Phenoconversion in Women and Men With Isolated REM Sleep Behavior Disorder: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: Isolated REM sleep behavior disorder (iRBD) is strongly associated with synucleinopathies. Previous iRBD cohort studies have primarily focused on older (>50 years), male-predominant cohorts. Risk of phenoconversion in women and younger adults remains unclear. The study aimed to determine clinical features associated with conversion to a defined neurodegenerative disorder in women and men with iRBD. METHODS: One hundred eighty-six women and 186 men with iRBD were matched by polysomnography month. Baseline clinical variables and subsequent neurodegenerative outcomes were abstracted by chart review. Kaplan-Meier curves assessed conversion rates. Cox proportional hazards modeling evaluated factors associated with phenoconversion risk. RESULTS: Age at iRBD diagnosis was younger in women compared with men (54.9 vs 62.5 years, p < 0.01). Forty-eight patients (12.9%), including 18 women (9.7%) and 30 men (16.1%), phenoconverted during a median follow-up of 6.0 years. Conversion rates were lower in antidepressant users and patients with chronic pain or psychiatric comorbidity while rates were higher in those with vascular comorbidity. Only age at diagnosis (HR 1.09, 95% CI 1.06-1.13) was associated with phenoconversion after adjusting for RBD symptom duration; sex; antidepressant use; and psychiatric, chronic pain, and vascular comorbidities. DISCUSSION: Age at diagnosis was independently associated with phenoconversion risk in women and men with iRBD.

REM sleep atonia loss distinguishes synucleinopathy in older adults with cognitive impairment.

OBJECTIVE: To determine whether quantitative polysomnographic REM sleep without atonia (RSWA) distinguishes between cognitive impairment phenotypes. BACKGROUND: Neurodegenerative cognitive impairment in older adults predominantly correlates with tauopathy or synucleinopathy. Accurate antemortem phenotypic diagnosis has important prognostic and treatment implications; additional clinical tools might distinguish between dementia syndromes. METHODS: We quantitatively analyzed RSWA in 61 older adults who underwent polysomnography including 46 with cognitive impairment (20 probable synucleinopathy), 26 probable non-synucleinopathy (15 probable Alzheimer disease, 11 frontotemporal lobar dementia), and 15 age- and sex-matched controls. Submentalis and anterior tibialis RSWA metrics and automated REM atonia index were calculated. Group statistical comparisons and regression were performed, and receiver operating characteristic curves determined diagnostic RSWA thresholds that best distinguished synucleinopathy phenotype. RESULTS: Submentalis-but not anterior tibialis RSWA-was greater in synucleinopathy than nonsynucleinopathy; several RSWA diagnostic thresholds distinguished synucleinopathy with excellent specificity including submentalis tonic, 5.6% (area under the curve [AUC] 0.791); submentalis any, 15.0% (AUC 0.871); submentalis phasic, 10.8% (AUC 0.863); and anterior tibialis phasic, 31.4% (AUC 0.694). In the subset of patients without dream enactment behaviors, submentalis RSWA was also greater in patients with synucleinopathy than in those without synucleinopathy. RSWA was detected more frequently by quantitative than qualitative methods (p = 0.0001). CONCLUSION: Elevated submentalis RSWA distinguishes probable synucleinopathy from probable nonsynucleinopathy in cognitively impaired older adults, even in the absence of clinical dream enactment symptoms. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that quantitative RSWA analysis is useful for distinguishing cognitive impairment phenotypes. Further studies with pathologic confirmation of dementia diagnoses are needed to confirm the diagnostic utility of RSWA in dementia.

Submentalis Rapid Eye Movement Sleep Muscle Activity: A Potential Biomarker for Synucleinopathy.

Accurate antemortem diagnosis of parkinsonism is primarily based on clinical evaluation with limited biomarkers. We evaluated the diagnostic utility of quantitative rapid eye movement (REM) sleep without atonia analysis in the submentalis and anterior tibialis muscles in parkinsonian patients (53 synucleinopathy, 24 tauopathy). Receiver operating characteristic curves determined REM sleep without atonia cutoffs distinguishing synucleinopathies from tauopathies. Elevated submentalis muscle activity was highly sensitive (70-77%) and specific (95-100%) in distinguishing synucleinopathy from tauopathy. In contrast, anterior tibialis synucleinopathy discrimination was poor. Our results suggest that elevated submentalis REM sleep without atonia appears to be a potentially useful biomarker for presumed synucleinopathy etiologies in parkinsonism. ANN NEUROL 2019;86:969-974.

Hypoglossal nerve stimulator generator migration: INSPIRE device reimplantation with parallels to cardiac implantable electronic devices.

Implantation rates of hypoglossal nerve stimulators, such as INSPIRE, are increasing. The device is still in its early stages of complication reporting, which to date includes implant related infection requiring device removal, and stimulation lead cuff dislodgement requiring replacement. Here we present a 48-year-old female who experienced generator migration and stimulator lead tension requiring an additional operation in order to resecure the generator device. This proved unsuccessful and a second surgery was performed with complete relocation of the device generator to inhibit device migration. This is the first documented case of INSPIRE migration to date, though the implant generator has comparable likeness to cardiovascular implantable electronic devices (CIEDs) where migration risk factors are better studied. Given our patient's case, we identify obesity and abundant breast tissue as potential risk factors for device migration. We believe such factors can be identified prior to initial device implantation to avoid migration and the need for surgical revision. Superior positioning of the generator proved successful, and can be a solution in those with similar body habitus as TYRX pouching and additional security sutures were ineffective. Also, for revisions requiring tunneling of the stimulation lead as in this case we recommend the use of zero degree endoscope for ease of adhesion lysis.