**3. Screening or diagnostic assessment**

A staging system, which has four stages, was used to provide a framework for diagnosis and management for DPN (**Table 1**) [36].


#### **Table 1.**

*The staging system of diabetic peripheral neuropathy.*

The prevalence of neuropathy is determined by subjective complaints, signs, or nerve conduction studies. Electrodiagnostic findings provide a higher level of specificity for the diagnosis of polyneuropathy and should be included as a part of the assessment. Nerve conduction studies (NCSs) are the most informative part of electrodiagnostic evaluation, which commonly includes both NCS and needle electromyography. NCSs have been a criterion or gold standard test for confirming the diagnosis of peripheral neuropathies.

A simplified scoring system, the Diabetic Neuropathy Symptom Score (DNS), assesses pain, numbness, tingling, and ataxia. The maximum score of DNS is four points, one point or more indicates neurological abnormalities [37–39]. To quantify clinical neuropathy, the Neuropathy Symptom Profile, the Neuropathy Symptom Score, and the Neuropathy Disability Score were developed. The Michigan Neuropathy Rating Scale consists of two parts. The first part is the Neuropathy Screening Instrument, which consists of a 15-item questionnaire on foot sensation, including numbness, burning, and sensitivity. The second part is the Diabetic Neuropathy Score, which consists of clinical neurological examination and nerve conduction studies. Sensation, including vibration, pin prick, and light touch; distal muscle strength; and reflexes (biceps, triceps, quadriceps femoris, and Achilles) are assessed [40].

The performance of the protective sensation of the foot in diabetic patients is monitored using a variety of instruments. Pain perception, vibration perception, temperature perception, and deep reflexes are some of the most popular screening methods for DPN. Monofilaments, such as Semmes-Weinstein Monofilament Testing (SWMT), are one of the safest and most cost-effective ways to screen DPNs. SWMT is calibrated to the point that if a force of 10 g is applied to the point where the monofilament bends, but the patient does not notice it, that point is deemed insensate. This is a basic test that predicts the likelihood of foot ulceration in diabetic patients. To assess the presence of sensation, certain points on the feet are

#### *Diabetic Peripheral Neuropathy DOI: http://dx.doi.org/10.5772/intechopen.100859*

stimulated by placing monofilament on the skin. It has a high sensitivity for detecting the possibility of foot ulceration and helps to prevent traumatic injuries [41–43].

In order to assess pain, several scales are used. Most common and oldest is the Numerical Pain Rating Scale, which is an 11-point Likert scale (0 = no pain to 10 = worst possible pain). Other validated scales such as Neuropathic Pain Symptom Inventory [44], Modified Brief Pain Inventory [45], neuropathic pain questionnaire [46], the LANNS pain scale [47], and McGill Pain Questionnaire [48] are often used.

Quality of life (QoL) might be assessed with neuropathy-specific instruments that are based on patient's experience of neuropathic pain, such as NeuroQoL [49], Norfolk Quality of Life Scale [50], and Neuropathic Pain Impact on Quality of Life Questionnaire (NePIQoL) [51]. The impact of painful symptomatology on mood can be evaluated using scales such as Hospital Anxiety and Depression Scale (HADS) [52].

The other scoring systems such as Clinical Neurological Examination (CNE), Diabetic Neuropathy Examination (DNE), Diabetic Neuropathy Symptom score (DNS), Michigan Neuropathy Screening Instrument (MNSI), Neuropathy Disability Score (NDS), Neuropathy Impairment Score (NIS), Neuropathy Impairment Score in the Lower Limbs (NIS-LL), Neuropathy Symptom Profile (NSP), Neuropathy Symptom Score (NSS), Toronto Clinical Scoring System (TCSS) can be used to screen and determine the severity of DPN [39]. Clinical care guidelines have recommended that annual screening for peripheral neuropathy occurs in all patients with diabetes, as part of routine evaluation to prevent complications.

Routine NCSs include evaluation of motor function of the median, ulnar, peroneal and tibial nerves and sensory function of median, ulnar, radial, and sural nerves. Different nerves attributes such as amplitudes are used in the assessment of axonal status; and latencies, conduction velocities, and F-waves latencies as function of myelination. Amplitudes are reduced in axonal damaged. In demyelinating neuropathies, nerve conduction latencies and F-waves latencies are prolonged and conduction velocities are reduced.

## **4. Management**

Clinicians face a significant challenge in assessing and treating DPN, and an empathic and multidisciplinary approach is essential because the effect of painful DPN is varied and multidimensional. Ideally, a multidisciplinary team might include input from nutritionists, endocrinologists, neurologists, pain specialists, nurse practitioners, podiatrists, psychologists, physiotherapists, and others [53].

There is a general consensus that good blood glucose control should be the first step in the management of any form of diabetic neuropathy. Hypertension and hyperlipidemia, which are risk factors of large vessel diseases, are also commonly seen in DPN, and it is also important to address them.

Some of the commonly prescribed treatments include physiological glucose control (HbA1C 6–7%), along with lifestyle modifications (i.e. diet, exercise). Tricyclic antidepressants (TCAs) such as amitriptyline and imipramine promote successful analgesia to thermal, mechanic, and electrical stimuli in diabetic patients by the inhibition of noradrenalin and/or serotonin reuptake synapses of central descending pain-controlled systems. Serotonin and noradrenalin reuptake inhibitors (SNRIs) such as duloxetine and venlafaxine relieve pain by increasing the synaptic availability of 5-hydroxytryptamine and noradrenaline in the descending inhibitory pathway

#### *Demyelination Disorders*

against pain. The two anticonvulsants most commonly used to treat neuropathic pain are gabapentin and pregabalin, which bind to the α-2-δ subunit of the calcium channel, reducing calcium influx and thereby resulting in decreased synaptic neurotransmitter release into the hyperexcited neuron [54–56].

According to the European Federation of Neurological Societies' recommendations, first-line therapies could include TCAs, SNRIs, gabapentin, or pregabalin. The National Institute for Health and Clinical Excellence in the United Kingdom recently released recommendations on the treatment of neuropathic pain in nonspecialist settings, which included a section on painful DPN management. Despite the fact that the level of evidence for pain effects with duloxetine, pregabalin, and gabapentin is comparable, the National Institute for Health and Clinical Excellence recommends that oral duloxetine be used first, with amitriptyline as an alternative and pregabalin as a second-line treatment [57–59].

There are wide ranges of alternative therapies available for DPN pain, which include acupuncture [60], near-infrared phototherapy [61], low-intensity laser therapy [62], transcutaneous electrical stimulation [63], frequency-modulated electromagnetic neural stimulation therapy [64], high-frequency external muscle stimulation [65], and as a last resort, the implantation of an electrical spinal cord stimulator [66].

The integrity of joints, muscles, and neural structures, especially the small joints and intrinsic muscles of the foot and ankle, is compromised as neuropathy progresses, resulting in poor dynamic stability of the foot, inadequate foot mobility, and impaired locomotor tasks. All of these losses have an impact on load absorption and transmission while the patient is walking, exposing the foot to mechanical overloads that lead to tissue breakdown and decreases the quality of life [67].

Most of the treatments that diabetic patients receive are passive. Plantar load relief is only recommended when critical neuropathy outcomes, such as foot deformities, ulcerations, and amputations, are already present. Active and preventive therapeutic actions, on the other hand, are strongly recommended for delaying or even preventing sensory, motor, and tissue complications, thus reducing the effect of disease on quality of life [68–70].

The uniform distribution of plantar pressure is hampered by foot deformities and defects in the extrinsic and intrinsic foot and ankle muscles. These factors cause the toes and hallux to participate inefficiently while the foot swings during walking, making the individuals at a higher risk of tissue damage. Ulceration is linked to both restricted joint mobility and high plantar loads. Thus preventive measures for the maintenance of joint mobility are highly recommended from the onset of disease [71, 72].

The reduction of tissue stress is considered as the main goal of interventions in patients with neuropathy. Those are achieved by prescribing shoes and custommade insoles, orthotics with rocker soles. The primary aim of these orthotic devices is to change the foot rollover and thus passively redistribute plantar pressure. Exercise therapy for the foot and ankle, on the other hand, has the potential benefit of actively adjusting the foot loading, resulting in improvements in force absorption and transmission due to improved muscle function and joint stability. Thus, the use of an orthotic device for the prevention of foot ulceration along with a regimen of therapeutic exercises to improve the functionality of the individual's foot is recommended [73, 74].

Even though exercises do not directly prevent ulcer development, they do target musculoskeletal defects by trying to maintain or enhance the muscle and joint function of the distal segments, which can lead to improved individual functioning, a better health status, a higher quality of life, and a lower risk of falling [75–77]. Therapeutic exercises also enable patients to maintain for as long as possible the

## *Diabetic Peripheral Neuropathy DOI: http://dx.doi.org/10.5772/intechopen.100859*

residual biomechanical capability of interacting safely with the ground while walking and standing, and they can potentially be associated with prevention of tissue breakdown. Interventions that combined foot-ankle strengthening exercises and balance exercises showed improvement in the support time during single stance, tandem, and functional reach as well as in the equilibrium and confidence scores on their Activities Specific Balance Confidence Scale Questionnaires [78, 79]. Also gait training strategies to reduce plantar loads have shown modest results in neuropathic individuals. The proposed exercise program aims to integrate peripheral benefits for foot function during everyday locomotor activities using segmental exercises (muscle strengthening and range of motion). The clinical outcomes were favorable, with improvements in foot muscle control, foot and ankle function, and neuropathy symptoms. For further information on the therapy of painful polyneuropathy, refer to chapter on Peripheral Neuropathy Treatment and Management.
