Parkinsons Disease

Parkinsons Disease (PD)

onset usually 60 years or older, early onset parkinsons disease exist as well

Motor Symptoms

1. Akinesia (difficulty initiating movement)

2. Bradykinesia (slowness of movement)

3. Tremor (feet or hands)

4. Stiffness or Rigidity

5. Balance Problems

Non-Motor Symptoms

1. Cognitive Challenges (memory loss, confusion)

2. Sleep Disturbances

3. Loss of Smell (often predates signs and symptoms, but it’s also associated with Alzheimer’s and without disease)

4. Speech Differences (Low amplitude or slurred speech)

Nigrostriatal Pathway

Substantia Nigra → Striatum (pars compacta and pars reticula)

SNPc/SNc

Dopamine Neurotransmitter

SNPr/SNr

GABA Neurotransmitter

Ventrolateral Subthalamic Nucleus (vlSN)

Subdivision of SNC, Dopamanergic (D2 Receptors), degeneration of dopamine neurons here (30-50%)

Alpha-Synuclein protein which is supports to regulate neuronal function, accumulates and forms Lewy bodies (insoluable, contributes to neuronal death)

Lewy Body Dementia

No symptoms of parkinsons

Other locations for LB accumulation

1. Olfactory Bulb (Smell, ~95%)

2. Cerebral Cortex (Hallucinations, Cognitive Challenges, Thinking and logic)

3. Amygdala (mood changes, depression)

4. Hippocampus (Memory Impairment)

Is there an effective treatment for LB buildup

No

Dorsomedial SNc

1. Dorsal Portion of SNc (and VTA) intact

2. Dorsomedial SNc projects to limbic (ventral striatum/nucleus accumbens, reward and emotion, motivation and reward is typically not affected by PD)

Why the difference between PD and SZ? Selective D2 receptor degeneration

Serotonin

1. Depression

2. Anxiety

3. Fatigue

4. Sleep Disturbances

Acetylcholine

1. Cognitive Impairement

2. Memory Loss

3. Dementia

4. Alpha-Synuclein

(in movement-related pathways, acetylcholine levels are too high which causes tremors and rigidity)

Norepinephrine

1. Mood Disturbances

2. Sleep Disturbances

3. May decrease cognitive function

Glutamate and GABA

Reduction in Dopamine → Increases glutamate → excitotoxicity

Balance disrupted in basal ganglia

1. Decreased control of movement

2. Memory Problems

Anticholinergic Drug

Helps with movement related issues with parkinsons, but side effects occur in 30-40% of people (not a first choice)

1. Confusion

2. Memory Impairement

3. Hallucinations

Diagnositc Criteria

Bradykinesia with either rest tremor, rigidity, or both

L-Dopa with Carbidopa (most common)

DA precursor (converted into dopamine by Dopa-B-carboxylase). Helps with early-to-mid stage Parkinsons Disease in 80-90% of patients recieving L-Dopa.

Side effects of L-Dopa

Acute:

1. Nausea

2. Vomiting

3. Dry Mouth

Long-term:

1. Hallucinations

2. Increased Movement

3. Disorganized Thoughts

Deep Brain Stimulation (DBS)

Wire electrodes implanted into specific brain areas. For the treatment of Parkinson’s disease that is often either globus pallidus (basal ganglia) or the subthalamic nucleus (structure where diencephalon and mesencephalon connect)

Effectiveness of DBS

30-50% effectiveness in reducing symptoms of Parkinsons disease AND there are some reports that DBS can be used in combination with medication. smaller doses with DBS produces 80-90% reduction in symptoms

Lesion surgery

Last option typically, destroy small connections between structures that produce symptoms of PD.

Pallidotomy (Lesion Surgery)

Target: Globus Pallidus

Signs and Symptoms: Dyskinesia stiffness, tremors

Thalamotomy (Surgery)

Target: Thalamus

Sings: Tremors