Semantic dementia associated with corticobasal syndrome: a further variant of frontotemporal lobe degeneration?

Abstract

The traditional clinical picture of corticobasal syndrome (CBS) is of a subcortical syndrome of akinesia and rigidity, combined with cortical features of limb apraxia and cortical sensory loss [1,2].In recent years, patients with 'cortical' deficits other than limb apraxia have been described, allowing delineation of ' cognitive' subtypes of CBS [3][4][5][6][7]. In particular, an association has been recognised between CBS and progressive nonfluent aphasia.The association between 'pure' semantic dementia and corticobasal syndrome is unusual. There is mention of a single case with corticobasal degeneration (CBD) pathology confirmed at autopsy who presented with word finding difficulty [5]. Formal exploration of semantic memory impairment and visual agnosia was not undertaken. Raggi et al. [8] reported the case of a 56-year-old woman who presented with behavioural disorder associated with fluent aphasia and mildly asymmetric (left [ right) melokinetic and ideomotor apraxia. The patient did not show the typical motor features of CBD and the authors could not exclude an atypical presentation of Alzheimer's disease [8].The patient presented here is worthy of note because her case shows, for the first time, the presence of a highly selective semantic breakdown, consistent with semantic dementia, combined with the neurological signs of CBS. The patient shows none of the features of nonfluent primary progressive aphasia that have hitherto been linked to CBS.Patient M, a 69-year-old right-handed Italian retired widow with 5 years of education came to neurological attention complaining of a 3-year history of progressive clumsiness associated with rigidity and pain in her left upper limb, and motor slowing. She had also noticed mild word finding problems. Aside from these problems, she was healthy with no previous neurological or medical illness of note. Family history was unremarkable.Neurological examination revealed a mild extrapyramidal syndrome, with hypomimia, bradykinesia and akinesia in her left upper limb. Mild cortical sensory loss was present in her left hand, evidenced by a difficulty recognising from touch objects that she could recognise from vision.Neuropsychological evaluation (Table 1) revealed deficits in two domains: gestural praxis and semantics.Structural imaging performed with MRI revealed prominent bitemporal atrophy more marked on the left (Fig. 1) together with mild biparietal atrophy. Cerebral SPECT was in keeping with the MRI scan and revealed hypometabolism in temporal (left \ right) and parietal lobes. A DAT scan showed reduced metabolism in the basal ganglia. Genetic screening for mutations in the progranulin gene was negative.We evaluated patient M at 6-month intervals over 2 years. Over that time, there was progression of her symptoms although the clinical picture remained qualitatively similar.

Atypical association of semantic dementia, corticobasal syndrome, and 4R tauopathy

“…Our patient's language was marked by confrontation naming deficits, corroborated by the very low BNT score and by our locally developed naming test. Moreover, his pattern of performance has been reported in a similar patient with SD and CBS (Luzzi et al, 2012). His score (25/40, 62%) was identical to our patient's on a locally developed picture naming test, and remained stable 2 years later (24/40).…”

“…Consistent with these findings is the known association of CBD with the other two clinical FTLD syndromes, progressive nonfluent aphasia and a behavioral variant of frontotemporal dementia (Kertesz et al, 2007;Kouri, Whitwell, Josephs, Rademakers, & Dickson, 2011;Murray et al, 2007;Rabinovici & Miller, 2010). Frontal behavioral manifestations are present in four of the reported SD-CBD cases (Ikeda et al, 1996;Mathuranath et al, 2000;McMonagle et al, 2006;Raggi et al, 2007), while abnormal performances on executive testing are reported in the fifth one (Luzzi et al, 2012). Our patient's language was marked by confrontation naming deficits, corroborated by the very low BNT score and by our locally developed naming test.…”

“…Infrequent cases of clinical MND are briefly mentioned (Hodges & Patterson, 2007;Ostberg & Bogdanovic, 2011). Some rare cases of concomitant SD and CBS/CBD have also been reported, though lacking neuropathological confirmation or detailed clinical description (Ikeda et al, 1996;Luzzi et al, 2012;McMonagle, Blair, & Kertesz, 2006;Raggi et al, 2007). One case of SD and neuropathological CBD, but without motor symptoms, has been published (Mathuranath, Xuereb, Bak, & Hodges, 2000).…”