Florey Department of Neuroscience and Mental Health - Research Publications
Now showing items 1-12 of 1818
Novel insights into stroke pain beliefs and perceptions
(TAYLOR & FRANCIS LTD, 2019-12-12)
BACKGROUND: Chronic pain is common following stroke, yet its characteristics are poorly understood. OBJECTIVES: To characterize the beliefs and perceptions of people with stroke who experience chronic pain and compare these to a non-stroke population with chronic pain. METHOD: An online survey of the Pain Beliefs and Perceptions Inventory for stroke and non-stroke individuals with chronic pain. Pain beliefs and perceptions, including perceived causes of pain, were compared across the two groups. RESULTS: A total of 223 participants completed all questions. The stroke group (N = 106) reported significantly higher pain intensities (p = <0.001) than the non-stroke group (N = 117). In addition, they identified the stroke as the primary cause of their pain, whereas the non-stroke group identified a body injury as the primary cause. When compared to the non-stroke group, people with stroke were more likely to report their pain as being constant (p = <0.001), demonstrate a lack of understanding regarding cause(s) of their pain (p = <0.001), believe less that their actions contribute to their pain (p = <0.001), and have greater belief that their pain is permanent (p = <0.001). CONCLUSION: These findings emphasize differences in the beliefs and perceptions associated with pain after stroke, supporting the value of targeted attention from research and therapy perspectives. Significant differences in the pain experienced by stroke and non-stroke groups may reflect a poor understanding of chronic pain following stroke. Future educational programs for stroke survivors should be tailored. Targets for future educational interventions are identified and include causes of pain, an understanding of its behavior and potential for improved prognosis.
Chronic pain following stroke: Current treatment and perceived effect
(ELSEVIER SCIENCE INC, 2021-01-01)
BACKGROUND: Chronic pain is common following stroke, however there is little known about the treatments for pain that are being accessed by stroke survivors, nor their perceived effectiveness. OBJECTIVES: The objectives were to: i) identify the number and type of treatments for pain currently used by stroke survivors with chronic pain; and ii) examine the self-perceived effectiveness of medication and non-medication treatments for pain. METHODS: Cross-sectional survey. Participants with stroke and self-reported chronic pain completed an online survey that measured demographics, stroke related factors, intensity of pain, treatments for pain, and perceived effect of medication and non-medication treatments for pain. RESULTS: Of 322 stroke survivors who completed the survey, the majority (90.1%) reported current use of pain treatment(s). Medications were accessed by 257 (79.8%), with the most common being anti-inflammatories (39.8%), anticonvulsants (29.5%) and antidepressants (24.8%). Paracetamol (12.1%) was the most common non-prescribed medication used. Polypharmacy was high, with 129 (40.1%) reporting taking 2 or more medications. Medication treatments were self-reported to be effective in 47.1% of those taking medication. Non-medication treatments were accessed by 208 (64.6%), with Physical Therapy/Physiotherapy being most common (48.1%), followed by Occupational Therapy (15.5%) and Psychology (11.8%). Use of multiple non-medication treatments was reported by 85 (26.4%). Non-medication treatments were reported to be effective by 52.4% of those receiving them. CONCLUSIONS: Survey findings indicate that stroke survivors with chronic pain demonstrate high utilization of pain treatments, despite the perception that treatment is often ineffective. This highlights the need to develop effective pain interventions for stroke survivors.
Genetic characterization identifies bottom-of-sulcus dysplasia as an mTORopathy
(LIPPINCOTT WILLIAMS & WILKINS, 2020-11-03)
OBJECTIVE: To determine the genetic basis of bottom-of-sulcus dysplasia (BOSD), which is a highly focal and epileptogenic cortical malformation in which the imaging, electrophysiologic, and pathologic abnormalities are maximal at the bottom of sulcus, tapering to a normal gyral crown. METHODS: Targeted panel deep sequencing (>500×) was performed on paired blood and brain-derived genomic DNA from 20 operated patients with drug-resistant focal epilepsy and BOSD. Histopathology was assessed using immunohistochemistry. RESULTS: Brain-specific pathogenic somatic variants were found in 6 patients and heterozygous pathogenic germline variants were found in 2. Somatic variants were identified in MTOR and germline variants were identified in DEPDC5 and NPRL3. Two patients with somatic MTOR variants showed a mutation gradient, with higher mutation load at the bottom of sulcus compared to the gyral crown. Immunohistochemistry revealed an abundance of dysmorphic neurons and balloon cells in the bottom of sulcus but not in the gyral crown or adjacent gyri. CONCLUSIONS: BOSD is associated with mTOR pathway dysregulation and shares common genetic etiologies and pathogenic mechanisms with other forms of focal and hemispheric cortical dysplasia, suggesting these disorders are on a genetic continuum.
What is the current practice of therapists in the measurement of somatosensation in children with cerebral palsy and other neurological disorders?
BACKGROUND/AIM: Somatosensation is the ability to detect and recognise body sensations such as touch, vibration, pressure, pain, temperature and proprioception. Cerebral palsy is a neurological disorder that is often accompanied by impairments in somatosensation. Current somatosensory assessments have limited psychometrics established for use with these children. The aim of this study was to identify therapists' current practice and perspectives related to the assessment of somatosensation in children with neurological disorders. METHODS: A cross-sectional questionnaire was used to identify the somatosensory assessments currently used in clinical practice, time allocated to assessment, and therapists' satisfaction and confidence using the available assessments of somatosensation. The questionnaire was adapted from a previously utilised questionnaire that identified therapists' use of somatosensory assessments with adults post-stroke. RESULTS: A total of 135 therapists responded to the questionnaire. Seventy-nine (92%) occupational therapists and 44 (89.7%) physiotherapists indicated that they currently assessed or treated children with somatosensory deficits. Sixty-four (82.1%) occupational therapists and 38 (86.3%) physiotherapists regarded assessment of somatosensation in children with neurological disorders as important to very important. However, only seven (8.8%) occupational therapists and seven (15.9%) physiotherapists reported confidence in their ability to do so. The methods with which therapists detect and measure somatosensory impairment in children with neurological disorders are variable, with non-standardised and/or informal assessments most frequently used. CONCLUSION: Despite there being recommendations of best practice for the assessment of specific domains of somatosensation in children with cerebral palsy, current practice does not yet mirror these recommendations. Additionally, therapists have low satisfaction and confidence with what they are currently using, highlighting the need for a comprehensive and standardised assessment of somatosensation for use in children with neurological disorders.
Three-dimensional neural cultures produce networks that mimic native brain activity
Development of brain function is critically dependent on neuronal networks organized through three dimensions. Culture of central nervous system neurons has traditionally been limited to two dimensions, restricting growth patterns and network formation to a single plane. Here, with the use of multichannel extracellular microelectrode arrays, we demonstrate that neurons cultured in a true three-dimensional environment recapitulate native neuronal network formation and produce functional outcomes more akin to in vivo neuronal network activity.
Measurement properties of instruments that assess participation in young people with autism spectrum disorder: a systematic review
AIM: To systematically review the measurement properties of instruments assessing participation in young people with autism spectrum disorder (ASD). METHOD: A search was performed in MEDLINE, PsycINFO, and PubMed combining three constructs ('ASD', 'test of participation', 'measurement properties'). Results were restricted to articles including people aged 6 to 29 years. The 2539 identified articles were independently screened by two reviewers. For the included articles, data were extracted using standard forms and their risk of bias was assessed. RESULTS: Nine studies (8 cross-sectional) met the inclusion criteria, providing information on seven different instruments. The total sample included 634 participants, with sex available for 600 (males=494; females=106) and age available for 570, with mean age for these participants 140.58 months (SD=9.11; range=36-624). Included instruments were the school function assessment, vocational index, children's assessment of participation and enjoyment/preferences for activities of children, experience sampling method, Pediatric Evaluation of Disability Inventory, Computer Adaptive Test, adolescent and young adult activity card sort, and Patient-Reported Outcomes Measurement Information System parent-proxy peer relationships. Seven studies assessed reliability and validity; good properties were reported for half of the instruments considered. Most studies (n=6) had high risk of bias. Overall the quality of the evidence for each tool was limited. INTERPRETATION: Validation of these instruments, or others that comprehensively assess participation, is needed. Future studies should follow recommended methodological standards. WHAT THIS PAPER ADDS: Seven instruments have been used to assess participation in young people with autism. One instrument, with excellent measurement properties in one study, does not comprehensively assess participation. Studies of three instruments that incorporate a more comprehensive assessment of participation have methodological limitations. Overall, limited evidence exists regarding measurement properties of participation assessments for young people with autism.
Renal haemodynamics and oxygenation during and after cardiac surgery and cardiopulmonary bypass
Acute kidney injury (AKI) is a common complication following cardiac surgery performed on cardiopulmonary bypass (CPB) and has important implications for prognosis. The aetiology of cardiac surgery-associated AKI is complex, but renal hypoxia, particularly in the medulla, is thought to play at least some role. There is strong evidence from studies in experimental animals, clinical observations and computational models that medullary ischaemia and hypoxia occur during CPB. There are no validated methods to monitor or improve renal oxygenation during CPB, and thus possibly decrease the risk of AKI. Attempts to reduce the incidence of AKI by early transfusion to ameliorate intra-operative anaemia, refinement of protocols for cooling and rewarming on bypass, optimization of pump flow and arterial pressure, or the use of pulsatile flow, have not been successful to date. This may in part reflect the complexity of renal oxygenation, which may limit the effectiveness of individual interventions. We propose a multi-disciplinary pathway for translation comprising three components. Firstly, large-animal models of CPB to continuously monitor both whole kidney and regional kidney perfusion and oxygenation. Secondly, computational models to obtain information that can be used to interpret the data and develop rational interventions. Thirdly, clinically feasible non-invasive methods to continuously monitor renal oxygenation in the operating theatre and to identify patients at risk of AKI. In this review, we outline the recent progress on each of these fronts.
Using minimalist self-assembling peptides as hierarchical scaffolds to stabilise growth factors and promote stem cell integration in the injured brain
Neurotrophic growth factors are effective in slowing progressive degeneration and/or promoting neural repair through the support of residual host and/or transplanted neurons. However, limitations including short half-life and enzyme susceptibility of growth factors highlight the need for alternative strategies to prolong localised delivery at a site of injury. Here, we establish the utility of minimalist N-fluorenylmethyloxycarbonyl (Fmoc) self-assembling peptides (SAPs) as growth factor delivery vehicle, targeted at supporting neural transplants in an animal model of Parkinson's disease. The neural tissue-specific SAP, Fmoc-DIKVAV, demonstrated sustained release of glial cell line derived neurotrophic factor, up to 172 hr after gel loading. This represents a significant advance in drug delivery, because its lifetime in phosphate buffered saline was less than 1 hr. In vivo transplantation of neural progenitor cells, together with our growth factor-loaded material, into the injured brain improved graft survival compared with cell transplants alone. We show for the first time the use of minimalist Fmoc-SAP in an in vivo disease model for sustaining the delivery of neurotrophic growth factors, facilitating their spatial and temporal delivery in vivo, whilst also providing an enhanced niche environment for transplanted cells.
Gain-of-function HCN2 variants in genetic epilepsy
Genetic generalized epilepsy (GGE) is a common epilepsy syndrome that encompasses seizure disorders characterized by spike-and-wave discharges (SWDs). Pacemaker hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are considered integral to SWD genesis, making them an ideal gene candidate for GGE. We identified HCN2 missense variants from a large cohort of 585 GGE patients, recruited by the Epilepsy Phenome-Genome Project (EPGP), and performed functional analysis using two-electrode voltage clamp recordings from Xenopus oocytes. The p.S632W variant was identified in a patient with idiopathic photosensitive occipital epilepsy and segregated in the family. This variant was also independently identified in an unrelated patient with childhood absence seizures from a European cohort of 238 familial GGE cases. The p.V246M variant was identified in a patient with photo-sensitive GGE and his father diagnosed with juvenile myoclonic epilepsy. Functional studies revealed that both p.S632W and p.V246M had an identical functional impact including a depolarizing shift in the voltage dependence of activation that is consistent with a gain-of-function. In contrast, no biophysical changes resulted from the introduction of common population variants, p.E280K and p.A705T, and the p.R756C variant from EPGP that did not segregate with disease. Our data suggest that HCN2 variants can confer susceptibility to GGE via a gain-of-function mechanism.
Carotid endarterectomy: the change in practice over 11years in a stroke centre
BACKGROUND: Recent research evidence has impacted the practice of carotid endarterectomy (CEA). We aim to characterize changes in the practice and outcome of CEA over time in a single large-volume stroke centre. METHODS: All patients who underwent CEA from 2004 to 2014 and carotid angioplasty and stenting (CAS) from 2003 to 2008 at an Australian metropolitan tertiary stroke centre hospital were included. Clinical data were analysed to identify time trends in choice of intervention, patient selection, preoperative imaging utilization, surgical timing and outcome. RESULTS: There were 510 CEAs performed during 2004-2014 and 95 CASs during 2003-2008. The proportion of patients undergoing CEA compared to CAS increased from 60% to 90% from 2004 to 2008 (P < 0.001). CAS patients were more likely to have cardiac co-morbidities. From 2004 to 2014, the proportion of CEA patients aged ≥80 years increased (P = 0.001) and the proportion of asymptomatic patients decreased (P = 0.003) over time. Median time from symptom onset to surgery decreased from 52 days (Q1: 25, Q3: 74) in 2004 to 8 days (Q1: 5, Q3: 37) in 2014 (P < 0.001). Use of preoperative ultrasonography decreased whilst CT angiography and the number of imaging modalities applied to each patient increased over time (P < 0.001). Overall, 5.9% of CEAs were complicated by death, stroke or acute myocardial infarction with no significant change over time. CONCLUSION: The trends in CEA practice at our centre align with international trends and guidelines. This study provides a representative indicator of Australian hospital practice, and illustrates how evidence from research is translated into clinical care.