Frontotemporal dementia with cerebral intraneuronal ubiquitin-positive inclusions but lacking lower motor neuron involvement

Yaguchi, Masamitsu; Okamoto, Koichi; Nakazato, Yoichi

doi:10.1007/s00401-002-0611-z

Cited by 11 publications

(6 citation statements)

References 18 publications

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“…A key finding was that, in many situations, the pathological features of FTD can be predicted in life. Thus, all patients with the syndrome of FTD‐MND in life had ubiquitin‐positive FTD‐MND pathology at postmortem examination 26–28. Similarly, when clinical criteria for CBD had been fulfilled, tau‐positive CBD pathology was overwhelmingly likely.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological correlates in frontotemporal dementia

Hodges

Davies

Xuereb

et al. 2004

Annals of Neurology

536

382

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The term frontotemporal dementia (FTD) encompasses a range of clinical syndromes that are believed not to map reliably onto the spectrum of recognized pathologies. This study reexamines the relationships between clinical and pathological subtypes of FTD in a large series from two centers (n = 61). Clinical subtypes defined were behavioral variant FTD (n = 26), language variants (semantic dementia, n = 9; and progressive nonfluent aphasia, n = 8), and motor variants (corticobasal degeneration, n = 9; and motor neuron disease, n = 9), although most cases presented with a combination of behavioral and language problems. Unexpectedly, some behavioral cases (n = 5) had marked amnesia at presentation. The pathological subtypes were those with tau-immunopositive inclusions (with Pick bodies, n = 20; or without, n = 11), those with ubiquitin immunopositive inclusions (n = 16), and those lacking distinctive histology (n = 14). Behavioral symptoms and semantic dementia were associated with a range of pathologies. In contrast, other clinical phenotypes had relatively uniform underlying pathologies: motor neuron disease predicted ubiquitinated inclusions, parkinsonism and apraxia predicted corticobasal pathology, and nonfluent aphasia predicted Pick bodies. Therefore, the pathological substrate can be predicted in a significant proportion of FTD patients, which has important implications for studies targeting mechanistic treatments.

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Section: Discussionmentioning

confidence: 99%

Clinicopathological correlates in frontotemporal dementia

Hodges

Davies

Xuereb

et al. 2004

Annals of Neurology

536

382

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“…13,15 UI were reported in some cases of dementia of the frontal lobe type, 51 and FTD with pyramidal tract degeneration lacking lower motor neuron involvement. 52 Minimum or sparse involvement of the upper and lower motor neurons with pronounced frontotemporal degeneration showing UI was reported as motor neuron disease-inclusion dementia, 26,53 primary progressive aphasia, 54 semantic dementia, 55 and motor neuron disease-inclusion dementia presenting as cortico-basal ganglionic degeneration. 56 Although detailed examination of the motor neuron system, including the spinal cord by ubiquitin immunohistochemistry and by checking the presence or absence of Bunina bodies, may reveal some motor neuron involvement in these other dementias, 57 it is thought that various combinations of lesion distribution and severity in the frontotemporal lobe and motor neuron system can develop in cases of ALS-D. 58 Distribution and density differed between UI and UN in our 28 studied cases: many UI were found in 20 of our 21 typical ALS-D cases, [9][10][11] numerous UN despite a smaller number of UI in only two cases (case 21 of ALS-D and case 28 of AP), 25 and UI and UN were seen not only in the frontotemporal cortices, including the precentral gyrus, but also in the putamen and caudate with high density in atypical ALS (cases 22 and 25-27) and PLS (cases 23 and 24).…”

Section: Discussionmentioning

confidence: 99%

“…Motor neuron disease with mild involvement of the frontotemporal cortices with UI was diagnosed as ALS without dementia 13,15 . UI were reported in some cases of dementia of the frontal lobe type, 51 and FTD with pyramidal tract degeneration lacking lower motor neuron involvement 52 . Minimum or sparse involvement of the upper and lower motor neurons with pronounced frontotemporal degeneration showing UI was reported as motor neuron disease‐inclusion dementia, 26,53 primary progressive aphasia, 54 semantic dementia, 55 and motor neuron disease‐inclusion dementia presenting as cortico‐basal ganglionic degeneration 56 .…”

Section: Discussionmentioning

confidence: 99%

Amyotrophic lateral sclerosis with dementia: The clinicopathological spectrum

Yoshida

2004

Neuropathology

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Amyotrophic lateral sclerosis with dementia (ALS-D) is a non-Alzheimer-type dementia characterized by both frontotemporal degeneration and motor neuron disease and marked by ubiquitin-positive, tau- and alpha-synuclein-negative intraneuronal inclusions and dystrophic neurites. New neuropathological diagnostic criteria for ALS-D are proposed on the basis of the present investigation of 28 autopsy cases. Clinical features included those of typical ALS-D, primary lateral sclerosis, atypical ALS with frontotemporal atrophy and atypical Pick's disease without Pick's bodies. Macroscopically anterior frontotemporal atrophy was observed involving or not involving the precentral gyrus. Microscopically non-specific neuronal loss and gliosis with spongiosis were seen, particularly in superficial layers II and III of the frontotemporal cortices. Diffuse fibrous gliosis was seen in the frontotemporal white matter. The substantia nigra and amygdala showed neuronal loss and gliosis. In all 28 cases, degeneration of both the lower and upper motor neuron systems, consistent with classic sporadic ALS, was present. The distribution and degree of degenerative frontotemporal lesions and motor neuron disturbance were of various patterns. Ubiquitin-positive and tau- and alpha-synuclein negative intraneuronal inclusions and dystrophic neurites in extramotor cortices were observed in all cases. Furthermore, ubiquitin-positive inclusions in lower motor neurons were found in all cases. The distribution pattern and density differed between neuronal inclusions and dystrophic neurites and correlated with clinicopathological phenotypes. Therefore, the ALS-D spectrum may be broader than that previously recognized, extending to primary lateral sclerosis, atypical ALS and to atypical Pick's disease without Pick bodies. Further investigation is needed to determine the characteristics of the ubiquitinated component in ALS-D.

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“…6 Recently, cases with motor neuron disease-inclusion dementia (MNDID), defined as FTD with similar inclusions but lacking clinicopathological evidence of motor neuron involvement, have been increasingly seen. [14][15][16][17] Relationships between classical MND, MND-D and MNDID as yet remain indistinct, but the inclusion formation suggests a link to the development of cognitive impairments.…”

Section: Discussionmentioning

confidence: 99%

“…However, it was speculated that the cognitive impairments in those cases might be either subclinical in the early stages of MND‐D, or undetectable in advanced stages of MND 6 . Recently, cases with motor neuron disease‐inclusion dementia (MNDID), defined as FTD with similar inclusions but lacking clinicopathological evidence of motor neuron involvement, have been increasingly seen 14–17 . Relationships between classical MND, MND‐D and MNDID as yet remain indistinct, but the inclusion formation suggests a link to the development of cognitive impairments.…”

Section: Discussionmentioning

confidence: 99%

Morphological differences of intraneuronal ubiquitin‐positive inclusions in the dentate gyrus and parahippocampal gyrus of motor neuron disease with dementia

Yaguchi

Fujita

Amari³

et al. 2004

Neuropathology

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Semiquantitative morphological analysis of cerebral intraneuronal ubiquitin-positive tau-negative inclusions, a pathologic marker for motor neuron disease with dementia (MND-D), was performed in the dentate gyrus and parahippocampal gyrus of 20 clinicopathologically confirmed patients with MND-D. The forms of the inclusions were tentatively classified into three types: (i) C-type, consisting of relatively large and intensely stained crescent or circular structures; (ii) L-type, showing fine linear structures around the nuclei; and (iii) G-type, showing faintly stained granular structures. The frequencies of the C-type, L-type and G-type was 0.5-9.3%,0.2-6.5% and 0-6.6% of dentate granule cells, respectively. In contrast to the dentate gyrus, almost all inclusions showed either the C-type or L-type form in the parahippocampal gyrus. A positive correlation was noted only between incidences of C-type inclusion of the dentate gyrus and that of the parahippocampal gyrus (r = 0.69, P < 0.05). The morphological differences of the inclusions probably reflect different stages of their formation.

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Frontotemporal dementia with cerebral intraneuronal ubiquitin-positive inclusions but lacking lower motor neuron involvement

Cited by 11 publications

References 18 publications

Clinicopathological correlates in frontotemporal dementia

Clinicopathological correlates in frontotemporal dementia

Amyotrophic lateral sclerosis with dementia: The clinicopathological spectrum

Morphological differences of intraneuronal ubiquitin‐positive inclusions in the dentate gyrus and parahippocampal gyrus of motor neuron disease with dementia

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