Neuroanatomy of Neurodegeneration - In-Depth Notes

Outline

  • Define and consider the main processes of neurodegeneration
  • Consider Focal Pathology - an anatomical approach for clinical localization
  • Gather insights into brain localization especially from Brodmann’s Legacy
  • Clinically relevant case examples of focal neurodegenerative conditions using a “Top to Toe” approach
    • Global Cortex - Dementias
    • Basal Ganglia - Huntington's Disease (HD), Parkinson's Disease (PD)
    • Cerebellum - Multiple System Atrophy (MSA)
    • Spinal - Hereditary Spastic Paraplegia (HSP)
    • Neuropathy – Motor Neuron Disease (MND), Hereditary Sensory Motor Neuropathy (HSMN)

General Clinical Characteristics of Neuro-Degenerative Diseases

  • Three notable characteristics:
    1. Affect specific parts or functional systems of the nervous system, allowing for clinic-pathological classification
    2. Begin insidiously after a prolonged normal nervous system function
    3. Exhibit a gradually progressive course; assigning a precise date of onset is often complex
    • Progressive over a time span that can range from years to decades, evolving into a global neurological issue (e.g., Alzheimer's Disease (AD) and PD).

Neurodegenerative Processes

  • Classification of neurodegenerative diseases includes:
    • Tauopathies (e.g., Multiple Systems Atrophy, Alzheimer’s Disease)
    • Synucleinopathies (e.g., Parkinson’s Disease, Dementia with Lewy Bodies (DLB))
    • Genetic conditions (e.g., Huntington’s Disease, Spinocerebellar Ataxia (SCA), HSP)
    • Neuro-inflammation (e.g., Progressive Multiple Sclerosis)
    • Repetitive Trauma (e.g., Chronic Traumatic Encephalopathy)
    • Toxins (e.g., Alcohol)

Genetic Components

  • Key genes involved include:
    • PRNP, APP, PSEN1, PSEN2 (associated with prion diseases and Alzheimer’s)
    • C9orf72, GRN, FUS (associated with frontotemporal dementia)
    • PARK2, LRRK2, SNCA (linked to Parkinson’s disease)

Alzheimer's Disease/Dementia

  • Represents 60% of global dementia cases
    • Characterized by an insidious onset and gradual cognitive decline, mainly impacting memory
    • Associated with two types of proteinopathies:
    1. β-amyloid (Aβ) plaques
    2. Hyperphosphorylated tau neurofibrillary tangles
  • Leads to synaptic and neuronal loss, gliosis visible in histopathological analysis.

Focal Pathologies and Clinical Examples

  • Huntington's Disease:
    • Genetic, autosomal dominant condition characterized by:
    • Motor symptoms: Chorea, dystonia, rigidity
    • Cognitive symptoms: Difficulties in planning, executing tasks, impulsivity
    • Psychiatric symptoms: Depression, anxiety, irritability
  • Multiple System Atrophy (MSA):
    • Features autonomic failure, parkinsonism, cerebellar degeneration
  • Spinal and Neuropathy Conditions:
    • HSP: genetic condition leading to progressive weakness, often with cognitive impairment.

Brain Localisation Insights from Brodmann’s Work

  • Overview of Brodmann areas:
    • Frontal Lobe: Motor cortex, behaviour, intelligence
    • Parietal Lobe: Sensory cortex, language, reading
    • Occipital Lobe: Visual processing
    • Temporal Lobe: Memory, auditory processing
    • Brain Stem: Vital functions like consciousness and respiration

Neurological Exam Insights

  • Clinical significance of neurological examinations as they correlate to neuroanatomical findings:
    • Conduct various tests like the Finger-to-Nose test, which indicates cerebellar function
    • Reflex tests assessing motor pathways and functionalities in various Neurodegenerative diseases.

Neurology and Pathology Correlation

  • Essential to join neuroanatomical changes to clinical symptoms for effective diagnosis and treatment planning.
  • Regular updates on evolving understandings through research such as those finding novel genetic mutations linked to specific conditions.