Pathology CPC CNS 2: Neurodegeneration Quiz
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Questions and Answers

What is the most likely diagnosis for a 31-year-old lady with weakness and numbness in her left leg and a history of painful blurred vision in her right eye?

  • Stroke
  • Amyotrophic Lateral Sclerosis
  • Multiple Sclerosis (correct)
  • Peripheral Neuropathy
  • Which of the following is an unusual sign of demyelination associated with Multiple Sclerosis?

  • Lhermitte’s sign (correct)
  • Trigeminal neuralgia
  • Bladder dysfunction
  • Gait disturbance
  • How would you categorize a case of Multiple Sclerosis that began with one clinical episode and later progressed?

  • Clinically isolated syndrome
  • Relapsing-remitting MS (correct)
  • Secondary progressive MS
  • Primary progressive MS
  • Which investigation is primarily used to support the diagnosis of Multiple Sclerosis?

    <p>MRI of Brain and Spine with contrast (D)</p> Signup and view all the answers

    What is the name given to the phenomenon where raised body temperature exacerbates symptoms in Multiple Sclerosis?

    <p>Uhtoff's phenomenon (D)</p> Signup and view all the answers

    What specific finding in CSF analysis supports a diagnosis of Multiple Sclerosis?

    <p>Oligoclonal bands (C)</p> Signup and view all the answers

    Which symptom is commonly associated with optic neuritis in Multiple Sclerosis?

    <p>Visual loss (B)</p> Signup and view all the answers

    Which of the following clinical features is seen in a neurological examination of a patient with Multiple Sclerosis?

    <p>Brisk reflexes in the affected limb (C)</p> Signup and view all the answers

    What name is given to the diagnostic criteria for multiple sclerosis (MS)?

    <p>McDonald Criteria (C)</p> Signup and view all the answers

    What pathologic process is occurring in the brain during an MS relapse?

    <p>Demyelination (C)</p> Signup and view all the answers

    How does demyelination affect axonal transport?

    <p>Impedes saltatory conduction (C)</p> Signup and view all the answers

    Which cell type is responsible for myelination in the central nervous system (CNS)?

    <p>Oligodendrocyte (D)</p> Signup and view all the answers

    What is one of the management goals for a patient with multiple sclerosis?

    <p>Shorten relapse duration (D)</p> Signup and view all the answers

    Which type of treatment is typically used for acute management of MS?

    <p>Steroids (B)</p> Signup and view all the answers

    What is a characteristic change in the brain due to the progressive phase of multiple sclerosis?

    <p>Brain atrophy (A)</p> Signup and view all the answers

    Which symptom is commonly managed within a multidisciplinary team for MS patients?

    <p>Fatigue management (D)</p> Signup and view all the answers

    What defines delirium?

    <p>An acute disorder of attention and global cognition that is reversible. (D)</p> Signup and view all the answers

    Which symptom is NOT associated with the man's delirium?

    <p>Memory loss about the event (D)</p> Signup and view all the answers

    What part of the brain is primarily affected in memory impairment?

    <p>The temporal lobe (B)</p> Signup and view all the answers

    What is a characteristic feature of dementia?

    <p>Progressive decline in cognitive function (C)</p> Signup and view all the answers

    What investigation is most important to exclude acute reversible causes of cognitive decline?

    <p>Urinalysis and urine culture (D)</p> Signup and view all the answers

    Which of the following assessments may help identify affected cognitive domains?

    <p>Montreal Cognitive Assessment (D)</p> Signup and view all the answers

    What could memory loss in this case suggest aside from delirium?

    <p>Possible dementia (A)</p> Signup and view all the answers

    Which of the following is NOT a step in investigating cognitive decline?

    <p>Conducting routine physical exams only (B)</p> Signup and view all the answers

    What is the most reliable method to confirm a diagnosis of Alzheimer's disease?

    <p>Autopsy (postmortem) brain examination (A)</p> Signup and view all the answers

    Which biomarker is associated with Alzheimer's disease pathology?

    <p>Presence of beta-amyloid plaques (C)</p> Signup and view all the answers

    What is a common symptom exhibited in the progression of Alzheimer's disease?

    <p>Total dependence on others (A)</p> Signup and view all the answers

    What role does Tau protein play in Alzheimer's disease?

    <p>Stabilizes microtubules in neurons (B)</p> Signup and view all the answers

    Why is the distribution of amyloid plaques significant in Alzheimer's disease?

    <p>They correlate with the level of cognitive decline. (C)</p> Signup and view all the answers

    What feature distinguishes Alzheimer's disease pathology from that of other dementias?

    <p>Specific pattern of amyloid and tau accumulation (A)</p> Signup and view all the answers

    Which of the following is a potential consequence of Tau depletion in nerve cells?

    <p>Failure of axonal elongation (C)</p> Signup and view all the answers

    What is the primary reason for conducting a postmortem examination in cases of Alzheimer's disease?

    <p>To provide definitive diagnosis confirmation (A)</p> Signup and view all the answers

    What are the key components of the McDonald Criteria for diagnosing MS?

    <p>Dissemination of CNS lesions in space and time through clinical and MRI findings (D)</p> Signup and view all the answers

    Which combination of symptoms is indicative of demyelination in Multiple Sclerosis?

    <p>Weakness in lower limbs and facial pain (D)</p> Signup and view all the answers

    Which pathologic changes are primarily observed during an active MS plaque?

    <p>Demyelination with perivascular and parenchymal inflammation (C)</p> Signup and view all the answers

    How does demyelination specifically disrupt axonal conduction in the CNS?

    <p>By impairing saltatory conduction (A)</p> Signup and view all the answers

    What is a common differential diagnosis for a patient presenting with symptoms similar to multiple sclerosis?

    <p>Guillain-Barré syndrome (C)</p> Signup and view all the answers

    What is the primary role of oligodendrocytes in the central nervous system?

    <p>Forming myelin sheaths around multiple axons (C)</p> Signup and view all the answers

    Which one of the following investigations is most crucial in confirming the diagnosis of Multiple Sclerosis?

    <p>Magnetic resonance imaging (MRI) with contrast (A)</p> Signup and view all the answers

    What is the likely mechanism behind Uhtoff’s phenomenon in Multiple Sclerosis patients?

    <p>Demyelination causing overheating effects on nerve conduction (C)</p> Signup and view all the answers

    What are the overall management goals for treating Multiple Sclerosis?

    <p>Shorten relapses and prolong remissions while improving quality of life (B)</p> Signup and view all the answers

    In the context of Multiple Sclerosis, what does the term 'clinically isolated syndrome' refer to?

    <p>First episode of neurological symptoms lasting more than 24 hours without evidence of another cause (A)</p> Signup and view all the answers

    Which treatment approach is typically NOT used for long-term management of MS?

    <p>Antibiotics to prevent infections (D)</p> Signup and view all the answers

    Which symptom is least likely to be associated with Multiple Sclerosis?

    <p>Chronic cough (B)</p> Signup and view all the answers

    What causes the characteristic brain atrophy associated with the progressive phase of Multiple Sclerosis?

    <p>Ongoing axonal loss and subsequent loss of white matter (B)</p> Signup and view all the answers

    Which symptom can be effectively managed by a multidisciplinary team in MS patients?

    <p>Fatigue and urogenital problems (D)</p> Signup and view all the answers

    What role do oligoclonal bands play in the diagnosis of Multiple Sclerosis?

    <p>Reflect an autoimmune process within the central nervous system (B)</p> Signup and view all the answers

    Which clinical presentation is associated with Lhermitte’s sign in patients with Multiple Sclerosis?

    <p>Electric shock-like sensations down the spine during neck flexion (B)</p> Signup and view all the answers

    Which of the following features distinguishes delirium from dementia?

    <p>Delirium has a rapid onset. (A)</p> Signup and view all the answers

    What component of the cognitive assessment can help determine the affected cognitive domains in a patient?

    <p>Montreal Cognitive Assessment. (A)</p> Signup and view all the answers

    Which anatomical structures in the brain are primarily associated with short-term memory impairment?

    <p>Hippocampus and surrounding cortices. (C)</p> Signup and view all the answers

    Which of the following is NOT considered a progressive cognitive decline?

    <p>Major Depressive Disorder. (B)</p> Signup and view all the answers

    In the investigation of cognitive decline, which test is least likely to indicate a reversible cause?

    <p>Mini-Mental State Examination. (C)</p> Signup and view all the answers

    Which of the following describes a characteristic symptom of dementia as opposed to delirium?

    <p>Progressive decline of function over time. (B)</p> Signup and view all the answers

    Which investigation is often done last when assessing a patient for cognitive decline?

    <p>Brain imaging (CT or MRI). (B)</p> Signup and view all the answers

    What cognitive change in personality and memory is often initially attributed to aging by family members?

    <p>Short-term memory loss. (B)</p> Signup and view all the answers

    What is the primary method to confirm a diagnosis of Alzheimer's disease postmortem?

    <p>Autopsy brain examination (A)</p> Signup and view all the answers

    Which of the following features is indicative of Alzheimer's disease pathology?

    <p>Presence of neurofibrillary tangles (C)</p> Signup and view all the answers

    Which biomarker alteration is most commonly associated with Alzheimer's disease?

    <p>Altered phosphorylated Tau levels (D)</p> Signup and view all the answers

    What change in amyloid beta levels might indicate the progression of Alzheimer's disease?

    <p>A decrease in Aβ42 and an increase in Aβ40 (B)</p> Signup and view all the answers

    Which clinical feature is most likely observed in advanced stages of Alzheimer's disease?

    <p>Complete loss of recognition of family members (A)</p> Signup and view all the answers

    What is a primary role of Tau protein in the context of Alzheimer's disease?

    <p>Stabilizing microtubules in neurons (C)</p> Signup and view all the answers

    In Alzheimer's disease research, what significance does the Pittsburgh Compound B (PiB) hold?

    <p>It labels amyloid plaques for imaging (C)</p> Signup and view all the answers

    What is one of the main macroscopic features observed during the diagnosis of Alzheimer's disease?

    <p>Cortical atrophy (A)</p> Signup and view all the answers

    Flashcards

    Clinical Isolated Syndrome (CIS)

    A single episode of neurological dysfunction suggestive of MS, with subsequent MRI findings of demyelination, but no further attacks or symptoms.

    Relapsing-remitting MS (RRMS)

    The most common type of MS, characterized by relapses (periods of new or worsening symptoms) followed by periods of remission (when symptoms improve or disappear).

    MRI Brain and Spine with contrast

    An imaging technique used to visualize the brain and spinal cord, identifying areas of inflammation and demyelination (characteristic features of MS).

    CSF analysis

    Examination of cerebrospinal fluid (the fluid surrounding the brain and spinal cord) to detect specific proteins, including oligoclonal bands (OCBs).

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    Oligoclonal Bands (OCBs)

    Specific proteins found in the CSF, that can provide evidence of an immune system response, often associated with MS. Disappearance of OCBs in the CSF is a strong indicator that the diagnosis is not MS.

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    Visual Evoked Potentials (VEPs)

    Tests that measure the electrical activity in the brain in response to visual stimuli, allowing assessment of the optic nerve and visual pathways.

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    Lhermitte's sign

    A tingling or 'electric shock-like' sensation that travels down the spine and extremities when the neck is flexed, suggestive of MS-related demyelination in the spinal cord.

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    Uhthoff's phenomenon

    Increased symptoms of MS with increased body temperature; the temperature increase causes worsening of symptoms.

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    McDonald Criteria

    Diagnostic criteria for multiple sclerosis (MS), based on the objective demonstration of central nervous system (CNS) lesion dissemination in both space and time. This can be determined from clinical findings alone or a combination of clinical and MRI findings.

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    MS relapse (active MS plaque)

    A period of MS exacerbation characterized by demyelination, inflammation in the brain, and the presence of lymphocytes and macrophages around blood vessels (perivascular and parenchymal inflammation).

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    Demyelination

    The loss of myelin, the fatty protective layer around nerve fibers in the CNS (and PNS).

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    Axonal Transport

    The process by which materials are transported along nerve axons, essential for maintaining neuron function.

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    Oligodendrocyte

    A type of glial cell responsible for myelination in the central nervous system (CNS).

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    Saltatory Conduction

    The rapid transmission of nerve impulses along myelinated axons by jumping from one node of Ranvier to the next.

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    MS Treatment (acute)

    Treatment focused on reducing the severity and shortening the duration of MS relapses, sometimes including corticosteroids and plasma exchange.

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    MS Treatment (long-term)

    Treatment focused on preventing further relapses, slowing disease progression, and improving quality of life, through the use of disease-modifying agents.

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    Delirium

    An acute disorder of attention and global cognition, which is reversible by treating the underlying cause. It often presents with sudden changes in mental state and can be triggered by infections, medications, or other medical conditions.

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    Delirium Symptoms

    The man's symptoms of delirium include disorientation, altered personality, and volatile behavior. Delirium is characterized by fluctuations in alertness and disturbances in cognitive abilities.

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    Dementia

    A progressive decline in cognitive abilities, affecting at least two cognitive areas. It is characterized by irreversible deterioration of mental functions, including memory, thinking, and language.

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    Detecting Dementia

    Dementia is detected through a detailed history of cognitive decline, assessment of cognitive areas, and exclusion of other causes like infections and treatable conditions.

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    Cognitive Assessment

    Cognitive assessments like the MMSE (Mini-Mental State Examination) and Montreal Cognitive Assessment help identify affected cognitive domains. They evaluate memory, attention, language, and other cognitive abilities.

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    Brain Imaging for Dementia

    Brain imaging techniques such as CT (Computed Tomography) and MRI (Magnetic Resonance Imaging) help visualize the brain and assess the extent of any atrophy (brain shrinking). PET (Positron Emission Tomography) can also be used to detect changes in brain activity.

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    Memory Impairment

    Memory impairment is a common symptom of dementia. It can affect both short-term and long-term memory, making it difficult to remember recent events or past experiences.

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    Short-Term Memory

    Short-term memory refers to the ability to hold information in your mind for a short period of time, usually a few seconds to a few minutes, allowing you to process information and make decisions. When your short-term memory is impaired, you might forget what you just read or what was said a few moments ago.

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    Alzheimer's Disease (AD)

    A progressive neurodegenerative disease characterized by memory loss, cognitive decline, and behavioral changes.

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    CSF Analysis in AD

    Measuring levels of Tau, Amyloid beta 42, and Phospho-Tau proteins in cerebrospinal fluid (CSF) can assist in diagnosing AD.

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    18F-FDG PET Scan

    A type of brain imaging test that uses a radioactive tracer to show brain activity, helpful in diagnosing AD.

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    Pittsburg Compound B (PiB) PET Scan

    A type of brain imaging test that detects amyloid plaques, which are characteristic of AD, in the brain.

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    Autopsy Brain Examination

    The only definitive way to confirm an AD diagnosis is by examining the brain tissue after death.

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    Amyloid Plaques

    Clumps of amyloid beta protein that accumulate in the brain in AD, contributing to neuronal dysfunction.

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    Tau Protein

    A protein found in neurons that helps stabilize microtubules, but in AD, it misfolds and forms tangles, disrupting neuronal function.

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    Neurodegeneration

    The progressive loss and damage of nerve cells, a hallmark of AD.

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    What is the most likely diagnosis in this case?

    Multiple sclerosis (MS) is the most likely diagnosis, given the patient's presentation of neurological symptoms, including weakness, numbness, blurred vision, and altered sensation.

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    What is Clinically Isolated Syndrome (CIS)?

    Clinically Isolated Syndrome (CIS) is a single episode of neurological dysfunction consistent with MS, often accompanied by MRI evidence of demyelination in the brain or spinal cord. However, there are no further attacks or symptoms at this stage.

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    What are the McDonald Criteria?

    The McDonald Criteria are a set of diagnostic guidelines for Multiple Sclerosis (MS). They are based on the objective demonstration of central nervous system (CNS) lesion dissemination in both space and time. This can be determined from clinical findings alone or a combination of clinical and MRI findings.

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    What are Uhthoff's Phenomenon and Lhermitte's Sign?

    Uhthoff's Phenomenon is when the body temperature goes up and causes MS symptoms to worsen, while Lhermitte's Sign is a tingling or electric shock-like feeling that passes down the spine and into the limbs when the neck is flexed.

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    What are 3 investigations that support a diagnosis of MS?

    MRI of the brain and spinal cord with contrast helps visualize areas of inflammation and demyelination. CSF analysis detects specific proteins, like oligoclonal bands, which are more common in MS. Visual evoked potentials test the optic nerve and visual pathways, which can be affected by demyelination.

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    What is Demyelination?

    Demyelination is the loss of myelin, the fatty protective layer around nerve fibers in the central nervous system (CNS) and peripheral nervous system (PNS). This disruption in insulation leads to slower nerve impulses and impaired nerve function.

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    What is Oligoclonal Bands (OCBs)?

    Oligoclonal Bands (OCBs) are specific proteins found in the cerebrospinal fluid (CSF) that are more common in MS. They are a potential sign that the immune system is attacking the brain or spinal cord - inflammation.

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    Explain the importance of MRI Brain and Spine with contrast in diagnosis of MS

    MRI with contrast is a key tool used in MS diagnosis. It can visualize lesions in the brain and spine, revealing areas of inflammation and demyelination. By observing the location, size, and pattern of lesions, it helps confirm the diagnosis, monitor disease progression, and guide treatment decisions.

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    Active MS Plaque

    An area of inflammation in the brain during an MS relapse, characterized by demyelination and infiltration of immune cells.

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    Acute MS Treatment

    Short-term treatment for MS relapses, aimed at rapidly reducing symptom severity and shortening relapse duration, often with steroids.

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    Long-Term MS Treatment

    Treatment aiming to prevent further relapses, slow disease progression, and improve quality of life, using disease-modifying agents.

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    Progressive Phase of MS

    The later stage of MS, characterized by irreversible neurological decline due to axonal damage and brain atrophy.

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    Cognitive Impairment

    Problems with thinking skills, such as memory, attention, language, and executive functions.

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    MMSE (Mini-Mental State Examination)

    A standard cognitive assessment tool used to screen for cognitive impairment, including dementia.

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    Progressive Cognitive Decline

    A gradual worsening of cognitive abilities over time, a characteristic feature of dementia.

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    Neurodegenerative Disease

    A chronic disease that progressively damages and destroys nerve cells, leading to cognitive decline and other neurological symptoms.

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    Study Notes

    CNS 2 Neurodegeneration/Demyelination

    • Course: Pathology CPC
    • Year: 2
    • Lecturer: Dr. Michael Farrell
    • Date: November 22nd, 2023

    Clinical Scenario

    • Patient: 31-year-old female
    • Symptoms: 4-day history of weakness and numbness in left leg, episode of painful blurred vision in right eye one year prior (resolved after a week)
    • Medical History: No other past medical history; not on regular medications
    • Examination: ↑ tone in left leg, power 3/5, brisk reflexes in left leg, ↓ pin prick and proprioception, pale right optic nerve

    Questions

    • What is the most likely diagnosis in this case?
    • How else can this condition present?
    • How would you categorise the patient's clinical syndrome of MS?
    • Name 3 investigations that will support your clinical diagnosis?
    • What name is given to the diagnostic criteria for MS?
    • What pathologic process is going on in the brain during a MS relapse (i.e. active MS plaque)?
    • How does demyelination affect axonal transport?
    • What cell is responsible for myelination in the CNS?
    • What types of treatment might be used for this patient?
    • What are the management goals?
    • What is the most likely clinical diagnosis?
    • Over the next year he shows progressive decline, fails to recognise close family member, becomes withdrawn, totally dependent on others until death. How might a diagnosis be confirmed?
    • A pathologic diagnosis of Alzheimer Type Pathology is made. What are the macroscopic and microscopic features?
    • Why is this type of postmortem examination so important?

    Answers

    • Multiple Sclerosis (MS): A clinical diagnosis supplemented by inflammation in the brain and/or spinal cord, which is dissociated in time and place.

    • Clinical presentation of MS: Visual loss, gait and lower limb weakness, facial pain, double vision, gait/balance disturbance, vertigo, bladder dysfunction, Lhermitte's sign (tingling or shock-like feeling when flexing the neck), Uhthoff's phenomenon (exacerbation of symptoms with raised body temperature).

    • MS Classifications: Clinically isolated syndrome, Relapsing-remitting MS (most common initial type), secondary progressive MS, primary progressive MS

    • MS Investigations: MRI brain & spine with contrast, CSF analysis and oligoclonal bands (OCBs), visual evoked potentials, delayed P100 potentials.

    • MS Diagnostic Criteria: McDonald Criteria

    • Active MS Plaque Pathophysiology: Demyelination, perivascular inflammation, parenchymal inflammation, presence of lymphocytes and macrophages.

    • Demyelination & Axonal Transport: Impairment of saltatory conduction and axonal transport

    • CNS Myelination Cell: Oligodendrocytes

    • MS Treatment: Steroids (sometimes plasma exchange) for acute attacks; Disease-modifying agents (injectable, oral, and infusion medications) for long-term.

    • MS Management Goals: Shorten relapse duration, prolong remissions, prevent progression, and improve quality of life.

    • Most likely clinical diagnosis for progressively declining 70-year-old male: Alzheimer Disease.

    • Confirming Alzheimer diagnosis: Autopsy (postmortem) brain examination.

    • Macroscopic and microscopic features of Alzheimer's pathology: Amyloid plaques (ßA4), neurofibrillary tangles (tau protein).

    • Importance of postmortem examinations in Alzheimer's and other neurodegenerative disorders: Overlap exists between clinical phenotypes and pathologies; clinical diagnosis may not always match pathologic diagnosis, crucial for family diagnosis and inheritance likelihood, contributes to understanding disease and response to treatments.

    Learning Objectives

    • Correctly interpret clinical histories
    • Provide appropriate investigations for suspected MS
    • Describe demyelination's pathology and physiology.
    • Distinguish delirium and dementia differences.
    • Describe cortical neurodegenerative disease investigations.
    • Describe the macroscopic and microscopic brain features in Alzheimer's disease.

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    Description

    Test your knowledge on neurodegeneration and demyelination with this quiz focused on clinical scenarios in pathology. Explore multiple aspects of multiple sclerosis (MS), including diagnosis, presentations, investigations, and the underlying pathophysiology. This quiz is designed for second-year medical students and covers key topics presented in the Pathology CPC course.

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