Stiffness and cramps

Stumbling, excessive startling or even complete freezing: stiff person syndrome (SPS), also known as stiff man syndrome (SMS), has many faces. Only around one to two people per million suffer from this rare autoimmune disease. In addition, the chronic disease is little known, so it often takes a long time for patients to receive a diagnosis and helpful treatment. Until then, they struggle with a wide range of symptoms.

In SPS, autoantibodies attack central inhibitory pathways that are responsible for muscle relaxation. The main symptoms are stiffness of the muscles (rigidity), often accompanied by painful cramps - especially in the legs and trunk. This often results in gait disorders, falls or poor posture and skeletal deformities such as fixed hyperlordosis (increased curvature of the lumbar spine). Other symptoms include increased jumpiness or sensitivity to external stimuli such as touch, heat, cold or loud noises. Such stimuli can also trigger rigidity and spasticity or promote their occurrence.

But that's not all: patients with SPS also frequently suffer from anxiety disorders. Situations in which those affected seem to have no chance of escaping - such as unfamiliar places or crowds of people - are a particular problem. Disorders of the autonomic nervous system, such as episodic excessive sweating or accelerated heartbeat, can also occur.

In rare cases, only one limb or one half of the body is affected. This form is known as stiff limb syndrome (SLS) and is considered a so-called minus variant. In the plus variant of stiff person syndrome, other neurological symptoms are added, such as eye movement disorders (oculomotor disorders), epileptic seizures or sensory disturbances. This variant of SPS is also known as progressive encephalomyelitis with rigidity and myoclonus (PERM).

As is so often the case with autoimmune diseases, gender also plays a role in stiff person syndrome: women fall ill about twice as often as men. In addition, many sufferers also have other autoimmune diseases such as type 1 diabetes or thyroid dysfunction. Stiff person syndrome can occur at any age - cases have been documented from infancy to 81 years of age. The average age of onset is 46 years and the course of the disease is chronic.

However, it is quite possible for patients to remain stable for months or years after phases of gradual deterioration and not experience a relapse. As the disease progresses, the symptoms may worsen or new ones may appear.

The diagnosis is primarily based on the typical symptoms such as rigidity in the legs and trunk as well as a pronounced sensitivity to stimuli. An electromyogram (EMG) examination can confirm the suspicion. Autoantibodies can also be detected, but Stiff Person Syndrome can also be present if the antibody findings are negative.

In 70 percent of cases, the autoantibodies are directed against glutamate decarboxylase (GAD), which normally catalyzes the conversion of glutamate to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Antibodies against the glycine α1 receptor can be found in 10 to 15 percent of patients. More rarely, the autoantibodies are directed against other inhibitory target structures such as amphiphysin, the GABA-A receptor or dipeptidyl peptidase-like protein-6 (DPPX).

According to the S1 guideline »Stiff Man Syndrome« published by the German Neurological Society in 2017, physiotherapy is helpful in most cases. It can only exacerbate symptoms under certain circumstances if there is a high level of stimulus sensitivity - i.e. hypersensitivity to external stimuli. According to the guideline, behavioural therapy can also have a positive influence on the course of the illness, but is usually not very effective in the treatment of anxiety attacks.

Benzodiazepines such as diazepam or clonazepam have a muscle relaxant and anxiolytic effect and are usually effective even at low doses. However, continuous dose adjustment is often necessary due to the development of tolerance. Addictive misuse is rare, even at higher doses. Alternatively, patients can be given muscle relaxants such as baclofen or tizanidine as well as anticonvulsants such as valproate, gabapentin or carbamazepine. In selected cases - for example if there is a risk of joint damage due to spasticity - an injection of botulinum toxin is also possible.

If symptomatic therapy is not sufficient, treatment with corticosteroids - such as prednisolone or methylprednisolone - may be considered, although the potential side effects of long-term use must be taken into account. Intravenous administration of immunoglobulins (IgG) is also an option. The effect usually sets in quickly and lasts for around two to three months after two infusions.