Stiff-Person Syndrome

Session Overview

Session Introduction

Introduction

Stiff-person syndrome (SPS) is a progressive, autoimmune disorder of the central nervous system characterised by muscle rigidity and superimposed paroxysms of muscle spasms. Although rare (reported prevalence of 1 in a million of the population), it is highly disabling and often undiagnosed precluding or delaying appropriate treatment.

This session explores the pathways to diagnosis of SPS, its underlying pathophysiology and the basis for symptomatic and immunologic interventions.

First it examines the distinguishing clinical features of the syndrome and the diagnostically useful investigations.

Then it explains the underlying pathophysiology of the disease.

Finally, it provides evidence-based recommendations for treatment.

The first section begins with an overview of the epidemiology, clinical features, associated conditions and the differential diagnosis of SPS.

Distinguishing Clinical Features of the Syndrome

Stiff-person syndrome (SPS) was first described by Moersch and Woltman in 1956.

SPS arises generally in the fourth and fifth decades of life, and affects twice as many women as men. The onset of symptoms is insidious and in the classical syndrome is characterised by muscular rigidity (stiffness) and episodic spasms superimposed on the rigidity.

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Clinical Features of Classical SPS

Fluctuating tightness of the axial musculature is often the first symptom, becoming constant usually in weeks to months and spreading to the limb girdles.

The muscle rigidity is usually symmetrical, and is characterised by tight, stony-hard, board-like muscles, most prominent in abdominal and thoracolumbar paraspinals, and proximal limb muscles.

Continuous co-contraction of agonist and antagonist muscles makes movement difficult and gives rise to an extraordinary rigid posture, hyperlordosis, which is a hallmark diagnostic sign in SPS. Limitation of truncal flexibility and limb mobility makes ambulation awkward and prone to accident.

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Clinical Features of Classical SPS

Associated Conditions

Variants of SPS

Since the original description of the classical stiff-person syndrome, several variants of the syndrome have been reported including progressive encephalomyelitis with rigidity and myoclonus (PERM), stiff-limb syndrome (SLS) and jerking SPS (J-SPS) (see table for discriminating clinical features).

A paraneoplastic form of SPS has been rarely reported in association with breast and small cell lung carcinoma presenting with upper limb rigidity and rapid progression of disease.

Differential Diagnosis

Considerations include:

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Tetanus

Spinal cord lesions

Dystonia

Neuromyotonia

Hyperekplexia

Psychogenic movement disorders 

Pathophysiology of SPS

Muscle rigidity and spasms in SPS occur due to the impairment of inhibitory circuits in the CNS. Impaired intracortical inhibition causes increased excitation to the motor neurons in the cord whilst loss of intraspinal inhibition enhances motor neuron hyperexcitability.

GABA is the predominant inhibitory neurotransmitter in the CNS whilst GAD is the rate limiting enzyme that synthesises GABA. Autoantibodies to GAD (GADAb) is thought to impair the synthesis and therefore deplete the CNS of GABA.

Investigations

Neurophysiology

In SPS, continuous motor unit activity (CMUA) occurs despite the patient's attempts at muscle relaxation. This involuntary CMUA at rest is the physiologic hallmark of SPS and is detected essentially in axial muscles.

Co-contraction is confirmed by recording CMUA simultaneously in agonist and antagonist muscles. The rigidity and CMUA in SPS typically lessen with diazepam. CMUA is not specific for SPS.

Enhanced exteroceptive or cutaneomuscular reflexes are characteristic of SPS. Often, responses can be recorded in muscles remote from the site of stimulation (e.g. from paraspinal muscles following digital nerve stimulation) and occur bilaterally following unilateral stimulation.

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Investigations

Serum anti-GAD Antibodies (GADAbs)

GADAbs in high titre is found in 60% to 80% of SPS patients. GADAbs are also found in the serum of patients with type 1 diabetes mellitus, but the titre is markedly lower than that of SPS, usually < 1000 U/ml.

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Serum anti-amphiphysin antibodies

Neuroimaging

Treatment

There are two strategies of treatment:

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• Symptomatic
• Immunologic interventions

These two strategies are either used independently or in combination depending on the severity of the disease.

Self Assessment

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Session Key Points

Session Summary