Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (110 page)

The majority of patients presenting with myasthenia gravis have thymoma and occasionally SCLC, thyroid, or breast cancer.
¹
Patients present with fluctuating weakness of the extraocular, bulbar, limb, and respiratory muscles. Weakness of the eyelid and extraocular muscles is present in most patients and precedes limb weakness; limb weakness alone is rare in myasthenia gravis. The differential diagnosis includes the Lambert-Eaton myasthenic syndrome, thyroid ophthalmopathy, amyotrophic lateral sclerosis, botulism, and cranial nerve or brain stem pathology.

   Laboratory Evaluation

Diagnosis is made by physical examination (Tensilon test), history, and serologic testing for AChR or MuSK antibodies. These tests are confirmatory in up to 94% of patients with generalized disease.
²
The most sensitive test for AChR-ab is the binding antibody test by radioimmunoassay, which is highly specific for myasthenia gravis. Antibody titers may be used to follow therapy on a particular patient but correlate poorly between patients.

References

1.  Fujita J, Yamadori I, Yamaji Y, et al. Myasthenia gravis associated with small-cell carcinoma of the lung.
Chest.
1994;105:624.

2.  Meriggioli MN, Sanders DB. Myasthenia gravis: diagnosis.
Semin Neurol.
2004;24:31.

LAMBERT-EATON MYASTHENIC SYNDROME

   Definition

Lambert-Eaton myasthenic syndrome (LEMS) an autoimmune disease associated with malignancy and results from the development of antibodies to the voltagegated calcium channel (VGCC), which interfere with the normal calcium flux required for the release of acetylcholine.
¹

   Clinical Presentation

Patients present with symmetrical proximal muscle weakness, which starts in the lower extremities (difficulty rising from a chair), and autonomic dysfunction (dry mouth). The differential diagnosis includes myasthenia gravis, muscular dystrophy, polyneuropathies, and multiple cranial mononeuropathies. The diagnosis is made on clinical examination and confirmed by electrodiagnostic studies and the presence of antibodies to VGCC in the serum.

   Laboratory Evaluation

Testing for VGCC is by radioimmunoassay. Two separate antibodies can be identified. The P/Q-type VGCC is found in 85–95% of patients.
²
The N-type VGCC is found in approximately 40% of patients with LEMS and is more likely to be seen in patients with small cell lung carcinoma.
³
Higher titers of antibody are found in patients with underlying carcinoma while lower titers of antibody may be seen in patients with other neurologic paraneoplastic disorders and amyotrophic lateral sclerosis.
⁴

References

1.  Motomura M, Johnston I, Lang B, et al. An improved diagnostic assay for Lambert-Eaton myasthenic syndrome.
J Neurol Neurosurg Psychiatry.
1995;58:85.

2.  Pellkofer HL, Armbruster L, Krumbholz M, et al. Lambert-Eaton myasthenic syndrome differential reactivity of tumor versus non-tumor patients to subunits of the voltage-gated calcium channel.
J Neuroimmunol.
2008;204:136.

3.  Lennon VA, Kryzer TJ, Griesmann GE, et al. Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes.
N Engl J Med.
1995;332:1467.

INFECTIONS OF THE CENTRAL NERVOUS SYSTEM
*

Infections of the central nervous system (CNS) are associated with significant morbidity and mortality. Infections are caused by all types of pathogens from viruses to parasites. Organisms gain access to CNS most commonly by

   Hematogenous spread (e.g., bacterial endocarditis, nasopharyngeal colonization by
Neisseria meningitidis
)

   Direct extension from a contiguous site of infection (e.g., infected sinus)

   Direct invasion (e.g., surgery, trauma, basilar skull fracture)

Pathogenesis and signs and symptoms depend on the pathogen and site of infection, as discussed in subsequent text of this Chapter and in other Chapters. Primary infection may occur in the parenchyma of the CNS, as seen in encephalitis and brain abscess. Infections may also occur outside the parenchyma in locations bounded by the meninges:

   Epidural abscesses are localized in the space between the dura mater and the vertebrae.

   Meningitis occurs in the subarachnoid space (between the arachnoid and pia mater).