IgLON5 disease responsive to immunotherapy

A 45-year-old man was seen with a history of confusion and disorientation for 1 year, during which time he was unable to identify relatives. He was unable to cope at his work as a plasterer, noticed neck pain, dysphagia, and unexplained weight gain. His family reported that his sleep pattern had changed, describing his sleep as disturbed with episodes consistent with stridor, myoclonus (the video at Neurology.org/nn), and semipurposeful movements. At his initial examination, he appeared mildly confused with a depressed affect. He was obese (body mass index of 33 kg/m) and was noted to be centrally cyanosed (figure e-1). He had mild gait ataxia, bulbar dysarthria, and dysphagia. The rest of his examination was normal. He was found to have established ventilatory failure and sleep-disordered breathing. EEG demonstrated a baseline of theta waves with a rhythm intermixed. CSF analysis was abnormal, suggesting inflammation (table). MRI of the head and neck was normal. Inpatient polysomnography with video was extremely limited by the patient’s limited sleep duration and nocturnal behavioral problems. The awake period evaluation revealed intermittent runs of theta wave activity suggesting an increased homeostatic sleep drive. Frequent spontaneous desaturations were noted, some of which were central in nature. The sleep period evaluation demonstrated an increased sleep onset latency and reduction in nonREM stage 2 sleep and a complete absence of REM sleep (figure e-2). His apnea-hypopnea index was 25, confirming moderate obstructive sleep apnea. Nocturnal noninvasive ventilation was issued for long-term use, but initial adherence was poor. The patient was initially treated with prednisolone and immunoglobulins. This was associated with improvement in behavior mirrored by improvement in CSF parameters, and he became well enough to be discharged home. However, he was admitted 6 weeks later with aspiration pneumonia and ventilatory failure requiring intensive care support. His sleep disorder was still prominent clinically and required further treatment with plasmapheresis followed by another course of IV immunoglobulins, which led to a rapid improvement over a few weeks. A repeat CSF analysis confirmed raised protein suggestive of persistent inflammation, and further IV-pulsed cyclophosphamide was given. After 2 pulses, his behavior normalized and sleep pattern improved with return of dreams, and resolution of neck pain and dysphagia. Serum antibodies to IgLON5 returned positive using indirect immunofluorescence (Euroimmun). CSF testing for the antibody was also positive (figure e-3). The patient continued treatment with cyclophosphamide, and he has received 8 pulses so far. His human leukocyte antigen (HLA) genotyping confirmed HLA-DQB1*05:01 and HLADRB1*10:01 alleles. At his last review (2 years from the onset of his initial symptoms), he continues to improve. He exhibited no evidence of cognitive impairment or abnormal behavior, and there were no involuntary movements. His gait remains mildly ataxic. Noninvasive ventilation has been established with improvement in his arterial blood gases. His spouse reports better sleep patterns.