K A Josephs

..The high prevalence of HpScl may be the cause of some of the clinical features observed in patients with frontotemporal lobar degeneration...

..Translational regulation by miRNAs may represent a common mechanism underlying complex neurodegenerative disorders...

..The distribution of the lesions in this cross-sectional analysis may suggest a progression of TDP-43 pathology in AD, with limbic structures in the medial temporal lobe affected first, followed by higher order association cortices...

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..The findings suggest that iLBD is preclinical PD and that the lack of symptoms is due to subthreshold pathology...

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..A syndrome characterized by progressive pure apraxia of speech clearly exists, with a neuroanatomic correlate of superior lateral premotor and supplementary motor atrophy, making this syndrome distinct from primary progressive aphasia...

..To describe 3 patients with a history of transient global amnesia (TGA) who developed primary progressive aphasia (PPA)...

..Here we examine the role of miRNAs in FTLD patients with TAR DNA-binding protein 43 pathology (FTLD-TDP) caused by genetic mutations in the progranulin (PGRN) gene...

..We identified three FTLD-UPS cases, which are negative for CHMP2B mutation, suggesting that the full complement of FTLD pathologies is yet to be elucidated...

..Neuronal loss and gliosis in cornu ammonis 1 and the subiculum of the hippocampus are features of hippocampal sclerosis (HpScl), which occurs in many cases of FTLD-U...

..To highlight the fact that patients with corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) can sometimes present with a progressive apraxia of speech, nonfluent aphasia, or a combination of the two disorders...

..Benign tremulous parkinsonism has never been precisely defined nor has the long-term course been studied...

..To determine the anatomic correlate of prosopagnosia in subjects with semantic dementia...

..Neurodegenerative dementias are typically characterized by an insidious onset and a relatively slowly progressive course. Less common are patients with a rapidly progressive course to death...

..To examine the relationship between early clinical features, pathologies, and biochemistry of the frontotemporal lobar degenerations (FTLDs), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD)...

..To determine the rates of cerebral atrophy and ventricular expansion in six patients with autopsy confirmed progressive supranuclear palsy (PSP) and multiple antemortem volumetric head MRI scans...

..The ability to detect the clinical signs of dementia and motor neuron disease in pathologically confirmed FTLD-MND has not been assessed...

..These associations could ultimately allow the identification of appropriate patient phenotypes for future targeted treatments...

..These results show regional differences between PSP and CBD that are useful in predicting the underlying pathology, and help to shed light on the in vivo distribution of regional atrophy in PSP and CBD...

..Capgras syndrome is characterized by a delusional belief that a person has been replaced by an imposter. It has been described in psychiatric and neurological (neurodegenerative and nonneurodegenerative) diseases...

..It is not known, however, whether patients who meet the criteria for PCA and have hallucinations are different from those who meet the criteria and do not have hallucinations...

..Stereotypies in FTLD are therefore associated with a greater proportion of striatal to cortical volume loss than those without stereotypies...

..02). The difference in frequency of HpScl in FTLD-U compared to FTLD-MND is further evidence that they are separate clinicopathologic entities...

..To test the hypothesis that beta-amyloid (Abeta) burden is associated with rates of brain atrophy...

..The pathology causing progressive aphasia is typically a variant of frontotemporal lobar degeneration, especially with ubiquitin-positive inclusions (FTLD-U). Less commonly the underlying pathology is Alzheimer disease (AD)...

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..We have observed severe caudate atrophy at autopsy in FTLD-FUS, and hence, we aimed to determine whether caudate atrophy on MRI is a feature that can distinguish FTLD-FUS from FTLD-TDP and FTLD-TAU...

..An analysis of patient outcomes in these cases reveals that FTLD-MND has significantly shorter survival than FTLD-U, suggesting that FTLD-MND is a more aggressive disease process...

..Various pathologic findings, including corticobasal degeneration (CBD), progressive supranuclear palsy, and frontotemporal degenerations, underlie CBS...

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..The absence of abnormalities on imaging studies suggests that central nervous system symptoms are related to functional rather than structural disruption of neural networks...

..Behavioral changes occur in progressive supranuclear palsy. This study aimed to identify the anatomic correlate of behavioral severity in progressive supranuclear palsy...

..Increased T1 MRI signal in the basal ganglia is a biologic marker of manganese accumulation. Recent studies have associated welding and parkinsonism, but generally without MRI corroboration...

..We aimed to determine whether right temporal FTD is a homogeneous clinical, imaging, and pathologic/genetic entity...

..In subjects presenting with CBS, prominent temporoparietal, especially posterior temporal and inferior parietal, atrophy may be a clue to the presence of underlying AD pathology...

..However, there appears to be some associations between clinical phenotypes and FTLD-FUS pathologies. Clinical diagnosis is therefore promising in predicting molecular pathology...

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..Imaging modalities are clinically useful in FTLD, although pathology remains the gold standard for definitive diagnosis. To date, four different genes have been identified that account for FTLD...

..These cases demonstrate that atypical PSP can present as AOS and PNFA without the classic features of PSP...

..NPC may initially present in adulthood with psychosis, and when psychosis is associated with VSGP, various dyskinesias, and seizures, NPC should be suspected...

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..We suggest that PSP with or without coexisting AD and AGD be included in the differential diagnosis of patients presenting with FTD...

..To use a case-control study to assess and compare patterns of gray matter loss across groups of subjects with different mutations in the microtubule-associated protein tau (MAPT) gene...

..To use multiple serial MRI to assess rates and trajectories of brain and hippocampal atrophy in subjects with frontotemporal dementia (FTD) with progranulin (GRN) or microtubule-associated protein tau (MAPT) gene mutations...

..The aim of this study was to determine whether patterns of atrophy on imaging could be useful to help predict underlying pathology in CBS...

..To use diffusion tensor imaging (DTI) to assess gray matter and white matter tract diffusion in behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SMD), and progressive nonfluent aphasia (PNFA)...

..To determine whether TDP-43 type is associated with distinct patterns of brain atrophy on MRI in subjects with pathologically confirmed frontotemporal lobar degeneration (FTLD)...

..To compare patterns of gray matter loss in subjects with mutations in the progranulin (PGRN) gene to subjects with mutations in the microtubule-associated protein tau (MAPT) gene...

..This study further expands the clinical and pathological spectrum of PGRN mutations, and suggests the diagnosis could be missed in some individuals with atypical presentations...

..We aimed to determine whether patterns of gray matter atrophy from antemortem MRI correlate with Braak staging of NFT pathology...

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..The authors present clinical, radiologic, and pathologic features of adult-onset, sporadic cases mimicking cerebral-type progressive MS...

..Primary lateral sclerosis (PLS) is a progressive upper motor neuron neurodegenerative condition. The diagnosis is made using clinical history, objective neurological assessment, and exclusion of other neurodegenerative disorders...

..FTLD-U or FTLD-MND should be considered in the differential diagnosis of progressive frontal dementia with an akinetic rigid syndrome and supranuclear gaze palsy or Steele-Richardson-Olszewski disease...

..Manganese accumulation may be responsible for the imaging and clinical findings...

..Underlying CBD should be considered in the differential diagnosis of patients with findings reflecting posterior cerebral dysfunction...

..We propose the term neurofilament inclusion body disease for this entity...

..Some kindreds with PGRN mutations exhibited lateralized topography of degeneration across all affected individuals...

..Idiopathic REM sleep behavior disorder (RBD) may be the initial manifestation of synucleinopathies (Parkinson disease [PD], multiple system atrophy [MSA], or dementia with Lewy bodies [DLB])...

..Sparse alpha-synuclein pathology was also detected in the substantia nigra, basal forebrain, amygdala, or cortex in all but two cases...

..To assess demographic and genetic determinants of Alzheimer type pathology in progressive supranuclear palsy (PSP)...

..On the other hand, there is no histopathologic feature or combination of features that is pathognomonic. Neuronal intranuclear inclusions are virtually always present, but they can be detected in PGRN(-) cases...

..Patterns of atrophy were distinct and different from each other. A localized pattern of frontal lobe atrophy was found in FTLD-MND with a more widespread pattern of atrophy affecting the frontal and temporal lobes in FTLD-U...

..We aimed to compare, for the first time, atrophy patterns, as well as white matter tract degeneration, between these two syndromes...

..Obsessions and compulsive (OC) behaviors are a frequent feature of behavioral variant frontotemporal dementia (bvFTD), but their structural correlates have not been definitively established...

..Significant resolution occurred once treatment was discontinued. Caution is required when prescribing memantine to patients with possible DLB...

..Across all three groups, the neuropsychological profiles suggest frontal and subcortical cognitive impairment, with more widespread abnormalities occurring in the non-welding groups...

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..We have been evaluating patients with clinical and imaging features partially consistent with bvFTD but with evidence also suggestive of brain sagging, which we refer to as frontotemporal brain sagging syndrome (FBSS)...

..Limited data exist regarding clinical features associated with dementia prior to the age of 45...

..These findings extend previously described clinicopathological associations of FTLD-TDP subtypes and support the notion that FTLD-TDP subtypes may be distinct clinicopathologic disorders...

..Mutations in the progranulin gene (PGRN) have recently been identified as a cause of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) in some families...

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..Therefore in our brain bank series of frontotemporal degeneration, most cases were non-tauopathies with FTLD-U accounting for 62% of all the diagnoses...

..To our knowledge, this is the first report of cases of CJD with autopsy confirmation that presented with a PSP syndrome...

..Damage to this network of structures in DLB may affect a number of different neurotransmitter systems which in turn may contribute to a number of the core clinical features of DLB...

..These results support the assertion that the H1/H1 genotype may contribute to the earlier occurrence of clinical symptoms...

..Compulsive behaviors provoked by dopamine agonists often go undetected in clinical series, especially if not specifically inquired about...

..Surprisingly, the data suggests that in PSP as duration of illness increases there is a decrease in oligodendroglial tau burden...

..Few data exist regarding the demographics characterizing this population or the etiologic diagnoses among those affected...

..AD patients with clinical CBS have similar characteristics to CBD patients. Functional brain imaging may have greater utility than the clinical and neuropsychological features in differentiating AD presenting as CBS from CBD...

..To characterize a cohort of individuals who have experienced rapidly progressive dementia with onset before age 45...

..The trajectories of brain and ventricular changes were similar in AD and FTLD-U suggesting that it is independent of pathology, although subjects with FTLD-U show a more rapidly progressive decline...

..42, P < 0.05). This study demonstrates that cardiac sympathetic degeneration and alpha-synuclein pathology is present in presymptomatic phase of PD, and that both increase with disease duration and severity...

..Our objective was to document the clinical and imaging features of Othello's syndrome (delusional jealousy)...

..15%, P = 0.02). Of the 19 patients with stereotypies, three had vocal stereotypies, and three had both vocal and motor stereotypies. Of the 16 subjects with motor stereotypies, 9(56%) were appendicular and 7 (44%) were craniocervical...

..This review highlights the range of clinical and pathologic presentations of PSP and its variants...

..Pathological gambling is a rare potential complication related to treatment of Parkinson disease (PD). However, the etiology of this behavior is poorly understood...

..Asymmetry is also emphasized on neuroimaging...

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..Acquired generalized repetitive myoclonus may be mistaken for tremor. Distinguishing myoclonus has etiologic and therapeutic implications...

..1)H MRS suggested loss of neuronal integrity and glial activation in subjects with PCA and typical AD. The differing patterns of atrophy on MRI suggest that PCA should be considered a distinct entity from typical AD...

..The clinicopathologic features of these 12 cases expand the spectrum of 4R tauopathies...

..Refining the classification of the degenerative aphasias and AOS may be necessary to improve our understanding of the relationships among behavioural, pathological and imaging correlations...

..These findings suggest that the insR352 PSEN1 is not pathogenic, and the IVS1+1G-->A mutation in PGRN causes FTDP associated with FTLD-U pathology and represents a new class of neurodegenerative disease--the 'hypoprogranulinopathies'...

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..Semantic dementia is a syndrome within the spectrum of frontotemporal lobar degenerations characterized by fluent progressive aphasia (particularly anomia) and loss of word meaning...

..Results from this grant will ultimately lead to better targeted future treatments for patients with problems with speech and language. ..

..A better understanding of the role of TDP-43 is important to the development of targeted treatments for both diseases. Alzheimer's disease and frontototemporal lobar degeneration affect over 5 million Americans. ..