Research highlights in Neurology and Neurosurgery ― September 2019

Aug. 30, 2019

Mayo Clinic Neurology studies presented at the 2019 American Academy of Neurology annual meeting and published in Neurology address checkpoint inhibitors and neurological immune-related adverse events, a tissue biomarker for patients with Parkinson's disease, glioma-related seizures and tumor molecular markers, and imaging factors related to cognitive aging.

Checkpoint inhibitors and neurological immune-related adverse events

The expanding use of immune checkpoint inhibitors highlights the importance of accurate diagnosis and prompt management of neurological immune-related adverse events. These events may present atypically and with overlapping signs and symptoms; optimal management is unknown. Comprehensive phenotypic characterization and long-term outcome data would therefore be clinically useful.

Mayo Clinic researchers and colleagues at Massachusetts General Hospital have described the clinical spectrum, management and outcomes of neurological immune-related adverse events in a large cohort of patients who received immune checkpoint inhibitors (ICIs).

Twenty-eight (1.5%) of the 1,851 patients who received immune checkpoint inhibitors at Massachusetts General from 2011 to 2017 had grade 3 or 4 neurological immune-related adverse events. The rate of adverse events was significantly higher with the use of anti-CTLA-4 therapy alone or in combination with anti-PD-1 therapy compared with anti-PD-1 monotherapy. Most of the adverse events (68%) occurred within the first one to four cycles of immune checkpoint inhibitor therapy.

Dubey D, et al. Immune checkpoint inhibitor related neurological adverse events: Clinical spectrum, management and outcomes. Neurology. 2019;92(suppl 15):S21.003.

Tissue biomarker for patients with Parkinson's disease

Mayo Clinic previously reported that submandibular gland biopsy detects Lewy-type synucleinopathy (LTS) in patients with early and advanced Parkinson's disease (PD). Mayo Clinic researchers recently found that repeat biopsies can demonstrate increased LTS density over time. The researchers performed repeat biopsies on seven patients with PD who previously underwent bilateral transcutaneous needle biopsies of the submandibular gland. Staining with a monoclonal antibody was performed. All study participants had sufficient submandibular gland tissue on at least one side; 12 of the 14 glands biopsied had sufficient tissue for assessment. All 12 glands were positive for LTS, with an average fourfold increase in LTS density.

The study is the first to demonstrate that bilateral biopsies can be performed safely and that LTS density increases over time.

Adler C, et al. Repeat submandibular gland biopsies as a progression marker in Parkinson's disease. Neurology. 2019;92(suppl 15):S10.002.

Glioma-related seizures and tumor molecular markers

Gliomas are commonly associated with the development of seizures; the two conditions sometimes share common pathogenic mechanisms. Mayo Clinic researchers have found that glioma-related preoperative seizures may be more closely associated with tumor molecular markers than with glioma grade or histopathology.

In a prospective cohort study, the researchers gathered clinical data from 68 patients with glioma. The presence of glioma-related preoperative seizures, electroencephalography, the characteristics of patients' tumors and postoperative seizure freedom were assessed. Forty-six of the 68 patients had glioma-related preoperative seizures; 31 of the 46 (67%) had seizure freedom at a mean follow-up of nine months after surgery.

Neither the presence of glioma-related preoperative seizures nor postoperative seizure freedom differed by the patients' age or sex, or by the glioma's location, grade or histopathological subtype. However, patients with IDH1 mutation had an increased likelihood of preoperative seizures and postoperative seizure freedom.

Feyissa A, et al. Glioma-related seizures: Beyond glioma grade and histopathology. Neurology. 2019;92(suppl 15):S3.002.

Imaging factors related to cognitive aging

Three anatomically distinct regions play an important role in cognitive aging: entorhinal cortex, parietal lobe and frontal lobe. The entorhinal cortex is susceptible to aging and pathology; the parietal lobe is an integrative functional hub; and the frontal lobe may reflect early cerebrovascular disease.

Mayo Clinic researchers have identified imaging biomarkers in those regions that capture unique aspects of cognitive aging. The researchers analyzed imaging from 796 participants in the population-based Mayo Clinic Study of Aging to identify protective and risk factors for entorhinal cortex thickness, superior parietal lobe thickness and diffusion-tensor imaging-based genu corpus callosum (GCC) fractional anisotropy.

Among study participants ages 30 to 49, higher GCC fractional anisotropy was related to greater total brain volume, and higher entorhinal cortex thickness was related to better memory performance.

Among 50- to 64-year-olds, higher imaging measures were related to lower current metabolic and vascular risk, greater total brain volume, higher global cognition, lower history of smoking and alcohol misuse, and higher prevalence of marriage.

People ages 65 and older with high imaging measures had a higher prevalence of marriage and lower history of alcohol misuse compared with young adults with high imaging measures.

Neth B, et al. Factors related to higher neurobiological capital across the lifespan: Mayo Clinic Study of Aging. Neurology. 2019;92(suppl 15):S34.002.