Polyneuropathy

Polyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. The clinical presentation varies by etiology as well as classification of the polyneuropathy, but generally manifests as sensorimotor disturbances ( pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, paresthesia, numbness, weakness, and loss of coordination and balance), which have a gradual onset and progressive course. Distal nerves are affected most commonly, but the disease process may progress proximally with time or progression of the underlying etiologic disease entity. Diagnosis is made clinically, but laboratory studies, electrodiagnostic testing, and/or nerve biopsy may be required in some cases. Management varies depending on the etiology.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition and terminology

Polyneuropathy is part of a spectrum of neurologic disorders affecting the integrity and function of the peripheral nerves. The nomenclature corresponds with the number of nerves involved:

  • Neuropathy: This is the general term; it may refer to any disorder of a nerve or nerves affecting the CNS or the peripheral nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System (PNS).
  • Mononeuropathy Mononeuropathy Neuropathy is a nerve pathology presenting with sensory, motor, or autonomic impairment secondary to dysfunction of the affected nerve. The peripheral nerves are derived from several plexuses, with the brachial and lumbosacral plexuses supplying the major innervation to the extremities. Mononeuropathies affect a single nerve. Mononeuropathy and Plexopathy: single nerve affected
    • Often due to a focal process: 
      • Trauma
      • Entrapment
      • Compression
    • Examples include:
      • Carpal tunnel syndrome Carpal Tunnel Syndrome Carpal tunnel syndrome (CTS) is a complex of signs and symptoms caused by compression of the median nerve as it crosses the carpal tunnel. Presentation is with pain and paresthesia of the dermatomal target tissues innervated by the median nerve as well as weakness and atrophy of the nerve's myotomal targets. Carpal Tunnel Syndrome
      • Radiculopathy
  • Mononeuropathy Mononeuropathy Neuropathy is a nerve pathology presenting with sensory, motor, or autonomic impairment secondary to dysfunction of the affected nerve. The peripheral nerves are derived from several plexuses, with the brachial and lumbosacral plexuses supplying the major innervation to the extremities. Mononeuropathies affect a single nerve. Mononeuropathy and Plexopathy multiplex (also known as multifocal neuropathy): several nerves (or nerve trunks) are affected by a common etiology, usually in an asymmetric fashion.
    • Often due to a more expansive focal process (may or may not be systemic):
      • Compression
      • Ischemia
      • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
    • Examples include:
      • Vasculitis
      • Tumor invasion
  • Polyneuropathy: numerous nerves are affected, generally in a symmetrical, distal-to-proximal fashion (glove-and-stocking distribution).
    • Due to a systemic process:
      • Autoimmune processes
      • Toxic/metabolic processes
    • Examples:
      • Diabetic neuropathy
      • Alcoholic neuropathy
  • Peripheral neuropathy: a more general term that may refer to a mononeuropathy, mononeuropathy multiplex, polyneuropathy, or radiculopathy.

Epidemiology

  • The overall prevalence of polyneuropathies is 2.5%–5% in the general population; prevalence increases with advancing age.
  • The number of causes of polyneuropathies is estimated at approximately 100.
  • Diabetes is the most common identifiable cause of polyneuropathy.
  • In approximately 20%–30% of individuals, the cause is undetermined (also known as idiopathic polyneuropathy).
  • Women > men (1.5–2 to 1)
  • More common in Western civilizations than in developing countries

Classification

Polyneuropathies may be classified on the basis of:

  • Anatomy: location of lesion 
  • Etiology: 
    • Axonopathies 
    • Demyelinating diseases 
    • Mixed lesions 
  • Types of impairment:
    • Sensory
    • Motor
    • Sensorimotor
    • Autonomic 
  • Clinical progression:
    • Acute
    • Subacute
    • Chronic
    • Relapsing

Etiology and Pathophysiology

Etiology

There are numerous causes of polyneuropathy; however, diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus (diabetic neuropathy) and chronic alcohol use (alcoholic neuropathy) are responsible for almost 50% of all polyneuropathies. Most cases are likely multifactorial. Therefore, the various etiologic entities will be presented as both risk factors and distinct etiologic causes.

  • Diabetes:
    • Occurs in approximately 50% of individuals with types 1 and 2 diabetes
    • Primarily axonal in nature
    • Metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome likely poses some degree of risk.
    • Sensory symptoms more common than motor symptoms:
      • Begins in lower extremities
      • Upper-extremity involvement presents later.
    • Neuropathic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain may be disabling.
    • Sensory loss compounds risk of fall and progression of diabetic wounds.
    • Autonomic neuropathy is often present.
  • Alcohol abuse:
    • Occurs in approximately 40% of individuals with chronic alcoholism
    • Primarily axonal in nature
    • Sensory symptoms and motor weakness:
      • Begins in lower extremities
      • Upper-extremity involvement presents later.
    •  Autonomic neuropathy is often present.
    • Contributing factors:
      • Direct/indirect toxic effects of alcohol
      • Thiamine deficiency
      • Inability to metabolize thiamine in the presence of alcohol
  • Family history:
    • Charcot-Marie-Tooth (CMT) disease is the most common inherited polyneuropathy:
      • Presents with polyneuropathy, high arches, hammer toes, and wasting of intrinsic muscles of the feet.
      • Due to mutations in the CMT gene(s), which may lead to axonal, demyelinating, or mixed polyneuropathy.
    • Friedreich ataxia is an inherited condition that causes progressive weakness and neurologic changes; it usually presents in late childhood.
  • Chronic inflammation:
    • Autoimmune disease:
      • Guillain-Barré syndrome Guillain-Barré syndrome Guillain-Barré syndrome (GBS), once thought to be a single disease process, is a family of immune-mediated polyneuropathies that occur after infections (e.g., with Campylobacter jejuni). Guillain-Barré Syndrome (GBS) is a rapid-onset progressive sensorimotor polyneuropathy that peaks in intensity in as few as 2–4 weeks, often following bacterial or viral infection that may resolve or persist.
      • Chronic inflammatory demyelinating polyneuropathy (CIDP) is a more gradual-onset version of GBS that is more likely to persist.
    • Vasculitis
  • Toxic exposure:
    • Chemotherapy:
      • Multiple neurotoxic chemotherapeutic agents
      • Most common are taxanes, platinums, and vinca alkaloids.
    • Drugs:
      • Fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones
      • Statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins
      • Amiodarone
  • Vitamin deficiencies:
    • B12
    • Folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12
    • Thiamine
  • Malignancy
  • Renal disease/failure
  • Liver disease/failure
  • Deposition disease:
    • Cryoglobulinemia
    • Amyloidosis Amyloidosis Amyloidosis is a disease caused by abnormal extracellular tissue deposition of fibrils composed of various misfolded low-molecular-weight protein subunits. These proteins are frequently byproducts of other pathological processes (e.g., multiple myeloma). Amyloidosis
  • Hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism
  • Critical illness
  • Infection:
    • HIV
    • Lyme disease Lyme disease Lyme disease is a tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. Lyme disease is transmitted by the black-legged Ixodes tick (known as a deer tick), which is only found in specific geographic regions. Patient presentation can vary depending on the stage of the disease and may include a characteristic erythema migrans rash. Lyme Disease

Pathophysiology

The following description is of the pathophysiology of diabetic polyneuropathy, as its pathogenesis is the most studied and most well understood. Many of the pathologic processes are common to other forms of polyneuropathy. Key distinguishing characteristics of other entities will be pointed out in the discussions of those entities.

  • Presents most commonly as a distal, symmetrical, sensorimotor polyneuropathy: 
    • Sensory manifestations more common than motor manifestations
    • A “dying back” phenomenon is often observed, progressing more proximally with time.
  • Primarily due to axonal degeneration with varying degrees of demyelination
  • May affect peripheral (primarily sensory) and autonomic nerves:
    • Distal portions of sensory and autonomic nerves are unmyelinated
    • Lack of myelination creates susceptibility to damage
  • Underlying mechanisms include:
    • Chronic inflammation:
      • Chronic hyperglycemia and hyperlipidemia overwhelm metabolic machinery and lead to increased circulating reactive oxygen species.
      • Damaged intracellular machinery may lead to impaired protein synthesis, cellular regeneration and repair, axonal transport of intracellular products, etc.
    • Exposure to circulating toxins:
      • Hyperglycemia
      • Glycosylated end products
      • Reactive oxygen species
    • Microvascular ischemia:
      • Morphologic abnormalities are observed in the vasa nervorum.
      • Endothelial dysfunction tips the balance of vascular autoregulation toward vasoconstriction.
      • Endothelial dysfunction is associated with increased local levels of cytokines and interleukins Interleukins Interleukins are a type of cytokines (signaling proteins) that communicate messages between different parts of the immune system. The majority of interleukins are synthesized by helper CD4 T lymphocytes along with other cells such as monocytes, macrophages, and endothelial cells. Interleukins.
      • Impairs delivery of oxygen and nutrients to the distal nerves
    • Impaired mitochondrial transport:
      • Mitochondria generate the metabolic energy for the cell.
      • Mitochondria must traverse the entire length from cell body to the end of the axon.
      • More distal sections of axon most likely to be deficient in mitochondria
      • Decreased availability of cellular energy to these vulnerable sections
The structure of a neuron

The structure of a neuron allows demonstration of the different areas that may be affected in polyneuropathies.

Image by Lecturio.

Clinical Presentation

History

  • Onset of presentation is usually insidious and progressive.
  • Glove-and-stocking sensorimotor disturbances in the extremities:
    • Usually lower extremities (feet) are affected first.
    • Longest nerve fibers are primarily affected.
    • Proximal progression and involvement of the upper limbs occurs over time.
  • Description of pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain with neuropathic features:
    • Radiating
    • Lancinating
    • Shooting
    • Burning
    • Stinging 
  • Hypoesthesia (loss of sensation):
    • Often described as numbness
    • Predisposes to:
      • Development of lower-extremity wounds (unnoticed by the individual)
      • Falls (combination of loss of sensation, position sense, and weakness)
    • Loss of vibratory sensation
    • Loss of position sense and proprioception
  • Paresthesia:
    • Tingling
    • Crawling sensation
    • Foreign-body sensation (“feels like I am wearing socks”)
    • Heaviness
  • Weakness:
    • Perceived loss of strength in the affected limb(s):
      • May or may not manifest as a loss of gradable strength on exam 
      • May manifest with symptoms of gait abnormality
    • Progressive inability to control limb movements (combination of sensory loss, proprioceptive loss, and motor weakness)

Signs of damaged motor nerve fibers

  • Gait abnormalities
  • Distal flaccid paresis ( foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot flexor paresis)
  • Loss of distal reflexes (Achilles tendon reflex)
  • Fasciculations
  • Muscle cramps
  • Muscle atrophy
  • Varying degrees of foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot drop (peroneal neuropathy) is common in the lower limbs with or without a compressive component.
  • Restless legs

Signs of damage to the autonomic nervous system Autonomic nervous system The ANS is a component of the peripheral nervous system that uses both afferent (sensory) and efferent (effector) neurons, which control the functioning of the internal organs and involuntary processes via connections with the CNS. The ANS consists of the sympathetic and parasympathetic nervous systems. Autonomic Nervous System

  • Vascular dysregulation with distal cyanosis 
  • Dry mouth
  • Orthostatic hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
  • Hyperhidrosis, anhidrosis
  • Trophic changes in the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and nails

Diagnosis

History

Take a complete history, including:

  • Past medical history
  • Family history
  • Exposure to drugs and toxins
  • Substance use history

Physical exam

Full neurologic exam to discover any focal neurologic deficits:

  • Sensory exam:
    • Light touch (performed with a standard Semmes-Weinstein monofilament):
      • Inability to feel the monofilament in the affected limbs is correlated with “loss of protective sensation.”
      • Loss of protective sensation is correlated with increased risk of wounds and/or ulcerations that may go unnoticed → increased risk of limb amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation
    • Pressure 
    • Vibration
    • 2-point discrimination
    • Position sense
  • Motor exam:
    • Grade strengths I–V
    • Screen for gait abnormalities.
    • Note quality of muscle tone Muscle tone The state of activity or tension of a muscle beyond that related to its physical properties, that is, its active resistance to stretch. In skeletal muscle, tonus is dependent upon efferent innervation. Skeletal Muscle Contraction and bulk.
    • Note presence of fasciculations and spasm.
    • Check deep tendon reflexes (DTRs).

Laboratory studies

  • Metabolic labs (screen for diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus and malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries):
    • Fasting glucose
    • HbA1c to screen for diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
    • CMP: 
      • Includes renal function (creatinine, GFR, BUN)
      • Includes liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver function (AST, ALT)
    • Vitamin B12, folate, thiamine levels for vitamin deficiency
    • Methylmalonic acid in the urine is an indirect marker of vitamin B12 deficiency.
  • Inflammatory markers:
    • Erythrocyte sedimentation rate
    • CRP
    • Antinuclear antibody test 
  • Infectious disease markers:
    • HIV
    • Hepatitis C Hepatitis C Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C virus can cause both acute and chronic hepatitis, ranging from a mild to a serious, lifelong illness including liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C Virus
    • Lyme disease Lyme disease Lyme disease is a tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. Lyme disease is transmitted by the black-legged Ixodes tick (known as a deer tick), which is only found in specific geographic regions. Patient presentation can vary depending on the stage of the disease and may include a characteristic erythema migrans rash. Lyme Disease 
    • EBV
    • Rapid plasma reagin
  • CBC
  • Immunoelectrophoresis for amyloidosis and other protein-related disorders
  • Testing for heavy metal toxicities: 
    • Heavy metals
    • Lead
    • Arsenic
    • Pesticides
  • Thyroid function test for hypothyroidism
  • Molecular genetic tests to evaluate for inherited disorders

Imaging

  • Magnetic resonance neurography:
    • Allows direct imaging of the nerves
    • More useful for proximal than for distal lesions
  • Magnetic resonance imaging if compression of nerve is suspected.

Other procedures

  • Electrodiagnostic studies:
    • Includes electromyography (EMG) and nerve conduction velocity testing 
    • Tool to distinguish between axonal, demyelinating, and axonal–demyelinating diseases:
      • In demyelinating diseases, the nerve conduction velocity is reduced.
      • In axonal diseases, the overall muscle action potential is reduced.
  • Nerve/muscle biopsy:
    • Reserved for if the cause is unknown after extensive workup.
    • Usually used for inflammatory processes or storage diseases 

Management

General concepts

  • After confirming the etiology, manage the underlying cause of disease:
    • Glycemic control
    • Weight loss
    • Alcohol cessation
    • Stop/modify offending toxic agents
  • Next steps include:
    • Prevention of further damage
    • Pain management Pain Management Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Pain is a subjective experience. Acute pain lasts < 3 months and typically has a specific, identifiable cause. Pain Management
    • Restoration of nerve and muscular function
    • Weight loss is often useful, along with exercise
    • Assistive devices:
      • Walker
      • Cane
      • Ankle– foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot orthotic(s) for foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot drop
    • Working with a physical therapist or occupational therapist is useful for many people.

Pharmacotherapy

Pain management Pain Management Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Pain is a subjective experience. Acute pain lasts < 3 months and typically has a specific, identifiable cause. Pain Management:

  • Anticonvulsants are 1st-line agents:
    • Gabapentinoids are most commonly used:
      • Gabapentin (multiple formulations available)
      • Pregabalin
    • Other anticonvulsants may be used (e.g., valproic acid, carbamazepine).
  • Antidepressants may also be 1st- or 2nd-line agents:
    • Serotonin–norepinephrine reuptake inhibitors (SNRIs): 
      • Venlafaxine
      • Duloxetine
    • Tricyclic antidepressants Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants
      • Amitriptyline
      • Clomipramine
  • Topical agents may be useful in cases with limited areas of pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain or as an adjuvant:
    • Capsaicin
    • Compounded topical preparations 
  • Muscle relaxants for cramps/spasms: 
    • Baclofen
    • Cyclobenzaprine
    • Quinine sulfate products

Disease-modifying therapies:

  • IV immune globulin:
    • May be useful for inflammatory/autoimmune neuropathies
    • Infusion therapies are administered in a monitored setting (i.e., certified infusion center).
  • There are no approved disease-modifying therapies for diabetic polyneuropathy.

Management of selected types of polyneuropathy

  • Diabetic polyneuropathy: 
    • Normalize metabolism with tight glucose control
    • Compliance with strict diet and exercise 
    • Pain management Pain Management Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Pain is a subjective experience. Acute pain lasts < 3 months and typically has a specific, identifiable cause. Pain Management with gabapentin
    • Physical rehabilitation for restoration of motor function
  • Alcoholic polyneuropathy:
    • Abstinence from alcohol 
    • Supplementation of vitamin B complex
  • Critical illness polyneuropathy (CIP):
    • Creates difficulty in individuals weaning off mechanical ventilation
    • Management is supportive.
    • Once individuals recover from the severe underlying disease, complete remission from CIP is possible and common. 

Clinical Relevance

  • Type 2 diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus: metabolic disease characterized by hyperglycemia due to dysfunction of regulation of glucose metabolism by insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin secondary to insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance. Type 2 diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus is associated with obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity. Because there is no definitive cure, management centers around close monitoring and maintenance of blood glucose levels. Complications of type 2 diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus include retinopathy, nephropathy, and neuropathy. Neuropathy typically presents many years into the disease course.
  • Guillain-Barré syndrome Guillain-Barré syndrome Guillain-Barré syndrome (GBS), once thought to be a single disease process, is a family of immune-mediated polyneuropathies that occur after infections (e.g., with Campylobacter jejuni). Guillain-Barré Syndrome (GBS): immune-mediated polyneuropathy that may occur after Campylobacter Campylobacter Campylobacter ("curved bacteria") is a genus of thermophilic, S-shaped, gram-negative bacilli. There are many species of Campylobacter, with C. jejuni and C. coli most commonly implicated in human disease. Campylobacter jejuni infection. Classically, this disease is associated with a recent outdoor vacation or trip. The extracellular lipooligosaccharide of the bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview is similar to that of the peripheral nerves, which are targeted by antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins. This syndrome is characterized by acute neuromuscular paralysis that is symmetric and ascending in nature. Guillain-Barré syndrome Guillain-Barré syndrome Guillain-Barré syndrome (GBS), once thought to be a single disease process, is a family of immune-mediated polyneuropathies that occur after infections (e.g., with Campylobacter jejuni). Guillain-Barré Syndrome can progress into respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure, requiring prolonged hospitalization. Management is mostly supportive and may require either plasma exchange or IV immunoglobulin. 
  • Alcohol use disorder Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. Alcohol Use Disorder (AUD): excessive consumption of alcohol leading to impaired daily functioning. Alcohol use disorder Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. Alcohol Use Disorder affects almost every part of the human body and has serious impacts on a person’s mental and physical health. Some complications of chronic AUD include hepatitis, pancreatitis, and neuropathy. Alcohol use disorder Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. Alcohol Use Disorder can be managed with psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy as well as medications; however, prognosis is usually poor, with high rates of relapse and complications. 
  • Critical illness polyneuropathy and myopathy: syndromes that occur in roughly 70% of critically ill individuals with sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock and multiorgan failure. This illness is characterized by diffuse, flaccid muscle weakness. Respiratory muscles and limbs are usually affected. Diagnosis requires EMG as well as nerve conduction studies. Management is supportive, and prognosis is positive if individuals recover from the severe underlying illness.

References

  1. Zhou, C., et al. (2014). Critical illness polyneuropathy and myopathy: a systematic review. Neural Regeneration Research 9:101–110. https://doi.org/10.4103/1673-5374.125337
  2. Rutkove, S. (2020). Overview of polyneuropathy. UpToDate. Retrieved October 17, 2021, from https://www.uptodate.com/contents/overview-of-polyneuropathy
  3. Feldman, E. (2020). Pathogenesis of diabetic polyneuropathy. UpToDate. Retrieved October 17, 2021, from https://www.uptodate.com/contents/pathogenesis-of-diabetic-polyneuropathy
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