Research highlights in Neurology and Neurosurgery – March 2019

Mayo Clinic Neurology studies published in 2018 explored patients with atypical presentations of rare, benign central nervous system tumors, the association between APOE e4 and Lewy bodies pathology, and the relationship of obstructive sleep apnea to sudden unexpected death in people with epilepsy.

DIA/DIG outcomes correlate to tumor location

Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are rare, benign central nervous system tumors that typically present within the first two years of life. Classically, patients present with a rapidly enlarging head circumference. Resection is typically curative; the prognosis is generally good, with long disease-free survival.

In light of reportedly similar clinical, radiological and pathological features, DIA and DIG are categorized together and designated grade I in the 2016 World Health Organization classification. But there have been reports of patients with atypical presentations of DIA/DIGs who may have markedly different clinical courses and long-term outcomes.

A study of patients treated for DIA/DIGs at Mayo Clinic has identified two subgroups, based on tumor location. Data of seven patients with histopathology-proven DIA/DIGs and preoperative imaging were retrospectively reviewed. Age, sex, clinical presentation, imaging characteristics, tumor location, surgical procedure, postoperative morbidity and overall mortality were recorded. Four patients had tumors in the cerebral hemispheres, and three had lesions in the suprasellar region.

Mayo researchers found that patients with suprasellar disease experienced ocular abnormalities, including nystagmus and a preference for downward gaze. These patients also experienced significant postoperative complications and had poor long-term outcomes. In contrast, patients with hemispheric tumors underwent more-extensive resection and had uneventful postoperative courses with no documented long-term comorbidities. The research is the first direct comparison of the clinical course of patients with suprasellar tumors and classically described hemispheric disease.

Naylor RM, et al. Novel suprasellar location of desmoplastic infantile astrocytoma and ganglioglioma: A single institution's experience. Journal of Neurosurgery: Pediatrics. 2018;22:397.

Independent association between APOE e4 and Lewy bodies pathology

The APOE e4 allele has been associated with an increased risk of Lewy body disease, although the causal mechanism hasn't been elucidated. Many people with Lewy body disease also have Alzheimer's pathology.

Mayo Clinic researchers have found that APOE e4 is associated with a greater severity of Lewy bodies pathology independently of Alzheimer's disease pathology. The researchers genotyped 652 autopsy-confirmed cases of Lewy body disease and 660 controls for APOE e4. In case-control analysis, Lewy body disease cases were classified into nine groups according to severity of both Lewy bodies pathology and Alzheimer's disease pathology. In the Lewy body disease, the researchers also measured Lewy body counts from five cortical regions, and evaluated associations with APOE e4 according to the severity of Alzheimer's disease pathology.

As expected, APOE e4 was associated with an increased risk of transitional and diffuse Lewy body disease in cases with moderate or high Alzheimer's disease pathology. However, APOE e4 was also associated with an increased risk of diffuse Lewy body disease in cases with low Alzheimer's disease pathology. In the Lewy body disease subgroup with low Alzheimer's pathology, APOE e4 was associated with significantly more Lewy body counts in the five cortical regions.

The results suggest that APOE e4 might function as a modifier of processes that favor Lewy bodies spread rather than acting directly to initiate Lewy bodies pathology.

Dickson DW, et al. APOE e4 is associated with severity of Lewy body pathology independent of Alzheimer pathology. Neurology. 2018;91:e1182.

Obstructive sleep apnea and refractory epilepsy

People with epilepsy are at 20 times greater risk of sudden death than are people in the general population. The mechanisms underlying sudden unexpected death in epilepsy (SUDEP) remain largely undefined, although several risk factors have been identified.

In a pilot study, Mayo Clinic researchers found a relatively high frequency of probable obstructive sleep apnea (pOSA) in people with refractory epilepsy. The researchers prospectively recruited 49 consecutive adult patients admitted to Mayo Clinic's Epilepsy Monitoring Unit with focal, generalized or unclassified epilepsy syndromes. The patients were evaluated for obstructive sleep apnea and patients with and without pOSA were compared. Among the patients studied, 35 percent had pOSA. Patients with pOSA were older and heavier, and more frequently had a focal epilepsy syndrome and longer epilepsy duration.

The researchers suggest that identification and treatment of obstructive sleep apnea in patients with epilepsy could conceivably provide a novel approach toward lowering the risk of SUDEP, although future studies with polysomnography are needed to confirm predictive features and to determine whether obstructive sleep apnea is associated with SUDEP risk.

McCarter AR, et al. Obstructive sleep apnea in refractory epilepsy: A pilot study investigating frequency, clinical features, and association with risk of sudden unexpected death in epilepsy. Epilepsia. 2018;59:1973.