Peripheral Neuropathy

Definition - A disease process affecting many peripheral nerves (nerves outside the CNS), with the distal nerves affected most prominently. The clinical presentation is typically characterized by symmetric distal sensory loss, burning, or weakness.

Etiology - The peripheral nerves are susceptible to a variety of toxic, inflammatory, hereditary, infectious, and parainfectious factors that can impair their function, leading to polyneuropathy. 

• Diabetic - Poor glycemic control leads to the accumulation of advanced glycosolation products which, simply, produce an inflammatory state and can cause damage to blood vessels, organs nerves (peripheral nerve in the case of diabetic peripheral neuropathy)
• Uremia
• Long-standing HIV infection
• Amyloidosis 
• Vitamin deficiency such as B12 and folate 
• Long-standing hypothyroidism
• Lyme Disease
• Guillian-Barre Syndrome -  an acute neuropathy, usually provoked by a preceding infection. The preceding infection causes autoantibodies to form and are directed towards the myelin sheath or axon of the peripheral nerves causing inflammation and damage. 
• Toxic exposure - history of chemotherapy, alcoholism or heavy toxic metals
• Hereditary - Charcot-Marie-Tooth is an X linked genetic disorder causing demyelination of the peripheral nerves. Other genetic diseases include metabolic diseases of childhood, such as Krabbe's disease, metachromatic leukodystrophy, and adrenoleukodystrophy
• Environmental - prolonged cold exposure and hypoxemia
• Idiopathic

History of Illness

• Chronic Polyneuropathies are slow in progression. Injury tends to be related to axon length. The longer axons are affected first, resulting in symptoms that begin in the lower extremities. Sensory symptoms usually precede motor symptoms. Patients will present with progressive sensory loss and complain of  numbness, a burning sensation and pain in the feet. As the syndrome progresses, the motor function begins to be affected and the patient will complain of mild weakness of the lower legs and hand.
• Acute Polyneuropathies - usually secondary to toxic exposures such as metals and pophyrias. The predominant symptom is pain over numbness and tingling and the symptoms are more fulminant and rapidly progressive 2-3 weeks often followed by a period of recovery follows in a few months. 

Physical Examination

Motor and sensory deficits will predominate depending on if the neuropathy is secondary to axonal damage or demyelination. In patients with axonal neuropathy, there may be intrinsic muscle wasting of the hands and feet as well as decreased sensation to light touch, pinprick, vibration and proprioception. In the case of neuropathy secondary to demyelination, generalized weakness is the more common physical exam finding and the distal muscles are more commonly affected. 

Diagnosis

EMG or nerve conduction studies are a good first diagnostic test in patients where there is not a clear etiology. Lab tests such as A1C, thyroid and B12/Folate are useful. Nerve biopsy is reserved for patients in the situation where it is difficult to diagnose whether the disease is demyelinating versus axonal.