Stiff person syndrome

Stiff person syndrome
ICD-10	G25.8
ICD-9	333.91
OMIM	184850
DiseasesDB	12428
MeSH	D016750

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Stiff person syndrome (SPS) (or occasionally, stiff-man syndrome) is a rare neurologic disorder of unknown etiology.

Historical Perspective

SPS was first described by Moersch and Woltman at the Mayo Clinic in 1956.

Classification

There are 3 categories of SPS, and they are as follows:

1. SPS
2. Progressive encephalomyelitis with rigidity (rapidly progressive disorder, fatal within 16 weeks)
3. Stiff-limb syndrome (asymmetric rigidity and spasms in the distal extremities or face)

Causes

Because many patients with SPS have circulating antibodies to the enzyme glutamic acid decarboxylase (GAD), an autoimmune cause of the disease has been postulated. However, GAD antibodies cannot be the sole cause, as most Type I diabetics possess anti-GAD antibodies, yet the frequency of SPS among Type I diabetics is 1 in 10,000. The GAD protein regions (epitopes) recognized by these antibodies may differ in each disease.

Differeniating Stiff Person Syndrome from other Diseases

One the basis of stiffness and fever it can be differentiated from:

• Tetanus
• Neuroleptic malignant syndrome
• Meningitis
• Tardive dyskinesia
• Parkinsonism

Differential Diagnosis of Stiffness

Disease	Diagnosis			Treatment
	Symptoms	Signs	Laboratory Findings
Tetanus	Tonic contraction of muscles between the spasmodic episodes Trismus or lockjaw Neck stiffness Swallowing difficulty Stiffening of the calf and pectoral muscle groups	Opisthotonos Leg extension with arm flexion Risus sardonicus respiratory distress	Not significant	Diazepam Magnesium  Human TIG
Neuroleptic Malignant Syndrome	History of intake of offending drugs e.g neuroleptics like: Fluphenazine Haloperidol Olanzapine Risperidone Autonomic instability Rigidity Disorientation Fever	Dysphagia Pallor Dyspnea Shuffling gait Agitation	Myoglobinemia Elevated LDH Elevated creatine kinase Hyperkalemia Elevated AST and ALT Hyperphosphatemia Elevated alkaline phosphatase Hyperuricemia	Supportive therapy Stop the offending agent Medical Therapy Dantrolene Amantadine Bromocriptine
Viral Meningitis	Fever Irritability Lack of appetite Lethargy Disoriented High grade fever Severe headache Stiff neck Sensitivity to bright light Nausea Vomiting	Headache Photophobia Phonophopia Pharyngitis in case of enterovirus infeciton Orchitis (In mumps) Vesicular or macular skin rash Petichiae Nuchal rigidity Signs of meningeal irritation: Kernig's sign Brudzinski's sign Altered mental status Hypotonia	CSF / plasma glucose ratio (>0.6) Lactate (mmols/l) (<2.1) Lymphocytes > granulocytes	Supportive Analgesics for pain. Acetaminophen for fever. Anti-viral therapy: Acyclovir Pleconaril
Stiff man syndrome	Marked rigidity Spasms Intermittent Painful Absent during sleep	Diaphoresis Arterial hypertension Tachypnea Cyanosis Apnea, tachypnea Respiratory arrest Dilatation of the pupils Tachycardia	CSF has Elevated IgG Oligoclonal bands Positive anti-GAD antibodies Elevated creatine kinase Normal CBC & ESR	Benzodiazepines Baclofen Vigabatrin  Valproic Acid, Neurontin Injected botulinum toxin  Prednisone, plasmapheresis, IVIG ( some success)
Drug induced (Tardive dyskinesia)	History of intake of the offending drug for at least one month Neuroleptics (antipsychotics) Metoclopramide Eye deviation Head and neck jerky movements No tonic contraction of the muscles between the spasms	Dyskinesia of the tongue and lips Dyskinesia of the limbs Dyskinesia of the neck	It is a clinical diagnosis depending on Dyskinetic movements Hx of > 1 month of antipsychotic use Labs may be done to rule out other differentials	Stop the offending agent Benztropine Benzodiazepines Injection of botulinum toxin Valbenzine Tetrabenazine
Strychnine poisoning	Hx of up to date tetanus immunizations History of intentional or accidental intake Strychnos nux vomica seeds Rodenticide	Hypervigilance Anxiety Mydriasis Hypereflexia Clonus Facial and neck stiffness	Blood assay Tissue assay Urine assay	Initial stabilization High dose Benzodiazepines Intubation and airway securing
Hypocalcaemia	Muscle twitching and cramping Circumoral and extremity paresthesia or tingling Altered mental status Irritability Depression Psychosis Seizure	Tetany (carpopedal spasm) Latent tetany Trousseau sign of latent tetany  Chvostek's sign  Hyperactive tendon reflexes	Decreased blood calcium levels	Two ampules of intravenous calcium gluconate 10% is given slowly in a period of 10 minutes, or If hypocalcemia is severe, calcium chloride is given instead Maintenance doses of both calcium and vitamin-D
Parkinson's disease	Stiffness Inability to write Jerky movements at rest Constipation Sleeping difficulty Walking difficulty	Tremor Rigidity Bradykinesia Postural instability Shuffling gait	Clinical diagnosis Improvement with dopaminergic therapy confirms diagnosis	Symptomatic therapy Dopamine agonists Levodopa Amantadine MAO inhibitors COMT inhibitors Anticholinergics

Natural History, Complications and Prognosis

Prognosis is variable and there is no reliable predictor of speed and severity of disease onset. Muscle tetany may lead to muscle rupture and broken bones, or problems swallowing and breathing in severe cases.

Diagnosis

History

• 10% of patients have generalized seizures or myoclonus.
• Fixed thoracolumbar lordosis of the spine develops in nearly all cases from co-contraction of abd/paraspinal muscles.

Symptoms

Those with the illness experience progressive, fluctuating tonic muscle contractions, particularly the axial musculature. Depression and anxiety are often noted although this may be a result of discomfort due to stiffness, rather than underlying neurochemical abnormalities. MRI detection of GABA in the brain have demonstrated reduced levels in stiff-person syndrome. Some of the symptoms are listed below.

• Marked rigidity and painful spasms, particularly in the thoracic and lumbosacral paraspinal, abdominal, and proximal lower extremity muscles
• Onset usually insidious
• Persistent contraction leads to a “board-like” quality.
• Intermittent painful spasms which may lead to falls due to instability.
• Spasms are NOT present during sleep.

Laboratory Findings

• Paraneoplastic cases often are GAD negative, and they have anti-Amphyphysin.
• The CSF is abnormal with increased IgG and oligoclonal bands.
• 65% have anti-GAD antibodies.
• Serum CK levels are often elevated due to a constant state of contraction of muscles.

Treatment

Treatment is mostly palliative with muscle relaxants which enhance GABA production such as benzodiazepines, which lose their effectiveness as the illness progresses.

In the absence of double-blind, placebo-controlled class A trials to determine treatment efficacy, some authorities recommend humane trials of immunosuppressive therapy, plasmapheresis or intravenous immunoglobulin infusion.

Pharmacotherapy

Acute Pharmacotherapies

• Benzodiazepines (enhance the affinity of GABA receptors)
• Oral or intrathecal baclofen
• Vigabatrin (irreversible inhibitor of GABA transaminase)
• Valproic Acid, Neurontin
• Injected botulinum toxin benefits some
• Prednisone, plasmapheresis, IVIG all used with some success, but no randomized trials

See also

• Hyperekplexia

External links

• A site about the link between GAD and SPS at University of Birmingham Medical School
• Template:NINDS
• Article at Cleveland Clinic
• Article at eNotes
• GAD antibodies at antibodypatterns.com
• Amphiphysin antibodies at antibodypatterns.com