We report a quantitative investigation of the visual identification and auditory comprehension deficits of 4 patients who had made a partial recovery from herpes simplex encephalitis. Clinical observations had suggested the selective impairment and selective preservation of certain categories of visual stimuli. In all 4 patients a significant discrepancy between their ability to identify inanimate objects and inability to identify living things and foods was demonstrated. In 2 patients it was possible to compare visual and verbal modalities and the same pattern of dissociation was observed in both. For 1 patient, comprehension of abstract words was significantly superior to comprehension of concrete words. Consistency of responses was recorded within a modality in contrast to a much lesser degree of consistency between modalities. We interpret our findings in terms of category specificity in the organization of meaning systems that are also modality specific semantic systems.

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The selective impairment of semantic memory is described in three patients with diffuse cerebrallesions. These patients, selected on the basis of a failure to recognize or identify common objects (agnosia for objects), were investigated in detail. In particular, their perceptual, language and memory functions were assessed, and the limits and properties of their recognition difficulties explored. It was found that knowledge of pictorial representations of objects, and of words, was impaired or impoverished, and in both instances knowledge of subordinate categories was more vulnerable than superordinate categories. Evidence is presented that this impairment of semantic memory cannot be accounted for by intellectual impairment, sensory or perceptual deficits, or expressive language disorder. The implications of damage to the semantic memory system for the operation of other cognitive systems, in particular short and long-term memory functions, are considered. Some tentative evidence for the structural basis for a hierarchically organized modality-specific semantic memory system is discussed.

We report a quantitative investigation of the visual identification and auditory comprehension deficits of 4 patients who had made a partial recovery from herpes simplex encephalitis. Clinical observations had suggested the selective impairment and selective preservation of certain categories of visual stimuli. In all 4 patients a significant discrepancy between their ability to identify inanimate objects and inability to identify living things and foods was demonstrated. In 2 patients it was possible to compare visual and verbal modalities and the same pattern of dissociation was observed in both. For 1 patient, comprehension of abstract words was significantly superior to comprehension of concrete words. Consistency of responses was recorded within a modality in contrast to a much lesser degree of consistency between modalities. We interpret our findings in terms of category specificity in the organization of meaning systems that are also modality specific semantic systems.

An expanded hexanucleotide repeat in the C9ORF72 gene has recently been identified as a major cause of familial frontotemporal lobar degeneration and motor neuron disease, including cases previously identified as linked to chromosome 9. Here we present a detailed retrospective clinical, neuroimaging and histopathological analysis of a C9ORF72 mutation case series in relation to other forms of genetically determined frontotemporal lobar degeneration ascertained at a specialist centre. Eighteen probands (19 cases in total) were identified, representing 35% of frontotemporal lobar degeneration cases with identified mutations, 36% of cases with clinical evidence of motor neuron disease and 7% of the entire cohort. Thirty-three per cent of these C9ORF72 cases had no identified relevant family history. Families showed wide variation in clinical onset (43–68 years) and duration (1.7–22 years). The most common presenting syndrome (comprising a half of cases) was behavioural variant frontotemporal dementia, however, there was substantial clinical heterogeneity across the C9ORF72 mutation cohort. Sixty per cent of cases developed clinical features consistent with motor neuron disease during the period of follow-up. Anxiety and agitation and memory impairment were prominent features (between a half to two-thirds of cases), and dominant parietal dysfunction was also frequent. Affected individuals showed variable magnetic resonance imaging findings; however, relative to healthy controls, the group as a whole showed extensive thinning of frontal, temporal and parietal cortices, subcortical grey matter atrophy including thalamus and cerebellum and involvement of long intrahemispheric, commissural and corticospinal tracts. The neuroimaging profile of the C9ORF72 expansion was significantly more symmetrical than progranulin mutations with significantly less temporal lobe involvement than microtubule-associated protein tau mutations. Neuropathological examination in six cases with C9ORF72 mutation from the frontotemporal lobar degeneration series identified histomorphological features consistent with either type A or B TAR DNA-binding protein-43 deposition; however, p62-positive (in excess of TAR DNA-binding protein-43 positive) neuronal cytoplasmic inclusions in hippocampus and cerebellum were a consistent feature of these cases, in contrast to the similar frequency of p62 and TAR DNA-binding protein-43 deposition in 53 control cases with frontotemporal lobar degeneration–TAR DNA-binding protein. These findings corroborate the clinical importance of the C9ORF72 mutation in frontotemporal lobar degeneration, delineate phenotypic and neuropathological features that could help to guide genetic testing, and suggest hypotheses for elucidating the neurobiology of a culprit subcortical network.