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Introduction Obesity hypoventilation syndrome (OHS) is an underrecognized chronic respiratory condition characterized by obesity (BMI > 30kg/m2) and hypoventilation (PaCO2 > 45mmHg) in the absence of other causes of hypoventilation. In OHS, obesity causes mass loading on the respiratory system, leading to CO2 retention, diminished ventilatory response, progressive hypoxia/hypercapnia, and eventual cardiopulmonary arrest. OHS is typically diagnosed while inpatient, wherein 18-month mortality approaches 23%. Non-invasive ventilation (NIV) improves OHS symptoms & prognosis which subsequently decreases healthcare utilization and mortality. With the proper tools and training, inpatient providers can facilitate accurate diagnosis and prompt treatment of OHS. Our team developed an EMR-integrated clinical pathway to increase recognition and facilitate treatment of OHS in hospitalized patients on the general medicine service. Methods The OHS Pathway was implemented among a large group of hospitalists at a tertiary academic medical center. A multi-disciplinary team of physicians, respiratory therapists, and care coordinators designed the pathway structure and content. Prior to integrating the OHS pathway into the EMR, hospitalists were surveyed to assess existing knowledge and experiences caring for patients with OHS. Hospitalists then participated in an educational series on OHS with orientation to the pathway. 12-months into the intervention, hospitalists were re-surveyed. Results Survey data analysis revealed that providers were significantly more familiar with the diagnostic criteria for OHS after (n=40) the introduction of the clinical pathway rather than before the introduction (n=24) of the pathway (t (62) = 2.88, p = .0027). Subjective success rates for prescribing NIV to patients upon discharge did not significantly improve Conclusion OHS diagnosed in the inpatient setting carries significant morbidity and mortality. Proper detection and prompt treatment of OHS are essential to improving the care and prognosis of this high-risk population. We demonstrate that our multi-disciplinary based, EMR-integrated clinical pathway increased provider familiarity with the diagnostic criteria for OHS. While treatment success did not significantly improve, numerous systems factors were at play, and further investigations are needed to address access to treatment. Support (if any)

Introduction Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a rare disorder caused by an autosomal recessive biallelic pentanucleotide repeat expansion in the replication factor C subunit 1 (RFC1) gene. Clinical features include gait disturbances, impaired vibratory sensation, autonomic dysfunction, cough, and slow disease progression. Spinocerebellar ataxias are frequently associated with sleep disturbances, including REM sleep behavior disorders, insomnia, obstructive sleep apnea (OSA), and central sleep apnea. This is thought to be secondary to involvement of several nervous system structures including the cerebellum. OSA is caused by repeated obstruction of the pharyngeal airway leading to sleep disturbances and fatigue. It is likely that cerebellar insults such as CANVAS may play a role in upper airway obstruction and resultant OSA. However, there is little characterization of this relationship in the medical literature. Report of case(s) We report a case of a 52-year-old female with a past medical history of CANVAS, anxiety, and depression who was referred to sleep medicine for evaluation of worsening daytime fatigue and fragmented sleep. She reported daytime sleepiness, morning headaches, and gasping arousals. Her Epworth sleepiness scale score was markedly elevated at 19 (normal < 10), and she was subsequently referred for home polysomnography testing for sleep apnea. Home sleep testing revealed an apnea-hypopnea index of 12.5 events/hour and a minimum oxygen saturation of 85%. Conclusion This patient is at higher risk for sleep disruption due to her diagnosis of CANVAS. She presented with excessive daytime sleepiness and was found to have mild OSA on home sleep testing. Little is known about the presentation of OSA in patients with CANVAS. OSA treatment has the potential to improve sleep symptoms, quality of life, and mood disruption in this patient with an otherwise progressive and disabling neurologic disorder. Therefore early recognition and intervention of OSA are important in the care of patients with CANVAS. Given the disease’s progressive nature and lack of a cure, it is necessary to ameliorate quality of life however possible. OSA leads to persistent fatigue and may result in psychiatric disturbances, therefore, it is necessary to address sleep disturbances secondary to movement disorders to combat these outcomes. Support (if any)

ObjectiveRepeat expansions in RFC1 and DAB1 have recently been identified as causing cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) and spinocerebellar ataxia 37 (SCA37), respectively. We evaluated the prevalence of these repeat-expansions in an undiagnosed ataxia cohort from the United States.MethodsA cohort of 596 patients with undiagnosed familial or sporadic cerebellar ataxia were evaluated at a tertiary referral ataxia center and excluded for common genetic causes of cerebellar ataxia. Patients were then screened for the presence of pathogenic repeat expansions in RFC1 (AAGGG) and DAB1 (ATTTC) using fluorescent repeat primed polymerase chain reaction (RP-PCR). Two additional undiagnosed ataxia cohorts from different centers, totaling 96 and 13 patients respectively, were subsequently screened for RFC1 resulting in a combined 705 subjects tested.ResultsIn the initial cohort, 42 samples were identified with one expanded allele in the RFC1 gene (7.0%), and 9 had two expanded alleles (1.5%). For the additional cohorts, we found 12 heterozygous samples (12.5%) and 7 biallelic samples (7.3%) in the larger cohort, and 1 heterozygous sample (7.7%) and 3 biallelic samples (23%) in the second. In total, 19 patients were identified with biallelic repeat expansions in RFC1 (2.7%). Of these 19 patients, 6 (32%) had a clinical diagnosis of CANVAS, 10 had cerebellar ataxia with neuropathy (53%), and 3 had spinocerebellar ataxia (16%). No patients were identified with expansions in the DAB1 gene.ConclusionIn a large undiagnosed ataxia cohort from the United States, biallelic pathogenic repeat expansion in RFC1 was observed in 2.7%. Testing should be strongly considered in ataxia patients, especially those with CANVAS or neuropathy.

ObjectiveWe evaluated the prevalence of pathogenic repeat expansions in replication factor C subunit 1 (RFC1) and disabled adaptor protein 1 (DAB1) in an undiagnosed ataxia cohort from North America.MethodsA cohort of 596 predominantly adult-onset patients with undiagnosed familial or sporadic cerebellar ataxia was evaluated at a tertiary referral ataxia center and excluded for common genetic causes of cerebellar ataxia. Patients were then screened for the presence of pathogenic repeat expansions in RFC1 (AAGGG) and DAB1 (ATTTC) using fluorescent repeat-primed PCR (RP-PCR). Two additional undiagnosed ataxia cohorts from different centers, totaling 302 and 13 patients, respectively, were subsequently screened for RFC1, resulting in a combined 911 subjects tested.ResultsIn the initial cohort, 41 samples were identified with 1 expanded allele in the RFC1 gene (6.9%), and 9 had 2 expanded alleles (1.5%). For the additional cohorts, we found 20 heterozygous samples (6.6%) and 17 biallelic samples (5.6%) in the larger cohort and 1 heterozygous sample (7.7%) and 3 biallelic samples (23%) in the second. In total, 29 patients were identified with biallelic repeat expansions in RFC1 (3.2%). Of these 29 patients, 8 (28%) had a clinical diagnosis of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), 14 had cerebellar ataxia with neuropathy (48%), 4 had pure cerebellar ataxia (14%), and 3 had spinocerebellar ataxia (10%). No patients were identified with expansions in the DAB1 gene (spinocerebellar ataxia type 37).ConclusionsIn a large undiagnosed ataxia cohort from North America, biallelic pathogenic repeat expansion in RFC1 was observed in 3.2%. Testing should be strongly considered in patients with ataxia, especially those with CANVAS or neuropathy.