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Article ; Online: The prosubiculum in the human hippocampus: A rostrocaudal, feature-driven, and systematic approach.

Rosenblum, Emma W / Williams, Emily M / Champion, Samantha N / Frosch, Matthew P / Augustinack, Jean C

2024 Volume 532, Issue 3, Page(s) e25604

Abstract: The hippocampal subfield prosubiculum (ProS), is a conserved neuroanatomic region in mouse, monkey, and human. This area lies between CA1 and subiculum (Sub) and particularly lacks consensus on its boundaries; reports have varied on the description of ... ...

Abstract	The hippocampal subfield prosubiculum (ProS), is a conserved neuroanatomic region in mouse, monkey, and human. This area lies between CA1 and subiculum (Sub) and particularly lacks consensus on its boundaries; reports have varied on the description of its features and location. In this report, we review, refine, and evaluate four cytoarchitectural features that differentiate ProS from its neighboring subfields: (1) small neurons, (2) lightly stained neurons, (3) superficial clustered neurons, and (4) a cell sparse zone. ProS was delineated in all cases (n = 10). ProS was examined for its cytoarchitectonic features and location rostrocaudally, from the anterior head through the body in the hippocampus. The most common feature was small pyramidal neurons, which were intermingled with larger pyramidal neurons in ProS. We quantitatively measured ProS pyramidal neurons, which showed (average, width at pyramidal base = 14.31 µm, n = 400 per subfield). CA1 neurons averaged 15.57 µm and Sub neurons averaged 15.63 µm, both were significantly different than ProS (Kruskal-Wallis test, p < .0001). The other three features observed were lightly stained neurons, clustered neurons, and a cell sparse zone. Taken together, these findings suggest that ProS is an independent subfield, likely with distinct functional contributions to the broader interconnected hippocampal network. Our results suggest that ProS is a cytoarchitecturally varied subfield, both for features and among individuals. This diverse architecture in features and individuals for ProS could explain the long-standing complexity regarding the identification of this subfield.
MeSH term(s)	Humans ; Mice ; Animals ; Hippocampus/physiology ; Neurons ; Pyramidal Cells/physiology
Language	English
Publishing date	2024-03-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3086-7
ISSN	1096-9861 ; 0021-9967 ; 0092-7317
ISSN (online)	1096-9861
ISSN	0021-9967 ; 0092-7317
DOI	10.1002/cne.25604
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Article ; Online: TDP-43 and tau concurrence in the entorhinal subfields in primary age-related tauopathy and preclinical Alzheimer's disease.

Llamas-Rodríguez, Josué / Oltmer, Jan / Marshall, Michael / Champion, Samantha / Frosch, Matthew P / Augustinack, Jean C

Brain pathology (Zurich, Switzerland)

2023 Volume 33, Issue 4, Page(s) e13159

Abstract: Phosphorylated tau (p-tau) pathology correlates strongly with cognitive decline and is a pathological hallmark of Alzheimer's Disease (AD). In recent years, phosphorylated transactive response DNA-binding protein (pTDP-43) has emerged as a common ... ...

Abstract	Phosphorylated tau (p-tau) pathology correlates strongly with cognitive decline and is a pathological hallmark of Alzheimer's Disease (AD). In recent years, phosphorylated transactive response DNA-binding protein (pTDP-43) has emerged as a common comorbidity, found in up to 70% of all AD cases (Josephs et al., Acta Neuropathol, 131(4), 571-585; Josephs, Whitwell, et al., Acta Neuropathol, 127(6), 811-824). Current staging schemes for pTDP-43 in AD and primary age-related tauopathy (PART) track its progression throughout the brain, but the distribution of pTDP-43 within the entorhinal cortex (EC) at the earliest stages has not been studied. Moreover, the exact nature of p-tau and pTDP-43 co-localization is debated. We investigated the selective vulnerability of the entorhinal subfields to phosphorylated pTDP-43 pathology in preclinical AD and PART postmortem tissue. Within the EC, posterior-lateral subfields showed the highest semi-quantitative pTDP-43 density scores, while the anterior-medial subfields had the lowest. On the rostrocaudal axis, pTDP-43 scores were higher posteriorly than anteriorly (p < 0.010), peaking at the posterior-most level (p < 0.050). Further, we showed the relationship between pTDP-43 and p-tau in these regions at pathology-positive but clinically silent stages. P-tau and pTDP-43 presented a similar pattern of affected subregions (p < 0.0001) but differed in density magnitude (p < 0.0001). P-tau burden was consistently higher than pTDP-43 at every anterior-posterior level and in most EC subfields. These findings highlight pTDP-43 burden heterogeneity within the EC and the posterior-lateral subfields as the most vulnerable regions within stage II of the current pTDP-43 staging schemes for AD and PART. The EC is a point of convergence for p-tau and pTDP-43 and identifying its most vulnerable neuronal populations will prove key for early diagnosis and disease intervention.
MeSH term(s)	Humans ; Alzheimer Disease/pathology ; Tauopathies/pathology ; tau Proteins/metabolism ; DNA-Binding Proteins/metabolism ; Entorhinal Cortex/metabolism ; Brain/pathology
Chemical Substances	tau Proteins ; DNA-Binding Proteins
Language	English
Publishing date	2023-04-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1051484-3
ISSN	1750-3639 ; 1015-6305
ISSN (online)	1750-3639
ISSN	1015-6305
DOI	10.1111/bpa.13159
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Article ; Online: Immune checkpoint inhibitor associated myocarditis occurs in both high-grade and low-grade forms.

Champion, Samantha N / Stone, James R

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

2019 Volume 33, Issue 1, Page(s) 99–108

Abstract: Immune checkpoint inhibitor therapy for malignancy has been associated with adverse events including myocarditis. It has been unclear if there are distinct pathologic grades of this myocarditis that are associated with distinct clinical outcomes. Cardiac ...

Abstract	Immune checkpoint inhibitor therapy for malignancy has been associated with adverse events including myocarditis. It has been unclear if there are distinct pathologic grades of this myocarditis that are associated with distinct clinical outcomes. Cardiac tissue from ten patients with immune checkpoint inhibitor myocarditis (nine biopsies and one autopsy) were evaluated using immunohistochemistry for CD3, CD8, CD68, tryptase, PD-L1, and C4D. The immune checkpoint inhibitor myocarditis cases were classified as either high grade (>50 CD3
MeSH term(s)	Aged ; Antibodies, Monoclonal, Humanized/adverse effects ; Antineoplastic Agents, Immunological/adverse effects ; Female ; Humans ; Ipilimumab/adverse effects ; Male ; Middle Aged ; Myocarditis/chemically induced ; Myocarditis/immunology ; Myocarditis/pathology ; Neoplasms/drug therapy ; Nivolumab/adverse effects
Chemical Substances	Antibodies, Monoclonal, Humanized ; Antineoplastic Agents, Immunological ; Ipilimumab ; Nivolumab (31YO63LBSN) ; pembrolizumab (DPT0O3T46P)
Language	English
Publishing date	2019-09-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	645073-8
ISSN	1530-0285 ; 0893-3952
ISSN (online)	1530-0285
ISSN	0893-3952
DOI	10.1038/s41379-019-0363-0
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Article: Seronegative necrotizing autoimmune myopathy with favorable response to intravenous immunoglobulin.

Liu, Rebecca / Fenves, Andrew Z / Champion, Samantha N / Dau, Jonathan

Proceedings (Baylor University. Medical Center)

2021 Volume 34, Issue 4, Page(s) 481–483

Abstract: We describe a 68-year-old man who presented with progressive weakness in proximal muscles of all four limbs and was found to have autoantibody-negative necrotizing autoimmune myopathy (NAM). His myopathy was refractory to corticosteroids and methotrexate, ...

Abstract	We describe a 68-year-old man who presented with progressive weakness in proximal muscles of all four limbs and was found to have autoantibody-negative necrotizing autoimmune myopathy (NAM). His myopathy was refractory to corticosteroids and methotrexate, but subsequently demonstrated successful response to intravenous immunoglobulin (IVIG). The patient also received rituximab, but the timing of his recovery favored IVIG as the more important factor in terms of efficacy. Treatment guidelines for seronegative necrotizing myopathies are lacking. This case suggests a potential efficacious treatment option for the seronegative subset of NAM.
Language	English
Publishing date	2021-02-26
Publishing country	United States
Document type	Case Reports
ZDB-ID	2703932-8
ISSN	1525-3252 ; 0899-8280
ISSN (online)	1525-3252
ISSN	0899-8280
DOI	10.1080/08998280.2021.1885091
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Article ; Online: Pathology of the Brain and the Eye in Severe Acute Respiratory Syndrome Coronavirus-2-Infected Patients: A Review.

Champion, Samantha N / Williams, Imani M / Lage, Maria Martinez / Stagner, Anna M

Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society

2021 Volume 41, Issue 3, Page(s) 285–292

Abstract: Background: Patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may present or eventually develop central nervous system and ophthalmic signs and symptoms. Varying reports have emerged regarding isolation of viral RNA from these ... ...

Abstract	Background: Patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may present or eventually develop central nervous system and ophthalmic signs and symptoms. Varying reports have emerged regarding isolation of viral RNA from these tissue sites, as well as largely autopsy-based histopathologic descriptions of the brain and the eye in patients with COVID-19. Evidence acquisition: A primary literature search was performed in literature databases such as PubMed, Google Scholar, and Cochrane Library. Keywords were used alone and in combination including the following: SARS CoV-2, COVID-19, eye, brain, central nervous system, histopathology, autopsy, ocular pathology, aqueous, tears, vitreous, neuropathology, and encephalitis. Results: The reported ophthalmic pathologic and neuropathologic findings in patients with SARS-CoV-2 are varied and inconclusive regarding the role of direct viral infection vs secondary pathology. The authors own experience with autopsy neuropathology in COVID-19 patients is also described. There is a particular paucity of data regarding the histopathology of the eye. However, it is likely that the ocular surface is a potential site for inoculation and the tears a source of spread of viral particles. Conclusions: Additional large postmortem studies are needed to clarify the role of SARS-CoV in the ophthalmic and neuropathologic manifestations of COVID-19.
MeSH term(s)	Brain/diagnostic imaging ; COVID-19/complications ; COVID-19/epidemiology ; Eye/diagnostic imaging ; Eye Diseases/diagnosis ; Eye Diseases/etiology ; Humans ; Nervous System Diseases/diagnosis ; Nervous System Diseases/etiology ; Pandemics
Language	English
Publishing date	2021-02-27
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1189901-3
ISSN	1536-5166 ; 1070-8022
ISSN (online)	1536-5166
ISSN	1070-8022
DOI	10.1097/WNO.0000000000001275
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Article ; Online: Case 22-2021: A 64-Year-Old Woman with Cognitive Impairment, Headache, and Memory Loss.

Bhattacharyya, Shamik / Gonzalez, R Gilberto / Chwalisz, Bart K / Champion, Samantha N

The New England journal of medicine

2021 Volume 385, Issue 4, Page(s) 358–368

MeSH term(s)	Biopsy ; Brain/diagnostic imaging ; Cerebral Amyloid Angiopathy/complications ; Cerebral Amyloid Angiopathy/diagnosis ; Cerebral Hemorrhage/diagnostic imaging ; Cognitive Dysfunction/etiology ; Diagnosis, Differential ; Female ; Frontal Lobe/pathology ; Headache/etiology ; Humans ; Magnetic Resonance Imaging ; Memory Disorders/etiology ; Meningoencephalitis/diagnosis ; Middle Aged
Language	English
Publishing date	2021-07-21
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMcpc2103460
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Article: Pentad: A reproducible cytoarchitectonic protocol and its application to parcellation of the human hippocampus.

Williams, Emily M / Rosenblum, Emma W / Pihlstrom, Nicole / Llamas-Rodríguez, Josué / Champion, Samantha / Frosch, Matthew P / Augustinack, Jean C

Frontiers in neuroanatomy

2023 Volume 17, Page(s) 1114757

Abstract: Introduction: The hippocampus is integral for learning and memory and is targeted by multiple diseases. Neuroimaging approaches frequently use hippocampal subfield volumes as a standard measure of neurodegeneration, thus making them an essential ... ...

Abstract	Introduction: The hippocampus is integral for learning and memory and is targeted by multiple diseases. Neuroimaging approaches frequently use hippocampal subfield volumes as a standard measure of neurodegeneration, thus making them an essential biomarker to study. Collectively, histologic parcellation studies contain various disagreements, discrepancies, and omissions. The present study aimed to advance the hippocampal subfield segmentation field by establishing the first histology based parcellation protocol, applied to Methods: The protocol focuses on five cellular traits observed in the pyramidal layer of the human hippocampus. We coin this approach the pentad protocol. The traits were: chromophilia, neuron size, packing density, clustering, and collinearity. Subfields included were CA1, CA2, CA3, CA4, prosubiculum, subiculum, presubiculum, parasubiculum, as well as the medial (uncal) subfields Subu, CA1u, CA2u, CA3u, and CA4u. We also establish nine distinct anterior-posterior levels of the hippocampus in the coronal plane to document rostrocaudal differences. Results: Applying the pentad protocol, we parcellated 13 subfields at nine levels in 22 samples. We found that CA1 had the smallest neurons, CA2 showed high neuronal clustering, and CA3 displayed the most collinear neurons of the CA fields. The border between presubiculum and subiculum was staircase shaped, and parasubiculum had larger neurons than presubiculum. We also demonstrate cytoarchitectural evidence that CA4 and prosubiculum exist as individual subfields. Discussion: This protocol is comprehensive, regimented and supplies a high number of samples, hippocampal subfields, and anterior-posterior coronal levels. The pentad protocol utilizes the gold standard approach for the human hippocampus subfield parcellation.
Language	English
Publishing date	2023-02-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452969-2
ISSN	1662-5129
ISSN	1662-5129
DOI	10.3389/fnana.2023.1114757
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Article ; Online: Atretic cephalocele and encephalocele: A single-institution clinicopathological study.

Lang-Orsini, Melanie / Champion, Samantha N / Duhaime, Ann-Christine / Rapalino, Otto / Hedley-Whyte, E Tessa / Louis, David N / Nazarian, Rosalynn M

Journal of cutaneous pathology

2023 Volume 50, Issue 7, Page(s) 653–660

Abstract: Background: Encephaloceles are neural tube defects characterized by herniation of meninges, neural tissue and cerebrospinal fluid, while atretic cephaloceles denote a rudimentary connection to the intracranial space with absence of herniated neural ... ...

Abstract	Background: Encephaloceles are neural tube defects characterized by herniation of meninges, neural tissue and cerebrospinal fluid, while atretic cephaloceles denote a rudimentary connection to the intracranial space with absence of herniated neural tissue and represent an infrequent dermatopathologic diagnosis. Limited reports of these entities confound the challenge in their histopathologic distinction. Accurate classification is important given associated anomalies and neurologic manifestations that impact prognosis. Methods: We describe the clinicopathological and immunohistochemical [glial fibrillary acidic protein (GFAP), S100, epithelial membrane antigen (EMA), and somatostatin receptor subtype 2A (SSTR2A)] features in a retrospective series encountered at a single institution between 1994 and 2020. Results: We identified 13 cases classified as atretic cephalocele (n = 11) and encephalocele (n = 2). Hamartomatous changes and multinucleated cells were unique to atretic cephaloceles while myxoid areas were unique to encephaloceles. At least focal staining for SSTRA was seen in all atretic cephaloceles with the majority (87.5%) staining for EMA; negative staining for GFAP and S100 confirmed absence of neural tissue. Encephaloceles were GFAP and S100 positive, and negative for SSTR2 and EMA. Atretic cephaloceles had a favorable prognosis compared to encephaloceles, with severe morbidity present in both encephalocele cases. Conclusion: Our study raises awareness of atretic cephalocele and encephalocele among dermatopathologists and reveals a mutually exclusive immunophenotype that facilitates their distinction for prognostication and management.
MeSH term(s)	Humans ; Encephalocele/pathology ; Retrospective Studies ; Meninges/pathology ; Prognosis
Language	English
Publishing date	2023-02-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	187078-6
ISSN	1600-0560 ; 0303-6987
ISSN (online)	1600-0560
ISSN	0303-6987
DOI	10.1111/cup.14399
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Article ; Online: Case 37-2021: A 60-Year-Old Man with Fevers, Fatigue, Arthralgias, a Mouth Ulcer, and a Rash.

Wallace, Zachary S / Rodriguez, Karen / Dau, Jonathan / Bloch, Donald B / Champion, Samantha N

The New England journal of medicine

2021 Volume 385, Issue 24, Page(s) 2282–2293

MeSH term(s)	Arthralgia/etiology ; Deltoid Muscle/pathology ; Dermatomyositis/complications ; Dermatomyositis/diagnosis ; Dermatomyositis/drug therapy ; Diagnosis, Differential ; Exanthema/etiology ; Fatal Outcome ; Fatigue/etiology ; Fever/etiology ; Humans ; Immunosuppressive Agents/therapeutic use ; Lung/diagnostic imaging ; Lung/pathology ; Male ; Middle Aged ; Oral Ulcer/etiology ; Tomography, X-Ray Computed
Chemical Substances	Immunosuppressive Agents
Language	English
Publishing date	2021-12-23
Publishing country	United States
Document type	Case Reports ; Clinical Conference ; Journal Article
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMcpc2107353
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Article ; Online: Nelson Syndrome: Clival Invasion of Corticotroph Pituitary Adenoma Resulting in Alternating Sixth Nerve Palsies.

Douglas, Vivian P / Douglas, Konstantinos A A / Rapalino, Otto / Champion, Samantha N / Chwalisz, Bart K

Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society

2021 Volume 41, Issue 1, Page(s) 114–118

Abstract: Abstract: A 44-year-old woman presented with 2 painful and self-limited episodes of binocular horizontal diplopia within 1 year that at the beginning were thought to be secondary to microvascular insult. Her medical history was significant for Cushing ... ...

Abstract	Abstract: A 44-year-old woman presented with 2 painful and self-limited episodes of binocular horizontal diplopia within 1 year that at the beginning were thought to be secondary to microvascular insult. Her medical history was significant for Cushing syndrome status post transsphenoidal resection with bilateral adrenalectomy 4 years prior, hypertension, and diabetes mellitus. Neuro-ophthalmic evaluation was significant for left abduction deficit and incomitant esotropia consistent with left abducens nerve palsy. Of note, the patient had experienced a similar episode but on the contralateral side a few months prior. Although initially MRI of the brain demonstrated stable residual postoperative finding in the sella, upon review, an heterogenous T-1 hypointense marrow in the clivus was noted. Hypermetabolism of the clivus was also noted on computed tomography positron emission tomography of the skull base. A clival biopsy demonstrated a corticotroph adenoma with elevated proliferation index and scattered mitoses. A corticotroph pituitary adenoma after adrenalectomy, also known as Nelson syndrome, was diagnosed. Radiation therapy was offered to the patient, and resolution of symptoms was gradually observed.
MeSH term(s)	ACTH-Secreting Pituitary Adenoma/pathology ; ACTH-Secreting Pituitary Adenoma/surgery ; Abducens Nerve Diseases/diagnosis ; Adenoma/pathology ; Adenoma/surgery ; Adrenalectomy ; Adrenocorticotropic Hormone/blood ; Adult ; Cranial Fossa, Posterior/pathology ; Diplopia/diagnosis ; Female ; Humans ; Magnetic Resonance Imaging ; Nelson Syndrome/diagnosis ; Neoplasm Invasiveness ; Skull Base Neoplasms/pathology ; Tomography, X-Ray Computed
Chemical Substances	Adrenocorticotropic Hormone (9002-60-2)
Language	English
Publishing date	2021-01-04
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	1189901-3
ISSN	1536-5166 ; 1070-8022
ISSN (online)	1536-5166
ISSN	1070-8022
DOI	10.1097/WNO.0000000000001141
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