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1.
Neurooncol Adv ; 6(1): vdae097, 2024.
Article in English | MEDLINE | ID: mdl-38962753

ABSTRACT

Background: Choroid plexus tumors (CPTs) are rare, potentially aggressive CNS tumors with defined histologic criteria for grading. In recent years, several patients within our practice have demonstrated discordance between the histologic diagnosis and clinical behavior. DNA methylation profiling has emerged as a potential diagnostic adjunct for aiding the clinical approach. Methods: We reviewed the clinical and pathologic data of all CPTs diagnosed at Boston Children's Hospital from 1995 to 2023. All cases with available material (38/48) underwent DNA methylation profiling at NIH/NCI, and the classifier results were correlated with the WHO histologic grade and patient outcomes. Survival information was analyzed using Kaplan-Meier curves. Results: There was good correlation (11/12, 92%) between methylation class and WHO histologic grade for choroid plexus carcinomas (CPC); one histologic CPC grouped with choroid plexus papilloma (CPP) group pediatric (P). Five CPPs grouped with methylation class CPC (5/17, 29%). In the group of atypical CPPs (n = 9), there were two that grouped with methylation class CPC. Survival analysis showed utility of methylation classes in the prediction of biologic behavior. Conclusions: Results indicated that methylation profiling may serve as a valuable tool in the clinical decision-making process for patients with CPTs, providing additional prognostic information compared to WHO histologic grade alone. The value of methylation array analysis is particularly important given the lack of consensus on treatment regimens for CPTs.

2.
J Neuropathol Exp Neurol ; 83(5): 331-337, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38501995

ABSTRACT

Medical autopsies have decreased in frequency due in part to advances in radiological techniques and increased availability of molecular and other ancillary testing. However, premortem diagnosis of CNS disease remains challenging; while ∼90% of brain tumor biopsies are diagnostic, only 20%-70% of biopsies for presumed nonneoplastic disease result in a specific diagnosis. The added benefits of performing an autopsy following surgical brain biopsy are not well defined. A retrospective analysis was performed of patients who underwent brain biopsy and autopsy at Brigham and Women's Hospital from 2003 to 2022. A total of 135 cases were identified, including 95 (70%) patients with primary CNS neoplasms, 16 (12%) with metastatic tumors, and 24 (18%) with nonneoplastic neurological disease. Diagnostic concordance between biopsy and autopsy diagnosis was excellent both for primary CNS neoplasms (98%) and metastatic tumors (94%). Conversely, patients with nonneoplastic disease received definitive premortem diagnoses in 7/24 (29%) cases. Five (21%) additional patients received conclusive diagnoses following autopsy; 8 (33%) received a more specific differential diagnosis compared to the biopsy. Overall, autopsy confirmed premortem diagnoses or provided new diagnostic information in 131/135 (97%) cases, highlighting the value in performing postmortem brain examination in patients with both neoplastic and nonneoplastic diseases.


Subject(s)
Brain Neoplasms , Brain , Humans , Female , Retrospective Studies , Autopsy , Biopsy , Brain Neoplasms/diagnosis
4.
J Neuropathol Exp Neurol ; 79(1): 113-117, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31794012

ABSTRACT

Hydrocephalus is a rare and devastating complication of mumps encephalitis. The histopathological correlates of mumps infection in central nervous system tissues are not well-characterized. We present the case of a 54-year-old patient who suffered long-term neuropsychiatric sequelae and hydrocephalus as a consequence of a childhood mumps infection. Brain autopsy revealed significant dilation of the lateral and third ventricles. Aqueductal stenosis was not observed on premortem imaging or on gross examination. Histology revealed loss of ependymal epithelium throughout the aqueduct and ventricular system. Macrophage conglomerates were identified within the cerebral aqueduct at the level of the pons in addition to subjacent periaqueductal gliosis and scattered Rosenthal fibers. Together, these findings support primary ependymal injury as a pathophysiological mechanism in the development of chronic hydrocephalus following mumps infection. Finally, we review the existing literature and discuss potential mechanisms of disease.


Subject(s)
Encephalitis/complications , Encephalitis/pathology , Hydrocephalus/etiology , Hydrocephalus/pathology , Mumps/complications , Mumps/pathology , Adolescent , Adult , Brain/pathology , Cerebral Aqueduct/pathology , Cerebral Ventricles/pathology , Child , Child, Preschool , Encephalitis/psychology , Ependyma/pathology , Fatal Outcome , Female , Gliosis/pathology , Humans , Hydrocephalus/psychology , Infant , Macrophages/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Mumps/psychology , Pons/pathology , Young Adult
5.
Acad Forensic Pathol ; 9(3-4): 181-190, 2019 Sep.
Article in English | MEDLINE | ID: mdl-32110253

ABSTRACT

Studies have demonstrated that autopsy is the gold standard for determining cause and manner of death. Indeed, the current National Association of Medical Examiners standard B3.7 states that a forensic pathologist (FP) shall perform a forensic autopsy when the death is by apparent intoxication by alcohol, drugs, or poison. Unfortunately, the recent increase in drug-related deaths has led to some question about the feasibility of maintaining compliance with standard B3.7. We constructed a voluntary survey to address consensus on standard B3.7 and the use of supervised accredited pathologists' assistants (PAs) in performing select medicolegal autopsies. Additional questions were included to help characterize variables related to FP's workload and experience. Each of these variables was predicted to influence FP's attitudes toward B3.7 and the use of PAs. Our respondent pool (n = 107) consisted primarily of actively practicing FPs with administrative responsibilities (42%) and actively practicing FPs without administrative responsibilities (41%). Sixty-five percent agreed that standard B3.7 is appropriate. Opinion on the use of PAs was split between those who agreed (45%) and those who did not (44%). Tendency to agree with either B3.7 or the use of PAs was not a function of FP's individual or office workload; however, respondents were more likely to agree with B3.7 if they previously experienced a case where internal autopsy findings radically altered diagnosis in an otherwise suggestive overdose case (P < 0.001). In certain offices and under certain conditions, the use of PAs may be one solution to ensuring all potential overdose deaths receive an autopsy.

6.
Neuroimage Clin ; 6: 408-14, 2014.
Article in English | MEDLINE | ID: mdl-25379454

ABSTRACT

Myelin water imaging provides a novel strategy to assess myelin integrity and corresponding clinical relationships in psychosis, of particular relevance in frontal white matter regions. In the current study, T2 myelin water imaging was used to assess the myelin water fraction (MWF) signal from frontal areas in a sample of 58 individuals experiencing first-episode psychosis (FEP) and 44 healthy volunteers. No differences in frontal MWF were observed between FEP subjects and healthy volunteers; however, differences in normal patterns of associations between frontal MWF and age, education and IQ were seen. Significant positive relationships between frontal MWF and age, North American Adult Reading Test (NAART) IQ, and years of completed education were observed in healthy volunteers. In contrast, only the relationship between frontal MWF and NAART IQ was significant after Bonferroni correction in the FEP group. Additionally, significant positive relationships between age and MWF in the anterior and posterior internal capsules, the genu, and the splenium were observed in healthy volunteers. In FEP subjects, only the relationship between age and MWF in the splenium was statistically significant. Frontal MWF was not associated with local white matter volume. Altered patterns of association between age, years of education, and MWF in FEP suggest that subtle disturbances in myelination may be present early in the course of psychosis.


Subject(s)
Frontal Lobe/pathology , Myelin Sheath/pathology , Schizophrenia/pathology , White Matter/pathology , Adolescent , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Water/analysis , Young Adult
7.
Int J Neuropsychopharmacol ; 15(10): 1441-55, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22071247

ABSTRACT

Tetrahydroprotoberberines (THPBs) are compounds derived from traditional Chinese medicine and increasing preclinical evidence suggests efficacy in treatment of a wide range of symptoms observed in schizophrenia. A receptor-binding profile of the THPB, d.l-govadine (d.l-Gov), reveals high affinity for dopamine and noradrenaline receptors, efficacy as a D2 receptor antagonist, brain penetrance in the 10-300 ng/g range, and thus motivated an assessment of the antipsychotic and pro-cognitive properties of this compound in the rat. Increased dopamine efflux in the prefrontal cortex and nucleus accumbens, measured by microdialysis, is observed following subcutaneous injection of the drug. d.l-Gov inhibits both conditioned avoidance responding (CAR) and amphetamine-induced locomotion (AIL) at lower doses than clozapine (CAR ED50: d.l-Gov 0.72 vs. clozapine 7.70 mg/kg; AIL ED50: d.l-Gov 1.70 vs. clozapine 4.27 mg/kg). Catalepsy is not detectable at low biologically relevant doses, but is observed at higher doses. Consistent with previous reports, acute d-amphetamine disrupts latent inhibition (LI) while a novel finding of enhanced LI is observed in sensitized animals. Treatment with d.l-Gov prior to conditioned stimulus (CS) pre-exposure restores LI to levels observed in controls in both sensitized animals and those treated acutely with d-amphetamine. Finally, possible pro-cognitive properties of d.l-Gov are assessed with the spatial delayed win-shift task. Subcutaneous injection of 1.0 mg/kg d.l-Gov failed to affect errors at a 30-min delay, but decreased errors observed at a 12-h delay. Collectively, these data provide the first evidence that d.l-Gov may have antipsychotic properties in conjunction with pro-cognitive effects, lending further support to the hypothesis that THPBs are a class of compounds which merit serious consideration as novel treatments for schizophrenia.


Subject(s)
Antipsychotic Agents/pharmacology , Avoidance Learning/drug effects , Berberine Alkaloids/pharmacology , Cognition/drug effects , Motor Activity/drug effects , Nootropic Agents/pharmacology , Animals , Antipsychotic Agents/chemistry , Avoidance Learning/physiology , Berberine Alkaloids/chemistry , Cognition/physiology , Drug Evaluation, Preclinical/methods , Male , Motor Activity/physiology , Nootropic Agents/chemistry , Rats , Rats, Long-Evans
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