Peripheral neuropathies are among the most common neurological diseases with an overall incidence of 77/100,000 per year. Prevalence of peripheral neuropathy is 1-12% in all age groups and 30% in the elderly. In the US the cost of diabetic peripheral neuropathy in $13 billion annually. The estimate of idiopathic neuropathies in the US outnumber Alzheimer’s patients threefold.
Peripheral neuropathy results from damage to the nerves located outside the brain and spinal cord. The peripheral nerves system sends information from your central nervous system (brain and spinal cord) to the rest of the body. The peripheral nerves send sensory information back to the central nervous system.
Peripheral neuropathy can affect a single nerve called a mononeuropathy, two or more nerves in different areas of the body called a multiple mononeuropathy or many nerves called a polyneuropathy.
The pathophysiology of peripheral neuropathy results from damage to small or large diameter nerve fibers. Damage can occur to the cell body, axon, myelin sheath or a combination of these leading to symptoms such as numbness, tingling, pain and weakness. Large fibers mediate motor, sensory, vibration and proprioception functions. Small fibers mediate pain, temperature and autonomic functions.
A systemic approach should always be used to evaluate peripheral neuropathy from other causes especially CNS causes.
CNS lesions should be suspected in patients with speech disturbance, ataxic gait, visual disturbance bowel or bladder incontinence or any cranial nerve involvement.
Symptoms and Signs of Peripheral Neuropathy
- Extreme sensitivity to touch
- Sharp, stabbing throbbing pain
- Burning pain numbness
- Pain during activities that normally does not cause pain such as foot pain when standing
- Falls, lack of coordination
- Paralysis if motor nerves are affected
- Feeling as if you are wearing gloves or socks when you are not
If autonomic nerves are involved:
- Drops in blood pressure causing dizziness and lightheadedness
- Bowel, bladder, digestive problems
- Excessive sweating or lack of sweat
- Heat intolerance
- Dry Eyes
- Dry Mouth
- Impotence
- Hair loss in the distal legs
Causes of Neuropathy
- Idiopathic
- Diabetes
- Toxic (Alcohol, drugs, chemotherapy)
- Inflammatory or Immune mediated
- Heredity
- Vasculitis, amyloid, sarcoid, connective tissue diseases
- Thyroid
- Uremic
- B12 deficiency
- Other such as leprosy, HIV
Evaluation
History and Physical can provide valuable diagnostic clues toward the cause of peripheral neuropathy
Clinical History
- Time course and evolution
- Family history
- Pain
- Fever, night sweats, weight loss
- Exposure to neurotoxic medications or toxic substances
- Alcohol
- Diabetes
Neurological Examination
- Sensory/sensory motor involvement
- Pure Motor
- Autonomic Nerve Involvement
- Distribution of Symptoms
Distal Symmetric
Proximal
Asymmetric/multifocal
Clinical Patterns
- Slowly progressive, distal symmetric, predominately sensory neuropathy.
This is the most common peripheral neuropathy. This is caused by a metabolic condition such as diabetes, chronic alcohol abuse or chemotherapy or neurotoxic drugs.
If the above diseases are excluded the diagnosis of chronic idiopathic axonal neuropathy is usually the diagnosis given.
- Slowly progressive, long-standing neuropathy with muscle wasting and foot abnormalities. Motor predominant and usually from infancy. Hereditary is usually etiology. Claw hands, wasting muscles, foot ulcers
- Neuropathy with subacute onset and proximal involvement. These types are immune mediated etiology
- Neuropathy with rapid progression, multifocal symptoms, neuropathic pain and autonomic dysfunction. Potentially caused by vasculitis, amyloidosis or paraneoplastic syndromes.
- Sensory ataxic neuropathy- patients have lack of proprioception and lack of vibration with relative preservation of muscle strength autoimmune disorders (Sjogren’s) and neoplastic syndromes
Neuropathies by Pattern of Involvement
Focal
- Entrapment
- Common sites of compression
- Myxedema
- Rheumatoid arthritis
- Amyloidosis
- Acromegaly
- Compressive neuropathies
- Trauma
- Ischemic lesions
Diabetes
Vasculitis
- Leprosy
- Sarcoidosis
- Neoplastic infiltration or compression
Multifocal
- Diabetes
- Vasculitis
Polyarteritis Nodosa
Systemic Lupus
Sjogren’s
- Sarcoidosis
- Leprosy
- HIV/AIDS
- Chronic inflammatory demyelinating polyradiculoneuropathy
- Pressure palsies
Time
Disease onset and evolution of symptoms can help make the diagnosis
- Symptoms from birth – genetic etiology
- Slow onset from months to years- metabolic etiology
- Rapid onset weeks to months – immune mediated, vasculitis, paraneoplastic, infectious
Diagnostic Studies
Electrodiagnostic studies are the major tests done for neuropathy diagnosis
- Nerve conduction studies (NCS)
- Needle electromyography (EMG)
Studies are carried out to
- Confirm the clinical diagnosis of peripheral neuropathy
- Exclude neuropathy mimics such as radiculopathy or myopathy
- Revel subclinical involvement of clinically unaffected nerves
- Assess the primary mechanism of damage (axonal vs demyelinating)
- Determine disease severity
Laboratory Testing
- CBC
- Sed Rate
- Comprehensive Metabolic Panel
- Thyroid Testing
- HA1C
- Serum Protein Electrophoresis (Approx. every 10Th patient positive)
- B12
- Cobalamine metabolites (Methylmalonic acid and Homocysteine) levels are usually elevated if B12 are low normal
CSF
Usually not instructive but is warranted when inflammatory, neoplastic or immune disorder is suspected.
Genetic testing
Genetic testing should be considered when clinical or history suggests a hereditary origin.
Nerve Biopsy
Nerve biopsy should be considered in patients presenting with signs of symptoms suggestive of inflammatory neuropathy. Usually, a sural nerve biopsy is performed.
Peripheral nerve imaging
MRI and Ultrasound can help identify affected nerve segments for nerve biopsy.
Treatment
The treatment of peripheral neuropathy focuses on the management of the underlying condition such as diabetes.
Nonpharmacologic treatment
- Weight loss
- D/C alcohol
- Physical therapy to aid with muscle weakness
- Braces, canes, walker, wheelchair
Medications
- Pain relievers- usually NSAID or Tylenol but stronger narcotic meds may be utilized if pain is severe (addiction potential high)
- Anti-Seizure meds- these meds were developed for seizure disorders but are now utilized for neuropathic pain (Neurontin, Lyrica) Now shown to have an addiction/abuse potential
- Topical creams- Capsaicin cream has been shown to benefit. Lidocaine patches are also used (side effects of skin sensitivity)
- Antidepressants- these drugs relieve pain by interfering with chemical transmitters and receptors (Amitriptyline, doxepin). This class of drugs includes serotonin and norepinephrine reuptake inhibitors. This class of drugs has multiple side effects. (Cymbalta, Effexor)
Therapies
- Transcutaneous Nerve Stimulators (TENS) has been shown to be moderately effective for pain relief
- Spinal Cord Stimulators have been FDA approved for pain control
- Plasma Exchange and Intravenous Gamma Globin may be used in patients with certain inflammatory immune mediated conditions
- Surgery is only considered for relief of nerve entrapment
Platelet Rich Plasma is an autologous blood concentrate, rich in cytokines, growth factors and bio-active molecules that have been utilized in multiple fields of medicine to repair and regenerate damaged tissues. Multiple studies have been done worldwide to alleviate the symptoms and pain of peripheral neuropathy utilizing Platelet Rich Plasma. The results have been extremely favorable. Below are a few of these studies.
Tissue Eng Part A 2014 Dec;20(23-24):3228-40 PMID 24901030
The objective of this article is to evaluate the effect of acellular nerve allografts supplemented with platelet rich plasma to improve nerve regeneration after surgical repair and to discuss the mechanisms that underlie this approach.
Conclusion- ANA loaded with PRP as tissue engineered scaffolds can enhance nerve regeneration and functional recovery after the repair of large nerve gaps.
Tissue Eng Part A 2020 Feb;26(3-4):178-192 PMID 31516089
Platelet Rich Plasma contains numerous growth factors and active proteins, and low dose ultrashort waves stimulate the formation of nerve nourishing vessels which are powerful for nerve regeneration. The goal of this study was to evaluate the synergistic effects of serial guided PRP injections combined with low dose USW radiation of peripheral nerve regeneration in a crush injury model.
Conclusion- Serial ultrasound guided PRP injections combined with low dose ultrashort wave treatment exert a synergistic effect on accelerating peripheral nerve regeneration. Our findings may help establish effective strategies for repairing peripheral nerve injury.
J Craniofac Surg 2017 Jan;28(1):e49-57 PMID 27893553
The aim of this study was to systematically review the effects of Platelet Rich Plasma on the regeneration of peripheral nerve injuries.
Conclusion- PRP demonstrated positive effects on healing of nerve function as well as histological improvements in cut nerve peripheral nerve injury models.
Scand J Pain 2017 Oct;17:287-293 PMID 29229214
An increasing number of studies have indicated that the immune system plays a critical role in the mediation of neuropathic pain. A literature review was performed to assess the role of pro-inflammatory and anti-inflammatory cytokines in the development of neuropathic pain.
Conclusion- in both human and animal studies neuropathic pain has been associated with the pro-inflammatory state. Analgesic therapies involving direct manipulation of various cytokines and indirect methods to alter the balance of the immune system have been explored. With better appreciation and understanding of the interaction between the immune system and neuropathic pain, new therapies may be developed to target this system.
Author note- Platelet Rich Plasma and Platelet Rich Fibrin target both pro and anti -inflammatory cytokines. The author of this study noted the cytokines themselves which are contained in the PRP concentrate.
Juventix Regenerative Medical is an industry leader in the regenerative medical field. Our Platelet Rich Plasma Kits are FDA approved and designed for safety, sterility and effectiveness. They are cost effective and easy to use. Our kits have been scientifically manufactured to provide a consistent platelet concentrate, devoid of red blood cells with a minimal number of leukocytes critical to the regenerative cascade.
Juventix Regenerative Medical offers a patent pending LED Activator to activate the platelets and begin the regenerative process. The activation is a critical step in the release of cytokines, growth factors and bio-active proteins and is accomplished with LED light. This negates the use of chemical additives such as Calcium Chloride, Thrombin or Collagen.
Juventix Regenerative Medical supplies a Bio-incubator that transforms the Platelet Rich Plasma into an injectable Platelet Rich Fibrin. The Platelet Rich Fibrin, commonly called “the second generation of platelet products” has different growth factors and cytokines than original PRP. These different cytokines provide a broader range of clinical uses due to their anti-inflammatory properties.
RESTORE, REVIVE, REGENERATE- JUVENTIX REGENERATIVE MEDICAL
Regenerative Regards,
Dr. Robert McGrath
