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Progressive Encephalomyelitis with Rigidity and Myoclonus: Anesthesia and Glycine Receptor Antibodies

Papadopoulou, Aikaterini MBBS; Samuels, Theophilus Luke MBBS; Dassanayake, Asitha MBBS; Spring, Colin MBBS; Willers, Johann MBChB; Uncles, David Roy MBBS

doi: 10.1097/ACC.0b013e3182a6d853
Case Reports: Case Report

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare autoimmune neurological condition. Antibodies targeting glycine receptors (GlyR) have been implicated in PERM. Because GlyR activity is enhanced by inhaled anesthetic drugs at clinically relevant concentrations, there is a theoretical possibility that these drugs may be less effective in the presence of GlyR antibodies. We describe a case of general anesthesia in a patient with PERM and GlyR antibodies. This patient did not demonstrate a clinically significant alteration in the behavioral effects of anesthesia using induction of anesthesia with sevoflurane and maintenance of anesthesia using sevoflurane and nitrous oxide.

From the Department of Anesthesia, Worthing Hospital, Worthing, United Kingdom.

Accepted for publication July 11, 2013.

Funding: None.

The authors declare no conflicts of interest.

Address correspondence to Aikaterini Papadopoulou, MBBS, Department of Anesthesia, Worthing Hospital, Lyndhurst Road, Worthing, West Sussex, BN11 2DH, United Kingdom. Address e-mail to

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is usually described within the spectrum of stiff person syndrome (SPS). PERM, a rare autoimmune neurological disorder, in a subgroup of patients with SPS, is associated with the presence of antibodies to glycine receptors (GlyR).1 While a few case reports describe the anesthetic implications of SPS, to our knowledge, there are no published reports specifically recording the conduct of anesthesia in PERM. Based on the fact that inhaled anesthetic drugs enhance GlyR activation, it is reasonable to assume a potential interaction might occur in which the disease mechanism has the capacity to influence the mechanism of anesthetic action. We present a case of general anesthesia in a patient with GlyR antibody-mediated PERM.

Written patient consent was obtained for publication of this report.

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A 40-year-old man recently diagnosed with GlyR antibody-mediated PERM presented for resection of a perianal tumor. His initial presentation included brainstem dysfunction manifesting as respiratory distress with stridor requiring prolonged respiratory support in our intensive care unit. At this stage, limb rigidity became apparent with the lower limbs being affected more than the upper limbs. This was accompanied by stimulus-sensitive myoclonus. GlyR antibodies were measured in serum and cerebrospinal fluid by binding of the patient’s antibodies to the surface of live human embryonic kidney cells expressing the GlyR α1 subunits, as described by Hutchinson et al.1 Shortly after presentation, the serum GlyR antibody titer measured was 1:600, and the cerebrospinal fluid GlyR antibody titer was 1:40. Thirty days before this operation and 2 days postoperatively, the serum antibody titer was 1:200. Immediately before the operation, the patient experienced dysarthria, ophthalmoplegia with diplopia, and intermittent stridor. Muscle tone was clinically increased, and there were fixed contractures of long finger flexor muscles bilaterally. Treatment included a course of IV immunoglobulins, plasma exchange, systemic steroids, and intrathecal baclofen after insertion of an intrathecal pump. To avoid damage to or compromise the function of the intrathecal device, we opted to administer general anesthesia to accommodate resection of the perianal tumor. Due to residual vocal cord dysfunction and previous difficulty achieving separation from mechanical ventilation, anesthesia was induced by inhalation of sevoflurane in oxygen (Dräger Primus, Hemel Hempstead, United Kingdom). Muscle rigidity was repeatedly assessed by passive flexion-extension of the patient’s forearm both before and during induction of anesthesia. The rigidity observed clinically before induction became markedly reduced (approaching “normality”) at an end-tidal sevoflurane concentration of 1.6%, although at this concentration the patient still responded to verbal commands. When the end-tidal sevoflurane concentration was increased further, the patient became progressively less responsive, and at an exhaled concentration of 2% sevoflurane, there was no response to painful stimulus. After breathing sevoflurane at 1 minimum alveolar concentration for 10 minutes, successful laryngeal mask insertion was achieved. Anesthesia was maintained with sevoflurane (recorded end-tidal sevoflurane concentration 2.2%) and 30% nitrous oxide (N2O). This corresponded to a minimum alveolar concentration value of 1.3 that was calculated by the anesthetic machine’s internal software program using the variables of age and the respective concentrations of sevoflurane and N2O. Surgery concluded after 2 hours. Muscle rigidity recurred approximately 10 minutes after discontinuing anesthesia, and the patient regained consciousness appropriately after 20 minutes with no recollection of awareness associated with the surgery.

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SPS is characterized by muscle rigidity and is associated with the presence of antibodies against glutamic acid decarboxylase (GAD), the rate limiting enzyme in the synthesis of γ-aminobutyric acid (GABA). Currently, it is unclear whether PERM is a severe form of SPS or a completely different syndrome. PERM manifests as muscle rigidity and encephalopathy with hyperekplexia, brainstem, and autonomic dysfunction. Our patient tested positive for GlyR but negative for GAD antibodies. The magnitude of the GlyR antibody titer recorded in our patient was similar to that published in the original report of a patient with acknowledged features of PERM in which the presence of GlyR antibodies was linked to this condition.1 Accordingly, our case constitutes a clinically significant titer.

GlyR are ligand-gated chloride channels involved in inhibitory neurotransmission and distributed mainly in the brainstem and spinal cord. General anesthetics alter the function of a variety of ligand-gated ion channels including GABAA, glycine, serotonin-3, and nicotinic acetylcholine receptors. The mechanism by which inhaled anesthetic drugs exert their behavioral effects remains unproven. Volatile drugs, including sevoflurane, administered in a clinically relevant range, enhance the activation of GlyR. Conversely, N2O appears to act predominantly via inhibition of N-methyl-D-aspartate receptors.2 Theoretically, propofol and particularly inhaled anesthesia might be less effective in the presence of GlyR antibodies. Propofol previously administered to this patient in the intensive care unit provided the requisite sedation intended, suggesting that propofol’s action is not necessarily altered clinically by GlyR antibodies alone. In our patient, the expected effects of volatile anesthesia were not affected in the presence of GlyR antibodies. This finding is consistent with the work of Borghese et al.3 who investigated the anesthetic potency in mature knock-in mice with GlyR mutations. Despite observing a change in volatile anesthetic enhancement using GlyR mutations incorporated within in vitro models, they did not demonstrate an alteration in anesthetic potency in vivo. This led them to infer that immobility associated with volatile anesthetics is not necessarily mediated entirely by GlyR and that other mechanisms may need to be considered.3 Our clinical experience in the patient we have described would tend to support Borghese et al.’s conclusions.3

Furthermore, in the case we have described, discontinuing sevoflurane did not delay arousal or result in prolonged hypotonicity during the recovery phase as previously described in a case of SPS with concurrent baclofen use, attributed to the pharmacodynamic interaction between baclofen and the inhaled drug on GABAB receptors.4 We elected to avoid muscle relaxants because their use has been associated with prolonged weakness, although it is unclear whether this was due to the persistence of relaxant activity or the inhalational-baclofen combination.5

We should point out a limitation to the interpretation of our results. The therapies received by our patient (IV immunoglobulins, plasma exchange, systemic steroids, and intrathecal baclofen—a GABAA agonist) may have decreased or countered the effect of the increased antibodies on anesthetic requirement. If so, it appears that the countering was done perfectly, perhaps fortuitously resulting in a normal response to the anesthesia with sevoflurane and N2O. Our purpose in publishing this report is to prompt similar reports of patients with antibody-mediated PERM—reports that might minimize or eliminate the application of confounding factors and thereby better test the effect of GlyR antibodies on the anesthetic state.

In conclusion, we provided inhaled anesthesia to a patient with PERM who tested positive for GlyR antibodies and negative for GAD antibodies and who was receiving intrathecal baclofen. We did not observe any clinically significant variation in the conduct of inhaled anesthesia using sevoflurane and N2O in this patient in spite of a significant GlyR antibody titer. At the present time, it is believed that general anesthetics act on multiple sites, including a variety of receptors, making 1 site unlikely to explain or determine anesthetic potency. Our case suggests that the presence of GlyR antibodies in isolation does not appear to alter the clinical outcome of inhaled anesthesia.

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We wish to acknowledge Professor A. Vincent for her assistance in the preparation of this manuscript.

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3. Borghese CM, Xiong W, Oh SI, Ho A, Mihic SJ, Zhang L, Lovinger DM, Homanics GE, Eger EI 2nd, Harris RA. Mutations M287L and Q266I in the glycine receptor α1 subunit change sensitivity to volatile anesthetics in oocytes and neurons, but not the minimal alveolar concentration in knockin mice. Anesthesiology. 2012;117:765–71
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