Papers by Dominic Thyagarajan
The Medical Journal of Australia, Dec 1, 1993
Vocal folds are the key body structures that are responsible for phonation and regulating air mov... more Vocal folds are the key body structures that are responsible for phonation and regulating air movement into and out of lungs. Various vocal fold disorders may seriously impact the quality of life. When diagnosing vocal fold disorders, CT of the neck is the commonly used imaging method. However, vocal folds do not align with the normal axial plane of a neck and the plane containing vocal cords and arytenoids does vary during phonation. It is therefore important to generate an algorithm for detecting the actual plane containing vocal folds. In this paper, we propose a method to automatically estimate the vocal fold plane using vertebral column and anterior commissure localization. Gray-level thresholding, connected component analysis, rule based segmentation and unsupervised k-means clustering were used in the proposed algorithm. The anterior commissure segmentation method achieved an accuracy of 85%, a good estimate of the expert assessment.
Journal of Clinical Neuroscience, 1999
Dystonia may be primary or symptomatic. Most, if not all, primary torsion dystonias are genetic d... more Dystonia may be primary or symptomatic. Most, if not all, primary torsion dystonias are genetic diseases and manifest as 'pure dystonia', without consistent biochemical or neuropathological changes. Symptomatic dystoNas may be (a) secondary to drugs or other environmental factors, (b) part of a 'dystonia plus' syndrome or (c) part of several heredodegenerative diseases. In the last few years, there have been rapid advances in the genetic classification of primary torsion dystonia. The gene for one form (DYTldystonia), particularly common in Ashkenazi Jews, has been isolated. In this review, I present a basic clinical overview of dystonia and focus on the recent advances in molecular genetics of primary torsion dystonia (PTD). Treatment of dystonia is a large subject, worthy of a review in itself, and is not covered here. Several of the paroxysmal movement disorders may manifest with dystonia, but these are usually considered separately, as I have done in this review.
PLOS ONE, Jan 18, 2023
Changes to the voice are prevalent and occur early in Parkinson's disease. Correlates of these vo... more Changes to the voice are prevalent and occur early in Parkinson's disease. Correlates of these voice changes on four-dimensional laryngeal computed-tomography imaging, such as the inter-arytenoid distance, are promising biomarkers of the disease's presence and severity. However, manual measurement of the inter-arytenoid distance is a laborious process, limiting its feasibility in large-scale research and clinical settings. Automated methods of measurement provide a solution. Here, we present a machine-learning module which determines the inter-arytenoid distance in an automated manner. We obtained automated inter-arytenoid distance readings on imaging from participants with Parkinson's disease as well as healthy controls, and then validated these against manually derived estimates. On a modified Bland-Altman analysis, we found a mean bias of 1.52 mm (95% limits of agreement-1.7 to 4.7 mm) between the automated and manual techniques, which improves to a mean bias of 0.52 mm (95% limits of agreement-1.9 to 2.9 mm) when variability due to differences in slice selection between the automated and manual methods are removed. Our results demonstrate that estimates of the inter-arytenoid distance with our automated machinelearning module are accurate, and represents a promising tool to be utilized in future work studying the laryngeal changes in Parkinson's disease.
PubMed, 1992
Mitochondrial DNA is a unique, maternally inherited molecule encoding several subunits of the res... more Mitochondrial DNA is a unique, maternally inherited molecule encoding several subunits of the respiratory enzyme chain. In several mitochondrial cytopathies mutations have been described in this genome viz. large-scale heteroplasmic deletions in syndromes with progressive external ophthalmoplegia and point mutations in MELAS and MERRF encephalomyopathies. We here report Southern blot analyses in the cases of CPEO we have seen and describe the search for point mutations in MELAS and MERRF. Mitochondrial genetic sequencing in normal and disease controls as well as in patients has confirmed the pathogenic nature of a tRNA Lys point mutation in MERRF. We propose a novel mitochondrial structural gene mutation in a MELAS--like encephalomyopathy: an A-->G substitution at position 11084 leading to a Thr to Ala replacement in the ND4 subunit of complex I.
BMJ Neurology Open, Sep 1, 2020
Background Human prion diseases are a group of rare neurological diseases with a minority due to ... more Background Human prion diseases are a group of rare neurological diseases with a minority due to genetic mutations in the prion protein (PRNP) gene. The D178N mutation is associated with both Creutzfeldt-Jakob disease and fatal familial insomnia with the phenotype modified by a polymorphism at codon 129 with the methionine/valine (MV) polymorphism associated with atypical presentations leading to diagnostic difficulty. Case We present a case of fatal familial insomnia secondary to a PRNP D178N mutation with 129MV disease modifying polymorphism who had no family history, normal MRI, electroencephalography (EEG), cerebrospinal fluid (CSF) and positron emission tomography findings and a negative real-time quaking-induced conversion result. Conclusion Patients with genetic prion disease may have no known family history and normal EEG, MRI brain and CSF findings. PRNP gene testing should be considered for patients with subacute progressive neurological and autonomic dysfunction.
Parkinson's disease is a neurodegenerative disorder that results in progressive degenerat... more Parkinson's disease is a neurodegenerative disorder that results in progressive degeneration of nerve cells. It is generally associated with the deficiency of dopamine, a neurotransmitter involved in motor control of humans and thus affects the motor system. This results in abnormal vocal fold movements in majority of the Parkinson's patients. Analysis of vocal fold abnormalities may provide useful information to assess the progress of Parkinson's disease. This is accomplished by measuring the distance between the arytenoid cartilages during phonation. In order to automate this process of identifying arytenoid cartilages from CT images, in this work, a rule-based approach is proposed to detect the arytenoid cartilage feature points on either side of the airway. The proposed technique detects feature points by localizing the anterior commissure and analyzing airway boundary pixels to select the optimal feature point based on detected pixels. The proposed approach achieved 83.33% accuracy in estimating clinically-relevant feature points, making the approach suitable for automated feature point detection. To the best of our knowledge, this is the first such approach to detect arytenoid cartilage feature points using laryngeal 3D CT images.
PubMed, 1992
Since 1983 at the Alfred Hospital 4 patients with thrombotic or embolic vertebrobasilar occlusion... more Since 1983 at the Alfred Hospital 4 patients with thrombotic or embolic vertebrobasilar occlusions have been treated with intra-arterial streptokinase (SK) infusions for the effects of persisting brainstem ischaemia despite anticoagulation with heparin. In 3 cases there was immediate and dramatic neurological improvement, in all cases associated with arteriographically demonstrated reperfusion of a blocked vessel. Two of these patients suffered further thromboembolic vertebral or basilar artery occlusions (3 days and 2 years later) but recovered fully without further thrombolytic therapy. The other patient was given intra-arterial SK 12 days after an apparently completed brainstem stroke: the therapy failed to cause reperfusion of a vertebral occlusion or produce any clinical improvement. Complications from the therapy were nausea requiring the termination of the SK infusion in one case, easily controlled bleeding from a recent surgical wound, and a clinically insignificant haemorrhagic transformation of cerebellar infarction in a third. The benefits of thrombolytic therapy in vertebrobasilar ischaemia and the dose of streptokinase required are discussed.
Scientific Reports, Sep 14, 2018
Parkinson's disease (PD) alters cortico-basal ganglia-thalamic circuitry and susceptibility to an... more Parkinson's disease (PD) alters cortico-basal ganglia-thalamic circuitry and susceptibility to an illusion of bodily awareness, the Rubber Hand Illusion (RHI). Bodily awareness is thought to result from multisensory integration in a predominantly cortical network; the role of subcortical connections is unknown. We studied the effect of modulating cortico-subcortical circuitry on multisensory integration for bodily awareness in 24 PD patients treated with subthalamic nucleus (STN) deep brain stimulation (DBS), in comparison to 21 healthy volunteers, using the RHI experiment. Typically, synchronous visuo-tactile cues induce a false perception of touch on the rubber hand as if it were the subject's hand, whereas asynchronous visuo-tactile cues do not. However, we found that in the asynchronous condition, patients in the off-stimulation state did not reject the RHI as strongly as healthy controls; patients' rejection of the RHI strengthened when STN-DBS was switched on, although it remained weaker than that of controls. Patients in the off-stimulation state also misjudged the position of their hand, indicating it to be closer to the rubber hand than controls. However, STN-DBS did not affect proprioceptive judgements or subsequent arm movements altered by the perceptual effects of the illusion. Our findings support the idea that the STN and subcortical connections have a key role in multisensory integration for bodily awareness. Decision-making in multisensory bodily illusions is discussed.
Movement Disorders, Sep 1, 2005
We describe an unusual form of facial myoclonus activated by speech in 3 patients with different ... more We describe an unusual form of facial myoclonus activated by speech in 3 patients with different underlying neurological diseases and present the electrophysiological investigations and results of structural and functional imaging. In 1 of 2 patients in whom jerk-locked electroencephalogram (EEG) back-averaging was done, a cortical potential clearly preceded the facial jerks. In the second patient, a cortical potential preceding the jerk was not certain. In the third patient, the resting EEG contained outbursts of symmetric, slower frequencies of indeterminate significance. An epileptiform disorder was suspected in this patient.
Neurology, Apr 1, 1997
Rapid-onset dystonia-parkinsonism (RDP), first described in a large Midwestern family, is now rep... more Rapid-onset dystonia-parkinsonism (RDP), first described in a large Midwestern family, is now reported in a second, apparently unrelated, family in which four individuals have this same syndrome. All four developed sudden onset of dysarthria, dysphagia, severe dystonic spasms, bradykinesia, and postural instability over less than 1 hour to a few days. Three of the four had stable limb dystonia for several years preceding the onset of combined dystonia-parkinsonism. Treatment with levodopdcarbidopa provided little benefit. We propose diagnostic criteria for RDP and further define the spectrum of this unusual disease.
The Medical Journal of Australia, Apr 20, 2009
Brain Sciences
Parkinson’s Disease (PD) has historically been considered a disorder of motor dysfunction. Howeve... more Parkinson’s Disease (PD) has historically been considered a disorder of motor dysfunction. However, a growing number of studies have demonstrated sensory abnormalities in PD across the modalities of proprioceptive, tactile, visual, auditory and temporal perception. A better understanding of these may inform future drug and neuromodulation therapy. We analysed these studies using a scoping review. In total, 101 studies comprising 2853 human participants (88 studies) and 125 animals (13 studies), published between 1982 and 2022, were included. These highlighted the importance of the basal ganglia in sensory perception across all modalities, with an additional role for the integration of multiple simultaneous sensation types. Numerous studies concluded that sensory abnormalities in PD result from increased noise in the basal ganglia and increased neuronal receptive field size. There is evidence that sensory changes in PD and impaired sensorimotor integration may contribute to motor abn...
Australian and New Zealand Journal of Medicine, Dec 1, 1991
Detailed biochemical and molecular investigations in a patient with Kearns-Sayre syndrome are pre... more Detailed biochemical and molecular investigations in a patient with Kearns-Sayre syndrome are presented. Polarographic studies in isolated mitochondria revealed a global impairment in respiratory capacity consistent with an admixture of functional and non-functional mitochondria. Cytochrome difference spectra revealed a selective deficiency in cytochrome aa,. Western immunoblot studies revealed normal subunit content of Complexes I, I11 and IV. Southern blot studies of mtDNA showed a deletion of approximately 5 Kb coexisting with wild type DNA. PCR analysis confirmed that this deletion lies between the ATPase8 and NAD coenzyme Q oxidoreductase subunit 5 (ND.5) genes. Breakpoint sequencing revealed a 13 nucleotide direct repeat flanking sequence (ACCTCCCTCACCA) consistent with slippage in mtDNA during replication as the mechanism of deletion. Histochemical studies of skeletal muscle revealed many cytochrome oxidase negative fibres and immunocytochemical studies showed cytochrome oxidase negative areas with abundant respiratory complex protein suggesting upregulation. The value of a multifaceted approach in unravelling the pathophysiology of mitochondrial diseases is emphasised.
Movement Disorders, Oct 1, 2004
Legends to the Video Segment 1. Before treatment, right laterocollis and mild trunk right deviati... more Legends to the Video Segment 1. Before treatment, right laterocollis and mild trunk right deviation are seen. (Two weeks later, the symptoms worsened with severe head and trunk right deviation and great difficulty in standing and walking.) Segment 2. After treatment, a clear improvement in head and trunk deviation is observed.
The Medical Journal of Australia, Jul 1, 1993
To describe the clinical and laboratory features of human T-lymphotropic virus type I (HTLV-I) as... more To describe the clinical and laboratory features of human T-lymphotropic virus type I (HTLV-I) associated myelopathy in an immigrant from the Seychelles. A slowly progressive myelopathy has been recently diagnosed in a 64-year-old woman who emigrated to Australia from the Seychelles in 1957. Sphincter disturbance and back pain were the first manifestations, followed by gait disturbance. Neurophysiological investigation supported the clinical diagnosis of a myelopathy and radiological investigations revealed no structural cause. Serum antibodies to HTLV-I were detected by enzyme-linked particle agglutination and the presence of antibodies to individual HTLV-I gene products in the serum was confirmed by western blot. The virus was detected in a culture of the patient's peripheral blood mononuclear cells by antigen capture assay and by sequencing a polymerase chain reaction product amplified from the env gene. The patient was advised of the nature and prognosis of her illness. Oral corticosteroids were tried without benefit. The prevalence of HTLV-I infection is low in Australia although it may be endemic in some Aboriginal communities. Most infections are asymptomatic but the chronic neurological disease associated with HTLV-I infection has now been shown to exist in this country. HTLV-I infection should be considered in the aetiology of myelopathy without another obvious cause.
Case Reports, Aug 19, 2013
Unexpected outcome (positive or negative) including adverse drug reactions
Neurology, Mar 1, 1995
We retrospectively reviewed the clinical records of all patients with cancer and brachial plexopa... more We retrospectively reviewed the clinical records of all patients with cancer and brachial plexopathy who had an MRI of the brachial plexus between 1984 and 1993 (71 patients). The MRIs were reevaluated in a blinded fashion. The presence of a mass adjacent to the brachial plexus on MRI was highly predictive of tumor infiltration as determined by clinicopathologic criteria and was the most useful feature in distinguishing radiation plexopathy from tumor infiltration. Increased T, signal in or near the brachial plexus was commonly seen in both groups and was not useful in this distinction. MRI was very sensitive for brachial plexus abnormalities in this condition, and limited comparison with CT suggested that MRI is superior to CT as an imaging modality. CT performed sufficiently well, however, to suggest that a prospective comparison study of the cost effectiveness and clinical utility of the two imaging modalities in this clinical setting is warranted. NEUROLOGY 1995;45:421-427
PLOS ONE, Nov 3, 2017
Background Voice change is one of the earliest features of Parkinson's disease. However, quantita... more Background Voice change is one of the earliest features of Parkinson's disease. However, quantitative studies of vocal fold dynamics which are needed to provide insight into disease biology, aid diagnosis, or track progression, are few.
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Papers by Dominic Thyagarajan