Stiff person syndrome

Stiff person syndrome, previously known as stiff man syndrome, is a very rare neuromuscular disease.

Epidemiology

Onset is usually between 30 and 50 years of age. An association with autoimmune disease and various malignancies is described and these are thought to play a role in the pathophysiology.

Clinical presentation

Clinical presentation is characterized by:

• progressive muscle stiffness predominately affecting the axial muscles (especially the abdominal and thoracolumbar paraspinal musculature)  and lower limbs
• muscle spasms triggered by external stimuli or emotional stress
• symptoms typically relieved by benzodiazepines

The diagnosis is usually confirmed with EMG and serology (anti-GAD and anti-amphiphysin antibodies). These are specific, however, they are only present in 60% of cases.

Pathology

Stiff person syndrome is part of the spectrum of autoimmune encephalitides. Anti-GAD antibodies may bind to and lead to the progressive destruction of GABAergic neurons involved in motor pathways .

Additionally, a paraneoplastic syndrome causing anti-amphiphysin antibodies is described (the most common malignancies being breast followed by thymic, colorectal and lung tumors) .

Radiographic features

Imaging is usually unremarkable . T2 hyperintensities of the brain and spinal cord on MRI have been described in a minority of case reports .

Treatment and prognosis

In addition to benzodiazepines, baclofen has been used for treatment. More recently, intravenous immunoglobulins (IVIG) have been used in combination with other drugs.

History and etymology

Stiff person syndrome was first described in 1956 by Moersch and Woltman of the Mayo Clinic .