What Is Stiff Person Syndrome?

Have you ever heard of Stiff Person Syndrome (SPS)? As you can tell from its name, it refers to the disorder where people with this syndrome find difficulty in moving their limbs. They usually experience muscle stiffness and painful spasms in the trunk and the parts of the limbs closer to the body

SPS is a rare progressive autoimmune neurological disorder involving the pathways in the central nervous system. Patients may start experiencing cramps and muscle stiffness in their legs but it varies from person to person. The symptoms worsen over time and can lead to permanent disability and death if untreated. There is no cure for this disorder currently but there are medications and therapies that can improve the symptoms.

Are you interested in knowing more about the causes and treatments of SPS? Keep scrolling and read on!

Introduction

Stiff Person Syndrome (SPS)

Stiff Person Syndrome (SPS) is a rare neurological autoimmune disorder affecting the central nervous system (CNS). It was first introduced by Moersch and Woltman in 1956. The symptoms are muscle stiffness and pain spasms in the centre part of the body and four limbs. It is usually related to the improper functioning of autoimmune antibodies. It is currently characterised by a continuous involuntary firing of motor units that causes contraction of agonist and antagonist muscles when patients are at rest. In a nutshell, due to the malfunctioning in the CNS, people with SPS experience continuous muscle contraction that they are unable to control. Therefore, the person’s movements become rigid and stiff. 

Prevalence

It is very rare, that it is estimated to be only one to two cases per million in a year. It is more common to find SPS in women than in men. The average age of the onset of symptoms is suggested to be in the mid-thirties, and diagnosed approximately after 6 years of symptom onset in the early forties. 

Symptoms

Muscle stiffness and spasms are the major symptoms of SPS. They come and go and progress over time. Patients usually experience painful muscle contraction and spasms in the legs and back. Some may also experience it in the abdomen but less common in the upper trunk, arms, neck and face. Some may also experience other symptoms such as unsteady gait, double vision and slurred speech. 

Although they experience continuous muscle contraction, the spasms occur in episodes where they can be triggered by the person’s emotions and actions like being surprised, shocked and sudden movement. Muscle spasms can also be triggered by emotional stress, cold temperatures, exercises and touch. Continuous muscle contraction leads to stiff body movement. 

If the person’s legs are affected, they will have difficulty walking and space their feet wide to balance themselves and be more steady in that position. 

If the person’s back and trunk are affected, they will have a stiff posture. For some people with their lower back affected, it can lead to a change in the spine alignment and spinal cord compression with the appearance of an exaggerated curved back. 

If they experience muscle contraction in the chest, they will have shortness of breath as their muscles in the chest are uncontrollable. 

As spasms can occur suddenly, the unsteadiness resulting from sudden spasms can lead to sudden imbalance and falling which can cause injuries. 

People may also feel anxious or even be diagnosed with anxiety because of the sudden onset of muscle spasms that they are afraid of leaving the place they consider as safe as they cannot predict what will happen when they leave their safe place. 

Causes and Risk Factors

Glutamic acid decarboxylase (GAD) antibodies

Although the cause of SPS is not clearly defined, it has been suggested that autoimmune antibodies play a role in the development of SPS. The antibodies involved in the disorder are anti-glutamic acid decarboxylase (GAD). GAD is important for the conversion of glutamic acid to GABA, an inhibitory neurotransmitter in the brain and spinal cord. As in SPS, the continuous muscle contraction is caused by an ongoing excitation signal to the muscles. 

Therefore, when antibodies are aiming at GAD and inhibiting its activity, the loss of inhibition from GABAergic neurons to the muscles is said to be causing the uncontrolled firing of motor units and hence leading to continuous involuntary muscle contraction and spasms. Studies have revealed that anti-GAD antibodies are found in up to 80% of the patients and up to 75% in the cerebrospinal fluid (CSF). However, it is still debatable whether anti-GAD antibodies have a pathological role in developing SPS. 

GABAergic neuronal circuits

Another possible cause of SPS is the dysfunction of GABAergic inhibitory neuronal circuits. This dysfunction leads to failure in inhibiting the downstream alpha-motor neurons and hence results in the non-stop firing of these neurons and sustained muscle contractions. Studies using transcranial magnetic stimulation revealed that this electrophysiological dysfunction originated from hyperexcitability in the motor cortex instead of spinal hyperexcitability. 

Associated conditions

SPS is found to be associated with other autoimmune disorders like type 1 diabetes, thyroiditis, which refers to the inflammation of the thyroid gland, and pernicious anaemia which is a rare autoimmune disorder resulting in B12 deficiency. 

Diagnosis

Clinical evaluation

The major clinical features of SPS are muscle stiffness and rigidity in axial and proximal limbs. People with SPS should also show abnormal axial posture and muscle spasms stimulated by stimuli such as voluntary movement, emotional upset and auditory stimuli. There should not be any cognitive impairment, chronic pain syndrome, or sensory disturbance. Muscle stiffness and spasms should not be found to be related to the activity in the brainstem, pyramidal, extrapyramidal and lower motor neurons.

Blood tests for GAD antibodies

Blood tests for GAD antibodies can be taken to diagnose SPS because most people with SPS have high levels of GAD antibodies. Taking blood tests for GAD antibodies can also prevent misdiagnosis for other diseases with similar symptoms such as Parkinson’s disease, multiple sclerosis and psychosomatic illness.

Electromyography (EMG)

As EMG can demonstrate motor unit activity in muscles when the agonist and antagonist muscles are triggered by specific stimuli and continuous muscle activity is measured by EMG, it can be a good indication of SPS and hence a useful way for the diagnosis of SPS. 

Differential diagnosis

Imaging techniques, such as magnetic resonance imaging (MRI), positron emission tomography (PET) and computerised tomography (CT) scans, can also be helpful in the diagnosis of SPS as they can visualise the brain, spinal cord and the nervous systems anatomically and functionally. The continuous excitatory signals to the affected muscles can be tracked and therefore it helps diagnose SPS.

Treatment

Although there is no cure for SPS, medications and therapies are helpful in the management of symptoms and the progression of the disorder.

Medications

GABAergic drugs

GABAergic drugs are used to improve muscle stiffness and spasms as these drugs enhance GABAergic transmission. The following are the drugs used for symptomatic relief:

• Benzodiazepines

Benzodiazepines, such as diazepam and clonazepam, are often used as anti-anxiety drugs and muscle relaxants. It is the first-line treatment for SPS. This drug enhances the inhibitory circuits by improving the neurotransmitter’s effect on the GABA receptor. Patients with SPS have shown improvement in muscle stiffness and spasms with long-term benzodiazepine treatment and other medications. However, the long-term and high dosage use of this drug can be concerning for the potential of withdrawal. Therefore, regular monitoring and management are advised when receiving this treatment.

• Oral and intrathecal baclofen

Oral baclofen is a second-line therapy for SPS often used alongside benzodiazepines. Intrathecal baclofen is also shown to be effective in strengthening the inhibition of GABA receptors. Patients receiving intrathecal baclofen are reported to have a decrease in spasm frequency and a reduction in muscle stiffness.

• Levetiracetam

Levetiracetam improves muscle stiffness and paroxysmal respiratory spasms in SPS patients. It also decreases the hyperexcitatory activity in spinal cord neurons. However, the underlying mechanism of this drug and the outcome of long-term therapy are uncertain.  

Immunotherapies

As SPS is an autoimmune disorder, the following medications are dedicated to intervening and suppressing the immune system: 

• Rituximab

Rituximab is an intravenous immunosuppressant treatment that has been shown to be effective in treating different autoimmune neurological diseases. Although there have been some cases showing rituximab improves muscle stiffness and spasms in SPS patients, there have not been consistent findings on whether rituximab is effective for all SPS patients. Further investigation and research are needed to find out the efficacy of rituximab. 

• Intravenous immunoglobulin therapy

Intravenous immunoglobulin therapy is found to be effective and safe. Patients receiving this treatment for three months had no difficulty walking and no spasms when doing household chores. It takes six weeks to one year for improvement in symptoms. As receiving this therapy improves their symptoms, they are reported to have improved quality of life, better mental health and energy levels.

• Plasma exchange (plasmapheresis) therapy

When the above treatments fail to improve the patient’s symptoms, plasma exchange is another alternative. It is proposed that the therapeutic effect of plasmapheresis is related to eliminating components, including cytokines and those with modulatory functions, in the immune system. It is reported that plasmapheresis is effective in improving symptoms or even remission of symptoms for some patients. Plasmapheresis can be a lifesaver in acute and long-term situations like respiratory depression.

Summary

All in all, SPS is an autoimmune neurological disorder that progresses and worsens over time. It is characterised by the continuous muscle contraction that leads to muscle stiffness in the trunk and proximal limbs, and muscle spasms that are stimulus-sensitive. With appropriate treatments, the symptoms can be improved so as the patient’s quality of life. If you notice you or someone around you are experiencing similar symptoms, you should always seek medical advice from professionals so that the situation can be assessed and appropriate treatments can be given.