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An abstract of the article "Distal Myopathy Secondary to A Mutation in Myotilin," by D. J. Dick, S. Hammans, and B. Udd is presented.

Background: Corticobasal degeneration (CBD) is a complex neurodegenerative disorder. Accurate diagnosis is increasingly important, with the advent of clinical trials of drugs aimed at modifying the underlying tau pathology. CBD often presents with a 'corticobasal syndrome' including impairments of movement and cognition. However, patients with similar corticobasal syndromes can have neurodegenerative pathologies that are not CBD. In addition, patients with CBD may present with aphasia or behavioural change. The clinical diversity of CBD and mimicry by non-CBD pathologies hinders accurate diagnosis., Methods: We applied the new consensus criteria of Armstrong and colleagues et al 1 to a cohort of patients with detailed longitudinal clinical evaluation and neuropathology., Results: In patients with pathologically confirmed CBD, accuracy of diagnosis was similar under the new and previous criteria: 9/19 (47%) met criteria for probable CBD at presentation, 13/19 (68%) at last clinical assessment. Patients with a corticobasal syndrome but without CBD pathology all (14/14) met the new diagnostic criteria of probable or possible CBD, demonstrating that the new criteria lacks the necessary specificity for an accurate ante mortem clinical diagnosis of CBD. None of the clinical features used in the new criteria were more common in the patients with CBD pathology (n=19) than without (n=14)., Conclusions: The Armstrong criteria usefully broadens the recognised clinical phenotype of CBD but does not sufficiently improve the specificity of diagnosis to increase the power of clinical trials or targeted applications of tau-based disease-modifying therapies. Further work is required to show whether biomarkers could be more effective than clinical signs in the diagnosis of CBD., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: Recent post-mortem studies indicate that 30-40% of patients with clinically diagnosed progressive aphasia (PA) have Alzheimer's disease pathology, while the remainder have pathology in the FTD spectrum. This study aimed to compare the clinical features of patients from these two groups., Materials and Methods: A retrospective chart review was conducted on 33 pathologically verified PA patients: n=13 AD and n=20 FTD-spectrum pathology. Demographics, global cognitive function, non-verbal memory, neuropsychiatric symptoms and structural imaging were compared between the two pathology-confirmed groups., Results: The median survival was 6.3 years in the FTD group versus 8.1 years in the AD group, in spite of the fact that onset for AD was on average 2.0 years older than FTD. Features highly specific in predicting FTD-spectrum pathology were age of onset before 60 years, preference for sweet food, disinhibition and focal knife-edge frontotemporal atrophy, although the sensitivity for each of these was remarkably low (highest sensitivity was 45% for disinhibition). Some clinical features hypothesised to distinguish AD from FTD-spectrum pathology, such as global functional impairment within 2 years of onset and poor non-verbal memory ability, were not useful in separating the two groups., Conclusions: If present, certain clinical and imaging features can help to identify PA with FTD-spectrum pathology, notably the presence of the neuropsychiatric features seen with behavioural presentations of FTD and knife-edge atrophy on structural imaging. The profile of non-linguistic cognitive deficits does not appear to be discriminatory, though prospective studies are needed to evaluate this issue further.

Objective: According to the existing viewpoint, Corticobasal degeneration (CBD) is thought of as a predominantly extrapyramidal motor disorder that is distinct and unrelated to frontotemporal dementia (FTD), the most common form of non-Alzheimer dementias. A lack of understanding of the aetiopathogenesis, and poor correlation between the pathology and the clinical syndromes, has resulted in a disparity in the classification of cases of non-Alzheimer dementias. This report intends to highlight the overlap between FTD and CBD in the light of the evolution of these terms, and to discuss the implications of these findings on the nosology of CBD and the classification of non-Alzheimer dementias., Methods and Results: Two cases who presented with cognitive dysfunction, which, on comprehensive neuropsychological testing warranted an antemortem diagnosis of FTD are reported. A detailed necropsy study of their brains, however, favoured a pathological diagnosis of CBD. The literature on the overlap between CBD and FTD is also reviewed., Conclusions: Firstly, evidence is emerging to suggest that the clear distinction drawn between FTD and CBD by the existing viewpoint, needs revision. Secondly, until such time that a comprehensive classification of non-Alzheimer dementias is evolved, it may be better to distinguish between the clinical and pathological levels of description and to classify cases, in vivo, on the basis of the clinical phenotype.

Objective: To correlate the degree of CAG repeat expansion with neuropathological findings in Huntington's disease., Methods: The CAG repeat polymorphism was analysed in a large series of brain samples from 268 patients with a clinical diagnosis of Huntington's disease in which full neuropathological data was available., Results: Analysis by polymerase chain reaction was successful in 63% of samples (169 of 268). Repeat expansions were detected in 152 of 153 (99%) samples with a neuropathological diagnosis of Huntington's disease. The exceptional case (22 CAG repeats) showed mild but definite pathological changes and had a typical clinical illness with a positive family history; it raises the possibility that an alternative mutation in the Huntington's disease gene may be responsible although it is more likely that a mutation in another gene has resulted in an Huntington's disease-like phenotype. Four of 16 cases without pathological changes of Huntington's disease also possessed an expanded repeat sequence; a glioblastoma masked the pathological changes of Huntington's disease in one case but the other three cases had a typical clinical history and a positive family history. These three cases may reliably be classified as Vonsattel's Huntington's disease grade 0. Three of 12 cases with a normal repeat length and no morphological changes of Huntington's disease showed other neuropathology; two had Alzheimer's disease and the other had multiple sclerosis. Review of the clinical notes of two other cases indicated a diagnosis of tardive dyskinesia complicating phenothiazine treatment of schizophrenia. The remaining pathology negative/expansion negative cases had been referred because of a family history of Huntington's disease; all but one were themselves symptom free. Apart from emphasising the possibility that an alternative mutation may result in a clinical phenocopy of Huntington's disease, this case suggests that such a clinical phenocopy may occur without gross or light microscopical neuropathological changes (Vonsattel's Huntington's disease grade 0)., Conclusions: The study confirms the value of molecular genetic analysis in cases of suspected Huntington's disease and shows the importance of detailed neuropathological study in the few cases of suspected Huntington's disease with normal CAG repeat lengths.

A patient with a spontaneously thrombosed arteriovenous malformation (AVM) presented with epilepsy. The CT and MRI appearances were of an intrinsic cerebral neoplasm with extensive surrounding vasogenic cerebral oedema and a mass effect. Histopathology confirmed a large thrombosed AVM. The natural history of AVMs and spontaneous thrombosis are reviewed.