Secondary Logo

Share this article on:

Stiff Person Syndrome and Anesthesia: Case Report

Bouw, Jans MD*; Leendertse, Karin MD*; Tijssen, Marina A. J. MD, PhD; Dzoljic, Misa MD, PhD*

doi: 10.1213/01.ANE.0000072701.97699.79

IMPLICATIONS: This case report describes the successful perioperative management of a patient with a rare and disabling neurologic disorder, the stiff person syndrome. The patient had a delayed emergence despite apparent full reversal of neuromuscular blockade. We suggest an interaction between the GABAergic effects of baclofen and volatile anesthetics as a possible cause.

*Departments of Anesthesiology and †Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

April 1, 2003.

Address correspondence and reprint requests to J. Bouw, MD, Department of Anesthesiology, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands. Address e-mail to

Stiff person syndrome (SPS) is a rare and disabling neurologic disorder characterized by muscle rigidity and episodic spasms that involve axial and limb musculature (1–3). The literature points toward an autoimmune disorder resulting in a malfunction of γ-aminobutyric acid (GABA)-mediated inhibitory networks in the central nervous system (4). Anesthetic implications are less well described. We report a case of prolonged hypotonicity after general anesthesia in a patient with SPS and discuss the possible anesthetic interactions.

Back to Top | Article Outline

Case Report

A 62-yr-old woman (height, 1.70 m; weight, 61 kg) was scheduled for resection of a colon carcinoma. Her medical history revealed hypothyroidism, vitamin B12 deficiency, and SPS. This syndrome started with low back pain, which rendered her unable to walk. She was experiencing stiffness, involuntary jerks, and painful cramps. Neurological examination revealed extreme hypertonia of the body and proximal legs, with intercurrent, painful spasms. Reflexes were symmetrical without Babinski signs. Laboratory findings showed positive glutamic acid decarboxylase (GAD) and negative amphiphysin antibodies. The patient was successfully treated with baclofen and diazepam. Subsequently, prednisone as immunosuppressive therapy was started. The stiffness diminished, and the patient was able to walk unaided. The neurological examination was unremarkable, except for a slight stiffness in the legs. Her medication at admission was prednisone 20 mg once a day, baclophen 12.5 mg twice a day (daily dose = 25 mg), diazepam 7.5 mg twice a day (daily dose = 15 mg), levothyroxine 25 μg once a day, and vitamin B12 injections. Her medical history included urological and gynecological surgery under general anesthesia before she experienced SPS.

No premedication was given. Anesthesia was induced with propofol (2.5 mg/kg) and sufentanil (0.25 μg/kg). After the administration of atracurium (0.6 mg/kg), the trachea was intubated, and anesthesia was continued with isoflurane (0.6–1.0 vol%) and oxygen/air for the duration of the procedure. Cefuroxime 1500 mg, clindamycin 600 mg, and dexamethasone 10 mg were administered IV. In the following 2 h, additional atracurium (35 mg), sufentanil (10 μg), and morphine (8 mg) were administered. At the end of the procedure, which was uneventful, neuromuscular monitoring showed four strong twitches. Although the patient was responsive, she could not open her eyes, grasp with either hand, or generate tidal volumes beyond 200 mL. Neostigmine 2 mg (0.03 mg/kg) and glycopyrrolate 0.2 mg did not alter the clinical signs of muscle weakness.

The patient was sedated with propofol 5 mg · kg−1 · h−1 and further mechanically ventilated in the recovery room. After 1 h, the sedation was stopped and mechanical ventilation was terminated. At that time, baclofen 12.5 mg was administered into the gastric tube. Two hours later she was in a good clinical condition, and her trachea was extubated.

Back to Top | Article Outline


SPS was recognized as a distinct entity in 1956 by Moersch and Woltman (5). An autoimmune pathogenesis is suspected because of the presence of antibodies against GAD, the rate-limiting enzyme for synthesis of the inhibitory neurotransmitter GABA, and the association of the disease with other autoimmune conditions such as diabetes and thyroiditis (6,7). Loss of inhibition from higher centers causes hyperactivity of the γ-motor neuron system and subsequent progressive muscle rigidity. Patients with SPS have high immunoglobulin G/anti-GAD-65 antibodies, which are synthesized intrathecally and seem to impair the in situ synthesis of GABA (8,9). Two types of drugs have been applied: drugs that enhance GABA activity and immunosuppressing drugs. Diazepam, which increases the frequency of opening of the GABAA receptor and leads to hyperpolarization, is the initial treatment of choice at daily doses up to 200 mg. Intrathecal or oral baclofen may improve the physical symptoms just like prednisone, plasmapheresis, and large-dose IV immunoglobulin (10).

In our case, several drugs could have caused muscle weakness (11). Initially atracurium could be suspected. Computer-simulated pharmacokinetic analyses suggested that plasma concentrations were far less than therapeutic levels. The same can be said for opioids, fentanyl, and morphine (Fig. 1) (12–15). In the recovery room while the patient was still ventilated, it showed a diazepam serum concentration of 0.317 mg/L (therapeutic range, 0.125–0.75 mg/L). Because IV drugs can be excluded as causing muscular weakness, perhaps volatile anesthetics were the cause. In the case report by Johnson and Miller (10), muscle weakness was observed only when baclofen was combined with inhaled desflurane or isoflurane. Delayed arousal and muscle weakness were also described, unrelated to SPS, in a patient receiving baclofen and undergoing anesthesia with isoflurane 1%(16). In addition, recent animal studies show that baclofen enhances volatile anesthetic-induced anesthesia (17). Perhaps the complicated course of recovery was most due to the interaction between isoflurane and baclofen causing muscle weakness.

Figure 1

Figure 1

We thus conclude that the prolonged muscle relaxation can be explained by the enhancement of general anesthetics via GABAB action on synaptic transmission (17). This case demonstrates a potential danger in combining baclofen with volatile anesthetics in patients with SPS.

Back to Top | Article Outline


1. Brown P, Marsden CD. The stiffman and stiffman plus syndromes. J Neurol 1999; 246: 648–52.
2. Meinck HM. Stiff man syndrome. CNS Drugs 2001; 15: 515–26.
3. Lorish TR, Thorsteinsson G. Stiff-man syndrome updated. Mayo Clin Proc 1989; 64: 629–36.
4. Levy LM, Dalakas MC. The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid. Ann Intern Med 1999; 131: 522–30.
5. Moersch FP, Woltman HW. Progressive fluctuating muscular rigidity and spasm (“stiff man” syndrome): report of a case and some observations in 13 other cases. Proc Staff Meet Mayo Clin 1956; 31: 421–7.
6. Dalakas MC, Fujii M, Li M, et al. The clinical spectrum of anti-GAD antibody-positive patients with stiff person syndrome. Neurology 2000; 55: 1531–5.
7. Solimena M, Folli F, Aparisi R, et al. Autoantibodies to GABAergic neurons and pancreatic beta cells in stiff man syndrome. N Engl J Med 1990; 322: 1555–60.
8. Dalakas MC, Li M, Fujii M, et al. Stiff person syndrome, quantification, specificity, and intrathecal synthesis of GAD65 antibodies. Neurology 2001; 57: 780–4.
9. Chang HC, Davis KM, Jin H, et al. Association of L-glutamic acid decarboxylase to the 17-kDa heat shock protein as a potential anchoring mechanism to synaptic vesicles. J Biol Chem 2000; 275: 20822–8.
10. Johnson JO, Miller KA. Anesthetic implications in stiff-person syndrome. Anesth Analg 1995; 80: 612–3.
11. Al Ahar O, Bevan DR. Clindamycin-induced neuromuscular blockade. Can J Anaesth 1995; 42: 614–7.
12. Maitre PO, Ausems ME, Vozeh S, et al. Evaluating the accuracy of using population pharmacokinetic data to predict plasma concentrations of alfentanil. Anesthesiology 1988; 68: 59–67.
13. Bovill JG, Sebel PS, Blackburn CL, et al. The pharmacokinetics of sufentanil in surgical patients. Anesthesiology 1984; 61: 502–6.
14. Murphy MR, Hug CC. The pharmacokinetics of intravenous morphine in patients anaesthetised with enflurane-nitrous oxide. Anesthesiology 1981; 54: 187–92.
15. Weatherley BC, Williams SG, Neill EA. Pharmacokinetics, pharmacodynamics and dose-response relationships of atracurium administered i.v. Br J Anaesth 1983; 55 (Suppl 1): 39S–45S.
16. Gomar C, Carrero EJ. Delayed arousal after general anesthesia associated with baclofen. Anesthesiology 1994; 81: 1306–7.
17. Sugimura M, Kitayama S, Morita K, et al. Effects of GABAergic agents on anesthesia induced by halothane, isoflurane and thiamylal in mice. Pharmacol Biochem Behav 2002; 72: 111–6.
© 2003 International Anesthesia Research Society