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Functional dependency in basic activities of daily living (ADLs) is a key outcome in Parkinson's disease (PD). We aimed to define dependency in PD, using the original and MDS versions of the Unified Parkinson's Disease Rating Scale (UPDRS).We developed two algorithms to define dependency from items of UPDRS Part 2 and MDS-UPDRS Part 2 relating to basic ADLs (feeding, dressing, hygiene and walking, and getting out of a chair). We validated both algorithms using data from 1110 patients from six community-based PD incidence cohorts, testing concurrent validity, convergent validity, and predictive validity.Our optimal algorithm showed high specificity and moderate to high sensitivity versus SchwabEngland80% (specificity 95% [95% confidence interval (CI) 93-97] and sensitivity 65% [95% CI 55-73] at baseline; 88% [95% CI 85-91] and 85% [95% CI 79-97] respectively at five-years follow-up). Convergent validity was demonstrated by strong associations between dependency defined by the algorithm and cognition (MMSE), quality of life (PDQ39), and impairment (UPDRS part 3) (all p 0.001). Algorithm-defined dependency status also predicted mortality: HR for mortality in those dependent vs independent at baseline was 1.6 (95%CI 1.2-2.1) and in those dependent vs independent at five-years' follow-up was 2.2 (1.6-3.0).We have demonstrated the concurrent validity, convergent validity, and predictive validity of a UPDRS-/MDS-UPDRS-based algorithm to define functional dependency in PD. This can be used for studying dependency in any study where UPDRS or MDS-UPDRS part 2 data have been collected.

Myasthenia gravis (MG) is an autoimmune disorder with heterogeneity. Antibodies against acetylcholine receptor (AChR), muscle-specific kinase (MuSK), titin and ryanodine receptor (RyR) were examined in 437 adult Chinese MG patients. The AChR, MuSK, titin and RyR antibodies were found in 82.2%, 2.3%, 28.4% and 23.8% of all patients. Autoantibody profiles vary among different MG subgroups. Thymoma MG patients had high frequencies of AChR (99.2%), titin (50.8%) and RyR antibodies (46.9%). The titin and RyR antibodies also showed high frequencies in late onset patients (54.4% and 33.3%, respectively). These two antibodies may indicate an underlying thymoma when combined. The patients with titin and RyR antibodies tend to have more severe disease and worse outcome, and may need more active immunosuppressive treatment.

Background Parkinson's disease is a progressive movement disorder recognized by motor symptoms which frequently are measured and longitudinally monitored using the Unified Parkinson Disease Rating Scale (UPDRS). The factor structure of the UPDRS has yet not been analyzed in early PD. Methods A population-based cohort of patients with PD was investigated at the time of diagnosis, one year and three years later. The factor structure of the motor section of the UPDRS was explored using Principal Component Analysis (PCA). Results We found that the factor structure, the interrelatedness among variables, is different in the first year from diagnosis compared to later stages, but evolves at three years to resemble the factor structure reported for more advanced PD. The only consistent factor throughout the observation period was an axial factor. Conclusion The factor structure differs in early versus more advanced PD, but resembles the factor structure of more advanced PD after three years. This is likely due to a higher proportion of subjects with unilateral motor symptoms in early stages of PD together with a changing distribution of motor symptoms with further disease progression. Initiation of PD medication did not alter the factor structure in early PD. The axial factor was the most consistent factor in early PD and could be the most appropriate factor to monitor progression across the earliest stages of PD.

There are few reports on the effect of gamma knife surgery (GKS) for brain metastases from colorectal cancer. The purpose of this study was to identify prognostic factors for local control, complications, and survival in our series of patients treated with GKS.Eighty patients (36 males, 44 females) with 140 metastases who received GKS between 1996 and 2008 were retrospectively reviewed. The mean tumor volume was 6.13 (0.01-35.5) cm(3); the prescription dose was 21.1 (10-25.1) Gy and the maximum dose 42.7 (17.2-66.7) Gy; and the tumor cover was 95.0% (72%-100%).Growth control was achieved in 93 of 121 tumors (76.9%) and 42 of 68 (61.8%) patients, while treatment failure was seen in 28 of 121 tumors (23.1%). Local control was better if a high prescription dose of 25 Gy was used, 88.4% vs. 71.4% (P = 0.017), or if tumor volume was5 cm(3) (86.4%), compared with 69.9% for 5-20 cm(3) and 51.9% for20 cm(3) (P = 0.002). The hazard ratio for local failure with lower prescription doses was 2.8 (P = 0.026) in the unadjusted, and 8.5 (P = 0.055) in the adjusted multivariate analysis (tumor volumes5 cm(3)). The median survival was 6 months (range 0-75) after GKS. Age70 years (P0.001) and high RPA class (P = 0.032) were associated with longer survival. Fifteen patients (22.1%) had persistent edema on follow-up MRI, possibly because of radiation damage to the tumor. Radiation-induced edema was asymptomatic in 93.8%. We found neither a decrease in the incidence of new metastases nor improved survival when whole-brain radiation therapy was given prior to GKS.GKS provides reasonable local tumor control. Local control rate is highest if the margin dose is 25 Gy and the tumor volume5 cm(3). Radiation edema was common but rarely symptomatic. Survival is longest for young, well-functioning patients.

We report four cases of focal myositis. The patients, three men and one woman, had painful muscle hypertrophy, affecting four different sites. MRI confirmed the muscle enlargement and oedema. Electromyography revealed evidence of acute and chronic denervation in all four cases. Muscle biopsy was available in three and confirmed features suggestive of focal myositis. Based on our patient material, we suggest that chronic nerve irritation, such as compression, can lead to muscle hypertrophy which, when prolonged, provokes fibre necrosis and secondary inflammation. Our finding in four patients having hypertrophy involving four different sites, leads us further to suggest that this may be the common mechanism behind focal myositis.

Interleukin 10 (IL-10) is secreted by several hemopoietic cells and suppresses the Th1 mediated immune response, while stimulating B cell differentiation and the humoral immune response. IL-10 expression in Con A-stimulated peripheral blood mononuclear cells is related to three polymorphisms in the promoter region of the IL-10 gene; G/A at position -1082, T/C at position -819 and A/C at position -592. We analyzed the distribution of these IL-10 polymorphisms in 64 MG patients and 87 healthy blood donors to determine any influence on MG susceptibility. MG patients had a significantly higher frequency of the ACC/ACC haplotype (12.5% vs 3.4% in controls), as had the subgroups with late onset MG and thymomatous MG (20.0% and 21.4%, respectively). Early onset MG patients had a high frequency of the ATA/ATA haplotype (19.2% vs 3.4% in controls). Titin Ab-positive MG patients had high ACC/ACC (20.0%). This study indicates a direct link between IL-10 and MG pathogenesis, although the complex role of this multi-faceted cytokine in vivo is as yet not fully elucidated.

Parkinson's disease (PD) may be associated with a number of different diseases due to common risk factors or overlapping symptomatology. We have asked for possible associated disorders in a Norwegian population of incident PD patients and controls, the Norwegian ParkWest study. The patients were diagnosed according to the Gelb criteria. 212 incident PD patients and 175 age and gender matched controls were included. PD patients and controls were asked for information on earlier medical history and family history. PD patients had a higher frequency of self-reported symptoms of depression (p = 0.003) and anxiety disorders (p = 0.004) before baseline. They tended to have a higher frequency of diabetes (p = 0.09) and had a higher frequency of prior stroke or TIA (p = 0.004).

Cortical-type thymomas are associated with myasthenia gravis (MG) in 50% of the cases. MG is caused by antibodies against the acetylcholine receptors (AChR), but additional non-AChR muscle autoantibodies such as those against titin and ryanodine receptor (RyR) are found in up to 95% of MG patients with thymoma. To elucidate the induction of non-AChR autoantibodies in thymoma-associated MG, we studied cortical-type thymomas from seven thymoma MG patients, and sera from six of them. All six had titin antibodies, and four had RyR antibodies. Titin and RyR epitopes were co-expressed along with LFA3 and B7 (BB1) costimulatory molecules on thymoma antigen-presenting cells (APC) in all thymomas. In normal thymus, the staining by anti-titin, anti-RyR, anti-LFA3, and anti-BB1 antibodies was weak and occurred exclusively in the medulla and perivascularly. Our results indicate a primary autosensitization against titin and RyR antigens inside the thymoma. In MG-associated thymoma, the mechanisms involved in the initial autosensitization against titin and RyR are probably similar to those implicated in the autosensitization against AChR. In all cases, there is an overexpression of muscle-like epitopes and costimulatory molecules indicating that the T-cell autoimmunization is actively promoted by the pathogenic microenvironment inside the thymoma.

Myasthenia gravis (MG) patients develop autoantibodies primarily against the acetylcholine receptor in the motor endplate, but also against intracellular striated muscle proteins, notably titin, the giant elastic protein of the myofibrillar cytoskeleton. Titin antibodies have previously been shown to be directed against a single epitope on the molecule, located at the A-band/I-band junction and referred to as the main immunogenic region (MIR) of titin. By using immunofluorescence microscopy on stretched single myofibrils, we now report that approximately 40% of the sera from 18 MG/thymoma patients and 8 late-onset MG patients with thymus atrophy contain antibodies that bind to a more central I-band titin region. This region consists of homologous immunoglobulin domains and is known to be differentially spliced dependent on muscle type. All patients with I-band titin antibodies also had antibodies against the MIR. Although a statistically significant correlation between the occurrence of I-band titin antibodies and MG severity was not apparent, the results could hint at an initial immunoreactivity to titin's MIR, followed by reactivity along the titin molecule in the course of the disease.

The Fc γ receptors, Fc γ RIIA and Fc γ RIIIB contain polymorphisms with different capacity for IgG binding and phagocytosis. Thirty myasthenia gravis (MG) patients and 49 healthy controls were genotyped for the Fc γ RIIA and Fc γ RIIIB polymorphisms using polymerase chain reaction. The frequency of the Fc γ RIIA-H/H genotype was increased in thymoma MG patients compared to other MG patients ( P =0.05) and controls ( P =0.02). The distribution of Fc γ RIIIB alleles in MG patients did not differ from the controls, but MG patients with the NA1/NA1 genotype had the most severe MG ( P =0.01). Levels of AChR-antibodies and frequency of titin or ryanodine receptor antibodies were not associated with the Fc γ RIIA or Fc γ RIIIB genotypes. The results suggest different pathogenetic mechanisms in paraneoplastic and non-paraneoplastic autoimmune MG.