Presentation varies with the type of neuropathy. Sensory neuropathy presents with asymmetric or symmetric numbness, tingling, parasthesia, tremors and a disturbed gait. Motor neuropathy presents as muscle cramps and twitching, tremors, difficulty in motion, sluggish movements and myalgia. Autonomic neuropathy includes loss of control of bladder, impotence, abdominal pain, fecal incontinence and altered bowel movements, CVS involvement such as altered heart rate (tachycardia/bradycardia) and hypotension.

• Splenomegaly

  […] onset, more severe D D HNPP AD Variable onset, compression neuropathies, S/M D Familial amyloidosis AD Variable onset, autonomic and S/M A Refsum’s disease AR Variable onset, ataxia, retinitis pigmentosa D Tangier disease AR Very rare, variable onset, splenomegaly [clevelandclinicmeded.com]

• Pain

  […] neuropathy and post-traumatic neuropathic pain only. [en.wikipedia.org]

  Peripheral neuropathy is a common cause of pain, and it is increasing in prevalence. Peripheral neuropathic pain is very hard to treat and can be resistant to multiple pain management modalities. [ncbi.nlm.nih.gov]

  […] of pain, such as musculoskeletal pain, as may occur with osteoarthritis. [racgp.org.au]

• Falling

  However, the role of gaming systems in fall risk reduction was not explored. [ncbi.nlm.nih.gov]

  Recent Examples on the Web Bobo has said the administration promised him a long leash and a wide berth, perhaps even a mulligan for last fall after the peripheral neuropathy that sent his 2018, and CSU’s, careening into a ditch. — Sean Keeler, The Denver [merriam-webster.com]

  Falls. Weakness and loss of sensation may be associated with lack of balance and falling. [mayoclinic.org]

• Heat Intolerance

  […] other body parts Emotional disturbances Sleep disruptions Loss of pain or sensation that can put you at risk, such as not feeling an impending heart attack or limb pain Autonomic neuropathy symptoms may include: Inability to sweat properly, leading to heat [columbianeurology.org]

  intolerance Excessive sweating or not being able to sweat Bowel, bladder or digestive problems Changes in blood pressure, causing dizziness or lightheadedness Peripheral neuropathy can affect one nerve (mononeuropathy), two or more nerves in different [mayoclinic.org]

  […] the loss of feeling in the legs, arms, or other body parts Emotional disturbances Sleep disruptions Loss of pain or sensation that can put you at risk, such as not feeling an impending heart attack or limb pain Inability to sweat properly, leading to heat [hopkinsmedicine.org]

  […] body parts Loss of balance or other functions as a side effect of the loss of feeling in the legs, arms, or other body parts Emotional disturbances Sleep disruptions Autonomic neuropathy symptoms may include: Inability to sweat properly, leading to heat [stlouischildrens.org]

• Limb Pain

  […] or sensation that can put you at risk, such as not feeling an impending heart attack or limb pain Autonomic neuropathy symptoms may include: Inability to sweat properly, leading to heat intolerance Loss of bladder control, leading to infection or incontinence [columbianeurology.org]

  […] or sensation that can put you at risk, such as not feeling an impending heart attack or limb pain Inability to sweat properly, leading to heat intolerance Loss of bladder control, leading to infection or incontinence Dizziness, lightheadedness, or fainting [hopkinsmedicine.org]

• Gangrene

  The development of gas gangrene coupled with Charcot neuroarthropathic changes ultimately resulted in a potentially life-saving transmetatarsal (TMT) amputation. [ncbi.nlm.nih.gov]

  Gangrene If you do develop a wound infection in one of your feet as a result of peripheral neuropathy, there's a risk this could lead to gangrene (death of part of the skin or underlying tissues). [nhsdirect.wales.nhs.uk]

  This can lead to gangrene if untreated, and in severe cases may mean the foot has to be amputated. [nhs.uk]

• Nausea

  — Pat Graham, The Denver Post, "Mike Bobo banks on raise in play after turning down raise in pay," 23 Aug. 2019 More than 10% of patients experienced side effects, including nausea, vomiting, anemia and a type of nerve damage called peripheral neuropathy [merriam-webster.com]

  Common side effects of tramadol include: nausea dizziness constipation sweating dry mouth confusion headache vomiting [hse.ie]

• Thrombosis

  In this study, a 2-year and 6- month-old girl, who had delayed brachial arterial thrombosis after a displaced humerus supracondylar fracture surgery treated with embolectomy, was reported. [ncbi.nlm.nih.gov]

• Foot Ulcer

  The risk of LEA associated with foot ulcers heightens the probable role of proper foot examination and care in detecting disease prior to foot ulcer and reducing subsequent complications. [cms.gov]

  This can aid in identifying patients at high risk of diabetic foot ulceration. [ncbi.nlm.nih.gov]

  In diabetic patients, the presence of peripheral neuropathy increases their risks for developing foot ulceration and subsequent necrosis that necessitates lower limb amputation. [doi.org]

  The importance of DPN in the etiopathogenesis of foot ulceration has been confirmed in numerous studies and was the subject of a recent review. 43 It must be remembered that the neuropathic diabetic foot does not ulcerate spontaneously. [clinical.diabetesjournals.org]

• Muscle Twitch

  On clinical examination, muscle twitches of fingers of both hands, as well as the abductor halluces and the dorsal interossei muscles of the right foot were observed. [ncbi.nlm.nih.gov]

  Motor neuropathy symptoms may include: Muscle weakness Cramps Muscle twitching Loss of muscle and bone Changes in skin, hair, or nails Sensory neuropathy symptoms may include: Numbness Loss of sensation or feeling in body parts Loss of balance or other [columbianeurology.org]

  They include: Numbness or reduced sensation Tingling Pain, often a burning or sharp, cutting sensation Sensitivity to touch Muscle twitches Muscle weakness Difficulty with walking Loss of coordination or balance Paralysis If untreated, peripheral neuropathy [uvahealth.com]

  Muscle weakness Cramps Muscle twitching Loss of muscle and bone Changes in skin, hair, or nails Numbness Loss of sensation or feeling in body parts Loss of balance or other functions as a side effect of the loss of feeling in the legs, arms, or other [hopkinsmedicine.org]

• Osteoporosis

  Comprehensive health information about cancer, osteoporosis, high blood pressure and more. Comprehensive health information including health news updates and health resources. [web.archive.org]

  Seung Woo Kim, Young‐Chul Choi, Seung Min Kim and Ha Young Shin, Risk factors for osteoporosis in chronic inflammatory demyelinating polyradiculoneuropathy, Muscle & Nerve, 58, 3, (407-412), (2018). [dx.doi.org]

• Restless Legs Syndrome

  I have restless leg syndrome discovered via a sleep clinic. A small tingling area developed in my back about 8 years ago. Nothing was disclosed to me about it and it progressed further up the back. [medical-dictionary.thefreedictionary.com]

  At the moment, restless leg syndrome is the second commonest MD (GA is the commonest) with more than 50% of patients responding positively when embarking on a GFD, even as a monotherapy. [doi.org]

• Muscular Atrophy

  Muscular atrophy of hand muscles persisted. Large fibers were involved more extensively than small fibers. CONCLUSIONS: A severe axonal sensorimotor polyneuropathy developed in the intensive care unit following severe hypothermia. [ncbi.nlm.nih.gov]

  Boulis works on novel treatments for several nerve disorders, including Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig's disease) and Spinal Muscular Atrophy (SMA). [emoryhealthcare.org]

• Foot Pain

  " 20 Mar. 2018 The spiky shoe inserts mimic peripheral neuropathy, the numbness and pain from nerve damage that often affects hands and feet. — Tara Bahrampour, The Seattle Times, "Loud banging, foot pain, flashes of light: a reporter’s 8 minutes as [merriam-webster.com]

• Guillain-Barré Syndrome

  While length-dependent sensorimotor axonal peripheral neuropathy is the most common presentation, several examples present in a subacute severe fashion, mimicking Guillain-Barré syndrome. [ncbi.nlm.nih.gov]

  Autoimmune with no specific causal infectious agent identified: Sarcoidosis Guillain-Barré Syndrome / Acute Inflammatory Demyelinating Polyneuropathy (AIDP) Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Vasculitis Polyarteritis Nodosa (PAN) [foundationforpn.org]

  Demyelinating patterns are suggestive of acute (Guillain-Barré syndrome) and chronic inflammatory polyneuropathies (CIDP), paraneoplastic disorders, and medications and toxins. [clinicaladvisor.com]

• Ataxia

  Multifocal motor or sensorimotor neuropathies and a more fulminant neuropathy, associated with ataxia and other neurologic manifestations, also have been reported. [ncbi.nlm.nih.gov]

  : Sporadic cerebellar ataxia associated with gluten sensitivity. Brain 2001, 124 :1013–1019. PubMed CrossRef Google Scholar 16. Sander HW, Magda P, Chin RL, et al. : Cerebellar ataxia and coeliac disease. Lancet 2004, 362 :1548. [doi.org]

  Ataxias, 2, 1, (2015). [dx.doi.org]

• Paresthesia

  Chemotherapy-induced peripheral neuropathy is a debilitating side effect of chemotherapy, which manifests as paresthesias, dysesthesias, and numbness in the hands and feet. [ncbi.nlm.nih.gov]

  Weakness and numbness in the affected limb or limbs may be accompanied by abnormal sensations (paresthesia) – that is, tingling, “pins and needles”, burning, pain etc. Frequently the symptoms are worse at night. [brainfoundation.org.au]

• Sciatica

  To be eligible studies needed to explicitly report that participants had sciatica or a synonym for sciatica. [bmj.com]

  If the pain is caused by sensitive or damaged nerves, as is the case with shingles or sciatica, it's usually treated with tablets that change the way the central nervous system works. The aim of taking medication is to improve your quality of life. [nhs.uk]

• Foot Drop

  CASE REPORT: A 47-yr-old female hyperbaric technician developed foot drop 2 d following her last hyperbaric exposure. She had worked in chamber once daily at 45 fsw for 90 min. [ncbi.nlm.nih.gov]

  Common peroneal nerve Caused by trauma or surgery. [ 3, 4 ] Leads to foot drop. Weakness on the everting foot. Inability to extend the toes. Paraesthesia over the dorsum of the foot. [patient.info]

  This leads to a condition called " foot drop ," in which it becomes difficult to lift the foot. Neuropathy can affect nerves that control muscle movement (motor nerves) and those that detect sensations such as coldness or pain (sensory nerves). [webmd.com]

Laboratory tests

• Complete blood count
• Thyroid function tests 
• Peripheral nerve biopsy: According to a study conducted on 100 elderly patients, all aged 65 years and above, it was found that nerve biopsy helped in the detection of potentially treatable disorders and influenced patient management in 81% of elderly subjects with peripheral neuropathy, thus confirming that it is a useful tool in diagnosing neuropathies in the elderly [8].
• Renal function tests
• Blood sugar level
• Urinalysis 
• Resting lactate and pyruvate levels

Imaging 

• Nerve conduction studies
• Electromyography
• CT scan and MRI
• Doppler ultrasound and nuclear imaging

Test results

A thorough physical examination, particularly a neurological examination is essential in diagnosing peripheral neuropathy. Laboratory tests and imaging studies can help confirm the diagnosis as well as identify the underlying disease.

A symptomatic approach to treatment is generally applied. Antidepressants and antiepileptic drugs are used to relieve nerve pain. Some current research conducted in animal models has shown that a factor called neurotrophin-3 can oppose the demyelination present in some peripheral neuropathies [9], but human studies and trials are still underway with no definite results yet. Transcutaneous electrical nerve stimulation therapy is also a promising treatment and a recent review of three clinical trials that constituted total 78 patients reported some improvement in pain scores after 4 and 6 weeks of treatment, and an overall improvement in neuropathic symptoms at 12 weeks of treatment was found [10].

Neuropathies do not have a good prognosis because they are progressive conditions. Once the pathway of nerve damage has begun, it tends to go on. Some drugs have been developed that may slow or in some rare cases reverse the ongoing damage and their use may help manage this condition. If the cause is a systemic disease, control of the underlying disease is also important and reflects heavily on the prognosis.

Peripheral neuropathy can be due to systemic diseases, most commonly diabetes mellitus. Up to 26% of people with diabetes mellitus type 2 have evidence of nerve damage at the time that diabetes is diagnosed [2]. Studies reveal that allele 936C of VEGF may serve as a genetic marker susceptible to diabetic peripheral neuropathy, while allele 936T may be a protective genetic marker of this condition [3]. Other systemic diseases like acquired and hereditary amyloidosis can cause peripheral neuropathy, but the mechanisms by which this occurs have not been established [4]. Leprosy is another systemic disease that damages nerves. Other causes include vitamin deficiency, alcoholism, toxins like insecticides, adverse reactions to some drugs and trauma.

Incidence

An American study conducted in late 1993-4 estimated that 47% of patients with diabetes have some extent of peripheral neuropathy [5]. An exact incidence is unknown because often mild stages go unnoticed or unreported.

Age

Neuropathies are typically disease of old age.

Sex

Predisposition to sex varies with the type of neuropathy, for example uremic neuropathy and diabetic neuropathy are more common in men but morbidity is higher in women.

The exact pathophysiology regarding neuropathy is unclear. Several factors and pathways are implicated and it is observed that mitochondrial dysfunction is a hallmark of many sensory neuropathies [6]. Several alterations in cytokine and neurotrophic factor levels have been reported in various neuropathies. According to a study conducted in which sural nerve gene expression of some cytokines and neurotrophic factors was observed, the results showed that IL-6 (p < 0.01) and IL-10 (p < 0.05) expression was higher in painful compared to painless neuropathies. It was also reported that skin IL-6 and IL-10 gene expression was increased in patients compared to control groups (p < 0.05), and IL-10 expression was higher in lower leg skin of patients with non-inflammatory neuropathies compared to inflammatory neuropathies (p < 0.05) [7]. Other factors include basement membrane thickening and vessel occlusion leading to microvascular insufficiency, lack of expression of Laminin beta-2 gene and inhibition of Na/K Atpases present in the axons of nerves.

The only prevention of peripheral neuropathy is the prevention of, or the control of the underlying disease or condition that may lead to nerve damage. Such diseases and conditions include vitamin deficiencies, excessive alcoholism, uncontrolled diabetes mellitus, hypothyroidism, amyloidosis, leprosy, porphyrias, exposure to toxins, prolonged use of fluoroquinolones, chemotherapy, systemic lupus erythematosus (SLE) and Lyme disease.

Peripheral neuropathy is a collective term that refers to damage to the peripheral nerves. It may occur due to myriad reasons. The presence of peripheral nervous system involvement is often an early signal of the generalization of inflammatory disease in blood vessels or extravascular tissues [1]. It also indicates a serious underlying disorder which is more often than not a systemic disease.

Definition

Peripheral neuropathy is a disease of the nerves as a result of injury to one or more nerves.

Cause

It may be due to genetic diseases, systemic diseases, trauma, drug reactions and chemotherapy, vitamin deficiencies and excessive consumption of alcohol.

Signs and symptoms

Signs and symptoms depend on the type of nerves that are damaged. For example, damage to the nerves that conduct sensations result in sensory loss, damage to nerves that control responses result in motor abnormalities and affected movement, etc.

Diagnosis

Diagnosis is made based on a thorough physical and neurological examination. Laboratory tests and imaging studies help in confirming the nerve damage and identifying the underlying cause.

Treatment

Treatment is symptomatic relief with the help of medication and control, and if possible, elimination of the underlying cause.

1. Reda H, Chin RL. Peripheral neuropathies of rheumatologic disease and gluten-related disorders. Semin Neurol. 2014 Sep;34(4):413-24. 
2. Davies M, Brophy S, Williams R, Taylor A. The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care 2006; 29:1518. 
3. Zhang X, Sun Z, Jiang H, Song X. Relationship between single nucleotide polymorphisms in the 3'-untranslated region of the vascular endothelial growth factor gene and susceptibility to diabetic peripheral neuropathy in China. Arch Med Sci. 2014 Oct 27;10(5):1028-34. 
4. Hafner J, Ghaoui R, Coyle L, Burke D, Ng K. Axonal excitability in primary amyloidotic neuropathy. Musc Ner. 2014 Nov 7. doi: 10.1002/mus.24508 PMID: 25381694
5. Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology. Apr 1993;43(4):817-24 
6. Katzman SM, Strotmeyer ES, Nalls MA, Zhao Y, Mooney S, Schork N, Newman AB, Harris TB, Yaffe K, Cummings SR, Liu Y, Tranah GJ. Mitochondrial DNA Sequence Variation Associated With Peripheral Nerve Function in the Elderly. J Gerontol A Biol Sci Med Sci. 2014 Nov 13. 
7. Uçeyler N, Riediger N, Kafke W, Sommer C. Differential gene expression of cytokines and neurotrophic factors in nerve and skin of patients with peripheral neuropathies. J Neurol. 2014 Nov 5. PMID: 25371017
8. Anish L, Nagappa M, Mahadevan A, Taly AB. Neuropathy in elderly: lessons learnt from nerve biopsy. Age Ageing. 2014 Nov 1. 
9. Liu N, Varma S, Tsao D, Shooter EM, Tolwani RJ. Depleting endogenous neurotrophin-3 enhances myelin formation in the Trembler-J mouse, a model of a peripheral neuropathy. J. Neurosci Res, 2010. 85 (13): 2863–9. 
10. Jin DM, Xu Y, Geng DF, Yan TB. Effect of transcutaneous electrical nerve stimulation on symptomatic diabetic peripheral neuropathy: a meta-analysis of randomized controlled trials. Diabetes Res. Clin. Pract. Jul 2010. 89 (1): 10–5.