Blinded review of hippocampal neuropathology in sudden unexplained death in childhood reveals inconsistent observations and similarities to explained paediatric deaths.

AIMS: Hippocampal findings are implicated in the pathogenesis of sudden unexplained death in childhood (SUDC), although some studies have identified similar findings in sudden explained death in childhood (SEDC) cases. We blindly reviewed hippocampal histology in SUDC and SEDC controls. METHODS: Hippocampal haematoxylin and eosin (H&E) slides (n = 67; 36 SUDC, 31 controls) from clinical and forensic collaborators were evaluated by nine blinded reviewers: three board-certified forensic pathologists, three neuropathologists and three dual-certified neuropathologists/forensic pathologists. RESULTS: Among nine reviewers, about 50% of hippocampal sections were rated as abnormal (52.5% SUDC, 53.0% controls), with no difference by cause of death (COD) (p = 0.16) or febrile seizure history (p = 0.90). There was little agreement among nine reviewers on whether a slide was within normal range (Fleiss' κ = 0.014, p = 0.47). Within reviewer groups, there were no findings more frequent in SUDC compared with controls, with variability in pyramidal neuron and dentate gyrus findings. Across reviewer groups, there was concordance for bilamination and granule cell loss. Neither SUDC (51.2%) nor control (55.9%) slides were considered contributory to determining COD (p = 0.41). CONCLUSIONS: The lack of an association of hippocampal findings in SUDC and controls, as well as inconsistency of observations by multiple blinded reviewers, indicates discrepancy with previous studies and an inability to reliably identify hippocampal maldevelopment associated with sudden death (HMASD). These findings underscore a need for larger studies to standardise evaluation of hippocampal findings, identifying the range of normal variation and changes unrelated to SUDC or febrile seizures. Molecular studies may help identify novel immunohistological markers that inform on COD.

National Association of Medical Examiners Position Paper: Recommendations for the Investigation and Certification of Deaths in People with Epilepsy.

Sudden unexpected death of an individual with epilepsy (SUDEP) can pose a challenge to death investigators, as most deaths are unwitnessed and the individual is commonly found dead in bed. Anatomic findings (e.g., tongue/lip bite) are commonly absent and of varying specificity, limiting the evidence to implicate epilepsy as a cause of or contributor to death. Thus, it is likely that death certificates significantly underrepresent the true number of deaths in which epilepsy was a factor. To address this, members of the National Association of Medical Examiners, North American SUDEP Registry, Epilepsy Foundation SUDEP Institute, American Epilepsy Society, and the Centers for Disease Control and Prevention convened an expert panel to generate evidence-based recommendations for the practice of death investigation and autopsy, toxicological analysis, interpretation of autopsy and toxicology findings, and death certification to improve the precision of death certificate data available for public health surveillance of epilepsy-related deaths. The recommendations provided in this paper are intended to assist medical examiners, coroners, and death investigators when a sudden, unexpected death in a person with epilepsy is encountered.

Intramedullary spinal cord metastasis from salivary ductal carcinoma of the parotid gland mimicking transverse myelitis in a patient with radiologically isolated syndrome.

Intramedullary spinal cord metastases (ISCMs) are rare lesions but their presence should not be underestimated in a cancer patient with rapidly progressive neurological compromise. Due to similar timing of clinical progression and imaging characteristics, these lesions may be misdiagnosed as transverse myelitis, an inflammatory disorder of the spinal cord that may be idiopathic or secondary to other diseases including infections, connective tissue disorders, nutritional deficiencies, and demyelinating disorders. We present a case of a 44 year-old male with a history of parotid gland metastatic salivary ductal carcinoma (SDC) and incidental demyelinating white matter lesions on brain magnetic resonance imaging (MRI) diagnosed as radiologically isolated syndrome with a CSF that was positive for oligoclonal bands. The patient initially presented with mid-thoracic dermatomal numbness, bilateral lower extremity weakness, and neurogenic bladder. MRI spine demonstrated an enhancing T5-7 intramedullary lesion initially diagnosed as transverse myelitis. After progressing to complete motor and sensory loss below T6 despite high-dose intravenous steroids and plasmapheresis, surgical biopsy was undertaken. Intraoperative findings revealed an intramedullary tumor for which a subtotal resection was performed. Pathology was consistent with a metastatic deposit from the patient's primary parotid SDC. The patient underwent postoperative chemotherapy but expired due to systemic disease progression seven months following surgery without neurological improvement. This is the first reported case of ISCM from a primary SDC. The median survival is 6 months for patients with ISCMs treated surgically. The goals of surgery are spinal cord decompression, functional preservation, and tissue diagnosis.