Peripheral Neuropathy
P.K. Ghatak, MD.
The part of the nervous system that lies outside the Brain and Spinal Cord is known as the Peripheral Nervous System. It consists of both somatic and autonomic divisions; and each division consists of sensory and motor nerves. There are two sets of peripheral nerves. One, those arise from the brain called Cranial Nerves- 12 pairs in number and two, those arise from the spinal cord called Spinal nerves- 31 pairs in number. All the spinal nerves are mixed nerves, made up of both sensory and motor fibers; whereas the cranial nerves can be pure motor, sensory or mixed containing both motor and somatic sensory and special senses. These are smell, vision, hearing and position of the head in space and taste sensations.
This anatomical characteristics require a thorough basic knowledge of the nervous system in order to fully comprehend the clinical spectrum of peripheral neuropathy.
The diagram below illustrates the anatomy of a spinal nerve formation and shows sympathetic fibers being carried by a spinal nerve.
Symptoms of Peripheral Neuropathy.
The development and progression of symptoms of peripheral neuropathy are depended on the cause.
Using diabetic neuropathy as an example, because it is the most common cause of Peripheral Neuropathy.
The symptom begins with numbness and loss of light touch sensation in the feet and progresses upwards in the legs and thighs. It is slow but progressive and generally bilateral and often symmetrical in distribution. Gradually the pain, pressure, vibration and temperature sensations are lost. Patients frequently fall to the ground because of a lack of sensation and develop progressive osteoarthritis of knees and ankles, due to the absence of pain from these joints. Similar changes also happen in fingers and hands. Frequently things fall off the hand and the burning of fingers are common occurrence. Others develop burning pain, which is felt more intensely at night in bed.
Loss of motor function of eyes results in double vision and difficulties in reading and writing. Wasting of muscles and loss of muscle mass, easy fallibility and generalized weakness follow. Autonomic functions abnormality manifests as decreased or absence of secretion from all glands, lack of sweating, hypotension, lightheartedness, dry mouth and eyes, difficulty in urination, impotency in males and constipation.
Causes of Peripheral Neuropathy:
Besides diabetes mellitus, the following are important causes:- Chronic alcoholism, Vitamin B1, B6, and B12 deficiency, Malignancy, Infection and Reactivation of dormant pathogens, direct injury to the nerves in accidents and burns, Systemic illnesses, Pressure on nerves by abnormal metabolite, Autoimmune diseases, Congenital, Poisoning, Side effects of prescribed medication, and idiopathic.
Chronic alcoholism. Malnutrition and vitamin deficiencies are components of alcoholism. Nerve fibers require a healthy myelin sheath in order to propagate nerve impulses; the myelin sheath is damaged by alcohol. Eventually, permanent damages occur in the nerve fibrils. Initial symptoms are double vision due to lateral rectus muscle paralysis of the eyes and difficulty in focusing for reading. Pain in arms and legs and numbness are the next common symptoms.
Vitamin B Deficiency. Vitamins B1, B6 and B12 are commonly referred to as nerve vitamins. RBC B12 level corresponds with nerve tissue B12 level, which is more accurate than the serum B12 level. Numbness and pins and needles are common symptoms and generally isolated nerves of one leg are common and if both legs are affected the areas are not symmetrical. Severe vitamin B1 deficiency is well known as Beriberi.
Infection of the peripheral nerves. The recent COVID-19 epidemic, and HIV/AIDS in the preceding years, recorded a high incidence of neuritis developed in various areas of the body. Lyme disease is another common cause of direct nerve infection. Leprosy is still a leading case of disabling and deforming disease due to direct invasion of peripheral nerves by Mycobacteria leprae in the South Asian countries. Reactivation of dormant chicken pox virus produces Shingles. It is an extremely painful vesicular eruption of the skin, Serious eye problems result when the 5th Cranial nerve is infected, ophthalmic branch lesions can produce blisters of the involved skin dermatome and cornea blisters can produce blindness.
Systemic diseases. Systemic disease is a process where every organ and tissue is vulnerable to the same pathological changes. Vasculitis is the worst disease in this aspect. Many peripheral nerves develop vasculitis at various locations, one at a time or several simultaneously. Both sensory and motor nerves are commonly involved. Nerve fibers derive nutrition from tiny arterial branches from muscular arteries, and vasculitis cuts arterial supply to the nerve fibers.
Collagen vascular diseases like Lupus, Sjorgen syndrome and occasionally Rheumatoid arthritis are examples of neuropathy due to many pathological processes affecting peripheral nerves.
Other systemic diseases, for example, Whipple disease of the intestine, prevents fat soluble vitamins A, D, E and K absorption from the small intestine. These vitamins are required for the maintenance of the Myelin sheath of the nerves, deficiency of these vitamins causes neuropathy.
Malignancy. Cancers of solid organs, Myeloma, Leukemia and Lymphoma produce peripheral neuropathy. In adults developing neuropathy for the first time, otherwise in good health, the malignancy becomes an important issue and must be excluded without further delays. Cancer cells generally infiltrate adjoining tissues and the nerve fibers that are contained in it. Relentless pain is the main symptom. Myeloma produces abnormal proteins in large amounts. These protein molecules are deposited in and around the nerve-vascular bundles and produce neuropathy. With the growth of myeloma, the bone marrow is over stretched and erosion of bone at the growing site produces deep-seated nagging pain over the spinal column in addition to distant neuropathy. Certain cancers secrete polypeptides which can interfere with neurotransmitters and produce numbness and pain.
Lymphomas are bulky tumors, they put pressure on the nearby nerves. Lymphoma can also produce antibodies which can mistakenly attack nerve tissue, causing an autoimmune disease.
Chronic Inflammatory Demyelinating Polyneuropathy is an autoimmune disease. It is rare but recurrent. The offending agent or antigen is unknown and responds poorly to usual therapy. Efgartigimod, a monoclonal antibody, produces rapid response but the effects do not last long.
Carpal tunnel syndrome. The median nerve at the front of the wrist has to negotiate through a tight bony passage between small wrist bones and any extra materials like amyloid, inflammatory cells in Sarcoidosis, or mucoproteins in Hypothyroidism usually accumulate in and around the median nerve and produce pain and weakness of fingers and thumb and claw hands develop in late cases. Carpal tunnel syndrome may be unilateral or bilateral.
Congenital. Acute Intermittent Porphyria is an autosomal dominant inherited disorder due to the absence of one or many of the 8 enzymes required for Heme synthesis. Heme is a part of Hemoglobin. This results in the accumulation of intermediate metabolites, chief among them is delta Aminolevulinic acid. Intermittent attacks consist of – (a) paralysis of limbs and muscles of respiration, and acute pain and (b) eruption of blisters on sun-exposed skin, and various GI symptoms including abdominal pain and (c) Hallucination, seizures, and psychosis. Attacks are precipitated by certain medications and food or starvation. An attack usually lasts 7 to 10 days, but attacks are recurrent.
Poisoning. Lead and Mercury are poison to humans, specially if it happens in a growing child. Lead pipes and paints are the primary sources of lead poisoning. Shrimp farming and bottom feeder fish cultures are the chief sources of mercury poisoning. FDA has successfully limited other sources of mercury poisoning by regulating its use in industries and laboratories. In lead poisoning, the paralysis of motor nerve fibers of the extensors of the wrist and ankles is primarily affected, resulting in wrist drop and foot drop. Motor skill in the developing child is markedly limited.
Mercury binds with sulfhydryl group on proteins and paralyzes enzymes and disrupts calcium movements in the neurons and myelin sheaths. Disruption of normal function produces neuropathy. The main features of mercury poisoning are tremors of fingers, eyelids and lips, numbness of hands and feet, incoordination of movements and ambulatory difficulties and memory.
Autoimmune inflammatory neuropathy. Guillain-Barré syndrome is an autoimmune disease, acquired in most cases after a viral infection, but other infections like Mycoplasma can produce this acute life-threatening illness. An acute inflammatory demyelinating polyradiculopathy and causes paralysis of the lower part of the body then rapidly progresses upwards and paralyzes the Diaphragm and other respiratory muscles. In some others, the paralysis starts in the eye muscles and muscles of the eyelids and lips, then spreads.
Peripheral neuropathy in adults must be investigated thoroughly, specially in an otherwise healthy individual, due to the possible presence of a developing malignancy. Just making a diagnosis of neuropathy is too simplistic and inadequate without finding the etiological cause in that individual.
Footnotes:- many diseases are very briefly mentioned here, one may read more about them by finding previous blogs on humiheath.blogspot.com
