Autoimmunity of the Nervous System



Autoimmunity of the Nervous System






Myasthenia gravis (MG)


Presentation



  • Patients complain of double vision, muscle weakness, and fatigue (worse later in the day).


  • Ptosis and diplopia are typical signs.


  • Examination reveals generalized fatiguable muscle weakness.


  • It is a heterogeneous condition with varying ages of presentation.


  • Diagnosis of a neuromuscular junction defect can be confirmed by electrophysiological tests and the Tensilon® test (see Box 5.1).



Immunogenetics



  • In younger patients there is an association with HLA-A1, B8, and DR3, and a strong female predominance.


  • Disease can also be induced by penicillamine, and is mostly found in those who are HLA-Bw35/DR1 positive.


Immunopathology



  • Muscle weakness is due to impaired action of acetylcholine (ACh) at the muscle endplate.


  • The cause is unknown but the disease is strongly associated with thymomas (benign and malignant), thymic hyperplasia, and other autoimmune diseases such as SLE, polymyositis, haemolytic anaemia, and thyroid disease (especially in those <40 years old).


  • Prevalence is 2-10/100 000.


  • Patients with thymoma are usually older and both sexes are affected equally; about 10% have thymomas, but removal of the tumour does not always affect the course of the disease.


Autoantibodies



  • IgG anti-ACh-receptor (AChRAb) is detected in 75-95% of patients.


  • 10% are seronegative.


  • 50% with pure ocular myasthenia are seronegative.


  • The disease is caused by direct receptor blockade, complementmediated endplate damage, and enhanced recycling of the receptor off the endplate surface membrane.


  • AChRAb levels are variable, but high titres are found in those <40 years old with thymic hyperplasia.



  • Antibodies are IgG isotype and therefore can be transmitted across the placenta, causing neonatal myasthenia.


  • The presence of striated muscle antibodies is a marker for the presence of a thymoma. These includes antibodies to the ryanodine receptor and titin antibodies.


  • Cardiac arrythmias may occur in the presence of anti-cardiac muscle antibodies.


  • Antibodies to MuSK (muscle-specific tyrosine kinase) have been shown in a proportion of patients with AChRAb negative MG.



    • MuSK is a receptor tyrosine kinase that is restricted to the neuromuscular junction.


    • Patients with these antibodies are typically female, with bulbar disease, who may be difficult to treat with immunosuppression.


    • Antibodies to MuSK interfere with agrin-triggered stimulation of MuSK.



Lambert-Eaton myasthenic syndrome (LEMS)


Presentation



  • LEMS is an idiopathic or paraneoplastic syndrome.


  • It is associated with small cell lung cancer (SCLC) as a paraneoplastic phenomenon (1-3% of cases).


  • Some cases occur without cancer (especially in children) and are associated with HLA-B8, DR3.


  • Proximal muscle weakness is marked, but bulbar and ocular muscles are spared.


  • Associated with other autoimmune diseases, especially thyroid and vitiligo.


Immunopathology



  • There is a decrease of voltage-gated calcium channels (VGCC) on presynaptic nerve terminals caused by an autoantibody reactive with the channels, particularly the P/Q-type.


  • Some patients have antibodies to synaptotagmin.



  • Patients with LEMS may also have antibodies to AchR.


  • Autoimmune aetiology has been established by demonstration of passive transfer of disease.



Acquired neuromyotonia (Isaac’s disease) and stiff person syndrome (SPS)


Acquired neuromyotonia (Isaac’s disease)


Presentation



  • This syndrome is marked by acquired spontaneous and continuous muscle contraction.


  • Patients develop stiffness, twitching, cramps, sweating, and other autonomic problems.


Immunopathology



  • Some cases are due to autoantibodies against voltage-gated potassium channels (VGKC) at presynaptic nerve terminals.



Stiff person syndrome


Presentation



  • It causes a fluctuating and progressive muscular rigidity, which is painful.


  • Men are more commonly affected than women.


  • Up to a third of patients will develop diabetes, and there may be features of autoimmune glandular disease.


  • In approximately 10% of patients, SPS develops as a paraneoplastic disorder associated with breast cancer.


Immunopathology



  • This rare neurological syndrome is associated with anti-GAD antibodies.


  • The finding of the autoantibody ties in with the neurological conclusion that GABAergic neurons, which regulate muscle tone, are involved.



Autoantibodies



  • Anti-GAD antibodies are found in >60% of patients with SPS (see Chapter 18).


  • Anti-amphiphysin antibodies are sometimes elevated in blood and CSF of patients with paraneoplastic SPS and, rarely, in non-neoplastic SPS.


  • There is some evidence that the autoantibodies are pathogenic in some cases of paraneoplastic SPS.



Morvan’s syndrome



  • Rare syndrome of neuromyotonia, hyperhidrosis, insomnia, and delirium.


  • Autoimmune aetiology; may be associated with thymoma (and solid tumours).


  • Associated with antibodies to VGKC and to CASPR2


  • May respond to corticosteroids, plasmapheresis, hdIVIg, and thymectomy.

Jul 22, 2016 | Posted by in GENERAL SURGERY | Comments Off on Autoimmunity of the Nervous System
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