Dataset Information

In vivo signatures of nonfluent/agrammatic primary progressive aphasia caused by FTLD pathology.

ABSTRACT:

Objective

To identify early cognitive and neuroimaging features of sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) caused by frontotemporal lobar degeneration (FTLD) subtypes.

Methods

We prospectively collected clinical, neuroimaging, and neuropathologic data in 11 patients with sporadic nfvPPA with FTLD-tau (nfvPPA-tau, n = 9) or FTLD-transactive response DNA binding protein pathology of 43 kD type A (nfvPPA-TDP, n = 2). We analyzed patterns of cognitive and gray matter (GM) and white matter (WM) atrophy at presentation in the whole group and in each pathologic subtype separately. We also considered longitudinal clinical data.

Results

At first evaluation, regardless of pathologic FTLD subtype, apraxia of speech (AOS) was the most common cognitive feature and atrophy involved the left posterior frontal lobe. Each pathologic subtype showed few distinctive features. At presentation, patients with nfvPPA-tau presented with mild to moderate AOS, mixed dysarthria with prominent hypokinetic features, clear agrammatism, and atrophy in the GM of the left posterior frontal regions and in left frontal WM. While speech and language deficits were prominent early, within 3 years of symptom onset, all patients with nfvPPA-tau developed significant extrapyramidal motor signs. At presentation, patients with nfvPPA-TDP had severe AOS, dysarthria with spastic features, mild agrammatism, and atrophy in left posterior frontal GM only. Selective mutism occurred early, when general neurologic examination only showed mild decrease in finger dexterity in the right hand.

Conclusions

Clinical features in sporadic nfvPPA caused by FTLD subtypes relate to neurodegeneration of GM and WM in frontal motor speech and language networks. We propose that early WM atrophy in nfvPPA is suggestive of FTLD-tau pathology while early selective GM loss might be indicative of FTLD-TDP.

SUBMITTER: Caso F

PROVIDER: S-EPMC3902758 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Publications

In vivo signatures of nonfluent/agrammatic primary progressive aphasia caused by FTLD pathology.

Caso Francesca F Mandelli Maria Luisa ML Henry Maya M Gesierich Benno B Bettcher Brianne M BM Ogar Jennifer J Filippi Massimo M Comi Giancarlo G Magnani Giuseppe G Sidhu Manu M Trojanowski John Q JQ Huang Eric J EJ Grinberg Lea T LT Miller Bruce L BL Dronkers Nina N Seeley William W WW Gorno-Tempini Maria Luisa ML

Neurology 20131218 3

<h4>Objective</h4>To identify early cognitive and neuroimaging features of sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) caused by frontotemporal lobar degeneration (FTLD) subtypes.<h4>Methods</h4>We prospectively collected clinical, neuroimaging, and neuropathologic data in 11 patients with sporadic nfvPPA with FTLD-tau (nfvPPA-tau, n = 9) or FTLD-transactive response DNA binding protein pathology of 43 kD type A (nfvPPA-TDP, n = 2). We analyzed patterns of cogni ...[more]

PMID: 24353332

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Project description:ImportanceWe provide novel evidence of specific clinical and neuroimaging features that may help for the in vivo prediction of underlying pathology in patients with nonfluent/agrammatic primary progressive aphasia (nfvPPA) and progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) proved by autopsy.ObjectiveTo characterize the neurological, cognitive, and neuroimaging features of patients with nfvPPA-in whom either PSP or CBD was eventually confirmed at autopsy-at initial presentation and at 1-year follow-up.Design, setting, and participantsA prospective longitudinal clinical-pathological study was conducted in a tertiary research clinic that specialized in cognitive disorders. Fourteen patients were evaluated between January 2002 and December 2014. Inclusion criteria for the study were a clinical diagnosis of nfvPPA; the availability of speech, language, and cognitive testing for at least 1 evaluation; magnetic resonance imaging within 6 months of initial evaluation; and a postmortem pathological diagnosis of PSP or CBD. Ten matched healthy control participants were also included.Main outcomes and measuresClinical, cognitive, and neuroimaging longitudinal data were analyzed to characterize the whole nfvPPA-4-repeat-tau group and identify differences between nfvPPA-PSP and nfvPPA-CBD both at presentation and longitudinally.ResultsPatient groups did not differ significantly in age, sex, or handedness (nfvPPA-PSP group: median [interquartile range (IQR)] age, 74 [67-76] years; 1 of 5 male [20%]; 1 of 5 left-handed [20%]; and nfvPPA-CBD group: mean [IQR] age, 65 [54-81] years; 3 of 9 male [33%]; 0 left-handed). Motor speech impairment and left frontal white matter atrophy were the most prominent common features. At presentation, dysarthria (Motor Speech Examination median [IQR] score: nfvPPA-PSP, 4 [2-7]; nfvPPA-CBD, 0 [0-4]; P = .02), depression (Geriatric Depression Scale median [IQR] score: nfvPPA-PSP, 19 [3-28]; nfvPPA-CBD, 4 [0-16]; P = .04), and relatively selective white matter atrophy were typical of the nfvPPA-PSP group, while greater gray matter atrophy and a trend toward greater sentence comprehension deficits (median [IQR] sentence comprehension correct: nfvPPA-PSP, 98% [80-100]; nfvPPA-CBD, 81% [65-98]; P = .08) were found in the nfvPPA-CBD group. At follow-up after 1 year, we observed no significant differences in any speech or language measures. Furthermore, atrophy in patients with PSP progressed within the subcortical/brainstem motor system generating greater oculomotors deficits and swallowing difficulty; atrophy in patients with CBD spread anteriorly in prefrontal regions consistent with their greater working memory impairment and development of behavioral symptoms.Conclusions and relevanceIn patients presenting with nfvPPA, presence of early severe dysarthria, relatively selective white matter atrophy at presentation, and a greater rate of change in the brainstem measured by longitudinal imaging may be useful for differentiating underlying PSP from CBD pathology during life.

Project description:ImportanceDespite being characterized as a disorder of language production, nonfluent/agrammatic variant primary progressive aphasia (nfvPPA) is frequently associated with auditory symptoms. However, to our knowledge, peripheral auditory function has not been defined in this condition.ObjectiveTo assess peripheral hearing function in individuals with nfvPPA compared with healthy older individuals and patients with Alzheimer disease (AD).Design, setting, and participantsThis cross-sectional single-center study was conducted at the Dementia Research Centre of University College London between August 2015 and July 2018. A consecutive cohort of patients with nfvPPA and patients with AD were compared with healthy control participants. No participant had substantial otological or cerebrovascular disease; all eligible patients fulfilling diagnostic criteria and able to comply with audiometry were included.Main outcomes and measuresWe measured mean threshold sound levels required to detect pure tones at frequencies of 500, 1000, 2000, 4000, and 6000 Hz in the left and right ears separately; these were used to generate better-ear mean and worse-ear mean composite hearing threshold scores and interaural difference scores for each participant. All analyses were adjusted for participant age.ResultsWe studied 19 patients with nfvPPA (9 female; mean [SD] age, 70.3 [9.0] years), 20 patients with AD (9 female; mean [SD] age, 69.4 [8.1] years) and 34 control participants (15 female; mean [SD] age, 66.7 [6.3] years). The patients with nfvPPA had significantly higher scores than control participants on better-ear mean scores (patients with nfvPPA: mean [SD], 36.3 [9.4] decibels [dB]; control participants: 28.9 [7.3] dB; age-adjusted difference, 5.7 [95% CI, 1.4-10.0] dB; P = .01) and worse-ear mean scores (patients with nfvPPA: 42.2 [11.5] dB; control participants: 31.7 [8.1] dB; age-adjusted difference, 8.5 [95% CI, 3.6-13.4] dB; P = .001). The patients with nfvPPA also had significantly higher better-ear mean scores than patients with AD (patients with AD: mean [SD] 31.1 [7.5] dB; age-adjusted difference, 4.8 [95% CI, 0.0-9.6] dB; P = .048) and worse-ear mean scores (patients with AD: mean [SD], 33.8 [8.2] dB; age-adjusted difference, 7.8 [95% CI, 2.4-13.2] dB; P = .005). The difference scores (worse-ear mean minus better-ear mean) were significantly higher in the patients with nfvPPA (mean [SD], 5.9 [5.2] dB) than control participants (mean [SD], 2.8 [2.2] dB; age-adjusted difference, 2.8 [95% CI, 0.9-4.7] dB; P = .004) and patients with AD (mean [SD], 2.8 [2.1] dB; age-adjusted difference, 3.0 [95% CI, 0.9-5.1] dB; P = .005).Conclusions and relevanceIn this study, patients with nfvPPA performed worse on pure-tone audiometry than healthy older individuals or patients with AD, and the difference was not attributable to age or general disease factors. Cases of nfvPPA were additionally associated with increased functional interaural audiometric asymmetry. These findings suggest conjoint peripheral afferent and more central regulatory auditory dysfunction in individuals with nfvPPA.

Project description:Crossed aphasia has been reported mainly as post-stroke aphasia resulting from brain damage ipsilateral to the dominant right hand. Here, we described a case of a crossed nonfluent/agrammatic primary progressive aphasia (nfvPPA), who developed a corticobasal syndrome (CBS). We collected clinical, cognitive, and neuroimaging data for four consecutive years from a 55-year-old right-handed lady (JV) presenting with speech disturbances. 18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) and DaT-scan with (123)I-Ioflupane were obtained. Functional MRI (fMRI) during a verb naming task was acquired to characterize patterns of language lateralization. Diffusion tensor MRI was used to evaluate white matter damage within the language network. At onset, JV presented with prominent speech output impairment and right frontal atrophy. After 3 years, language deficits worsened, with the occurrence of a mild agrammatism. The patient also developed a left-sided mild extrapyramidal bradykinetic-rigid syndrome. The clinical picture was suggestive of nfvPPA with mild left-sided extrapyramidal syndrome. At this time, voxel-wise SPM analyses of (18)F-FDG PET and structural MRI showed right greater than left frontal hypometabolism and damage, which included the Broca's area. DaT-scan showed a reduced uptake in the right striatum. FMRI during naming task demonstrated bilateral language activations, and tractography showed right superior longitudinal fasciculus (SLF) involvement. Over the following year, JV became mute and developed frank left-sided motor signs and symptoms, evolving into a CBS clinical picture. Brain atrophy worsened in frontal areas bilaterally, and extended to temporo-parietal regions, still with a right-sided asymmetry. Tractography showed an extension of damage to the left SLF and right inferior longitudinal fasciculus. We report a case of crossed nfvPPA followed longitudinally and studied with advanced neuroimaging techniques. The results highlight a complex interaction between individual premorbid developmental differences and the clinical phenotype.

Dataset Information

In vivo signatures of nonfluent/agrammatic primary progressive aphasia caused by FTLD pathology.

Objective

Methods

Results

Conclusions

Publications

In vivo signatures of nonfluent/agrammatic primary progressive aphasia caused by FTLD pathology.

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