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J M Schott

Publications and source records attributed to J M Schott.

17 recordsLinked to original sources
PubMed2006

Combining short interval MRI in Alzheimer's disease: Implications for therapeutic trials.

Cerebral atrophy calculated from serial MRI is a marker of Alzheimer's disease (AD) progression, and a potential outcome measure for therapeutic trials. Reducing within-subject variability in cerebral atrophy rates by acquiring more than two serial scans could allow for shorter clinical trials requiring smaller patient numbers. Forty-six patients with AD and 23 controls each had up to 10 serial MR brain scans over two years. Whole brain atrophy was calculated for each subject from every scan-pair. 708 volumetric MRI scans were acquired: 2199 measures of atrophy were made for patients, and 1182 for controls. A linear mixed model was used to characterise between and within-individual variability. These results were used to investigate the power of combining multiple serial scans in treatment trials of varying lengths. In AD, the mean whole brain atrophy rate was 2.23%/year (95% CI: 1.90-2.56%/year). The linear mixed model was shown to fit the data well and led to a formula (0.99(2) + (0.82/t)2) for the variance of atrophy rates calculated from two scans "t" years apart. Utilising five optimally timed scans with repeat scans at each visit reduced the component of atrophy rate variance attributable to within-subject variability by approximately 56%, equating to a approximately 40% sample size reduction (228 vs 387 patients per arm to detect 20% reduction in atrophy rate) in a six-month placebo-controlled trial. This benefit in terms of sample size is relatively reduced in longer trials, although adding extra scanning visits may have benefits when patient drop-outs are accounted for. We conclude that sample sizes required in short interval therapeutic trials using cerebral atrophy as an outcome measure may be reduced if multiple serial MRI is performed.

Aged↗
PubMed2006

Automatic calculation of hippocampal atrophy rates using a hippocampal template and the boundary shift integral.

We describe a method of automatically calculating hippocampal atrophy rates on T1-weighted MR images without manual delineation of hippocampi. This method was applied to a group of Alzheimer's disease (AD) (n=36) and control (n=19) subjects and compared with manual methods (manual segmentation of baseline and repeat-image hippocampi) and semi-automated methods (manual segmentation of baseline hippocampi only). In controls, mean (S.D.) atrophy rates for manual, semi-automated, and automated methods were 18.1 (53.5), 15.3 (50.2) and 11.3 (50.4) mm3 loss per year, respectively. In AD patients these rates were 174.6 (106.5) 159.4 (101.2) and 172.1 (123.1) mm3 loss per year, respectively. The automated method was a significant predictor of disease (p=0.001) and gave similar group discrimination compared with both semi-automated and manual methods. The automated hippocampal analysis in this small study took approximately 20 min per hippocampal pair on a 3.4 GHz Intel Xeon server, whereas manual delineation of each hippocampal pair took approximately 90 min of operator-intensive labour. This method may be useful diagnostically or in studies where analysis of many scans may be required.

Aged↗
PubMed2006

MRS shows abnormalities before symptoms in familial Alzheimer disease.

BACKGROUND: Pathologic change in Alzheimer disease (AD) begins some years before symptoms. MRS has the potential to detect metabolic abnormalities reflecting this early pathologic change. Presenilin 1 (PS1) and amyloid precursor protein (APP) mutation carriers have a nearly 100% risk of developing AD and may be studied prior to symptom onset. METHODS: Short echo time proton MR spectra were acquired from a midline posterior cingulate voxel in presymptomatic carriers of PS1 or APP mutations ("presymptomatic mutation carriers" [PMCs]; n = 7) and age- and sex-matched control subjects (n = 6). Ratios of N-acetyl aspartate (NAA), myo-inositol (MI), and choline-containing compounds (Cho) to creatine (Cr) were measured and NAA/MI calculated. Regression analyses and t tests were performed after log transformation. RESULTS: PMC and control subjects were matched for age and sex. PMC subjects were 1.7 to 21.6 years (mean 9.8 years) before expected symptom onset, predicted from family-specific mean age at onset. Age did not significantly affect metabolite ratios. Geometric mean ratios in control subjects were as follows: NAA/Cr = 1.75, MI/Cr = 0.59, and NAA/MI = 2.95. NAA/Cr and NAA/MI were significantly reduced in PMC relative to controls (NAA/Cr mean decrease 10% [95% CI 2 to 18%]; NAA/MI mean decrease 25% [95% CI 3 to 44%]). MI/Cr was increased in PMC, but the differences did not achieve significance (19% increase [95% CI 1% decrease to 41% increase]; p = 0.07)). In PMCs, reduction in NAA/MI (p = 0.001) and MI/Cr (p = 0.002) were related to proximity of expected age at onset. CONCLUSIONS: Metabolic changes are detectable in presymptomatic mutation carriers years before expected onset of Alzheimer disease. Their magnitude is related to proximity of expected age at onset.

Adolescent↗
PubMed2005

Measuring atrophy in Alzheimer disease: a serial MRI study over 6 and 12 months.

BACKGROUND: Global brain atrophy rate calculated from serial MRI scans may be a surrogate marker of Alzheimer disease (AD) progression. Few studies have assessed atrophy in AD over short intervals. METHODS: Thirty-eight patients with AD and 19 control subjects had MRI scans at baseline, 6 months, and 1 year. Ventricular change and whole-brain volume loss were calculated directly from the regions manually outlined on registered scans and using the automated (boundary shift integral [BSI]) technique. Sample sizes required to power placebo-controlled treatment trials over 6 months and 1 year were calculated using these techniques. RESULTS: Increased rates of ventricular expansion and whole-brain atrophy were seen in AD compared with control subjects at both 6 and 12 months using manual and automated techniques (p < 0.001). Using the BSI consistently reduced measurement variability especially for whole-brain change. In clinical trials, at 6 months, significantly fewer patients would be required using the ventricular BSI (VBSI) compared with the brain BSI (BBSI) (e.g., 165 vs 410 per arm to provide 90% power to detect a 20% reduction in rate of change). At 1 year, sample size estimates were smaller than at 6 months, and the advantage of using VBSI instead of BBSI was less marked. CONCLUSIONS: In short-interval studies, using the ventricular boundary shift integral instead of the brain boundary shift integral may allow for disease-modifying effects to be demonstrated using significantly smaller sample sizes. This potential benefit must be balanced against the possibility that ventricular volumes may be more likely to be affected by factors other than neurodegeneration.

Aged↗
PubMed2005

Brain biopsy in dementia.

Brain biopsy has an uncertain role in the diagnosis of dementia. Here we report a retrospective analysis of 90 consecutive cerebral biopsies undertaken for the investigation of dementia in adults at a tertiary referral centre between 1989 and 2003. In most cases (90%), biopsy consisted of a right frontal full thickness resection of cortex, white matter and overlying leptomeninges. Fifty-seven per cent of biopsies were diagnostic: the most frequent diagnoses were Alzheimer's disease (18%), Creutzfeldt-Jakob disease (12%) and inflammatory disorders (9%). Other diagnoses in individual patients included Pick's disease, corticobasal degeneration and other tauopathies, Lewy body dementia, multiple sclerosis, Whipple's disease, progressive multifocal leucoencephalopathy, cerebral autosomal dominant arteriopathy with subcortical ischaemic leucoencephalopathy, vasculopathies and paraneoplastic encephalopathy. The most frequent biopsy finding in the non-diagnostic group and for the series as a whole (37%) was non-specific gliosis variably affecting both cortex and white matter. Complications (11%) included seizures, intracranial and wound infections, and intracranial haemorrhage; there were no deaths or lasting neurological sequelae attributable to the procedure. No trends in diagnostic yield or complication rate over the course of the series were identified. Information obtained at biopsy determined treatment in 11%. A raised cerebrospinal fluid cell count was the only robust predictor of a potentially treatable (inflammatory) process at biopsy. The constellation of behavioural change, raised CSF protein and matched oligoclonal bands in CSF and serum was associated with non-specific gliosis at biopsy. This series underlines the value of cerebral biopsy in the diagnosis of dementia, and suggests that certain clinical and laboratory features may be useful in guiding the decision to proceed to brain biopsy where a treatable disease cannot be excluded by other means.

Adolescent↗
PubMed2005

Knight's move thinking? Mild cognitive impairment in a chess player.

We report the case of a chess player with superior premorbid cognitive function who presented to the Cognitive Disorders clinic at the National Hospital for Neurology and Neurosurgery with a 2-year history of symptoms of possible memory loss. Initially the MRI scan appearance was within normal limits and his cognitive scores inside the normal range; subsequently his cognitive function deteriorated and he fulfilled criteria for Mild Cognitive Impairment (MCI) two years later. Unexpectedly he died of an unrelated illness seven months later and post mortem examination of the brain was carried out, revealing advanced Alzheimer's disease (CERAD definite and NIA-Regan Institute high likelihood). This case highlights the difficulties encountered in assessing patients with superior premorbid function in the early stages of Alzheimer's disease, and reveals the value of serial MRI and neuropsychological assessment in detecting and monitoring early neurodegenerative disease.

Aged↗
PubMed2005

Mapping the onset and progression of atrophy in familial frontotemporal lobar degeneration.

BACKGROUND: Frontotemporal lobar degeneration (FTLD) may be inherited as an autosomal dominant disease. Studying patients "at risk" for developing FTLD can provide insights into the earliest onset and evolution of the disease. METHOD: We carried out approximately annual clinical, MRI, and neuropsychological assessments on an asymptomatic 51 year old "at risk" family member from a family with FTLD associated with ubiquitin-positive and tau-negative inclusion bodies. We used non-linear (fluid) registration of serial MRI to determine areas undergoing significant regional atrophy at different stages of the disease. RESULTS: Over the first 26 months of the study, the patient remained asymptomatic, but subsequently developed progressive speech production difficulties, and latterly severe orofacial dyspraxia, dyscalculia, frontal executive impairment, and limb dyspraxia. Regional atrophy was present prior to the onset of symptoms, and was initially centred on the left dorsolateral prefrontal cortex and the left middle frontal gyrus. Latterly, there was increasing asymmetric left frontal and parietal atrophy. Imaging revealed excess and increasing global atrophy throughout the study. Neuropsychological evaluation revealed mild intellectual impairment prior to the onset of these clinical symptoms; frontal executive and left parietal impairment subsequently emerged, culminating in widespread cognitive impairment. Fluid registered MRI allowed the emerging atrophy patterns to be delineated. CONCLUSION: We have demonstrated the onset and progressive pattern of in vivo atrophy in familial FTLD using fluid registered MRI and correlated this with the clinical features. Fluid registered MRI may be a useful technique in assessing patterns of focal atrophy in vivo and demonstrating the progression of degenerative diseases.

Atrophy↗
PubMed2004

EEG abnormalities in frontotemporal lobar degeneration.

The EEG appearances in patients with frontotemporal lobar degeneration (FTLD) were compared with those in patients with Alzheimer disease (AD). EEG abnormalities were found in 61% of FTLD patients, with the degree of EEG abnormality increasing with dementia severity. There was no significant difference in the severity of EEG abnormality between the FTLD and AD patient groups. These data suggest a need for reappraisal of the role of the EEG in the diagnostic differentiation of FTLD from AD.

Alpha Rhythm↗
PubMed2004

Mirror writing, left-handedness, and leftward scripts.

This minireview concerns a new observation on mirror writing. An uncommon form of writing, mirror writing is seen among healthy individuals, but it can also follow a variety of neurological diseases; it is nearly always carried out with the left hand and is more easily undertaken by left-handers. We have found that a particularly high prevalence of left-handed mirror writing has been reported among those whose native languages are traditionally written in a leftward direction, including Chinese, Japanese, and Hebrew. Innate left-handers and those whose languages are written leftward thus share an unusual facility for left-handed mirror writing, an observation that may have implications for understanding hemisphere specialization in relation to handedness.

Dominance, Cerebral↗
PubMed2004

Pathological substrate for regional distribution of increased atrophy rates in progressive supranuclear palsy.

BACKGROUND: Most magnetic resonance imaging (MRI) studies of progressive supranuclear palsy (PSP) are cross-sectional and lack post mortem confirmation of the diagnosis. MRI features described previously in PSP correspond to regions of pathological involvement demonstrated in separate studies, but serial MRI with pathological follow up has not been undertaken. OBJECTIVE: To investigate whether regions of increased atrophy rates demonstrated in PSP during life using fluid registered serial MRI correspond with pathological findings in confirmed PSP. METHODS: A 59 year old male presented with a six month history of balance problems and dysarthria. He had a symmetrical, levodopa unresponsive akinetic-rigid syndrome with a vertical supranuclear gaze palsy. A clinical diagnosis of probable PSP was made. His disease progressed relentlessly and he died five years after onset. Two serial MRI scans undertaken during life were reviewed and fluid (non-linear) registration of the images carried out. Post mortem histopathological analysis of the brain was undertaken to definitively confirm the diagnosis and compare regional pathology with the serial imaging. RESULTS: Fluid registration demonstrated greatest rates of atrophy in the brainstem and frontal cortex, in keeping with the distribution of pathology seen at autopsy. CONCLUSION: Fluid registration of serial MRI allows the topography and rates of regional atrophy in PSP to be delineated in life. Atrophy patterns correlated well with regional pathological load. These observations suggest that serial MRI with registration may help differentiate PSP from clinically similar conditions and supports its use as a surrogate marker of disease progression.

Brain↗
PubMed2003

Transient ischaemic attacks are associated with increased rates of global cerebral atrophy.

OBJECTIVES: To determine whether patients presenting with a first transient ischaemic attack (TIA) subsequently show increased rates of brain atrophy compared with age matched controls; and to assess potential risk factors for brain atrophy in this group. METHODS: 60 patients with a first, isolated TIA and 26 age and sex matched controls were recruited. None had evidence of cognitive impairment. Vascular risk factors were treated appropriately. All subjects had volumetric imaging at the start of the study and one year later, when they were clinically reassessed. TIA patients also had serial dual echo brain imaging. Rates of whole brain atrophy were calculated from the registered volumetric scans, as was the incidence of new ischaemic lesions. In the TIA group, the degree of white matter disease was assessed. Atrophy rates and blood pressure were compared between patients and controls. RESULTS: 22 patients (37%) developed new "clinically silent" infarcts during follow up. The mean (SD) annualised percentage atrophy rate in the TIA group was significantly higher than in the controls, at 0.82 (0.39)% v 0.33 (0.3)% (p < 0.0001). In the TIA group, diastolic blood pressure (p = 0.004) and white matter disease severity (p < 0.001) were correlated with cerebral atrophy rate. Increased white matter disease was found in patients in whom new ischaemic lesions developed (p < 0.001). CONCLUSIONS: Patients presenting with a first TIA have excess global brain atrophy compared with age matched controls over the subsequent year. Increased atrophy rates following a TIA may be directly or indirectly related to increasing white matter disease and diastolic hypertension. Future studies should assess whether this atrophy inevitably leads to cognitive decline, and whether aggressive treatment of risk factors for cerebrovascular disease (particularly hypertension) after a TIA can influence outcome.

Aged↗
PubMed2003

Development of selective verbal memory impairment secondary to a left thalamic infarct: a longitudinal case study.

A 68 year old man suffered an acute dysphasic episode with persistent memory disturbance while taking part as a control in a longitudinal magnetic resonance imaging (MRI) study. A small new left thalamic infarct involving the mamillo-thalamic tract could be demonstrated on volumetric MRI, coinciding with the development of a selective verbal memory impairment. This suggests that lateralisation of cognitive processing of visual and verbal material exists at the thalamic as well as the cortical level. High resolution volumetric MRI may be helpful in demonstrating small subcortical infarcts that may not be seen using computed tomography or conventional MRI.

Aged↗
PubMed2003

The grasp and other primitive reflexes.

Primitive reflexes are typically present in childhood, suppressed during normal development, and may reappear with diseases of the brain, particularly those affecting the frontal lobes. In this review we discuss some historical aspects surrounding these reflexes, how they might be elicited and interpreted, and their potential clinical utility in modern neurological practice.

Brain Diseases↗