Polyneuropathies: Test and Diagnosis

1st order laboratory parameters – obligatory laboratory tests.

  • Small blood count
  • Differential blood count [eosinophilia?, macrocytic anemia?, MCV elevation in alcohol abuse/alcohol dependence?]
  • Inflammatory parameters – CRP (C-reactive protein) or ESR (erythrocyte sedimentation rate).
  • Urine status (rapid test for: pH, leukocytes, nitrite, protein, glucose, ketone, blood), sediment, if necessary urine culture (pathogen detection and resistogram, that is, testing of suitable antibiotics for sensitivity / resistance), albumin (microalbuminuria?).
  • Fasting glucose (fasting blood glucose), if necessary also oral glucose tolerance test (esp. in distal symmetric sensitive PNP).
  • HbA1c (long-term blood glucose value).
  • Thyroid parameters – TSH
  • Liver parameters – alanine aminotransferase (ALT, GPT), aspartate aminotransferase (AST, GOT), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase (gamma-GT, GGT).
  • Renal parameters – urea, creatinine, creatinine clearance.
  • Serum protein electrophoresis
  • Immunoglobulin (oligoclonal bands) [monoclonal gammopathy?] Note: Approximately 10% of distal symmetric PNP are due to paraproteinemia
  • Bence Jones protein (urine).
  • Carbodeficient transferrin (CDT) ↑ (in chronic alcoholism; positive with consumption of one bottle of wine or three bottles of beer per day)* .
  • Vitamin B12 (in addition methylmalonic acid in low normal levels) – in subacute PNP with and without central nervous system involvement.

* With abstinence, the values normalize within 10-14 days.

Laboratory parameters 2nd order – depending on the results of the history, physical examination, etc. – for differential diagnostic clarification of a polyneuropathy (PNP).

  • ANA, pANCA, cANCA, dsDNA, auto-Ak against vascular endothelium (AECA), SS-A (Ro), SS-B (La), snRNP, cryoglobulins-suspicion of vasculitis [see below Vasculitides (immunoreactively triggered inflammation of blood vessels)/laboratory diagnostics].
  • Antibody anti-FGF3 (“antifibroblast growth factor receptor 3 antibody”) – causative for a subset of neuronopathies and small fiber neuropathies.
  • Infectious serology studies
    • Borrelia serology [see below Borrelia/lab diagnostics].
    • Advanced examinations: Cytomegaly, TPHA (Treponema pallidum hamagglutination assay), HIV, hepatitis B and C.
  • Porphyrins in urine
  • Vitamin status – vitamin B1, vitamin B6 and vitamin E
  • Intoxication parameters – arsenic, lead, mercury, thallium.
  • CSF puncture (collection of cerebrospinal fluid by puncture of the spinal canal) for CSF diagnosis (cell count, CSF cytology, proteins and immunoglobulins (CSF protein profile), oligoclonal bands, Borrelia AK); indications:
  • Skin biopsy (removal of tissue from the skin); indications:
    • Diagnosis of neuropathic pain and
    • Small-fiber neuropathies (special form of sensitive polyneuropathies in which mainly the thin “C-fibers” not surrounded by “myelin sheaths” are affected), if conventional electrophysiological methods do not show any abnormalities and/or small-fiber neurpathy is suspected.
  • Nerve biopsy; indications:
    • In case of suspected inflammatory genesis
    • Moderate/severe progressive neuropathy when non-invasive methods have not led to a diagnosis
  • Molecular genetic testing (PMP22 gene; most common cause: duplication at PMP22 gene on chromosome 17) – Indications:
    • Positive family history for neuropathies.
    • Suspected hereditary (inherited) PNP (high arch, claw toes, indolent course, young age of onset present)
    • Suspected hereditary motor-sensitive neuropathy type I (HMSN I) or from English “Hereditary Neuropathy with liability to Pressure Palsies” (HNPP)).

    Other molecular genetic studies: GJB1, MPZ and MFN2, gene panel, trio exome/genome.