Stiff Person Syndrome

Definition

Stiff person syndrome (SPS) is a rare acquired neurological disorder characterized by fluctuating muscle rigidity and stiffness, painful spasms, and continuous motor unit activity.[1][2][3] This condition was originally described as “stiff man syndrome” (SMS) by Moersch and Woltman in 1956. They reported observations from 14 cases of patients who experienced progressive stiffness, episodic painful muscle spasms, and difficulty walking without any other neurological signs.[4] The rigidity and continuous motor unit activity is most pronounced in muscles of the trunk (thoracolumbar paraspinals and rectus abdominis), but may also occur in the legs and arms, and persists even when relaxation is attempted.[3]

SPS includes the following variants: classical SPS, focal SMS, Stiff Leg Syndrome (SLS), jerking SMS, progressive encephalomyelitis with rigidity and myoclonus (PERM), paraneoplastic SMS, gait ataxia, dysarthria, and abnormal eye movements.[1][3]

Etiology / Epidemiology

The exact etiology of SPS remains unclear, however it is widely accepted as an autoimmune disease.[1][2][3][4] The majority of SPS cases contain the glutamic acid decarboxylase (GAD) autoantibody. GAD is a GABA synthesizing enzyme, with two primary isoforms: GAD-65 and GAD-67.[1][2] GAD-65 is primarily associated with SPS; it is also associated with diabetes mellitus, cerebellar ataxia, and limbic encephalitis.[1] When GAD is inhibited by the anti-GAD in SPS, GABA becomes less readily available, thus reducing GABA’s inhibitory effect. This process leads to continuous stimulation of muscles by motor neurons, resulting in muscle rigidity.[1][3]

SPS is a very rare disease, prevalent in 1-2 in a million.[1][2] It is mostly reported in women, with 2 women affected per every one man.[1][5]SPS usually manifests later in life; the patient typically presents with initial symptoms between 40-60 years of age, although onset has been reported in patients younger and older.[1][3][5] Over half of SPS patients have, or will develop, diabetes at some point. SPS is also related to thyroid disease and vitiligo.[5]

Clinical Presentation

SPS is characterized by progressive stiffening of the muscles in the trunk and limbs.[6] Fluctuating levels of pain and muscle rigidity spread slowly throughout the body and become progressively worse, until it becomes difficult to perform activities of daily living independently.[2] As a result of stiffening, a fixed hyperlordosis develops in the lumbar spine that remains evident in supine lying, but relaxes during sleep.[2]

The clinical features of SPS may vary based on the region of rigidity:

  • Lower limbs: Abnormally slow and wide gait pattern, in an effort to maintain balance.
  • Facial muscles: Appearance of an emotionless mask (this symptom is rare in SPS).
  • Thoracic muscles: Limited chest expansion, leading to difficulty breathing.[2]

In addition to stiffness, SPS produces painful and disabling muscle spasms in response to certain stimuli, such as psychological distress, being startled by touch or noise, and active or passive muscle movement.[2] These spasms may be short-lasting or occur in tetanus-like bouts.[2] A heightened sensitivity to stimuli often leads to a fear of walking or leaving the house, as ordinary stimuli (e.g. the noise from a car horn) can set off muscle spasms that cause patients to lose balance, making this population more prone to falling.[7]

Pain is a chronic symptom of SPS, but it can flare up acutely in response to muscle spasms.[2]

Diagnostic Procedures

The wide variation in clinical presentation of SPS makes it difficult to diagnose, and diagnosis is often delayed considerably with an average of a 6.2-year delay.[2]

A blood test can be performed to measure the level of GAD antibodies in the blood, with a high level indicating a positive SPS diagnosis, however; the absence of GAD antibodies does not rule out SPS.[6]

A detailed history and physical examination should be carried out to investigate for typical characteristics of the condition. The Dalakas Criteria are used worldwide to diagnose typical SPS, with patients who do not meet these criteria being identified as atypical (Table 1).[2]

Electromyography (EMG) testing can be used to aid in diagnosis. The typical pattern indicative of SPS is continuous motor unit activity occurring simultaneously in both the agonist and antagonist muscles of the affected area.[6]


Table 1: Dalakas Criteria for diagnosis of Typical Stiff Person Syndrome[2]
Dalakas Criteria for diagnosis of Typical Stiff Person Syndrome
  • Stiffness in the axial muscles, prominently in the abdominal and thoracolumbar paraspinal muscle leading to a fixed deformity (hyperlordosis)
  • Superimposed painful spasms precipitated by unexpected noises, emotional stress, tactile stimuli
  • Confirmation of the continuous motor unit activity in agonist and antagonist muscles by electromyography
  • Absence of neurological or cognitive impairments that could explain the stiffness
  • Positive serology for GAD65 (or amphiphysin) autoantibodies, assessed by immunocytochemistry, western blot or radioimmunoassay

Prognosis and Outcome Measures

The progression of SPS can vary depending on the individual and how it initially presents. From symptom onset to death, the course of SPS can range from 6-28 years.[2] The rate at which SPS progresses depends on several factors:

  • Whether symptoms initially presented as classic SPS (prognosis is more favourable)[8]
  • If symptoms belong to the ‘stiff man plus’ category, a more complicated form of non-classic SPS (poorer treatment response)[8]
  • Accompanied by diabetes mellitus or malignancy (prognosis is less predictable)[9]

Patients with classic SPS usually respond well to treatment[8] and their condition usually stabilizes over time with intermittent relapses and remissions.[10] Early detection and neurological treatment is important to limit progression of SPS.[2] Even with treatment, the quality of life of individuals with SPS usually declines as stiffness limits many activities of daily living.[2][8] SPS also varies in severity of symptoms, with loss of functional independence in about 65 percent of patients, and intensive care requirements at one point or another for 10 percent of patients.[2] Sudden death occurs in about 10 percent of patients due to metabolic acidosis or autonomic crisis caused by an over activated sympathetic nervous system.[10]

Although no formal measurement tools exist for stiff person syndrome, both the Functional Independence Measure (FIM) and the Timed up and Go (TUG)  assessment tools have been used as objective measures in the assessment of SPS symptoms.[11]

Physical Therapy Management

It is important to note that physical therapy could worsen symptoms of SPS during certain phases of the disease; the efficacy of physical therapy is highly variable, and certain precautions should be taken before proceeding with treatments.


Scott Newsome, DO, Department of Neurology at Johns Hopkins Medical[12] recommends that physical therapy involve:

  • Deep tissue myofacial techniques
  • Ultrasound
  • Passive range of motion (any type of contractile exercise can reproduce or worsen symptoms), and
  • Heat therapy or possibly hydrotherapy, as any type of cold therapy can exacerbate symptoms

Ultimately, physical therapy should be tailored to the individual with SPS, as patients may present in different ways. It is important to comply with patient goals, understand symptom triggers, and help in the best way possible in order to reduce pain and increase the quality of life in those living with SPS.

Differential Diagnoses

SPS is often misdiagnosed as a more common neurological or psychological condition, including but not limited to the following[7]:

Resources

Rare Disease Report Website - SPS Videos
http://www.raredr.com/search?get1=search&keywordTerm=stiff+person+syndrome

SPS - Canadian Stem Cell Foundation
http://stemcellfoundation.ca/en/tag/stiff-person-syndrome/

Clinical Trials for those with SPS
https://clinicaltrials.gov/search/term=Stiff-Person%20Syndrome


Physical Therapy Research

One of the more notable case studies to be published about SPS and physical therapy was by Kristen Potter in 2006. She found that inpatient rehabilitation twice daily for 30 minute sessions, and one 30 minute session on weekends focusing on exercise (stretching and relaxation) and functional retraining (transfers, stairs, sit to stand, etc.) improved range of motion, posture, and gait in a male patient with SPS, despite his continued spasms, pain, and stiffness.[11]

Recently, a case study by Christopher Hegyi[13], found that physical therapy treatments including: ultrasound, soft tissue mobilization, passive stretching, education, and exercise were most beneficial for a 24 year old woman with SPS. Over the course of 15 weeks (one treatment per week) the woman’s spasms and stiffness significantly reduced. Near the end of treatment, she could achieve full range of motion and flexibility, however these achievements were only seen seated or lying down. Since her symptoms were worse when standing, they issued an ankle foot orthosis (AFO) which greatly improved her gait by allowing her foot to be placed flat on the floor.

References

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  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Bhatti AB, Gazali ZA. Recent advances and review on treatment of stiff person syndrome in adults and pediatric patients. Cureus. 2015 Dec;7(12). DOI: 10.7759/cureus.427
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 Hadavi S, Noyce AJ, Leslie RD, Giovannoni G. Stiff person syndrome. Practical neurology. 2011 Oct 1;11(5):272-82. DOI: 10.1136/practneurol-2011-000071
  3. 3.0 3.1 3.2 3.3 3.4 3.5 Meinck HM, Thompson PD. Stiff man syndrome and related conditions. Movement Disor-ders. 2002 Sep 1;17(5):853-66. DOI: 10.1002/mds.10279
  4. 4.0 4.1 Sarva H, Deik A, Ullah A, Severt WL. Clinical spectrum of stiff person syndrome: a review of recent reports. Tremor and Other Hyperkinetic Movements. 2016;6. DOI: 10.7916/D85M65GD
  5. 5.0 5.1 5.2 Division of Neuroimmunology and Neurological Infections, Johns Hopkins Hospital. Stiff Person Syndrome. Available from https://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/neuroimmunology_and_neurological_infections/conditions/stiff_person_syndrome.html (accessed May 4, 2017).
  6. 6.0 6.1 6.2 Yale School of Medicine. Stiff-Man Syndrome. https://medicine.yale.edu/neurology/patients/neuromuscular/sms.aspx# (accessed May 4 2017).
  7. 7.0 7.1 National Institute of Neurological Disorders and Stroke. Stiff-Person Syndrome Information Page. https://www.ninds.nih.gov/Disorders/All-Disorders/Stiff-Person-Syndrome-Information-Page (accessed May 4 2017).
  8. 8.0 8.1 8.2 8.3 Brown P, Marsden CD. The stiff man and stiff man plus syndromes. Journal of neurology. 1999 Aug 1;246(8):648-52. DOI: doi:10.1007/s004150050425
  9. Jung YJ, Jeong HG, Kim R, Kim HJ, Jeon BS. Stiff-person syndrome: Case series. Journal of movement disorders. 2014 Apr 30;7(1):19-21. DOI: https://doi.org/10.14802/jmd.14004
  10. 10.0 10.1 Duddy ME, Baker MR. Stiff person syndrome. InImmune-Mediated Neuromuscular Diseases 2009 (Vol. 26, pp. 147-165). Karger Publishers. DOI: doi: 10.1159/000212375
  11. 11.0 11.1 Potter K. Physical Therapy During In‐Patient Rehabilitation for a Patient with Stiff‐Person Syn-drome. Journal of Neurologic Physical Therapy. 2006 Mar 1;30(1):28-38. DOI: 10.2522/ptj.20100303
  12. Newsome S. Management of Stiff Person Syndrome [Internet]. Raredr.com. 2017 [cited 2 May 2017]. Available from: http://www.raredr.com/videos/Management-Stiff-Person-Syndrome
  13. Hegyi CA. Physical therapist management of stiff person syndrome in a 24-year-old woman. Physical therapy. 2011 Sep 1;91(9):1403. DOI: 10.1097/01.NPT.0000282147.18446.b8