WEEK 11 - PROGRESSIVE NEURODEGENERATIVE DISORDERS

Question 1

Symptoms of Cerebellar injury

Answer 1

Dizzy ANT balancing 3 dys’es

Dizziness

Ataxia - lack of coordination

Nystagmus - involuntary twitching of the eyes

Tremor

Imbalance

Dysdiadochokinesia - inability to engage in rapid, changing movements

Dysarthria - unsteadiness in pitch and rhythym of speech

Dysmetria - inability to judge distances when moving

Question 2

Parkinsons Disease

Answer 2

DESCRIPTION

• one of the most common brain diseases
• Neurodegenerative condition

pathology

• dopamine producing cells are damaged or destroyed
  
  • dopamine is a transmitter that coordinates movement as well as feelings of motivation and reward
• gradual degeneration of neurons within the substantia nigra (in basal ganglia)
  
  • dopamine released from here stimulates the Striatium where inhibitory and stimulatory motor movement pathways are located.
    
    • decreased dopamine reduces activity of the stimulatory pathway and increases activity of the inhibitory pathway, overall reducing movement

RISK FACTORS / CAUSES

• usually idiopathic
• age (60+)
• genetic predisposition
• environmental factors
  
  • exposure to pesticides
  • infection
  • head injuries
• gender - more common in males

SYMPTOMS

• walking imbalance problems
• resting tremor
  
  • pill rolling tremor
• stiffness
• slowness of movements (bradykinesia)
• rigidity
  
  • cog wheel (short, rigid movements)
  • lead pipe (increased rigidity throughout)
• bowel issues (constipation)
• cognitive changes
• depression
• gait disturbance (shuffling)

DIAGNOSIS

• medical history + medical examination
  
  • resting tremor
  • stiffness
  • slowness of movement
• Movement Disorder Society Parkinsons Disease Criteria
  
  • Bradykinesia + resting tremor
  • 2 supportive criteria
  • no exclusion or red flag criteria

Question 3

Huntingdons disease

Answer 3

DESCRIPTION

• gives rise to involuntary movements
• genetically predisposed
• mutated Huntington protein leads to decay of neurons in the brain
• age of onset: 35-44
• degeneration of neurons in the indirect pathway (inhibitory) of the basal ganglia (control of involuntary actions)
  
  • causes the inability to switch off uncontrollable patterns
• especially destructive to neurons in the striatum, part of the basal ganglia

RISK FACTORS /CAUSES

• genetically predisposed

SYMPTOMS

• cognitive changes - depression
• speech and swallowing difficulties
• chorea - uncontrollable, jerky movements
• unsteady gait
• forgetfulness and impaired judgement

TREATMENT

• antipsychotics - control movements
• OT
• speech therapy

Question 4

Cerebellar problems

Answer 4

• complex movements appear as a range of simple and clumsy movements without precision
• disruption to the feedback circuit between the cerebellar cortex and the cerebral cortex

symptoms

• hypotonia (decreased muscle tone, issue with feedback of unconscious proprioceptive values from muscles (muscle spindle fibres, golgi tendon organ))
• lessening resistance to passive movement
• ataxia (abnormal gait)
• decomposition of movement (jerky)
• disarthria
• intention tremor
  
  • only occurs when engaging in a movement
    
    • differs from parkinsons/huntingtons as there is an intention tremor rather than a resting tremor
  • Dysmetria - unable to judge depth and length
• dysdiadochokinesia
  
  • imapired ability to perform rapid, alternating movements
    
    • demonstrated clinically with pronation/supination test
• nystagmus

Question 5

Dementia

Answer 5

• umbrella term for neurodegenerative diseases in which cognition and motor function gradually declines due to loss of CNS neurons.
  
  • causes poor memory and difficulty learning new concepts
• forms:
  
  • alzheimers
  • vascular dementia
  • Lewy Body dementia
  • Front-temporal dementia

Question 6

Alzheimers disease

Answer 6

Processes in which neurons are lost

• Development of neurfibrillary tangles
• Development of beta-amyloid plaques
• Reduced production of Acetylcholine
• Increased production of glutamate (glutamate toxicity) leading to excessive calcium entering neurons, leading to cell death.

Alzheimers - causes

Plaques

Cell membrane consists of a protein called Amyloid Precursor Protein (APP) APP helps to grow and repair neurons.

After considerable use, APP is broken down and recycled by alpha secretase and gamma secrates. the broken down APP is soluble and is natural.

But, when beta secretase breaks down APP, problems occur

• the leftover fragment is non-soluble, and termed a monomer called amyloid beta.
• these monomers bind together outside neurons and form beta amyloid plaques (clump of monomers)
• these plaques can interfere with neuron to neuron signalling by getting in the way
  
  • impairs brain function
  • possible can induce an inflammatory reaction
  • plaque binds to blood vessels, causing an amyloid angiopathy, which can lead to hemorrhaging

Tangles

Neurons of the brain are held in place by their cytoskeleton, partly made up of microtubules.

• assist in transporting nutrients and molecules along the length of the cell

Tau protein is found within the cytoskeleton to ensure the microtubules do not fall apart.

Although not fully understood, it is thought that the alteration of the Tau protein (causing it to lose its function, allowing microtubules to fall out of place is caused by beta amyloid plaque build up outside the cell.

The alteration of the Tau protein causes them to move away from the neuron cytoskeleton and tangle together, known as neurofibrillary tangles.

The lack of Tau protein holding together the microtubules of the neuron causes disruption in the signalling process along the neuron, making the neurons dysfunctional.

This can lead to apoptosis

types of alzheimers

sporadic (90-95%)

• late onsnet
• genetic and environmental
• risk factors
  
  • age 60+
  • genetic predisposition

familial

• dominant gene
  
  • speeds up progression of disease (early onset)

Symptoms - progression

• short term memory loss
• loss of some motor skills and language
• long term memory loss
• disorientated
• bedridden

Question 7

MND

Answer 7

• an umbrella term for a variety of diseases that affect motor neurons only. types:
  
  • Amyotrophic lateral sclerosis (ALS)

Question 8

Amyotrophic lateral sclerosis (ALS)

Answer 8

• progressive neurological disease chracterised by a combination of either one of LMN or UMN signs
  
  • degenerates motor nerves
  • no effect on sensory neurons
• most common type is Amyotrophic lateral sclerosis (ALS)
  
  • amyotrophic - loss of nerve signals to cells
  • sclerosis - hardened nature of spinal cord
  • EFFECTS BOTH UPPER AND LOWER MN
    
    • spastic paralysis and overactive reflexes in LL
    • flaccid paralysis and reduced reflexes in UL
      
      • 90% die
• Progressive bulbar palsy (PBP)
  
  • affects LMN
    
    • difficulty chewing, swallowing and speaking
• Primarly Lateral Sclerosis
  
  • affects UMN
    
    • progresses slowly
    • can develop into ALS

PATHOPHYSIOLOGY

• cause is unclear

CAUSES/RISK FACTORS

• sporatic 90% (random)
• genetic predisposition (10%)
• environmental factors
  
  • age
  • smoke
  • physical stress
  • pesticides

2-5 years expected life

SYMPTOMS

• UMN signs
  
  • increased tone
  • spasticity
  • overresponsive reflexes
  • extensor plantars (Babinskis sign)
• LMN sign
  
  • assymetrical weakness
  • msucle weakness
  • hypotonia
  • flaccid paralysis