Pins and needles, electric shock-like pain, burning sensation, tingling, and numbness─ symptoms commonly associated with neuropathy. However, these only account for the sensory type of peripheral neuropathy. Much to the surprise of many, peripheral neuropathies also manifest with motor and autonomic symptoms.
Peripheral neuropathy (PN) is said to be prevalent in 1 to 3% of the general population with increasing prevalence of 7% among the elderly.1 Using these estimates, 1 to 3 out of 108 million Filipinos may be affected by the condition as of August 2019.2 More alarming is the possibility of 7 million elderly Filipinos suffering from PN.
Due to its highly prevalent state, many cases of peripheral neuropathy are seen at primary care level.1 However, no specific clinical guideline exists in diagnosing and managing PN. The primary care physician is faced with the challenge of managing PN and knowing when to refer cases to specialists.
The primary care physician would at some point recommend electromyography (EMG) and nerve conduction studies (NCS) for some cases of PN. However, the cost of such tests could be burdensome for the average Filipino. Added to this burden is the cost of medications, rehabilitation, hospitalizations, and emergency department visits from complications such as fractures from falls or non-healing wounds if the PN is from diabetes.
Understanding Peripheral Neuropathy
Peripheral neuropathy is an umbrella term for a number of abnormalities pertaining to damaged peripheral nerves. To make a complete understanding of the disease, terms such as mononeuropathy, mononeuropathy multiplex, polyneuropathy, radiculopathy, and neuronopathy must be defined.
Mononeuropathy refers to a dysfunction of a single cranial or peripheral nerve. It may result from compression such as in carpal tunnel syndrome which results to pain and weakness along the distribution of the median nerve.4 Mononeuropathy multiplex, on the other hand, pertains to simultaneous involvement of a few nerves in separate areas of the body whereas polyneuropathy affects many nerves on both sides of the body.5
Radiculopathy or polyradiculopathy pertains to damage to the nerve roots that may result to severely disabling pain and motor weakness along a large area such as the thorax, abdomen, back, thigh, hip or legs.4 Neuronopathy and ganglionopathy refers to diseased cell bodies of nerves whereas axonopathy pertains to damaged axons.
The nerve can be damaged by a specific disease condition and sensory, motor, autonomic, or a combination of functions may be affected resulting to signs and symptoms. Underlying mechanisms of nerve damage include metabolic derangements, oxidative stress, ischemia of blood vessel supply to nerves, and inflammatory processes.6 Although, the majority of PN is attributed to diabetes, 50% is idiopathic or cryptogenic.4
Aside from diabetes, PN could be the direct effect of genetic disease such as Charcot-Marie Tooth (CMT) or hereditary sensory polyneuropathy. Infectious causes can also contribute to the development of PN such as leprosy, HIV, and Lyme disease. Furthermore, the etiologies also include Guillain Barre Syndrome (GBS), chronic intermittent demyelinating polyneuropathy, toxic neuropathy from chemotherapy, alcohol-induced, or a result of vitamin deficiency. The pathophysiology of PN depends on the specific cause.
Symptoms of PN are diverse and range from sensory, motor, autonomic, or a combination. Sensory symptoms tend to occur before motor and autonomic ones.3 Large diameter nerve fibers for vibration and position sense may be affected resulting to loss of proprioception and vibration sense. When small diameter nerve fibers are affected, numbness, tingling, aching, and burning sensations may be experienced.4
Neuropathic pain occurs in one-third of patients with PN.3 It can be burning, dull, and poorly localized when type C nerve fibers are affected or sharp and lancinating if A-delta fibers are damaged.4 Motor symptoms of PN is weakness over the area distributed by the nerve.3
Autonomic peripheral neuropathy manifest with vasomotor symptoms such as dry eyes, mouth, and skin, blurring of vision from pupillomotor abnormality, orthostatic hypotension, decreased heart rate variability, resting tachycardia, flushing, delayed gastric emptying or gastroparesis, diarrhea, constipation, neurogenic bladder, and erectile dysfunction.3
Physical examination findings for PN include sensory loss or deficit to 10g-monofilament test. Furthermore, there could be loss of vibration sense, loss of ankle deep tendon reflexes, abnormal position sense, muscular atrophy, and foot drop.4
Primary Care Level Approach
The primary care physician must be prudent in diagnosing PN. The history and physical examination must be compatible with PN before diagnostic tests are ordered. There are seven key questions that the primary care must answer with regard to PN. The system/s involved must be determined whether it is motor, sensory, autonomic, or a combination.4
If there is motor involvement, the distribution of weakness should be identified whether it involves proximal and distal muscles or distal muscles alone or if it is focal or asymmetric versus symmetric. The next key question that must be addressed is the nature of sensory involvement (loss of temperature sensation, burning, or stabbing pain versus loss of vibratory or position sense).4
Evidence of upper motor neuron involvement must also be sought. When there is symmetric distal sensory signs and symptoms along with symmetric upper motor signs (spasticity, hyperreflexia, and presence of pathological reflexes), a combined system degeneration with neuropathy usually from vitamin B 12 deficiency must be considered.4
The temporal evolution must also be investigated. Acute symptoms last from days to 4 weeks and is usually indicative of GBS, vasculitis, and radiculopathy related to diabetes. Subacute disease lasts 4 to 8 weeks and chronic ones are those presenting 8 weeks and longer.4 The course of disease whether monophasic, progressive, or relapsing must also be noted.
A slowly progressive distal weakness over several years with sensory signs and symptoms and physical deformities such as hammer toes and high arched feet is indicative of Charcot Marie Tooth (CMT).4 This, along with other evidence of hereditary neuropathy, must be sought.
Finally, comorbidities must be identified and these include diabetes, systemic lupus erythematosus, vasculitis, cancer, HIV, varicella zoster virus, and diarrheal illness preceding GBS. Furthermore, nutritional deficiencies such as vitamin B1, B6, and B12 deficiencies as well as gastric surgery, alcoholism, medications (isoniazid, metronidazole, metformin causing vitamin B12 deficiency), chemotherapy (platinum-based such as cisplatin, taxanes, vinca alkaloids, and proteasome inhibitors like bortezomib), and exposure to toxins from seafood (saxitoxin and brevetoxin), amyloid, and inorganic compounds (mercury, arsenic) must be duly investigated.4
Identification of the cause of peripheral neuropathy leads to prompt diagnosis and appropriate management. Due to the multitude of causes, the primary care physician must know which cases need further diagnostic tests to support or confirm the diagnosis specially if hereditary neuropathy, vasculitis, and GBS or CIDP is suspected.
Nerve Conduction Studies (NCS) and Electromyography (EMG) can confirm whether the PN is a mononeuropathy, monoeuropathy multiplex, radiculopathy, or polyneuropathy.4 It can also determine if sensory, motor, autonomic, or a combination of nerve fibers are affected. Aside from these, it can distinguish whether the problem is an axonopathy or a myelinopathy (myelin sheath).
Laboratory evaluation for PN may include CBC, electrolytes, renal and liver function tests, fasting blood sugar, glycosylated hemoglobin, thyroid function test, B12, folate, rheumatoid factor, erythrocyte sedimentation rate (ESR), anti-nuclear antibody (ANA), and serum protein electrophoresis. Nerve biopsies are rarely performed but may help identify amyloid neuropathy and vasculitis.4
The primary care physician must be prudent in ordering which tests may be supportive of the etiology of PN that he or she has in mind. When a specific cause has already been established, some laboratory tests are no longer necessary.
Management of PN depends on the specific cause. Generally, a well-balanced diet is recommended with emphasis on vitamin supplementation if there is a deficiency. PN resulting from medications or from chemotherapy must properly be addressed. When there is an acceptable alternative for the specific medication, it must be offered. Exposure to toxins and inorganic compounds must be stopped.7
Preventive strategies include exercise which can help in blood circulation and preservation of muscle tone and strength. For diabetics, good glycemic control can help prevent nerve damage. Vaccination with shingles vaccine prevent the infection as well as the neuropathic pain associated with it.7
Certain medications help manage neuropathic pain and these include pregabalin, gabapentin, and duloxetine. They must be appropriately prescribed by the primary care physician or a neurologist. Decompressive surgery is recommended for some cases of carpal tunnel syndrome and trigeminal neuralgia. Surgery is also an option for protruding intervertebral discs that impinge nerve roots.7
The primary care physician must tailor-fit a management strategy best suited to his or her patient. Refractory cases must be carefully noted and can be referred to specialists. More importantly, the primary care physician must be reminded that about half of PN cases have no known cause and must therefore reassure the patient and manage the symptoms if diagnostic tests yield negative or equivocal results.
- Haniwinckel, R. et al. The epidemiology and risk factors of chronic polyneuropathy. European Journal of Epidemiology. 2016.
- (August 12, 2019) Philippines Population. Retrieved from: https://www.worldometers.info/...
- Doughty, C. and Seyedsajadi, R. Approach to Peripheral Neuropathy for the Primary Care Clinician. The American Journal of Medicine. 2018.
- Jameson, J. et al. Harrisons Principles of Internal Medicine 20th McGraw-Hill Education. 2018.
- Multiple Mononeuropathy. Retrieved from: https://www.msdmanuals.com/home/brain,-spinal-cord,-and-nerve-disorders/peripheral-nerve-disorders/multiple-mononeuropathy
- Staff, N. and Windebank, A. Peripheral Neuropathy due to Vitamin Deficiency, Toxins, and Medications. Continuum. American Academy of Neurology. 2014.
- Peripheral Neuropathy Fact Sheet. Retrieved from: https://www.ninds.nih.gov/Diso...