1. Historical background of stiff-person syndrome
•The original description by Moersch and Woltman
•Timeline of discoveries of antibodies
•Treatment advances in the field
2. Clinical phenomenology (including diagnostic criteria) of stiff-person syndrome and stiff-person syndrome variants
•How to differentiate stiffness in stiff-person syndrome from other phenomenologies
oSpasticity/hypertonia
oDystonia
oCramps
•Clinical features of classic stiff-person syndrome
oCore features
oAssociated features including associated autoimmunity
•Diagnostic criteria of stiff-person syndrome and its limitation
•Clinical features of stiff-person syndrome variants
oStiff-limb syndrome (SLS)
oProgressive encephalomyelitis with rigidity and myoclonus (PERM)
oOverlapping syndromes
oHyperekplexia: A stiff-person syndrome variant or distinguished entity?
oConfusion about terminology in clinical practice
•Clinical pearls and pitfalls in the diagnosis of stiff-person syndrome
3. Differential diagnosis of stiff-person syndrome
•Central hyperexcitability
oFocal spinal cord lesions
oToxic/parainfectious causes
oAutoimmune causes e.g. LGI-associated faciobrachial dystonic seizures
oParoxysmal movement disorders
Paroxysmal kinesigenic dyskinesia (PKD)
Paroxysmal non-kinesigenic dyskinesia (PNKD)
Paroxysmal exercise dystonia (PED)
Secondary paroxysmal kinesigenic dyskinesias
•Paroxysmal tonic spasm in multiple sclerosis
•Other structural spinal cord lesions
Episodic ataxia
•Peripheral hyperexcitability (overview here with further dedicated information on this subtopic in chapter 14)
oPeripheral nerve hyperexcitability syndromes
oDisorders of skeletal muscle membrane hyperexcitability
4. Electrophysiology of stiff-person syndromes
•Electrophysiologic techniques in studying stiff-person syndrome
oNeedle electromyography vs. surface electromyography
oSpecial techniques
•Key electrophysiologic findings in stiff-person syndrome
oContinuous motor unit activity (CMUA)
oLoss of vibration-induced inhibition of H-reflex
oEnhanced exteroceptive reflexes including blink reflexes
oCo-contraction of agonist and antagonist muscles
5. Neurochemistry of inhibitory synapses and clinical applications in stiff-person syndromes
•GABA-ergic synapses
•Antigenic targets of GABA-ergic synapses in stiff-person syndrome
oGlutamic acid decarboxylase (GAD)
oAmphiphysin
oGABAA receptor (GABA AR)
oGABAA receptor-associated protein (GABARAP)
•Glycinergic synapses
•Antigenic targets of glycinergic synapses in stiff-person syndrome
oGlycine receptor
oGlycine transporter 2 (GlyT2)
oGephyrin
6. Immunopathogenesis of stiff-person syndromes
•GAD-65 vs. GAD-67
In each subtopic below, we will discuss the controversies and current supporting and arguing evidence.
•Is GAD-65 pathogenic or epiphenomenon?
•Cell-mediated immunity vs. humoral immune response
•Role of T-cell vs. B-cell
•Future directions of research in stiff-person syndromes
7. Antibodies in stiff-person syndrome and their correlations with clinical phenotypes
•Eight main antibodies: anti-GAD, anti-amphiphysin, anti- GABA AR, anti-GABARAP...
