Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease

Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis (FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene.     

Motor imagery as a complementary technique for functional recovery after stroke: a systematic review

Objective: To evaluate factors associated with 1-year mortality after discharge for acute stroke.

Methods: In this retrospective cohort study, we studied 305 patients with ischemic stroke or intracerebral hemorrhage discharged in 2010/2011. We linked Get With The Guidelines®-Stroke clinical data with New York State administrative data and used multivariate regression models to examine variables related to 1-year all-cause mortality poststroke.

Results: The mean age was 68.6 ± 14.8 years and 51.1% were women. A total of 146 (47.9%) were discharged directly home, 96 (31.5%) to inpatient rehabilitation facilities (IRFs), and 63 (20.7%) to skilled nursing facilities (SNFs). Overall, 24 (7.9%) patients died within 1-year post-discharge. Older age (adjusted odds ratio [OR] 1.05, 95% confidence interval [CI] 1.00–1.10), higher National Institutes of Health Stroke Scale (NIHSS) on admission (OR 1.10, 95% CI 1.03–1.17), and discharge destination (IRF vs. home, OR 0.10, 95% CI 0.01–0.94; and SNF vs. home, OR 2.22, 95% CI 0.71–6.95) were factors associated with 1-year all-cause mortality. When ambulation status at discharge was added to the model, ambulation with assistance and non-ambulation were significantly associated with mortality (ambulatory with assistance vs. ambulatory, OR 9.42, 95% CI 1.87–47.61; nonambulatory vs. ambulatory, OR 12.65, 95% CI 1.89–84.89).

Conclusions: While age and NIHSS on admission are important predictors of long-term outcomes, factors at discharge – ambulation status at discharge and discharge destination – are associated with 1-year mortality post-discharge for acute stroke and therefore could represent therapeutic targets to improve long-term survival in future studies.     

The diagnosis and management of temporal arteritis

Temporal arteritis (TA), or giant cell arteritis, is a systemic autoimmune vasculitis affecting patients over 50 years of age. It can cause rapid, irreversible bilateral vision loss in older adults and is therefore considered an ophthalmological emergency. Many of the symptoms and signs of TA can be vague, non-specific and gradual in onset, often leading to a delayed or inaccurate diagnosis. As such, it is important for a wide variety of primary optometrists and health practitioners to maintain a robust understanding of the clinical presentation, key investigations and time-sensitive management of this disease, as early initiation of treatment for TA can be vision- and life-saving.     

Expression of platelet-derived growth factor and its receptors by two pre-B acute lymphocytic leukemia cell lines

Platelet-derived growth factors (PDGF) are potent regulators of cell proliferation. The three isoforms of PDGF AA, AB, and BB are encoded by two genes: PDGF A and PDGF B. The v-sis oncogene is homologous to the PDGF-B gene. v-sis can transform cells that express the appropriate PDGF receptors. Two different types of receptors, PDGF-alpha and PDGF- beta, also encoded by two genes, have been identified. We show that two cell lines. SMS-SB and NALM-6, both derived from pre-B-cell acute lymphocytic leukemias, express the PDGF-A chain gene, and one of them, SMS-SB, releases PDGF-A chains into the media. The SMS-SB cells also express the PDGF-beta receptor, whereas NALM-6 cells express the PDGF- alpha receptor and bind PDGF. This extends the possible targets for PDGF to the B-cell lineage lymphocytes.