Anesthetic considerations in scoliosis patient with dopa-responsive dystonia or Segawa’s syndrome

Abstract

Segawa’s syndrome or dopa-responsive dystonia is a rare hereditary disorder characterized by progressive dystonia of childhood onset, diurnal fluctuation of symptoms and complete or near complete alleviation of symptoms with administration of low-dose oral levodopa. From our literature search in PubMed, we found only three related publications: two on anesthesia for cesarean section and one on anesthesia for electroconvulsive therapy. We report our experience in providing anesthesia for corrective scoliosis surgery in two biological sisters with Segawa’s syndrome. A review of the literature is also included.

Introduction

Segawa’s syndrome or dopa-responsive dystonia (DRD) is a rare hereditary disorder with an estimated prevalence of 0.5 per million population. ¹ Clinically, it is characterized by three hallmarks of presentation: progressive dystonia of childhood onset, diurnal fluctuation of symptoms, and complete or near complete alleviation of symptoms with administration of low-dose oral levodopa. ²

Given the rarity of DRD, we only found three publications on PubMed: two on anesthesia for cesarean section and one for electroconvulsive therapy. ^{3 –5} Here, we report our experience in providing anesthesia for scoliosis surgery in two sisters. Permission to publish was obtained from the children’s parents.

Case reports

Case 1

A 14-year-old, 44-kg girl with DRD and neuromuscular scoliosis presented to our center for posterior spinal fusion. Since 7 years of age, she started experiencing generalized muscle weakness, clumsiness, and involuntary dystonic movement at rest. Her symptoms have a diurnal fluctuation. Metabolic, connective tissue and inborn error of metabolism screening, magnetic resonance imaging of brain, nerve conduction study, and muscle biopsy were done but unremarkable. At the age of 12, the diagnosis of DRD was made after a positive phenylalanine-loading test. She had a complete resolution of muscle weakness and dystonic movement after commencement of low-dose oral levodopa, 31.25 mg twice daily. Her thoracic scoliosis has a Cobb angle of 50° (Figure 1) and posterior fusion from T2 to T12 was planned. Preoperatively, she was asymptomatic and physical examination was unremarkable. Lung function test and preoperative blood investigations were normal. Oral levodopa was continued on the morning of surgery.

Figure 1.

Preoperative radiograph showed a thoracic scoliosis with a Cobb angle of 50°. Postoperative radiograph showing an instrumentation fusion performed from T2 to T12 with a Cobb angle of 18°. A correction rate of 64% was achieved.

Total intravenous anesthesia (TIVA) was used for this patient. She was induced with target controlled infusion (TCI) propofol (Marsh model) with target effect site concentration (c_et) of 4 μg/ml, TCI remifentanil (Minto model) with c_et of 5 ng/ml, and intravenous (IV) rocuronium 0.6 mg/kg to facilitate tracheal intubation. Anesthetic monitoring includes pulse oximetry, capnography, electrocardiogram, intra-arterial blood pressure, and bispectral index. Neurophysiological monitoring was in the form of somatosensory-evoked potential (SSEP) and motor-evoked potential. IV dexamethasone 4 mg was given at induction followed by IV tranexamic acid 20 mg/kg. Acute normovolemic hemodilution (ANH) was performed in which 700 ml of blood was collected with concurrent replacement of equal volume of 6% hydroxyethyl starch 130/0.4 (Voluven®, Fresenius Kabi Deutschland GmbH, Germany). Intraoperative autologous blood recovery system (Cell Saver® 5+, Haemonetics Corporation, Brintree, MA) was also used.

TIVA was maintained to achieve bispectral index (BIS) value of 40–60. Estimated blood loss was 2 l. Intraoperative fluid losses were replaced with 0.5 l normal saline, 1.5 l Ringer’s lactate solution, 700 ml autologous blood harvested from ANH, and 600 ml autologous blood salvaged via cell saver. No allogenic blood products were transfused. Urine output was 0.8–1 ml/kg/h. Patient was kept normothermic with the use of forced air warming device (Bair Hugger®, 3M, USA) and fluid warming device (HOTLINE®, Smith Medical ASD Inc, USA). The surgery lasted 4 h 30 min.

At the end of surgery, IV morphine 0.15 mg/kg and IV ondansetron 4 mg were given. Muscle relaxation was reversed with IV neostigmine 0.05 mg/kg and IV atropine 0.02 mg/kg. At emergence of anesthesia, patient was awake, able to lift head with good handgrip strength. She was extubated to face mask oxygen 5 l/min. In the postanesthetic care unit, patient was started on patient-controlled analgesia morphine before discharged to high dependency unit. There was no residual motor weakness or dystonia. In the ward, levodopa was restarted at the same preoperative dose. She was discharged home on postoperative day 3.

Case 2

This second 11-year-old, 37-kg girl is the younger sibling who presented to our center for posterior spinal fusion. She presented to our hospital with similar symptoms at the age of 6. She was diagnosed with DRD at 9-years old at about the same time as her sister, following a positive phenylalanine-loading test. Like her sister, she made a full recovery after receiving levodopa 31.25 mg twice daily. Her thoracic scoliosis has a Cobb angle of 70° (Figure 2), and posterior fusion from T2 to T12 was planned.

Figure 2.

Preoperative radiograph showed a thoracic scoliosis with a Cobb angle of 70°. Postoperative radiograph showing an instrumentation fusion performed from T2 to T12 with a Cobb angle of 25°. A correction rate of 67% was achieved.

Anesthesia was induced with IV fentanyl 2 μg/kg, IV propofol 2.5 mg/kg, and IV rocuronium 0.6 mg/kg to facilitate tracheal intubation. Anesthesia was maintained using sevoflurane in oxygen with end-tidal concentration of 2.0–2.5% (minimum alveolar concentration of 0.8–1.0). Only SSEP monitoring was used. ANH was performed in which 425 ml of blood was withdrawn and replaced with Voluven® in 1:1 ratio. She received IV morphine 0.25 mg/kg and IV rocuronium infusion at 0.1–0.3 mg/kg/h to maintain a train-of-four (TOF) count of less than 2 intraoperatively. Estimated blood loss was 1.8 l. She received 1.5 l Ringer’s lactate solution, 425 ml of autologous blood harvested from ANH, and 700 ml of autologous blood salvaged via cell saver. Allogenic blood products were not used intraoperatively. Urine output was 0.6–0.9 ml/kg/h. Surgery duration was 4 h 20 min.

At the end of surgery, rocuronium infusion was stopped at skin closure. TOF ratio before reversal of muscle relaxant was 0.65. IV sugammadex 2 mg/kg was administered and TOF ratio improved to 1.0 within 100 s. Patient was extubated to face mask oxygen 5 l/min. Levodopa was restarted as soon as patient tolerated orally. Her postoperative recovery was uneventful, and she was discharged on postoperative day 4.

Discussion

These are the first reported cases of general anesthesia for patient with DRD presented for corrective scoliosis surgery.

Segawa’s syndrome or DRD is a rare disorder with a prevalence of 0.5 per million. ^1,6 Majority of DRD is inherited in an autosomal dominant manner caused by heterozygous mutations in GCH-1 gene coded in chromosome 14q.22.1–q22.2, with 75% of DRD index cases showing this defect. ⁷ The gene is responsible for conversion of tyrosine to dopamine. ⁸ Its mutation results in dopamine deficiency, which is an important neurotransmitter in the nigrostriatal pathway in the basal ganglia.

Clinically, onset of dystonia is between 4- and 6-years old with female-to-male ratio of 2.5:1. ^7,9 The dystonia is often insidious in onset with diurnal fluctuation, leading to unsteady gait, clumsiness, and abnormal posture. ^2,10,11 Physical examination will demonstrate a hypomimic child with wide-based gait, normal mentation, and muscle bulk. Muscle tone is increased, reflexes are exaggerated, and extensor plantar response is elicited. ^6,10,12

Diagnosis of DRD is made on clinical ground with characteristic history and complete resolution with low-dose levodopa. Phenylalanine loading test has been shown to have high sensitivity and specificity. ¹³ Lumbar puncture for cerebrospinal fluid examination will demonstrate a decreased level of tetrahydrobiopterin and homovanillic acid, but it is not usually done due to its invasiveness. ^14,15

Treatment of DRD involves low-dose oral levodopa and would have good prognosis if treated. ^3,7,12 For both our patients, levodopa was continued until morning of surgery and resumed immediately after surgery as levodopa has a short half-life of 60–90 min due to its rapid conversion in the peripheral circulation. ¹⁶

Medications with antagonistic action on dopamine receptor, such as phenothiazines, butyrophenones, and metoclopramide, may induce or worsen dystonia. ^17,18 Thus, these medications are best avoided perioperatively. We did not use metoclopramide as postoperative nausea vomiting prophylaxis; however, one case reported its safe use. ⁴

Propofol administration has been associated with excitatory phenomena in human, including opisthotonus, dystonia, and myoclonic seizure, which could be refractory to treatment. ¹⁹ Propofol exerts a strychnine-like effect on subcortical glycine receptors, leading to neuroexcitation. It also increases GABAergic inhibition to the thalamus, leading to thalamocortical oscillations. ²⁰ In addition to propofol, ondansetron has also been associated with dystonic movement especially when both used together. ²¹ We used TCI propofol for our first patient without precipitating dystonia. Ondansetron was also used safely in both our patients.

Inhalational anesthetics at clinically relevant concentration have been shown to inhibit synaptic reuptake of dopamine, therefore increasing its extracellular concentration. ²² This is made worse by concurrent use of levodopa, which is converted in the peripheral circulation to dopamine. It is suggested that halothane, which sensitizes the heart to catecholamines, should be avoided, but sevoflurane and isoflurane are less arrhythmogenic and are safe. ²³

A case report of suxamethonium used in patient with DRD undergoing cesarean section showed that hyperkalemia does not occur even at higher dose of 1.5 mg/kg. ³ However, the author did use a pre-curare dose of atracurium, which reduces fasciculation, and therefore reducing the risk of hyperkalemia. Another report showed that the use of suxamethonium in a patient with DRD undergoing serial electroconvulsive therapy (ECT) did not lead to motor function impairment. ⁵ Both our patients received non-depolarizing muscle relaxant with neuromuscular monitoring. We noted that monitoring of neuromuscular junction showed comparable pattern of onset, duration, and reversal as in normal subjects.

Neuromuscular disorders are associated with increased perioperative pulmonary complications related to muscle weakness. The use of sugammadex, the first selective relaxant binding agent, is safe in patients with neuromuscular disease, which has led to complete reversal of rocuronium in our second case. ²⁴

Conclusion

In conclusion, anesthesia for patients with DRD should be meticulously planned and carried out. Dystonic symptoms should be optimized, interruption of oral levodopa administration should be minimized, potential worsening of dystonia with dopamine receptor antagonist should be noted, and muscle relaxation should be reversed completely prior to extubation. Both TIVA and inhalational anesthesia seem safe for patients with DRD.