A critical survey of stiff-man syndrome

doi:10.1016/0002-9343(67)90057-5

The American Journal of Medicine

Volume 42, Issue 4, April 1967, Pages 582-599

https://doi.org/10.1016/0002-9343(67)90057-5 Get rights and content

Abstract

From forty-four cases in the world's literature and one case of our own, diagnostic criteria have been adduced for the stiff-man syndrome in the original sense of Moersch and Woltman [1]. A unique pattern of tonic muscle rigidity emerges, based on clinical and electromyographic findings and objective effects of neuromuscular blocking agents monitored by the electromyograph. These criteria are utilized to establish the validity or probable validity of thirty-four of the forty-five cases and to reject eleven which appear to represent neuraxis disease, myopathy, chronic recurrent tetanus, fibrosis replacement of muscle of obscure origin and other conditions.

A tentative hypothesis is formulated to account for the state of tonic muscle rigidity of stiff-man syndrome. Persistent extrafusal (α-neurone) muscle contractility is probably maintained by abnormal activity of the γ-motor system, itself possibly subjected to a drive from suprasegmental regions. Painful spasm is due to further intensification of muscle contraction triggered by new trains of enteroceptive, exteroceptive and emotional stimuli directly or indirectly influencing the hyperexcitable α-neurone system. Metabolic factors may also be implicated, as suggested by the presence of a nonglucose reducing substance in the urine and a rise in inorganic serum phosphorus during glycogen deposition. These metabolic deviations and the heightened drive of the γ-motor system need further clarification.

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Cited by (162)

Psychiatric Symptoms in Stiff-Person Syndrome: A Systematic Review and a Report of Two Cases
2023, Journal of the Academy of Consultation-Liaison Psychiatry
The clinical spectrum of stiff-person syndrome (SPS) encompasses a wide range of signs including psychiatric symptoms (PS).
Our objective was to provide an overview of the spectrum of PS in SPS through a systematic literature search and 2 illustrative case reports.
We reported 2 anti-glutamic acid decarboxylase-positive SPS cases that presented with phobic disorder, and we performed a systematic review by following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles published in PubMed, MEDLINE on Ovid, Embase, and via a manual search before October 20, 2020, were selected by 2 independent reviewers. Original studies, case reports, editorials, commentaries, and letters to the editor reporting cases of SPS with PS were all included. Conference abstracts, reviews and book chapters, unavailable articles, and those not reporting SPS cases or PS were excluded. Quantitative summary data were calculated.
In addition to our 2 cases, we identified 237 cases of SPS with PS from 74 additional included publications totaling 239 patients. Anxiety (56%) and depression (45%) were the most common PS in SPS. Mean diagnostic delay was 4.7 years. Among the 3 SPS phenotypes, the classic form was predominant (77%), followed by stiff-limb syndrome (13%) and progressive encephalomyelitis with rigidity and myoclonus (10%). The most frequent etiology of SPS with PS was autoimmune (90%), followed by cryptogenic (7%) and paraneoplastic forms (7%). These patients were mainly treated with immune-mediated therapies and GABAergic drugs.
Our review revealed that the most common PS of SPS are anxiety and depression occurring mostly in autoimmune and classic forms, allowing a clearer understanding of this entity, which may lead to earlier diagnosis and better outcome.
Treatment and Management of Disorders of Neuromuscular Hyperexcitability and Periodic Paralysis
2021, Neuromuscular Disorders: Treatment and Management
The syndromes of neuromuscular hyperexcitability encompass a large group of clinical conditions characterized by prominent muscle stiffness, cramps, and spasms. The differential diagnosis of these symptoms includes disorders of the central nervous system, peripheral nerves, and muscles. In this chapter, we discuss the major syndromes of neuromuscular hyperexcitability including stiff person syndrome, tetanus, disorders of peripheral nerve hyperexcitability, rippling muscle disease, and muscle channelopathies. The clinical presentations of these disorders, approaches to their diagnosis, and current treatment options are reviewed.
SPS: Understanding the complexity
2019, Journal of the Neurological Sciences
Citation Excerpt :
A high index of clinical suspicion is crucial to making the diagnosis. In 1967, Gordon et al. [137] proposed diagnostic criteria for SPS based on the clinical phenotype and the EMG findings. These criteria have subsequently been updated and expanded by Dalakas.
Stiff-person syndrome (SPS), first described in 1956 by Moersch and Woltman, is a progressive autoimmune disorder with core features of chronic fluctuating progressive truncal and limb rigidity and painful muscle spasms leading to gait difficulties, falls and an appearance that resembles tin soldiers. The syndrome is a rare, highly disabling disorder of the central nervous and frequently results in significant disability. Understanding of the etiology, clinical spectrum, diagnostic workup and therapeutic modalities for this painful and disabling disorder has vastly evolved over the past few years with more confidence in classifying and treating the patients. The purpose of this review is to increase the awareness, early detection, and treatment of this disabling disease.
PubMed was searched, all date inclusive, using the following phrases: stiff person syndrome,anti-Glutamic acid decarboxylase (Anti-GAD) antibody syndrome, Progressive encephalomyelitis with rigidity and myoclonus (PERM), and Paraneoplastic Stiff Person syndrome. No filters or restrictions were used. A total of 888 articles were identified.
The results were narrowed to 190 citations after excluding non-English and duplicate reports. Clinical presentation, laboratory testing, treatment, and prognosis were categorized and summarized.
In this article we will discuss the epidemiology, presentation and classification. Explain the pathophysiology of SPS and the autoimmune mechanisms involved. Discuss the diagnostic approach and treatments available, as well as, the prognosis and outcome.
Serotonin Syndrome and Stiff-Person Syndrome: Diagnostic Challenges in Psychosomatic Medicine
2014, Psychosomatics
Citation Excerpt :
Even after the discovery of anti-GAD antibodies, SPS remains a clinical diagnosis. Since initially created by Gordon et al. in 1967,10 the diagnostic criteria have been refined to the 2009 Dalakas criteria. These include (1) axial muscle stiffness, (2) painful spasms triggered by emotional stress or startle, (3) positive serology for GAD65 autoantibodies, (4) characteristic continuous motor unit activity in agonist and antagonist muscles by electromyography, (5) response to diazepam, and (6) all in the absence of another neurologic syndrome that would better explain the patient's symptoms.9
Stiff-person syndrome
2013, Pratique Neurologique - FMC
Le syndrome de l’homme raide (SHR) est une affection auto-immune rare : sa prévalence est comprise entre un et deux cas par million d’habitants. Son diagnostic est souvent très retardé à cause de sa présentation trompeuse et pourtant tellement caractéristique. L’expression clinique est purement motrice, progressive. Elle comporte une rigidité fluctuante du tronc et des membres, à laquelle se superposent des spasmes musculaires très évocateurs. Le diagnostic repose sur un faisceau d’arguments cliniques, immunologiques et électromyographiques. La présence d’anticorps anti-GAD65 à taux élevés est très caractéristique mais pas constante. Une minorité de cas est de cause paranéoplasique. Les benzodiazépines et le baclofène constituent le traitement symptomatique de référence. Le traitement étiologique, mal codifié, est basé sur l’immunothérapie. L’évolution est longue et, si l’aggravation peut être stoppée, l’amélioration est souvent incomplète. Nous présentons un cas de SHR chez une patiente de 72 ans, diagnostiqué après plus de deux ans d’errance diagnostique. Les aspects diagnostiques et thérapeutiques actuels sont décrits ainsi que les hypothèses physiopathologiques et des propositions concernant les modalités de suivi.
Stiff-person syndrome (SPS) is a rare disorder characterized by muscle stiffness and painful spasms. Its prevalence is one to two cases per million inhabitants. The diagnosis is often delayed due to a misleading presentation. Neurophysiology helps with the diagnosis. SPS is an autoimmune disorder: a high level of anti-GAD65 antibodies is frequently but not constantly reported. A minority of cases are paraneoplastic. Guidance for treatment is insufficient due to the rarity of the disorder. Drug therapy using gabaergic (benzodiazepine, baclofen) or immunosuppressive agents is generally proposed. The course is chronic with incomplete improvement. We report the clinical, electrophysiological and therapeutic findings in a 72-year-old woman whose clinically severe anti-GAD65-positive SPS was misdiagnosed after more than 2 years of diagnostic search. The pathophysiological hypotheses are briefly reviewed.
Exaggerated startle reactions
2012, Clinical Neurophysiology
Citation Excerpt :
Patients with startle epilepsy are commonly young and experiencing infantile cerebral hemiplegia or diffuse or localized static brain encephalopathy due to different causes. Startle-induced stiffness is mainly seen in stiff-person syndrome (Gordon et al., 1967;Lorish et al., 1989;Brown and Marsden, 1999). Stiff-person syndrome is characterized by progressive intermittent spasms and stiffness in the legs and axial lumbar area, lasting from seconds to minutes.
The origin of the startle reflex lies in the caudal brainstem; it can be elicited by an unexpected stimulus resulting in a bilateral activation of many muscles. Two subsequent responses can be measured during EMG recordings; after the initial motor reflex, lasting until about 150 ms, a second response can occur. The second response contains more emotional and voluntary behavioral responses. Clinically, syndromes with hyperstartling as common feature can be divided into three groups: hyperekplexia, stimulus-induced disorders, and neuropsychiatric disorders. Classification of startle syndromes within these three groups remains challenging. Generalized stiffness at birth, excessive startling and temporary generalized stiffness after being startled point towards hyperekplexia. Stimulus-induced disorders are distinguished by careful clinical and neurophysiological evaluation, including video recordings. Neuropsychiatric disorders usually have additional behavioural and psychiatric symptoms. Polymyographic EMG startle recordings exhibit an exaggeration of the initial motor startle reflex in hyperekplexia, while neuropsychiatric startle syndromes demonstrate a variable response pattern and abnormal behavioural features. Neurophysiological investigation of the startle reflex can help to further delineate between the startle syndromes and unravel the aetiology of neuropsychiatric startle disorders.

View all citing articles on Scopus

¹: From the Division of Physical Medicine and Rehabilitation of the Department of Medicine, and the Department of Medicine, Michael Reese Hospital and Medical Center, Chicago, Illinois.

^†: Present address: Mount Sinai Hospital, New York, New York.

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ReviewA critical survey of stiff-man syndrome

Abstract

Am. J. Med.

Am. J. Med.

Progressive fluctuating muscular rigidity and spasm (stiff-man syndrome)

A new and effective drug in the treatment of stiff-man syndrome

Stiff-man syndrome

The stiff-man syndrome

Brit. M. J.

Stiff-man syndrome

Rev. clin. Españ

The stiff-man syndrome. Report of a case

Arthritis & Rheumat.

The “stiff-man” syndrome

Arch. Neurol.

Chronic generalized fibromyositis

Ann. Surg.

A woman with stiff-man syndrome

Brit. M. J.

Correspondence

Brit. M. J.

The stiff-man syndrome in a boy

Arch. Dis. Childhood

Stiff-man syndrome in a child

New York J. Med.

“Stiff-man” syndrome

J. Indian M. A.

Stiff-man syndrome

J.A.M.A.

The stiff-man syndrome

The stiff-man syndrome

Am. J. Phys. Med.

An unusual muscle affection characterized by progressive contractures

Deutsch. Ztschr. Nervenk.

Dysphagia—an unusual symptom of the stiff-man syndrome

Review
A critical survey of stiff-man syndrome