Dr Antonia Carroll

Dr Antonia Carroll, Rouse Senior Research Fellow, Neurologist and PhD candidate, The University of Sydney.

Antonia is a neurologist, neurophysiologist and clinician-researcher with interests in neuromuscular, neuroinflammatory and neuro-haematological disorders. She received her medical degree from the University of Sydney and completed neurology training in Sydney at Royal Prince Alfred, Concord and St Vincent’s Hospitals.

In 2017, she was awarded an ANZAN fellowship to the National Hospital for Neurology and Neurosurgery, Queen Square, London, where she developed expertise in the investigation and management of neuromuscular disorders. She has undertaken further sub-specialty training in neuromuscular disease and neurophysiology. Antonia is a staff specialist neurologist and neurophysiologist at St Vincent’s Hospital and provides subspecialty outreach services to Wagga Wagga.

Antonia is currently undertaking PhD studies in peripheral nerve disorders associated with protein deposition, particularly relating to amyloidosis and haematological conditions. In addition, she has been recently appointed the Rouse Senior Research Fellow for ongoing clinical and pathophysiological research in Inclusion Body Myositis.

Forefront Group: Kiernan Group (PhD and Fellowship), Barnett Group (Fellowship)

Supervisors:

Prof Matthew Kiernan, Prof Steve Vucic, Prof Mary Reilly, (NHNN/UCL, UK), Dr Neil Simon

Affiliate Organisations:

USyd, RPA, Westmead, St Vincent’s, NHNN Queen Square/UCL, London

Expertise:

  • Clinical phenotyping of complex neuromuscular disease
  • Neurophysiology
  • Biomarker development

Neurodegeneration of interest:

Inflammatory, genetic and degenerative Neuropathies including CIDP, AIDP, Amyloidosis, Paraproteinaemic neuropathy, CMT Inflammatory, genetic and degenerative Myopathies including Inclusion body myositis, polymyositis, NAM, dystrophic myopathies.

Specific Skills:

  • Clinical and Research Neurology
  • Neurophysiology
  • Clinical Researcher
  • Axonal excitability and motor unit number estimation
  • Nerve and muscle ultrasound

Project - Inclusion Body Myositis towards targeted treatments: Phenotypes and pathophysiological correlates

Research Project Abstract

Inclusion body Myositis (IBM) is a slowly progressive muscle disorder with both inflammatory and degenerative features. There are currently no validated treatments for IBM, however research is ongoing and clinical trials are in development. Due to the slowly progressive natural history of disease prior clinical trials have been limited by the inability to measure disease progression over the short time periods. This research aims to deep phenotype patients with IBM by evaluating clinical, neurophysiological and imaging characteristics, biopsy specimens, protein and inflammasome features to better understand the pathophysiology of disease, improve diagnostics and optimise treatments. Funded 2021-2023

Disease area:

Neuromuscular disease, Inclusion body myositis

Challenges within the field

  • Limited availability of clinically relevant, responsive and objective biomarkers of disease progression allowing assessment of progression and monitoring of treatment effect in clinical trials.
  • Variability in disease phenotypes, potentially with variable responses to treatment trials.
  • Unknown pathophysiology of disease with both inflammatory and degenerative components, which limits targeted pathophysiologically-driven treatment trials.

Research Project Description and Objectives

  • Set up of a multidisciplinary centre of excellence of clinical care, research and clinical trial node.
  • Develop a structured clinical research longitudinal IBM database
  • Retrospective analysis of muscle biopsy cohort with phenotype-pathophysiology-time correlations.
  • Deep phenotyping of prospective IBM cohorts identifying subtypes with differing characteristics which may respond differently to disease modification. Using techniques including:
    • Clinical parameters (clinical phenotype, MRC scores, functional rating scales, quantitative strength assessments via Dynamometry and QMT)
    • Neurophysiological techniques (quantitative EMG, Axonal excitability, motor unit number estimation)
    • Imaging (ultrasound, MRI, PET)
    • Plasma and Serum biomarkers for biomarker, proteomic and inflammasome assessments
    • oBiopsy specimens for phenotype, proteomic, genomic
  • Development of early diagnostic and treatment monitoring biomarkers
  • Development of pathophysiology-guided treatment algorithms.

Key Publications from this project

N/A – just started

Infographic / Medical Diagram / Scientific Diagram / Picture

We may be able to get a muscle biopsy image if this would be useful

Project - Improving the early diagnosis of amyloid- and paraprotein-associated neuropathies: a heterogeneous group with emerging treatments

Disease area:

Neuromuscular: Amyloidosis, Paraproteinaemic neuropathy, Anti-MAG neuropathy, Neurolymphomatosis, CIDP

Research Project Description and Objectives

The aim of this research is to deeply phenotype the amyloid- and paraprotein- associated neuropathies (APAN) in order to determine the key diagnostic features and refine algorithms for diagnosis, thereby improving time to diagnosis and patient outcomes. Specifically, this research will identify the key clinical and imaging characteristics of this disease group, assess for biomarkers of disease progression and disability that can be used to guide and monitor treatment, and prognosticate.

Objectives

  • Identify the distinguishing clinical and investigative characteristics (neurophysiology, imaging, biochemical and histological) of APAN.
  • Compare the causes of previous misdiagnosis and treatment delay for APAN between regional cohorts.
  • Evaluate potential neurophysiological and imaging biomarkers of APAN in pre-symptomatic and symptomatic patients.
  • Evaluate potential biochemical biomarkers of APAN in pre-symptomatic and symptomatic patients.
  • Develop diagnostic algorithms to guide treatment decisions using the biomarkers identified in Objectives 3 and 4.

The APAN are a heterogenous group of neuropathies that are difficult to identify and frequently misdiagnosed, leading to delays in diagnosis and treatment, accumulated disability and poor quality of life. The pathophysiology of these entities are poorly understood and treatment approaches are often ineffective. Novel treatment options have emerged with the capacity to significantly improve outcomes for patients, however these are reliant on the ability to diagnose APAN at early stages. Moreover, we currently have no validated markers of disease progression. This research aims to define the diagnostic characteristics of the APAN in retrospective and prospective cohorts by deeply phenotyping the individual cases based on the key clinical, neurophysiological, imaging, biochemical and histological features. Prospective evaluation of nerve conduction, axonal excitability, motor unit number estimation and ultrasound will assess for differentiating features and early markers of disease progression. Novel biochemical markers of disease will be assessed for utility in early diagnosis and monitoring. Subsequently diagnostic algorithms will be refined, utilising these methods, with the aim of improving time to diagnosis, aiding treatment decision-making and improving patient outcomes. Further research is essential in order to improve diagnostic and treatment outcomes in APAN.

Specific projects:

  • Develop an axonal excitability and motor unit number estimation protocol for use in amyloidosis, where there is frequently a concurrent median neuropathy at the wrist.
  • Genotype-phenotype associations in Australian and UK cohorts of hereditary transthyretin amyloidosis (ATTRv)
  • Evaluate axonal excitability, motor unit number estimation, small fibre and autonomic studies in normal controls, asymptomatic TTR gene carriers and patients with symptomatic TTR amyloidosis.
  • Neurofilament light chain as a biomarker of disease progression in ATTRv
  • Neurological phenotypes in wild-type TTR amyloidosis
  • Comparative phenotypes in varied haemato-neurological neuropathies.
  • Distinguishing inflammatory and haematology associated neuropathies: the role of CSF studies.
  • Deep phenotyping to guide treatment in anti-MAG neuropathies

Key Publications from this project

  • Carroll, A., Burns, J., Nicholson, G., Kiernan, M., Vucic, S. (2019). Inherited Neuropathies. Seminars in Neurology, 39(5), 620-639
  • Carroll AS, Simon NG. Current and future applications of ultrasound imaging in peripheral nerve disorders. World Journal of Radiology. 2020 28;12(6):101.

In submission:

  • Sommer. C, Carroll AS, Koike H et al. Nerve biopsy in acquire neuropathies. JPNS
  • Carroll AS, Lunn MP. Paraproteinaemic neuropathy: MGUS and Beyond. Practical neurology
  • Carroll AS, Doherty CM, Blake J et al. Neurology and the Histiocytoses: a case of Rosai-Dorfman-Destombes disease with widespread neurological manifestations. Practical neurology
  • Taylor M, Baumwol, J, Carroll AS, et al. Amyloidosis in 2021. Internal Medicine Journal

Conference proceeding/ Published abstracts:

  • AS Carroll, C Doherty, J Blake, et al. Rosai-Dorfman-Destombes disease: Case report with widespread neurological disease including in the peripheral nervous system. JPNS 2020 25 (4), 543544
  • AS Carroll, J Howells, C Lin, et al. Axonal excitability in hereditary TTR amyloidosis is consistent with sensory disease burden JPNS 2020 25 (4), 472472
  • AS Carroll, A Carr, S D'sa, M Lunn. Episode two: Attack (and reattack) of the clones JPNS 2020 25, s8s8
  • JA Bomsztyk, P Jareonsettasin, A Rismani,… AS Carroll et al. Treatment of bing neel syndrome: using a sledgehammer to crack a nut? Hematological Oncology 2019 37, 460460
  • JA Bomsztyk, P Jareonsettasin, AS Carroll, et al. Bing neel syndrome: first suspect, then prove‐a role for CSF IgM analysis? Hematological Oncology 2019 37, 46046
  • AS Carroll, J Howells, CY Lin et al. Nerve excitability properties of upper limb sensory and motor axons: a comparative study. PNS 2019.

Infographic / Medical Diagram / Scientific Diagram / Picture

Upper limb Sensory peripheral nerve excitability in normative controls. Red: Median, Green: Radial, Blue: Ulnar (A) Peak response curve, (B) Stimulus Response curve, (C) Current Threshold relationship (I/V), (D) Strength Duration relationship, (E) Threshold Electrotonus, (F) Recovery Cycle