Pathology CPC Year 2: Neurodegeneration Quiz

CNS 2 Neurodegeneration/ Demyelination

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

Clinical Scenario

• A 31-year-old woman presented with a 4-day history of weakness and numbness in her left leg
• A year prior, she had an episode of painful blurred vision in her right eye that resolved within a week.
• No other significant medical history or regular medications.
• Physical exam revealed increased tone in the left leg, a power of 3/5, brisk reflexes in the left leg, and decreased pin prick and proprioception sensation.
• Her right optic nerve was pale.

Questions

• What is the most likely diagnosis in this case?
• How else can this condition present?

Answers: Common presenting symptoms of MS

• Visual loss
• Gait and lower limb weakness
• Facial pain
• Double vision
• Gait/balance disturbance
• Vertigo
• Bladder dysfunction
• Optic neuritis
• Transverse myelitis
• Trigeminal neuralgia (Pons)
• Brain stem-MLF
• Cerebellum/spinal cord
• Brain stem
• Spinal cord

Unusual Signs of Demyelination

• Lhermitte's sign: Neck flexion resulting in rapid tingling or electric shock-like sensations that travel down the spine and into the limbs.
• Uhthoff's phenomenon: Raised body temperature can cause an exacerbation of symptoms.

Questions

• How would you categorize the patient's clinical syndrome of MS?

Answers

• Clinically isolated syndrome
• Relapsing-remitting MS (majority of cases at onset)
• Secondary progressive MS
• Primary progressive MS

Questions

• Name 3 investigations that will support your clinical diagnosis

Answers

• MRI brain & spine with contrast
• CSF analysis and SPEP: Oligoclonal bands (OCBs) should be unmatched.
• Visual evoked potentials, Delayed P100 potentials

MRI Brain + Contrast - MS

• Images illustrating inflammatory disease in the brain, potentially a sign of MS.

Questions

• What name is given to the diagnostic criteria for MS?

Answer

• McDonald criteria

Diagnosis - McDonald Criteria

• Objective demonstration of dissemination of CNS lesions in both space and time based on either clinical findings alone or in combination with MRI findings.
• Specific details of clinical presentation and additional data needed for diagnosis are outlined.

Questions

• What pathologic process is going on in the brain during a MS relapse (active MS plaque)?

Answer

• Demyelination: Reactive astrocytes, lymphocytes, and microglia and/or macrophages (foamy macrophages) in the perivascular and/or parenchymal environment.

Demyelination

• Short segment of remyelination with a thin myelin sheath
• Demyelinated axon
• Lymphocytes, microglia, foamy macrophages, and reactive astrocytes

Questions

• How does demyelination affect axonal transport?

Answer

• Impaired saltatory conduction

Demyelination

• Progressive decline, impaired saltatory conduction

Questions

• What cell is responsible for myelination in the CNS?

Answer

• Oligodendrocyte

Myelin & the Oligodendrocyte

• CNS: One oligodendrocyte myelinates several internodes
• PNS: One Schwann cell myelinates only one internode

Questions

• What types of treatment might be used for this patient?
• What are the management goals?

Answer

• Acute: Steroids (sometimes plasma exchange)
• Long-term: Disease-modifying agents (injectable, oral, infusion medications)
• Management Goals: Shorten relapses, prolong remissions, prevent progression, improve quality of life
• Multidisciplinary team, dedicated clinics, address fatigue, spasticity, urogenital problems

Learning Objectives 1

• Range of symptoms of multiple sclerosis
• Clinical classification of MS
• Investigation of MS (Multiple sclerosis progresses to a progressive degenerative phase characterized by axonal loss (leading to spinal cord thinning) and brain atrophy due to white matter loss).

Learning Objectives 2

• Distinguish between delirium and dementia
• How to investigate above
• List clinical features of neurodegenerative disease affecting different anatomic sites
• Discuss how to make a diagnosis of a neurodegenerative disease
• List pathologic features of a neurodegenerative disease

Next Case

• A 70-year-old man presented with fever, disorientation, altered personality, and volatile behavior for two days.
• Urinalysis showed nitrites, leukocytes, and ketones.
• Urinary culture showed pure growth of E. coli. He was treated with appropriate antibiotics and recovered.
• After returning home, he had no memory of the hospital visit and couldn’t recall what hospital he was in.

Questions

• What do you understand by the term delirium?
• List the symptoms of this man's delirium

Answer

• Delirium = acute, reversible cognitive disorder
• Symptoms = disorientation, altered personality, and volatile behavior.

Questions

• What is there in the man's story that might indicate he has more than just delirium?

Answer

• Inability to recall the hospital event and the location.

Answer

• Possible dementia (progressive cognitive decline in at least two cognitive areas)

Investigation of Progressive Cognitive Decline

• Exclude acute reversible causes (infection)
• Detailed history (including family history) and cognitive assessment (MMSE, Montreal cognitive assessment).
• Exclude treatable conditions (e.g., metabolic causes, thyroid function tests, vitamin B12 levels, U&E, LFTs, autoantibody workup).
• Brain imaging (CT, MRI, or PET) to assess for stroke or atrophy distribution.
• Brain biopsy (rarely) to identify treatable causes (e.g., vasculitis, lymphoma).

History From Family Members

• Family members reported a change in personality and increasing forgetfulness over the previous 18 months.

Questions

• What anatomical parts of his brain are affected by memory impairment?

Answer

• Areas associated with memory impairment in the brain: Parietal lobe, frontal lobe, medial temporal lobe (hippocampus, amygdala, limbic system), and temporal neocortex. The frontal lobe manages judgment, abstract reasoning, strategic planning, and emotional restraint. The temporal neocortex is associated with receptive dysphasia and automatisms; the occipital lobe is associated with failure of visual sensory systems.

More Detailed Examination

• Examination revealed moderate short-term memory impairment.

Questions

• What is the most likely clinical diagnosis?
• How may the diagnosis be confirmed?

Answer

• Alzheimer's disease
• A definitive diagnosis may be difficult to achieve definitively in life but can be confirmed post-mortem via brain examination, analysis, and or study of tissues.

Question

• Over the next year he progressively declines, fails to recognize close family members, becomes withdrawn, dependent on others, until death.
• How might a diagnosis be confirmed?

Answer

• Autopsy (postmortem) and brain examination. This is the only way to definitively confirm the diagnosis of Alzheimer's disease or other conditions.

Question

• A pathologic diagnosis of Alzheimer type pathology is made.
• What are the macroscopic and microscopic features?

Answer

• Macroscopic features: Atrophy of the brain, especially in the medial temporal lobe, frontal lobes
• Microscopic features: Amyloid plaques and neurofibrillary tangles.

Alzheimer's Disease Gravestones

• Aloiz Alzheimer
• Auguste Deter
• Plaques & Tangles
• AD - clinical entity, AD - pathologic process with a prodrome

β A4 Amyloid Plaques in Cerebral Cortex

• Microscopic image of 𝛽A4 amyloid plaques in cerebral cortex.

AD Plaque Distribution

• Diagram of amyloid plaques in the brain, particularly concentrated in the frontal and temporal cortex and hippocampus.

Vascular Amyloid

• Micrographs of vascular amyloid deposits

Alzheimer's Disease - Tau

• Figures demonstrating pathologic process of tau in the brain, severity and percentage of affected cases correlated with age.

Tau Function Transgenics

• Tau -/- nerve cells: Neuritic sprouting but no axon elongation.
• Tau +/+ non-neural cells: Elaborate long, thin process with compacted MTs

Neurodegeneration - Amyloid-Tau

• Illustration of neurodegeneration with amyloid and tau.

Questions

• Why is this type of postmortem examination so important?

Answer

• Overlap between clinical phenotypes and pathologies.
• Clinical diagnosis of Alzheimer's disease isn't always matched by pathology.
• Important for family diagnosis.
• Aids in understanding the disease and response to treatments.

Learning Outcomes

• Correctly interpret a clinical history of a patient with MS
• Provide appropriate key investigations for a patient suspected of having MS.
• Describe the pathology and physiologic effects of demyelination & why they cause neurological symptoms
• Distinguish and demonstrate clinical differences between delirium and dementia
• Describe key investigations for cortical neurodegenerative disease
• Describe macroscopic and microscopic features seen in the brain of a patient with Alzheimer's disease.

Test your knowledge on neurodegeneration and demyelination with this quiz from the Year 2 Pathology CPC course. Analyze a clinical scenario involving a patient with possible multiple sclerosis and answer key questions about presentation and symptoms. This quiz will enhance your understanding of important concepts in neuro pathology.