-
[show abstract]
[hide abstract]
ABSTRACT: Gray matter atrophy has been implicated in the development of secondary progressive multiple sclerosis (SPMS). Cortical function may be assessed by transcranial magnetic stimulation (TMS). Determining whether cortical dysfunction was a feature of SPMS could be of pathophysiological significance.
Consequently, novel paired-pulse threshold tracking TMS techniques were used to assess whether cortical dysfunction was a feature of SPMS.
Cortical excitability studies were undertaken in 15 SPMS, 25 relapsing-remitting MS patients (RRMS) and 66 controls.
Short interval intracortical inhibition (SPMS 3.0 ± 2.1%; RRMS 12.8 ± 1.7%, p < 0.01; controls 10.5 ± 0.7%, p < 0.01) and motor evoked potential (MEP) amplitude (SPMS 11.5 ± 2.2%; RRMS 26.3 ± 3.6%, p <0.05; controls 24.7 ± 1.8%, p < 0.01) were reduced in SPMS, while intracortical facilitation (SPMS -5.2 ± 1.9%; RRMS -2.0 ± 1.4, p < 0.05; controls -0.9 ± 0.7, p < 0.01) and resting motor threshold were increased (SPMS 67.5 ± 4.5%; RRMS 56.0 ± 1.5%, p < 0.01; controls 59.0 ± 1.1%, p < 0.001). Further, central motor conduction time was prolonged in SPMS (9.1 ± 1.2 ms, p < 0.001) and RRMS (7.0 ± 0.9 ms, p < 0.05) patients compared with controls (5.5 ± 0.2 ms). The observed changes in cortical function correlated with the Expanded Disability Status Scale.
Together, these findings suggest that cortical dysfunction is associated with disability in MS, and documentation of such cortical dysfunction may serve to quantify disease severity in MS.
Multiple Sclerosis 09/2011; 18(4):425-32. · 4.26 Impact Factor
-
The Medical journal of Australia 04/2010; 192(7):413-6. · 2.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Skull-base osteomyelitis (SBO) occurs secondary to invasive bacterial and fungal infection. Distinguishing between fungal and bacterial aetiologies of SBO has significant therapeutic implications. An 18-year (1990-2007) retrospective review of patients with SBO presenting to Westmead Hospital was performed. Epidemiological, clinical, laboratory and radiology data were collated. Twenty-one patients (median age 58 years) with SBO were identified: ten (48%) had bacterial and 11 (52%) had fungal SBO. Diabetes mellitus (57%) and chronic otitis externa (33%) were the most frequent co-morbidities; immunosuppression was present in five cases (24%). Cranial nerve deficits occurred in ten (48%) patients. The commonest pathogens were Pseudomonas aeruginosa (50% bacterial SBO) and a zygomycete (55% fungal SBO). Compared to bacterial SBO, fungal SBO was more frequently associated with underlying chronic sinusitis, sinonasal pain, facial/periorbital swelling and nasal stuffiness or discharge and the absence of purulent ear discharge (all p <0.05). Bacterial SBO was more frequently associated with deafness, ear pain or ear discharge (all p <0.05). Median time to presentation was longer in patients with bacterial SBO (26.3 weeks vs. 8.1 weeks, p 0.08). Overall 6-month survival was 88% (14/18 patients). All four deaths occurred in patients with fungal SBO. Immunosuppression was a risk factor for death (p <0.05). Early diagnostic sampling is recommended in patients at increased risk of fungal SBO to enable optimal antimicrobial and surgical management.
Clinical Microbiology and Infection 04/2010; 17(2):306-11. · 4.54 Impact Factor
-
Richard I Lindley,
Jie Jin Wang,
Meng-Cheong Wong,
Paul Mitchell,
Gerald Liew,
Peter Hand,
Joanna Wardlaw,
Deidre A De Silva,
Michelle Baker,
Elena Rochtchina,
Christopher Chen,
Graeme J Hankey,
Hui-Meng Chang,
Victor S C Fung, Lavier Gomes,
Tien Y Wong
[show abstract]
[hide abstract]
ABSTRACT: Lacunar stroke accounts for a quarter of cases of acute ischaemic stroke; however, its underlying pathophysiology remains unclear. Our aim was to establish whether there is an association between changes in the retinal microvasculature and lacunar stroke that might provide clues to the pathology of cerebral small vessel disease.
In this cross-sectional study, we recruited patients who presented with acute stroke at three centres in two countries (Sydney and Melbourne, Australia, and Singapore). Each patient had standardised clinical assessments, retinal photography, and CT or MRI of the brain. Changes in the retinal microvasculature were assessed from retinal photographs by graders who were masked to the patients' clinical details. Lacunar stroke was diagnosed according to a modified version of the TOAST criteria (Treatment of Acute Stroke Trial) or the OCSP criteria (Oxfordshire Community Stroke Project) and by MRI findings.
We recruited 1321 patients aged 19 to 94 years with acute ischaemic stroke; 410 (31%) had lacunar stroke. Patients with acute lacunar stroke were no more likely to have hypertension (p=0.12), diabetes (p=0.51), or hypercholesterolaemia (p=0.91) than were patients with other types of ischaemic stroke. However, patients with lacunar stroke were more likely to have retinal microvessel signs, particularly when stroke subtype was confirmed using diffusion-weighted MRI, than were patients with other stroke subtypes. After adjustment for age, sex, study site, smoking history, hypertension, and diabetes, the patients with lacunar stroke were more likely than those with other stroke subtypes to have microvessel signs, and when stroke subtype was confirmed by diffusion-weighted MRI the odds ratios were: 3.55 (95% CI 1.77-7.12) for focal arteriolar narrowing; 1.96 (1.19-3.24) for arteriovenous nipping; 2.32 (1.42-3.79) for enhanced light reflex of the arteriolar wall; 1.33 (0.74-2.41) for generalised retinal arteriolar narrowing; 1.45 (0.84-2.51) for small retinal arteriole:venule ratio; and 1.35 (0.80-2.26) for retinal venular widening.
Our findings suggest that acute lacunar stroke is a manifestation of non-atherothrombotic occlusive small vessel disease, which might have implications for the prevention and treatment of this stroke subtype.
National Health and Medical Research Council of Australia; National Medical Research Council of Singapore; Scottish Funding Council; New South Wales Health.
The Lancet Neurology 08/2009; 8(7):628-34. · 23.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Of the few studies that have directly investigated the neuroanatomical correlates of delusions in patients with recent-onset schizophrenia, a number have paradoxically reported a positive correlation between delusion severity and regional grey matter volume. In order to explore this relationship, 31 patients with first-episode schizophrenia (FES) underwent a clinical interview and a T1-weighted structural MRI scan. Patients' scores on the Delusions subscale of the Positive and Negative Syndrome Scale were correlated with the volume of every voxel in their grey matter images in SPM99. Patients' delusion scores were found to correlate with the volume of a cluster of voxels located in the dorso-medial frontal cortex, centred on the medial frontal gyrus. Post-hoc analysis revealed that this 'region-of-correlation' was volumetrically reduced in the FES patients relative to a group of 21 matched healthy controls. The results of this study support the hypothesis that while a certain level of structural brain atrophy is necessary for delusion formation in patients with FES, excessive structural atrophy may in fact preclude the formation of highly systematized delusions.
Psychiatry Research 05/2009; 172(3):175-9. · 2.52 Impact Factor
-
Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 04/2009; 30(5):688-9. · 1.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although schizophrenia has been characterized by disruptions to neural synchrony, it remains unknown whether these disturbances are related to symptoms and loss of grey matter. We examined relations between 40 Hz Gamma band synchrony and grey matter in patients with schizophrenia at first episode and after 2.5 years.
From an initial recruitment of 35 medicated patients with a first episode of schizophrenia, 25 patients completed clinical and oddball task-elicited Gamma synchrony within 3 months of health service contact and again after 2.5 years, 23 completed magnetic resonance imaging (MRI) at these time points, and 13 completed all sessions. We compared patients with 35 matched healthy controls. We identified early (0-150 ms) and late (250-500 ms) peaks in Gamma synchrony locked to oddball targets, and we analyzed MRI data using voxel-based morphometry. We evaluated group and test-retest differences using repeated-measures analyses of variance.
Compared with controls, at first contact, patients with a first episode of schizophrenia showed a disruption to the laterality of early Gamma synchrony and global reduction in late Gamma synchrony, with a corresponding loss of fronto-temporal-parietal grey matter. Gamma synchrony was increased at follow-up among patients with a first episode of schizophrenia. It related negatively to further loss of grey matter, but positively to improvement in reality distortion symptoms. These relations could not be explained by medication dose.
Our study did not include unmedicated patients or normative follow-up testing.
Gamma synchrony may track the progression of schizophrenia from first episode. An increase in Gamma synchrony over time might reflect an attempt to adapt to a progressive loss of cortical grey matter and associated changes in cognitive and emotional function.
Journal of psychiatry & neuroscience: JPN 02/2009; 34(1):21-9. · 5.34 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study explored the concurrent courses of the neuroanatomical and neuropsychological changes that occurred over the first 2-3 years of illness in patients with first-episode schizophrenia (FES).
Fifty-two patients with FES underwent neuropsychological testing and a structural magnetic resonance imaging (sMRI) scan within three months of their first presentation to mental health services with psychotic symptoms (time1). Patients' cognitive performance was evaluated via an extensive neuropsychological test battery, which assessed 9 cognitive domains. Of the 52 patients at time1, 32 returned 2-3 years later (time2) for follow-up neuropsychological testing, and 20 of these also underwent follow-up sMRI. MR images were preprocessed in SPM99. Grey matter volumes of patients' whole-brain, frontal lobes and temporal lobes were calculated by convolving the preprocessed images with manually-drawn binary masks.
Patients exhibited longitudinal improvements in full-scale IQ, performance IQ and visual memory. In contrast, concurrent reductions in grey matter were observed for the whole-brain (3% reduction) and the frontal lobe (3.65% reduction). Furthermore, the extent of patients' whole-brain and frontal-lobe grey matter changes were positively correlated with longitudinal changes in verbal learning and memory.
The results of this study suggest that while the early stages of schizophrenia are associated with a mild improvement in patients' overall cognitive functioning, they are also associated with progressive grey matter atrophy.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 03/2008; 32(2):531-8. · 3.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: While schizophrenia has long been considered a disorder of brain connectivity, few studies have investigated white matter abnormalities in patients with first-episode schizophrenia, and even fewer studies have investigated whether there is progressive white matter pathology in the disease.
The authors obtained a T1-weighted structural magnetic resonance imaging (MRI) scan on 41 patients with first-episode schizophrenia. These first-episode schizophrenia patients were analyzed relative to 47 age- and sex-matched healthy comparison subjects who also underwent an MRI scan. Of the baseline participants, 25 first-episode schizophrenia patients and 26 comparison subjects returned 2 to 3 years later for a follow-up scan. To identify regional volumetric white matter differences between the two groups at baseline, voxel-based morphometry in statistical parametric mapping-2 (SPM2) was used, while tensor-based morphometry was used to identify the longitudinal changes over the follow-up interval.
The first-episode schizophrenia patients exhibited volumetric deficits in the white matter of the frontal and temporal lobes at baseline, as well as volumetric increases in the white matter of the frontoparietal junction bilaterally. Furthermore, these first-episode schizophrenia patients lost considerably more white matter over the follow-up interval relative to comparison subjects in the middle and inferior temporal cortex bilaterally.
These results indicate that patients with schizophrenia exhibit white matter abnormalities at the time of their first presentation of psychotic symptoms to mental health services and that these abnormalities degenerate further over the initial years of illness. Given the role that white matter plays in neural communication, the authors suggest that these white matter abnormalities may be a cause of the dysfunctional neural connectivity that has been proposed to underlie the symptoms of schizophrenia.
American Journal of Psychiatry 08/2007; 164(7):1082-9. · 12.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although there is substantial evidence indicating that patients with first-episode schizophrenia exhibit both anatomical and electrophysiological abnormalities, there has been little research investigating the relationship between these two indices. We acquired structural magnetic resonance images and resting electroencephalographic recordings from 19 patients with schizophrenia, both at the time of their first presentation to mental health services and 2-3 years subsequently. Patients' grey matter images were parcellated into four brain lobes, and slow-wave, alpha- and beta-electroencephalographic power was calculated in four corresponding cortical regions. Although grey matter volume decreased longitudinally, particularly fronto-parietally, electroencephalographic power increased in the slow-wave and beta-frequency bands. These results suggest that first-episode schizophrenia may be associated with abnormally elevated levels of neural synchrony.
Neuroreport 04/2007; 18(5):435-9. · 1.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although there is substantial evidence indicating that patients with first-episode schizophrenia exhibit both anatomical and electrophysiological abnormalities, there has been little research investigating the relationship between these two indices. We acquired structural magnetic resonance images and resting electroencephalographic recordings from 19 patients with schizophrenia, both at the time of their first presentation to mental health services and 2-3 years subsequently. Patients' grey matter images were parcellated into four brain lobes, and slow-wave, α- and β-electroencephalographic power was calculated in four corresponding cortical regions. Although grey matter volume decreased longitudinally, particularly fronto-parietally, electroencephalographic power increased in the slow-wave and β-frequency bands. These results suggest that first-episode schizophrenia may be associated with abnormally elevated levels of neural synchrony.
Neuroreport 03/2007; 18(5):435-439. · 1.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Little is known about the structural brain changes that occur over the first few years of schizophrenia, or how these changes differ from those associated with healthy brain development in adolescence and early adulthood. In this study, we aimed to identify regional differences in grey matter (GM) volume between patients with first-episode schizophrenia (FES) and matched healthy controls, both at the time of the patients' first psychotic episode (baseline condition) and 2-3 years subsequently (follow-up condition). Forty-one patients with FES and 47 matched healthy controls underwent a T1-weighted structural MRI scan. Of these participants, 25 FES patients and 26 controls returned 2-3 years later for a follow-up scan. Voxel-based morphometry in SPM2 was used to identify the regions of GM difference between the groups in the baseline condition, while tensor-based morphometry was used to identify the longitudinal change within subject over the follow-up interval. The FES patients exhibited widespread GM reductions in the frontal, parietal, and temporal cortices and cerebellum in the baseline condition, as well as more circumscribed regions of GM increase, particularly in the occipital lobe. Furthermore, the FES subjects were observed to lose considerably more GM over the follow-up interval than the controls, especially in the parietal and temporal cortices. We argue that the progressive GM atrophy we have found to be associated with the onset of schizophrenia arises from a dysfunction in the dramatic period of healthy brain development typically associated with adolescence.
NeuroImage 09/2006; 32(2):511-9. · 5.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We examined gray- and white-matter brain volumes in first episode psychosis (FEP) at initial presentation and at two-year follow-up. We predicted that FEP subjects would show longitudinal reductions in fronto-temporal gray- and white-matter volumes compared with controls. Furthermore, we expected groups to be differentiated by diagnosis-related reductions.
Twenty-five schizophrenia and 8 bipolar disorder FEP patients underwent a structural MRI scan at first presentation and 2 years later. Matched healthy subjects (n = 22) underwent a single identical scan.
At initial presentation FEP subjects had significantly less gray- and white-matter than healthy subjects. Diagnostic dissociations were revealed both at first presentation and at follow-up. In schizophrenia patients, gray-matter deficits were observed in lateral and medial frontal regions and in bilateral posterior temporal lobe regions, with additional extensive losses over time in lateral fronto-temporal regions and left anterior cingulate gyrus. By contrast, gray matter deficit in bipolar patients was localized to bilateral inferior temporal gyri with additional loss over time observed only in the anterior cingulate cortex.
The results are consistent with a dual process model of psychosis, in which the diagnosis-related gray matter loss is determined by neurodevelopmental gray-matter volumetric differences which predate symptom onset, and diagnosis-related neurodegenerative gray-matter loss over time.
Biological Psychiatry 12/2005; 58(9):713-23. · 8.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Several studies have investigated grey matter reductions in first episode schizophrenia (FES), but few have examined the relationship between grey matter reduction and clinical profile. A group of 31 patients with strictly defined FES and 30 healthy controls underwent T1-weighted magnetic resonance imaging (MRI) scan. Voxel-based morphometry in SPM99 was used to identify four distinct regions of grey matter reduction in the FES subjects. The regions of interest (ROIs) were in the left ventral prefrontal cortex (ROI 1), left parietal and temporal cortices (ROI 2), right cerebellum (ROI 3), and right frontal and parietal cortices (ROI 4). These regions of reduction were transformed into binary masks, which were convolved with patients' pre-processed grey matter images. Patients' grey matter volumes in these regions were correlated with their composite scores on the following three symptom dimensions: Psychomotor Poverty, Disorganization and Reality Distortion. The volumes of ROIs 1, 2 and 4 were found to be significantly correlated with the Reality Distortion syndrome score. Our findings indicate that distinct, widespread grey matter reductions are present very early in the course of schizophrenia. The results also suggest a possible structural underpinning for the abnormal brain activity typically associated with symptoms of Reality Distortion.
Psychiatry Research 09/2005; 139(3):229-38. · 2.52 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the feasibility of a statistical classification strategy (SCS) and the identity of metabolites of bacterial and host origins that potentially contributed to the most discriminatory regions of magnetic resonance (MR) spectra from Staphylococcus aureus abscesses of biopsy material from controls, gliomas, and staphylococcal abscesses.
Human and animal study received ethics committee approval, and informed patient consent was obtained. A rat model of S aureus brain abscess was developed. Histologic and microbiologic examination was performed to assess abscess development 3-4, 6-8, and 10-15 days after initiation. Metabolite profiles in pus (n = 62) and controls (n = 37) were characterized with ex vivo MR spectroscopy and compared with data from rat gliomas (n = 27). SCS, optimal region selection, and development of pairwise classifiers allowed MR spectra of abscesses (n = 42, day 6-8) to be distinguished from those of glioblastoma multiforme and controls. MR spectroscopy profiles of pus from animal abscesses were compared with in vivo MR spectra from patients with staphylococcal brain abscesses (n = 7, aged 6-67 years) and ex vivo pus MR spectra from patients with S aureus abscesses.
Histologically confirmed abscesses were present 6-8 days after stereotactic injection of S aureus in 42 of 47 rats (89%). MR spectra of abscesses and glioblastoma multiforme in the animal model were similar. Typical metabolites of abscesses due to anaerobe bacteria (acetate, succinate, amino acids) were not detectable in S aureus abscesses in rats or humans. MR spectroscopic findings from controls, abscesses, and gliomas were distinguished by means of SCS with an accuracy of 99%. Analysis of the most discriminatory regions with two-dimensional correlation spectra indicated that glutamine and/or glutamate and aspartate potentially contributed to successful classification.
S aureus is detectable in abscesses with a non-culture-based method in an animal model.
Radiology 08/2005; 236(1):261-70. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The clinical, imaging and pathological features of a skull base chordoid meningioma (CM) are described. The huge tumour resulted in obstructive hydrocephalus and partial erosion of the clivus such that a chordoma was suspected. The lesion's MRI findings were similar to those of a meningioma. Light microscopic, immunohistochemistry and ultrastructural features were diagnostic of CM. Chordoid meningioma is a rare subtype of meningioma and has a great tendency to recur should surgical resection be incomplete.
Australasian Radiology 07/2004; 48(2):233-6. · 0.51 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We describe a patient with multiple cerebral lesions that initially were believed to be tumor metastases but were later found to be caused by Nocardia asteroides, after magnetic resonance spectroscopy (MRS) findings suggested that the lesions were infective in origin. This case report demonstrates the ability of MRS, a noninvasive imaging modality, to aid in the diagnosis of brain infection.
Clinical Infectious Diseases 04/2002; 34(6):849-52. · 9.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To examine the clinical profile, treatment and social functioning of a community-based sample of young people presenting with their first episode of psychosis.
Over a 2-year period, young people with their first episode of psychosis referred to early intervention services in two area mental health services in western Sydney were assessed with a battery of clinical, neuropsychological, psychophysiological and neuroanatomical measures. This paper reports the clinical results of the baseline section of the study.
Of the 224 referrals to the project, 94 subjects meet inclusion criteria and agreed to take part. Subjects were divided into three diagnostic groups--'Schizophrenia', 'Mood Disorders' and 'Mixed Psychosis', the latter principally comprised of substance induced psychotic disorders. Subjects from the 'Schizophrenia' group differed significantly from the other two groups in that they had higher levels of negative symptoms and general psychopathology, and were less likely to be employed or engaged in study. They had poorer overall social functioning. Subjects with 'Mixed Psychosis' were similar to those from the 'Schizophrenia' group in that they were older and male, but they did not have the same burden of negative symptoms as the 'Schizophrenia' group. The 'Mood Disorders' group was younger, female and had overall a higher level of psychosocial functioning than the other two groups. Subjects from the 'Mood Disorders' group were more likely to be managed with mood stabilisers and multiple drug therapies. The use of atypical antipsychotic medication was almost universal.
Even shortly after the time of presentation to mental health services young people with a schizophrenia spectrum diagnosis have a heavier burden of symptoms and are significantly more impaired by them than young people with other psychotic illnesses. This and their symptom profile differentiated them from young people with other psychotic disorders.
Australian and New Zealand Journal of Psychiatry 39(1-2):36-43. · 2.93 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Objective
This study explored the concurrent courses of the neuroanatomical and neuropsychological changes that occurred over the first 2–3 years of illness in patients with first-episode schizophrenia (FES).Methods
Fifty-two patients with FES underwent neuropsychological testing and a structural magnetic resonance imaging (sMRI) scan within three months of their first presentation to mental health services with psychotic symptoms (time1). Patients' cognitive performance was evaluated via an extensive neuropsychological test battery, which assessed 9 cognitive domains. Of the 52 patients at time1, 32 returned 2–3 years later (time2) for follow-up neuropsychological testing, and 20 of these also underwent follow-up sMRI. MR images were preprocessed in SPM99. Grey matter volumes of patients' whole-brain, frontal lobes and temporal lobes were calculated by convolving the preprocessed images with manually-drawn binary masks.ResultsPatients exhibited longitudinal improvements in full-scale IQ, performance IQ and visual memory. In contrast, concurrent reductions in grey matter were observed for the whole-brain (3% reduction) and the frontal lobe (3.65% reduction). Furthermore, the extent of patients' whole-brain and frontal-lobe grey matter changes were positively correlated with longitudinal changes in verbal learning and memory.DiscussionThe results of this study suggest that while the early stages of schizophrenia are associated with a mild improvement in patients' overall cognitive functioning, they are also associated with progressive grey matter atrophy.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 32(2):531-538. · 3.25 Impact Factor
