para>Hemibody deficits or sensory loss below a spinal cord level suggest a CNS process.
ALERT
Hyperreflexia and spasticity are upper motor neuron signs not seen with isolated PN.
DIFFERENTIAL DIAGNOSIS
The following categories of PN can be identified (differential diagnosis [DDx] listed when applicable):
- Pure sensory neuropathy
- DDx: SFN, sensory ganglionopathy, polyradiculopathy
- Distal symmetric sensorimotor axonal PN
- Most common type of PN
- DDx: distal acquired demyelinating symmetric PN (DADS)
- Motor predominant PN
- DDx: motor neuron disease, polyradiculopathy, immune-mediated multifocal motor neuropathy (MMN)
- Mononeuropathy
- Most likely due to compression, entrapment, or trauma
- DDx: monoradiculopathy
- Mononeuropathy multiplex
- DDx: plexopathy, polyradiculopathy
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Nerve conduction studies and electromyography (NCS/EMG)
- Best performed by physicians with specialty training in electrodiagnostic medicine
- Delineate axonal versus demyelinating, anatomic pattern, chronicity, and severity of PN.
- Blood tests
- CBC, BUN, creatinine, fasting glucose, HgA1C, vitamin B12, serum protein electrophoresis, and immunofixation
- Specialized skin biopsy
- In clinically suspected SFN if NCS/EMG is normal
- Analysis of lower limb epidermal nerve fiber density (ENFD) (1)[A]
- Autonomic tests
- Not routinely done but useful to characterize autonomic PN
- Neuroimaging
- Generally not indicated in evaluation of PN but useful in evaluation of brachial plexopathies, radiculopathies, or where findings are attributable to the CNS
Follow-Up Tests & Special Considerations
- Additional blood tests are done based on the medical history, the PN type, and NCS/EMG findings.
- Genetic testing for diagnosis of hereditary PN should be ordered by neurologists with expertise in PN.
- Screen patients with distal symmetric PN for unhealthy alcohol use with CAGE-AID or AUDIT-C.
ALERT
Ordering of laboratory batteries (e.g., peripheral nerve antibody panels) without careful consideration of the clinical and NCS/EMG features should be avoided.
Diagnostic Procedures/Other
Nerve biopsy (sural or superficial peroneal nerve): useful if vasculitis, amyloidosis, granulomatous disorders, or neoplastic infiltration is suspected; rarely helpful in late-onset chronic, slowly progressive distal symmetric PN
- Lumbar puncture
- Cytoalbuminologic dissociation in GBS or CIDP
- Infection, inflammation, or neoplasia in polyradiculopathies
Test Interpretation
- Demyelinating PN: disproportionate slowing of conduction velocities or prolonged distal latencies on NCS
- Axonal PN: reduced amplitude in sensory or motor responses, with relatively preserved conduction velocities on NCS
- Reduced ENFD on distal leg skin biopsies is supportive of SFN.
TREATMENT
GENERAL MEASURES
Manage associated medical conditions; disease-modifying therapy for specific forms of PN (e.g., CIDP); symptomatic relief of pain and dysautonomia; rehabilitation to optimize function.
MEDICATION
First Line
- Treatment of neuropathic pain: evidence of efficacy derived from clinical trials in diabetic painful neuropathy (DPN) and postherpetic neuralgia (PHN):
- Pregabalin: for DPN and PHN
- Duloxetine: for DPN
- Lidocaine patch: for PHN
- Gabapentin: (off-label) for DPN
- Tricyclic antidepressants: (off-label) for DPN
- Venlafaxine: (off-label) for DPN
- Tramadol: (off-label) for DPN
- Targeted treatment for underlying systemic conditions:
- Glycemic control, thyroid hormone supplementation, vitamin supplementation, antimicrobial therapy (e.g., Lyme disease, HIV), glucocorticoids for sarcoidosis, and cytotoxic therapy for vasculitis
- Immunotherapy for dysimmune PN
- Intravenous immunoglobulin (IVIG): within the first 2 weeks of GBS to hasten recovery (2)[A]; as a first-line alternative to corticosteroids for treatment of CIDP (3)[A]; and for prevention of secondary axonal loss in MMN (4)[A]
- Loading dose 2 g/kg body weight divided into 2 to 5 days; maintenance regimen variable for CIDP and MMN
- Adverse effects (AE): headache, fever, hypertension, and rarely pulmonary embolism
- Plasma exchange: first agent shown to improve functional outcome for patients with GBS (5)[A]; short-term benefit in CIDP (6)[A]
- AE: catheter complication, hypotension, and others
- Corticosteroids: a first-line option in treatment of CIDP (7)[C]; oral or pulsed IV regimen can induce remission
- Treatment of autonomic symptoms
- Compression stockings, hydration, midodrine, and fludrocortisone for orthostatic hypotension
- Pyridostigmine for immune-mediated dysautonomia (off-label)
ISSUES FOR REFERRAL
- Rapidly progressive symptoms, suspected demyelinating PN, or hereditary PN should be referred to a neurologist with expertise in neuromuscular disorders.
- Patients with vasculitic PN should be referred to rheumatology.
- Patients with paraproteinemia should have a skeletal bone survey and be referred to hematology.
- Patients with imbalance, ataxia, or falls should be referred to physical therapy for gait and balance training.
ADDITIONAL THERAPIES
- Combination therapy (e.g., gabapentin with TCA or venlafaxine or tramadol) can be more effective than monotherapy for neuropathic pain.
- Long-acting opiates can be considered for refractory neuropathic pain.
- Additional immunosuppressant agents (e.g., cyclophosphamide) may be used in refractory chronic dysimmune PN.
ALERT
Opiates have significant side effects and may cause rebound headaches, tolerance, and dependence.
SURGERY/OTHER PROCEDURES
- Decompressive surgery for entrapment neuropathy (e.g., carpal tunnel syndrome)
- Foot and ankle surgery to improve symptoms or function in hereditary PN
- Radiation, surgery, or bone marrow transplantation for plasmacytoma or osteosclerotic myeloma or POEMS syndrome
- Liver transplantation for amyloidotic PN
COMPLEMENTARY & ALTERNATIVE MEDICINE
Low-intensity transcutaneous electrical nerve stimulation (TENS), acupuncture, mediation
ALERT
Vitamin B6 supplementation may cause peripheral neurotoxicity and should be avoided except for a deficiency state.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
- Patients with suspected GBS should be admitted for diagnosis, monitoring (30 " 60% may develop cardiovascular or respiratory failure), and for acute treatment.
- Elective intubation may be required in GBS when forced vital capacity is <15 mL/kg body weight.
- Other rapidly progressive undiagnosed PNs that impair independent ambulation may require admission.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Physical therapy and gait assistive devices as needed
- Flu vaccination should be avoided in the first year following GBS.
PROGNOSIS
- Late-onset idiopathic distal symmetric axonal PN are indolent
- 80% of GBS have a near complete or good recovery. 80% of CIDP have moderate or good response with treatment but can be relapsing.
REFERENCES
11 Lauria G, Hsieh ST, Johansson O, et al. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol. 2010;17(7):903 " 912, e44 " e49.22 Hughes RA, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barre syndrome. Cochrane Database Syst Rev. 2014;(9):CD002063.33 Nobile-Orazio E, Cocito D, Jann S, et al. Intravenous immunoglobulin versus intravenous methylprednisolone for chronic inflammatory demyelinating polyradiculoneuropathy: a randomised controlled trial. Lancet Neurol. 2012;11(6):493 " 502.44 Cats EA, van der Pol WL, Piepers S, et al. Correlates of outcome and response to IVIg in 88 patients with multifocal motor neuropathy. Neurology. 2010;75(9):818 " 825.55 Plasmapheresis and acute Guillain-Barre syndrome. The Guillain-Barre syndrome Study Group. Neurology. 1985;35(8):1096 " 1104.66 Dyck PJ, Daube J, O 'Brien P, et al. Plasma exchange in chronic inflammatory demyelinating polyradiculoneuropathy. N Engl J Med. 1986;314(8):461 " 465.77 Dyck PJ, O 'Brien PC, Oviatt KF, et al. Prednisone improves chronic inflammatory demyelinating polyradiculoneuropathy more than no treatment. Ann Neurol. 1982;11(2):136 " 141.
CODES
ICD10
- G62.9 Polyneuropathy, unspecified
- G60.9 Hereditary and idiopathic neuropathy, unspecified
- G60.8 Other hereditary and idiopathic neuropathies
- G60.0 Hereditary motor and sensory neuropathy
- G62.89 Other specified polyneuropathies
- G90.09 Other idiopathic peripheral autonomic neuropathy
- G90.9 Disorder of the autonomic nervous system, unspecified
ICD9
- 337.00 Idiopathic peripheral autonomic neuropathy, unspecified
- 337.09 Other idiopathic peripheral autonomic neuropathy
- 337.1 Peripheral autonomic neuropathy in disorders classified elsewhere
- 337.9 Unspecified disorder of autonomic nervous system
- 356.0 Hereditary peripheral neuropathy
- 356.2 Hereditary sensory neuropathy
- 356.8 Other specified idiopathic peripheral neuropathy
- 356.9 Unspecified hereditary and idiopathic peripheral neuropathy
SNOMED
- 128208007 peripheral axonal neuropathy (disorder)
- 193157005 Hereditary and idiopathic peripheral neuropathy
- 230551000 Peripheral neuropathy - hereditary or idiopathic (disorder)
- 23414001 Peripheral demyelinating neuropathy
- 277879009 Autonomic neuropathy (disorder)
- 302226006 peripheral nerve disease (disorder)
- 95662005 Sensory neuropathy (disorder)
- 95663000 Peripheral motor neuropathy (disorder)
CLINICAL PEARLS
- There are many causes of PN. Diagnosis is made by history and physical exam, targeted laboratory testing, NCS/EMG, skin biopsy, or ANS testing.
- Consider hereditary neuropathy if patient has an early age of PN symptom onset, family history of PN, or foot deformity.
- GBS is monophasic and progresses for up to 4 weeks; CIDP progresses beyond 8 weeks, and if untreated, usually has a progressive course.