Keith A Josephs

..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...

..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...

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

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..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...

..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...

..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...

..Our findings suggest behavioural variant of frontotemporal dementia can therefore be subdivided into four different anatomical subtypes...

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

..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...

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

..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 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...

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..037). Physiologically-confirmed psychogenic tremor carries a poor prognosis, with unremitting or worse tremor persisting 3-years after diagnosis in most...

..8%). The proposed approach establishes a direct a priori relationship between specific topographic patterns on MRI and "gold standard" of pathology which can then be used to predict underlying dementia pathology in new incoming patients...

..To determine the neuropathologic correlates of antemortem hydrogen 1 ((1)H) magnetic resonance (MR) spectroscopy metabolite measurements in subjects with Alzheimer disease (AD)-type pathology...

..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...

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

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..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...

..Argyrophilic grains (AG) are silver-positive spindle-shaped lesions found at postmortem. Their significance is controversial...

..In summary, survival in 4R tauopathies seemed independent of the presenting clinical phenotype, and there may be subtle clinical differences between bv-FTD patients with 3R and 4R tauopathies...

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..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...

..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...

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..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...

..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...

..Asymmetry is also emphasized on neuroimaging...

..Clinicopathologic studies are helpful in understanding the underlying neurodegenerative process in such cases...

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

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

..Temporoparietal atrophy may therefore provide a useful marker of the presence of AD pathology even in subjects with atypical clinical presentations, especially in the context of relative sparing of the hippocampus...

..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'...

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

..To explore whether associations of potential risk factors for incidental Lewy body disease (iLBD) are similar to those for Parkinson disease (PD)...

..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...

..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...

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

..Othello's syndrome (OS) is a delusion of infidelity. We describe seven cases of OS in Parkinson's disease (iPD) patients using dopamine agonists...

..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...

..To define the diagnostic characteristics and predictors of treatment response in patients with suspected autoimmune dementia...

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

..This disorder has an uncertain pathophysiologic relationship to idiopathic Parkinson disease. Deep brain stimulation (DBS) should be efficacious for this condition, but there is no previously published experience...

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

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

..The findings raise the possibly of an as yet identified protein that may play a pathogenic role in tau-negative FTLD...

..A systematic literature review of pathological hypersexuality in PD revealed similar medication histories; combining these cases with our series, 26 of 29 patients (90%) were on adjuvant dopamine agonists...

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

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

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

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

..Frontotemporal dementia and amyotrophic lateral sclerosis are neurodegenerative diseases associated with TAR DNA-binding protein 43- and ubiquitin-immunoreactive pathologic lesions...

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

..The antemortem consensus diagnosis of FTLD was moderately sensitive and very specific. With experienced clinicians and awareness of the unique manifestations of FTLD, accurate antemortem diagnosis was feasible...

..We compared our two cases to all previously published pathological cases of combined LBD and motor neuron degeneration...

..The substrate for DHS is controversial, with some concluding that the cause is myopathic and others, exclusively dystonic. We report our clinical series of DHS arising in the setting of parkinsonism...

..Patients with cognitive complaints after gastric bypass surgery may have focal thalamic brain atrophy that could result in cognitive impairment...

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

..The MRI brain scan in both had unique focal abnormalities in the corresponding leg area of the homunculus that may be the substrate for the alien limb features...

..This case extends the clinical and pathological spectrum of NFID to include cases with predominant parkinsonian and pyramidal features...

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

..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...

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

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

..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...

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

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

..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...

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

..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...

..To examine the relationship between progranulin gene mutation and apraxic agraphia...

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..These clinical and pathological findings suggest that PSP-PNLA should be considered a variant of PSP...

..Thalamic and basal ganglia infarcts are common in patients with vascular PSP and, when present, may contribute to misdiagnosis...

..To identify clinical features in behavioral-variant frontotemporal dementia that may help predict tau-positive pathology...

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..The significance of Lewy bodies detected at autopsy in the brains of clinically normal individuals is uncertain but may represent preclinical Parkinson disease (PD)...

..It also reveals subclinical MND in a subset of cases of FTLD without clinical or pathologic evidence of MND...

..CONCLUSIONS: Behavioral features in familial and sporadic cases were similar, but semantic dementia only occurred in sporadic cases. Diagnostic confusion with Alzheimer disease and corticobasal degeneration occurred in some cases...

..Given the impact for potential treatment of similar cases, recognition of this possible association and additional studies are warranted...

..Patterns of atrophy on magnetic resonance imaging may help distinguish these diseases and aid diagnosis...

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

..The VBM findings were supported by blinded visual assessment. CONCLUSION: These findings suggest that MRI patterns of regional gray matter atrophy constitute signatures of tissue pathology in FTD...

..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...