Parkinson's disease

From Ganfyd

A neurodegenerative disease. Described by James Parkinson in his essay on the shaking palsy in 1817. The disease was named after him by Jean-Martin Charcot, the French neurologist. It should be distinguished from Parkinsonism which can be caused by this as well as many other conditions that have a different prognosis and responses to treatment. The term Parkinson's Syndrome is used by some to cover conditions which do not clearly fit a diagnostic label by reason of features.

Aetiology

An imbalance of neurotransmitter and neurone function associated with a loss of dopaminergic neurones in the substantia nigra and basal ganglia. Other types of neurons and wider parts of the nervous system are also affected. The underlying aetiology is unknown. Oxidative damage, viral infection, environmental toxins have all been suggested. The negative association of parkinsonism with smoking ^[1] and positive one with pesticide exposure^[2] which may be more important in late onset parkinsonism^[3] are consistent with mitochondrial metabolism producing chronic neurotoxins but the likely large separation in time between initiating cause(s) and the complex polygenetics make this extremely difficult to unravel.^[4] Indeed there are other associations such as the one with malignant melanoma that may well have a genetic basis but have distracted doctors into blaming therapy (levodopa).^[5] The genetics are a factor in the age of onset, as has been confirmed with the mutations of the glucocerebrosidase encoding gene that increase the risk of the condition by over 5 times^[6]. The well characterised monogenetic forms of familial Parkinsons's disease are extremely rare and usually present in patients aged in their early 30s or before.

Pathology

See Pathology of Parkinson's disease

Symptoms

• Tremor
• Difficulty with fine movements e.g. trouble doing buttons or deteriorating handwriting
• Deteriorating mobility with or without shuffling gait
• Muscle stiffness
• Falls
• Fatigue
• Constipation
• Lethargy
• Aches
• Reduced sense of smell or taste
• Impotence
• Depression - a major cause of morbidity in PD. Should be actively sought and treated
• Dementia - typically late in disease. Early onset may suggest dementia with lewy bodies

Signs

Some use the acronym 'TRAP'

• Tremor - pill rolling tremor, predominantly at rest
• Rigidity - lead pipe or with tremor becomes cogwheel
• Akinesia or bradykinesia
• Postural Instability

These are the cardinal signs of parkinsonism with bradykinesia being the key sign and postural instability depreciated due to its presence in many other common conditions that never strictly manifest parkinsonism.

In the early stages of Parkinson's disease, the signs are typically asymmetrical and most commonly affect the upper body. Symmetrical and/or lower body Parkinsonism should raise the possibility of an alternate diagnosis.

Other signs

• Siallorhoea
• Hypomimia
• Hypophonia
• Flexed posture
• Festinant gait with reduced arm swing
• Glabellar tap
• Micrographia

Differential diagnosis

• Multiple systems atrophy
• Progressive supranuclear palsy
• Dementia with Lewy Bodies
• Vascular Parkinsonism
• Drug induced Parkinsonism
• Dementia associated Parkinsonism - commonly Alzheimer's disease but also other dementias
• Essential tremor

Investigations

These are done for the exclusion of the wide range of other conditions that can cause or mimic Parkinsonism. While certain types of PET and SPECT scans can give consistent information, they do not add to the clinical formulation in most patients, so are not usefully routinely. A DAT scan can be useful in certain tremor presentations, as the initial differential diagnosis of patients presenting with parkinsonian tremor alone can be narrowed earlier than would otherwise be the case.

Treatment

The Team

Patients widely perceive that a consistent and comprehensive approach appropriate to their current disease manifestations is most effective. In advanced disease they may be interacting routinely with several, or almost all of a general practitioner, district nurses, professional carers, Parkinson's disease nurse, speech therapist, physiotherapist, occupational therapist, geriatrician, pyschiatrist, neuropsychologist, neurologist and neurosurgeon. Increasingly in the UK such services are being networked with usually geriatricians and neurologists with a subspeciality interest providing best access to core support services like the Parkinson's disease nurse and dealing with the more complex patient.

The coordination of the team

This remains a challenge in a number of ways, including informatics, human relations and disruption due to resource allocation.

Education

This has been the subject of numerous studies. There is a wide range of educational material available and evidence for successful approaches, including support networks. Guidance on this range of material can be an important role for the clinical team, particularly as the available material or information previously known may not be relevant to the patient.

Drug therapy

• L-Dopa The remarkable benefits of L-Dopa was accepted following a paper in the New England Journal of Medicine in 1967 although it had been convincingly demonstrated in 1961 by Birkmayer and Hornykiewicz (archive film exists). Significant benefits were seen on a group of patients with Parkinsonian features. With the addition of a peripheral decarboxylase inhibitor in the early 1970s the side effects and dose of drug could be increased and efficacy improved. The COMT inhibitors work by inhibiting catechol O-methyltransferase which increases levodopa availabilty by stopping its metabolism to 3 O-methyldopa.
• Dopamine agonists These drugs have been introduced more recently. They can be used as first line therapy for Parkinson's disease or as adjunctive therapy given longside l-Dopa. Early use of these drugs alone in younger patients is associated with delay in the onset of motor complications, particularily dyskinesias. However they provide less symptomatic relief than levodopa prepartions and tend to have poor clinical effectiveness or large incidence of adverse effects in conditions other than idiopathic Parkinson's disease. They include:
  • The Ergot alkaloids -whose use is increasingly being depreciated to second or third line with limits on total exposure. The long half life of carbergoline was a major advantage.
    • Bromocriptine
    • Pergolide
    • Cabergoline
    • Lisuride
  • The non-ergoline dopamine antagonists- these presently have a good evidence base for use in early disease in young patients
    • Ropinirole
    • Pramipexole
    • Rotigotine - Available as a patch
    • Piribedil
  • Apomorphine - The last resort, and a very effective one in some it is too.
• Anticholinergic agents The first effective drug treatment for Parkinson's disease. Rarely used nowadays especially in the elderly as they tend to cause profound confusion as the disease progresses. May be more beneficial in tremor dominant disease.
• COMT inhibitors
  • Entacapone
  • Tolcapone - requires special monitoring for hepatotoxicity
• MAO B inhibitors
  • Selegiline
  • Rasagiline
• Other
  • Amantidine This drug with a limited but distinct role has multiple neurotransmitter actions and with increasing knowledge of the properties of other neurotransmitter specific drugs yet to come on the market is perhaps best left unclassified. Used with tremor and dyskniesias

• • Sildenafil and similar drugs may be prescribed at NHS expense for men with Parkinson's disease. (GPC News 11, 21.05.99

http://web.bma.org.uk/gpc.nsf/daf48a34f30ad59580256706003d9556/588659c4eef25eda80256778004d06dd?OpenDocument )

Surgery

Has a place in selected patients. The proven techniques rely on neurostimulation and are:

• Subthalamic stimulation
• Pallidal stimulation

Complex complications

There are many with some specific treatments including:

• Cognitive impairment
  • A complex area to be distinguished from the dementia found in other diseases with parkinsonism
• Psychosis
  • Classically visual, more rarely auditory (10%) and tactile (8%)
  • In up to 40% during course of illness
• Dopamine dysregulation syndrome
  • Often manifest as behavioural phenomena such as punding or pathological gambling
• Other non motor symptoms
  • Very important for patients and their quality of life. Include:
  • Pain
  • Constipation

Tools exist for evaluating theses symptoms : see NMSQuest and NMSS

NICE Key Recommendations

In June 2006 NICE published guidelines for England and Wales. The key recommendations which are edited for brevity were:

• Referral to expert for accurate diagnosis
  • People with suspected PD should be referred quickly and untreated to a specialist with expertise in the differential diagnosis.
• Diagnosis and expert review
  • The diagnosis of PD should be reviewed regularly and reconsidered if atypical features develop.
  • Acute challenge tests should not be used in the differential diagnosis of parkinsonian syndromes.
• Regular access to specialist nursing care for:
  • Clinical monitoring and medication adjustment
  • A continuing point of contact for support, including home visits
  • Information about clinical and social matters of concern to patients and their carers,
• Access to physiotherapy for:
  • Gait re-education, improvement of balance and flexibility
  • Enhancement of aerobic capacity
  • Improvement of movement initiation
  • Improvement of functional independence, including mobility and activities of daily living
  • Advice regarding safety in the home.
• Access to occupational therapy for:
  • Maintenance of work and family roles, employment, home care and leisure activities
  • Improvement and maintenance of transfers and mobility
  • Improvement of personal self-care activities
  • Environmental issues to improve safety and motor function
  • Cognitive assessment and appropriate intervention.
• Access to speech and language therapy for:
  • Improvement of vocal loudness and pitch range, including speech therapy programmes such as Lee Silverman Voice Treatment (LSVT)
  • Teaching strategies to optimise speech intelligibility
  • Ensuring effective means of communication throughout the course of the disease, including use of assistive technologies
  • Review and management to support the safety and efficiency of swallowing and to minimise the risk of aspiration.
• Palliative care
  • Requirements for this should be considered throughout all phases of the disease.
  • Patients and their carers should be given the opportunity to discuss end-of-life issues with appropriate healthcare professionals.

Prognosis

Relatively good for a progressive neurodegenerative disease. It is interesting that during the first three years after diagnosis mortality appears to be less than that in the general population but by 20 years follow up matters are much more bleak. The death rate is 74% by then, three times that of the matched population, with only 4.5% of the original cohort escaping either death or dementia by then^[7]. Apart from dementia very advanced Parkinson's disease is associated with:

• Falls (87%)
• Freezing (81%)
• Dysarthria (81%)
• Hallucinations (74%)
• Urinary incontinence (71%)
• Excessive daytime sleepiness (70%)
• Postural hypotension (48%)
• Choking (48%)
• Fractures (35%)

See Also

Video http://medweb.bham.ac.uk/http/depts/clin_neuro/teaching/tutorials/parkinsons/parkinsons2.html an excellent medium for demonstrating this condition. Birmingham University.

References