"If it helps someone, then I want to do it": Perspectives of persons living with dementia on research registry participation.

Registries are an important platform to which persons with dementia and other cognitive impairments can contribute to research studies. Registries also provide an opportunity for patients to stay informed about current studies. Engaging patients in registry development can increase sustainability of a registry and patient retention in clinical registries. We sought the perspective of persons with dementia and their accompanying family members about their registry participation experiences, barriers and facilitators to participation, and potential avenues for improvement of registry processes such as recruitment, data collection, and knowledge translation. Two semi-structured focus groups with persons with dementia and their family members (n = 18) were conducted and analyzed using thematic content analysis. Participants were recruited from an existing patient registry made up of patients currently being seen in a dementia assessment clinic. The main themes identified included altruistic motives with regards to registry participation; and access to and privacy of personal health information. As electronic health records are becoming more common, understanding barriers and facilitators from the perspectives of people with dementia is essential to inform the future development of cognitive condition-related registries. The results from our focus groups identified engagement strategies and solutions to overcome perceived barriers for individuals experiencing progressive cognitive decline to participate in longitudinal registry projects.

Establishing a Canadian registry of patients with amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating cause of progressive weakness, respiratory failure and death. To date there is no effective therapy to meaningfully extend survival but continuously emerging targets and putative treatments are studied in clinical trials. Canadian epidemiological data on ALS is scarce and the socioeconomic impact of ALS on Canadian society is unclear. The Canadian Neuromuscular Disease Registry (CNDR) is a national clinic-based registry of patients with neuromuscular diseases with the goal of facilitating the design and execution of clinical research. METHODS: We conducted a national stakeholder survey to assess interest for a Canadian ALS registry and an assessment of expected case ascertainment. A dataset derivation meeting was held to establish the registry medical dataset. RESULTS: We report the results of the national stakeholder survey, case ascertainment assessment, and the derived dataset that have resulted in the current implementation of a Canadian registry of patients with ALS. CONCLUSIONS: The development of this long sought-after resource is a significant step forward for the Canadian ALS patient and research communities that will result in more efficient clinical trial recruitment and advancements in our understanding of ALS in Canada.

Overexpression of human HSP27 protects sensory neurons from diabetes.

OBJECTIVES: To evaluate whether augmenting neuronal protective mechanisms might slow or arrest experimental diabetic peripheral neuropathy (DPN). DPN is one of the most common neurodegenerative disorders and is rising in prevalence. How it targets sensory neurons is uncertain; the disorder is irreversible and untreatable. We explored the intrinsic protective properties of overexpressed human HSP27 on experimental DPN. HSP27 is a small pro-survival heat shock protein that also increases axonal regeneration. METHODS: Experimental diabetes was superimposed on mice overexpressing a human HSP27 transgene and its impact was evaluated on epidermal innervation, behavioral tests of sensation and electrophysiological indices of DPN. RESULTS: Mice that overexpress human HSP27 in their sensory and motor neurons and that were made diabetic for 6 months by streptozotocin treatment were protected from a range of neuropathic abnormalities, including loss of footpad thermal sensation, mechanical allodynia, loss of epidermal innervation, and slowing of sensory conduction velocity. The protection was selective for sensory neurons in comparison to motor neurons and at 6 months provided better protection in female than male mice. Markers of RAGE-NFκB activation were attenuated by the transgene. CONCLUSIONS: The findings support the idea that diabetic polyneuropathy involves a unique, sensory-centric neurodegenerative process which can be reduced by overexpressing a single gene, an important starting point for new disease-modifying therapeutic approaches.

Irreversible brain injury following status epilepticus.

Described here is a patient with medically intractable generalized epilepsy who developed status epilepticus (SE) affecting his right cerebral hemisphere for about 48 hours, which led to irreversible injury to that hemisphere. His partial SE did not respond to the first-line therapies, repeated doses of midazolam, or continuous intravenous infusion of propofol. Extensive investigations failed to find a cause of his SE except for a low serum valproic acid. A minor trauma that he suffered 1 week prior to his SE was of questionable significance. Neurological examination, neuropsychological testing, electroencephalography, and magnetic resonance imaging all demonstrated striking abnormalities limited to the affected cerebral hemisphere that did not resolve with repeated testing. This case illustrates permanent focal brain injury following prolonged partial SE in a patient with previously known generalized seizure disorder.

Characterisation of the human GFRalpha-3 locus and investigation of the gene in Hirschsprung disease.

BACKGROUND: The GDNF family receptor alpha (GFRalpha) proteins are extracellular cell surface bound molecules that act as adapters in binding of the GDNF family of soluble neurotrophic factors to the RET receptor. These molecules are essential for development of many neural crest derived cell types and the kidney. Mutations in RET and in two members of the GDNF ligand family are associated with Hirschsprung disease (HSCR), a congenital absence of the enteric ganglia. Members of the GFRalpha family are also candidates for HSCR mutations. One such gene is GFRalpha-3, which is expressed in the peripheral nervous system and developing nerves. OBJECTIVE: We have characterised the structure of the human GFRalpha-3 locus and investigated the gene for sequence variants in a panel of HSCR patients. METHODS: Long range PCR or subcloning of PAC clones was used to investigate GFRalpha-3 intron-exon boundaries. A combination of single strand conformation polymorphism (SSCP) analysis and direct sequencing was used to investigate GFRalpha-3 sequence variants. RESULTS: GFRalpha-3 spans eight coding exons and has a gene structure and organisation similar to that of GFRalpha-1. We identified three polymorphic variants in GFRalpha-3 in a normal control population, a subset of which also occurred in HSCR patients. We did not detect any sequence variants within the coding sequence of GFRalpha-3. We found a base substitution in the 5' UTR of GFRalpha-3, 15 base pairs upstream of the translation start site. A second substitution was identified in intron 4 (IVS4-30G>A) between the splice branch site and the splice acceptor site. The final variant was a 2 base pair insertion within the splice donor consensus sequence of exon 7 (IVS7+4ins GG). CONCLUSIONS: We did not detect any correlation between variants of GFRalpha-3 and the HSCR phenotype. Our data suggest that mutations of this gene are not a cause of HSCR.

Prepulse inhibition following lesions of the inferior colliculus: prepulse intensity functions.

The magnitude of the acoustic startle response can be reduced by a relatively weak sound presented immediately before the startle-eliciting sound; this phenomenon has been termed prepulse inhibition (PPI). Previous studies reported that PPI was present in the decerebrate rat, indicating that the primary neural pathways mediating PPI are located in the brainstem. The present study investigated the effects of focal excitotoxic lesions of the inferior colliculus (IC) on acoustic PPI in rats. In the first part, startle magnitudes were measured in six normal rats as the interstimulus interval (ISI) between the prepulse and startle-eliciting sounds varied between 10 and 100 ms. Prepulse-inhibited startle changed in an ISI-dependent manner with the most effective ISI at 50 ms. In the second part, 21 rats were assigned to three groups: normal unoperated, cortical lesion, and IC lesion. With the ISI fixed at 50 ms, as the prepulse sound level increased from 29 to 49 dB SPL, startle responses decreased quickly in both normal and cortical lesion rats. However, rats with unilateral IC lesions made with ibotenic acid had significantly lower PPI but did not display any increase in startle magnitude. These data suggest that the IC is an important structure in the neural circuit mediating acoustic PPI.