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Frontotemporal dementia is associated with considerable clinical, genetic and pathological heterogeneity. The objective of this study is to characterise the imaging signatures of the main FTD phenotypes along the ALS-FTD spectrum. A total of 100 participants underwent comprehensive multimodal neuroimaging, genetic testing and neuropsychological evaluation. Seven patients with behavioural variant FTD (bvFTD), 11 patients with non-fluent-variant primary progressive aphasia (nfvPPA), two patients with sematic-variant primary progressive aphasia(svPPA), 10 patients with amyotrophic lateral sclerosis and FTD carrying the C9orf72 hexanucleotide repeat (C9 + ALS-FTD), 10 patients with ALS-FTD without hexanucleotide repeats (C9-ALS-FTD), 20 ALS patients without behavioural or cognitive deficits (ALSnci) and 40 healthy controls (HC) were included in a prospective quantitative neuroimaging study. Phenotype-specific spatial patterns of pathology were identified along the ALS-FTD spectrum, highlighting a strikingly focal distribution of disease burden as opposed to global atrophy. Significant motor cortex and corticospinal tract degeneration was identified in both bvFTD and nfvPPA patients. C9-ALS-FTD patients exhibited widespread extramotor pathology and significant precentral gyrus atrophy compared to ALSnci patients. ROI analyses confirmed focal grey matter alterations in Broca's and Wernicke's area in language variant FTD cohorts. Our findings confirm that the clinical manifestations of FTD are underpinned by phenotype-specific patterns of white and grey matter degeneration.

Background Diagnostic uncertainty in ALS has serious management implications and delays recruitment into clinical trials. Emerging evidence of presymptomatic disease-burden provides the rationale to develop diagnostic applications based on the evaluation of in-vivo pathological patterns early in the disease. Objectives To outline and test a diagnostic classification approach based on an array of complementary imaging metrics in key disease-associated anatomical structures. Methods Data from 75 ALS patients and 75 healthy controls were randomly allocated in a ‘training’ and ‘validation’ cohort. Spatial masks were created for anatomical foci which best discriminate patients from controls in the ‘training sample’. In a virtual ‘brain biopsy’, data was then retrieved from these key disease-associated brain regions. White matter diffusivity indices, grey matter T1-signal intensity values and basal ganglia volumes were evaluated as predictor variables in a canonical discriminant function. Results Following predictor variable selection, a classification specificity of 85.5% and sensitivity of 89.1% was achieved in the training sample and 90% specificity and 90% sensitivity in the validation sample. Discussion This study evaluates disease-associated imaging measures in a dummy diagnostic application. Although larger samples will be required for robust validation, the study confirms the potential of multimodal quantitative imaging in future clinical applications., Graphical abstract Image 1, Highlights • Reliable diagnostic, monitoring and prognostic biomarkers are urgently in ALS. • Accurate diagnostic classification may be achieved based on MRI metrics. • Basal ganglia, grey and white matter indices were integrated in a diagnostic model. • 85.5% specificity and 89.1% sensitivity were achieved in the training sample. • 90% specificity and 90% sensitivity were achieved in the validation sample.

Frontotemporal dementia (FTD) phenotypes have distinctive and well-established cortical signatures, but their subcortical grey matter profiles are poorly characterised. The comprehensive characterisation of striatal and thalamic pathology along the ALS-FTD spectrum is particularly timely, as dysfunction of frontostriatal and cortico-thalamic networks contribute to phenotype-defining cognitive, behavioral, and motor deficits. Ten patients with behavioral-variant FTD, 11 patients with non-fluent-variant primary progressive aphasia, 5 patients with semantic-variant primary progressive aphasia, 14 ALS-FTD patients with C9orf72 hexanucleotide expansions, 12 ALS-FTD patients without hexanucleotide repeats, 36 ALS patients without cognitive impairment and 50 healthy controls were included in a prospective neuroimaging study. Striatal, thalamic, hippocampal and amygdala pathology was evaluated using volume measurements, density analyses and connectivity-based segmentation. Significant volume reductions were identified in the thalamus and putamen of non-fluent-variant PPA patients. Marked nucleus accumbens and hippocampal atrophy was observed in the behavioral-variant FTD cohort. Semantic-variant PPA patients only exhibited volumetric changes in the left hippocampus. C9-positive ALS-FTD patients showed preferential density reductions in thalamic sub-regions connected to motor and sensory cortical areas. C9-negative ALS-FTD patients exhibited striatal pathology in sub-regions projecting to rostral-motor and executive cortical areas. The bulk of striatal and thalamic pathology in non-fluent-variant PPA patients was identified in foci projecting to motor areas. Subcortical density alterations in svPPA patients were limited to basal ganglia regions with parietal projections. Striatal and thalamic changes in FTD exhibit selective, network-defined vulnerability patterns mirroring cortical pathology. Multi-modal cortico-basal imaging analyses confirm that the subcortical grey matter profiles of FTD phenotypes are just as distinct as their cortical signatures. Our findings support emerging concepts of network-wise degeneration, preferential circuit vulnerability and disease propagation along connectivity patterns.

Background\ud Motor Unit Number Index (MUNIX) is a neurophysiological measure that provides an index\ud of the number of lower motor neurons in a muscle. Its performance across centres in healthy\ud subjects and patients with Amyotrophic Lateral Sclerosis (ALS) has been established, but\ud inter-rater variability between multiple raters in one single subject has not been\ud investigated.\ud Objective\ud To assess reliability in a set of 6 muscles in a single subject among 12 examiners (6 experienced\ud with MUNIX, 6 less experienced) and to determine variables associated with variability\ud of measurements.\ud Methods\ud Twelve raters applied MUNIX in six different muscles (abductor pollicis brevis (APB),\ud abductor digiti minimi (ADM), biceps brachii (BB), tibialis anterior (TA), extensor dig. brevis\ud (EDB), abductor hallucis (AH)) twice in one single volunteer on consecutive days. All raters\ud visited at least one training course prior to measurements. Intra- and inter-rater variability as\ud determined by the coefficient of variation (COV) between different raters and their levels of\ud experience with MUNIX were compared.\ud Results\ud Mean intra-rater COV of MUNIX was 14.0% (±6.4) ranging from 5.8 (APB) to 30.3% (EDB).\ud Mean inter-rater COV was 18.1 (±5.4) ranging from 8.0 (BB) to 31.7 (AH). No significant differences\ud of variability between experienced and less experienced raters were detected.\ud Conclusion\ud We provide evidence that quality control for neurophysiological methods can be performed\ud with similar standards as in laboratory medicine. Intra- and inter-rater variability of MUNIX is\ud muscle-dependent and mainly below 20%. Experienced neurophysiologists can easily\ud adopt MUNIX and adequate teaching ensures reliable utilization of this method.

Introduction The incidence of neurosyphilis has declined markedly since the introduction of penicillin therapy. While there are a number of case reports in the literature of neurosyphilis causing focal decreased 18F-fluorodeoxyglucose uptake on positron emission tomography/computed tomography scans, to the best of our knowledge this is the first published report of neurosyphilis presenting with intensely increased 18F-fluorodeoxyglucose uptake in the hippocampus. Case presentation A 55-year-old Caucasian man presented to our facility with acute collapse against a background of memory difficulties over the previous six months. The results of his initial physical examination were normal. He scored 24 out of 30 on the Montreal Cognitive Assessment test. A magnetic resonance imaging scan of his brain revealed high T2 signal intensity and atrophy within the right frontal area in addition to high T2 signal intensity in the bilateral mesial temporal areas. Blood and cerebrospinal fluid analysis revealed an active syphilis infection. An 18F-fluorodeoxyglucose positron emission tomography brain scan showed intensely increased 18F-fluorodeoxyglucose uptake limited to the head of the right hippocampus. He responded to penicillin treatment with an improvement in his cognition, which was further reflected in a complete resolution of the findings previously seen on magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography scans. Conclusions Diagnosis of neurosyphilis can be difficult, as many patients are either asymptomatic or present with non-specific symptoms such as memory disturbance or seizures. This report highlights the importance of considering neurosyphilis in the differential diagnosis when mesiotemporal changes are seen on magnetic resonance imaging or 18F-fluorodeoxyglucose positron emission tomography scans.

The authors report a 19-year-old woman who developed convulsions preceded by nasal ingestion of a cocaine mimic named 'the bubble' or mephedrone, obtained legally from a 'headshop' in Dublin. Characteristic posterior white matter oedema on brain imaging after the seizure suggested a diagnosis of posterior reversible encephalopathy syndrome (PRES). While PRES has been rarely associated with cocaine ingestion, this is the first report of an association with mephedrone.