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Parkinson’s Disease

Parkinson’s disease is a neurodegenerative disorder characterized by cardinal symptoms of 
stiffness , resting tremor , slowness ( bradykinesia ) and reduction of movement 
( hypokinesia ) Clarke CE BMJ 2007 

Parkinsonism describes the motor features of PD and Parkinson’s disease is the most 
common cause of Parkinsonism. 

PD can also be divided into two types based on origin (1 ) Primary or Idiopathic (2) secondary or acquired where the disease is linked to various offending agents such as drugs , toxins , infection , tumour etc.

How common ? PD is the second most common neurodegenerative disease after Alzheimer disease Named after London GP James Parkinson who described this it in 1817 in ‘ Essay on the shaking palsy ‘ Lifetime risk is approximately 3-7 % Parkinson’s disease typically develops between the ages of 55 -65 It affects 1-2 % of people over the age of 60 which rises to 1-3 % by the age of 85-89 About 0.3 % of the general population is affected More common in men and in people of white descent compared to people of Asian and African descent The global prevalence of PD is increasing over time and is expected to double by 2036 The disease has significant socioeconomic costs for e.g in Europe in 2010 the cost of PD alone was 13.6 Billion euros.

What happens –Chronic progressive disorder with no cure Syndrome involving multiple motor and non-motor neuronal circuits Two major pathological processes
1 premature selective loss of dopamine neurons in the SN pars compacta
2 accumulation of Lewy bodies in multiple systems throughout the brain
Lewy bodies are composed of numerous proteins ( alpha-synuclein ) – ie accumulation of protein is thought to play an important role in the pathogenesis of PD

This lead to lack of dopamine in the brain.
Dopamine is a neurotransmitter involved in movement , motivation , memory and other functions. It is also thought that dopamine deficiency is also responsible for the cognitive deficits seen in some PD patients.
 Symptoms of PD usually do not develop until 70-80 % of dopaminergic neurons have been lost Six neuropaptholgical stages of the disease based on localization of the involved brain regions have been identified (Braak et al 2003 ).

Risk factors –About 10-15 % of cases are early onset familial PD- Family history and genetics
First degree member with PD
Atleast 11 different linkages and 6 gene mutations have been found Exposure to environmental toxins fo e,g pesticide and herbicide exposure
Accumulation of heavy metals in Substantia nigra enhances the risk of developing PD increasing age ethnicity- more common in whites head trauma ( injury to head , neck or upper cervical spine )- not conclusive.

Barriers in diagnosis –Motor symptoms usually begin asymmetrically and gradually spread to the contra-lateral side Presentation may vary from patient to patient Features of early PD are often subtle and the disease often goes unrecognized classic symptoms reflect advanced disease Current diagnosis relies on recognising the motor symptoms and assessing the response to treatment In primary care setting nearly 47 % of the PD diagnosis is incorrect and specialists whose expertise is not specific to PD have an error rate of about 25 % , while movement disorder specialists get it wrong only in about 6-8 % of cases.

Diagnosis –PD is a clinical diagnosis NICE suggests to suspect PD in people with tremor , stiffness , slowness, balance problems and or gait disorder Although PD is predominantly a movement disorder -Non-motor symptoms are seen in 90 % of all IPD ( Idiopathic PD ) patients in all stages of the disease The diagnosis is clinical -no diagnostically conclusive test yet hence missed or misdiagnosis is common leading to delays in treatment. NICE recommends using the UK Parkinson’s Disease Society Brain Bank ( UKPDSBB) criteria for the diagnosis of PD which suggests a stepwise approach.

Differentials –Side effects of medicines- drug induced parkinsonism is very common and may constitute the 2nd most common cause of parkinsonism benign essential tremor cerebro-vascular disease metabolic causes degenerative conditions as progressive supranuclear palsy and multi-system atrophy Lewy body dementia Corticobasal degeneration Alzheimers disease with Parkinsonism Wilson’s disease Creutzfeldt-Jakob disease normal pressure hydrocephalus basal ganglia tumour olfactory dysfunction Post-traumatic brain injury PD

Motor symptoms
Bradykinesia –slowness in initiation of voluntary movements more disabling feature and present in 80-90 % of patients decreased amplitude of movement Inability to rise from chair , difficulties getting in and out of the car If bradykinesia is combined with rigidity – this may manifest as micrographia if the dominant hand is involves May also manifest as slow-movement hypophonia- weak voice or whispering due to un-cordination of muscles of vocalization reduced dexterity masked face drooling decreased blink rate slow shuffling gait.

Rigidity-velocity independent increase in muscle tone affects > 90 % of patients can be tested by passive flexion/ extension and pronation / supination of the elbow and forearm Cogwheeling – is the ratchety ( ie resistance fluctuates in intesity ) motion elicited on circumduction of the wrist and represents rigidity interrupted by periodic tremor and is ubiquitous of PD.

Tremor -Common initial symptom Unilateral on onset Most commonly 5Hz affecting the upper limbs Tremor amplitude is often enhanced at rest , during walking , distraction , concentration on a cognitive or motor task and during stress Resistance to passive movements in both flexors and extensors with limb relaxed Pill-rolling motion of thumb and index finger Tremor is more likely to be the presenting symptom in younger patients , whereas older patients may have more prominent bradykinesia

Postural instability-Often represents advanced stage of the disease predisposes to falls and injuries can be tested by pull test- a tendency to fall backwards after a sharp pull from the examiner pronounced postural instability at initial presentation may reflect another diagnosis for e.g progressive supranuclear palsy rather than iPD responds poorly or no response to dopaminergic therapy.

Non-motor symptoms-Non-motor symptoms manifest in PD long before motor symptoms They offer an early opportunity for detection and treatment of PD as by the time motor symptoms appear over 60 % of all dopaminergic neurons within the specific regions of basal ganglia may have
been lost Initial suggestion that PD is a mainly nigrostriatal disorder is no more sustainable and it is now thought that pathology first starts in the the entire nervous system of yhe gut and in the medulla and olfactory bulband from here it spreads through neurons to the 
substantia nigra ( Braak et al 2003 )- this called the Braak theory.

Autonomic dysfunction –orthostatic hypotension gastro-intestinal dysfunction e.g constipation urinary frequency and urgency ( OAB ) erectile dysfunction sweating abnormalities- xerostomia dysphagia and choking hypersalivation.

Neuropsychiatric-depression ( in up to 50 % ) anxiety including panic attacks cognitive dysfunction/ decline dementia premorbid personality traits confusion or delirium psychosis apathy.

Sleep disturbance –common but cause is unclear insomnia nightmares excessive day time sleepiness restless legs and periodic limb movements rapid eye movement disorder.

Sensory-olfactory dysfunction- common pain paraesthesia
Others-fatigue diplopia , blurred vision weight loss seborrhea

Refer all people urgently and
untreated to a neurologist if PD is 
suspected ( CKS ) Drugs most commonly associated with DIP are those with dopamine receptor blocking properties such as ant-psychotics If you suspected PD and the patient is taking one of these drugs- consider reducing/ stopping if possible and appropriate but do not delay referral to assess response ( CKS )

LINKS AND RESOURCES

 

PATIENT INFORMATION

A complete handbook for the patient from the American Parkinson’s Disease Association –https://www.aafp.org/afp/2014/0115/p99.html

American Association of Neurological Surgeons https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Parkinsons-Disease

Parkinson’s Foundation https://www.parkinson.org/understanding-parkinsons

National Institute of Neurological Disorders and Stroke https://www.ninds.nih.gov/Disorders/All-Disorders/Parkinsons-disease-Information-Page

Michael J Fox web page https://www.michaeljfox.org/parkinsons-101

American Parkinson Disease Association https://www.apdaparkinson.org/

Downloadable leaflets from Parkinson’s Australia https://www.parkinsons.org.au/information-sheets

Parkinsons treatment summary – information about drugs https://www.parkinsons.org.uk/information-and-support/parkinsons-drugs

HSE Ireland on Parkinson’s https://www.hse.ie/eng/health/az/p/parkinson’s-disease/treating-parkinson’s-disease.html

INFORMATION FOR HEALTHCARE PROFESSIONALS

A useful section for primary care workers from Parkinson’s org UK https://www.parkinsons.org.uk/professionals/resources

NICE guideline https://www.nice.org.uk/guidance/qs164/resources/parkinsons-disease-pdf-75545600441029

European Medicine Agency guideline 2012 https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-investigation-medicinal-products-treatment-parkinsons-disease_en-0.pdf

Spanish Guidelines for PD https://portal.guiasalud.es/wp-content/uploads/2018/12/GPC_546_Parkinson_IACS_comp_en.pdf

 

 

References

  1. Parkinson’s Disease – Part 1 : Pathophysiology , Symptoms , Burden , Diagnosis and Assessment by Daniel Weintraub MD et al www.ajmc.com 2008 The Diagnosis and Management of Parkinson’s Disease Sanad Esmail Sch J Appl Sci Res 2018 Volume 1:9
  2. Parkinsons Disease : Biomarkers , Treatment and Risk Factors Fatemeh N Emanzadeh et al Front Neurosci 2018 :12:612
  3. The Value of Early Diagnosis and Treatment in Parkinson’s Disease The London School of Economics and Political Science 2016
  4. The management of Parkinsons disease – Which Treatment to start and When  BPAC Org NZ BPJ Issue 58
  5. Pathophysiology of Parkinson’s disease Michael J Zigmond et al via ACNP Org
  6. Diagnosis and Differential Diagnosis of Parkinson’s Disease Paul Lingor et al via Intechopen com
  7. A review of Parkinson’s Disease by CA Davie British Medical Bulletin 2008 ;86:109-127
  8. Parkinson’s disease and its Management Part-1 : disease entity , risk factors , pathophysiology , clinical presentations and diagnosis George DeMaagd et al PT.2015 Aug ; 40 (8) : 504-510 , 532
  9. Parkinson’s Disease in Adults NICE July 2017
  10. Parkinson’s disease : Research Update and Clinica Management Thomas Fritsch et al The Southern Medical Association 2012
  11. CKS NHS Parkinsons disease https://cks.nice.org.uk/parkinsons-disease
  12. BMJ Best Practice Parkinsons’ Disease https://bestpractice.bmj.com/topics/en-gb/147

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