Martin O'Connell - Academia.edu (original) (raw)

Papers by Martin O'Connell

Brain, 2015

Frontotemporal lobar degeneration comprises a group of disorders characterized by behavioural, ex... more Frontotemporal lobar degeneration comprises a group of disorders characterized by behavioural, executive, language impairment and sometimes features of parkinsonism and motor neuron disease. In 1994 we described an Irish-American family with frontotemporal dementia linked to chromosome 17 associated with extensive tau pathology. We named this disinhibition-dementia-parkinsonism-amyotrophy complex. We subsequently identified mutations in the MAPT gene. Eleven MAPT gene splice site stem loop mutations were identified over time except for 5' splice site of exon 10. We recently identified another Irish family with autosomal dominant early amnesia and behavioural change or parkinsonism associated with the 'missing' +15 mutation at the intronic boundary of exon 10. We performed a clinical, neuropsychological and neuroimaging study on the proband and four siblings, including two affected siblings. We sequenced MAPT and performed segregation analysis. We looked for a biological effect of the tau variant by performing real-time polymerase chain reaction analysis of RNA extracted from human embryonic kidney cells transfected with exon trapping constructs. We found a c.915+15A>C exon 10/intron 10 stem loop mutation in all affected subjects but not in the unaffected. The c.915+15A>C variant caused a shift in tau splicing pattern to a predominantly exon 10+ pattern presumably resulting in predominant 4 repeat tau and little 3 repeat tau. This strongly suggests that the c.915+15A>C variant is a mutation and that it causes frontotemporal dementia linked to chromosome 17 in this pedigree by shifting tau transcription and translation to +4 repeat tau. Tau (MAPT) screening should be considered in families where amnesia or atypical parkinsonism coexists with behavioural disturbance early in the disease process. We describe the final missing stem loop tau mutation predicted 15 years ago. Mutations have now been identified at all predicted sites within the 'stem' when the stem-loop model was first proposed and…

American Journal of Roentgenology, Nov 1, 2002

Our purpose was to evaluate the use of whole-body MR imaging in the assessment of the extent and ... more Our purpose was to evaluate the use of whole-body MR imaging in the assessment of the extent and distribution of muscle inflammation in patients with polymyositis. Whole-body turbo short tau inversion recovery imaging is a convenient complete method of evaluating patients with muscle inflammation caused by polymyositis. This imaging technique allows us to evaluate the total inflammatory burden by revealing multiple muscle groups not seen with standard protocols.

Emergency Radiology, 2005

The objective of the study was to evaluate the clinical impact of coronal oblique imaging of the ... more The objective of the study was to evaluate the clinical impact of coronal oblique imaging of the lumbrosacral junction and the sacrum at initial presentation for MR imaging of the lumbar spine in patients presenting with low back pain or sciatic pain. Two hundred and sixty consecutive patients attending for MRI of the lumbar spine underwent simultaneous coronal oblique turbo short tau inversion recovery (STIR; TR 2500, TE 40, TI 150, echo train length 7, number of scan acquisitions 2) imaging of the sacrum and the sacroiliac joints with a field of view of 30-cm and 3-mm slices (acquisition time 3 min and 20 s). Images were reviewed by two experienced radiologists to determine the cause of back pain, with and without images of the sacrum and sacroiliac joints. The added value of the additional sequence was assessed. Correlation was made with surgery, response to nerve root injection or clinical follow-up at 3 months. Subgroup analysis was performed to determine if patient stratification according to sex or symptoms would be useful. In total, in 19 of 260 patients (7.3%), abnormalities were identified at coronal STIR imaging. In 7 of 260 patients (2.7%), pathology was identified in the sacrum thought to account for back pain, altering the diagnosis made on the standard sequences. These diagnoses were sacroiliitis (n=2), sacral stress fracture (n=1), degenerative sacroiliac joints (n=1), degenerative accessory articulation between the lumbar spine and the sacrum (n=1), Tarlov cyst of nerve root (n=1) and retroverted uterus causing sciatic pain (n=1). Patient stratification according to sex or the presence or absence of sciatic symptoms was not useful in predicting the added benefit of the additional sequence. Routine coronal STIR imaging of the sacrum as part of lumbar spine MRI improves assessment of patients presenting with low back pain or sciatica in only a small number of patients.

Parkinsonism & Related Disorders, 2014

Journal of the Neurological Sciences, 2013

Seminars in musculoskeletal radiology, 2010

This article outlines the expanding approaches to whole-body imaging in oncology focusing on whol... more This article outlines the expanding approaches to whole-body imaging in oncology focusing on whole-body MRI and comparing it to emerging applications of whole-body CT, scintigraphy, and above all PET CT imaging. Whole-body MRI is widely available, non-ionizing and rapidly acquired, and inexpensive relative to PET CT. While it has many advantages, WBMRI is non-specific and, when compared to PET CT, is less sensitive. This article expands each of these issues comparing individual modalities as they refer to specific cancers.

Archives of Neurology, 2007

You are seeing this message because your Web browser does not support basic Web standards. Find o... more You are seeing this message because your Web browser does not support basic Web standards. Find out more about why this message is appearing and what you can do to make your experience on this site better. ... Add to CiteULike Add to Connotea Add to ...

Annals of Neurology, 2012

Symptomatic carotid stenosis is associated with a 3-fold risk of early stroke recurrence compared... more Symptomatic carotid stenosis is associated with a 3-fold risk of early stroke recurrence compared to other stroke subtypes. Current carotid imaging techniques rely on estimating plaque-related lumen narrowing but do not evaluate intraplaque inflammation, a key mediator of plaque rupture and thromboembolism. Using combined (18) F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography, we investigated the relation between inflammation-related FDG uptake and stroke recurrence. Consecutive patients with a recent (median, 6.5 days; interquartile range, 4-8) stroke, transient ischemic attack (TIA), or retinal embolism and ipsilateral carotid stenosis (≥50%) were included. FDG uptake was quantified as mean standardized uptake values (SUVs, g/ml). Patients were followed prospectively for stroke recurrence. Sixty patients were included (25 stroke, 29 TIA, 6 retinal embolism). Twenty-two percent (13 of 60) had stroke recurrence within 90 days. FDG uptake in ipsilateral carotid plaque was greater in patients with early recurrent stroke (mean SUV, 1.85 g/ml; standard deviation [SD], 0.44 vs 1.58 g/ml; SD, 0.32, p = 0.02). On life-table analysis, 90-day recurrence rates with mean SUV greater than a 2.14 g/ml threshold were 80% (95% confidence interval [CI], 41.8-99.2) versus 22.9% (95% CI, 12.3-40.3) with SUV ≤2.14 g/ml (log-rank, p < 0.0001). In a Cox regression model including age and degree of stenosis (50-69% or ≥70%), mean plaque FDG uptake was the only independent predictor of stroke recurrence (adjusted hazard ratio, 6.1; 95% CI, 1.3-28.8; p = 0.02). In recently symptomatic carotid stenosis, inflammation-related FDG uptake was associated with early stroke recurrence, independent of the degree of stenosis. Plaque FDG-PET may identify patients at highest risk for stroke recurrence, who may be selected for immediate revascularization or intensive medical treatment.

American Journal of Roentgenology, 2009

The purpose of this study was to compare FDG PET; whole-body MRI; and the reference standard, bon... more The purpose of this study was to compare FDG PET; whole-body MRI; and the reference standard, bone marrow aspiration and biopsy, to determine the best imaging technique for assessment of disease activity in multiple myeloma. Twenty-four patients (13 women, 11 men; mean age, 67.1 years; range, 44-83 years) with bone marrow biopsy-proven multiple myeloma were included in the study. All patients underwent PET/CT and whole-body MRI within 10 days of each other. Eight patients underwent more than one follow-up PET/CT and whole-body MRI examination, for a total of 34 pairs of images. Activity was defined as lesions with a maximum standardized uptake value greater than 2.5 at PET and as evidence of marrow packing at whole-body MRI. PET and whole-body MRI results were correlated with findings at bone marrow aspiration biopsy. PET had a sensitivity of 59%, specificity of 75%, positive predictive value of 81%, and negative predictive value of 50% (p = 0.08). Whole-body MRI had a sensitivity of 68%, specificity of 83%, positive predictive value of 88%, and negative predictive value of 59% (p = 0.01). In 62% of cases, PET and whole-body MRI findings were concordant. When PET and whole-body MRI findings were concordant and positive, no false-positive results were found, yielding a specificity and a positive predictive value of 100% (p = 0.04). Whole-body MRI performed better than PET in the assessment of disease activity, having a higher sensitivity and specificity. The positive predictive value of whole-body MRI in the assessment of active disease was high at 88%. When used in combination and with concordant findings, PET and whole-body MRI were found to have a specificity and positive predictive value of 100%, which may be of value to clinicians assessing the effectiveness of aggressive and expensive treatment regimens.

American Journal of Roentgenology, Nov 23, 2012

The objectives of our study were, first, to use MRI to determine the prevalence of osteitis pubis... more The objectives of our study were, first, to use MRI to determine the prevalence of osteitis pubis and of adductor dysfunction at the symphysis pubis in soccer players presenting with pubalgia and, second, to determine whether the two entities are mechanically related and whether one of the entities precedes or predisposes the development of the other. One hundred consecutive soccer players with debilitating groin pain were referred for MRI. One hundred asymptomatic age- and sex-matched elite athletes were included as control subjects. The "secondary cleft" sign was used to indicate an adductor microtear at the symphyseal enthesis. Osteitis pubis was recorded if paraarticular bone edema was identified along the symphyseal margins but was remote from the adductor attachment. Images were reviewed independently by two radiologists who were blinded to the side of symptoms. Statistical analysis was performed using the chi-square test. Of 100 patients, groin pain was directly attributed to inflammation at the symphysis pubis or its muscular attachments in 97 (isolated adductor microtears, n = 47; isolated osteitis pubis, n = 9; both, n = 41). An "accessory cleft," reflecting an adductor enthetic microtear, was identified in 88 of these patients (p < 0.001); it correlated with the side of symptoms in all cases. Bone edema was identified in 91 of 100 patients: 49 had focal edema at the attachment site of the adductor tendons accompanying an adductor microtear, two patients had focal edema without an adductor tear, and 40 patients had diffuse edema in the pubic bones secondary to osteitis pubis. There was no evidence of either adductor dysfunction or symphyseal inflammation in the control subjects (p < 0.001). In soccer players with pubalgia, adductor dysfunction is a more frequent MRI finding than osteitis pubis. The findings of this study suggest that both entities are mechanically related and that osteitis pubis and adductor dysfunction frequently coexist but, because adductor dysfunction is commonly identified in the absence of osteitis, that adductor dysfunction most likely precedes the development of osteitis pubis in soccer players. The presence of edema on fat-suppressed images of the symphysis is a strong predictor of abnormality at this site in soccer players when compared with age- and sex-matched control subjects.

Brain, 2015

Frontotemporal lobar degeneration comprises a group of disorders characterized by behavioural, ex... more Frontotemporal lobar degeneration comprises a group of disorders characterized by behavioural, executive, language impairment and sometimes features of parkinsonism and motor neuron disease. In 1994 we described an Irish-American family with frontotemporal dementia linked to chromosome 17 associated with extensive tau pathology. We named this disinhibition-dementia-parkinsonism-amyotrophy complex. We subsequently identified mutations in the MAPT gene. Eleven MAPT gene splice site stem loop mutations were identified over time except for 5' splice site of exon 10. We recently identified another Irish family with autosomal dominant early amnesia and behavioural change or parkinsonism associated with the 'missing' +15 mutation at the intronic boundary of exon 10. We performed a clinical, neuropsychological and neuroimaging study on the proband and four siblings, including two affected siblings. We sequenced MAPT and performed segregation analysis. We looked for a biological effect of the tau variant by performing real-time polymerase chain reaction analysis of RNA extracted from human embryonic kidney cells transfected with exon trapping constructs. We found a c.915+15A>C exon 10/intron 10 stem loop mutation in all affected subjects but not in the unaffected. The c.915+15A>C variant caused a shift in tau splicing pattern to a predominantly exon 10+ pattern presumably resulting in predominant 4 repeat tau and little 3 repeat tau. This strongly suggests that the c.915+15A>C variant is a mutation and that it causes frontotemporal dementia linked to chromosome 17 in this pedigree by shifting tau transcription and translation to +4 repeat tau. Tau (MAPT) screening should be considered in families where amnesia or atypical parkinsonism coexists with behavioural disturbance early in the disease process. We describe the final missing stem loop tau mutation predicted 15 years ago. Mutations have now been identified at all predicted sites within the 'stem' when the stem-loop model was first proposed and…

American Journal of Roentgenology, Nov 1, 2002

Our purpose was to evaluate the use of whole-body MR imaging in the assessment of the extent and ... more Our purpose was to evaluate the use of whole-body MR imaging in the assessment of the extent and distribution of muscle inflammation in patients with polymyositis. Whole-body turbo short tau inversion recovery imaging is a convenient complete method of evaluating patients with muscle inflammation caused by polymyositis. This imaging technique allows us to evaluate the total inflammatory burden by revealing multiple muscle groups not seen with standard protocols.

Emergency Radiology, 2005

The objective of the study was to evaluate the clinical impact of coronal oblique imaging of the ... more The objective of the study was to evaluate the clinical impact of coronal oblique imaging of the lumbrosacral junction and the sacrum at initial presentation for MR imaging of the lumbar spine in patients presenting with low back pain or sciatic pain. Two hundred and sixty consecutive patients attending for MRI of the lumbar spine underwent simultaneous coronal oblique turbo short tau inversion recovery (STIR; TR 2500, TE 40, TI 150, echo train length 7, number of scan acquisitions 2) imaging of the sacrum and the sacroiliac joints with a field of view of 30-cm and 3-mm slices (acquisition time 3 min and 20 s). Images were reviewed by two experienced radiologists to determine the cause of back pain, with and without images of the sacrum and sacroiliac joints. The added value of the additional sequence was assessed. Correlation was made with surgery, response to nerve root injection or clinical follow-up at 3 months. Subgroup analysis was performed to determine if patient stratification according to sex or symptoms would be useful. In total, in 19 of 260 patients (7.3%), abnormalities were identified at coronal STIR imaging. In 7 of 260 patients (2.7%), pathology was identified in the sacrum thought to account for back pain, altering the diagnosis made on the standard sequences. These diagnoses were sacroiliitis (n=2), sacral stress fracture (n=1), degenerative sacroiliac joints (n=1), degenerative accessory articulation between the lumbar spine and the sacrum (n=1), Tarlov cyst of nerve root (n=1) and retroverted uterus causing sciatic pain (n=1). Patient stratification according to sex or the presence or absence of sciatic symptoms was not useful in predicting the added benefit of the additional sequence. Routine coronal STIR imaging of the sacrum as part of lumbar spine MRI improves assessment of patients presenting with low back pain or sciatica in only a small number of patients.

Parkinsonism & Related Disorders, 2014

Journal of the Neurological Sciences, 2013

Seminars in musculoskeletal radiology, 2010

This article outlines the expanding approaches to whole-body imaging in oncology focusing on whol... more This article outlines the expanding approaches to whole-body imaging in oncology focusing on whole-body MRI and comparing it to emerging applications of whole-body CT, scintigraphy, and above all PET CT imaging. Whole-body MRI is widely available, non-ionizing and rapidly acquired, and inexpensive relative to PET CT. While it has many advantages, WBMRI is non-specific and, when compared to PET CT, is less sensitive. This article expands each of these issues comparing individual modalities as they refer to specific cancers.

Archives of Neurology, 2007

You are seeing this message because your Web browser does not support basic Web standards. Find o... more You are seeing this message because your Web browser does not support basic Web standards. Find out more about why this message is appearing and what you can do to make your experience on this site better. ... Add to CiteULike Add to Connotea Add to ...

Annals of Neurology, 2012

Symptomatic carotid stenosis is associated with a 3-fold risk of early stroke recurrence compared... more Symptomatic carotid stenosis is associated with a 3-fold risk of early stroke recurrence compared to other stroke subtypes. Current carotid imaging techniques rely on estimating plaque-related lumen narrowing but do not evaluate intraplaque inflammation, a key mediator of plaque rupture and thromboembolism. Using combined (18) F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography, we investigated the relation between inflammation-related FDG uptake and stroke recurrence. Consecutive patients with a recent (median, 6.5 days; interquartile range, 4-8) stroke, transient ischemic attack (TIA), or retinal embolism and ipsilateral carotid stenosis (≥50%) were included. FDG uptake was quantified as mean standardized uptake values (SUVs, g/ml). Patients were followed prospectively for stroke recurrence. Sixty patients were included (25 stroke, 29 TIA, 6 retinal embolism). Twenty-two percent (13 of 60) had stroke recurrence within 90 days. FDG uptake in ipsilateral carotid plaque was greater in patients with early recurrent stroke (mean SUV, 1.85 g/ml; standard deviation [SD], 0.44 vs 1.58 g/ml; SD, 0.32, p = 0.02). On life-table analysis, 90-day recurrence rates with mean SUV greater than a 2.14 g/ml threshold were 80% (95% confidence interval [CI], 41.8-99.2) versus 22.9% (95% CI, 12.3-40.3) with SUV ≤2.14 g/ml (log-rank, p < 0.0001). In a Cox regression model including age and degree of stenosis (50-69% or ≥70%), mean plaque FDG uptake was the only independent predictor of stroke recurrence (adjusted hazard ratio, 6.1; 95% CI, 1.3-28.8; p = 0.02). In recently symptomatic carotid stenosis, inflammation-related FDG uptake was associated with early stroke recurrence, independent of the degree of stenosis. Plaque FDG-PET may identify patients at highest risk for stroke recurrence, who may be selected for immediate revascularization or intensive medical treatment.

American Journal of Roentgenology, 2009

The purpose of this study was to compare FDG PET; whole-body MRI; and the reference standard, bon... more The purpose of this study was to compare FDG PET; whole-body MRI; and the reference standard, bone marrow aspiration and biopsy, to determine the best imaging technique for assessment of disease activity in multiple myeloma. Twenty-four patients (13 women, 11 men; mean age, 67.1 years; range, 44-83 years) with bone marrow biopsy-proven multiple myeloma were included in the study. All patients underwent PET/CT and whole-body MRI within 10 days of each other. Eight patients underwent more than one follow-up PET/CT and whole-body MRI examination, for a total of 34 pairs of images. Activity was defined as lesions with a maximum standardized uptake value greater than 2.5 at PET and as evidence of marrow packing at whole-body MRI. PET and whole-body MRI results were correlated with findings at bone marrow aspiration biopsy. PET had a sensitivity of 59%, specificity of 75%, positive predictive value of 81%, and negative predictive value of 50% (p = 0.08). Whole-body MRI had a sensitivity of 68%, specificity of 83%, positive predictive value of 88%, and negative predictive value of 59% (p = 0.01). In 62% of cases, PET and whole-body MRI findings were concordant. When PET and whole-body MRI findings were concordant and positive, no false-positive results were found, yielding a specificity and a positive predictive value of 100% (p = 0.04). Whole-body MRI performed better than PET in the assessment of disease activity, having a higher sensitivity and specificity. The positive predictive value of whole-body MRI in the assessment of active disease was high at 88%. When used in combination and with concordant findings, PET and whole-body MRI were found to have a specificity and positive predictive value of 100%, which may be of value to clinicians assessing the effectiveness of aggressive and expensive treatment regimens.

American Journal of Roentgenology, Nov 23, 2012

The objectives of our study were, first, to use MRI to determine the prevalence of osteitis pubis... more The objectives of our study were, first, to use MRI to determine the prevalence of osteitis pubis and of adductor dysfunction at the symphysis pubis in soccer players presenting with pubalgia and, second, to determine whether the two entities are mechanically related and whether one of the entities precedes or predisposes the development of the other. One hundred consecutive soccer players with debilitating groin pain were referred for MRI. One hundred asymptomatic age- and sex-matched elite athletes were included as control subjects. The "secondary cleft" sign was used to indicate an adductor microtear at the symphyseal enthesis. Osteitis pubis was recorded if paraarticular bone edema was identified along the symphyseal margins but was remote from the adductor attachment. Images were reviewed independently by two radiologists who were blinded to the side of symptoms. Statistical analysis was performed using the chi-square test. Of 100 patients, groin pain was directly attributed to inflammation at the symphysis pubis or its muscular attachments in 97 (isolated adductor microtears, n = 47; isolated osteitis pubis, n = 9; both, n = 41). An "accessory cleft," reflecting an adductor enthetic microtear, was identified in 88 of these patients (p < 0.001); it correlated with the side of symptoms in all cases. Bone edema was identified in 91 of 100 patients: 49 had focal edema at the attachment site of the adductor tendons accompanying an adductor microtear, two patients had focal edema without an adductor tear, and 40 patients had diffuse edema in the pubic bones secondary to osteitis pubis. There was no evidence of either adductor dysfunction or symphyseal inflammation in the control subjects (p < 0.001). In soccer players with pubalgia, adductor dysfunction is a more frequent MRI finding than osteitis pubis. The findings of this study suggest that both entities are mechanically related and that osteitis pubis and adductor dysfunction frequently coexist but, because adductor dysfunction is commonly identified in the absence of osteitis, that adductor dysfunction most likely precedes the development of osteitis pubis in soccer players. The presence of edema on fat-suppressed images of the symphysis is a strong predictor of abnormality at this site in soccer players when compared with age- and sex-matched control subjects.