Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (100 page)

   Urinary porphyrins and erythrocyte porphobilinogen deaminase levels for porphyria

References

1.  Klein CM, Vernino S, Lennon VA, et al. The spectrum of autoimmune autonomic neuropathies.
Ann Neurol.
2003;53:752.

2.  Sandroni P, Vernino S, Klein CM, et al. Idiopathic autonomic neuropathy: comparison of cases seropositive and seronegative for ganglionic acetylcholine receptor antibody.
Arch Neurol.
2004;61(1):44–48.

3.  Schroeder C, Vernio S, Birkenfeld AL, et al. Plasma exchange for primary autoimmune autonomic failure.
N Engl J Med.
2005;353:1585.

4.  Vernino S, Freeman R. Peripheral autonomic neuropathies.
Continuum Lifelong Learning Neurol.
2007;13(6):89–110.

GUILLAIN-BARRÉ SYNDROME

   Definition

Guillain-Barré syndrome (GBS) is the name given to a group of heterogeneous disorders comprising the acute immune-mediated polyneuropathies. There are several variant forms including the acute inflammatory demyelinating polyradiculoneuropathy (AIDP), seen in the United States and Europe, and the acute motor axonal neuropathy (AMAN) and acute sensory motor axonal neuropathy (AMSAN), which are usually seen in China, Japan, and Mexico
¹

   Clinical Presentation

The usual presentation is that of an acute monophasic paralyzing illness following an infection.
²
In 70% of cases, it is reversible, but 10% of patients die and 20% have residual defects. Dysautonomia occurs in 70% of patients, and severe autonomic dysfunction is occasionally associated with sudden death.
^3,4

A number of glycolipid antibodies have been found to be the underlying cause of GBS. These include antibodies against GQ1b, which is a ganglioside component of nerve seen in the Miller-Fisher variant, and antibodies to GM1, GD1a, GalNac-GD1a, and GD1b, which are associated with axonal variants.
⁵
Electromyography and nerve conduction studies may be helpful in diagnosing GBS by revealing the predominantly demyelinating polyneuropathy of AIDP or the axonal neuropathy of AMAN or AMSAN.

   Laboratory Findings

The CSF shows albumin–cytologic dissociation with normal cell count and increased protein (average 50–100 mg/dL). The protein increase parallels increasing clinical severity, and the increase may be prolonged. The CSF may be normal at first.

Commercial testing for antibody to GQ1b is now available and may be useful in the diagnosis.
⁶
A biopsy of the nerve will show evidence of demyelination and remyelination.

Laboratory findings due to associated disease may be present (e.g., evidence of recent infection with
Campylobacter jejuni
in 15–40% of cases and CMV in 5–20% of cases; EBV and
Mycoplasma pneumoniae
in <2% of cases in developed countries, other viral and rickettsial infections, immune disorders, DM, exposure to toxins [e.g., lead, alcohol], neoplasms). No agent was identified in ≤70% of cases.
⁷

References

1.  McKhann GM, Cornblath DR, Griffin JW, et al. Acute motor axonal neuropathy: a frequent cause of acute flaccid paralysis in China.
Ann Neurol.
1993;33:333.

2.  Ropper AH. The Guillain-Barré syndrome.
N Engl J Med.
1992;326:1130–1136.

3.  Zochodne DW. Autonomic involvement in Guillain-Barré syndrome: a review.
Muscle Nerve.
1994;17:1145–1155.

4.  Köller H, Kieseier BC, Jander S, et al. Chronic inflammatory demyelinating polyneuropathy.
N Engl J Med.
2005;352:1343–1356. Review.

5.  Nagashima T, Koga M, Odaka M, et al. Clinical correlates of serum anti-GT1a IgG antibodies.
J Neurol Sci.
2004;219:139.

6.  Chiba A, Kusunoki S, Obata H, et al. Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barré syndrome: clinical and immunohistochemical studies.
Neurology.
1993;43:1911.

7.  Sivadon-Tardy V, Orlikowski D, Rozenberg F, et al. Guillain-Barré syndrome, greater Paris area.
Emerg Infect Dis.
2006;12:990.

MULTIPLE SCLEROSIS

   Definition

Multiple sclerosis (MS) is an inflammatory disorder of the brain and spinal cord resulting in the loss of myelin, which insulates the neurons. It is the most common autoimmune demyelinating disease of the CNS.

   Clinical Presentation

Patients present with distinct episodes of neurologic deficits separated in time. It is caused by an inflammatory demyelination of distinct foci of white matter that are separated in space. Women are twice as likely to be affected as men, and the disease is rare in children or in patients >50 years of age. At autopsy, histology of the brain reveals multifocal areas of demyelination with loss of oligodendrocytes and astroglial scarring (see eBook Figure 4-18). Diagnosis should not be made by CSF evaluation alone unless there are
multiple clinical lesions in time
(by clinical history) and
anatomic location
(by MRI, evoked potentials, or physical examination). The diagnosis of MS is most commonly made using the McDonald criteria, which have undergone recent revision and require both MRI and CSF findings for definitive diagnosis.
^1,2

   Laboratory Findings

CSF changes are found in >90% of patients with MS.
³
The opening pressure, glucose, and albumin levels are normal, and leukocyte count is normal in two thirds of patients. Less than 5% of patients have a white blood cell (WBC) count >50 cells/μL. Cells are predominantly T lymphocytes. There are two significant CSF tests that are positive in MS: oligoclonal bands (OCBs) and the IgG index.
¹

   Oligoclonal IgG Bands