Neuromuscular control of motion
Valerie Swanston and Carter Allen
Learning Objectives
By the end of this section, the reader will be able to:
- Define peripheral neuropathy
- Identify the causes of neuropathy
- Explain the pathophysiology of diabetic neuropathy
Neuropathy is defined as a disease of the nervous system, especially as it pertains to damage to the nerves. There are several types of neuropathy, to simplify we will think in three distinct classes, the location of the neuropathy, the type of damage being done to a nerve, and the type of nerve affected.
| Classification by damage | Classification by location | Classification by affected nerve |
| Axonal: Neuropathy that is caused by damage of the axon | Polyneuropathy: Neuropathy in multiple sites simultaneously | Motor |
| Demyelinated: Neuropathy that is caused by damage to the myelin sheath | Mononeuropathy: Neuropathy in one site. typically the result of trauma or entrapment | Sensory |
| Mixed: Neuropathy that relates both to the axon and to the myelin sheath | Distal Symmetric Polyneuropathy: neuropathy on both sides on limbs distant from the torso | Autonomic |
| Proximal polyneuropathy: neuropathy on limbs close to the torso |
Table 12-6 Classification of neuropathy based on location, type of damage, and affected nerve
Etiology Of Neuropathies
Neuropathies can occur both in the CNS and PNS. However, most of the etiologies listed here pertain to PNS, referred to as peripheral neuropathies.
Peripheral neuropathies are a group of diseases with many possible etiologies but one common result: damage to peripheral nerves. Peripheral neuropathies may be caused problems with nerves being made (i.e. congenital), maintaining nerve function (i.e. impaired perfusion, nutritional deficiencies), and direct damage by toxins (ie ethanol) or antibodies (i.e. autoimmune), and mechanical compression (i.e. entrapment).
Entrapment
The nerve is mechanically compressed by some anatomical feature which can be caused by swelling (like swelling of tendons in the wrist causing carpal tunnel syndrome) or development of a growth or cyst. Additionally it can be caused by trauma that causes internal features to put pressure on a nerve, such as a fracture or compartment syndrome, or by a penetrating injury where a foreign object is putting pressure on or severing a nerve. [1]
Accumulation of substances
Ethanol and certain drugs like chemotherapy drugs will cause toxicity and damage to nerves in high doses over time. Depending on the substance the pathology differs.[1]
Autoimmunity
Autoantibodies can be mistakenly generated to recognize some component of the nerve as foreign and proceed to attack the nerve. For example, Guillain Barre is an autoimmune peripheral neuropathy which is thought to happen as a result of identification of nerve gangliosides as foreign. Antibodies are produced which target nerve gangliosides which lead to degradation of these structures, which in turn affects nerve function. There are many types of Guillain Barre, which can manifest as either axonal or demyelinating neuropathy. [1]
Impaired perfusion
Poor blood flow to nerves will cause both decreased delivery of oxygen, water, and nutrients and accumulation of wastes to the affected nerve. There are many causes of reduced blood flow, such as atherosclerotic plaques, which affect all nerves downstream of the obstruction. The reduced oxygen delivery will force the nerve tissue to anaerobic metabolism causing toxic byproducts which will further damage the nerve.
Nutritional deficiencies.
Deficiency of vitamin B1, B6, B12 can lead to peripheral neuropathy as these vitamins are important in nerve metabolism and cellular reproduction.
Vitamin B1 is an essential factor of glucose metabolism and energy production, being an electron transporter in the citric acid cycle. Due to the fact that nerve cells consume so much energy, a lack of B1 can lead to additional oxidative damage to nerve cells specifically. B1 deficiency is also very common in diabetics and alcoholics, which may be one of the factor in diabetic neuropathy and neuropathy related to alcohol substance use disorder.
Vitamin B6 is a coenzyme involved in the production of neurotransmitters and GABA. GABA is an inhibitory chemical in the nervous system, so low GABA levels will lead to hyperactive nerve activity which can lead to nerve toxicity.
Vitamin B12 is involved in the synthesis of chemicals necessary for nerve health and for the synthesis of myelin. Therefore a Vitamin B12 deficiency can lead to decreased upkeep of nerve cell health and lack of remyelination of nerves. [8]
Exemplar to damage to the PNS: Diabetic Neuropathy
Diabetes mellitus (DM) is one of the most common chronic health complications worldwide, and has been steadily increasing in prevalence in recent years. DM is commonly classified into two major categories: type one DM is due to autoimmune causes and commonly begins in childhood whereas type two DM occurs later in life and is a multifactorial disease caused by a combination of a person’s genetics, lifestyle, and environment. You can review the detailed pathophysiology of DM in Diabetes Mellitus. In summary, both type one and type two DM are due to a deficit or lack of function or production of insulin, which is a hormone that normally reduced blood sugar. The result is chronically raised blood sugars, known as hyperglycemia.
Pathophysiology of diabetic peripheral neuropathy
Though the exact process is unknown, there are two leading hypothesis for the manifestation of diabetic neuropathy. The first is the metabolic theory: over time, hyperglycemia leads to a buildup of certain substances in the bloodstream and tissues which damage nerves, such as reactive oxygen species (ROS) and sugar alcohols. Additionally, factors in the blood such as insulin-like growth factor which promote neuronal growth are downregulated in patients with DM. The second hypothesis is concerned with impeded perfusion to nerves as a result of atherosclerosis caused by hyperglycemia. Nerves are damaged by the buildup of toxic byproducts of anoxic energy production in the nerves.[7]
Hyperglycemia and Peripheral Nerves
The most widespread type of peripheral neuropathy is that caused by exposure of nerves to a state of chronic hyperglycemia in insufficiently treated DM. The exact pathophysiology of diabetic peripheral neuropathy is unknown, and there are thought to many possible contributing factors. Over time, hyperglycemia leads to increased substances in the bloodstream and tissues which damages nerves, such as reactive oxygen species (ROS) and sugar alcohols. In addition, factors in the blood such as insulin-like growth factor which promote neuronal growth are downregulated. Damage may also occur due to dysfunction of endothelial cells within blood vessels , leading to decreased blood flow to nerves and hypoxia.
Over time, damage to peripheral nerves results in deficits to sensation, motor function, proprioception, and most commonly, pain. Neuropathic pain from diabetic peripheral neuropathy has negative consequences for a patient’s quality of life, and there are few effective therapies. It is estimated that as many as 30% of patients with DM experience neuropathic pain. Sensory deficits are a result of damage to the somatosensory nerves that detect pressure on the body’s surface and transmit action potentials to higher brain regions to create the perception of touch. A patient with damage to their somatosensory nerves may complain of numbness in their hands and feet. As the damage progresses motor nerves may become involved, causing muscle weakness and, in advanced cases, muscle atrophy.
Clinical Presentation of diabetic peripheral neuropathy:
Sensory: Tingling sensation, neuropathic pain, slower healing, and complete loss of sensation. Complete loss of sensation in patients can lead to lack of attention to injury, which can lead to the formation of ulcers and infection.
Motor: Movement becomes more difficult, get tired quicker, loss of motor function which can lead to atrophy of muscles
Autonomic: Delayed changes in heart rate during movement. slowed digestion or paralysis of the digestive tract which can have a host of repercussions. Hypoglycemia unawareness can lead people to not properly manage their blood sugar and enter hypoglycemic states.[6]
Critical thinking Exercise: Consider the following etiologies of neuropathy, and what you might think appropriate treatments may be, then reveal the answer. a) Diabetic Neuropathy b) Entrapment of nerve c)Autoimmune damage to nerve d)Nutritional deficiencies causing neuropathy
Diabetes Mellitus:
Diabetes management, better blood glucose monitoring, proper insulin administration, proper diet. Type 2 diabetics may benefit from a variety of medications to help manage their glucose levels and reduce their insulin resistance.
Entrapment:
Surgical intervention to clear the entrapment, if entrapment is caused by swelling then antihistamines, or arthritis medications can be used.
AutoImmunity
Immune suppressing medications such as corticosteroids, low dose chemotherapy drugs.
Nutritional deficiencies:
Rectifying the nutritional deficiency, which in this case would mean the supplementing of a b vitamin into the diet.
References
- Tavakoli M, Mojaddidi M, Fadavi H, Malik RA. Pathophysiology and treatment of painful diabetic neuropathy. Current Pain and Headache Reports. 2008;12(3):192–7.
- Diabetic Peripheral Neuropathy: Epidemiology, Diagnosis, and Pharmacotherapy – ScienceDirect
- Peripheral Neuropathy: Differential Diagnosis and Management | AAFP
- Peripheral Neuropathy: Evaluation and Differential Diagnosis | AAFP
- General aspects of diabetes mellitus – ScienceDirect
- Autonomic Neuropathy – NIDDKD
- Peripheral Neuropathy: Differential Diagnosis and Management
- B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin
