They further illustrate the desirability of controlled introduction of new drugs into clinical practice when RCTs have only suggested a modest level of efficacy.