Parkinsons Disease: Pathophysiology

Define parkinsons disease?

It is a progressive neurodegenerative disease caused by a loss of nerve cells in the basal ganglia

What is the basal ganglia?

Refers to a large group of subcortical nuclei in the forebrain anterior to the thalamus

What is the basal ganglia responsible for?

Responsible primarily for motor control aswell as motor learning, executive function, behaviours and emotions. It also plays a role in reward and reinforcement, addictive behaviours and habit formation.

What does disruption to the basal ganglia cause?

Can lead to movement disorders

What are the parts of the Basal Ganglia?

• Caudate nucleus

• Putamen

• Globus Pallidus

• Subthalamic nucleus

• Substantia Nigra

What is the role of the substantia nigra?

Produces dopamine which allows accurate control of movement pathways

Name an excitatory neuro transmitter?

Glutamate

name an inhibitatory neurotransmitter?

GABA

Is dopamine inhibitory or excitatory?

Dopamine is both inhibitory and excitatory depending on which pathway it is acting upon either direct or indirect

What is the role of the basal ganglia?

It is responsible for putting ‘the intention to move into action’ in a smooth manner also plays a part in running well-learnt, voluntary and semi-automatic motor patterns and sequences.

describe symptoms of the hyperkinetic movement diorders?

• Tremor - A rhythmic oscillation

• Dystonia - involuntary muscle contraction

• Myoclonus - jerk of a body part

• Tic/sterotypy - recurrent, rhythmic movement

• Chorea - random, fleeting movements

• tourettes

• Huntingtons disease

Describe symptoms of hypokinetic movement disorders

• Parkinsonism (umbrella term)

• Parkinsons’s disease (80% of cases)

• Progressive supranuclear palsy

• Cortico-basal-ganglionic degeneration

• Striato - Nigral degeneration

• Shy - drager syndrome

What percentage of PD is genetic/ environmental cause?

5%

What percentage of neurons need to be lost before symptoms occur?

70-80%

What are the 3 cardinal signs of parkinsosn disease?

• Bradykinesia

• Rigidity

• Tremor

What is Bradykinesia?

Slowness of movement can effect either both sides or just one

What is rigidity?

A form of hypertonicity with increased resistance to slow passive movement. it is usually asymmetrical and effects both agonists and antagonists

What are the two types of rigidity? and describe them

• Lead pipe - Uniform rigidity, low and sustained resistance

• Cogwheel - Tremor is superimposed, intermittent rigidity

What is tremor?

Involuntary, rhythmic oscillation of a body part

What are the 2 types of tremor?

• resting tremor - 4-6Hz, pill rolling, usually stops when carrying out an action

• Action tremor - When moving a limb or maintaining posture

Why is postural Instability not a cardinal symptom of PD?

Tends to present later in disease

What is meant by postural instability?

Inability to maintain equilibrium under static or dynamic conditions

What are signs of postural instability?

• Flexed posture, weakness in antigravity musculature

• Shuffling or freezing of gait

• difficulty initiating movements

• Difficulty terminating movements

• Altered balance reactions

• Muscle weakness

• high risk of falls

What are the common motor features of PD

• Shuffling Gait

• Flexed posture

• Loss of trunk rotation

• Reduced arm swing

• Festinating Gait

• freezing

• Micrographia

• Lack of facial expression

What are some common non-motor features of PD?

• Anxiety disorders

• Apathy

• Depression

• Psychosis/hallucinations

• Dementiasleep disturbance

• Autonomic disturbance ( constipation, sexual dysfunction, orthostatic hypotension, weight loss, dysphagia, hyperhidrosis, sialorrhoea, pain, olfactory dysfunction)

What treatments are available to relieve some symptoms for PD?

• Medication

• Surgery (for those who meet the specific criteria)

• Supportive therapies (physios, OTs and SaLt)

What is the drug which is first line of treatment?

Levadopa

What are the sideeffects of levadopa?

• Dyskinesias

• Psychiatric disturbance

• Nausea and vomiting

• hypotension

• anxiety and depression

What can levadopa be combined with to increase effectivness?

• Co-beneldopa (Madopar)

• Co-careldopa (Sinemet)

What do dopamine agonists do?

Increase sensitivity of dopamine receptor sites, Mimic dopamine

When are dopamine agonists used?

Used alone in early stage or in combination with Levadopa

Give 2 examples of Dopamine agonists

• Pramipexole.

• Ropinirole

What is the role MAOB inhibitors?

Prevent breakdown of dopamine in brain

When are MAOB inhibitors used

Can be used alone when motor symptoms are mild and con be combined with other drugs in later stages of PD

Give 2 examples of MAOB inhibitors?

• Rasagiline

• Selegine

What is the role of COMT inhibitors?

Prevent breakdown of Levadopa too soon, this helps too reduce down time

When are COMT inhibitors taken?

Always taken with Levadopa

Give 2 examples of COMT inhibitors?

• Entacapone

• Opicapone

What can medication management in PD help with?

• Sleep problems

• Anxiety and depression

• Pain

• Dementia

• Orthostatic hypotension

• Sialorrhea - excessive saliva flow

• Hyperhidrosis - excessive sweating

• Psychotic symptoms

What is deep brain stimulation (DBS)?

DBS is a type of surgery that can be used to treat PD, in this tretment a pulse generator is placed under the skin and and high frequency stimulation change some of the electrical signals in the brain

When is DBS used ?

It may be used when symptoms are no longer controlled by medication

What symptoms may be improved by DBS?

Improved motor control symptoms including tremor, speed of movements and involuntary movements