Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (109 page)

   Clinical Presentation

Patients may present with various neurologic symptoms depending on the area of the brain affected and the severity of the disease. In giant cell arteritis, patients present with neurologic symptoms of headache and visual disturbances. Amyloid angiopathy (see Vascular Dementia) may also occur in the central nervous system.
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The differential diagnosis of vasculitis is broad, and diagnostic testing includes clinical examination and history, neuroimaging such as MRA or CTA, and evaluation of the blood and CSF.

   Laboratory Evaluation

Blood work should include a sedimentation rate and C-reactive protein, which may be elevated in collagen vascular diseases, infection, and temporal arteritis. These are normal in primary angiitis. Serologic evaluation should be carried out to rule out syphilis, Lyme disease, catscratch disease, tuberculosis, herpes virus, hepatitis B and C virus, HIV, and cysticercosis. Rheumatologic studies should be performed to rule out collagen vascular disease (ANA, rheumatoid factor, antineutrophilic cytoplasmic antibody).

A lumbar puncture with analysis of the CSF should be performed to rule out infection (cell count and culture), malignancy (cytology), or hemorrhage with evidence of xanthochromia.

If the diagnosis cannot be made with less invasive means, a biopsy should be performed. Biopsy will help in the diagnosis of giant cell arteritis. Vascular changes include loss of the internal elastic lamina and inflammatory infiltrates of the vascular wall by histiocytes, giant cells, and lymphocytes.

References

1.  Calabrese LH, Duna GF, Lie JT. Vasculitis in the central nervous system.
Arthritis Rheum.
1997;40:1189.

2.  Calabrese LH, Mallek JA. Primary angiitis of the central nervous system. Report of 8 new cases, review of the literature, and proposal for diagnostic criteria.
Medicine (Baltimore).
1988;67:20.

3.  Fountain NB, Eberhard DA. Primary angiitis of the central nervous system associated with cerebral amyloid angiopathy: report of two cases and review of the literature.
Neurology.
1996;46:190.

PARANEOPLASTIC SYNDROMES AFFECTING THE CNS

   Definition

A group of disorders resulting from an immunologic response to a shared antigen between a tumor and antigens normally expressed by the nervous system are classified as paraneoplastic neurologic syndromes.

   Clinical Presentation

Patients present with muscle weakness and autonomic dysfunction. Both humoral and cell-mediated immune response is believed to be involved in these disorders. Antibodies can be detected in both the serum and CSF of patients with these disorders. A group of antibodies have been identified associated with small cell lung carcinoma (SLCL), and additional antibodies have been associated with other tumors including thymoma, breast and GYN carcinomas, Hodgkin lymphoma, teratoma, melanoma, and other lung cancers. In addition, several antibodies may occur either with or without an associated carcinoma; these include the Lambert-Eaton myasthenic syndrome (LEMS) and myasthenia gravis (see Sections on LEM and Myasthenia gravis below).

   Laboratory Evaluation

Screening for patients suspected of having a paraneoplastic neurologic syndrome requires evaluation of both serum and CSF for antibodies.
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Patients with small cell lung carcinoma may have multiple antibodies with or without symptoms. Some patients without an underlying carcinoma may also have antibodies causing neurologic disease. Paraneoplastic symptoms and antibodies may be present years before a malignancy is diagnosed. The identification of antibodies in a patient does not necessarily predict symptomatology.

The well-characterized paraneoplastic antibodies that most often are found in the symptomatic patients include anti-Hu, anti-Yo, anti-Ri, anti-Tr, anti-CV2/ CRMP5, anti-Ma 1 and 2, anti-amphiphysin, and anti-recoverin.
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Small cell lung carcinoma is the tumor most commonly associated with paraneoplastic neurologic syndromes and include LEMS and autonomic neuropathy (anti-VGCC antibody), cerebellar ataxia and encephalomyelitis (associated with several antibodies), sensory neuropathy (anti-Hu antibody), retinopathy, and opsomyoclonus.
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In addition to evaluation of antibodies in the CSF, spinal fluid should be evaluated for malignant cells by cytology and for inflammatory changes such as pleocytosis and oligoclonal bands to rule out MS.
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References

1.  McKeon A, Pittock SJ, Lennon VA. CSF complements serum for evaluating paraneoplastic antibodies and NMO-IgG.
Neurology.
2011;76:1108.

2.  Graus F, Saiz A, Dalmau J. Antibodies and neuronal autoimmune disorders of the CNS.
J Neurol.
2010;257:509.

3.  Honnorat J, Antoine JC. Paraneoplastic neurological syndromes.
Orphanet J Rare Dis.
2007;2:22.

4.  Psimaras D, Carpentier AF, Rossi C; PNS Euronetwork. Cerebrospinal fluid study in paraneoplastic syndromes.
J Neurol Neurosurg Psychiatry.
2010;81:42.

MYASTHENIA GRAVIS

   Definition

Myasthenia gravis results from the development of autoantibodies directed against the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) resulting in destruction of proteins in the postsynaptic membrane of the neuromuscular junction.

   Clinical Presentation