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Parkinson Disease

Introduction
With increasing life expectancy the prevalence of Parkinson disease (PD) has increased. Around 1% of people over the age 60 years have this disease, making it a common neurological disorder in the elderly. PD is one of the most common diseases seen by me in my clinic.

Parkinson's disease (PD) was first described in 1817 by James Parkinson, in "An Essay on the Shaking Palsy." It is a neurodegenerative disease, meaning it is caused by degeneration (dysfunction and death) of neurons within the brain. Several drugs are available to treat symptoms. PD symptoms can be controlled but unfortunately there is no permanent cure for PD. Several forms of surgery and numerous nonpharmacological (non-drug) approaches are also available, but a cure or therapy to slow the disease still eludes modern medicine.

PD is not a single disease but a heterogeneous group of diseases associated with a spectrum of clinical and pathological change.

Symptoms of Parkinson Disease
Parkinson's disease greatly shortens life as well as causing debility during life. PD typically begins at age of 50 or 60s and slowly progresses with increasing age. The average age of onset is 62.4 years. Onset before age 30 is rare, but up to 10% of cases begin by age 40 (young onset PD). PD presents with slowness of activities, shaking (tremors) of the hands, expressionless facial appearance. There is loss of automatic motions of arms while walking which causes frozen shoulder. This mistakenly leads patients to orthopedic surgeon. Misdiagnosis of PD is common. The underlying cause of the frozen shoulder is loss of postural reflexes. Rigidity (stiffness) stooped posture and shuffling gait can cause a peculiar appearance while walking. Due to the slowness patients require more time for daily routine.

Patients can have several other symptoms like diminished sense of smell, Low voice volume, Painful foot cramps, Sleep disturbance, depression, constipation, drooling, increased sweating, urinary frequency/urgency, male erectile dysfunction.

Advanced PD has symptoms of fluctuations and dyskinesias, freezing, dementia, psychosis, depression.

Pathology
Dopamine is a neurotransmitter that controls movement and balance and is essential to the proper functioning of the central nervous system (CNS). Substantia Nigra (SN) is a black substance in the mid brain region of brainstem. Dopamine is produced by SN cells. In PD, cells of the SN degenerate, and therefore can no longer produce adequate dopamine. This ultimately results in a loss of control of movements, leading to slowed movements, tremor, and rigidity. Thus therapy of PD involves replacement of dopamine in the form of L Dopa (a precursor of dopamine).

Etiology
The etiology is unknown and it is likely due to a multifactorial interaction of genes and the environment on the background of ageing. Findings in the last decade suggest that the contribution of genetics to familial forms of PD is much greater than previously appreciated.

Toxins - Pesticides or herbicides, drinking well water may be implicated in some cases. There are many cases of individuals with none of these risk factors who develop PD, and many with them who do not.

Genetics - There are several genes that are known to cause PD, but they account for a very small minority of cases. The most important is a gene called parkin. When the parkin gene is altered, or mutated, its function is impaired. It is hypothesized that the accumulation of defective proteins contributes to death of neurons. Parkin mutations are the most common genetic cause of PD, but still account for less than one percent of all cases. Other known genes for PD include alpha-synuclein, DJ-1, PINK-1, and UCHL-1, LRRK but altogether these represent only a small number of PD cases.

Diagnosis
There is no specific test or marker to diagnose PD. Thus the diagnosis is clinical based on presence of two important features of PD, slowness and tremors, rigidity or postural impairment. The examination also involves recording a careful medical history, especially for exposure to medications that can block dopamine function (antipsychotics) in the brain. There are several drugs with similar properties used for other purposes.

PD mimics
Several other disorders have certain features that are similar to PD. These are sometimes mistaken for P.

Drug induce PD is the commonest cause of secondary parkinsonism. Essential tremor, Vascular (related to blood vessels) parkinsonism, Progressive supranuclear palsy, Multiple system atrophy, Poisoning by carbon monoxide, manganese, or certain pesticides can imitate PD.

Treatment
The good news is that there is effective treatment for the symptoms of PD. For almost all patients with PD medicines can give symptom free survival for many years. Unfortunately, no therapy has yet been conclusively shown to slow or reverse the disease.

Drugs used to treat PD -
The treatment of PD is symptomatic, that is relief of symptoms by use of drugs acting on the dopaminergic system.

Motor symptoms (Tremors, rigidity, bradykinesia or slowness) - Levodopa remains the mainstay and most effective medicine which reverses all the symptoms of PD. Several levodopa preparations are available in the market.

Dopamine agonists like ropironole, pramipexole, bromocryptine are freely available. COMT inhibitors like entacapone, tolcapone , MAO B inhibitors like Rasagiline, Selegiline are used to prolong action of levodopa. Anticholinergics like benztropine, Trihexyphenidyl, procyclidine are used for treatment of tremors.

Treatment of Nonmotor symptoms of PD
- Dementia- Donepezil, rivastigmine
- Depression- SSRI, mirtazipine
- Psychosis- Clozapine, Quetiapine, olanzepine
- Stress/anxiety- benzodiazepines ( alprazolam, clonazepam)
- Fatigue - modafinil, SSRI
- REM sleep behavior disorder- clonazepam
- Daytime sleepiness- modafinil
- Orthostatic hypotension- fludrocortisones
- Urinary urgency- oxybutinin
- Impotence- sildenafil
- Constipation- high fiber diet, polyethylene glycol
- Nausea- domeperidone
- Salivation- propantheline, botulinum toxin injections

Surgical treatment for PD
Lesionectomy and Deep brain stimulation (DBS) is an option for advanced PD with motor complications. Patients have to be carefully selected for these procedures for optimal results.