Acquired disorders
Examples
Metabolic diseases
• Diabetes
• Vitamin deficiency (B12, B6)
• Uremia
• Hypothyroidism
• Secondary amyloidosis
Immune-mediated diseases
• Guillain-Barré syndrome
• Chronic inflammatory demyelinating polyneuropathy
• Multifocal motor neuropathy
• Vasculitis
• Connective tissue diseases
• Paraproteinemia
• Cryoglobulinemia
• Plexus neuritis
Infectious diseases
• Herpes zoster (shingles)
• Neuroborreliosis
• HIV/AIDS
• Syphilis
• Sarcoidosis
• Leprosy
Toxic diseases
• Alcohol abuse
• Chemotherapy, medication
• Heavy metal intoxication
Paraneoplastic diseases
• Sensory neuronopathy
Hereditary disorders
Examples
HMSN (CMT)
• HMSN 1–3
• HNPP
HSAN
• HSAN 1–3
Hereditary neuralgic amyotrophy
Others
• Familial amyloidosis
• Porphyria
• Fabry’s disease
• Metachromatic leukodystrophy
• Adrenoleukodystrophy
• Refsum’s disease
CMT, Charcot-Marie-Tooth disease; HMSN, hereditary motor and sensory neuropathy; HNPP hereditary neuropathy with liability to pressure palsy; HSAN, hereditary sensory and autonomic neuropathy.
• Underlying and concomitant diseases.
• Medication history.
• Age at onset of symptoms.
• Time course of symptom development:
– Acute (up to 4 weeks).
– Subacute (4–8 weeks).
– Chronic (> 8 weeks).
• Type of clinical manifestation:
– Symmetric/asymmetric.
– Sensory/sensorimotor/motor.
– With/without autonomic impairments.
– With/without pain.
• Neurophysiological characteristics:
– Demyelinating.
– Axonal.
– Mixed.
Stepped analysis. Laboratory tests guide the diagnosis of metabolic, immune-mediated, infectious, and hereditary polyneuropathies. Relevant additional information is largely obtained from serological screening tests and a more detailed serological analysis. CSF analysis is helpful if an immune-mediated or infectious etiology is suspected. Molecular genetic analysis helps with the precise classification of hereditary etiologies; as this is cost-intensive, it should always be used in a targeted manner, depending on the clinical and neurophysiological manifestation. In a very few cases, nerve biopsy is required as the final diagnostic step to elucidate the etiology.
Serum Analysis
Basic analysis. As a first step, a few serological screening tests (Table 13.2) will give an indication of:
• The presence of any of the main metabolic causes of polyneuropathy (diabetes mellitus, renal failure, vitamin deficiency).
• Any signs of inflammation or hepatic dysfunction, indicating immune-mediated disease or chronic alcohol abuse.
Detailed analysis. The next stage in laboratory analysis includes as a first step:
• Serological detection of various immunological markers.
• Infection serology.
• Selective laboratory diagnosis of suspected hypovitaminosis and nondiabetic metabolic disorders.
• CSF analysis.
If the results are negative, screening for rare metabolic and toxic etiologies can be done as a second step, depending on the manifestation of the neuropathy (Table 13.3). Molecular genetic analysis also forms part of this stage in the stepped screening program.
Serum Analysis: Stage 1
Immune-mediated diseases. Laboratory diagnosis of immunemediated neuropathies is discussed in detail in Chap. 10, “Guillain-Barré Syndrome and Other Immune-Mediated Neuropathies.” Determination of autoantibodies against gangliosides is primarily helpful when the following disorders are suspected:
• Miller-Fisher syndrome: strong association with anti-GQ 1 b antibody.
• Multifocal motor neuropathy (MMN): association with anti-GM1 antibody and, in rare cases, anti-GM2 antibody.
The diagnostic importance of other antibody reactivities for immune-mediated neuropathies is low (e. g., antibodies against gangliosides GD 1 a and GalNac-GD 1 a, disialosyl gangliosides GD 1 b, GD 3, GT1 b, and GQ 1 b, acidic glycolipids SGPG and SGLPG, and sulfatides), and broad screening for these is therefore not generally recommended. Indications for targeted testing are listed in Chap. 10, “Guillain-Barré Syndrome and Other Immune-Mediated Neuropathies.”
On the other hand, all patients with polyneuropathic syndromes of undetermined etiology should be screened for paraproteins. Serum immunoelectrophoresis and serum immunofixation electrophoresis are sensitive screening methods, as is detection of Bence Jones proteins in urine by immunofixation electrophoresis. If IgM paraproteins are detected, the serum should be tested specifically for antibodies against myelin-associated glycoprotein (MAG), since about 50% of IgM paraproteins bind this target antigen. Other IgM subspecificities (e. g., against sulfatides, disialosyl gangliosides) are rare, and they are tested for only on particular selected indications.
Suspected cause of polyneuropathy | Laboratory parameters | Diagnostic importance |
Step 1 |
|
|
Immune-mediated diseases | Antibodies to GQ 1b | Miller-Fisher syndrome, Guillain-Barré syndrome with ophthalmoplegia |
| IgM antibodies to GM1 and GM2 | Multifocal motor neuropathy |
| • IgM, IgG, IgA paraproteins • MAG antibody • Bence Jones protein in the urine | Monoclonal gammopathy of undetermined significance, malignant paraproteinemia |
| Cryoglobulins | Cryoglobulinemic vasculitis |
|
