A recently published review focuses on the role of neurophysiological techniques to reveal pathophysiological mechanisms of stiff‐person spectrum disorders (SPSD). 1 We would like to extend that review by proposing that neurophysiological testing could also be clinically useful to diagnose SPSD.
There is no gold standard for the diagnosis of SPSD, which is based on clinical features supported by antibody or neurophysiological testing. 2 This means that the sensitivities and specificities of diagnostic tests will remain approximate. Moreover, any test will have a low positive predictive value given the presumably low prevalence of SPSD. Nonetheless, neurophysiological testing could provide useful information in conjunction with the results of antibody testing or when antibody testing is unrevealing (i.e., seronegative) or unavailable. 3
The most common neurophysiological findings used to diagnose SPSD are continuous motor unit activity (CMUA) and enhanced exteroceptive reflexes. 1 , 2 , 3 , 4 , 5 This is probably because the equipment required to test for CMUA (needle or surface electromyography [EMG]) and exteroceptive reflexes (electrical stimulation and EMG) is usually available in clinical neurophysiology laboratories. We searched PubMed and selected 49 articles reporting cases of SPSD that included neurophysiological testing for CMUA or enhanced exteroceptive reflexes (Table 1). Final diagnoses were made based on a combination of clinical, immunological, and neurophysiological features. 1 , 2 The diagnoses included classical SPSD, stiff‐limb syndrome, progressive encephalomyelitis with rigidity and myoclonus, and SPSD plus. We estimated the sensitivities of CMUA and enhanced exteroceptive reflexes. It was not possible to estimate specificities because of lack of enough control groups without SPSD. CMUA had an overall sensitivity of 72.7% (266/366). Enhanced exteroceptive reflexes triggered by cutaneomuscular stimuli had 50% sensitivity (45/90). Blink reflexes were enhanced in all cases (6/6). Abnormal exteroceptive reflexes triggered by auditory stimuli had 51.4% sensitivity (38/74). Enhanced head retraction reflex had 53.3% sensitivity (32/60), and enhanced masseter reflex had 45.5% sensitivity (5/11). Reflexes triggered by visual stimuli were negative in all cases (0/9).
TABLE 1.
Summary of reported cases of stiff person spectrum disorder including neurophysiological testing for continuous motor activity or enhanced exteroceptive reflexes
| First author | Year | Continuous motor unit activity | Exteroceptive reflexes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cutaneomuscular | Blink reflex | Auditory reflex | Head retraction | Masseter reflex | Visual reflex | ||||||||||
| + | − | + | − | + | − | + | − | + | − | + | − | + | − | ||
| Armon | 1990 | 3 | 0 | ||||||||||||
| Balint | 2014 | 1 | 0 | 1 | 0 | ||||||||||
| Barker | 1997 | 1 | 0 | ||||||||||||
| Barker | 1998 | 21 | 0 | 18 | 2 | 11 | 6 | ||||||||
| Bartsch | 2002 | 1 | 0 | ||||||||||||
| Berger | 2004 | 27 | 23 | ||||||||||||
| Borrelini | 2017 | 1 | 0 | ||||||||||||
| Brown | 1997 | 4 | 0 | 4 | 0 | 2 | 2 | ||||||||
| Butler | 2000 | 1 | 0 | ||||||||||||
| Caviness | 2014 | 2 | 0 | ||||||||||||
| Dalakas | 2000 | 20 | 0 | ||||||||||||
| Degeneffe | 2018 | 1 | 0 | ||||||||||||
| Derksen | 2013 | 1 | 0 | ||||||||||||
| Edip Gürol | 2001 | 1 | 0 | ||||||||||||
| Ehler | 2011 | 1 | 0 | ||||||||||||
| Fogan | 1996 | 1 | 0 | ||||||||||||
| Folli | 1993 | 1 | 0 | ||||||||||||
| Goodson | 2017 | 1 | 0 | ||||||||||||
| Gouider‐Khouja | 2002 | 1 | 0 | ||||||||||||
| Harding | 1989 | 3 | 0 | ||||||||||||
| Holmøy | 2007 | 1 | 0 | ||||||||||||
| Iwata | 2011 | 1 | 0 | ||||||||||||
| Jing | 2018 | 1 | 0 | ||||||||||||
| Karlson | 1994 | 3 | 0 | ||||||||||||
| Khasani | 2004 | 5 | 5 | 5 | 5 | ||||||||||
| Leigh | 1980 | 1 | 0 | 0 | 1 | ||||||||||
| Logullo | 1999 | 2 | 0 | ||||||||||||
| Lorenzoni | 2012 | 3 | 1 | 1 | 3 | ||||||||||
| Mamoli | 1977 | 2 | 0 | 0 | 2 | ||||||||||
| Martinelli | 1978 | 1 | 0 | 0 | 1 | ||||||||||
| Martinelli | 1996 | 1 | 0 | ||||||||||||
| Martinez‐Hernandez | 2016 | 48 | 32 | ||||||||||||
| McKeon | 2012 | 16 | 35 | 14 | 37 | 23 | 28 | ||||||||
| Meinck | 1984 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | ||||||
| Meinck | 1995 | 8 | 0 | 8 | 0 | 0 | 8 | ||||||||
| Molloy | 2002 | 5 | 0 | ||||||||||||
| Murinson | 2008 | 97 | 26 | ||||||||||||
| Rossi | 2010 | 1 | 0 | ||||||||||||
| Sabatino | 2017 | 0 | 4 | ||||||||||||
| Saiz | 1998 | 2 | 0 | ||||||||||||
| Saiz | 1999 | 1 | 0 | ||||||||||||
| Sasse | 2016 | 3 | 0 | ||||||||||||
| Schmierer | 1998 | 1 | 0 | ||||||||||||
| Schulte‐Mattler | 1996 | 0 | 1 | ||||||||||||
| Sechi | 2008 | 3 | 0 | ||||||||||||
| Souissi | 2019 | 1 | 0 | ||||||||||||
| Squintani | 2012 | 1 | 0 | ||||||||||||
| Vinjam | 2016 | 0 | 1 | ||||||||||||
| Warren | 2002 | 1 | 0 | ||||||||||||
| Total | 266 | 100 | 45 | 45 | 6 | 0 | 38 | 36 | 32 | 28 | 5 | 6 | 0 | 9 | |
Note: +, positive test (abnormal); −, negative test (normal).
Diagnostic criteria based on neurophysiological testing usually include a battery of complementary findings. Neurophysiological criteria to diagnose SPSD and guidelines to standardize the relevant techniques are needed. In the meantime, the finding of pathologic CMUA and enhanced exteroceptive reflexes could be regarded as the “minimum neurophysiologic criteria” to support the clinical suspicion of SPSD. This suggestion is based on the complementary characteristics of CMUA and enhanced exteroceptive reflexes. Considering that symptomatic medications could ameliorate CMUA, we suggest first sampling one symptomatic muscle briefly with needle EMG to rule out abnormal waveforms of peripheral origin and document CMUA if present. Next, we suggest conducting surface EMG to include prolonged recordings during tasks associated with baseline tone (e.g., neutral position), increased tone (e.g., volitional or synergistic contraction), and reduced tone (e.g., during distraction or synergistic relaxation). Multi‐channel surface EMG could allow simultaneous examination of multiple muscles to evaluate synergistic patterns in agonist/antagonist pairs during repetitive active and passive movements. After EMG testing, we suggest proceeding with exteroceptive reflex testing as guided by the clinical picture and possibly including the cranial region, particularly blink reflexes. Exteroceptive reflex testing could be useful in suspected stiff‐limb syndrome, when it might be harder to find CMUA. 4 , 5
Author Roles
(1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique.
K.J.L.: 1A, 1B, 1C, 2A, 2B, 2C, 3A
P.P.: 1A, 1B, 1C, 2A, 2B, 2C, 3A
R.C.: 1A, 2C, 3B
M.H.: 1A, 2C, 3B
Disclosures
Ethical Compliance Statement: Institutional review board or ethics committee approval was not necessary for this work. Informed patient consent was not necessary for this work. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.
Funding Sources and Conflict of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work.
Financial Disclosures for the previous 12 months: K.J.L. has consulted for FHC; has received honoraria from the International Parkinson and Movement Disorder Society, and the National Institutes of Health (NIH); and has received research support from Bluerock and the National Institutes of Health (National Institute of Neurological Disorders and Stroke). P.P. has nothing to declare. R.C. has consulted for AbbVie, Ipsen, and Merz; has received research support from the Canadian Institutes of Health Research, Natural Science and Engineering Research Council of Canada, Parkinson Foundation, Dystonia Medical Research Foundation and National Organization for Rare Diseases, and was involved in a study sponsored by AbbVie. M.H. has consulted for Neurocrine; is on the medical advisory boards of Brainsway, QuantalX, and VoxNeuro; and is the inventor of a patent held by NIH for the H‐coil for magnetic stimulation for which he receives license fee payments from the NIH (form Brainsway).
Acknowledgments
K.J.L. and P.P. thank the Task Force on Stiff Person Spectrum Disorders of the International Parkinson and Movement Disorder Society. M.H. is supported by the National Institute of Neurological Disorders and Stroke Intramural Program.
Relevant disclosures and conflict of interest are listed at the end of this article.
Data Availability Statement
Data sharing is not applicable to this article as no new data were created or analyzed in this study.
References
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Data Availability Statement
Data sharing is not applicable to this article as no new data were created or analyzed in this study.