Approach to polyneuropathy: Clinical sciences

Polyneuropathy is a condition associated with demyelination or axonal injury of multiple peripheral nerves, which can result in numbness, weakness, and pain. Now, hereditary polyneuropathies, which are caused by genetic mutations, include conditions like Friedreich ataxia, adrenomyeloneuropathy, and Charcot-Marie-Tooth disease. On the flip side, acquired polyneuropathies, which can be caused by autoimmune disease, infections, chronic conditions, or nutritional deficiencies, include conditions like Guillain-Barré syndrome, diabetic neuropathy, chronic alcohol use, and vitamin B12 deficiency.

Now, if your patient presents with chief concerns suggestive of polyneuropathy, first, obtain a focused history and physical examination. History will typically reveal progressive bilateral symptoms, such as numbness and tingling of the extremities. Sometimes, the patient might report muscle weakness and trouble with walking. On the exam, assess the patient’s sensation, using different modalities, such as light touch, pinprick, and vibration. Also, be sure to check their muscle strength in extremities. The exam will reveal bilateral symmetric loss of sensation, sometimes in combination with muscle weakness. Additionally, you will notice hyporeflexia or areflexia.

The physical exam might also reveal muscle atrophy and gait ataxia. Finally, be sure to perform Romberg testing. First, ask the patient to stand with their feet together and arms at their sides, and instruct them to close their eyes. By closing their eyes, you will remove visual cues that help maintain balance. If you notice any swaying or loss of balance, the test is positive, indicating impaired proprioception.

These findings are suggestive of polyneuropathy, so be sure to assess for the family history of neuropathy. If present, consider hereditary polyneuropathies, such as Friedreich ataxia, adrenomyeloneuropathy, and Charcot-Marie-Tooth disease.

First, let’s focus on Friedreich ataxia, which is an autosomal recessive condition that affects not just the peripheral nerves, but also the cerebellum and dorsal root ganglia, as well as dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts. The patient will usually report symptom onset during childhood or adolescence. In addition to the previously mentioned symptoms of polyneuropathy, they will complain of frequent staggering or falling while walking. They might also report slurred speech or difficulty swallowing, while their history might reveal chronic conditions like cardiomyopathy or diabetes.

Next, the exam will reveal loss of proprioceptive and vibratory sensation and a positive Romberg test. You will also notice limb ataxia, such as dysmetria on finger-to-nose testing, and truncal ataxia, like a wide-based unsteady gait. Finally, in some individuals, you might notice scoliosis, pes cavus, and hammer toes. With these findings, consider Friedreich ataxia and obtain genetic testing. If you identify a mutation in the frataxin gene and expanded GAA trinucleotide repeats, diagnose Friedreich ataxia.

Now, let’s move on to adrenomyeloneuropathy, which is an X-linked condition characterized by impaired peroxisomal oxidation and accumulation of very long-chain fatty acids. Ultimately, this results in dysfunction of the adrenal glands, spinal cord, and peripheral nerves. In this case, symptoms typically start in early or middle adulthood. Patients report stiffness, weakness, numbness, and tingling in the legs, causing difficulty walking. Also, they will report urinary dysfunction because of progressive spinal cord atrophy. Some patients might develop white matter disease, causing cognitive decline, as well as vision and hearing loss. Because of adrenal insufficiency, they might also complain of fatigue, weight loss, and darkening of focal areas of the skin.

In addition to findings of peripheral neuropathy, the exam will reveal spasticity and weakness, particularly in the lower extremities. There is loss of proprioception and vibration, and a positive Romberg. Finally, you may find skin hyperpigmentation, especially in areas of high sunlight exposure or friction, such as the hands, elbows, and knees. With these findings, you should suspect adrenomyeloneuropathy, so proceed with genetic testing and be sure to check levels of very long-chain fatty acids. If testing reveals mutations in the ABCD1 gene and elevated levels of very long-chain fatty acids, diagnose adrenomyeloneuropathy.

Here's a clinical pearl to keep in mind! Another form of the disease is adrenoleukodystrophy, with the main clinical manifestations related to the disease of the white matter, leukodystrophy, and the adrenal glands. This phenotype usually presents in early childhood.

Finally, let’s discuss Charcot-Marie-Tooth disease, which is the most common type of hereditary neuropathy. Charcot-Marie-Tooth disease consists of several different variants, the most common being Type 1A, which is inherited in an autosomal dominant pattern. Your patient will typically present during childhood or adolescence and report leg or ankle weakness with difficulty walking.

In addition to bilateral loss of sensation, the exam will reveal the loss of deep tendon reflexes and muscle atrophy of the legs, causing an “inverted champagne bottle” appearance. Additionally, you will notice unilateral or bilateral foot drop due to ankle dorsiflexion weakness, causing a steppage gait. In other words, the patient will lift their leg higher than usual to avoid dragging their toes on the ground. You will also find foot deformities, like pes cavus and hammer toes. With these findings, consider Charcot-Marie-Tooth disease, and proceed with genetic testing. If genetic testing shows duplication of the PMP22 gene on chromosome 17, diagnose Charcot-Marie-Tooth type 1A.

Here’s a high-yield fact! Charcot-Marie-Tooth Type 1 is associated with demyelination, while Charcot-Marie-Tooth Type 2 is characterized by axonal injury and tends to present later in life.

Alright, let’s switch gears and discuss individuals with no family history of neuropathy. In this case, consider acquired polyneuropathies, so your first step is to determine the timing of symptom progression. If symptoms progress rapidly over days to weeks, think of Guillain-Barré syndrome and critical illness polyneuropathy.

First, let’s take a look at Guillain-Barré syndrome, also known as acute inflammatory demyelinating polyradiculoneuropathy, which is associated with progressive weakness that starts in the legs and spreads upwards. Additionally, history might reveal blurry or double vision, facial weakness, and difficulty swallowing or speaking. The patient might also report back pain. Several important clues to keep in mind include recent vaccination as well as a recent respiratory or gastrointestinal infection. Moreover, the most common gastrointestinal infection associated with this condition is Campylobacter pylori infection, which usually occurs when eating raw or undercooked meat.