Stiff person syndrome and other immune-mediated movement disorders – new insights

Abstract

Clinicians should be aware of new antibodies such as dipeptidyl-peptidase-like protein-6, gamma-aminobutyric acid type A receptor and glycine transporter 2 in stiff person syndrome and related disorders, as well as of the expanding spectrum of immune-mediated movement disorders.

Pseudoagoraphobia, a Diagnostic Clue in Stiff‐Limb Syndrome

“…SPSD encloses a group of rare autoimmune movement disorders associated with antibodies targeting proteins expressed by inhibitory synapses in the central nervous system . The presence of anti‐GAD (the enzyme that converts glutamate to gamma‐aminobutyric acid [GABA]) is reported in approximately 70% of the SPS, the most common disorder of the group . However, other antibodies have been associated with SPSD, such as anti‐glycine receptors, anti‐Gephyrin, anti‐dipeptidyl peptidase‐like protein 6, and anti‐amphyphisin …”

“…Anti‐GADs are found also among the general population with a prevalence of 1.0% to 1.7%, and an even higher prevalence can be found in patients suffering from diabetes and thyroid dysfunctions . Given their low sensitivity and specificity, the presence of anti‐GAD has just a supporting role for the diagnosis of SPSD …”

“…Gait disturbances are frequently reported in movement disorder clinics and some of them could fluctuate, making the diagnostic processes challenging . Stiff person syndrome (SPS) is a rare and heterogeneous autoimmune disorder which could present with fluctuating gait impairment and superimposed episodic muscle spasms, especially in stiff‐limb syndrome (SLS)—a focal variant of stiff person spectrum disorder (SPSD) that could affect the leg . Anxiety is the psychiatric counterpart of the syndrome, which could also manifest with task‐specific paroxysmal phobias, such as pseudoagoraphobia (i.e., gait‐specific phobia) .…”

Clinical characteristics of patients with cerebellar ataxia associated with anti-GAD antibodies

“…The association between SPS and CA-GAD-ab is even more unusual and creates additional challenges to diagnosis and treatment 20,21,22,23,24,25,26 . This overlap emphasizes a possible common mechanism, which is probably related to the widespread distribution of GAD throughout the CNS 1,2,4,6 .…”

“…Continuous contraction of opposing muscles is caused by involuntary motor unit firing at rest and represents a clinical and electrophysiological hallmark of the disease 10,20 . It is also related to the autoimmune pathogenesis of the disease, and, although the antibody spectrum associated with SPS has broadened, GAD-ab and anti-amphiphysin remain those most typically associated with SPS 10,11,20,21 .…”