Journal of Neurology

, Volume 259, Issue 8, pp 1566–1573 | Cite as

Glycine receptor antibodies are detected in progressive encephalomyelitis with rigidity and myoclonus (PERM) but not in saccadic oscillations

  • Takahiro Iizuka
  • Maria I. Leite
  • Bethan Lang
  • Patrick Waters
  • Yoshiaki Urano
  • Saori Miyakawa
  • Junichi Hamada
  • Fumihiko Sakai
  • Hideki Mochizuki
  • Angela Vincent
Original Communication


Glycine receptor (GlyR) antibodies were recently identified in a few patients with progressive encephalomyelitis with rigidity and myoclonus (PERM); none of these patients had antibodies against glutamic acid decarboxylase (GAD). An inhibitory glycinergic transmission defect has also been implicated in the mechanism underlying saccadic oscillations, including ocular flutter or opsoclonus; GlyR antibodies have not been reported in these patients. The purpose was to determine whether GlyR antibodies are found in patients with PERM, ocular flutter syndrome (OFS), and opsoclonus-myoclonus syndrome (OMS). GlyR antibodies were first measured in archived sera and CSF from five patients, including one patient with GAD antibody-positive PERM, two patients with OFS, and two patients with OMS. GlyR antibodies were also measured in archived sera from nine other adult patients with OMS. GlyR antibodies and GAD antibodies were both found at high titers in the serum and CSF of the patient with PERM, and their levels paralleled disease activity over time. GlyR antibodies were not found at significant levels in 13 patients with saccadic oscillations. GlyR and GAD antibodies can co-exist in PERM and follow the clinical course. Although saccadic oscillations are a feature of this condition, GlyR antibodies are not commonly found in patients with isolated saccadic oscillations.


Glycine receptor Autoantibodies Opsoclonus–myoclonus syndrome Stiff-person syndrome 



We are extremely grateful to all participants and staff for their contributions to this study and for clinical data collection, and to Dr. Alexander Carvajal for some of the GlyR antibody assays. AV, BL, and Oxford University hold patents and receive royalties and payments for the antibody assays. AV is a consultant for Athena Diagnostics and receives occasional honoraria for lectures; AV and MIL receive support from the National Institutes of Health Research (NIHR) Oxford Biomedical Research Centre. The other authors have nothing to disclose regarding conflicts of interest or commercial relationships including grants, honoraria, speaker’s lists, significant ownership, or financial support from pharmaceutical or other companies.

Conflicts of interest


Supplementary material

415_2011_6377_MOESM1_ESM.doc (28 kb)
Supplementary material: (DOC 28 kb)
415_2011_6377_MOESM2_ESM.eps (2.4 mb)
Supplementary figure: Schematic representation of neuronal machinery for horizontal conjugate eye movements [13]. Horizontal eye movements are controlled by the horizontal gaze-holding network (neural integrator), including the NPH and MVN. The abducens nucleus (horizontal gaze center) contains abducens motoneurons and abducens internuclear neurons. The abducens nucleus receives excitatory cholinergic signals from the ipsilateral NPH and excitatory glutamatergic signals from the contralateral MVN as well as excitatory saccadic commands from the ipsilateral EBNs. The abducens nucleus also receives inhibitory glycinergic signals from the contralateral NPH and ipsilateral MVN as well as inhibitory saccadic commands from the contralateral IBNs. The OPNs send inhibitory glycinergic signals to the EBSs and IBNs. Excitatory projections are shown in red, and inhibitory projections in blue. Ach; acetylcholine, ATD; ascending tract of Deiters, asp; aspartate, CN III; oculomotor nucleus, CN IV; trochlear nucleus, EBNs; excitatory burst neurons, glu; glutamate, gly; glycine, HC; horizontal semicircular canal, IBNs; inhibitory burst neurons, LR; lateral rectus, MLF; medial longitudinal fasciculus, MR; medial rectus, MVN; medial vestibular nucleus, NPH; nucleus prepositus hypoglossi, OPNs; omnipause neurons, PPRF; paramedian pontine reticular formation (EPS 2,472 kb)

Video 1a: Video 1a and b was recorded on admission before treatment (July 2008) when the patient was re-admitted to our hospital with relapse of symptoms. Video 1 shows the stiff face, stiffness in the lower facial and cervical muscles, left gaze palsy, slow saccade to the left, and right gaze-evoked counterclockwise rotatory nystagmus (MP4 14,131 kb)

Video 1b: (MP4 14,383 kb)

Video 2 was recorded on discharge after treatment (September 2008). Video 2 shows resolution of the symptoms (MP4 8,018 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Takahiro Iizuka
    • 1
  • Maria I. Leite
    • 2
  • Bethan Lang
    • 2
  • Patrick Waters
    • 2
  • Yoshiaki Urano
    • 1
  • Saori Miyakawa
    • 1
  • Junichi Hamada
    • 1
  • Fumihiko Sakai
    • 3
  • Hideki Mochizuki
    • 1
  • Angela Vincent
    • 2
  1. 1.Department of NeurologyKitasato University, School of MedicineSagamiharaJapan
  2. 2.Nuffield Department of Clinical NeurosciencesJohn Radcliffe Hospital, Oxford UniversityOxfordUK
  3. 3.Saitama International Headache CenterSaitama Neuropsychiatric InstituteSaitamaJapan

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