A 19-year-old girl with history of CP was scheduled for DBS of the globus pallidus pars internus (GPi) bilaterally due to medically refractory dystonia and rigidity . Her medication consisted of 300 mg/day levodopa, 2 mg/day diazepam, and 60 mg/day baclofen. It was not necessary to gain clinical information by intraoperative stimulation during surgery because the operation was carried out under monitored anesthesia care (MAC) with propofol and continuous infusion of remifentanil. So she took routine medication in the morning of operation day. During the DBS prcedure, she was lightly sedated with dose adjustment of propofol and remifentanil to maintain bispectral index of 60-80. The procedure was uneventful, with an implantation of DBS electrodes in the GPi bilaterally (Medtronic 3387 electrodes; Medtronic, Minneapolis, MN, USA). A postoperative brain computer tomography showed no intracranial abnormality and confirmed optimal lead placement (Fig. 1). The patient initially showed a normal awakening and normal laboratory findings except mild respiratory acidosis (Table 1). However, on postoperative 2 h, she manifested spasticity and muscle rigidity and took her medications, such as levodopa to relieve these symptoms. At that time, she had a high fever (40.6℃) resistant to anti-pyretic drugs (propacetamol 1 g). We suspected that hyperthermia was caused by postoperative atelectasis, but chest X-ray showed no significant abnormality except postoperative ileus (Fig. 2). On postoperative 16 h, her general condition worsened convulsively despite aggressive care. She developed severe rigidity, tachycardia (heart rate: 170 beats/min), hyperventilation (respiration rate: 30 frequencies/min), and agitation. Her temperature had risen to 42°C, which was refractory to copious cooling treatment such as surface tepid massage, and her blood pressure had increased to 149/77 mmHg (Fig. 3).

On postoperative 20 h, she fell rapidly into a coma and showed bilateral pupil fixation (Glasgow Coma Scale: 3). Immediately thereafter, she suffered cardiac arrest, We then started cardiopulmonary resuscitation (CPR) on her. A subsequent laboratory investigation showed leukocytosis (leukocyte count, 19.3 × 10⁹ /L) with a shift to the left (Table 2). The serum creatine kinase (CK) level was markedly elevated to 50,038 IU/L. She also had high liver transaminases (serum glutamic-oxaloacetic transminase: 767 IU/L, serum glutamic-pyruvic transminase: 116 IU/L), hyperkalemia (serum potassium level: 6.4 mmol/L) and metabolic acidosis on blood gas analysis (pH 7.13, PCO₂ 42.0 mmHg, HCO₃ 11.9 mmol/L). We tried to revive her with CPR for 50 minutes, but failed to resuscitate her.

This is the first case report of NMS related to the DBS in a CP patient without a dose reduction of dopaminergic agents during perioperative period.

NMS is a rare, fatal, and adverse reaction to neuroleptic drugs.[8] This could be triggered by the introduction of dopaminergic antagonist drugs (e.g. haloperidol) or the withdrawal of dopaminergic agonists (e.g. levodopa). Due to the association of NMS with dopaminergic agents, NMS is hypothesized to be related to a dopaminergic blockade in the hypothalamus. A defined diagnosis of NMS requires both essential features (hyperthermia and severe rigidity) and associated symptoms and signs (elevation of CK level, tachycardia, and altered mental status), which are listed in the Diagnostic and Statistical Manual of Mental Disorders. [8,9] A life-threatening complication of NMS is rhabdomyolysis, which is evidenced by an extreme elevation of the CK levels, myoglobinuria and acute renal failure.[10] Treatment of NMS is the rapid withdrawal of neuroleptic agents or replacement of dopaminergic agonists depending on early clinical recognition along with supportive care, which includes temperature control, rehydration, alkalization of urine to prevent renal failure, and repair of electrolyte balance.[5] In addition, bromocriptine (a dopaminergic agonist), amantadine (a dopaminergic agonist and a cholinergic antagonist), and dantrolene (a direct-acting skeletal muscle relaxant) can be also used.

Dopaminergic agents such as levodopa, are usually used in patients with Parkinson’s disease (PD). It also has been used in cases with dystonic symptoms related to CP.[11] In these days, DBS has been used as a major therapeutic modality for movement disorders, such as PD, essential tremor and dystonia.[12,13] In particlar, DBS in GPi has been reported to be significantly useful in patients with dystonia.[14] Vidalihet et al.[1] showed that bilateral DBS also resulted in the improvement of motor symptoms and functional disability in CP patients with dystonia over a year.

The standard procedure of DBS is to use local anesthesia for intraoperative MER. This method allows intraoperative evaluation of the stimulation-induced improvement. [15] Thus, discontinuation of dopaminergic medication is, in clinical practice, common prior to DBS surgery, which can induce NMS in a previous study.[16] In our study, we performed the procedure under MAC. Therefore, her medications were not stopped preoperatively because we would not awaken the patient during the operation to evaluate stimulation-induced improvement. Moreover, dopaminergic medication was continued and anti-psychotic agents that have anti-dopaminergic effects were not administered during postoperative period. Nevertheless, this case report shows that symptoms and signs of NMS can be presented without reducing or discontinuing the drug. We did not explain the exact reason why NMS occurred in this patient postoperatively. A possible explanation is that DBS surgery per se might disrupt the absorption of dopaminergic drug by altering bowel movement and subsequently resulting in low blood concentration of dopaminergic agents. A previous study demonstrated that NMS resulted from a decreased intestinal absorption of dopaminergic agents in a patient with ileus.[17]

There are some diseases showing clinical manifestations similar with NMS. We can easily distinguish NMS from malignant hyperthermia because of different triggering agents. Succinylcholine and inhalation agents are triggering agents for malignant hyperthermia while neuroleptic agents for NMS. Status epilepticus rarely causes high fever. Encephalitis also causes an elevation in body temperature, but the peak value of fever is lower in encephalitis than in NMS. Moreover, rhabdomyolysis is rarely shown in encephalitis. [18,19]

In conclusion, clinicians should consider NMS as a differential diagnosis when high fever refractory to conventional treatments, spasticity, and severe rigidity following the DBS surgery are manifested in a CP patient, who take dopaminergic medication on schedule time during the perioperative period. Early diagnosis and rapid aggressive management for NMS should be needed to prevent the regrettable result.