Peripheral Neuropathy Quiz

BMS 200 - Cardiology 9

• Course covers pericarditis, myocarditis, endocarditis, and orthostatic/vasovagal syndromes.

Outcomes

• Students need to describe the pathogenesis, major clinical features, and prognosis of acute, subacute, and constrictive pericarditis.
• Describe pathogenesis, major clinical features, and prognosis of both infectious and non-infectious forms of myocarditis.
• Describe pathogenesis, major clinical features, and prognosis of acute and subacute bacterial endocarditis.
• Outline biology, life cycle, major virulence factors, diagnosis, and clinical manifestations of Borrelia burgdorferi, trypanosoma cruzi, and ehrlichia chaffeensis infections.
• Examine the biology, virulence factors, diagnosis, and clinical manifestations of coxsackie virus, echovirus, and COVID-19 coronavirus infections.
• Evaluate the HACEK group of bacteria, staph epidermidis, and viridans streptococci, describing the biology, virulence factors, diagnosis, and clinical manifestations.
• Describe the pathophysiology of Postural Tachycardia Syndrome (POTS) and its associated clinical features.

Inflammation of the Structures of the Heart

• Acute, subacute, and constrictive pericarditis.
• Infectious causes of myocarditis.
• Overview of inflammatory causes.
• Acute and subacute bacterial endocarditis.

Pericardium - Recall

• The pericardium is a double-walled sac surrounding the heart and the roots of the great vessels.
• It has a fibrous layer (tough, inelastic) and a serous layer (thinner, mesothelium).
• The visceral layer is also known as the epicardium and the parietal layer.

Normal pericardial Fluid

• 15-50 mL

Acute Pericarditis

• Most common cause of acute chest pain.
• Commonly seen in younger patients.
• Causes include Viral causes – coxsackie virus A and B, echovirus, other less common organisms, bacterial infections, rheumatic fever, autoimmune disorders, and cancer.
• Kidney disease (CKD) can also increase pericardial fluid.

Acute Pericarditis – General Pathogenesis

• Fluid buildup (pericardial effusion) can occur due to long-term conditions like heart failure (CHF) or kidney disease (CKD).
• Pericarditis inflammation is often mild with this type of effusion.
• Fibrinous inflammation is a specific type of pericarditis inflammation where fibrin is deposited on the heart's surface, making it appear shaggy.

Acute Pericarditis – Clinical Features

• Chest pain, which is often severe, sharp, and pleuritic (associated with pleural inflammation).
• Pain is usually better while sitting up and leaning forward than lying down.
• Elevated troponin and ECG results can be confusing and may not always indicate cardiac issues.
• Pericardial friction rub, a sound resembling a scratchy or raspy sound, may be heard during systole and diastole.
• More fluid accumulation can cause the friction rub to be transient.

Acute Pericarditis – ECG & Auscultatory Findings

• ST elevation is not indicative of a heart attack (MI) if it is present across multiple leads. This is not typical for an MI, where it is present in only one specific area related to the blocked artery.

Acute Pericarditis - Diagnosis, Treatment, Prognosis

• Echocardiography is the primary diagnostic method.
• CT or MRI can also be utilized to gather more detailed information about pericardial thickening.
• Most cases of idiopathic or viral pericarditis are self-limiting and respond well to anti-inflammatory medications.
• High-dose aspirin, NSAIDs, colchicine, and steroids may be indicated depending on the cause.
• Recurrences may be possible depending on the cause.
• Complications can include constrictive pericarditis, recurrence, or cardiac tamponade.

Acute Pericarditis - Additional Info

• Most acute pericarditis cases are presumed viral in nature (an organism is not reliably found).
• Atypical presentation includes a fever accompanied by sharp chest pain within 10-12 days of infection.
• The condition may progress into acute pericarditis or constrictive pericarditis (symptoms or effusions persist for 4-6 weeks).
• Large effusions (2L or more) may present and cause tamponade without being rapidly fatal.
• Pericardiotomy can be needed to drain the excess fluid if recurrences occur.

Constrictive Pericarditis

• Chronic pericardial scarring, a common outcome of acute pericarditis, can cause constrictive pericarditis or even calcification.
• This constriction limits cardiac filling.
• Causes include TB pericarditis, post-traumatic/surgical/radiation pericarditis, neoplastic disease, CKD, or idiopathic pericarditis.
• Symptoms may mimic restrictive cardiomyopathy; these include congestion throughout the venous system (despite relatively preserved stroke volume, fatigue, neck vein distension and hepatosplenomegaly)
• Diagnosed with ultrasound (US) or magnetic resonance imaging (MRI).
• Treatment typically involves pericardial resection.

Pericardial Tamponade

• Severe pericardial fluid accumulation can lead to a rapid onset fatal condition called cardiac tamponade. This is an obstructive shock state.
• Causes include ruptured ventricular aneurysm, severe acute pericarditis, cardiac trauma, and aortic dissection.
• Clinical features include hypotension, muffled heart sounds, and distended neck veins.
• Treatment involves urgent fluid removal via pericardiocentesis.

Myocarditis – Inflammation of the Heart Muscle

• Potential consequences include dilated cardiomyopathy, heart failure, conduction blocks (or predisposition to ventricular tachycardia), and even sudden cardiac death (likely due to dysrhythmias).
• Common causes include viral infections like coxsackievirus and echovirus and Lyme disease.

Myocarditis – Pathogenesis

• Infection can cause damage by invading myocytes and causing lysis.
• Early inflammation associated with infection triggering the release of cytokines, can depress myocardial function, but not directly cause damage.
• Adaptive immune response can also contribute to myocarditis through granuloma formation, prolonging cytokine release and increasing cardiac and ECM damage/dilation.

Myocarditis - Clinical Features, Diagnosis

• Acute viral myocarditis may present as acute heart failure.
• Symptoms may also appear like chest pain (possible pericarditis or acute myocardial infarction).
• Common symptoms may include progressive dyspnea and weakness (appearing few days or weeks after a viral syndrome which includes fever and myalgias).
• Initial diagnostic options include ECG, echocardiogram, and troponin assays.
• MRI may also be useful for visualizing soft tissues of the heart to further investigate inflammation and scarring.

Bacterial Endocarditis

• A sequential pathologic course begins with damage to the endocardium (and abnormal surface) followed by the formation of a thrombus.
• Bacteria with virulence factors can then colonize the thrombus. This leads to damage to the endocardium (in particular, heart valves), which can break off and cause strokes or form thromboembolic arterial obstructions (causing inflammation).
• Resulting inflammation can also produce unique hemorrhagic or ischemic findings such as retinal hemorrhages.

Acute Bacterial Endocarditis

• Typically involves valves and endocardium, but can also occur on devices or areas of endocardium near turbulent flow.
• Bacterial masses called vegetation are composed of platelets, fibrin, microorganisms, and inflammatory cells.
• Vegetations are weak and prone to breakage, which may lead to the spread of bacteria.
• Common etiologies include large bacterial loads from dental/gingival disease, injection drug use (common in right-sided valves), and congenital heart disease (like VSD).

Acute Bacterial Endocarditis (Continued)

• The type of microbe involved influences whether the course of endocarditis is acute or sub-acute, and the speed of valve damage.
• Nasty acute bugs (staphylococcus aureus, streptococcal species, rarely pneumococcus) can result in acute and rapid damage. Less problematic bugs (such as HACEK group or enterococcus) produce a more slow and sub-acute form.

Signs and Symptoms of Infective Endocarditis

• Infective endocarditis symptoms are commonly associated with fever, chills, sweats (mostly acute and high in onset, but can be low and intermittent), anorexia, weight loss, malaise (sub-acute), myalgias, arthralgias, and back pain.
• Heart murmurs may not appear until some time after onset.
• Arterial emboli, splenomegaly, and nail clubbing are also commonly observed.
• Neurologic manifestations (like CVA) and peripheral manifestations can also occur.

Infective Endocarditis - Additional Info

• Peripheral manifestations include Osler nodes (painful raised papules, nodules on digits), Janeway lesions (painless hemorrhagic pustular lesions on soles or palms), and Roth spots (retinal hemorrhages with a pale center).
• Duke criteria are used to diagnose infective endocarditis.

Microbes Impacting the Heart

• Microbes such as Borrelia burgdorferi (Lyme disease), coagulase-negative staphylococci, streptococcus viridans, enterococcus faecalis, and HACEK organisms are infectious microbes and can cause infections in the heart.

Lyme Disease - Overview

• Caused by Borrelia burgdorferi.
• Common in Northern Hemisphere.
• 30,000 cases per year in the US.
• Bacteria has a complex structure with a peptidoglycan layer and flagella for movement through tissues.
• Difficult to culture as it is fastidious and requires a complex medium.
• It lacks the ability to synthesize amino acids, fatty acids, nucleotides, and enzyme cofactors (thus needing a complex medium).

Lyme Disease - Life Cycle and Virulence Factors

• Lyme disease life cycle does not involve humans. Ticks maintain the bacteria and transmit to offspring—with nymphs being more efficient (especially in spring).
• Lyme disease-causing microbes have factors to bind to complement regulatory proteins, hence protecting against immune system attack.
• Bacteria frequently changes its surface proteins to mimic the immune system.
• Preferred locations for division include avascular areas (tendons or joints).

Lyme Disease - Natural Cycle

• Larval ticks hatch uninfected and acquire the spirochete Borreliae by feeding on infected rodents.
• Larvae molt into nymphs in fall, become dormant through winter.
• Late spring and early summer, infected nymphs feed on rodents and the population of chronically infected rodents transmits Lyme borreliae to the next generation of ticks.
• Nymphs feed on humans, leading to peak Lyme disease in the late spring and summer.
• Adult ticks can also transmit the disease but fewer cases develop compared to nymphs.

Stages of Lyme Infection in Humans

• Stage 1* - Erythema migrans skin rash, spreading and reflects ability of spirochete to spread through skin; often painful or itchy; associated with arthralgias and myalgias, fever, fatigue, and headaches
• Stage 2* - Disseminated infection with potential involvement of blood vessels, CNS, heart, and skin; includes fatigue, aseptic meningitis, and cranial nerve palsies (Bell's palsy); heart involvement (myocarditis), skin rash, or joint involvement (arthralgias or myalgias).
• Stage 3 -* Late-stage is primarily arthritis in one or several large joints, which may have intermittent occurrences (most common long-term outcome).

Lyme Disease - Additional Clinical Details

• Lyme disease is treatable at all stages, but many patients develop Post-Treatment Lyme Disease Syndrome (PTLDS), including chronic pain, neurocognitive disturbances, and fatigue—antibiotics often provide limited or no relief from symptoms.
• Diagnosis is difficult as the causative organism is often not detected in patients with this chronic condition.
• Two-tiered serological testing (ELISA followed by immunoblot) can test for antibodies but do not discriminate between past or present infection.

Endocarditis Microbes - General Virulence Factors

• Common streptococcal species have extracellular enzymes (dextrans) that facilitate adhesion to thrombotic vegetations or damaged valvular endothelium.
• Dextrans facilitate binding to platelet-fibrin complexes.
• FimA, a protein produced by streptococci, promotes adherence to the endocardium or valves (part of the ECM).
• Fibronectin, obscured by the endothelium/endocardium (part of ECM) surfaces, becomes exposed during inflammation allowing for microbes adhesion.
• E. Faecalis, S. aureus, and viridans Streptococcus effectively bind to exposed fibronectin.
• Medical devices can also be coated with fibronectin leading to biofilm formation.

Endocarditis Microbes - General Virulence Factors (Continued)

• S. aureus can produce tissue factor aiding in clot building and invasion onto heart structures.
• HACEK group (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) microbes commonly reside in the oral cavity and are fastidious, require carbon dioxide for growth—an unknown reason behind their ability to cause endocarditis.

Postural Orthostatic Tachycardia Syndrome (POTS)

• Characterized by a rapid increase (greater than 30 beats per minute) in heart rate greater than prior resting heart rate when moving from a seated or lying position to standing.
• This increase is not accompanied by a reduction in blood pressure, but occasionally causes hypotension.
• Potentially a complex series of related but unique conditions or pathophysiological mechanisms.
• Diagnosis requires tilt table testing and is complicated by the lack of distinct mechanisms or diagnostic criteria.

POTS - Key Clinical Features

• Hallmark of POTS is symptomatic orthostatic intolerance (uncomfortable symptoms like light-headedness, weakness, blurred vision, nausea, and palpitations) that arises with shifting positions from a lying or seated posture.
• The elevation is associated with an increase of heart rate over baseline
• There may be pre-syncopal occurrences (but not necessarily).

POTS – Why Does It Happen?

• Partial autonomic neuropathy (decreased venous return/reduced stroke volume, and baroreceptor offloading).
• Hypovolemia (reduced blood volume).
• Hyperadrenergic state (altered cerebral perfusion and SNS activity).
• Combination factors increase the risk.

Peripheral Nervous System

• The peripheral nervous system (PNS) consists of all neural structures external to the spinal cord and brainstem, including cranial nerves (III-XII, excluding I and II), dorsal/ventral spinal roots, spinal nerves, and ganglia.
• These contain somatic motor fibers, somatic sensory fibers, and visceral sensory fibers.
• The supporting layers, epineurium, and perineurium stay continuous with the dura mater.

Peripheral Nervous System—Continued

• The endoneurium is responsible for the delicate connective tissue sheath encasing individual nerve fibers (along with blood vessels for nourishment and support).
• Spinal nerves travel through constricted foramina (in the vertebral column) and narrow passages (in limbs).
• The axons possess a sophisticated internal microtubular apparatus for maintaining membrane integrity and transporting substances across distances.
• Nerve fiber damage (axonal degeneration, segmental demyelination) is classified by specific characteristics.
• Axonal degeneration is confined to distal portions of larger nerve fibers (remaining portions are unaffected).
• In Wallerian degeneration, the parts of the axon distal to the injury break down and the part of the myelin sheath associated with that portion of the axon degenerates.
• Segmental demyelination is characterized by deterioration of the myelin sheath (with the underlying axon remaining functional).

Peripheral Neuropathies (PN): Overview

• Generally associated with nerve damage from systemic illness or specialized diseases.
• The majority of conditions are axonopathic (80–90%).
• Demyelinating disorders tend to have hereditary and/or immunological origins.
• Large diameter sensory fibers are responsible for proprioception and vibration sensation.

Peripheral Neuropathies (PN): Main Causes

• Metabolic conditions (diabetes mellitus, thyroid issues).
• Nutritional deficiencies (Vitamin B12).
• Systemic diseases (HIV infection, Lyme disease, hepatitis B/C, shingles).
• Toxic substances (alcoholism, chemotherapy).

Etiological Classification of Peripheral Neuropathies

• Immune-mediated neuropathies (Guillain-Barré syndrome, acute motor and sensory axonal neuropathy, Fisher syndrome, chronic inflammatory demyelinating polyradiculoneuropathy).
• Metabolic neuropathies (diabetic polyneuropathy, uremic neuropathy, critical illness polyneuropathy, hypothyroid neuropathy, acromegalic neuropathy).
• Nutritional neuropathies (Vitamin B1, B6, B12, or E deficiency).
• Toxic and drug-induced neuropathies.
• Hereditary neuropathies.
• Neuropathies linked to infections (Leprosy, HIV, CMV, Hepatitis B/C).
• Paraneoplastic neuropathies (associated with tumors).
• Sarcoid neuropathies.
• Radiation neuropathies.
• Traumatic neuropathies.
• Miscellaneous Neuropathies (Copper deficiency myeloneuropathy, chronic idiopathic axonal polyneuropathy).

Peripheral Neuropathy: Clinical Features

• Muscle weakness and atrophy.
• Sensory loss, paresthesia (pins and needles), pain.
• Autonomic dysfunction (affecting the sympathetic and parasympathetic nervous systems).
• Type of fibers affected: large-diameter sensory (position, vibration) or small-diameter (pain, temperature).

Topography and Clinical Patterns of Peripheral Neuropathy

• Polyneuropathy - Generalized symmetrical weakness starting distally and progressing bilaterally. Loss of reflexes are common.
• Radiculopathy or polyradiculopathy - Characterized by asymmetrical weakness and sensory loss, with frequent pain localized to the sensory distribution of the affected nerve root.
• Mononeuropathy multiplex - Characterized by accumulation of multiple mononeuropathies.

Peripheral Neuropathy: Clinical Feature (Continued)

• Motor nerve impairment: muscle weakness, wasting, spasms, and diminished reflexes.
• Sensory nerve impairment: reduced ability to feel touch (often in hands and feet), decreased overall sensation, altered reflexes, and compromised perception of pain and temperature.
• Autonomic nerve impairment: impaired sweating leading to heat intolerance; loss of control over bowel & bladder functions.

Diabetic Neuropathy

• Diabetes is associated with various chronic forms of neuropathy, including distal symmetric sensory or sensorimotor polyneuropathy, autonomic neuropathy, diabetic cachexia, polyradiculoneuropathies, and cranial neuropathies..
• Risk factors include prolonged/poorly managed diabetes, retinopathy, and nephropathy.

Diabetic Neuropathy: Pathophysiology

• High blood sugar triggers the activation of the polyol pathway, excessive production of fructose and sorbitol in nerves causing nerve damage.
• Glucose levels exceeding 7 mmol/L leads to elevated polyol pathway activity (30% or more of glucose metabolism) with high glucose leading to sorbitol.
• This process generates reactive oxygen species (oxidative stress).
• Factors like nitric oxide insufficiency, homocysteine elevations, abnormalities in sodium potassium ATPase (Na+/K+-ATPase), and impaired endoneural vascular function contribute to nerve tissue damage.

Diabetic Neuropathy: Clinical Features

• Typically presents with stocking-glove pattern, sensory loss, and painful paresthesias—predominantly in lower limbs.
• Frequent symptoms include paresthesias, burning/freezing/sharp/stabbing pain, increased sensitivity to touch, muscle weakness, and balance issues.

Chemotherapy-induced Peripheral Neuropathy (CIPN)

• Frequently encountered adverse outcome of chemotherapy, often dose-dependent sensory polyneuropathy, presenting weeks after treatment.
• CIPN symptoms affect sensory, motor, and autonomic functions, often displaying a glove and stocking distribution of symptoms, primarily in larger nerve fibers.
• Pathophysiological mechanisms are tied to platinum concentration within tissue, with highest levels in dorsal root ganglia.
• Chemotherapy affects neurotubule depolymerization, impacting large nerve fibers (particularly in patients treated with paclitaxel or docetaxel—used for ovarian cancer treatment).

Hypothyroidism and Neuropathy

• Thyroid hormones play a significant role in regulating nervous system processes.
• Proximal myopathy is common, less generalized sensory polyneuropathy (painful paresthesias and numbness in hands and legs) may develop.
• Potential factors influencing neuropathy include elevated BMI in people with hypothyroidism, water retention from mucopolysaccharides, chondroitin sulfate, and hyaluronic acid accumulation.

Shingles (Herpes Zoster) and Neuropathy

• Reactivation of latent varicella-zoster virus (VZV) infection, usually preceded by chickenpox, can cause shingles.
• Two-thirds of adult cases exhibit a characteristic dermal zoster rash accompanied by pain and paresthesia, distributing along the affected dermatome.
• 5-30% of patients experience weakness in muscles innervated by affected dermatomes.

Hepatitis B & C and Peripheral Neuropathy

• Peripheral neuropathy is the most common neurological complication of Hepatitis C virus (HCV) infection.
• Cryoglobulinemia (extrahepatic manifestation of chronic HCV) and HCV-mediated vasculitis may lead to nerve damage.
• Immune-mediated mechanisms, such as antibody production, immune complex formation, and damage to peripheral nerves may also arise.

Leprosy and Peripheral Neuropathy

• Leprosy (Hansen's disease), caused by Mycobacterium leprae (acid-fast bacteria), often involves nerve damage.
• Tuberculoid leprosy involves localized, asymmetric nerve damage; lepromatous leprosy involves symmetrical, distal nerve damage.
• Borderline leprosy presents as a range between the two, often resulting in more rapid and severe nerve damage.

HIV and Peripheral Neuropathy

• HIV-1 infection can lead to a variety of peripheral neuropathies, such as distal symmetric polyneuropathy, autonomic neuropathy, Lumbosacral polyradiculopathy, mononeuropathy, and mononeuropathy multiplex.
• Distal symmetric polyneuropathy is the most common type in HIV patients; occurring in the later stages of AIDS and characterized by axonal degeneration in the distal nerves.
• The etiology of axonal degeneration remains uncertain, and there are currently no effective treatments.

Alcoholism and Peripheral Neuropathy

• Poor nutritional habits (especially vitamin B1, B6, B12 deficiencies and folate), alongside direct alcohol toxicity (interferes with nerve signal transmission, damages nerve cell membranes, and causes inflammation) and impaired blood flow negatively impact nerve function and structure.
• Metabolic abnormalities (abnormal glucose metabolism, insulin resistance) may also contribute to nerve damage and resultant neuropathies, and include oxidative stress.
• Endogenous antioxidants are reduced, and oxidative stress (increased ROS) may lead to neuronal damage and neuropathic pain.

Sleep Deprivation and Epilepsy

• Sleep deprivation can heighten cortical excitability, predisposing to seizures (particularly generalized epilepsy), especially with prolonged wakefulness.
• Epilepsy can disrupt normal sleep patterns, increasing wake time after sleep onset, decreasing REM sleep quality, and delaying the first REM episode.

Tænia - Worm Infestations

• Cattle/pigs become infected by eating vegetation.
• Taenia invades muscle and survives, affecting humans who eat raw/undercooked meat.
• Mild abdominal symptoms (mild sickness).
• Proglates that exit in the stool develop (often after months).

Cysticercosis and Neurocysticercosis

• Cysticercosis is a Taeniabrusei larval cystic infection in tissues (predominantly muscle), and neurocysticercosis is a larval cystic infection in the brain that causes seizures).
• Cysticercosis is often variable: minimal symptoms initially, then sudden onset of seizures and increased intracranial pressure (ICP).
• MMP-9 polymorphism has been associated with neurological symptoms (seizures) in cysticercosis patients (compared to those without symptoms; potentially due to increased vascular permeability).

Trypanosoma brucei and Sleeping Sickness

• Caused by the unicellular parasite Trypanosomainvasive, extra-cellular parasite transmitted by the tse-tse fly, often affecting Sub-Saharan Africa.
• Three stages include an early stage (bloodstream and interstitial space) where parasitic spread is initially observed, potentially causing mild intermittent fevers, headache, pruritus, and lymphadenopathy and later stage where parasite invades the CNS and causes sleep disturbances. and possibly neuropsychiatric disorders (more severe).

Test your knowledge on peripheral neuropathy with this quiz that covers key symptoms, distinctions between conditions, and the anatomical structures involved. From understanding fiber damage to assessing regenerative potential, this quiz is tailored for those interested in neurology and the peripheral nervous system.