Chronic Herpes Simplex Virus Encephalitis: Two Surgical Cases with Novel Neuropathologic Findings (P12-10.001)
Bibliographic record
Abstract
Objective: N/A Background: Chronic granulomatous herpes simplex encephalitis (CGHSE) is a rare complication following infantile and pediatric herpes simplex virus encephalitis (HSVE). Clinically, it follows a biphasic course, with acute HSVE later followed by drug-resistant seizures and progressive neurologic deterioration. Convincing evidence is lacking for whether CGHSE occurs due to virus reactivation versus post-infectious inflammatory sequelae. Design/Methods: The neuropathologic findings of two patients who underwent epilepsy surgery following remote infectious encephalitis are herein discussed. The first case is previously unreported and confirmed to be associated with HSV-I, and the second case, newly re-examined, is previously reported and of presumed HSV-I encephalitis. Results: The histological findings in the current cases were consistent with chronic, ongoing inflammation, both of which harboured parenchymal HSV-I DNA by PCR. There were no HSV antigens detected via immunohistochemistry nor viral inclusions seen on the H&E sections. A novel finding, shared by both cases, is the identification of cytoplasmic phosphorylated tau-immunopositive components: neurofibrillary tangles, pretangles and neuropil threads. These were demonstrated within regions of inflammation as well as seemingly uninvolved areas. Conclusions: Tau hyperphosphorylation has been reported following other infections, such as post-measles subacute sclerosing panencephalitis and HIV-associated neurocognitive disorders. HSV-I infection has been postulated to promote tau protein hyperphosphorylation. HSV-I primary infection and reactivation have been associated with phosphorylated tau accumulation in murine models. HSV-I in vitro infection models exposed to acyclovir treatment demonstrate dose-dependent reductions in phosphorylated tau accumulation. While in vitro murine, monkey and human experimental data have demonstrated hyperphosphorylated tau accumulates following HSV-I infection, to our knowledge, this may represent the first patient report of abnormal phosphorylated tau accumulation associated with neuropathologic chronic granulomatous HSVE. Further investigation into the possibility that tau accumulation contributes to long-term neurologic sequelae among HSVE survivors may be warranted. Disclosure: Dr. Sjonnesen has nothing to disclose. Dr. Appendino has nothing to disclose. Walter J. Hader, MD has nothing to disclose. Dr. Xu has nothing to disclose. The institution of Prof. Jacobs has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB. Prof. Jacobs has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epilog. Prof. Jacobs has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Prof. Jacobs has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pendopharm. Prof. Jacobs has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley. Prof. Jacobs has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Prof. Jacobs has received research support from Alberta Childrens Hospital Foundation. Dr. Federico has nothing to disclose. Dr. Langdon has nothing to disclose.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".