By Marcello Cherchi, MD PhD
For patients
The phrase “peripheral neuropathy” refers to a collection of diseases that can cause reduced sensation (such as sensation of touch, temperature, pain, vibration, joint position) in the feet. Reduced sensation in the feet can contribute to a sense of unsteadiness. Depending on a patient’s specific situation, a doctor may consider checking whether peripheral neuropathy is causing or contributing to disequilibrium.
For clinicians
Overview
Somatosensory input is one of the three main afferent systems (the other two being vision and labyrinthine input) on which the brain depends for vestibular function. One would think that isolated peripheral neuropathy (which impairs somatosensory input) could cause disequilibrium, but this is difficult to study because peripheral neuropathy commonly occurs in the broader context of systemic diseases, including diseases that can interfere with vestibular function through other mechanisms (besides peripheral neuropathy), thus it is difficult to isolate the effects of peripheral neuropathy alone.
Introduction
Somatosensory input is one of the three main afferent systems (the other two being vision and vestibular input) on which the brain depends for calculating one’s position in, and movement through, space. Reducing somatosensory input deprives the brain of information it needs to make these calculations, so intuitively one would expect that equilibrium should deteriorate.
The problem
While this seems intuitive, it is somewhat difficult to disentangle peripheral neuropathy from other diseases because peripheral somatosensory neuropathy does not commonly occur in complete isolation from other diseases. There may be several reasons for this. The first reason is that although the vestibular nerve is a cranial nerve, cranial nerves 3 – 12 share many physiologic characteristics with peripheral nerves (Rueda-Lopes 2021) and are often regarded as such; thus, one could reasonably expect that disease processes that cause peripheral neuropathy could also cause vestibular neuropathy. The second reason is that peripheral neuropathies often (not always) occur in the context of some other disease (often a systemic disease), a disease which may interfere with equilibrium in other ways; for example, diabetes can cause peripheral somatosensory neuropathy (resulting in sensory ataxia), diabetic autonomic neuropathy (resulting in orthostatic hypotension) and diabetic retinopathy (interfering with visual input), all of which are deficits that can interfere with a person’s equilibrium.
As an example of the difficulty of separating peripheral neuropathy from other diseases that can interfere with equilibrium, consider that:
- Palla and colleagues (Palla et al. 2009) showed that in patients with electrophysiologically proven axonal and demyelinating peripheral neuropathy, there was a statistically significant reduction of the vestibulo-ocular reflex gain (as assessed through head impulse testing with scleral search coils) compared to healthy controls. Akdal and colleagues identified vestibular weakness (by video head impulse testing) in patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP, Guillain-Barre syndrome) (Akdal et al. 2023) and in chronic inflammatory demyelinating polyneuropathy (CIDP) (Akdal et al. 2018). Blanquet and colleagues (Blanquet et al. 2018) identified vestibular weakness (by video head impulse testing, cervical and ocular vestibular evoked myogenic potentials) in those (AIDP, CIDP) and other inflammatory neuropathies (anti-myelin-associated glycoprotein IgM neuropathy, multifocal motor neuropathy).
- Conversely, investigators have also observed (Buetti and Luxon 2014) that in patients with vestibular weakness, particularly when bilateral (Zingler et al. 2007), there is a greater than chance association with peripheral neuropathy.
In short, patients with diagnosed peripheral neuropathy seem to have a higher rate of vestibular weakness, and patients with vestibular weakness seem to have a higher rate of peripheral neuropathy.
There are two consequences of the bidirectional association between peripheral neuropathy and vestibular weakness.
First, in a patient with a confirmed diagnosis of peripheral neuropathy whose disequilibrium seems out of proportion to the sequelae of the neuropathy alone, it is reasonable to do screening vestibular testing for vestibular weakness, because if discovered, then intervention with vestibular rehabilitation therapy is appropriate.
Second, in a patient with confirmed vestibular weakness — especially if bilateral (Zingler et al. 2007) — who is not responding to appropriate vestibular rehabilitation therapy, or who has clinical evidence of peripheral neuropathy (e.g., distal sensory deficits; muscle atrophy; reduced or absent myotatic reflexes; reduced sweating) it is reasonable to undertake a screening workup for peripheral neuropathy, or refer to a peripheral neuropathy clinic. The American Academy of Neurology’s practice parameter for evaluation of distal symmetric polyneuropathy (England et al. 2009), which was reaffirmed on 1/22/2022, suggests that it is reasonable to check serum glucose, vitamin B12 (with methylmalonic acid with or without homocysteine) and serum protein immunofixation electrophoresis.
We have been discussing the afferent (sensory) component of neuropathy, but of course neuropathies can also affect motor function. Hamel and Logigian (Hamel and Logigian 2023) studied 40 patients with acute nutritional neuropathy (deficiencies of vitamin B1, vitamin B6, folate, vitamin E, copper and vitamin B12); these patients had either pure sensory neuropathy (14/40 = 35%), pure motor neuropathy (3/40 = 7.5%), or mixed sensorimotor neuropathy (23/40 = 56%); of the 37 patients who followed-up, only 13 (35%) were walking independently; while the patients with sensory deficits likely had some component of sensory ataxia, those with only motor deficits still had impaired ambulation.
What studies suggest
Despite this difficulty, there have been studies claiming to evaluate the sequelae of isolated peripheral neuropathy with respect to balance. The usual theme of these studies is fall risk, which is a reasonable, though imperfect, proxy for disequilibrium. For example:
- Homann and colleagues (Homann et al. 2013) studied fall risk in an older population of 228 patients (age 74.5±7.8 years). Of patients with peripheral neuropathy (age 71.0±8.1 years), the odds ratio of falling compared to healthy controls was 6.4 (confidence interval 3.4 to 12.3, p=0.000), and 43% of these patients suffered multiple falls.
- Richardson and colleagues (Richardson et al. 1992) studied 25 patients with axonal peripheral polyneuropathy compared to age- and sex-matched healthy controls and found that peripheral neuropathy was significantly associated with falling (14/25 = 56%) compared to controls (2/25 = 8%), with an odds ratio of 23.0. They also found that the neuropathy was significantly associated with repetitive falling (10/25 = 40%) compared to controls (1/25 = 4%), with an odds ratio of 6.3.
In other words, these studies claim to show that the presence of peripheral neuropathy alone is associated with a statistically significant increase in fall risk, even though the quantification of that risk varies among studies.
Taking such associations into account, Buetti and colleagues (Buetti and Luxon 2014) note that:
“Vestibular involvement is a common and consistent finding in many peripheral neuropathies of different etiologies and should be specifically sought when there is any suggestion that unsteadiness/ataxia is out of proportion to objective signs of somatosensory loss or muscle weakness” (Buetti and Luxon 2014).
They further state that:
“In terms of clinical management, balance depends on visual, vestibular, and proprioceptive inputs and, in cases of peripheral neuropathy, imbalance is commonly attributed to proprioceptive/somatosensory/cerebellar loss. However, in the patient with peripheral neuropathy and imbalance, all three systems should be investigated. This is particularly important if the severity of imbalance appears to be out of proportion to the degree of neuropathy, as vestibular involvement may be the main cause of the unsteadiness, although complicated by the loss of somatosensory inputs and/ or associated cerebellar dysfunction” (Buetti and Luxon 2014).
They conclude that:
“From a patient perspective, imbalance may be improved with appropriate physiotherapy, which facilitates symptomatic compensation and adaptive plasticity” (Buetti and Luxon 2014).
References
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Akdal G, Tanriverdizade T, Sengun I, Bademkiran F, Kocoglu K, Yuceyar AN, Ekmekci O, Karasoy H, Halmagyi GM (2018) Vestibular impairment in chronic inflammatory demyelinating polyneuropathy. J Neurol 265: 381-387. doi: 10.1007/s00415-017-8712-8
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