Parkinson’s Disease

International school of medicine

neurology

Mini alekya

Group 4

Neurological Basis

• “Neurodegenerative Disease” : caused by degeneration (dysfunction and death) of neurons within the brain (nigrastriatal pathway of the basal ganglia) Parkinson’s disease affects the nerve cells in the brain that produce dopamine. Parkinson’s disease affects the nerve cells in the brain that produce dopamine.

• NORMAL BRAIN FUNCTION – Basal Ganglia• Cells in substantia nigra produce/release dopamine

• Dopamine released by SN neurons lands on neurons of other brain centers, controlling their firing

• Main targets are caudate nucleus and putamen (striatum)

• This basal ganglia pathway is involved in regulation of movement

Neurological Basis

• PARKINSON’S BRAIN FUNCTION–Basal Ganglia

• Cells of substantia nigra degenerate• These cells can no longer produce adequate amounts of

dopamine• Neurons of striatum, etc. are no longer well regulated,

thus do not behave in normal manner• Results in loss of control of movements – leads to

symptoms characteristic of Parkinson’s disease

• The term parkinsonism is used for a motor syndrome whose main symptoms are tremor at rest, stiffness, slowing of movement and postural instability. Parkinsonian syndromes can be divided into four subtypes according to their origin:

• primary or idiopathic• secondary or acquired• hereditary parkinsonism, and• Parkinson plus syndromes or multiple system

degeneration

CORE BIOCHEMICAL PATHOLOGY

• IS DECREASED DOPAMINE NEUROTRANSMISSION IN THE BASAL GANGLIA. MOST PARKINSON SYNDROMES HAVE DEGENERATION OF THE NIGROSTRIATAL DOPAMINE SYSTEM WITH MARKED LOSS OF STRIATAL DOPAMINE. IN SOME – STRIATAL DEGENERATION WITH LOSS OF DOPAMINE RECEPTORS OCCURS.

DRUG INDUCED PARKINSON

RESULTS FROM:• BLOCKAGE OF DOPAMINE RECEPTORS OR• DEPLETION OF DOPAMINE STORAGE,

DECREASED DOPAMINERGIC ACTIVITY IN THE STRIATUM LEADS TO DISINHIBITION OF THE SUBTHALMIC NUCLEUS AND THE MEDIAL GLOBUS PALLIDUS, THE PROMINENT EFFERENT NUCLEUS OF THE BASAL GANGLIA. UNDERSTANDING HAS LED TO DOPAMINE REPLACEMENT, SURGICAL TREATMENT

Characteristic Symptoms

• MOTOR– tremor– bradykinesia– rigidity/freezing in

place– lack of facial

expression– postural instability– stooped, shuffling gait

• NONMOTOR– diminished sense of

smell– low voice volume– foot cramps– sleep disturbance– depression– constipation– drooling

1817 – DESCRIBED BY JAMES PARKINSON

SIX CARDINAL FEATURES• REST TREMOR• RIGIDITY• FLEXED POSTURE• BRADYKINESIA – HYPOKINESIA• LOSS OF POSTURAL REFLEXES• FREEZING PHENOMENON TO DIAGNOSE: TWO OF ABOVE, WITH AT

LEAST ONE BEING REST TREMOR OR BRADYKINESIA

Diagnosis

• Diagnosing Parkinson's Disease

• There's no precise test for Parkinson's disease. This article describes how doctors diagnose the condition.

• PET Scan

• For patients with Parkinson's disease (PD), a PET scan is used to assess activity and function of brain regions involved in movement.

• CT Scan

• CT, or computed tomography, uses X-rays and computers to produce images of inside the body including the brain. This test is used to look for signs of disease like Parkinson's in the body .

• MRI

• MRI, or magnetic resonance imaging, is a test that produces very clear pictures, or images, of the human body without the use of X-rays. Instead, MRI uses a large magnet, radio waves, and a computer to produce these images

• The central sulcus is more posteriorly on more cranial images.

•

TREATMENT OF PARKINSON DISEASE

• MEDICAL– DOPAMINERGIC AGENTS – ANTI-CHOLINERGICS;

etc.

• SURGICAL – ABLATIVE– RESTORATIVE– D.B.S.

• PHYSICAL THERAPIES– P.T.– O.T.– SPEECH– OMT, BIOFEEDBACK– EXERCISE Rx, TAI-CHI

• PSYCHOTHERAPIES– COUNSELLING– SOCIAL WORK– MEDS., etc.

Conventional Treatments: Medication

• LEVODOPA (L-DOPA)• precursor to dopamine, converted to dopamine by

nerve cells in the brain• Treatment with dopamine not possible, because

dopamine can’t cross blood-brain barrier• Generally combined with carbidopa (Sinemet) –

helps levodopa get to the brain + reduces some side effects

• Extended use often produces dyskinesias – uncontrolled movements (writhing, twitching, shaking) among other minor side effects

Conventional Treatments: Medication

• DOPAMINE AGONISTS• not changed into dopamine, but rather act LIKE

dopamine at brain synapses where dopamine is usually present (nigrostriatal pathways in Parkinson’s patients)

• Used both as adjuncts to L-Dopa therapy and in younger Parkinson’s disease patients

• Side effects similar to levodopa, but less likely to develop involuntary movements, more likely to cause hallucinations

Conventional Treatments: Medication

• MAO Inhibitors (Selegiline)

• COMT Inhibitors

• Anticholinergics

Conventional Treatments: Surgery

• Thalamotomy• Involves destruction of small amounts of tissue in

the thalamus—major center for relaying messages/transmitting sensations

• Can cause slurred speech and lack of coordination

• Pallidotomy• electric current used to destroy small amount of

tissue in the pallidum (globus pallidus)• May improve tremors, rigidity by interrupting

pathway between globus pallidus and thalamus

Conventional Treatments: Surgery

• Deep Brain Stimulation

• implant device, pacemaker-like unit transmits impulses to electrodes placed in subthalamic nucleus

• Produces same effects of lesion surgeries, but can be turned on and off

Experimental Treatment: Surgery

• Fetal Cell Transplant Therapy• stem cells obtained via aborted fetus, grown in culture,

transplanted into Parkinson’s patient at nigrostriatal pathway• New cells establish connections and “replace” cells originally

lost, these cells function normally and even produce dopamine

• Autologous “Self” Transplant• analagous to fetal cell transplant, except that precursor

nerve cells are taken from patient and coaxed to produce dopamine, then implanted back into original patient

• Reduces threat of autoimmune response and reduced “controversial baggage” associated with FCT therapy