ORCID Profile
0000-0002-8543-7767
Current Organisations
Alfred Health
,
Monash University
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Publisher: Wiley
Date: 09-12-2006
Publisher: SAGE Publications
Date: 06-2023
DOI: 10.1177/03331024231180562
Abstract: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAb) are an effective treatment of migraine however may have possible off-target effects. Pre-clinical studies implicate CGRP in several aspects of bone turnover and homeostasis. The clinical effect of CGRP mAb on bone turnover is not known, however. Between June 2021 and July 2022, a multi-centre prospective cohort study was undertaken with eligible patients undergoing paired testing of the validated bone turnover markers procollagen type I N-terminal propeptide (P1NP) and serum C-terminal telopeptide of type I collagen (CTX) prior to and at least three months following administration of a CGRP mAb. A total of 45 patients with a mean age of 41.8 (SD 11.9) were included in the final analysis, all of whom received a ligand-targeting CGRP mAb. Administration of a CGRP mAb was associated with a statistically significant increase in P1NP from 44.5 microg/L to 51.5 microg/L (p = 0.004), but no significant change in CTX. In otherwise homeostatic conditions, short-term administration of a CGRP mAb is associated with increased P1NP, a bone formation marker but not with increased CTX, a bone resorption marker. Further study is required to validate these findings over longer time periods, in a larger cohort, and in pre-existing states of increased calcium stress and bone-turnover.
Publisher: Informa UK Limited
Date: 03-2010
DOI: 10.1586/ECI.09.80
Abstract: This review focuses on recent developments in the treatment of inflammatory neuropathies arising from immune dysregulation, rather than from infectious causes. The dysimmune inflammatory neuropathies are diseases of the peripheral nerves that have varying etiologies and may respond to immunomodulatory therapies. They are characterized by inflammatory changes in the nerve with associated destruction of myelin and axons. The underlying immune mechanisms are better understood in some of these conditions than others. Correct diagnosis and treatment is important to prevent clinical progression. Randomized controlled trials of some treatments in the more common inflammatory neuropathies have clarified their effectiveness however, there are still groups of patients who are resistant to currently available treatments and for whom little effective treatment is available. Newer, targeted biologics and larger controlled trials of existing and novel therapies in these conditions offer promise of improved morbidity and mortality in this group of diseases.
Publisher: Wiley
Date: 12-2011
DOI: 10.1111/J.1529-8027.2011.00360.X
Abstract: Schwann cell dedifferentiation following nerve injury is important to permit neural survival and axonal regrowth. Animal studies have shown that the transcription factor c-Jun is upregulated in Schwann cells of injured and pathological nerves where it acts as an important regulator of Schwann cell plasticity, promoting dedifferentiation and demyelination. This pilot immunohistochemical study investigates whether c-Jun is also upregulated in human neuropathies. We examined c-Jun expression in normal and diseased human nerves, as well as in dermal myelinated nerve fibres. Our findings show that although as predicted c-Jun is rarely expressed in normal nerves, it is expressed in Schwann cell nuclei of pathological nerves as predicted by animal studies. Pathological dermal myelinated nerve fibres also show clear nuclear c-Jun expression. Further studies of c-Jun expression will help clarify its role in human neuropathies.
Publisher: BMJ
Date: 24-05-2018
DOI: 10.1136/JNNP-2018-ANZAN.76
Abstract: Recurrent Guillain-Barre syndrome (GBS) is very rare. It occurs in 2% to 5% of GBS patients. It is unclear as to why some patients have a recurrence and whether this occurs more frequently in a distinct group of patients. We report a case of a 75 year old man who had five discreet attacks of GBS in 30 years. He had an excellent response to intravenous immunoglobulin (IVIG) and achieved full clinical recovery after each attack. A 75 year old man presented to the hospital with progressive ascending pattern of numbness and weakness in upper and lower limbs. This was in the setting of 10 days history of upper respiratory tract infective (URTI) symptoms. Neurological examination revealed distal sensory loss and distal weakness in upper and lower limbs. Deep tendon reflexes were absent. Nerve conduction studies showed features in keeping with GBS. He was treated with 5 days of intravenous immunoglobulin (IVIG) with significant improvement. Interestingly, this was on the background of having had 4 previous attacks of GBS in 1986 (preceded by acute gout), 1997 (preceded by the flu), 2010 (preceded by small bowel obstruction) and 2016 (preceded by viral gastroenteritis). He responded to IVIG each time and returned to his premorbid level function promptly after each attack. Recurrent GBS is rare. It is important for clinician to be able to distinguish between recurrent GBS, treatment related fluctuations (GBS-TRF) and chronic inflammatory demyelinating polyneuropathy as the treatment and outcomes are different for each of these conditions. . Kuitwaard K, Van Koningsveld R, Ruts L, Jacobs B, Van Doorn P. Recurrent Guillain Barre Syndrome. J Neurol Neurosurg Psychiatry2009 :56–59. . Pyun SY, Jeong JH, Bae JS. Recurrent Guillain-Barré syndrome presenting stereotypic manifestations, positive antiganglioside antibodies, and rapid recovery. Clin Neurol Neurosurg2015Dec :230–3. . Mossberg N, Nordin M, Movitz C, Nilsson S, Hellstrand K, Bergström T, Andersson B, Andersen O. The recurrent Guillain-Barré syndrome: A long-term population-based study. Acta Neurol Scand2012Sep (3):154–61.
Publisher: Springer Science and Business Media LLC
Date: 04-04-2023
DOI: 10.1186/S10194-023-01572-7
Abstract: The role of inflammation and cytokines in the pathophysiology of primary headache disorders is uncertain. We performed a systematic review and meta-analysis to synthesise the results of studies comparing peripheral blood cytokine levels between patients with migraine, tension-type headache, cluster headache, or new daily persistent headache (NDPH), and healthy controls and in migraine between the ictal and interictal stages. We searched PubMed/Medline and Embase from inception until July 2022. We included original research studies which measured unstimulated levels of any cytokines in peripheral blood using enzyme-linked immunosorbent assay or similar assay. We assessed risk of bias using the Newcastle–Ottawa Quality Assessment Scale. We used random effects meta-analysis with inverse variance weighted average to calculate standardised mean difference (SMD), 95% confidence intervals, and heterogeneity for each comparison. This study is registered with PROSPERO (registration number CRD42023393363). No funding was received for this study. Thirty-eight studies, including 1335 patients with migraine (32 studies), 302 with tension-type headache (nine studies), 42 with cluster headache (two studies), and 1225 healthy controls met inclusion criteria. Meta-analysis showed significantly higher interleukin (IL)-6 (SMD 1.07, 95% CI 0.40–1.73, p = 0.002), tumour necrosis factor (TNF)-α (SMD 0.61, 95% CI 0.14–1.09, p = 0.01), and IL-8 (SMD 1.56, 95% CI 0.03–3.09, p = 0.04), in patients with migraine compared to healthy controls, and significantly higher interleukin-1β (IL-1β) (SMD 0.34, 95% CI 0.06–0.62, p = 0.02) during the ictal phase of migraine compared to the interictal phase. Transforming growth factor (TGF)-β (SMD 0.52, 95% CI 0.18–0.86, p = 0.003) and TNF-α (SMD 0.64, 95% CI 0.33–0.96, p = 0.0001) were both higher in patients with tension-type headache than controls. The higher levels of the proinflammatory cytokines IL-6, IL-8 and TNF-α in migraine compared to controls, and IL-1β during the ictal stage, suggest a role for inflammation in the pathophysiology of migraine, however prospective studies are required to confirm causality and investigate the mechanisms for the increase in cytokine levels identified. Cytokines may also have a role in tension-type headache. Due a lack of data, no conclusions can be made regarding cluster headache or NDPH.
Publisher: BMJ
Date: 07-2019
DOI: 10.1136/JNNP-2019-ANZAN.53
Abstract: Migraine is the leading cause of age-adjusted neurological disability in Australia, but little is known about headache training in our region. We aimed to assess the quantity of teaching in headache subjects during undergraduate and postgraduate years. This is a cross-sectional survey study where questionnaires were sent to 137 delegates from Australia, New Zealand and Asia, prior to the Headache Master School in Sydney in August 2018. The Main outcome measured are recalled number of hours of teaching in undergraduate year and postgraduate years in: 1) Migraine 2) Trigeminal autonomic cephalalgias (TACs) 3) Asthma 4) Myasthenia gravis (MG). The questionnaire response rate was 73% (100 of 137), of which 29 delegates were within 10 years of completing their undergraduate degree and 98 were neurologists. In undergraduate training, there was much greater quantity of teaching in asthma than migraine (Z=5.007, p .000) despite both being high-prevalent (asthma 11%, migraine 15–20%) conditions. Similarly, for diseases of medium-to-low prevalence, there was less training in TACs (1/1000), compared to MG (1.2/10,000) (Z=6.196, p .000). These major differences in training were also seen in postgraduate years even though overall headache teaching was greater in postgraduate than undergraduate training (p .000). Despite the high prevalence and morbidity of headache disorders, they receive less attention in training than conditions with similar prevalence. We propose that headache training opportunities should be improved in our region, particularly in the undergraduate course and preceptorships or fellowships in postgraduate years.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Jaypee Brothers Medical Publishers (P) Ltd.
Date: 2018
Publisher: BMJ
Date: 07-2019
DOI: 10.1136/JNNP-2019-ANZAN.108
Abstract: Migraine is the greatest cause of disability under the age of 50. It impairs ability to function, work and maintain relationships. This survey aimed to assess the impact of migraine and its management. A questionnaire was sent to patients years old who had taken at least one preventive treatment for migraine in the past. We report here the Australian results. 68% were women, mean age 41 years. 53% were in paid employment whilst 13% received a disability allowance due to migraine. All patients (n=320) in the Australian survey had ≥ 4 migraine days each month. 90% had taken at least one preventive (274), with 80% (194) needing to change the preventive treatments previously. Common comorbidities were depression (41%), anxiety (40%), chronic pain (29%), sleep disorder (25%) and overweight (24%). Diagnosis rate on initial GP visit was 57%, with 26% receiving a diagnosis in month and 55% by 6 months. There was greater retention of use (60%) and satisfaction (60%) with acute therapies, compared with use (43%) and satisfaction (53%) with preventives. Dissatisfaction with preventives included lack of efficacy (54%) and too many side effects (36%). Most ( %) patients reported fear of the next attack, feeling hopeless and difficulty thinking clearly during attacks. Employers were often (69%) aware of the migraines, but only 24% offered any support. Migraine had negative impacts on relationships. The Migraine Voice Survey highlights the true burden of migraine in Australia and limitations of current management options.
Publisher: BMJ
Date: 25-01-2021
Abstract: Migraine is the second largest cause of years lost to disability globally among all diseases, with a worldwide prevalence over 1 billion. Despite the global burden of migraine, few classes of therapeutics have been specifically developed to combat migraine. After 30 years of translational research, calcitonin gene-related peptide (CGRP) inhibitors have emerged as a promising new tool in the prevention of migraine. Like all new therapeutics however, we have limited real-world experience and CGRP has several known systemic actions that warrant consideration. This article provides a narrative review of the evidence for CGRP antagonists and summarises the known and potential side effects that should be considered.
Publisher: BMJ
Date: 10-06-2022
Abstract: Arterial and venous thromboembolic events (TEEs) have been associated with intravenous Ig use, but the risk has been poorly quantified. We aimed to calculate the risk of TEEs associated with exposure to intravenous Ig. We included participants from UK Biobank recruited over 3 years, data extracted September 2020. The study endpoints were incidence of myocardial infarction, other acute ischaemic heart disease, stroke, pulmonary embolism and other venous embolism and thrombosis. Predictors included known TEE risk factors: age, sex, hypertension, smoking status, type 2 diabetes mellitus, hypercholesterolaemia, cancer and past history of TEE. Intravenous Ig and six other predictors were added in the sensitivity analysis. Information from participants was collected prospectively, while data from linked resources, including death, cancer, hospital admissions and primary care records were collected retrospectively and prospectively. 14 794 of 502 492 in iduals had an incident TEE during the study period. The rate of incident events was threefold higher in those with prior history of TEE (8 .7%) than those without previous history of TEE (3.0%). In the prior TEE category, intravenous Ig exposure was independently associated with increased risk of incident TEE (OR=3.69 (95% CI 1.15 to 11.92), p=0.03) on multivariate analysis. The number needed to harm by exposure to intravenous Ig in those with a history of TEE was 5.8 (95% CI 2.3 to 88.3). Intravenous Ig exposure did not increase risk of TEE in those with no previous history of TEE. Intravenous Ig is associated with increased risk of further TEE in in iduals with prior history of an event with one further TEE for every six people exposed. In practice, this will influence how clinicians consent for and manage overall TEE risk on intravenous Ig exposure.
Publisher: Frontiers Media SA
Date: 03-11-2022
DOI: 10.3389/FNEUR.2022.1036798
Abstract: To assess the prevalence and burden of autonomic symptoms in migraine, and determine the relationship with migraine frequency. Autonomic symptoms in migraine have been theorized to occur in the setting of inter-ictal sympathetic hypoactivity and hyper-sensitivity. There is limited data prospectively assessing cranial and extra-cranial autonomic symptoms with a validated instrument, or longitudinal data on the relationship between migraine disease activity and autonomic symptoms. Patients attending a single tertiary academic center were recruited into a prospective cohort study between September 2020 and June 2022. In addition to standard clinical care, they completed several surveys including the Composite Autonomic Symptom Scale (COMPASS-31) questionnaire, a validated survey of autonomic symptoms. A total of 43 patients (66.7% female, median age 42, IQR 17) were included in the final analysis. There was a baseline 20 monthly headache days (MHD) (IQR 21.7), and 65.1% of the population had chronic migraine by ICHD-3 criteria. A significantly elevated weighted COMPASS-31 score was reported in 60.5% of respondents (mean 30.3, SD 13.3) at baseline. After 12 months treatment, significant improvements were reported in migraine frequency (median MHD 20–8.7) and disability (median Migraine Disability Assessment Score 67–48), but not in autonomic symptoms (mean score 30.3, SD 11.2). Autonomic symptoms were frequently reported in patients with migraine. However, they did not correlate with headache frequency or reversion to episodic frequency. Further study is required to elucidate specific approaches and treatments for autonomic symptoms, and further evaluate the underlying pathophysiological mechanisms.
Publisher: Springer Science and Business Media LLC
Date: 09-10-2021
DOI: 10.1186/S10194-021-01330-7
Abstract: Calcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response. We present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy. This case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward.
Publisher: Wiley
Date: 12-2014
DOI: 10.1111/JNS.12100
Abstract: Gait analysis of people with Charcot-Marie-Tooth (CMT) disease revealed proximal adaptive gait strategies to compensate for foot drop. We previously demonstrated that hip flexor muscle fatigue can limit walking endurance. This pilot study used a single-blinded cross over design to investigate the effect of a 16-week home-based programme of resistance training on hip flexor muscle strength. Measures of walking endurance, gait speed, exertion, fatigue, and general activity were also recorded. The exercise protocol was based on American College of Sports Medicine recommendations. A mixed effects model was used for analysis. Twenty-six people finished the study, with average reported exercise participation of 93%. No negative effects of exercise were observed. Significant increase in hip flexor muscle strength was observed on the left, but not the right. No changes were observed in walking speed and endurance measures. This pilot study of home-based resistance training showed a modest improvement in hip strength but only on one side. The lack of a more significant improvement and no improvement in walking measures suggests that this training protocol may not be optimal for people with CMT and that patients may need to stratified differently for training studies in CMT.
Publisher: The Royal Australian College of General Practitioners
Date: 12-2021
Publisher: Wiley
Date: 29-09-2020
DOI: 10.1111/HEAD.13968
Abstract: To determine the effectiveness and safety of erenumab in patients with chronic migraine in the real‐world setting of 3 headache centers in Australia. Patients with migraine were prescribed erenumab (70 or 140 mg) in the setting of either a product familiarization program or paid access to the medication in 3 headache centers in Australia. We obtained baseline and monthly prospective data on monthly headache days, monthly migraine days, monthly triptan use days, monthly codeine use days, Headache Impact Test‐6 scores, and adverse reactions. In this paper, we present our data at 3 and 6 months in our subgroup of patients with chronic migraine with and without medication overuse. A total of 170 patients with chronic migraine were prescribed erenumab in the 3 headache centers. At 3 months, 100/170 (58.8%) had 50% or greater reduction in monthly migraine days. At 6 months, 79/170 (46.5%) had 50% or greater reduction in monthly migraine days. At 6 months, there was a mean reduction in monthly headache days of 9.2 days, a mean reduction in monthly migraine days of 10.2 days. There were few adverse events reported. This is the first report from 3 Australian headache centers about erenumab in the real world. Our analysis has supported erenumab as an effective and well‐tolerated migraine preventative therapy for patients with chronic migraine who have failed many preventative therapies.
Publisher: Frontiers Media SA
Date: 13-10-2021
DOI: 10.3389/FNEUR.2021.746099
Abstract: The diagnosis of fat embolism syndrome typically involves neurological, respiratory and dermatological manifestations of microvascular occlusion 24–72 h after a precipitating event. However, fat embolism causing cerebral large vessel occlusion strokes and their sequelae have rarely been reported in the literature. This case series reports three patients with fat emboli post operatively causing cerebral large vessel occlusions, as well as a review of the literature to identify differences in clinical presentations and outcomes in stroke secondary to fat emboli causing large vessel occlusions compared to those with fat embolism syndrome.
Publisher: Wiley
Date: 25-07-2022
DOI: 10.1111/ENE.15496
Abstract: This study was undertaken to explore associations between plasma neurofilament light chain (pNfL) concentration (pg/ml) and disease activity in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and examine the usefulness of pNfL concentrations in determining disease remission. We examined pNfL concentrations in treatment‐naïve CIDP patients ( n = 10) before and after intravenous immunoglobulin (IVIg) induction treatment, in pNfL concentrations in patients on maintenance IVIg treatment who had stable ( n = 15) versus unstable disease ( n = 9), and in clinically stable IVIg‐treated patients ( n = 10) in whom we suspended IVIg to determine disease activity and ongoing need for maintenance IVIg. pNfL concentrations in an age‐matched healthy control group were measured for comparison. Among treatment‐naïve patients, pNfL concentration was higher in patients before IVIg treatment than healthy controls and subsequently reduced to be comparable to control group values after IVIg induction. Among CIDP patients on IVIg treatment, pNfL concentration was significantly higher in unstable patients than stable patients. A pNFL concentration 16.6 pg/ml distinguished unstable treated CIDP from stable treated CIDP (sensitivity = 86.7%, specificity = 66.7%, area under receiver operating characteristic curve = 0.73). Among the treatment withdrawal group, there was a statistically significant correlation between pNfL concentration at time of IVIg withdrawal and the likelihood of relapse ( r = 0.72, p 0.05), suggesting an association of higher pNfL concentration with active disease. pNfL concentrations may be a sensitive, clinically useful biomarker in assessing subclinical disease activity.
Publisher: Wiley
Date: 31-07-2015
DOI: 10.1111/ENE.12783
Abstract: Charcot-Marie-Tooth disease (CMT) is a very slowly progressive neuropathy which makes it difficult to detect disease progression over time and to assess intervention efficacy. Experience from completed clinical trials with ascorbic acid and natural history studies confirm difficulties in detecting such changes. Consequently, sensitive-to-change outcome measures (OMs) are urgently needed. The relative responsiveness of clinical scales of the Italian-UK ascorbic acid trial (placebo arm) were assessed by using the standardized response mean (SRM), which is the ratio of the paired scores mean change over time to the standard deviation of the score change (0 is worst responsiveness). Little worsening of OM scores was found over 2 years. In detail, the primary OM of the trial, the CMT Neuropathy Score version 1 (CMTNSv1), showed low responsiveness (SRM 0.13). Some CMTNS items showed slightly greater responsiveness (CMT Examination Score 0.17 CMTNS Signs 0.19). Myometric assessments of handgrip and foot dorsiflexion strength were the most responsive (SRM -0.31 and -0.38, respectively). Amongst the other measures, the nine-hole peg test, which assesses upper limb functioning, showed the best sensitivity to change (SRM 0.28). Overall these OMs showed low or negligible responsiveness, confirming the need to improve current OMs and to develop novel ones for prognostic and interventional studies. However, handgrip and foot dorsiflexion myometry are worth retaining for future trials as they were the most responsive and are likely to be clinically relevant for patients.
Publisher: BMJ
Date: 03-2022
DOI: 10.1136/BMJOPEN-2021-059647
Abstract: Status migrainosus is a disabling complication of migraine, which frequently results in hospitalisation. For patients who fail to respond to simple analgesia, triptans and intravenous prochlorperazine or chlorpromazine, there are limited treatment options, and a paucity of high-quality evidence to guide clinical practice. Eptinezumab, an intravenous monoclonal antibody specific for the calcitonin gene-related peptide ligand which achieves maximal plasma concentration immediately following administration and may improve migraines from day one. Intravenous lignocaine is an anaesthetic medication used in treatment of status migrainosus, often requiring prolonged admissions and with potential cardiac adverse events. The aim of this study is to assess the efficacy and safety of eptinezumab in the treatment of status migrainosus in comparison to intravenous lidocaine. Status migrainosus inpatient treatment with eptinezumab is a randomised, controlled, single-centre clinical trial conducted in a parallel design with an active comparator conducted in Melbourne, Australia. This study randomises forty patients (1:1) to receive either eptinezumab or an infusion of intravenous lignocaine for up to 5 days. It will assess the effect of eptinezumab compared with intravenous lignocaine in aborting status migrainosus, with the primary outcome of time from infusion until resolution of pain. It will explore several secondary measures including change in health resource utilisation, effect on patient reported outcomes of migraine disability and the safety and tolerability of each medication. This study has been reviewed and approved by the Human Research Ethics Committee of Alfred Health, local reference number 443/21, and all participants will provide informed consent for participation in the trial and dissemination of results. The trial registration number is ACTRN12621001616864. The results of this study will be disseminated through peer-reviewed journals, conference presentations and social media.
Publisher: Wiley
Date: 03-2006
DOI: 10.1002/CNE.20864
Abstract: The development of the primary sensory innervation of the superficial dorsal horn (SDH) was studied in postnatal opossums Monodelphis domestica by using DiI labelling of primary afferents and with GSA-IB(4) lectin binding and calcitonin gene-related peptide (CGRP) immunoreactivity to label primary afferent subpopulations. We also compared the timing of SDH innervation in the cervical and lumbar regions of the spinal cord. The first primary afferent projections to SDH emerge from the most lateral part of the dorsal root entry zone at postnatal day 5 and project around the lateral edge of the SDH toward lamina V. Innervation of the SDH occurs slowly over the second and third postnatal weeks, with the most dorsal aspect becoming populated by mediolaterally oriented varicose fibers before the rest of the dorsoventral thickness of the SDH becomes innervated by fine branching varicose fibers. Labelling with GSA-IB(4) lectin also labelled fibers at the lateral edge of the dorsal horn and SDH at P5, indicating that the GSA-IB(4) is expressed on SDH/lamina V primary afferents at the time when they are making their projections into the spinal cord. In contrast, CGRP-immunoreactive afferents were not evident until postnatal day 7, when a few short projections into the lateral dorsal horn were observed. These afferents then followed a pattern similar to the development of GSA-IB(4) projects but with a latency of several days. The adult pattern of labelling by GSA-IB(4) is achieved by about postnatal day 20, whereas the adult pattern of CGRP labelling was not seen until postnatal day 30. Electron microscopy revealed a few immature synapses in the region of the developing SDH at postnatal day 10, and processes considered to be precursors of glomerular synapses (and thus of primary afferent origin) were first seen at postnatal day 16 and adopted their definitive appearance between postnatal days 28 and 55. Although structural and functional development of forelimbs of neonatal Monodelphis is more advanced than the hindlimbs, we found little evidence of a significant delay in the invasion of the spinal cord by primary afferents in cervical and lumbar regions. These observations, together with the broadly similar maturational appearance of histological sections of rostral and caudal spinal cord, suggest that, unlike the limbs they innervate, the spinal regions do not exhibit a large rostrocaudal gradient in their maturation.
Publisher: BMJ
Date: 12-2020
DOI: 10.1136/BMJNO-2020-000101
Abstract: COVID-19 is a significant global health burden. The pulmonary morbidity and mortality of COVID-19 is well described, however, there is mounting evidence of neurological manifestations of SARS-CoV-2, which may be of prognostic significance. This paper summarises the available evidence in order to provide clinicians with a concise summary of the peripheral and central neurological manifestations of COVID-19, discusses specific issues regarding the management of chronic neurological disease in the context of the pandemic, and provides a summary of the thrombotic implications of the disease for the neurologist.
Publisher: Wiley
Date: 20-10-2021
DOI: 10.1111/JNS.12470
Abstract: Regular immunoglobulin treatment maintains strength and prevents disability in chronic inflammatory demyelinating polyneuropathy (CIDP). Discrimination between active disease, with optimum symptom control on treatment, and disease in remission not requiring treatment is essential for therapeutic decision‐making and clinical trial design. To compare treatment cessation versus gradual dose reduction in assessment of disease activity (immunoglobulin dependence) in a cohort of stable CIDP patients on maintenance immunoglobulin treatment. An approach to restabilization of immunoglobulin‐dependent in iduals is also described. Retrospective review of IVIg cessation or gradual reduction in 33 patients with stable CIDP on maintenance IVIg. Demographic, clinical and treatment data were collected clinical monitoring data were recorded prospectively as part of routine clinical practice. A total of 21/33 patients (62.6%) were immunoglobulin dependent, (gradual dose reduction:11, cessation:10). Mean change in Inflammatory Rasch‐built Overall Disability Scale (I‐RODS) (−15, standard deviation [SD] 16) and Medical Research Council Sum Score (MRC‐SS) (−4, SD: 4) was clinically and statistically meaningful ( % exceeded minimum clinically important differences). Mean time to deterioration was 5.0 (SD: 4.6) months, shorter in cessation group (3.5 months) than gradual reduction group (8.8 months). All patients were restabilized to previous baseline (M: 2.3, SD: 4.3 months), half within 1 week of retreatment. A total of 12 patients (37.4%) remained stable without treatment for ≥2 years (remission). A total of 50% were identified rapidly by cessation and 50% by gradual dose reduction requiring mean 4.8 (SD: 2.8) years follow‐up and costing £113 623 per person Ig spend. No predictors of disease activity were identified. A treatment cessation trial with close clinical monitoring is an efficient, cost‐effective and safe approach to assessing disease activity in CIDP.
Publisher: Wiley
Date: 28-03-2016
DOI: 10.1111/CNS.12542
Publisher: Wiley
Date: 15-05-2014
DOI: 10.1002/MUS.24169
Abstract: Charcot-Marie-Tooth (CMT) disease type 1A is the most common form of CMT. The main clinical features are distal weakness, sensory loss, and skeletal deformities. Although pain is a frequent complaint, small fiber involvement in CMT1A has not been studied extensively. We assessed pain and small fiber involvement in 49 CMT1A patients using a variety of pain scales, pain questionnaires, and thermal thresholds. Forty-three of 49 patients (88%) complained of pain. The pain was localized to the feet in 61% of patients. Only 18% of patients had neuropathic pain. Cold and warm detection thresholds were elevated in 53% and 12% of patients, respectively. Our findings confirm that CMT1A patients have significant pain, which is more likely to be multifactorial in origin and suggests that a proportion of patients have small fiber dysfunction affecting mainly thinly myelinated Aδ fibers.
Publisher: BMJ
Date: 07-2019
DOI: 10.1136/JNNP-2019-ANZAN.62
Abstract: Erenumab is available in Australia since October 2018. We review the effectiveness and safety in 2 Australian headache centres. Erenumab (70 mg or 140 mg) was prescribed. We monitored headache days, migraine days, analgesic use, adverse reactions, Headache Impact Test-6 (HIT6) score and Migraine Disability Assessment (MiDAS) score, at baseline and at 3 months. Primary outcomes were reduction in headache and migraine days, and adverse effects. Secondary outcomes were improvement in functional scores and analgesic use. 65 patients (ages 18–73 mean 44 years) commencing Erenumab were assessed before and after 3 monthly treatments. The duration of chronic migraine (CM) ranged from 1 to 40 years, with 3 to 16 previous failed prophylactic treatments. There was a % response in overall headache days and migraine days in 29% (19/65) and 46% (27/59), respectively. There was a modest (10–49%) response in overall headache days and migraine days in 29% (19/65) and 27% (18/59), respectively. There was no improvement in headache days and migraines in 42% (27/65) and 27% (14/59), respectively. At onset, the mean HIT-6 and MiDAS scores were 66 and 65, decreasing after 3 treatments to 59 and 32, respectively. The mean monthly days taking triptan and codeine medications reduced from 9 and 6 days, to 5 and 3 days, respectively. There were few reported side effects. This Australian cohort in tertiary referral refractory migraine patients achieved a significant rate of reduced headache and migraine days with good safety and tolerability.
Publisher: Elsevier BV
Date: 04-2011
Publisher: Wiley
Date: 02-1999
DOI: 10.1016/S0736-5748(98)00054-9
Abstract: Although long known to be a liver-derived fetal plasma glycoprotein, fetuin has more recently been shown to be present in sub-populations of neurons in the developing nervous system of a number of mammalian species. We have extended these observations to examine the fetuin immunoreactivity (IR) in developing rat retina and cerebellum. Fetuin-IR was first seen in the retina on embryonic day (E)19 in a sub-population of cells in the retinal ganglion cell layer and a small proportion of cells in the neuroblastic layer. The proportion of cells in the ganglion layer exhibiting fetuin-IR increased until postnatal day (P)10 when all cells in this layer were strongly immunoreactive. From P14 onwards fetuin-IR was absent or very weak and restricted to a small proportion of ganglion cells. In the developing cerebellum, the outer and inner granule cell layers, the deep nuclei and cells in the sub-cortical white matter exhibited fetuin-IR from E19 to P10. There was little fetuin-IR in the cerebellum at ages P14 and older, and Purkinje cells did not exhibit fetuin-IR at any time. The results show that fetuin appears in many neurons in the retina and cerebellum that are differentiating during the period from E19 to P10. The concentration of fetuin in cerebrospinal fluid is at its highest in this same period which suggests that some sub-populations of neurons could obtain fetuin from extracellular fluid during this period however, the lack of fetuin-IR in other neuronal populations suggests that fetuin uptake is not a general property of developing neurons.
Publisher: SAGE Publications
Date: 10-04-2023
DOI: 10.1177/03331024231168089
Abstract: To perform a systematic review and meta-analysis of the epidemiology, precipitants, phenotype, comorbidities, pathophysiology, treatment, and prognosis of primary new daily persistent headache. We searched PubMed/Medline, EMBASE, Cochrane, and clinicaltrials.gov until 31 December 2022. We included original research studies with any design with at least five participants with new daily persistent headache. We assessed risk of bias using National Institutes of Health Quality Assessment Tools. We used random-effects meta-analysis where suitable to calculate pooled estimates of proportions. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis compliant study is registered with PROSPERO (registration number CRD42022383561). Forty-six studies met inclusion criteria, predominantly case series, including 2155 patients. In 67% (95% CI 57–77) of cases new daily persistent headache has a chronic migraine phenotype, however new daily persistent headache has been found to be less likely than chronic migraine to be associated with a family history of headache, have fewer associated migrainous symptoms, be less vulnerable to medication overuse, and respond less well to injectable and neuromodulatory treatments. New daily persistent headache is a well described, recognisable disorder, which requires further research into its pathophysiology and treatment. There is a lack of high-quality evidence and, until this exists, we recommend continuing to consider new daily persistent headache a distinct disorder.
Publisher: MDPI AG
Date: 29-06-2021
DOI: 10.3390/JCM10132898
Abstract: The efficacy of onabotulinumtoxinA (OnaB-A) as a preventative treatment for chronic migraine, emerging fortuitously from clinical observation is now supported by class one evidence and over two decades of real-world clinical data. There is still limited ability to predict a clinically meaningful response to OnaB-A for in idual patients, however. This review summarises briefly the proposed mechanism of OnaB-A in chronic migraine, the literature of predictors of clinical response, and recent developments in the field.
Publisher: BMJ
Date: 07-2019
DOI: 10.1136/JNNP-2019-ANZAN.26
Abstract: Erenumab has been studied in Randomised Controlled Trials (RCT), with stricter exclusion criteria than real world populations. 65 patients from two Australian headache centres on Erenumab had primary outcomes of ≥ 50% response in monthly migraine days (MMD) and monthly headache days (MHD), compared to their demographics, frequency, duration of Chronic Migraine (CM), failed prophylactic medications, severity scores and medication overuse headache (MOH). 35% (23/65) had daily headaches, with ≥ 50% MHD and MMD reduction in this subgroup of 17% (4/23) and 65% (13/20), respectively. Duration of CM was years in 48% (29/61), with ≥ 50% MHD and MMD reduction in 28% (8/29) and 48% (13/27), respectively. 100% (64/64) had failed 3 prophylactic medications with ≥50% MHD and MMD reduction in 30% (19/64) and 47% (27/58), respectively, with reducing rates of ≥ 50%MMD reduction if (29% 17/58) and (22% /9). 95% had high severity scores (HIT-6 score ), with a ≥ 50% MMD reduction in 43% (23/54). MOH occurred in 41% (24/58) for triptan and 29% (17/58) for codeine medications, with a ≥ 50% MMD reduction in 71% (17/24) and 41% (7/17), respectively (all groups p .05). This real world cohort treated with Erenumab included patients that would be excluded from RCT analysis- including more chronic, frequent, severe and refractory migraine. Despite this, there were still ≥50% responders in more severe subgroups, particularly daily headache, high severity scores and triptan MOH. Measuring MMD may be more sensitive for assessing improvement than MHD.
Publisher: BMJ
Date: 05-10-2023
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Elspeth Hutton.