P 83 Parasomnia, parkinsonism, impulse control disorder and bulbar palsy with IgLON5 antibodies: A new case report

Abstract

Background In 2014 a complex neurological syndrome with parasomnia, sleep breathing dysfunction and variable bulbar symptoms associated with antibodies to IgLON5, a neuronal cell-adhesion protein, was described (Sabater et al., 2016). Postmortal studies revealed tauopathy predominately involving the hypothalamus and tegmentum of the brainstem (Gelpi et al., 2016). To the best of our knowledge, there are 16 published cases so far. Methods (clinical presentation) We report a 72-year-old highly educated male Caucasian patient with a 6 year history of parasomnia with RBD in the beginning, following of multiple falls, parkinsonism, hypomania, frontal lobe disorder and impulse control disorder (ICD; leading to sentence of detention) with aggressive tendencies. By transcranial ultrasound hyperechogenicity of substantia nigra was demonstrated, FDG-PET imaging showed lower 18F-FDG activity in temporal lobes. Thus idiopathic Parkinson’s disease was assumed. Due to neuropsychiatric complications the antiparkinson medication was gradually reduced and eventually discontinued in 2014. Interestingly, there were no relevant changes in symptoms of parkinsonism thereafter. In 2016, after acute coronary syndrome the patient developed a sudden bilateral vocal cord paresis with stridor leading to intubation and following tracheotomy. Subsequently, he showed dysphagia, increasing rigidity, fluctuating level of consciousness with intermittent hypoventilation and hypercapnia, and autonomic dysregulation. Critical decompensation with need of short CPR occurred twice, continuous monitoring with mechanical ventilation was required. Results (workup and treatment, Table 1 ) Brain MRI showed iron accumulation in globus pallidus and dentate nucleus, and a small pineal cyst ( Fig. 1 a). The initial multiple EEGs were normal. Diverse EEGs from 2016 registered generalized slowing with intermittent hyperexcitability; nonconvulsive status epilepticus was captured once ( Fig. 1 b). Laboratory tests displayed neutrophil leukocytosis with MGUS IgG-kappa and -lambda. In serum (1:100) and in CSF (1:10) IgLON5 antibodies (IgG subclass) were detected. HLA-typing revealed HLA-DRB1∗10:01 and HLA-DQB1∗05:01 alleles. Tumor screening (thoracic and abdominal CT, bone marrow examination) did not detect malignancy. Because of suspected IgLON5-syndrome with autoimmune origin an immunosuppressive therapy with initial IV methylprednisolone pulse therapy following oral prednisolone (75 mg/d) and rituximab was initiated. Subsequently, after achieving better vigilance, it was possible to start weaning again. Conclusion Parasomnia, ICD, beginning frontal lobe syndrome with parkinsonism, multiple falls and bulbar symptoms is a new combination in IgLON5 antibody-linked syndrome. A connection to neurodegeneration with brain iron accumulation (NBIA) is possible and requires further investigation.