Stiff Person Spectrum Disorder

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

TBX4, TRAK1, GAD2, GP6, GAD1, AMPH, SEPHS1, PDSS1, GLUL, GAS6, SMS, NOL3, SLC7A10, POU2F3, DPYSL5, NUDT10, GABARAP, PEAR1, SLC6A5, PNOC, PLA2G6, APOH, PLG, PLA2G2A, PLA2G1B, OPRL1, ATXN3, INS, HLA-DQB1, GLRA1

Drugs

Human normal immunoglobulin ( GAMMAGARD, GAMMAGARD LIQUID, GAMMAPLEX, ENDOBULINE, FLEBOGAMMA DIF, HIZENTRA, HYQVIA, KIOVIG, OCTAGAM, INTRAGLOBIN F, PRIVIGEN, SANDOGLOBULINE, TEGELINE )

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A rare neurological disorder comprising fluctuating trunk and limb stiffness, painful muscle spasms, task-specific phobia, an exaggerated startle response, and ankylosing deformities such as fixed lumbar hyperlordosis.

Epidemiology

The prevalence is estimated at about 1/1,000,000. Approximately 2/3 of patients are female.

Clinical description

Age of onset peaks around 45 and symptoms develop over months or years. Progressive muscle stiffness renders the trunk and hips immobile, and the gait becomes stiff and awkward. Superimposed painful spontaneous or reflex-induced muscle spasms may cause serious falls. A specific fear of crossing open spaces (pseudo-agoraphobia) may induce freezing of gait, sudden spasms, and falls. Focal neurological signs are absent. Clinical variants of SMS include the stiff limb syndrome (SLS) where symptoms affect only one limb, and progressive encephalomyelitis with rigidity and myoclonus (PERM) where stiffness and myoclonic spasms are associated with focal neurological signs. Many patients with SMS, SLS, or PERM have insulin-dependent diabetes mellitus (30%), autoimmune thyroiditis (10%), atrophic gastritis with pernicious anaemia (5%), and some have tumours of the breast, lung, or colon.

Etiology

The presence of antibodies against glutamic acid decarboxylase (GAD-Abs) in more than 70% of cases suggests an autoimmune pathogenesis. GAD-Abs may block synthesis of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) thereby attenuating inhibition of spinal motoneurones.

Diagnostic methods

Diagnosis essentially relies on clinical observation, and is substantiated by detection of GAD-Abs in the serum and by characteristic electromyographic abnormalities. Scans of the spinal cord can help to exclude mechanical causes such as a cyst or disc compression of the spinal cord. Cerebrospinal fluid (CSF) examination is necessary to detect GAD-Abs in CSF and exclude active inflammation.

Differential diagnosis

Differential diagnosis includes an atypical manifestation of a spinal cord disease (e.g. multiple sclerosis; tumours), axial dystonia, neuromyotonia, acquired hyperekplexia (startle disease), and psychogenic movement disorders (see these terms).

Management and treatment

Benzodiazepines and baclofen are standard drugs for symptomatic treatment. Immunomodulating therapies (corticosteroids, intravenous immunoglobulin, and plasmapheresis) have been proposed with variable results. Treatments help to control symptoms in the majority of patients affected by SMS and SLS. PERM is slightly harder to control and may have a poor prognosis.