Mostly Parkinson’s disease but also few other movement disorders due to

diseases of the basal ganglia

Direct and indirect pathways

• Dopamine excites the Direct pathway leading to cortical excitation and movement.

• Dopamine inhibits the Indirect pathway leading to cortical excitation and movement.

Hypokinetic disorders• Lack of dopamine leads to over-activity of

the indirect pathway and under-activity of the direct one.

Hyperkinetic disorders

• Dopamine excess leads to under-activity of the indirect pathway and over-activity of the direct one.

Hypokinetic disorders

Resting tremor, bradykinsesia, rigidity and postural instability

Parkinsonism

Neurodegenerativeprocess

Drug-induced

Idiopathic Parkinson’s

Disease

Parkinson Plus Syndromes:1. Multiple System Atrophy (MSA)2. Progressive Supranuclear palsy (PSP)3. Corticobasal Degeneration (CBD)4. Others

Dopamine deficiency in the striatum

Parkinsonism

Neurodegenerativeprocess

Drug-induced

Idiopathic Parkinson’s

Disease

Parkinson Plus Syndromes:1. Multiple System Atrophy (MSA)2. Progressive Supranuclear palsy (PSP)3. Corticobasal Degeneration (CBD)4. Others

Parkinson’s disease

1. Resting tremor - Usually involves a hand, “Pill-rolling” tremor.

2. Rigidity – increased resistance to passive movement.

3. Bradykinesia – slowness of voluntary movements, reduction of automatic movements (arm swinging, hypomimia, blinking)

4. Postural instability.

Usually asymmetrical and responds to

Levodopa.

Natural History of Parkinson’s Disease

Time (years)

Sev

erit

y O

f D

isea

se

Symptoms resistant totherapy (dementia, gait and balance, bulbar)

Motor symptoms (tremor, rigidity, bradykinesia)

Pre-motor symptoms (depression, constipation,Impaired smell sensation,acting out of dreams)

Epidemiology of Parkinson’s disease

Pathology

Normal Parkinson’s Disease

α-synuclein containingintracytosolic Lewy Bodies

Progression of Lewy bodies

Braak staging

Etiology

• No clear etiology is found for the majority of patients.

• Organic solvents and rural living were associated with higher risk.

https://www.michaeljfox.org

Gan-Or, Neurogenetics, 2010

Treatment

Time (years)

Sev

erit

y O

f D

isea

se

Diagnosis

Motor complications

Therapy honeymoon(minimal symptomson treatment)

Levodopa induced dyskinesia

Surgical treatment

• Deep brain stimulation of substantia nigra or Glubus Pallidus interna has replaced palidotomy.

Hyperkinetic disorders

Hyperkinetic disorders

• Chorea / Athetosis• Tics• Ballismus• Dystonia

Example: Chorea

• Rapid, semi purposeful, graceful vs jerky, irregular movement that tends to occur in the distal limb or face.

• Inherited diseases – Huntington, Wilson• Rheumatic – Sydenham, Chorea gravidarum• Systemic – SLE, APLA• Drug-induced – Neuroleptics, cocain, excess L-dopa

The End