The midbrain-to-pons ratio distinguishes progressive supranuclear palsy from non-fluent primary progressive aphasias.

BACKGROUND AND PURPOSE: To determine the clinical utility of the midbrain-to-pons (M/P) ratio as a clinical biomarker of progressive supranuclear palsy (PSP) in patients with non-fluent primary progressive aphasia syndromes. METHODS: Patients with PSP, progressive non-fluent aphasia (PNFA) and logopenic progressive aphasia (LPA) were recruited. Patients were diagnosed clinically, but pathological confirmation was available in a proportion of patients. Midbrain and pons areas were measured using Osirix Lite, a free DICOM viewer. The M/P ratio and Magnetic Resonance Parkinsonism Index were calculated and their diagnostic utility compared. RESULTS: A total of 72 participants were included (16 PSP, 18 PNFA, 16 LPA and 22 controls). Patients with PSP had motor features typical of the syndrome. Both the M/P ratio and Magnetic Resonance Parkinsonism Index differed significantly in PSP compared with controls. The M/P ratio was disproportionately reduced in PSP compared with PNFA and LPA (PSP, 0.182 ± 0.043; PNFA, 0.255 ± 0.034; LPA, 0.258 ± 0.033; controls, 0.292 ± 0.031; P < 0.001). An M/P ratio of ≤0.215 produced a positive predictive value of 77.8% for the diagnosis of PSP syndrome. Pathological examination revealed Alzheimer's disease in three cases (all LPA), pathological PSP in two cases (one clinical PSP and one PNFA) and corticobasal degeneration in one case (PNFA). The M/P ratio was ≤0.215 in both pathological cases of PSP. CONCLUSIONS: The M/P ratio was disproportionately reduced in PSP, suggesting its potential as a clinical marker of the PSP syndrome. Larger studies of pathologically confirmed cases are needed to establish the M/P ratio as a biomarker of PSP pathology.

Motor function and behaviour across the ALS-FTD spectrum.

BACKGROUND: Behavioural/functional disturbances, characteristic of frontotemporal dementia (FTD), are also a feature of amyotrophic lateral sclerosis (ALS) and patients with combined ALS and FTD (FTD-ALS). AIM OF THE STUDY: To investigate the progression of behavioural disturbances in ALS and FTD using the FTD functional rating scale (FTDFRS). METHODS: Patients with ALS, FTD-ALS and FTD were recruited from specialist clinics. Baseline assessments included the FTDFRS and the ALS functional rating scale-revised (ALSFRS-R). Baseline assessments were included, as were longitudinal assessments in a proportion of patients. RESULTS: In total, 21 ALS, 12 FTD-ALS and 14 behavioural variant FTD (bvFTD) patients were included in the study. Moderate or severe behavioural disturbance was common in patients with ALS at baseline (47.6%), although less frequent than in bvFTD patients; patients with FTD-ALS displayed intermediate impairment. The ALSFRS-R showed the opposite pattern and did not correlate with the FTDFRS. During the follow-up period, significant (P < 0.05) behavioural deterioration was demonstrated in patients with bvFTD and FTD-ALS, with a trend for decline in patients with ALS (P = 0.06). CONCLUSION: Motor disturbance is the primary marker of disease severity in ALS, but behavioural and functional impairment are common, and may decline independently of motor function. As such, the FTDFRS may provide valuable information in the assessment and monitoring of ALS.

Job variation in advanced training in adult neurology in Australia and New Zealand: a follow-up study.

BACKGROUND: Six years ago, a survey of Australian trainees in neurology highlighted several differences in the training offered by the various positions. There has been a subsequent increase in trainee numbers. AIM: This survey aimed to re-examine the workload and exposure provided by individual positions and to compare training in Australia and New Zealand. METHODS: A questionnaire was circulated in 2012 to all advanced trainees in core adult neurology positions in Australia and New Zealand, looking at ward work, outpatient clinics, neurophysiology exposure and on-call commitments. RESULTS: The response rate was 85.7%. There was a 48.7% increase in the number of core training positions in Australia, but an average increase in inpatient workload of 56%. General neurology clinic numbers were unchanged while specialist clinic exposure had risen from 1.0 to 1.8 clinics/week. In some cases, exposure to neurophysiology had fallen. The requirement for out-of-hours on-call had fallen. There were no major differences between positions in Australia and New Zealand. CONCLUSION: There have been significant improvements in advanced training in adult neurology in the 5 years between 2007 and 2012: numbers of trainees have increased, on-call commitments have fallen and exposure to specialist clinics has risen. However, inpatient workload has increased significantly, accompanied by a slight reduction in exposure to training in neurophysiology in some cases. Overall, the changes are encouraging, but more work is still needed to ensure that individual positions meet the training needs of trainees.

Utility of the Addenbrooke's Cognitive Examination III online calculator to differentiate the primary progressive aphasia variants.

The Addenbrooke's Cognitive Examination III is a brief cognitive screening tool that is widely used for the detection and monitoring of dementia. Recent findings suggest that the three variants of primary progressive aphasia can be distinguished based on their distinct profiles on the five subdomain scores of this test. Here, we investigated the utility of the Addenbrooke's Cognitive Examination III to differentiate the primary progressive aphasia variants based on their item-by-item performance profiles on this test. From these results, we created an interactive primary progressive aphasia Addenbrooke's Cognitive Examination III calculator which predicts the variant based on a patient's unique item-by-item profile. Twenty-eight logopenic variant, 25 non-fluent variant and 37 semantic variant primary progressive aphasia patients and 104 healthy controls completed the Addenbrooke's Cognitive Examination III at first clinical presentation. Multinomial regression analyses were conducted to establish performance profiles among groups, and R Shiny from RStudio was used to create the interactive Addenbrooke's Cognitive Examination III diagnostic calculator. To verify its accuracy, probability values of the regression model were derived based on a 5-fold cross-validation of cases. The calculator's accuracy was then verified in an independent sample of 17 logopenic, 19 non-fluent and 13 semantic variant primary progressive aphasia patients and 68 Alzheimer's disease patients who had completed the Addenbrooke's Cognitive Examination III (or an older version of this test: Revised) and had in vivo amyloid-PET imaging and/or brain autopsy pathological confirmation. Cross-validation of cases in the calculator model revealed different rates of sensitivity in classifying variants: semantic = 100%, non-fluent = 80.6% and logopenic = 79.9%; healthy controls were distinguished from primary progressive aphasia patients with 100% sensitivity. Verification of in vivo amyloid and/or autopsy-confirmed patients showed that the calculator correctly classified 10/13 (77%) semantic variant, 3/19 (16%) non-fluent variant and 4/17 (24%) logopenic variant patients. Importantly, for patients who were not classified, diagnostic probability values mostly pointed toward the correct clinical diagnosis. Furthermore, misclassified diagnoses of the primary progressive aphasia cohort were rare (1/49; 2%). Although 22 of the 68 Alzheimer's disease patients (32%) were misclassified with primary progressive aphasia, 19/22 were misclassified with the logopenic variant (i.e. falling within the same neuropathological entity). The Addenbrooke's Cognitive Examination III primary progressive aphasia diagnostic calculator demonstrates sound accuracy in differentiating the variants based on an item-by-item Addenbrooke's Cognitive Examination III profile. This calculator represents a new frontier in using data-driven approaches to differentiate the primary progressive aphasia variants.

Disability in atypical parkinsonian syndromes is more dependent on memory dysfunction than motor symptoms.

BACKGROUND: There is a gap in the systematic description and investigation of functional disability in corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). Additionally, the relations between disability, apraxia, cognitive and behavioural changes are not well understood in atypical parkinsonian syndromes. METHODS: Fifty patients were included in this study (CBS = 18; PSP = 11), including a subgroup of primary progressive aphasia-nonfluent variant (PPA-nfv = 21) who were used as a control group given the clinic-pathological overlap. Functional disability (basic and instrumental activities of daily living), general cognition and behavioural changes were evaluated at baseline, with a subgroup of patients being reassessed after 16 months. RESULTS: The corticobasal syndrome group had the most marked disability in basic activities in comparison to progressive supranuclear palsy and primary progressive aphasia-nonfluent variant. Longitudinal decline was marked for all three groups. In a linear regression examining factors behind functional disability in CBS and PSP, memory dysfunction emerged as the main factor (48.5%), followed by apraxia (14.9%) and atypical parkinsonian symptoms (9.6%). CONCLUSIONS: Memory dysfunction is the most important factor in functional disability in CBS and PSP, which has to be taken into consideration in disease management, prognosis and planning of services to fully address patients' and families' needs.

Saccadic abnormalities in frontotemporal dementia.

OBJECTIVE: To characterize saccadic eye movements, as a marker of decision-making processes, in frontotemporal dementia (FTD). METHODS: Saccadometry was performed on a cross-section of patients with FTD, using a portable saccadometer, and results compared to matched control subjects. We used the Linear Approach to Threshold with Ergodic Rate model to generate measures of decision-making speed and incidence of early saccades. Patterns of cortical atrophy were related to decision-making processes using voxel-based morphometry (VBM) analysis. RESULTS: A total of 45 subjects (22 FTD: 10 with behavioral variant FTD and 12 with primary progressive aphasia, and 23 controls) were studied. A measure of decision-making speed, µ, was reduced in FTD, resulting in prolonged saccadic latency, but the incidence of early saccades was increased compared to controls. In addition, performance on an antisaccade task was poor in FTD compared to controls. Decision-making speed and the incidence of early saccades were independently correlated with atrophy of the left frontal eye field, and decision-making speed also correlated with atrophy of the left cingulate eye field. CONCLUSION: Saccades are abnormal in FTD, reflecting reduced decision-making speed, and these abnormalities related to atrophy of the left frontal eye field. In addition, patients with FTD had an increased incidence of early saccades, which may be due to reduced inhibition of primitive responses.