Peripheral Neuropathies BMS200 PDF

Peripheral Neuropathies (PN) BMS200 Dr. Lakshman, PhD Date: November 4th, 2024 Learning Outcomes Describe the pathophysiologic mechanisms underlying diabetic neuropathy, including hyperglycemia-induced metabolic changes, high insulin, microvascular damage, and oxidative stress. Descri...

Peripheral Neuropathies (PN) BMS200 Dr. Lakshman, PhD Date: November 4th, 2024 Learning Outcomes Describe the pathophysiologic mechanisms underlying diabetic neuropathy, including hyperglycemia-induced metabolic changes, high insulin, microvascular damage, and oxidative stress. Describe the etiology, risk factors, and pathophysiology of vitamin B12 deficiency neuropathy, including impaired absorption, parasite infections, dietary deficiencies, and pernicious anemia. Describe the pathophysiologic mechanism of chemotherapy-induced peripheral neuropathy Describe the association between hypothyroidism and peripheral neuropathy, including the underlying hormonal imbalances and metabolic abnormalities. Describe the role of microbial infections in the pathophysiology of peripheral neuropathy, including shingles, Lyme disease, hepatitis B and C, leprosy and HIV. Integrate the toxic and nutrient deficiency effects of alcoholism with pathophysiology of peripheral neuropathies Pre-Assessment YouTube Video: Peripheral Neuropathy and its Impact on Mental Health Peripheral Nervous System The Peripheral Nervous System (PNS) encompasses all neural structures located external to the spinal cord and the brainstem. - Cranial Nerves III-XII (I and II are special extensions of the brain) - Dorsal and ventral spinal roots - Spinal nerves and their continuation - Ganglia Type of fibers: - Somatic motor fibers - Somatic sensory - Visceral sensory - Autonomic Peripheral Nervous System The epineurium (EP) is in direct continuity with the dura mater (DM). The endoneurium (EN) remains unchanged from the peripheral nerve and spinal root to the junction with the spinal cord. At the subarachnoid angle (SA), the greater portion of the perineurium (P) passes outward between the dura mater and the arachnoid (A), but a few layers appear to continue over the nerve root as part of the root sheath (RS). At the subarachnoid angle, the arachnoid is reflected over the roots and becomes continuous with the outer layers of the root sheath. At the junction with the spinal cord, the outer layers of the root sheath become continuous with the pia mater (PM).  Peripheral Nervous System The endoneurium refers to the delicate connective tissue sheath that encases individual nerve fibers. This tissue also contains longitudinally aligned, interconnected blood vessels that provide nourishment to the nerve fibers and are susceptible to various diseases. Spinal nerves travel through constricted foramina, both intervertebral and cranial, and a subset also transverse narrow passages in the limbs, such as the median nerve within the carpal tunnel between the carpal ligament and the tendon sheaths of the flexor forearm muscles, or the ulnar nerve in the cubital tunnel. These anatomical characteristics elucidate the locations where specific nerves are vulnerable to compression, entrapment, and ischemic injury. Peripheral Nervous System Axon microtubular apparatus: The axons house a sophisticated internal microtubular structure that serves to uphold the integrity of their membranes and facilitate the transport of substances, including neurotransmitters, across considerable distances between the nerve cell body and the remote extremities of the nerve fiber. Peripheral Nervous System Types of nerve fiber damage: - Axonal degeneration - Segmental demyelination *PNS fibers are able to regenerate and remyelinate to recover function Peripheral Nervous System Axonal Degeneration: - Distal axonal degeneration – Confined to the distal portions of longer, larger nerve fibers, while neuron cell bodies and proximal axons remain unaffected. - Neuronopathy - Axonal degeneration can occur due to the demise of a neuronal cell body, as seen in conditions like autoimmune dorsal root ganglionitis. Peripheral Nervous System Axonal Degeneration: - Wallerian degeneration - Axonal degeneration takes place in a nerve beyond a point where it's been severed or compressed. If the injury occurs too close to the nerve's origin, it may allow for nerve regeneration. In Wallerian degeneration, there is deterioration of the axis cylinder and myelin that occurs beyond the location of axonal interruption (indicated by an arrow), as well as central chromatolysis.  Peripheral Nervous System Segmental Demyelination - The myelin sheath deteriorates, but the underlying axon remains functional. - Primary demyelination – direct injury to the Schwan cell or myelin sheath - Secondary demyelination – underlying axonal abnormalities - Macrophages invade the nerve and eliminate the myelin debris. - Functional recovery – degeneration is followed by Schwan cell proliferation, then remyelination Peripheral Nervous System Segmental Demyelination - Remyelinated sections display reduced internode lengths. - Hypertrophic neuropathy – repeated episodes of segmental peripheral nerve demyelination and remyelination – accumulation of supernumerary Schwan cells that encircle the axons (onion bulbs).  Peripheral Neuropathy Peripheral neuritis, also referred to as peripheral neuropathy, is a prevalent neurological condition arising from peripheral nerve damage. It can stem from nerve-related diseases or result from systemic illnesses. Most of the neuropathies are axonal – 80-90% - clinically helpful to find the etiology Demyelinating neuropathy – limited number of etiology, most likely hereditary or immunologically mediated. Large diameter sensory fibers – proprioception and vibratory sensation Smaller diameter myelinated and unmyelinated fibers – pain and temperature sensation  Peripheral Neuropathy Main Causes: - Metabolic: Diabetes mellitus, Thyroid disease - Nutritional deficiencies: Vitamin B12 deficiency - Systemic: HIV infection, Lyme disease, Hepatitis B and C, Shingles, Leprosy - Toxic: Alcoholism, Chemotherapy-induced Despite a thorough history and physical examination, the origin remains a mystery in approximately 50% of cases. Most common cause - Diabetes Peripheral Neuropathy Peripheral Neuropathy Clinical features - Muscle weakness and atrophy, sensory loss, paresthesia, pain and autonomic disfunction - Type of fibers affected: Large-diameter sensory fibers – affects position and vibration sense; Small diameter fibers – deters pain and temperature sensation - Development of symptoms: Acute (day to weeks), subacute (weeks to months), chronic (month to years) In approaching a patient with a neuropathy, the clinician has three main goals: - Identify the location - Identify the cause - Determine the proper treatment Peripheral Neuropathy Topography and Clinical Patterns Polyneuropathy – generalized process, weakness is relatively symmetrical from the beginning and progresses bilaterally; loss of reflexes in affected parts but mainly at the ankles; sensory issues and decreased sensation are most notable in the extremities' distal regions. Radiculopathy or polyradiculopathy – Neurological signs exhibit asymmetry, displaying a sporadic distribution, such as proximal involvement in one limb and distal in another. This is accompanied by weakness, areas of sensory loss, and frequently, pain within the sensory distribution of the affected nerve root. Mononeuropathy – most circumscribed form of peripheral nerve disease. Weakness and sensory loss in the territory of a single peripheral nerve. Peripheral Neuropathy Topography and Clinical Patterns: Multiple mononeuropathies (mononeuropathy multiplex) – accumulation of multiple mononeuropathies. Difficult to differentiate from polyneuropathy. Plexopathy (involvement of multiple nerves in a plexus) – brachial or lumbosacral. While only a single limb is impacted, the motor, sensory, and reflex deficits do not align with a pattern associated with multiple adjacent nerve roots or nerves. Understanding the innervation of the affected muscles at the plexus level typically helps in resolving this situation. Neuronopathy (motor or sensory) – ganglion cells are predominantly affected. Leads to symptoms and signs of sensory deficits distributed both proximally and distally. Peripheral Neuropathy Symptoms vary depending on: Motor Nerve Impairment Typically linked with muscular weakness Can encompass distressing muscle spasms, twitching Muscular wasting Diminished reflex responses  Peripheral Neuropathy Symptoms vary depending on: Sensory Nerve Impairment: Impairment of larger sensory fibers (surrounded by myelin) results in: - Reduced ability to feel touch, most notably in the hands and feet - Decreased overall sensation - Loss of reflex responses - Impairment of the sense of limb position Impairment of smaller fibers (lacking a myelin sheath) leads to: - Compromised perception of pain and temperature sensations, particularly in cases of injury from cuts, infected wounds, or angina Peripheral Neuropathy Symptoms vary depending on: Autonomic Nerve Impairment: The parasympathetic and sympathetic nerves of the peripheral nervous system (PNS) have control over various organs in the body. Autonomic nerve damage can result in a wide range of symptoms: - Impaired ability to sweat normally, resulting in heat intolerance. - Loss of control over bowel and bladder functions. - Inability to regulate blood pressure. - Malfunction of gastrointestinal muscles, which may manifest as symptoms like diarrhea, constipation, or incontinence.  Diabetic neuropathy Diabetes mellitus (DM) is linked to several forms of polyneuropathy, including distal symmetric sensory or sensorimotor polyneuropathy, a u t o n o m i c n e u r o p a t h y, d i a b e t i c n e u r o p a t h i c c a c h e x i a , polyradiculoneuropathies, cranial neuropathies, and other mononeuropathies. Risk factors contributing to the development of neuropathy encompass prolonged, inadequately managed DM, along with the coexistence of retinopathy and nephropathy.  Diabetic neuropathy Pathophysiology: Persistent high blood sugar levels are believed to boost the activity of the polyol pathway, leading to the accumulation of fructose and sorbitol within nerves, ultimately causing nerve damage. In conditions of elevated blood glucose levels exceeding 7 mmol/L, there is an augmented flow of glucose through the polyol pathway, which constitutes over 30% of glucose metabolism. The critical step that regulates the pace of the polyol pathway involves the conversion of glucose into sorbitol, a reaction facilitated by the enzyme aldose reductase (AR) and involving the consumption of reduced nicotinamide adenosine dinucleotide phosphate (NADPH).  Diabetic neuropathy Pathophysiology: Immunological mechanisms are also implicated in the onset of diabetic neuropathy. Damage results from the presence of antineural autoantibodies found in the blood of certain diabetic patients. Additionally, the presence of antiphospholipid antibodies may further exacerbate nerve damage, often in conjunction with vascular irregularities. Endoneural vascular insufficiency arises from reduced nitric oxide levels or impaired endothelial function, as well as compromised sodium/potassium-adenosine triphosphatase (Na+/K+-ATPase) activity and elevated homocysteinemia. Over time, vessel occlusion may ensue, resulting in compromised vascular permeability and hindered endoneural blood flow. Various multifaceted mechanisms implicated in the development of diabetic neuropathy include body composition, environmental influences (such as alcohol consumption, smoking, and exposure to heavy metals), and genetic predisposition.  Diabetic neuropathy Pathophysiology: Diabetic neuropathy Clinical features: - Typically presents with a "stocking-and-glove" pattern of distribution, resulting in sensory loss, abnormal sensations (dysesthesias), and often painful paresthesias, predominantly affecting the lower limbs. - Frequent symptoms include tingling, pricking, or numbness; sensations of burning or freezing pain; sharp, stabbing, or electric-like pain; heightened sensitivity to touch; muscle weakness; and a decline in balance and coordination.  Vitamin B12 deficiency neuropathy Pernicious anemia stands as the most prevalent cause of cobalamin deficiency. It is an autoimmune condition marked by the production of antibodies targeting parietal cells and intrinsic factor, resulting in a deficiency of intrinsic factor. Simultaneously, the presence of antiparietal cell antibodies triggers the onset of atrophic gastritis, accompanied by the absence of gastric acid secretion, referred to as achlorhydria. Additional triggers include dietary restrictions (common among vegetarians), gastrectomy, gastric bypass surgery, inflammatory bowel disease, pancreatic insufficiency, bacterial overgrowth, and potentially the use of histamine-2 blockers and proton pump inhibitors. Vitamin B12 deficiency causes neurological symptoms such as peripheral neuropathy and cognitive disturbances, and in severe cases, demyelination of nerve fibers. Physiologically, vitamin B12 plays a vital role in the one-carbon cycle and acts as a coenzyme for methionine synthesis, essential for DNA and RNA nucleotide production. When B12 is lacking, homocysteine accumulates, indirectly impacting folate metabolism and nerve fibers damage which contributes to peripheral neuropathy.  Vitamin B12 deficiency neuropathy B12 is also crucial for the conversion of methylmalonyl-CoA to succinyl CoA, a prerequisite for myelin synthesis and stability. In B12 deficiency, methylmalonyl- CoA leads to the formation of abnormal fatty acids, contributing to abnormal myelination or demyelination. The utilization of nitrous oxide, whether as an anesthetic agent or recreationally, can lead to the onset of acute cobalamin deficiency neuropathy and subacute combined degeneration. In a study conducted by Kalita et al. involving 66 patients with B12 deficiency neurological syndrome, nerve conduction studies revealed abnormalities in 54.5% of patients, with 22.2% displaying axonal involvement, 11.1% showing demyelinating changes, and the remainder exhibiting mixed features. Nerve biopsy indicated early-stage axonal involvement, progressing to axonal with demyelinating changes in the late stage. Vitamin B12 deficiency neuropathy (A) Acute axonal degeneration and formation of myelin ovoids evident on longitudinal sections (arrow). The myelin was preserved in these nerve fibers. (B) Focal depletion of large, myelinated fibers with prominent remyelination was seen in cases with short duration of illness (2 months). (C). Increasing fibrosis of endoneurium accompanied by fiber depletion. (D) prominent axonal regeneration was seen with increasing duration of disease (24 months). Vitamin B12 deficiency neuropathy Patients often first report numbness in their hands, which typically precedes the development of paresthesia in the lower extremities. A distinct pattern of sensory loss primarily affecting large fibers, impacting proprioception and vibration, while sparing small-fiber modalities, becomes evident. The presence of an unsteady gait, coupled with diffuse hyperreflexia and the absence of Achilles reflexes, should raise suspicions of cobalamin deficiency.  Chemotherapy-induced Peripheral Neuropathy Chemotherapy-induced peripheral neuropathy (CIPN) represents a frequently encountered adverse effect associated with various antineoplastic agents, its severity often contingent on the administered dose. CIPN has the potential to necessitate undesirable reductions in treatment dosage or even treatment discontinuation, significantly compromising the quality of life for cancer survivors. Clinically, CIPN manifests as impairments in sensory, motor, and autonomic functions, exhibiting a pattern similar to a glove and stocking distribution, primarily affecting longer axons. The pathophysiological mechanism through which chemotherapy adversely impacts neural structures, leading to chemotherapy-induced peripheral neuropathy (CIPN), is complex and encompasses a variety of factors. These factors include disturbances in microtubules, oxidative stress-induced mitochondrial damage, changes in ion channel function, injury to the myelin sheath, DNA damage, immunological responses, and neuroinflammation.  Chemotherapy-induced Peripheral Neuropathy Cisplatin, carboplatin, and bortezomib are recognized for inducing a dose-dependent sensory polyneuropathy that typically emerges several weeks after the completion of treatment, affecting at least half of the patients. The extent of histopathological changes in the peripheral nervous system is directly related to the concentration of platinum within these tissues, with the highest levels observed in the dorsal root ganglia. Paclitaxel and the more potent docetaxel, both known for inhibiting neurotubule depolymerization, are primarily used in the treatment of ovarian cancer and can produce a sensory polyneuropathy like that caused by cisplatin. Pathological studies have revealed neuronopathy and distal axonopathy, predominantly impacting large fibers. Vincristine and thalidomide may also lead to similar neuropathies, with paresthesia being the most common early symptom and the early loss of ankle jerks serving as an initial sign. Weakness typically precedes objective sensory loss to some degree.  Hypothyroidism and Peripheral Neuropathy Thyroid hormones play a pivotal role in regulating numerous functions and processes within the nervous system. While proximal myopathy is a more common association with hypothyroidism, some patients may experience neuropathic symptoms, with Carpal Tunnel Syndrome (CTS) being the most typical manifestation. In rare cases, individuals may develop a generalized sensory polyneuropathy characterized by painful paresthesia and numbness affecting both the legs and hands. One potential mechanism for the deterioration of nerve conduction parameters may be linked to weight gain, as indicated by significantly higher BMI in individuals with hypothyroidism. In hypothyroidism, there is an accumulation of mucopolysaccharides, chondroitin sulfate, and hyaluronic acid in the interstitial spaces, leading to water retention and subsequent weight gain. When these substances deposit in the tissues surrounding the nerves, they can cause compression of the peripheral nerves, resulting in swelling and nerve degeneration.  Hypothyroidism and Peripheral Neuropathy Peripheral neuropathy in hypothyroidism can arise from an energy deficit stemming from reduced nutrient oxidation, as thyroid hormones are responsible for stimulating mitochondrial respiratory activity to generate adenosine triphosphate (ATP) during aerobic metabolism. Furthermore, decreased glycogen degradation can result in the accumulation of glycogen deposits around the nerves. The metabolic changes induced by hypothyroidism can initially impair nerve functions and subsequently lead to structural alterations. In healthy individuals, thyroid hormones also enhance ATPase activity, consequently increasing Na-K pump activity. However, in hypothyroidism, the shortage of ATP and reduced ATPase and Na-K pump activity disrupts pump-dependent axonal transport, contributing to peripheral neuropathy. The reduction in thyroid hormones can additionally trigger primary axonal degeneration, characterized by axon shrinkage, disintegration of neurofilaments and neurotubules, and active axonal breakdown. The combined effects of nerve compression and axonal degeneration play a role in the development of peripheral neuropathy in hypothyroidism.  Shingles and PN - Peripheral neuropathy from herpes varicella-zoster (HVZ) infection can result from the reactivation of latent virus or a primary infection. - Two-thirds of adult infections are characterized by dermal zoster, leading to severe pain and paresthesia in a dermatomal region. Within a week or two, a vesicular rash develops in the same distribution as the pain. - Weakness in muscles innervated by roots corresponding to the affected dermatome occurs in 5–30% of patients. - About 25% of affected patients experience continued pain known as postherpetic neuralgia (PHN).. Shingles and PN During the primary infection, VZV establishes latent infection in perineuronal satellite cells of the dorsal nerve root ganglia. Viral genes continue to be transcribed during latency, and viral DNA can be detected years after the initial infection. Shingles occurs when virus replication happens in ganglion cells, travels down sensory nerves, and infects the corresponding skin area, leading to a localized, painful vesicular eruption. The risk of shingles increases with age, and most cases occur in the elderly population. Impaired cell-mediated immunity also raises the risk of VZV reactivation. Lyme disease and PN Neuropathy occurs in 10 to 15 percent of patients with Lyme disease and takes several forms. Cranial nerve involvement is common, with facial palsy being the most frequent manifestation. Other cranial nerves and spinal roots can also be affected, primarily in the cervical or lumbar region. Concurrent aseptic meningoradiculitis (characterized by a mild to moderate presence of mononuclear cells in cerebrospinal fluid) is characteristic of Lyme disease. Lyme disease can manifest with a triad of cranial nerve palsies, radiculitis, and aseptic meningitis during its disseminated phase, which typically occurs 1 to 3 weeks after a tick bite or the appearance of the typical rash. Pathological studies of peripheral nerves in Lyme disease are limited, but evidence of perivascular inflammation and vasculitic changes in small nerve vessels suggests an inflammatory response which leads to neuropathies. Hepatitis B and C and PN Peripheral neuropathy is the most common neurologic complication of hepatitis C virus (HCV) infection. The pathophysiology of the neuropathy associated with HCV is not definitively known; however, proposed mechanisms include cryoglobulin deposition in the vasa nervorum and HCV-mediated vasculitis. Cryoglobulinemia is a common extrahepatic manifestation of chronic hepatitis C infection. When cryoglobulinemia affects nerves or the vascular supply to nerves, it can lead to peripheral neuropathies. Immune-Mediated Mechanisms: Both hepatitis B and C infections can trigger an autoimmune response, leading to the production of antibodies and immune complexes. These immune responses can damage peripheral nerves and cause demyelination or axonal injury. The immune system's attack on nerve tissues can lead to neuropathies. Hepatitis B and C and PN Direct Viral Invasion: Hepatitis B and C viruses may directly infect nerve cells or nerve tissue. Although they primarily affect the liver, these viruses have been detected in other tissues and organs, including peripheral nerves. The direct viral invasion of nerve cells can lead to nerve damage and neuropathies. Toxic Metabolites: The liver plays a crucial role in metabolizing various substances in the body, including drugs and toxins. In patients with chronic hepatitis B or C, liver dysfunction can lead to the accumulation of toxic metabolites. These metabolites can damage nerve cells and peripheral nerves, leading to neuropathies. Vitamin Deficiencies: Chronic liver disease, including hepatitis B and C, can impair the absorption and utilization of essential nutrients, such as vitamins. Deficiencies in vitamins like B12 and folate can contribute to peripheral neuropathies.  Leprosy and PN Leprosy, which results from the presence of the acid-fast bacteria Mycobacterium leprae, stands as the prevailing source of peripheral neuropathy in Southeast Asia, Africa, and South America. This infectious disease primarily affects the skin and peripheral nerves. The bacterium has a predilection for nerve tissue and can directly damage peripheral nerves, leading to various forms of peripheral neuropathy. Clinical symptoms can vary from tuberculoid leprosy on one end of the spectrum to lepromatous leprosy on the other, with borderline leprosy in the middle. Neuropathies are most frequently observed in individuals with borderline leprosy. Nerve Conduction Study – Sensory are usually absent in the lower limb and are reduced in amplitude in the arms; Motor may demonstrate reduced amplitudes in affected nerves but occasionally can reveal demyelinating features. Leprosy and PN Peripheral neuropathy in Tuberculoid Leprosy is usually asymmetric and typically confined to the nerves underlying or encircling the skin lesion. This type of neuropathy is linked to a heightened level of cell-mediated immunity, which not only eliminates the bacilli in the tissue but also leads to concurrent nerve damage wherever the bacilli are present. In Lepromatous Leprosy, peripheral neuropathy progresses relatively slowly compared to other forms. It is more extensive, giving rise to bilateral, symmetrical distal polyneuropathy. Peripheral neuropathy in Borderline Leprosy results in some of the most severe deformities, as multiple nerves are affected more rapidly than in Lepromatous Leprosy. This condition may lead to irreversible nerve damage, similar to what is observed in Tuberculoid Leprosy. It is characterized by immunological instability, with an upgrading response potentially causing a transition to the tuberculoid form and a downgrading response to the lepromatous form.  HIV and PN HIV-1 can lead to various peripheral neuropathies, resulting in different clinical manifestations. They may include distal symmetric p o l y n e u r o p a t h y, a u t o n o m i c n e u r o p a t h y, l u m b o s a c r a l polyradiculopathy, mononeuropathy, or mononeuropathy multiplex. Distal symmetric polyneuropathy is the most prevalent neuropathy among HIV-positive individuals. Typically, it occurs in the later stages of AIDS and is characterized by axonal degeneration in the distal nerves. The exact cause of axonal degeneration remains unclear, and there is currently no effective treatment available. Inflammatory Demyelinating Polyradiculoneuropathy in HIV can manifest as acute (AIDP) or chronic (CIDP) in HIV-infected individuals and is immune-mediated. HIV and PN Some mononeuropathies and lumbosacral polyradiculopathies in AIDS are attributed to cytomegalovirus infection of the peripheral nervous system. Vasculitic neuropathy can present as a mononeuropathy or mononeuropathy multiplex in certain AIDS patients. Some drugs used to treat AIDS can induce toxic neuropathies. These antiretroviral-induced axonal neuropathies may clinically resemble HIV- associated distal symmetric polyneuropathy. Diffuse infiltrative lymphocytosis syndrome in AIDS may lead to acute or subacute axonal polyneuropathy. Histopathological examination of peripheral nerves may reveal perivascular CD8+ lymphocytic infiltrates. Alcoholism and PN Nutritional Deficiencies: Chronic alcohol abuse often results in poor dietary habits and impaired nutrient absorption. This leads to deficiencies in essential vitamins and minerals, including thiamine (vitamin B1), vitamin B6, vitamin B12, and folic acid. These deficiencies can contribute to nerve damage. Thiamine deficiency is strongly associated with neuropathy. Thiamine serves as an important coenzyme in carbohydrate metabolism and neuron development. Its deficiency affects the cellular structure and can cause cell membrane damage and irregular ectopic cells. Toxic Effects of Alcohol: Ethanol, the active component in alcoholic beverages, can exert direct toxic effects on nerve tissues. It disrupts nerve cell function, interferes with nerve signal transmission, and damages nerve cell membranes. Over time, these effects can lead to neuropathy. Impaired Blood Flow: Alcohol abuse can lead to poor circulation and reduced blood flow to the extremities. Inadequate blood supply deprives nerve cells of oxygen and essential nutrients, which can cause damage and contribute to neuropathy.  Alcoholism and PN Inflammation: Chronic alcohol consumption can lead to systemic inflammation, a known contributor to nerve tissue damage. Inflammatory processes within the body can harm nerve tissues and contribute to neuropathy. Metabolic Changes: Alcoholism can result in metabolic disturbances, including abnormal glucose metabolism and insulin resistance. These metabolic changes may directly contribute to nerve damage and the development of neuropathies. Oxidative Stress: The metabolism of alcohol generates reactive oxygen species (ROS) and oxidative stress. This oxidative damage to nerve cells can be a significant factor in the development of neuropathies. Alcoholism and PN Post-Assessment - MCQ 1) Which of the following statements accurately describes the pathophysiology of peripheral neuropathy associated with vitamin B12 deficiency? A) Vitamin B12 deficiency neuropathy is primarily caused by dietary deficiencies alone. B) Impaired absorption, parasite infections, and dietary deficiencies are unrelated to the pathophysiology of vitamin B12 deficiency neuropathy. C) Pernicious anemia, resulting from impaired intrinsic factor production, can contribute to vitamin B12 deficiency neuropathy. D) Vitamin B12 deficiency neuropathy is exclusively caused by parasite infections. Post-Assessment - MCQ 1) Which of the following statements accurately describes the pathophysiology of peripheral neuropathy associated with vitamin B12 deficiency? A) Vitamin B12 deficiency neuropathy is primarily caused by dietary deficiencies alone. B) Impaired absorption, parasite infections, and dietary deficiencies are unrelated to the pathophysiology of vitamin B12 deficiency neuropathy. C) Pernicious anemia, resulting from impaired intrinsic factor production, can contribute to vitamin B12 deficiency neuropathy. D) Vitamin B12 deficiency neuropathy is exclusively caused by parasite infections. Post-Assessment - MCQ 2) Which microbial infection is primarily associated with peripheral neuropathy due to direct nerve damage? A) Shingles (Herpes zoster) B) Lyme disease (Borreliosis) C) Hepatitis B virus (HBV) D) Leprosy (Hansen's disease) E) HIV (Human Immunodeficiency Virus) Post-Assessment - MCQ 2) Which microbial infection is primarily associated with peripheral neuropathy due to direct nerve damage? A) Shingles (Herpes zoster) B) Lyme disease (Borreliosis) C) Hepatitis B virus (HBV) D) Leprosy (Hansen's disease) E) HIV (Human Immunodeficiency Virus) Post-Assessment - MCQ 3) Which of the following mechanisms best explains the association between alcoholism and the pathophysiology of peripheral neuropathies? A) Elevated levels of vitamin B12 and folate B) Enhanced neuronal regeneration and repair C) Impaired metabolism of thiamine and other essential nutrients D) Increased production of nerve growth factors Post-Assessment - MCQ 3) Which of the following mechanisms best explains the association between alcoholism and the pathophysiology of peripheral neuropathies? A) Elevated levels of vitamin B12 and folate B) Enhanced neuronal regeneration and repair C) Impaired metabolism of thiamine and other essential nutrients D) Increased production of nerve growth factors References: Amato A.A., & Barohn R.J. (2022). Peripheral neuropathy. Loscalzo J, & Fauci A, & Kasper D, & Hauser S, & Longo D, & Jameson J(Eds.), Harrison's Principles of Internal Medicine, 21e. McGraw Hill. Chapter 446: Peripheral Neuropathy Misra UK. Clinical Neurophysiology: Nerve Conduction, Electromyography, Evoked Potentials. 3rd ed. Elsevier; 2014. Rakel D. Integrative Medicine. 4th ed. 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Clinical, nerve conduction and nerve biopsy study in vitamin B12 deficiency neurological syndrome with a short-term follow-up. Nutr Neurosci. 2014;17(4):156-163. doi:10.1179/1476830513Y.0000000073 Gupta N, Arora M, Sharma R, Arora KS. Peripheral and Central Nervous System Involvement in Recently Diagnosed Cases of Hypothyroidism: An Electrophysiological Study. Ann Med Health Sci Res. 2016;6(5):261-266. doi:10.4103/amhsr.amhsr_39_16 Areti A, Yerra VG, Naidu V, Kumar A. Oxidative stress and nerve damage: role in chemotherapy induced peripheral neuropathy. Redox Biol. 2014;2:289-295. Published 2014 Jan 18. doi:10.1016/ j.redox.2014.01.006