One of the most distinct symptoms of sensory neuropathy is early-onset ataxia. This manifestation is mainly due to the disruption of the afferent neurons, which transmit impulses from the extremities of the body.[9] If these symptoms progress, resultant “writhing” movements will manifest in the hands and feet as the patient closes their eyes.[10] Positive sensory symptoms are also common when small- and medium-sized fibers are affected. Classic clinical findings include complaints of “pins and needles’ and “electricity” in the affected extremities, which follow a stocking-glove pattern. Especially in people with diabetes, a clinician must be vigilant in assessing for negative neuropathic symptoms, which manifest in small-fiber neuropathies. Numbness, as a negative neuropathic symptom, is commonly seen in the feet and is non-length dependent and multifocal.

When performing a subjective patient interview, variability in disease progression will be significant. Subacute sensory neuropathies are commonly seen in immune-mediate and post-infectious cases, whereas idiopathic variants have proven to be more stagnant.[11] In many cases, motor weakness does not accompany sensory neuropathy. However, the motor output may be affected in those with paraneoplastic sensory neuropathies resulting in absent stretch reflexes.

Evaluation criteria regarding sensory neuropathy mainly revolve around neurophysiological examination and dermatopathological studies such as skin biopsy. When diagnosing small fiber neuropathies, electromyography (EMG) results may appear normal, and the presence of sural and plantar responses does not exclude purely small fiber neuropathy. In EMG studies, sensory neuropathies demonstrate a reduced or absent sensory nerve action potential.[12] For patients with diabetic peripheral sensory neuropathy, a Semmes-Weinstein 5.07 monofilament nylon test is often performed at varying locations of the foot to test for a protective threshold (formally defined as 10 grams of force).

Regarding autonomic sensory testing, there are quantitative exams that assess for hot and cold sensation, transient changes in the electrical potential of the skin (e.g., sweat gland activity), and noninvasive electrochemical skin conductance studies for detection of sudomotor dysfunction.[13] For small fiber-dominant neuropathy, some of the most useful studies are thermoregulatory sweat testing and the quantitative sudomotor axon reflex test. Though these studies are not readily available, recent literature shows that their clinical additions yield higher diagnostic success.[14]

The current validated gold standard for the diagnosis of small fiber neuropathy is a skin biopsy.[15] Depending on the research, sensitivities for skin biopsy can be as high as 90%, with specificities as high as 97%.[15][16] The benefits of skin biopsy include ease of use and low morbidity. Common sites of the acquisition include the distal leg, just 10 cm. proximal to the lateral malleolus and the lateral distal or proximal thigh.[1] In general, nerve biopsy is not necessary for the diagnosis of sensory neuropathy.

Imaging studies also have a role in diagnosing sensory neuropathies and are of greatest utility when assessing for paraneoplastic etiologies. Magnetic resonance imaging and its analogs, inversion recovery MRI pulse sequencing and T2-weighted spoiled gradient-echo sequencing, are of particular merit in visualizing dorsal column pathology.[17]

Guidelines pertaining to specific treatment modalities for sensory neuropathies generally do not exist. Much of the data regarding treatments are based on expert opinions, along with well-constructed research. Some treatments include injection of intravenous immunoglobulins, methotrexate, corticosteroids, infliximab, and plasma exchange, among others, depending on the etiology.[18] Recent data suggest that sensory symptomatology generally plateaus after 7 to 10 months.[19] If possible, treatment protocols should initiate within this period.

The efficacy of various oral drugs such as anticonvulsants (pregabalin and oxcarbazepine), serotonin-norepinephrine reuptake inhibitors (duloxetine and venlafaxine), tricyclic antidepressants, opioids (tramadol and tapentadol), and botulinum toxin A (with and without chemodenervation) have demonstrated more effectiveness than a placebo in numerous randomized controlled trials.[20][21] Topical agents such as lidocaine and capsaicin have been recommended with level B evidence per standards from the American Academy of Neurology.

Future clinical avenues for research are promising for the utility of physical exercise in sensory neuropathy secondary to diabetes mellitus. Some of the most current studies show increased nerve fiber density in patients with diabetes mellitus, as well as a measured pain response to exercise in those with established neuropathy.[22][23] Results such as these are encouraging and much warranted as the general etiologies of sensory neuropathy are considered rare as compared to those cases caused by diabetes mellitus, which is far more widespread.

In a substantial portion of patients, an exact cause of sensory neuropathy is not readily apparent, and the disease is considered idiopathic.[24] Literature suggests that an idiopathic sensory neuropathy is a diagnosis of exclusion and that there may be an autoimmune component of the pathophysiology behind the disease.[25] 

Other diseases that may present in a similar clinical fashion include distal acquired demyelinating symmetric neuropathy as well as sensory chronic inflammatory demyelinating polyradiculoneuropathy. These symptoms may also mimic those of other radiculopathies, myelopathies, and various autoimmune diseases.

Outcomes for patients who suffer from different forms of sensory neuropathy will vary. When Wallerian degeneration occurs, a series of events leads to complete structural and chemical disintegration of the nerve and results in a more guarded prognosis. Recovery is contingent on the regeneration of the nerve and depends largely upon how well the transected nerve endings are aligned as well as the severity of any adjacent soft tissue injury and scarring. To achieve a noticeable clinical outcome, the affected muscles and/or organs must become reinnervated after adequate nerve regeneration and remyelination occurs. If the pathology causing any sensory neuropathic symptoms is purely due to segmental demyelination, the prognosis will be much more positive as it entails a shorter recovery with a quicker return to function. Pain and temperature are typically the first sensations to recover.

Regarding those patients with glucose dysregulation, it is vital to monitor their hemoglobin A1c lab value to track the progression of the disease. Current recommendations from the American Diabetes Association underscore maintenance of a value less than 7.0% in conjunction with a healthy lifestyle (diet and exercise) for those with established diabetes.[26]

If sensory neuropathy is not managed within an acute time frame, the results can be debilitating. Patients will often suffer from varying degrees of burns and other traumatic dermal injuries due to the lack of protective sensation. This sensory loss, in turn, increases the risk of infection secondary to these traumatic events as these injuries are usually not treated quickly and efficiently. In older populations, the risk of accidental falls also increases as balance and strength diminish.

Again, in patients with diabetes mellitus who present with concomitant sensory neuropathy, the complications are significant and life-altering. As a protective threshold is lost, it is not uncommon for a patient to step on a sharp object such as glass or a rusty nail and remain unaware until they notice bleeding from their socks. These injuries are extremely common in the emergency room and constitute a significant challenge for the medical team.

Severe infections leading to sepsis and gangrene of the lower extremities due to chronic neuropathic ulcerations or retention of a foreign body is one of the leading causes of amputation in people with diabetes. The overall risk of developing diabetic foot ulceration is around 2% per year; that statistic increases to about 7% in those with sensory neuropathy, a staggering causal finding.[8] To mitigate these risks, proper patient education in conjunction with a communicative multidisciplinary healthcare team is essential.

To effectively deter the course of this disease, clinicians must adequately educate patients on the potential signs and symptoms previously discussed. It is also equally important to make necessary alterations in daily life if a patient does begin to notice symptoms. Patients with established sensory neuropathy should limit their exposure to temperature extremes and monitor sudden, obvious changes in gait patterns to diminish the effects of repetitive micro-motion to their feet; modifications in shoe gear may also be necessary.

For diabetic patients, an established daily foot screening protocol should be performed daily for early detection of possible lesions. These patients should also schedule frequent visits with their podiatric physician at least every 2 to 3 months for formal evaluation and care as part of a holistic approach to the management of their sensory neuropathy. A primary care physician or an endocrinologist also plays a vital role in the overall management of diabetes and the limitation of sensory neuropathy symptomatology.

The availability of healthcare as a whole is not genuinely ubiquitous in all parts of the world, and strides are necessary to provide evidence-based treatment via multidisciplinary team approaches to those in need. As patient education is essential in the prevention of sensory neuropathy-related morbidities, so are the neurologists, vascular surgeons, physical and occupational therapists, infectious disease specialists, endocrinologists, and podiatric physicians who each provide essential tools from their armamentaria to combat this disease and its symptoms.