The applause sign in frontotemporal lobar degeneration and related conditions

Journal of Neurology - The applause sign, i.e., the inability to execute the same amount of claps as performed by the examiner, was originally reported as a sign specific for progressive...     

The applause sign and neuropsychological profile in progressive supranuclear palsy and Parkinson's disease

Background

The applause sign has been associated with various neurodegenerative diseases. We investigate its validity in the differential diagnosis of progressive supranuclear palsy and Parkinson's disease, and its relationship with neuropsychological tests.

Patients and methods

23 patients with progressive supranuclear palsy and 106 patients with Parkinson's disease were included and administered the following scales: progressive supranuclear palsy rating scale, unified Parkinson's disease rating scale (UPDRS), mini-mental state examination (MMSE), frontal assessment battery (FAB), neuropsychiatric inventory and three-clap test.

Results

73.9% with progressive supranuclear palsy and 21.7% with Parkinson's disease showed a positive applause sign. Only a positive applause sign, UPDRS II score and disease duration were found to be predictors of progressive supranuclear palsy. Both patient-groups showed statistically significant correlations between the applause sign and neuropsychological tests: in progressive supranuclear palsy patients MMSE correlation coefficient: 0.62 (p: 0.002) and FAB correlation coefficient: 0.48 (p: 0.02), and in Parkinson's disease patients MMSE correlation coefficient: 0.47 (p < 0.001) and FAB correlation coefficient: 0.43 (p < 0.001). Verbal fluency and inhibitory control (FAB) and writing and orientation in time (MMSE) discriminated between patients with normal and positive applause sign.

Conclusions

A positive applause sign is not specific to progressive supranuclear palsy and may also be observed in Parkinson's disease patients with altered cognition, and it's related to cortical frontal abnormalities such as language disorders and inhibitory control.     

Visuospatial ability in cortical dementia

The level and pattern of visuospatial ability were comparatively examined in patients with putative cortical dementia (CD) and acute right hemisphere (RH) injury. Visuospatial ability was evaluated using measures of block construction, spatial reasoning, hemispatial search, and visuoconstructive copy. The incidence of neglect was also determined using special index measures derived from the spatial tasks. There was no difference between the CD and RH groups on measures of block construction, visuoconstructive copy, and spatial reasoning. While the overall incidence and severity of neglect was generally equivalent between the two clinical groups, 50% of the CD patients exhibited a pattern of right spatial neglect. In addition, a strong relationship was not evident between neglect laterality in CD and corresponding asymmetric cognitive and sensory-perceptual compromise, suggesting that neglect in CD may be due to different mechanisms than those causing neglect following right hemisphere injury. The findings indicate that while patients with putative CD perform like individuals with recent right hemisphere injury with respect to mean level of visuospatial ability, many exhibit a differential pattern of compromise related to the laterality of visuospatial neglect. The relevance of these results for the clinical diagnosis of CD is discussed.     

The concept of subcortical and cortical dementia: another look

The subcortical dementias such as progressive supranuclear palsy, Huntington's disease, and Parkinson's disease are said to be characterized by the presence of slowed mentation, apathy, and the absence of aphasia, agnosia, and apraxia, symptoms that are claimed to be more common in cortical dementias such as Alzheimer's disease. Conceptual problems (such as vagueness of terms and difficulties with symptom definition) and methodological problems (such as improper matching of comparison groups and inadequate assessment techniques) found in currently available studies require a reappraisal of this classification of dementias into cortical and subcortical forms. A review of recent clinical, neuropathological, and neurochemical studies offers little support for this classification system, although adequate systematic studies have not been performed.     

Altered speech-related cortical network in frontotemporal dementia

BackgroundIn healthy subjects (HS), transcranial magnetic stimulation (TMS) demonstrated an increase in motor-evoked potential (MEP) amplitudes during specific linguistic tasks. This finding indicates functional connections between speech-related cortical areas and the dominant primary motor cortex (M1).ObjectiveTo investigate M1 function with TMS and the speech-related cortical network with neuroimaging measures in frontotemporal dementia (FTD), including the non-fluent variant of primary progressive aphasia (nfv-PPA) and the behavioral variant of FTD (bv-FTD).MethodsM1 excitability changes during specific linguistc tasks were examined using TMS in 24 patients (15 with nfv-PPA and 9 with bv-FTD) and in 18 age-matched HS. In the same patients neuroimaging was used to assess changes in specific white matter (WM) bundles and grey matter (GM) regions involved in language processing, with diffusion tensor imaging (DTI) and voxel-based morphometry (VBM).ResultsDuring the linguistic task, M1 excitability increased in HS, whereas in FTD patients it did not. M1 excitability changes were comparable in nfv-PPA and bv-FTD. DTI revealed decreased fractional anisotropy in the superior and inferior longitudinal and uncinate fasciculi. Moreover, VBM disclosed GM volume loss in the left frontal operculum though not in the parietal operculum or precentral gyrus. Furthermore, WM and GM changes were comparable in nfv-PPA and bv-FTD. There was no correlation between neurophysiological and neuroimaging changes in FTD. Atrophy in the left frontal operculum correlated with linguistic dysfunction, assessed by semantic and phonemic fluency tests.ConclusionWe provide converging neurophysiological and neuroimaging evidence of abnormal speech-related cortical network activation in FTD.     

Complex visual hallucination and mirror sign in posterior cortical atrophy

Objective: In posterior cortical atrophy (PCA), visual hallucinations are rare symptoms and mirror sign has not been described. Method: Single case report. Results: We reported a 60‐year‐old woman with PCA who reported complex visual hallucinations, such as a man walking in her room, and mirror sign, which was the perception of a stranger staring at her when she looked into a mirror. She could not recognize images of herself in the mirror correctly, although she could recognize that a person standing next to her and the images of that person reflected in the mirror were the same person. Conclusion: Early complex visual hallucinations in this patient appeared to be more characteristic of dementia with Lewy body than Alzheimer's disease (AD). It is hard to explain mirror sign in this patient as being because of either prosopagnosia, Balint's syndrome or advanced AD. This patient may have other underlying cognitive dysfunction.     

The neuropsychological profile of alcohol-related dementia suggests cortical and subcortical pathology

The neuropathology associated with chronic alcohol abuse varies across studies, though research suggests generalized reductions in cortical and subcortical grey and white matter. Neuropsychological findings also differ within the literature. The inconsistent findings with respect to the neuropathology and neurobehavior of patients with histories of alcohol abuse may be due, at least in part, to differing nosology and the highly variable inclusion/exclusion criteria employed by researchers. Oslin et al. [Int J Geriatr Psychiatry 1998;13:203-212] have proposed and recently validated specific criteria for probable alcohol-related dementia (ARD). We were interested in comparing the neuropsychological profile of ARD patients with the neurocognitive profiles of typical cortical and subcortical dementia patients. Participants included 14 ARD patients, 15 patients diagnosed with Alzheimer's disease (AD), 13 patients diagnosed with subcortical vascular dementia (VaD), and 20 normal controls. Patient subgroups were similar with respect to age (mean = 79), education (mean = 12 years) and dementia severity (MMSE; mean = 22.1). The three dementia patient subgroups demonstrated significantly worse performance than the normal controls subgroup on all neuropsychological tests. The ARD subgroup exhibited very similar executive control deficits to VaD patients. However, the different neurocognitive profiles of the patient subgroups suggest that ARD patients may also, in fact, demonstrate some degree of amnesia given that they perform slightly worse than subcortical patients on delayed verbal free recall and recognition. Nonetheless, the ARD patients did not display as severe impairment as the AD patients on the memory tasks. No significant differences between the three patient groups were identified on language tests. In sum, we present preliminary evidence of a distinct neuropsychological profile for ARD patients that includes impairment on both executive control and memory tests. This pattern of performance suggests that long-term alcohol abuse, in comparison to AD and VaD, may be associated with both cortical and subcortical neuropathology.     

White matter hyperintensities and cortical acetylcholinesterase activity in parkinsonian dementia

OBJECTIVE: To investigate the relationship between the severity of white matter hyperintensities (WMH) and cortical acetylcholinesterase (AChE) activity in parkinsonian dementia (PDem). METHODS: PDem (n = 11) and control subjects (n = 14) underwent [11C]methyl-4-piperidinyl propionate (11C-PMP) AChE brain positron emission tomography and magnetic resonance (MR) imaging. Presence of WMH on proton density and T2 MR images was scored using a modified version of the semi-quantitative rating scale by Scheltens et al. [J Neurol Sci114 (1993)]. RESULTS: Analysis demonstrated significantly lower mean cortical (11)C-PMP k3 hydrolysis rates in PDem (-19.9%) when compared with control subjects (P < 0.0001). PDem subjects had higher mean severity of WMH (+20.1%) when compared with control subjects (P < 0.05). When WMH severity was entered into the analysis of variance model, there was no significant co-variate effect on cortical AChE activity (F = 0.24, ns). CONCLUSIONS: The concomitant presence of mild to moderate WMH in patients with PDem does not have a significant effect on cortical AChE activity.     

Ultrastructural and histochemical studies of cortical biopsies in subacute dementia

Summary The electron microscopic and histochemical findings in biopsies of two cases of subacute dementia have revealed neurons containing numerous lipofuscin bodies and increased acid phosphatase. Although these changes are considered to indicate neuron disease, they are believed to represent a secondary process because of their similarity and because other more distinctive cell alterations are present. In the first case, the primary abnormality is believed to be thickening of the vascular basement membrane, while in the second case, astroglial dilatation is considered a primary change. Since these structures appear to have important transport functions, these abnormalities could easily impair the nutrient supply to neurons and, in this way, produce the neuronal alteration. The significance of glycogen in these tissues is discussed.This work was supported by grant (NB-04161-04) from the National Institute of Neurological Diseases and Blindness of the National Institutes of Health.     

Adult-onset Hallervorden-Spatz syndrome presenting as cortical dementia

The authors examined behavioral and pathophysiologic substrates in a patient with adult-onset Hallervorden-Spatz syndrome who presented with insidious cognitive decline but no motor impairment. The authors combined longitudinal case history and serial neuropsychologic testing with functional neuroimaging (positron emission tomography), structural neuroimaging (magnetic resonance imaging), and brain tissue analyses. Serial assessments of a 29-year-old woman showed progressive dementia. Marked cognitive and behavioral deficits were seen on neuropsychologic testing, corresponding to striking cortical abnormalities on positron emission tomography, magnetic resonance imaging, and histopathologic studies. Typical motor manifestations of the disorder did not emerge until the patient was 34 years old, 5 years after the onset of cognitive symptoms. Hallervorden-Spatz syndrome should be considered in the differential diagnosis of progressive cortical dementia in a young adult, even in the absence of motor dysfunction.     

Neuropsychology of cortical versus subcortical dementia syndromes

Neuropsychological studies have shown that there are several prominent differences in the patterns of cognitive deficits that occur in neurodegenerative disorders that have their primary etiology in either cortical or subcortical brain dysfunction. Quantitative and qualitative differences are apparent across many cognitive domains, including memory (in all its aspects), attention, executive functions, language and semantic knowledge, and visuospatial abilities. These distinct patterns of deficits have been broadly characterized as forming cortical and subcortical dementia syndromes. Differentiating between cortical and subcortical dementia provides a heuristically useful model for understanding brain-behavior relationships in neurodegenerative diseases and may improve the ability to clinically distinguish among various dementing disorders.     

White matter integrity and cortical metabolic associations in aging and dementia

BackgroundStudies show that white matter hyperintensities, regardless of location, primarily affect frontal lobe metabolism and function. This report investigated how regional white matter integrity (measured as fractional anisotropy [FA]) relates to brain metabolism, to unravel the complex relationship between white matter changes and brain metabolism.ObjectiveTo elucidate the relationship between white matter integrity and gray matter metabolism using diffusion tensor imaging and fluorodeoxyglucose-positron emission tomography in a cohort of 16 subjects ranging from normal to demented (age, >55 years).MethodsMean FA values from white matter regions underlying the medial prefrontal, inferior-lateral prefrontal, parietal association, and posterior temporal areas and the corpus callosum were regressed with glucose metabolism (by positron emission tomography), using statistical parametric mapping (P < 0.005; voxel cluster, >100). Regional cerebral glucose metabolism was the primary outcome measure. According to our hypothesis, those hypometabolic cortical regions affected by Alzheimer's disease would correlate with a lower FA of associated tracks.ResultsOur data show inter-regional positive correlations between FA and gray matter metabolism for the prefrontal cortex, temporal, and parietal regions. Our results suggest that left prefrontal FA is associated with left temporal and parietal metabolism. Further, left posterior temporal FA correlated with left prefrontal metabolism. Finally, bilateral parietal FA correlated with bilateral temporal metabolism.ConclusionsThese regions are associated with cognitive processes affected in Alzheimer's disease and cerebrovascular disease, suggesting a link with white matter degeneration and gray matter hypometabolism. Therefore, cortical function and white matter degeneration are related in aging and dementia.     

Presenile dementia diagnosed as posterior cortical atrophy

Posterior cortical atrophy (PCA) was originally proposed in 1988 based on five cases of dementia presenting characteristic clinical symptoms. The concept of PCA is still not generally accepted. Herein, we present a case of a presenile female with PCA. A 57‐year‐old woman was brought to the hospital by her older sister. The patient's chief complaints were that she could not drive a car safely and had caused numerous traffic accidents. Construction apraxia and unilateral spatial agnosia were detected by neuropsychological tests. The patient could not write a coherent the letter even though she was well educated. In addition, she demonstrated slight memory disturbance and she needed her sister's support in daily life. Magnetic resonance imaging and single photon emission computed tomography examinations confirmed bilateral posterior atrophy and significant hypoperfusion in the occipital regions. The neuropathological background of PCA remains unclear. Therefore, the concept of PCA should be validated by the accumulation of information from more cases.     

Auditory hallucination as an initial sign of frontotemporal dementia

A 58-year-old right-handed man presented with a 9-year history of stereotyped behaviors and auditory hallucinations. At 49 years of age, he began to complain about auditory hallucinations that said offensive things about him, and around the same time, he began exhibiting stereotyped behaviors. For example, he traveled the same long route from his office to home every evening. Disinhibitory behavior occurred at 53 years of age, and he was forced to retire at 54 years of age. After retirement, the patient stayed in bed or showed a stereotyped behavior of repeatedly going to a nearby shrine every day. The complaint of auditory hallucinations disappeared around this time. At 57 years of age, he began using a day service, and soon after, several stereotyped behaviors appeared in this setting as well. Brain magnetic resonance imaging at 59 years of age showed severe atrophy and knife-blade-like appearance in the bilateral temporal poles. A clinical diagnosis of frontotemporal dementia (FTD) was made based on the neurobehavioral, neuropsychological, and neuroimaging findings. FTD patients have been reported to show hallucinations very rarely. However, recent studies have reported that frontotemporal lobar degeneration (FTLD) patients with ubiquitin-positive and transactive response-DNA-binding protein-43 (TDP-43)-positive pathologies (FTLD-U-TDP) and FTD patients with progranulin gene mutations often develop hallucinations. The current patient may belong to this group of patients with similar neuropathological and molecular biological bases.