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Peripheral Neuropathy

Peripheral Nervous System Disease or Syndrome

Peripheral neuropathy refers to damage to one or more than one nerves which results in gradual axonal damage and disturbed functioning.


Presentation

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.

Pain
  • 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]
  • Neuropathic pain was present in 13 of 60 patients (21%), who reported shooting or burning pain in the hands (n 9) and the feet (n 12).[ncbi.nlm.nih.gov]
  • Nerve decompression surgery was able to alleviate pain in patients with painful diabetic peripheral neuropathy.[ncbi.nlm.nih.gov]
  • Mean pain level after 12 weeks of treatment was 0.20 0.41.[ncbi.nlm.nih.gov]
  • […] the prevalence of neuropathic pain in diabetic peripheral neuropathy was 21.2%.[ncbi.nlm.nih.gov]
Heat Intolerance
  • […] 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]
  • […] 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]
  • […] and arms Sharp, jabbing, throbbing, freezing or burning pain Extreme sensitivity to touch Lack of coordination and falling Muscle weakness or paralysis if motor nerves are affected If autonomic nerves are affected, signs and symptoms might include: Heat[mayoclinic.org]
Lower Extremity Pain
  • The patient is a 20-year-old male, with well-controlled type 1 diabetes mellitus, presenting with a short duration of bilateral lower extremity pain following a 10-day course of levofloxacin for suspected epididymitis.[ncbi.nlm.nih.gov]
  • Pain is vital -... read more April 9, 2018 Research Study for Painful Diabetic Peripheral Neuropathy Dual Field Pulsed Electromagnetic Field (PEMF) Therapy Device in Lower Extremity Painful Diabetic Distal Symmetric Peripheral Neuropathy (DSPN) Research[foundationforpn.org]
Foot Ulcer
  • This can aid in identifying patients at high risk of diabetic foot ulceration.[ncbi.nlm.nih.gov]
  • Lipsky: Preventing foot ulcers in patients with diabetes. JAMA 293 (2):217-228, 2005 2. Tuttle, L. J., M. K. Hastings, and M. J.[huffingtonpost.com]
  • In particular, foot ulcers have been targeted for prevention and intervention since foot ulcers precede over 80% of diabetic amputations. 11 In the presence of peripheral vascular disease and neuropathy, the development of a foot ulcer may be the start[cms.gov]
  • The population prevalence is about 2400 per 100 000 (2.4%), rising with age to 8000 per 100 000 (8%). 1 In Europe the commonest cause is diabetes mellitus, which can produce painful neuropathy, disabling foot ulcers, and death from autonomic neuropathy[bmj.com]
Muscle Twitch
  • 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]
  • 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[stlouischildrens.org]
  • 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]
Muscular Atrophy
  • Muscular atrophy of hand muscles persisted. Large fibers were involved more extensively than small fibers. 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
  • […] hands and feet. — Tara Bahrampour, The Seattle Times , "Loud banging, foot pain, flashes of light: a reporter’s 8 minutes as a dementia patient," 26 Dec. 2017 The spiky shoe inserts mimic peripheral neuropathy , the numbness and pain from nerve damage[merriam-webster.com]
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]
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]
  • We also include a separate category of complex inherited relapsing neuropathy syndromes, some of which may mimic Guillain-Barré syndrome, as many will have a metabolic aetiology and be potentially treatable.[ncbi.nlm.nih.gov]
  • Rare cases clinically resemble Guillain-Barré syndrome. In the absence of prospectively collected data on possible associations between LCIG and PN, it is prudent to explore potential mechanisms that may explain a possible relationship.[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]
  • ., Guillain-Barré syndrome, porphyria, paraneoplastic, vasculitic, medications, tick paralysis, critical illness polyneuropathy, post-diphtheria, and buckthorn toxicity).[clinicaladvisor.com]
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]
  • Patients present with pain, paresthesias, or weakness along a specific nerve distribution or experience generalized peripheral neuropathy.[ncbi.nlm.nih.gov]
  • MEDLINE/PubMed, EBSCO, and Google Scholar were searched through February 2017 using the search terms metronidazole and peripheral neuropathy, or polyneuropathy, or paresthesia, or neurotoxicity.[ncbi.nlm.nih.gov]
  • […] failure Radiculopathy Vitamin deficiencies Signs and Symptoms Diagnosis Treatment Although there are numerous causes of peripheral neuropathies, they do share some common symptoms, including: Weakness, numbness and pain in the hands, legs and/or feet Paresthesia[ucsfhealth.org]
  • 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]
Ataxia
  • Spinocerebellar ataxias (SCAs) are a group of autosomal dominant, clinically heterogeneous neurodegenerative disorders.[ncbi.nlm.nih.gov]
  • Using this approach, we associated neuropathy with one of three major syndromic categories: (1) ataxia, (2) spasticity and (3) global neurodevelopmental impairment.[ncbi.nlm.nih.gov]
  • ) of 76 patients with SS as the underlying disease; three were cases of multiple mononeuropathy, two cases had sensory ataxic neuropathy, one of which was autonomic neuropathy, and one case was diagnosed as painful sensory neuropathy without sensory ataxia[ncbi.nlm.nih.gov]
  • Side effects at higher charges include increasing gait ataxia. However, at the right levels, marked improvement has been reported in activities of daily living and in the amplitude of the tremor.[news-medical.net]
  • On occasion, when significant proprioceptive deafferentation occurs, patients are found to have altered joint position sense that can manifest as an ataxia or tremor of the affected limbs and an imbalance of gait and station.[clevelandclinicmeded.com]
Foot Drop
  • 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. The breathing gas was air until the last 15 min, during which she breathed oxygen.[ncbi.nlm.nih.gov]
  • 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]
  • Foot braces may also be helpful if you have problems with foot drop. If you have weakness in your arms, a wrist splint may be helpful. A physiotherapist may be the best person to help you with such aids.[patient.info]
Dysesthesia
  • 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]
  • ., pain, dysesthesias) or 'negative' (e.g., loss of touch, vibration, position sense) neuropathic symptoms or signs.[clinicaladvisor.com]
  • […] role in the continued experience of chronic pain symptoms. ( 4 ) Some of the specific types of disordered pain that may be experienced in neuropathy include: Allodynia – pain from what is normally a non-painful touch, such as being stroked by a feather Dysesthesia[neuromodulation.com]
  • These include allodynia (pain evoked by light stimuli that are not normally pain-evoking) and various abnormal sensations termed dysesthesias (e.g., electric shock sensations, “pins and needles,” sensations of coldness or heat, numbness, and other types[journalofethics.ama-assn.org]

Workup

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.

Albuminuria
  • […] diabetic peripheral neuropathy with neuropathic pain should be considered for people with older age, elevated glycated haemoglobin, low high-density lipoprotein cholesterol and overt proteinuria, with particular attention given to increased levels of albuminuria[ncbi.nlm.nih.gov]
Tropheryma Whipplei
  • Whipples disease is a chronic multisystem inflammatory disease with predominantly gastrointestinal manifestations due to Tropheryma whipplei infection.[ncbi.nlm.nih.gov]

Treatment

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].

Prognosis

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.

Etiology

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.

Epidemiology

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.

Sex distribution
Age distribution

Pathophysiology

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.

Prevention

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.

Summary

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.

Patient Information

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.

References

Article

  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. 

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Last updated: 2018-06-22 01:48