Jm Stevens

Quantitative MRI measurement of superior cerebellar peduncle in progressive supranuclear palsy

Background: Postmortem studies have shown atrophy of the superior cerebellar peduncle (SCP) to distinguish progressive supranuclear palsy (PSP) from other neurodegenerative diseases. It is not clear whether MRI-based measurements can differentiate this relative atrophy of the SCP during life. Methods: Volumetric MRI was acquired prospectively in 53 subjects: 19 with PSP, 10 with multiple system atrophy (MSA), 12 with Parkinson disease (PD), and 12 healthy controls. SCP volume was assessed by detailed quantitative volumetric measurement and independently by blinded visual rating of SCP atrophy. Results: The mean SCP volume, corrected for total intracranial volume, was lower in patients with PSP than controls (p < 0.001), patients with MSA (p = 0.001), and patients with PD (p = 0.003). There was an overlap between individual SCP volume measurements in the PSP subjects and the other groups. Neuroradiologic rating correctly identified PSP cases based on the presence of SCP atrophy with a sensitivity of 74% and a specificity of 94%. Conclusions: The authors propose that together with other radiologic features of progressive supranuclear palsy (PSP) such as midbrain atrophy, a visual assessment of the superior cerebellar peduncle may help increase the clinical diagnostic accuracy in PSP.

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.

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.

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.

Cerebral and cerebellar atrophy on serial magnetic resonance imaging in an initially symptom free subject at risk of familial prion disease.

Prion diseases are transmissible neurodegenerative conditions which occur in sporadic, acquired, or inherited forms. Sporadic Creutzfeldt-Jakob disease presents as a rapidly progressive dementia with myoclonus, most patients showing characteristic pseudoperiodic complexes on electroencephalography. A new variant of Creutzfeldt-Jakob is characterised by a younger age at onset, longer survival, and non-specific initial symptoms including behavioural changes, dysaesthesias, and ataxia but without the expected electroencephalographic changes.1 Some of these features are also found in 5-15% of all cases of the inherited forms of Creutzfeldt-Jakob disease and are associated with mutations in the prion protein gene.2 We report the case of a woman with a family history of prion disease in whom progressive cerebral and cerebellar atrophy was seen when two magnetic resonance scans were compared using registration. A 42 year old woman from a family with histologically confirmed prion disease entered …

Brain-water diffusion coefficients reflect the severity of inherited prion disease

Objective: Inherited prion diseases are progressive neurodegenerative conditions, characterized by cerebral spongiosis, gliosis, and neuronal loss, caused by mutations within the prion protein (PRNP) gene. We wished to assess the potential of diffusion-weighted MRI as a biomarker of disease severity in inherited prion diseases. Methods: Twenty-five subjects (mean age 45.2 years) with a known PRNP mutation including 19 symptomatic patients, 6 gene-positive asymptomatic subjects, and 7 controls (mean age 54.1 years) underwent conventional and diffusion-weighted MRI. An index of normalized brain volume (NBV) and region of interest (ROI) mean apparent diffusion coefficient (ADC) for the head of caudate, putamen, and pulvinar nuclei were recorded. ADC histograms were computed for whole brain (WB) and gray matter (GM) tissue fractions. Clinical assessment utilized standardized clinical scores. Mann-Whitney U test and regression analyses were performed. Results: Symptomatic patients exhibited an increased WB mean ADC (p = 0.006) and GM mean ADC (p = 0.024) compared to controls. Decreased NBV and increased mean ADC measures significantly correlated with clinical measures of disease severity. Using a stepwise multivariate regression procedure, GM mean ADC was an independent predictor of Clinicians Dementia Rating score (p = 0.001), Barthel Index of activities of daily living (p = 0.001), and Rankin disability score (p = 0.019). Conclusions: Brain volume loss in inherited prion diseases is accompanied by increased cerebral apparent diffusion coefficient (ADC), correlating with increased disease severity. The association between gray matter ADC and clinical neurologic status suggests this measure may prove a useful biomarker of disease activity in inherited prion diseases.

Cerebral achromatopsia as a presentation of Trousseau's syndrome.

A 67-year-old man developed a sudden onset of achromatopsia. Magnetic resonance imaging showed occipital lobe infarction. Repeated episodes of neurological deficit referable to the posterior circulation initially suggested an embolic source, but subsequently proved to be due to a coagulopathy related to a carcinoma of the bladder. This has implications for the management of patients presenting with achromatopsia, and progressive or recurrent neurological episodes, and in particular the use of anticoagulation in this situation.

Cerebral atrophy variation over short time intervals in transient ischaemic attack (TIA) patients

41 Missing data % Responders (seizure freedom) % Non-responders % Yes % No % Yes % No % Regular access to specialist services 15 18.3 81.6 34 66 Current depression 11.86 5.2 94 9.7 90.3 Seizures extremely bothersome 15.7 20 80 75 25 Receiving disability living allowance 15.9 6.7 93.4 21 79 ABN abstracts 1455