Re: CMT 1A : with superimposed inflammatory polyneuropathy in children.

[Guest guest]

My daughter has CMT 1A. How would I know if she also has acute inflammatory

demyelinating polyneuropathy (AIDP)? Thanks!

Joe

[Guest guest]

Joe,

There are some tests and results that can pinpoint AIDP.

http://emedicine.medscape.com/article/1169959-overview

Laboratory Studies

Laboratory tests help to support the diagnosis of acute inflammatory

demyelinating polyneuropathy (AIDP) and monitor patients with the syndrome. No

associated hematologic or urinary findings are characteristic of the diagnosis.

The erythrocyte sedimentation rate is normal. Serum protein electrophoresis does

not show an abnormality. Hyponatremia due to inappropriate ADH secretion may

occur.

Cerebrospinal fluid

Increased CSF protein without an increased WBC count (albuminocytologic

dissociation) is observed classically in AIDP. However, this finding is not

specific to AIDP.

About two thirds of patients have this CSF finding during the first week of

symptoms and 82% have it by 2 weeks after symptom onset.

Although protein values can be elevated by 10-fold or more, no association

exists between protein level and clinical severity.

Some patients have oligoclonal banding of the CSF.

Myelin basic protein also is increased in some patients.

More than 90% of patients have fewer than 10 WBC/µL, with a mean of 3 WBC/µL. If

more than 50 WBC/µL are present, an alternative diagnosis should be considered,

including HIV, Lyme disease, polio, or other infections. Patients with

HIV-associated AIDP often have >50 WBC/µL (mean, 23 WBC/µL).

In non-HIV cases, the cells are overwhelmingly lymphocytes, whereas a

nonlymphocytic pleocytosis is seen in patients with HIV.

Blood tests have little role in the diagnosis of AIDP but may help to exclude

other conditions and to serially monitor patients with AIDP in the hospital

(especially those who are critically ill).

Recently, an association has been found between acute axonal motor variants and

immunoglobulin G (IgG) directed against ganglioside GM1 and/or GD1a.

Furthermore, most patients with the -Fisher variant of AIDP have

antibodies directed against ganglioside GQ1b. Some patients with pure sensory

variants have antiganglioside GD1b antibodies. These tests are seldom beneficial

in classic AIDP, but can help when patients present with variants.

Rabbit ataxic neuropathy and several case reports have suggested a close

association of IgG anti-GD1b antibodies with ataxia in Guillain-Barré syndrome.

However, about half of the patients with Guillain-Barré syndrome having IgG

anti-GD1b antibodies with no reactivities against other gangliosides (GD1b-mono

IgG) do not exhibit ataxia. Antibodies specific to ganglioside complexes (GSCs)

containing GD1b have been found in sera from some patients with Guillain-Barré

syndrome. IgG antibodies highly specific for GD1b may induce ataxia in

Guillain-Barré syndrome.

Although not necessary for diagnosis, measurement of antiviral or antibacterial

antibodies may confirm an association.

Measurement of potassium, phosphate, and porphyrin metabolism products may help

exclude alternative diagnoses in atypical cases.

Some critically ill patients with AIDP develop the syndrome of inappropriate

antidiuretic hormone (SIADH) with associated hyponatremia and reduced serum

osmolarity.

Additionally, liver enzymes sometimes are elevated in AIDP.

If intravenous immunoglobulin (IVIg) therapy is anticipated in noncritical

cases, immunoglobulin A (IgA) levels should be drawn before treatment.

Urine tests to exclude heavy metal intoxication may be necessary in some

patients.

Stool cultures may confirm C jejuni enteritis. Patients with this condition may

have a more aggressive course and a slightly worse prognosis.

Imaging Studies

Imaging is seldom necessary for diagnosing acute inflammatory demyelinating

polyneuropathy, but it may be necessary to exclude alternative diagnoses and to

monitor critically ill patients.

MRI of the spine is sometimes necessary to rule out spinal cord and/or nerve

root processes that mimic AIDP.

Nerve root, cauda equina, or cranial nerve enhancement is observed sometimes on

T1-weighted, gadolinium-contrasted scans. This can help diagnose some atypical

cases.

Cytomegalovirus radiculitis, meningeal carcinomatosis, lymphomatosis, and

sarcoidosis may have similar MRI findings.

Chest radiography in children may reveal a pattern that is consistent with

mycoplasmal pneumonia. Additionally, chest and abdominal radiography may be

necessary in critically ill patients to evaluate for possible pneumonia and

ileus.

Other Tests

Electrodiagnostic testing is always necessary to confirm the diagnosis of acute

inflammatory demyelinating polyneuropathy.

Nerve conduction studies (NCS) can document demyelination, the hallmark of acute

inflammatory demyelinating polyradiculoneuropathy.

Early on, findings of NCS studies are often normal. However, 90% are abnormal

within 3 weeks of symptom onset.

Patients who meet 3 of the 4 NCS criteria listed below have a clear primary

demyelinating neuropathy, although patients who meet fewer than 3 criteria still

may have AIDP. Severe slowing of conduction velocities may be more consistent

with chronic inflammatory demyelinating polyneuropathy (CIDP). Details of

electrodiagnostic criteria are provided in Cornblath.

Reduced conduction velocity

Conduction block or abnormal dispersion

Prolonged distal latencies

Prolonged F-waves

Needle EMG can document the extent of denervation.

Findings of other electrophysiologic tests, such as blink reflexes, phrenic

nerve conduction, and somatosensory evoked responses, may be abnormal but do not

offer any advantages to typical NCS studies.

Autonomic tests such as sympathetic skin responses and cardiovagal testing may

be indicated in patients with autonomic failure.

Pulmonary function tests, useful in determining the timing of intensive care

unit (ICU) transfers and elective intubation, should be performed in all

patients.

Transfer to an ICU generally is indicated when forced vital capacity (FVC) is

less than 20 mL/kg.

Intubation is usually warranted when FVC drops to 15 mL/kg or negative

inspiratory pressure drops to less than -25 cm H2 O.

Electrocardiography (ECG) and cardiac monitoring can be helpful when arrhythmias

occur. Other possible abnormalities include atrioventricular block, QRS

widening, and T-wave abnormalities.

Jin et al measured the CSF tau protein levels in 26 patients with Guillain-Barré

syndrome. The levels of the poor outcome group ( grade at 6 months was

between II and VI, n = 6) were higher than those of the good outcome group (0 or

I, n = 20) (p < 0.0005).

The higher levels of CSF tau may reflect axonal degeneration and could predict a

poor clinical outcome in Guillain-Barré syndrome.

Procedures

Lumbar puncture is performed to obtain CSF for analysis (see Lab Studies).

Histologic Findings

Nerve biopsy is seldom required to diagnose acute inflammatory demyelinating

polyradiculoneuropathy. However, in patients with prolonged clinical courses,

histologic examination can help to differentiate CIDP from AIDP. Nerve biopsies

in AIDP show an inflammatory infiltrate during the first few days.

Later on, macrophages are seen, sometimes with myelin stripping. Axons are

usually spared. Under electron microscopy, macrophages (which are stripping

myelin) are seen beneath the basement membrane and are usually advancing along

the minor dense line.

More at http://emedicine.medscape.com/article/1169959-overview

Gretchen

>

> My daughter has CMT 1A. How would I know if she also has acute inflammatory

demyelinating polyneuropathy (AIDP)? Thanks!

>

> Joe

>