-Parkinson’s disease is a neurodegenerative disorder due to dopamine depletion in the substantia nigra and in the nigrostriatal pathway to the caudate and putamen.
-the second most common age-related neurodegenerative disease, exceeded only by Alzheimer’s disease (AD)
-The mean age of onset of PD is about 60 years
-The cause remains largely unknown
-The only known cause of PD: Genetic mutations
-Occurs in all ethnic groups with equal sex distribution
-Prior use of ibuprofen is associated with a decreased risk of developing Parkinson disease
Symptoms & Signs
rest tremor, rigidity (stiffness), bradykinesia (slowing), and gait dysfunction with postural instability. freezing of gait, speech difficulty, swallowing impairment, autonomic disturbances,
Cardinal features: Tremor (most conspicuous at rest, enhanced by stress)Rigidity, Bradykinesia(the most disabling symptom; a slowness of voluntary movement)
Craniofacial: Masked facial expression (hypomimia), hypophonia, Dysphagia, Repetition of a phrase or word with increasing rapidity (palilalia), speech impairment
Visual: blurred vision, Eyelid opening apraxia, hypometric saccades, impaired vestibuloocular reflex
Musculoskeletal: Stooped posture, micrographia, dystonia, myoclonus, difficulty turning in bed
Gait: A loss of the normal automatic arm swinging, Shuffling, Short-stepped gait, freezing, festination
Psychosis: Visual, auditory, olfactory, and tactile hallucinations
Olfactory dysfunction: loss of smell
Sensory disturbances: Pain
Mood disorders: Depression (most common psychiatric disturbance seen in PD), anxiety, loss of motivation,
Sleep disturbances: Rapid eye movement sleep behavior disorder (RBD), sleep fragmentation, early morning awakening, restless legs syndrome
Gastrointestinal disturbances Constipation, Dysphagia
Genitourinal disturbances Urinary difficulties
Sexual dysfunction: underactivity, hypersexuality
There are no diagnostic tests for PD
Primarily a clinical diagnosis based on symptoms and signs
Myerson Sign: Repetitive tapping (about twice per second) over the bridge of the nose producing a sustained blink response
Dopamine Replacement Therapy
Dopamine: Given the deficiency of dopamine, it would be nice if we could just give dopamine itself. However, dopamine does not cross the blood-brain barrier.
Logic behind Levodopa-Carbidopa combination:
Levodopa can cross the blood-brain barrier, but large doses are required because much of the drug is decarboxylated to dopamine in the periphery causing side-effects like nausea, vomiting, and orthostatic hypotension.
Carbidopa is a dopamine decarboxylase inhibitor that does not cross the blood–brain barrier. It reduces the peripheral metabolism of levodopa, thereby increasing the amount of levodopa that reaches the brain.
-It is the most effective symptomatic treatment for PD
-It controls classic motor features of PD, improves quality of life, and increases the lifespan
Selegiline, Rasagiline, Safinamide
At lower doses, Selegiline and rasagiline are not associated with a cheese effect (hypertensive crisis), usually seen when MAO-B inhibitors are taken with tyramine-rich containing foods
Side-effects: nausea, headache, confusion, hallucinations
-Tolcapone, Entacapone, Opicapone
-Inhibitors of COMT prolong the elimination half-life of levodopa and enhance its brain availability.
Side-effects of Tolcapone: Severe diarrhea, Fatal hepatic toxicity; periodic monitoring of liver function required
-Antiviral drug effective in the treatment of influenza
-it ameliorates dyskinesias resulting from prolonged levodopa therapy
-Side-effects: Livedo reticularis, weight gain; should always be discontinued gradually to prevent withdrawal-like symptoms
Dopamine Agonists (DAs)
Ergot DAs: Bromocriptine
Nonergot DAs: Pramipexole, Ropinirole, Rotigotine, Apomorphine
Due to their serious side-effects, the first generation dopamine agonists (bromocriptine, pergolide, cabergoline) were replaced by second generation agonists such as pramipexole, ropinirole, rotigotine.
-Side-effects: Sedation with sudden unintended episodes of falling asleep, impulse-control disorders (compulsive eating, shopping, hypersexuality, pathologic gambling)
Trihexyphenidyl(most widely prescribed anticholinergic), benztropine, biperiden
-Contraindicated in patients with prostatic hypertrophy, narrow-angle glaucoma, or obstructive intestinal disease
Side-effects: Dryness of the mouth, constipation, urinary retention, cardiac arrhythmias, palpitations, mydriasis, agitation, restlessness.
Olanzapine, Quetiapine, Risperidone, Clozapine
-Clozapine can cause marrow suppression, necessitating weekly cell counts
Antidepressants: selective serotonin-norepinephrine reuptake inhibitor (SNRI) or a selective serotonin reuptake inhibitor (SSRI), cognitive behavioral therapy
Stimulants: Modafinil, methylphenidate
Exercise and physical therapy
Cognitive behavioral therapy
Deep Brain Stimulation
The serum urate level may be a prognostic indicator in men—the rate of progression declines as the urate level increases.