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Letter to the Editor

Variant Stiff Person Syndrome or Multiple Sclerosis?

See case report by Naik et al

Variant Stiff Person Syndrome or Multiple Sclerosis?

To the Editor: We read with interest a recently published case report by Naik et al1 wherein the authors describe a man who presented with symptoms of progressive myelopathy with elevated antiglutamic acid decarboxylase (GAD) antibodies, for whom the authors made a diagnosis of variant stiff person syndrome (SPS). The authors indicate that the man also carried a diagnosis of multiple sclerosis (MS), which is quite interesting, as to our knowledge there have been no reports of co-occurrence of MS with SPS. SPS can certainly masquerade as MS and vice versa2; hence, we raise some concerns regarding this patient’s concurrent diagnoses. SPS indeed presents with varied phenotypes, which have been increasingly recognized over the years, including stiff limb syndrome, cerebellar ataxia, and progressive encephalomyelitis with rigidity and myoclonus (PERM) among others.3,4

PERM with antiglycine receptor antibodies in the serum was first described in 2008 in a report5 of a 54-year-old man who presented with myoclonus, hyperkplexia, rigidity, and autonomic dysfunction. Features of PERM include early brain stem involvement, myoclonus, and prominent autonomic symptoms.5,6 Brain stem abnormalities most commonly include bulbar symptoms and oculomotor dysfunction.5,6 There is an association of PERM with both anti-GAD antibodies and antiglycine receptor antibodies.5,6 Brain and spinal cord imaging is typically normal in individuals with SPS and its variants, including PERM,5-7 and should have been described in this case report, especially given the individual’s prior diagnosis of MS, as MS can present with progressive myelopathy and bulbar symptoms as described in this case. Diagnosis of SPS and its variants is quite difficult—it is a rare condition, and extensive evaluation of alternative diagnoses should be pursued, as misdiagnosis can have significant consequences.2 Other important features that are helpful in supporting an SPS diagnosis include presence of anti-GAD antibodies in the cerebrospinal fluid, electromyography findings of cocontraction of agonist and antagonist muscles or continuous motor unit activity in affected muscles (commonly paraspinal muscles or legs), and early robust response to GABAergic agonist therapies.3,7 In addition, it is important to recognize the occurrence of anti-GAD antibodies in both type I and II diabetes mellitus, as anti-GAD is also an antibody against pancreatic antigens.8 The presence of anti-GAD antibodies has been recognized in the majority of individuals with type I diabetes mellitus, as well as a proportion of patients with type II diabetes mellitus, with prior studies citing prevalence of the antibody reported to be up to 10% of individuals with type II diabetes mellitus.8 Moreover, these antibodies have been seen in other disorders (such as thyroid disease), and in up to 5% of individuals with other neurologic conditions and 1% of healthy controls.9 Hence, there is a potential for diagnostic errors when relying too heavily on individual paraclinical test results, especially in neurologic conditions that have overlapping symptoms and signs.

Yujie Wang, MDa

ywang80@jhmi.edu

Scott D. Newsome, DOa

Dr Naik and colleagues were shown this letter and declined to comment.

aDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland

Potential conflicts of interest: Dr Newsome has attended scientific advisory boards meetings for Biogen, Genentech, Celgene, and EMD Serono; has served as an advisor to Gerson Lehrman Group; and has received grant/research funding (paid directly to institution) from Biogen, Genentech, US Department of Defense, National Multiple Sclerosis Society, and Patient Centered Outcomes Research Institute. Dr Wang reports no conflicts of interest related to the subject of this report.

Funding/support: None.

Published online: November 27, 2019.

Prim Care Companion CNS Disord 2019;21(6):19l02459

To cite: Wang Y, Newsome SD. Variant stiff person syndrome or multiple sclerosis? Prim Care Companion CNS Disord. 2019;21(6):19l02459.

To share: https://doi.org/10.4088/PCC.19l02459

© Copyright 2019 Physicians Postgraduate Press, Inc.

References

1.Naik S, Kolikonda MK, Lippmann S. Progressive encephalomyelitis with rigidity: stiff person syndrome variant associated with multiple sclerosis. Prim Care Companion CNS Disord. 2019;21(1):18l02360. PubMed CrossRef

2.Sabatino JJ Jr, Newsome SD. Stiff person syndrome masquerading as multiple sclerosis. J Neurol Sci. 2017;372:297-299. PubMed CrossRef

3.McKeon A, Robinson MT, McEvoy KM, et al. Stiff-man syndrome and variants: clinical course, treatments, and outcomes. Arch Neurol. 2012;69(2):230-238. PubMed CrossRef

4.Newsome SD. Other proven and putative autoimmune disorders of the CNS: anti-GAD associated neurological disorders, stiff-person syndrome and progressive encephalopathy with rigidity and myoclonus (PERM). In: Johnston MV, Adams HP, Fatemi A, eds. Neurobiology of Disease. 2nd ed. New York, New York: Oxford University Press; 2016:675-682.

5.Hutchinson M, Waters P, McHugh J, et al. Progressive encephalomyelitis, rigidity, and myoclonus: a novel glycine receptor antibody. Neurology. 2008;71(16):1291-1292. PubMed CrossRef

6.Crisp SJ, Balint B, Vincent A. Redefining progressive encephalomyelitis with rigidity and myoclonus after the discovery of antibodies to glycine receptors. Curr Opin Neurol. 2017;30(3):310-316. PubMed CrossRef

7.Rakocevic G, Floeter MK. Autoimmune stiff person syndrome and related myelopathies: understanding of electrophysiological and immunological processes. Muscle Nerve. 2012;45(5):623-634. PubMed CrossRef

8.Turner R, Stratton I, Horton V, et al; UK Prospective Diabetes Study Group. UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. Lancet. 1997;350(9087):1288-1293. PubMed CrossRef

9.Meinck HM, Faber L, Morgenthaler N, et al. Antibodies against glutamic acid decarboxylase: prevalence in neurological diseases. J Neurol Neurosurg Psychiatry. 2001;71(1):100-103. PubMed CrossRef

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