Causes of peripheral neuropathy: Diabetes and beyond

Testing and treatment. Diagnosis of CIDP is made by a combination of EDX that shows demyelination and lumbar puncture that demonstrates albuminocytologic dissociation. Treatments include long-term immunosuppression with oral prednisone, IVIg, plasmapheresis, and rarely, agents such as mycophenolate mofetil, azathioprine, cyclosporine, and rituximab.⁹

Entrapment neuropathy

This is the result of compression or entrapment of a nerve by another anatomic structure. It can be caused by internal or external factors, including fluid retention.¹¹ Damage from compression or entrapment progresses in stages and, over time, can result in demyelination and distal degeneration of the nerve.¹¹ More interior nerve fibers, such as pain nerve fibers, are often the last to be affected.¹¹ Therefore, patients often first experience loss of motor function or loss of sensation to light touch.

Common fibular nerve (formerly known as common peroneal nerve) entrapment at the fibular head is the most common entrapment neuropathy in the lower extremities. It’s usually the result of direct trauma, such as prolonged positioning in debilitated patients or surgical patients, habitual leg-crossing, tight boots, or tight casts.^11,12 Uncoordinated gait due to poor dorsiflexion of the foot at the ankle (foot drop) is common while plantar flexion is preserved. Pain and sensory loss depend on the degree of compression and the exact location of compression.

Testing and treatment. EDX is useful for identifying the location of compression or entrapment and can guide further imaging, if needed. Conservative treatments aimed at modifying or correcting the underlying etiology, such as removing a tight-fitting cast or brace or instructing a patient to stop leg crossing, can be effective. Occasionally, surgery is required.

Anterior tarsal tunnel syndrome is compression of the deep fibular nerve as it passes through the inferior extensor retinaculum of the distal lower leg. Characteristic symptoms include pain and burning over the dorsum of the foot.¹¹ Paresthesias in the first dorsal web space are also common.¹¹ This can be seen in athletes who perform repetitive ankle plantar flexion, such as ballet dancers, soccer players, and runners.¹² It can also be caused by recurrent ankle sprains, ganglion cysts, and tight-fitting shoes or boots.^11,12 Chronic cases can result in toe extensor weakness or atrophy of the extensor digitorum brevis muscle.

Testing and treatment. Again, EDX is very useful in identifying the exact area of compression and involved nerve segments. Management requires correcting the underlying etiology, which can usually be done conservatively. Surgical decompression may be needed.

Suspect a paraneoplastic process if a patient presents with subacute progressive onset of neuropathic symptoms in the upper extremities.

Paraneoplastic neuropathies

Paraneoplastic neuropathies are exceptionally rare but often develop before cancer is diagnosed. Therefore, early suspicion and recognition can greatly affect cancer prognosis.¹³ Certain characteristics should increase suspicion of a paraneoplastic process. For example, symptoms with a subacute progressive onset that involve the upper extremities early in the disease are characteristic of a paraneoplastic process.¹³

Coexisting CNS symptoms and/or constitutional symptoms of malignancy should also increase suspicion.¹³ Consider a paraneo­plastic process in patients who have a past history of cancer or significant cancer risk factors, such as smoking.

Testing. When you suspect a paraneoplastic process, the work-up should include antibody testing for the most common or likely cancers according to patient characteristics. Panels of the most common paraneoplastic antibodies are available from many commercial labs. Obtain imaging to identify a possible underlying malignancy.

That said, it’s also important to perform a basic work-up for the more common causes of neuropathy in patients you suspect may have cancer. The reason: Paraneoplastic neuropathies are rare, and not all neuropathies in patients with cancer are paraneoplastic.¹³

CASE 1 › Ms. G describes diffuse paresthesias that are worse in her lower extremities, but she has a normal neurologic exam. Her physician suspects a neuropathic cause, and a normal exam makes small fiber neuropathy more likely. EDX is normal. The initial work-up includes an HbA1c, thyroid-stimulating hormone, vitamin B12 level, antinuclear antibody, erythrocyte sedimentation rate, IFE, and free light chain assay.

Testing reveals that Ms. G has a high free light chain ratio, which suggests a monoclonal gammopathy is the most likely etiology. Skin biopsy demonstrates decreased nerve fiber density consistent with a small fiber neuropathy. Her physician refers her to Hematology for bone marrow biopsy, and also prescribes gabapentin 300 mg/d at bedtime for symptomatic relief. Ms. G is currently being closely monitored for conversion to multiple myeloma.

CASE 2 › In Ms. T’s case, the exam helps localize the lesion. Areas supplied by the common fibular nerve, tibial nerve, and sural nerve are affected, while the area innervated by the femoral nerve and saphenous nerve and the proximal hip muscles are spared. This localizes a lesion to the sciatic nerve. EDX confirms a proximal sciatic lesion, but not the underlying etiology. Since the lesion had been precisely localized, her physician orders imaging.