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Acute ischemic stroke of the posterior circulation

Chapter by: Boyd, Clara
in: Emergency stroke care : advances and controversies by Jagoda, Andy; Lay, Cappi; Thurman, R; Anana, Michael (Eds)
Norcross, GA : EB Medicine, 2017
pp. 41-48
ISBN: 0998451932
CID: 2849872

Multimodal imaging evidence of pathology-mediated disease distribution in corticobasal syndrome

McMillan, Corey T; Boyd, Clara; Gross, Rachel G; Weinstein, Jessica; Firn, Kim; Toledo, Jon B; Rascovsky, Katya; Shaw, Leslie; Wolk, David A; Irwin, David J; Lee, Edward B; Trojanowski, John Q; Grossman, Murray
OBJECTIVE: To use multimodal neuroimaging to evaluate the influence of heterogeneous underlying pathology in corticobasal syndrome (CBS) on the neuroanatomical distribution of disease. METHODS: We performed a retrospective evaluation of 35 patients with CBS with T1-weighted MRI, diffusion tensor imaging, and neuropathologic, genetic, or CSF evidence of underlying pathology. Patients were assigned to 2 groups: those with evidence of Alzheimer pathology (CBS-AD) and those without Alzheimer pathology (CBS-non-AD). Group comparisons of CBS-AD and CBS-non-AD assessed clinical features, gray matter (GM) cortical thickness, and white matter (WM) fractional anisotropy. RESULTS: CBS-AD was found in 34% (n = 12) and CBS-non-AD in 66% (n = 23) of CBS patients. Clinical evaluations revealed that CBS-non-AD had a higher frequency of asymmetric rigidity compared to CBS-AD, but groups otherwise did not differ in dementia severity, impairments in cognition, or rates of extrapyramidal symptoms. We found frontoparietal GM and WM disease in each group compared to healthy, demographically comparable controls, as well as multimodal neuroimaging evidence of a double dissociation: CBS-non-AD had WM disease in the corpus callosum, corticospinal tract, and superior longitudinal fasciculus relative to CBS-AD, and CBS-AD had reduced temporoparietal GM relative to CBS-non-AD, including the precuneus and posterior cingulate. CONCLUSIONS: Patients with CBS have a pathology-mediated dissociation of GM and WM disease. Multimodality neuroimaging may be useful for improving in vivo pathologic diagnosis of CBS.
PMID: 27543644
ISSN: 1526-632x
CID: 2694252

Diagnostic utility of aquaporin-4 in the analysis of active demyelinating lesions

Popescu, Bogdan F G; Guo, Yong; Jentoft, Mark E; Parisi, Joseph E; Lennon, Vanda A; Pittock, Sean J; Weinshenker, Brian G; Wingerchuk, Dean M; Giannini, Caterina; Metz, Imke; Bruck, Wolfgang; Shuster, Elizabeth A; Carter, Jonathan; Boyd, Clara D; Clardy, Stacey Lynn; Cohen, Bruce A; Lucchinetti, Claudia F
OBJECTIVE: To assess, in a surgical biopsy cohort of active demyelinating lesions, the diagnostic utility of aquaporin-4 (AQP4) immunohistochemistry in identifying neuromyelitis optica (NMO) or NMO spectrum disorder (NMOSD) and describe pathologic features that should prompt AQP4 immunohistochemical analysis and AQP4-immunoglobulin G (IgG) serologic testing. METHODS: This was a neuropathologic cohort study of 20 surgical biopsies (19 patients; 11 cord/9 brain), performed because of diagnostic uncertainty, interpreted as active demyelinating disease and containing 2 or more of the following additional features: tissue vacuolation, granulocytic infiltrates, or astrocyte injury. RESULTS: AQP4 immunoreactivity was lost in 18 biopsies and increased in 2. Immunopathologic features of the AQP4 loss cohort were myelin vacuolation (18), dystrophic astrocytes and granulocytes (17), vascular hyalinization (16), macrophages containing glial fibrillary acid protein (GFAP)-positive debris (14), and Creutzfeldt-Peters cells (0). All 14 cases with available serum tested positive for AQP4-IgG after biopsy. Diagnosis at last follow-up was NMO/NMOSD (15) and longitudinally extensive transverse myelitis (1 each relapsing and single). Immunopathologic features of the AQP4 increased cohort were macrophages containing GFAP-positive debris and granulocytes (2), myelin vacuolation (1), dystrophic astrocytes (1), Creutzfeldt-Peters cells (1), and vascular hyalinization (1). Diagnosis at last follow-up was multiple sclerosis (MS) and both tested AQP4-IgG seronegative after biopsy. CONCLUSIONS: AQP4 immunohistochemistry with subsequent AQP4-IgG testing has diagnostic utility in identifying cases of NMO/NMOSD. This study highlights the importance of considering NMOSD in the differential diagnosis of tumefactive brain or spinal cord lesions. AQP4-IgG testing may avert biopsy and avoid ineffective therapies if these patients are erroneously treated for MS.
PMID: 25503621
ISSN: 1526-632x
CID: 2694262

Visuoperception test predicts pathologic diagnosis of Alzheimer disease in corticobasal syndrome

Boyd, Clara D; Tierney, Michael; Wassermann, Eric M; Spina, Salvatore; Oblak, Adrian L; Ghetti, Bernardino; Grafman, Jordan; Huey, Edward
OBJECTIVE: To use the Visual Object and Space Perception Battery (VOSP) to distinguish Alzheimer disease (AD) from non-AD pathology in corticobasal syndrome (CBS). METHODS: This clinicopathologic study assessed 36 patients with CBS on the VOSP. All were autopsied. The primary dependent variable was a binary pathologic outcome: patients with CBS who had primary pathologic diagnosis of AD (CBS-AD, n = 10) vs patients with CBS without primary pathologic diagnosis of AD (CBS-nonAD, n = 26). We also determined sensitivity and specificity of individual VOSP subtests. RESULTS: Patients with CBS-AD had younger onset (54.5 vs 63.6 years, p = 0.001) and lower memory scores on the Mattis Dementia Rating Scale-2 (16 vs 22 points, p = 0.003). Failure on the VOSP subtests Incomplete Letters (odds ratio [OR] 11.5, p = 0.006), Position Discrimination (OR 10.86, p = 0.008), Number Location (OR 12.27, p = 0.026), and Cube Analysis (OR 45.71 p = 0.0001) had significantly greater odds of CBS-AD than CBS-nonAD. These associations remained when adjusting for total Mattis Dementia Rating score, disease laterality, education, age, and sex. Receiver operating characteristic curves demonstrated significant accuracy for Incomplete Letters and all VOSP spatial subtests, with Cube Analysis performing best (area under the curve 0.91, p = 0.0004). CONCLUSIONS: In patients with CBS, failure on specific VOSP subtests is associated with greater odds of having underlying AD. There may be preferential involvement of the dorsal stream in CBS-AD. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that some subtests of the VOSP accurately distinguish patients with CBS-AD from those without AD pathology (e.g., Cube Analysis sensitivity 100%, specificity 77%).
PMID: 24991033
ISSN: 1526-632x
CID: 2694272

Hydrocephalus in neuromyelitis optica [Case Report]

Clardy, Stacey L; Lucchinetti, Claudia F; Krecke, Karl N; Lennon, Vanda A; O'Toole, Orna; Weinshenker, Brian G; Boyd, Clara D; Krieger, Stephen; McGraw, Corey; Guo, Yong; Pittock, Sean J
PMID: 24759842
ISSN: 1526-632x
CID: 2694282

Treatment of Alzheimer's Disease: Current Management and Experimental Therapeutics

Honig, Lawrence S; Boyd, Clara D
Alzheimer's disease (AD) is a major cause of morbidity in the elderly. AD affects aver 5 million persons in the United States, but because it increases in incidence in the elderly, and the "graying" population, AD is projected to increase in prevalence by many-fold over the coming decades. AD causes progressive mental impairment, resulting in the inability of persons to care for themselves. As a consequence, AD results in enormous costs to society due to both lost productivity, and required care. Thus, improved management and treatment is essential. In this review we will briefly review current understanding of the disease, including roles of beta-amyloid and tau proteins. We will then discuss current therapies in use, including the evidence for treatments with supplements, established drugs, and investigational therapeutic strategies, recently completed and ongoing.
PMID: 24093080
ISSN: 2162-4941
CID: 2694292