Common Neurological Conditions

• Gross Features of Alzheimer's Disease Pathology.

  Gross Features:

  • Brain Atrophy: This includes significant shrinkage in key brain regions such as the cerebral cortex and hippocampus, which are critical for cognitive functions like memory and reasoning.
  • Ventricular Enlargement: The lateral and third ventricles are notably enlarged due to the loss of surrounding brain tissue, a phenomenon known as hydrocephalus ex vacuo.
• Ultrastructural Features of Alzheimer's Disease Pathology.

  • Amyloid Plaques: Composed of amyloid-beta peptide aggregates, these plaques are found extracellularly and disrupt neuron-to-neuron communication.
• Ultrastructural Features of Alzheimer's Disease Pathology.

  • Neurofibrillary Tangles: These are composed of hyperphosphorylated tau protein found within neurons, disrupting intracellular transport and leading to cell death.
• Ultrastructural Features of Alzheimer's Disease Pathology.

  • Neuronal Loss: Particularly significant in the hippocampus and entorhinal cortex, leading to the characteristic memory loss seen in Alzheimer's disease.
• Ultrastructural Features of Alzheimer's Disease Pathology.

  • Gliosis: An increase in glial cells, mainly astrocytes and microglia, which attempt to clean up the debris from dead neurons but also contribute to inflammation.
• Amyloid Cascade Hypothesis of Alzheimer’s Disease

  Hypothesis:

  • Initiating Event: The abnormal cleavage of amyloid precursor protein (APP) by beta-secretase and gamma-secretase enzymes, leading to the production of amyloid-beta peptides.
• Amyloid Cascade Hypothesis of Alzheimer’s Disease

  Hypothesis:

  • Plaque Formation: These amyloid-beta peptides aggregate into insoluble plaques that accumulate outside neurons.
• Amyloid Cascade Hypothesis of Alzheimer’s Disease

  Hypothesis:

  • Downstream Effects: The presence of amyloid plaques triggers a series of events, including:
  • Tau Hyperphosphorylation: Leads to the formation of neurofibrillary tangles.
  • Inflammation: Activated microglia and astrocytes release inflammatory cytokines.
  • Synaptic Dysfunction: Plaques disrupt synaptic communication.
  • Neuronal Death: Cumulative damage leads to progressive neuronal loss.
• Amyloid Cascade Hypothesis of Alzheimer’s Disease

  Hypothesis:

  • Outcome: These events culminate in the cognitive decline characteristic of Alzheimer’s disease.
• Tau Hypothesis of Alzheimer’s Disease

  Hypothesis:

  • Primary Event: Tau protein becomes abnormally phosphorylated due to various kinase activities.
• Tau Hypothesis of Alzheimer’s Disease

  Hypothesis:

  • Tangle Formation: Hyperphosphorylated tau proteins lose their ability to stabilize microtubules and instead form paired helical filaments, which aggregate into neurofibrillary tangles inside neurons.
• Tau Hypothesis of Alzheimer’s Disease

  Hypothesis:

  • Propagation: Misfolded tau can spread from cell to cell, promoting tangle formation throughout the brain.
• Tau Hypothesis of Alzheimer’s Disease

  Hypothesis:

  • Disruption: These tangles disrupt normal cellular functions such as axonal transport, leading to cell death.
• Tau Hypothesis of Alzheimer’s Disease

  Hypothesis:

  • Primary Event
  • Tangle Formation
  • Disruption
  • Propagation
• Key Issues Associated with Ageing of the Brain.

  • Cognitive Decline
  • Neurodegeneration
  • Vascular Changes
  • Inflammation
  • White Matter Changes
• Key Issues Associated with Ageing of the Brain

  Cognitive Decline:

  • Reduced processing speed, memory impairment, and decreased executive function.
• Key Issues Associated with Ageing of the Brain

  Neurodegeneration:

  • Increased prevalence of neurodegenerative diseases such as Alzheimer's and Parkinson's.
• Key Issues Associated with Ageing of the Brain

  Vascular Changes:

  • Reduced cerebral blood flow and increased risk of small vessel disease and strokes.
• Key Issues Associated with Ageing of the Brain

  Inflammation:

  • Chronic low-grade inflammation, often referred to as "inflammaging," which can contribute to cognitive decline and neurodegeneration.
• Key Issues Associated with Ageing of the Brain

  White Matter Changes:

  • Loss of white matter integrity, affecting the speed and efficiency of neural communication.
• Main Aetiological Features of Bacterial Meningitis.

  Aetiology:

  • Causative Agents: Bacteria such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae.
  • Transmission: Bacteria invade the bloodstream and cross the blood-brain barrier, infecting the meninges.
• Main Pathological Features of Bacterial Meningitis.

  Pathology:

  • Inflammation: Intense inflammatory response in the meninges.
  • Exudate: Accumulation of purulent exudate in the subarachnoid space.
  • Vascular Complications: Blood vessel inflammation can lead to thrombosis, infarction, and cerebral edema.
• Primary Brain Injury:

  • Definition: Immediate and direct damage to brain tissue at the moment of impact or insult.
  • Examples: Skull fractures, cerebral contusions, intracerebral hemorrhages, and diffuse axonal injury.
• Secondary Brain Injury:

  • Definition: Damage that occurs as a delayed response to the initial injury, often due to physiological and biochemical changes.
  • Examples: Cerebral edema, increased intracranial pressure, ischemia, hypoxia, and metabolic derangements.
• Primary Brain Injuries:

  • Examples: Traumatic brain injury (TBI) from a fall or accident, skull fracture, concussion, gunshot wound to the head.
• Secondary Brain Injuries:

  • Examples:
  • Cerebral Edema: Swelling of brain tissue.
  • Increased Intracranial Pressure (ICP): Pressure buildup within the skull.
  • Ischemic Stroke: Lack of blood flow leading to tissue death.
  • Brain Herniation: Displacement of brain tissue due to high ICP.
• Monro-Kellie Doctrine

  Doctrine:

  • Concept: The cranial vault is a rigid, fixed space, and the total volume of its contents (brain tissue, blood, and cerebrospinal fluid) must remain constant.
  • Compensation: If the volume of one component increases, there must be a compensatory decrease in another component to maintain a stable intracranial pressure.
• Three Signs of Cushing's Triad

  1. Hypertension: Elevated blood pressure as the body attempts to maintain cerebral perfusion.
  2. Bradycardia: Slowed heart rate due to increased intracranial pressure affecting the vagus nerve.
  3. Irregular Respirations: Abnormal breathing patterns caused by brainstem compression.
• Intracranial Pressure Compensation Mechanisms

  Mechanism 1: Cerebrospinal Fluid (CSF) Shifts:

  • Reduction: CSF can be displaced from the cranial vault into the spinal subarachnoid space, or its production can be decreased, and its absorption increased.
• Intracranial Pressure Compensation Mechanisms

  Mechanism 2: Blood Volume Reduction:

  • Venous Volume: Venous blood can be displaced from the intracranial vault to extracranial veins, reducing blood volume within the skull.
• Intracranial Pressure Compensation Mechanisms

  Brain Herniation:

  • Issue: When compensatory mechanisms are exhausted, increased intracranial pressure can force brain tissue to herniate through openings in the skull, such as the foramen magnum.
  • Outcome: Brain herniation can compress vital brain structures, leading to severe neurological damage or death.
• Intracranial Pressure Compensation Mechanisms

  • Mechanism 1: Cerebrospinal Fluid (CSF) Shifts
  • Mechanism 2: Blood Volume Reduction
  • Brain Herniation