Contact: heleen.biersteker@radboudumc.nl PC097 Case report: Hyperthermia and rhabdomyolysis of unknown origin, a ryanodine receptor problem? H.A.R. Biersteker¹, C. Horlings², J. Raaphorst2, T. Frenzel3 ¹Department of Anesthesiology, pain and palliative care/Radboudumc, ²Department of Neurology/Radboudumc, ³Department of Intensive Care/Radboudumc Introduction We describe a 57-year old patient having a RYR-1 mutation of unknown pathological origin; she was admitted to the intensive care unit (ICU) with rhabdomyolysis and hyperthermia. She was previously treated for Post-traumatic stress syndrome (PTSS) and psychogenic non-epileptic seizures. Family-history was negative for myopathies. Over seven years ago, she started having involuntary contractions of her arms and legs. These contractions became worse when she was emotional and stopped after taking benzodiazepines. They could be triggered by sudden noise or movements. . Results and Treatment Laboratory results showed a raised creatine kinase (CK) of maximum 58.400. EEG was negative for epileptic activity. EMG showed no co-contraction or spasmodic reflex myoclonus (Fig1)(1). All cultures remained negative. CSF examination showed a raised IgG (31mg/L) and anti-GAD antibodies (1604kU/L); both diagnostic markers for stiff-person syndrome (SPS)(2). Genetic testing showed a RYR-1 gene mutation of unknown pathological origin. (C23420 G>A) Muscle biopsy showed some cytoplasmatic bodies and the possibility of multiple core like structures. An In-vitro contracture test was normal. She was treated with intravenous globulines and sedation was reduced, after 3 weeks she could be discharged to the neurology ward, a abnormal stiff walking pattern and spinal lumbal hyperlordosis (Fig2) were noted. Treatment with pregabaline was started, this reduced the seizure frequency and her ambulation improved. Discussion and Conclusion We describe a patient (57yr) with SPS and a RYR-1 mutation of unknown pathological origin. Treatment with sedatives, IVIG and pregabaline reduced symptoms and improved ambulatory status. SPS was deemed the most likely diagnosis considering the fact that she suffered from a hyperlordosis, induced painful spasms and had a raised intrathecal anti-GAD level (3). SPS is heterogeneous as are the RYR-1 related myopathies. This makes diagnosing SPS challenging, to our knowledge this RYR-1 mutation and phenotype with relation to SPS have not been described earlier. Symptoms At admission to the ER the patient was conscious while having involuntary contractions of her arms and legs. Spells slowly disappeared after 4 to 5 minutes without using any medication. She had several myoclonic spells a day, which never-led to loss of consciousness. The seizures were irregular in frequency at the moment of presentation at the ER multiple a day but before admission there could be a seizure free interval of a couple of weeks. Her Glasgow coma scale score in the ER was E4M5V2. She had a fever of 42˚ Celsius and oxygen saturation (SpO2) of 77%. She was intubated because of acute respiratory failure and oxygenation improved after starting mechanical ventilation. In between seizures the patient was able to communicate, neurological examination showed no abnormalities. During the seizures we saw jerking of the arms and legs both symmetrical and asymmetrical, head and neck musculature only participated once. Seizures were triggered by nursing care, monitor alarms or started spontaneously. m. hamstrings m. tibialis anterior Fig 2: Lumbal hyperlordosis m. rectus abdominis left and right 1 Meinck HM et al.. J Neurol. 1995;242(3):134–42. 2 Baizabal-Carvallo JF et al.. J Neurol Neurosurg Psychiatry. 2014;1–9. 3 Snoeck M et al., Eur J Neurol. 2015;22(7):1094–112. Fig 1:Polymyogram: No signs of cortical or propriospinal myoclonus Contact: heleen.biersteker@radboudumc.nl