Parkinson's disease

Parkinson’s disease

Degenerative disease of the substantia nigra characterized by a triad of resting tremor, rigidity and bradykinesia and akinesia.  

Demographics
Parkinson’s disease is the most common akinetic condition, it has a prevalence of around 170 per 100000 population. It tends to affect men more than woman with the average age of onset at 60.

pathophysiology
In parkinson’s disease there is degeneration of cells within the pars compacta of the substantia nigra of the basal ganglia. There are also abnormal lewy bodies in the surviving cells. These cells transmit dopamine to the striatum, so there is a loss of dopamine in this area. Other areas of the brain which are not dopaminergic are also affected in Parkinson’s disease.

Aeitiology

Causes of parkinsons disease is unclear. There may be a familial link in some cases, and certain chemicals such as MPTP found in contaminated heroin has been shown to produce similar symptoms.

Presentation

Symptoms of parkinsons disease tends to be very asymmetrical. Gradual onset of reduced dexterity and foot drag are common presentations of Parkinson’s. 

 

stooped shuffling gait.

Tremor

60% of patients present with a coarse resting tremor on first presentation. This tends to affect the hands and is often described as a ‘pill rolling’ tremor. The tremor increases on distraction and emotions (when using contralateral limbs) and reduces during voluntary movement and sleep. Tremor can also affect other parts of the body such as the chin, tongue and legs.

Rigidity

In additional to the tremor patients with parkinsons present with asymmetrical rigidity which when combined with the tremor can create a ‘cogwheel’ rigidity. This is exaggerated with movement of the opposite arm.
 

Bradykinesia/hypokinesia
Bradykinesia refers to the slowing of movement and fatigue when performing repetitive movements, and hypokinesia refers to reduced amplitude of movements. This affects both the limbs, face and muscles of mastication, speech and swallowing. This causes a mask like face with reduced blinking, a monotonous weak voice. Handwriting becomes smaller (micrographia. In addition, the patients may have difficulty with walking, having a shuffling gait, and difficulty turning. There is difficulty initiating movements when the patient starts to walk, and when turning both whilst walking or when lying in bed. Patient will have frequent falls as they loose their normal balancing reflexes.

Posture
Patients with Parkinson’s becomes flexed  

Cognitive problems
Patients often become depressed and dementia may occur later in the disease.

Other symptoms
Patients with parkinson’s also have issues with sensory changes and pain, weight loss, constipation, detrusor hyperreflexia causing urge incontinence and frequency and erectile dysfunction in men, loss of libido, postural hypotension, and sleep problems. These may be a result of both the disease and its treatment.

Diagnosis can be made by the UK Parkinson’s disease society brain bank criteria which requires bradykinesia and other symptoms and the exclusion of alternative causes of parkinsonism to make a diagnosis of parkinson’s disease. Full criteria can be found here:  http://www.patient.co.uk/doctor/parkinsonism-and-parkinsons-disease
Where new parkinson’s disease is suspected, the patient should be referred to a neurologist within 2-6 weeks depending on the extent and complexity of the disease at time of presentation.

Differential diagnoses:

• Benign essential tremor – usually worse on movement, rare at rest. 
• Drug induced tremor – SSRIs, caffeine, amphetamines, b-blockers, tricyclics, lithium.
• Psychogenic tremor – increases on observation, decreases on reduced observation.

Alternative causes of parkinsonism include:

• trauma – subdural haematoma, repetitive head injury
• Cerebrovascular event – lacunar infarcts of the basal ganglia and small vessel disease – tends to cause some upper motor neuron signs as well as extrapyramidal signs, tends to affect the lower legs, with asmall stepped gait and upright stance.
• Infections – encephalitis lethargica, Japanese encephalitis
• Tumors
• Wilson’s disease – copper deposition in the brain causes parkinsonism – tends to occur in younger patients (young adults)
• Antipsychotics and antiemetics  - eg. Haloperidol, chlorpromazine, metoclopermide and prochlorperazine may cause parkinsonism.
• Atypical parkinsonian disorders – progressive supranuclear palsy, multisystem atrophy, corticobasal degeneration. 
• Gait disorders – gait apraxia/ disease of the cerebellum.

Investigations:
Parkinsons is diagnosed clinically. A dopamine transporter single photon emission computed tomography (SPECT) may show reduced dopamine transporter binding but is not used routinely for diagnosis. It is used as a test to rule out parkinsons where it is difficult to differentiate an essential tremor from parkinsonism. Other investigations may be used where an alternative diagnosis is suspected.

Management:
Medical management should be informed by the patients lifestyle and preferences. Management primarily consists of drugs which increase dopamine levels. Surgical deep brain stimulation can also be considered where medical management fails. Physiotherapy, occupational therapy and language therapy may be helpful in difficulties with balance, speech, and gait where limb disorders are optimally medically treated. Dementia may be worsened by medications for parkinsons disease and is difficult to treat but may be treated with atypical antipsychotics without worsening symptoms.  When a patient with Parkinson’s disease presents with confusion, reversible causes should first be considered.

Levodopa

Combined peripheral decarboxylase inhibitor and inactivated dopamine. Improves bradykinesia and rigidity. Duration of action of medication decreases and fluctuation of motor symptoms occur. As effectiveness decreases it can cause unpredictable ‘on periods’ with choreiform movements, and ‘off periods’ with freezing. Also causes drowsiness, postural hypotension, and psychiatric complications (nightmares, illusions, hallucinations)

Dopamine agonists
Directly stimulate dopamine receptors. Appart from apomorphine dopamine agonists are often used first line to delay the need for L-dopa. Older agonists can cause fibrosis and are no longer used.

Anticholinergic
Anticholinergics can be used to reduce tremor but does not affect rigidity and bradykinesia as much. They can cause multiple side effects including dry mouth, constipation, urinary retention, visual blurring, hallucinations, confusion and memory problems.

Monoamine oxidase B inhibitors

MOAB blocks the degradation of dopamine. They can be used to delay the need of L-dopa or to increase their efficacy.

COMT inhibitors

Prevent break down of dopamine peripherally. Used in conjunction with Ldopa.

Prognosis:

Parkinsons tends to progress over several years, usually about 10-15 years with increasing immobility, falls and cognitive problems. Death often occurs from bronchopneumonia. 

References
Yogarajah, Crash course in Neurology, 4th ed. Edinburgh, Mosby elsevier, 2013.
http://www.patient.co.uk/doctor/parkinsonism-and-parkinsons-disease

http://en.wikipedia.org/wiki/File:Paralysis_agitans-Male_Parkinson%27s_victim-1892.jpg