LENGTH DEPENDENT NEUROPATHIES (Guidelines)

Presentation

Chronic 'length dependent neuropathies' is the most common neuropathy.
Presentation is in adults over 50 years old who have a symmetrical, slowly progressive neuropathy. The symptoms begin in feet and work their way upwards. There may be mild weakness of feet, dysasthesia and mild proprioceptive problems. It can be due to a number of underlying disorders. It is often due to diabetes (including impaired glucose tolerance which can cause a mild and painful neuropathy) but may be idiopathic if blood tests looking for causes prove negative.

Assessment

Nerve conduction studies in these patients are unlikely to be useful because they will show an axonal neuropathy in the vast majority (and won't explain the underlying cause of the neuropathy.)
A set of 'screening' blood tests is below. Some tests are 'general health bloods' which may point to a systemic issue causing the neuropathy rather than direct pathology. In addition (in those who may be at risk) checking HIV, syphilis and borrelia serology may be helpful.

Blood Test	Looking for	Outcome
Full blood count	General health screen MCV - vitamin B12 deficiency	Investigate underlying abnormality.
Renal function	General health screen Neuropathy can be caused by chronic renal failure	Investigate underlying abnormality. Consider renal failure as cause in those with long standing renal failure
Liver function	General health screen	Investigate underlying abnormality. Can be associated with hepatitis B infection. Can be associated with hepatitis C infection due to cryoglobulinaemia (refer patient)
Thyroid function	Hypothyroidism	Treat.
Vitamin B12	Low vitamin B12	Investigate and treat. Consider trial of treatment in those with a low normal vitamin B12 level.
Immunoglobulin protein, electropheresis and plasma viscosity	Monoclonal gammopathy is more common in those with peripheral neuropathy, particularly IgM paraprotein. IgG (light chain usually lambda) associates with POEMs.	Follow local haematology guidelines. Refer/discuss cases if it is unclear whether result is relevant to neuropathy.
Plasma viscosity and CRP	Elevated - consider vasculitis or active autoimmune condition	ANA, ANCA, rheumatoid factor in those with an unexplained elevates plasma viscosity and refer patient.
Serum glucose HbA1c	Diabetes	Treat which may slow progression of neuropathy.
Glucose tolerance test	Even 'pre-clinical diabetes' can cause a mild, usually painful neuropathy	Healthy lifestyle may slow progression neuropathy and diabetes.

In addition ask

Drug history - some do cause neuropathies / neuritis.
Family history - if there are first degree relatives with unexplained neuropathies and there are concerns that this is an inherited neuropathy, refer.

Diagnosis

There are many causes of neuropathy, two ways of trying to work out the underlying cause is to look at speed of onset and the predominant problem ie weakness or sensory symptoms.

Diagnosis on the basis of symptom onset.
Acute	Relapsing	Subacute/Chronic
Guillian Barre syndrome Vasculitis Paraneoplastic sensory neuropathy Diabetic lumbosacral radiculoplexus neuropathy (used to be known as diabetic amyotrophy)	Chronic inflammatory demyelinating polyneuropathy (CIDP) Vasculitis Porphyria	Vitamin B12 deficiency Uraemic neuropathy Neuropathy due to hypothyroidism Neuropathy associated with paraproteins Diabetes and impaired glucose tolerance Hereditary neuropathies eg Charcot Marie Tooth

Diagnosis on basis of most prominent symptom

Pure motor weakness.
No sensory symptoms or signs on examination

Mixes sensory and motor neuropathy

Predominantly proprioceptive loss
causing sensory ataxia

Predominantly pain

Multifocal motor neuropathy
Some hereditary neuropathies

Consider other causes:
Motor Neurone Disease
Myasthenia gravis
Myopathies

Most common - see blood screening for more common causes

Paraneoplastic (check paraneoplastic antibodies and look for underlying cancer)
Sjogrens syndrome
Cisplatin toxic neuropathy
Pyridoxine toxicity
IgM paraprotein demyelinating neuropathies (check anti GD1b antibodies)
Guillian Barre syndrome uncommonly

Diabetes or impaired glucose tolerance
Vasculitic neuropathy
Guillian Barre syndrome
HIV related neuropathy
Toxic neuropathy eg arsenic
Amyloid (familial or primary)
Fabry's disease
Inherited syndromes

Referral

Refer/ discuss with neurology (or if acute issue to medical team)

Rapidly progressive neuropathy.
'Neuropathy' which only has motor and no sensory symptoms/ signs.
Neuropathy where proprioceptive loss is the prominent symptom.
Asymmetrical neuropathy, particularly if mononeuritis multiplex is considered.
Patient with hepatitis C, elevated plasma viscosity or paraproteins.
Strong family history.

Urgent referral

Any neuropathy which is worsening on a daily or weekly basis should be referred to neurology clinic as urgent. If there is a concern the neuropathy may be Gullain Barre syndrome due to rapid worsening; refer to medical team for in-patient assessment.

Management

If a patient has neuropathic pain; amitriptyline, nortriptyline, gabapentin, pregabalin or duloxetine could be trialled. See formulary

Physiotherapy for review of mobility and consideration of aids may be useful and give an opinion as to whether aids eg foot splints may be useful for patients with foot drop.

References:
Overell J. Peripheral neuropathy: pattern recognition for the pragmatist. Practical neurology 2011; 11: 62-70
Sumner CJ, Sheh S, Griffin JW, et al. The spectrum of neuropathy in diabetes and impaired glucose tolerance. Neurology 2003; 60: 108-11

Abbreviations

Abbreviation	Meaning
MCV	Mean corpuscular volume
CRP	C-reactive protein
HbA1C	Hemoglobin A1c