Meredith Wicklund

Quantitative application of the primary progressive aphasia consensus criteria

Objective: To determine how well the consensus criteria could classify subjects with primary progressive aphasia (PPA) using a quantitative speech and language battery that matches the test descriptions provided by the consensus criteria. Methods: A total of 105 participants with a neurodegenerative speech and language disorder were prospectively recruited and underwent neurologic, neuropsychological, and speech and language testing and MRI in this case-control study. Twenty-one participants with apraxia of speech without aphasia served as controls. Select tests from the speech and language battery were chosen for application of consensus criteria and cutoffs were employed to determine syndromic classification. Hierarchical cluster analysis was used to examine participants who could not be classified. Results: Of the 84 participants, 58 (69%) could be classified as agrammatic (27%), semantic (7%), or logopenic (35%) variants of PPA. The remaining 31% of participants could not be classified. Of the unclassifiable participants, 2 clusters were identified. The speech and language profile of the first cluster resembled mild logopenic PPA and the second cluster semantic PPA. Gray matter patterns of loss of these 2 clusters of unclassified participants also resembled mild logopenic and semantic variants. Conclusions: Quantitative application of consensus PPA criteria yields the 3 syndromic variants but leaves a large proportion unclassified. Therefore, the current consensus criteria need to be modified in order to improve sensitivity.

Frontotemporal brain sagging syndrome An SIH-like presentation mimicking FTD

Background: Behavioral variant frontotemporal dementia (bvFTD) is a relatively well-defined clinical syndrome. It is associated with frontal and temporal lobe structural/metabolic changes and pathologic findings of a neurodegenerative disease. 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). Methods: Retrospective medical chart review to identify all patients seen at our institution between 1996 and 2010, who had a clinical diagnosis of FTD and imaging evidence of brain sag. Results: Eight patients, 7 male and 1 female, were diagnosed with FBSS. The median age at symptom onset was 53 years. All patients had insidious onset and slow progression of behavioral and cognitive dysfunction accompanied by daytime somnolence and headache. Of the 5 patients with functional imaging, all showed evidence of hypometabolism of the frontotemporal regions. On brain MRI, all patients had evidence of brain sagging with distortion of the brainstem; 3 patients had diffuse pachymeningeal enhancement. CSF opening pressure was varied and CSF protein was mildly elevated. A definite site of CSF leak was not identified by myelogram or cisternography, except in one patient with a site highly suggestive of leak who subsequently underwent surgery confirming a CSF leak. In 2 patients with a neuropathologic examination, there was no evidence of a neurodegenerative disease. Conclusions: This case series demonstrates that FBSS may mimic typical bvFTD but should be recognized as an unusual presentation that is potentially treatable.

Emerging Biomarkers in Cognition

Knowledge of aging and dementia is rapidly evolving with the aim of identifying individuals in the earliest stages of disease processes. Biomarkers allow clinicians to show the presence of a pathologic process and resultant synapse dysfunction and neurodegeneration, even in the earliest stages. This article focuses on biomarkers for mild cognitive impairment caused by Alzheimer disease, structural magnetic resonance imaging, fluorodeoxyglucose positron emission tomography (PET) or single-photon emission computed tomography, and PET with dopamine ligands. Although these biomarkers are useful, several limitations exist. Several new biomarkers are emerging and a more biological characterization of underlying pathophysiologic spectra may become possible.

Standardized sign-out improves completeness and perceived accuracy of inpatient neurology handoffs

Objectives: As residency programs adjust to new duty hour restrictions, the use of cross-coverage systems requiring handoffs will rise. Handoffs are vulnerable to communication failures when unstructured. Accordingly, we implemented a standardized sign-out process on our inpatient neurology services and assessed its effect on completeness and perceived accuracy of handoffs. Methods: Residents spent the first half of their rotations utilizing unstructured sign-out. They transitioned to a structured sign-out system (using the situation-background-assessment-recommendation format) during the second half of their rotations. We analyzed survey responses before and after implementation to evaluate for an effect. Results: Residents utilizing structured sign-out were significantly more likely to share test results with patients/families prior to shift changes (p = 0.037), update our electronic service list (p = 0.045), and feel all important data were being transmitted (p = 0.041). Overall satisfaction (scale 1–10) increased from 6.2 ± 1.6 to 7.4 ± 1.3 (p = 0.002). Conclusions: Our findings demonstrate that standardized sign-out improves the completeness and perceived accuracy of handoffs. Such improvement has the potential to improve patient safety and quality of care.

Aphasia with left occipitotemporal hypometabolism: a novel presentation of posterior cortical atrophy?

Alzheimers disease is a common neurodegenerative disease often characterized by initial episodic memory loss. Atypical focal cortical presentations have been described, including the logopenic variant of primary progressive aphasia (lvPPA) which presents with language impairment, and posterior cortical atrophy (PCA) which presents with prominent visuospatial deficits. Both lvPPA and PCA are characterized by specific patterns of hypometabolism: left temporoparietal in lvPPA and bilateral parietoccipital in PCA. However, not every patient fits neatly into these categories. We retrospectively identified two patients with progressive aphasia and visuospatial deficits from a speech and language based disorders study. The patients were further characterized by MRI, fluorodeoxyglucose F18 and Pittsburgh Compound B (PiB) positron emission tomography. Two women, aged 62 and 69, presented with a history of a few years of progressive aphasia characterized by fluent output with normal grammar and syntax, anomia without loss of word meaning, and relatively spared repetition. They demonstrated striking deficits in visuospatial function for which they were lacking insight. Prominent hypometabolism was noted in the left occipitotemporal region and diffuse retention of PiB was noted. Posterior cortical atrophy may present focally with left occipitotemporal metabolism characterized clinically with a progressive fluent aphasia and prominent ventral visuospatial deficits with loss of insight.

A kindred with familial frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72

FRONTOTEMPORAL DEMENTIA AND/OR AMYOTROPHIC LATERAL SCLEROSIS ASSOCIATEDWITH THE GGGGCC REPEAT EXPANSION IN C9ORF72 Meredith Wicklund, Bradley Boeve, Jasper Daube, Mariely DejesusHernandez, Joseph Parisi, Dennis Dickson, Keith Josephs, Matthew Baker, Karen Kuntz, Kris Johnson, David Knopman, Robert Ivnik, Ronald Petersen, Rosa Rademachers, Mayo Clinic, Rochester, Minnesota, United States; 2 Mayo Clinic, Jacksonville, Florida, United States.