Pre-stroke activities of daily living do not predict functional decline after stroke in a cohort of community dwelling older subjects at risk for vascular disease.

BACKGROUND & PURPOSE: Pre-stroke impairment of activities of daily living (ADL) is considered a major determinant for functional outcome after stroke. However, findings are based on studies in stroke patients in which pre-stroke information is gathered retrospectively, with inherent risks of selection and recall bias. The objective of this study was to verify the predictive value of pre-stroke ADL with respect to ADL decline in a large prospective cohort of community dwelling older subjects with known vascular risk factors or vascular disease, thereby minimizing selection and recall bias. METHODS: Within the four-year study follow-up of a cohort including 5,804 community dwelling older subjects from three countries at risk for vascular disease, incident stroke survivors were identified. Incident myocardial infarction (MI) survivors and the remaining study survivors without incident vascular events served as comparison groups. Multivariate logistic regression analyses for each of the aforementioned groups were performed to assess associations between pre-stroke ADL by the Barthel Index (BI) and Instrumental Activities of Daily Living (IADL) scale and risk for ADL decline. RESULTS: In stroke survivors, neither pre-event BI (n = 230, OR 1.00 (95% CI 0.83-1.23)) nor IADL (OR 1.07 (95% CI 0.94 - 1.20)) predicted risk of post-stroke ADL decline in contrast to ADL decline after MI (n = 443, OR 0.83 (95% CI 0.70-0.98) and 0.87 (95% CI 0.78-0.97) respectively) and the group without vascular events (n = 4336, OR 0.85 (95% CI 0.78-0.92) and 0.87 (95% CI 0.83-0.92) respectively). CONCLUSIONS: In the present prospective cohort of community dwelling older subjects with known vascular risk factors, pre-stroke ADL measured by BI and IADL scale did not predict post-stroke ADL decline.

Systematic mutation analysis of seven dystonia genes in complex regional pain syndrome with fixed dystonia.

Complex regional pain syndrome type 1 (CRPS-1) is a chronic pain disorder that in some patients is associated with fixed dystonia. The pathogenesis of CRPS and its relation to dystonia remain poorly understood. Several genes (so-called DYT genes) identified in other causes of dystonia play a role in mechanisms that have been implicated in CRPS. Because different mutations in the same gene can result in diverse phenotypes, we sequenced all coding exons of the DYT1, DYT5a, DYT5b, DYT6, DYT11, DYT12, and DYT16 genes in 44 CRPS patients with fixed dystonia to investigate whether high-penetrant causal mutations play a role in CRPS. No such mutations were identified, indicating that these genes do not seem to play a major role in CRPS.

Spontaneous onset of complex regional pain syndrome.

Complex Regional Pain Syndrome (CRPS) usually develops after a noxious event, but spontaneous onsets have been described in 3-11% of the cases. The existence of spontaneous-onset CRPS is highly debated and the aim of the present study was therefore to compare the phenotypic characteristics of CRPS patients with a spontaneous onset, with those of patients with a trauma-induced onset. Data of 537 CRPS patients followed up at four departments of anesthesiology were analyzed and comprised 498 (93%) patients with and 39 (7%) patients without a known eliciting event. There where no significant differences between the two groups in gender, or in onset in upper or lower limb or left or right side of the body. Compared to CRPS patients with a trauma-induced onset, spontaneous-onset cases were on average 9 years younger at disease onset and had a 1.4 years longer median disease duration. No significant differences in frequency were found for any of the 34 compared signs and symptoms when the effect of multiple testing was controlled. In conclusion, CRPS may develop both with and without a precipitating noxious event, with both groups exhibiting a largely similar clinical presentation. Spontaneous-onset CRPS patients generally develop the syndrome at a younger age, possibly indicating a susceptibility to develop the condition. The longer disease duration in spontaneous-onset cases may reflect a more gradual disease onset, poorer prognosis, or a delay in diagnosis, possibly as a result of reluctance to make this diagnosis in the absence of a clear initiating event.

Increased risk of complex regional pain syndrome in siblings of patients?

UNLABELLED: An increased risk among siblings of probands with complex regional pain syndrome (CRPS) may be indicative of a genetic contribution. We calculated the sibling recurrence risk ratio (lambda(sibling)), a measure of familial aggregation. We surveyed 405 CRPS patients to collect information on the occurrence of CRPS in their siblings and compared this risk with the population risk to develop the syndrome. Information on disease status was collected from 1242 siblings, of which 24 were possibly affected according to their siblings. The diagnosis was confirmed in 16 patients, rejected in 2, and could not be verified in the remaining 6. Age-specific risk ratios were calculated for younger (<50 years) and older (> or =50 years) age groups. The strongest effects were seen in the younger age group, with a lambda(sibling) for possibly affected and confirmed cases of 5.6 (95% CI, 3.0 to 9.8) and 3.4 (95% CI, 1.5 to 6.8), respectively. We concluded that this study yielded no indications for an overall increased risk of developing CRPS for siblings of CRPS patients but that the risk was significantly increased in siblings younger than 50, which may indicate that genetic factors play a more pronounced role in this subgroup. PERSPECTIVE: We studied the risk of developing CRPS for siblings of patients with this syndrome. Although the overall risk for siblings was not increased compared with the population risk, the risk for younger siblings was elevated. To enhance chances of success, future genetic studies may consider restricting inclusion to younger-onset cases.

HLA-B62 and HLA-DQ8 are associated with Complex Regional Pain Syndrome with fixed dystonia.

Complex Regional Pain Syndrome (CRPS) is clinically characterized by pain in combination with sensory, autonomic, and motor symptoms that may include weakness, tremor, myoclonus and dystonia of the affected limb(s). The syndrome is multifactorial in origin and mostly attributed to tissue injury. There is some evidence that the human leukocyte antigen (HLA) system plays a role in the pathophysiology of CRPS, but previous studies lacked power. Here we performed the most extensive study investigating the contribution of HLA alleles (i.e. HLA-A, HLA-B, HLA-DRB1, and HLA-DQB1) in 150 CRPS patients who also had fixed dystonia. HLA-B62 (OR=2.05 [95% CI 1.41-2.99], P=0.0005) and HLA-DQ8 (OR=1.75 [95% CI 1.20-2.57], P=0.005) were found significantly associated with CRPS and dystonia. The association remained significant after correction (HLA-B62 P(corrected) [P(c)] = 0.02 and HLA-DQ8 P(c)=0.04). The involvement of HLA-B62 and HLA-DQ8 in CRPS with dystonia may indicate that these HLA loci are implicated in the susceptibility or expression of the disease.

Familial occurrence of complex regional pain syndrome.

Genetic factors are suggested to play a role in complex regional pain syndrome (CRPS), but familial occurrence has not been extensively studied. In the present study we evaluated familial occurrence in Dutch patients with CRPS. Families were recruited through the Dutch Association of CRPS patients and through referral by clinicians. The number of affected members per family, the phenotypic expression and inheritance were assessed. Demographic and clinical characteristics of familial CRPS (fCRPS) patients were compared with those of sporadic CRPS (sCRPS) patients from a Dutch population-based study and with a group of sCRPS patients that was proportionally matched for referral center of the fCRPS probandi to control for referral bias. Thirty-one CRPS families with two or more affected relatives were identified, including two families with five, four with four, eight with three and 17 with two affected relatives. In comparison with sCRPS patients, fCRPS patients had a younger age at onset and more often had multiple affected extremities and dystonia. We conclude that CRPS may occur in a familial form, but did not find a clear inheritance pattern. Patients with fCRPS develop the disease at a younger age and have a more severe phenotype than sporadic cases, suggesting a genetic predisposition to develop CRPS.