Introduction. Fronto-temporal dementias (FTD) were described a century ago on the macroscopic basis of frontal and/or temporal lobe atrophy. Progress in ne uropathology, immunohistochemistry, biochemistry and genetics...Introduction. Fronto-temporal dementias (FTD) were described a century ago on the macroscopic basis of frontal and/or temporal lobe atrophy. Progress in ne uropathology, immunohistochemistry, biochemistry and genetics has since shown th at they are heterogeneous entities, encompassing many different diseases with si milar clinical presentations. A few, such as tauopathies due to mutations of the gene coding for tau protein (MAPτ .form a well-defined group. Definition and grouping of other types of FTD is still problematic. Material and method. We st udied a family where the mother and 4/8 children were affected with FTD. Clinica l presentation was typical of FTD. Onset was ill-defined with early (at age 40 years or less) personality changes. The clinical course was protracted (about 3 0 years). For a long period, the patients were able to live in the community in spite of obvious signs such as hyperorality and loss of verbal initiative; opera tive orientation as to place was preserved for a long time: a mute patient was s till able to drive. Signs of extrapyramidal or motoneuron involvement were not o bserved. Results. The genetic study failed to detect any mutation in MAPτ ; the lod score for flanking markers was positive but not significant. Biochemical st udy showed no qualitative abnormality in tau protein. Neuropathological study of one affected subject showed brain atrophy (962g), with elective frontal lobe in volvement. Cortical nerve cell loss was more marked in superficial layers and in frontal areas; glia was inconspicuous; pseudolaminar spongiosis was present in the more severely affected zones. No argentophilic “ Pick bodies” were seen; ubiquitin-positive, tau-negative round inclusions were present in the cytopl asm of fascia dentata neurones. “ Tangles” were mostly restricted to the ento rhinal cortex, partly correlated with tau immunoreactivity, but better with ubiq uitin immunoreactivity. Large, ovoid or reniform, moderately dense, spongy, gran ular or filamentous argentophilic cytoplasmic nerve cell inclusions were observe d. They were ubiquitin-positive, but did not react with other antibodies, part icularly anti-tau. They were present in swollen nerve cells in the deeper cort ical layers but were most conspicuous in the brain stem: in the magnocellular re ticular nuclei (e.g. nucleus centralis pontis), in the pes pontis, in the inferi or olive and in motor nuclei, especially in the trigeminal motor nucleus. They w ere not associated with nerve cell loss, atrophy nor pycnosis. Cerebellar relay nuclei neurones were swollen, and their cytoplasm contained argentophilic filame nts. Conclusion. In our opinion, “ ubiquitinopath” would be non-specific an d “ Motor Neuron Disease-Inclusion Dementia” (MNDID) would not be satisfact ory as a diagnosis for the present cases of FTD. Hopefully, progress in genetics may allow a causal, and thence definitive, classification.展开更多
文摘Introduction. Fronto-temporal dementias (FTD) were described a century ago on the macroscopic basis of frontal and/or temporal lobe atrophy. Progress in ne uropathology, immunohistochemistry, biochemistry and genetics has since shown th at they are heterogeneous entities, encompassing many different diseases with si milar clinical presentations. A few, such as tauopathies due to mutations of the gene coding for tau protein (MAPτ .form a well-defined group. Definition and grouping of other types of FTD is still problematic. Material and method. We st udied a family where the mother and 4/8 children were affected with FTD. Clinica l presentation was typical of FTD. Onset was ill-defined with early (at age 40 years or less) personality changes. The clinical course was protracted (about 3 0 years). For a long period, the patients were able to live in the community in spite of obvious signs such as hyperorality and loss of verbal initiative; opera tive orientation as to place was preserved for a long time: a mute patient was s till able to drive. Signs of extrapyramidal or motoneuron involvement were not o bserved. Results. The genetic study failed to detect any mutation in MAPτ ; the lod score for flanking markers was positive but not significant. Biochemical st udy showed no qualitative abnormality in tau protein. Neuropathological study of one affected subject showed brain atrophy (962g), with elective frontal lobe in volvement. Cortical nerve cell loss was more marked in superficial layers and in frontal areas; glia was inconspicuous; pseudolaminar spongiosis was present in the more severely affected zones. No argentophilic “ Pick bodies” were seen; ubiquitin-positive, tau-negative round inclusions were present in the cytopl asm of fascia dentata neurones. “ Tangles” were mostly restricted to the ento rhinal cortex, partly correlated with tau immunoreactivity, but better with ubiq uitin immunoreactivity. Large, ovoid or reniform, moderately dense, spongy, gran ular or filamentous argentophilic cytoplasmic nerve cell inclusions were observe d. They were ubiquitin-positive, but did not react with other antibodies, part icularly anti-tau. They were present in swollen nerve cells in the deeper cort ical layers but were most conspicuous in the brain stem: in the magnocellular re ticular nuclei (e.g. nucleus centralis pontis), in the pes pontis, in the inferi or olive and in motor nuclei, especially in the trigeminal motor nucleus. They w ere not associated with nerve cell loss, atrophy nor pycnosis. Cerebellar relay nuclei neurones were swollen, and their cytoplasm contained argentophilic filame nts. Conclusion. In our opinion, “ ubiquitinopath” would be non-specific an d “ Motor Neuron Disease-Inclusion Dementia” (MNDID) would not be satisfact ory as a diagnosis for the present cases of FTD. Hopefully, progress in genetics may allow a causal, and thence definitive, classification.
