Multiple System Atrophy (MSA)
|Parkinson Plus syndromes
|Idiopathic Parkinson disease
|Progressive Supranuclear Palsy
|Drug Induced Parkinson disease
- Potentially progressive and disabling disease
- Seen in elderly and genetic variants in younger patients
- Generally poorly understood. There is a loss of the pigmented cells of the substantia nigra.
- Resultant disruption of negative and positive feedback circuits from frontal cortex via basal ganglia to the thalamus and substantia nigra and back
- Brain studies show intraneuronal inclusions containing aggregated alpha-synuclein
- Could there be a Prion or Ingested environmental toxin
Pathology : Braak staging of Parkinson disease
- Disease process commences in the lower brainstem in the dorsal motor nucleus of the vagus nerve (DMV), as well as anterior olfactory structures.
- Ascends rostrally from the DMV through susceptible regions of the medulla, pontine tegmentum, midbrain, and basal forebrain, eventually reaching the cerebral cortex
- This is a non-random, progressive process, with specific nuclei and neuronal types giving rise to the development of Lewy pathology in a stereotypic pattern
- As the pathology advances upwards from the brainstem, both the severity of the lesions and the clinical manifestations of the disease increase
Cross section through midbrain shows loss of Dopamine releasing substantia nigra (pigmented area)
- Genetic clues to PD are several genetic causes of Parkinson's disease in those under 40. The ones to remember are
- Park1 - Mutation in gene for alpha-synuclein which is a component of Lewy bodies which are found in almost all cases of IPD. Gene is Chromosome 4 Autosomal dominant
- Park2 - Mutation in Park2 gene which codes for Parkin Chromosome 6q Autosomal recessive
- Patients with Parkin mutations have extreme sensitivity for L-Dopa and respond well to treatment over decades with minimal doses and a low threshold to develop dyskinesias. With treatment, they also have great sleep!
- Idiopathic PD can only be diagnosed in the presence of upper limb bradykinesia
- The tremor is 4Hz pill-rolling rest tremor when the hand is motionless.
- Benign Essential tremor can be postural
- Either Lead pipe or cogwheel rigidity is seen in IPD
- Signs are often asymmetrical especially early on and this is quite typical
- Hypophonia, Micrographia, mask face
- Loss of arm swing is an early sign, flexed posture, festinant gait, freezing
- Siallorhoea -actually drooling more to do with reduced swallowing rather than overproduction of saliva
- There are 2 out of 4 of Tremor, Rigidity, Akinesia and Postural instability (TRAP)
- It is progressive, there is a clinical response to Levodopa
- There is no alternative cause for the parkinsonism
Use of Imaging
- MRI or CT if MRI not possible: recommended in patients where it would be clinically helpful to identify: the degree and extent of cerebrovascular disease, in particular in subcortical brain areas including the basal ganglia, to differentiate idiopathic Parkinson's disease from vascular parkinsonism
- DaT Scan (DaT scan or Dopamine Transporter Scan) 123I-FP-CIT SPECT scanning should be considered as an aid to clinical diagnosis in
patients where there is uncertainty between Parkinson's disease and non-degenerative parkinsonism/tremor disorders. So indicated when the diagnosis is between PT and Essential tremor. Routine use of functional imaging is not recommended for the differential diagnosis of Parkinson's disease and Parkinson's plus disorders such as progressive supranuclear palsy and multiple system atrophy
Commas are normal. Full stop/period is abnormal
Stages of Parkinson's Disease
- Stage One: During this initial stage, the person has mild symptoms that generally do not interfere with daily activities. Tremor and other movement symptoms occur on one side of the body only. Friends and family may notice changes in posture, walking and facial expressions.
- Stage Two: In stage two of Parkinson, the symptoms start getting worse. Tremor, rigidity and other movement symptoms affect both sides of the body. Walking problems and poor posture may become apparent. In this stage, the person is still able to live alone, but completing day-to-day tasks becomes more difficult and may take longer.
- Stage Three: Stage three is considered mid-stage in the progression of the disease. Loss of balance and slowness of movements are hallmarks of this phase. Falls are more common. Though the person is still fully independent, symptoms significantly impair activities of daily living such as dressing and eating.
- Stage Four: During this stage of Parkinson's, symptoms are severe and very limiting. It's possible to stand without assistance, but movement may require a walker. The person needs help with activities of daily living and is unable to live alone.
- Stage Five: This is the most advanced and debilitating stage of Parkinson's disease. Stiffness in the legs may make it impossible to stand or walk. The person requires a wheelchair or is bedridden. Around-the-clock nursing care is required for all activities. The person may experience hallucinations and delusions.
- General: Patients with suspected Parkinson's disease should be referred untreated to a hospital clinician with sufficient expertise in movement disorders to make the diagnosis. Patients should be offered long term, regular, follow up to review the diagnosis of Parkinson's disease. This should include a review of the ongoing benefits in those started on dopamine replacement therapy. Patients initially considered to have a possible diagnosis of Parkinson's disease may benefit from a trial of dopamine replacement therapy to assist with an accurate diagnosis.
- Early disease: The diagnosis is clinical and early on there is often no rush to start treatment until there is an impact on functional abilities. Clinicians should be aware of the poor specificity of a clinical diagnosis of Parkinson's disease in the early stages of the disease and consider this uncertainty when giving information to the patient and planning management. No medications have been shown to be neuroprotective. This gives a chance to monitor. IPD will usually progress with time and patients can be reviewed every 6 months. Rasagiline 1 mg OD is often used as an MAOI B inhibitor in early PD and can later be given with formulations of levodopa
- Levodopa: When activities of life affected then consider starting a combination of Levodopa and a peripheral decarboxylase inhibitor as Madopar or Sinemet. If the diagnosis is uncertain a trial of therapy can be considered. The main issue is that the most effective drug Levodopa over the years then tends to cause extra movements so-called dyskinesias as well as becoming less effective. Levodopa helps relieve bradykinesia, rigidity, tremor and improvement of ADLs. It is Low cost. Given 3-5 times a day. Slow titration to therapeutic dose to avoid adverse effects. Long term causes dyskinesias. A dispersible form is available. It is given as Levodopa with a peripheral decarboxylase inhibitor e.g. Sinemet or Madopar which prevents breakdown peripherally and so reduces toxicity.
- COMT Inhibitors: Levodopa and a decarboxylase inhibitor may also be combined with COMT inhibitors such as entacapone. The Levodopa dose may need to be reduced. This can help reduce Off periods. Catechol-o-methyl transferase inhibitors may be considered for the reduction in off time in patients with advanced Parkinson's disease who have motor fluctuations. Entacapone should be used in preference to tolcapone.
- Dopamine agonists e.g. ropinirole, pramipexole: Dopamine agonists are useful but are less effective and often more popular in younger patients. Long-acting, once-daily preparations available if tablet burden problematic. Lower incidence of long term motor fluctuations and dyskinesias. Less effective for bradykinesia and improving ADLs. Adverse effects: hallucinations, low blood pressure, sudden onset of sleep, confusion in older patients and possible gambling/hypersexuality or punding. Patients should be warned about the potential for dopamine agonists to cause impulse control disorders and excessive daytime somnolence and be informed of the implications for driving/operating machinery
- Rotigotine is a dopamine agonist available in a patch and may be used for patients intolerant of or unable to take other dopamine agonists or those with prominent nocturnal /early morning symptoms. Also indicated in patients that are nil by mouth or unable to swallow where appropriate. See Wirral clinical guideline - 'Parkinson's Disease Initial Medical and Surgical Management Checklist (rotigotine conversion table)'
- MAO B Inhibitors. Selegiline/Rasagiline: Once daily administration. Possible disease-modifying effect. Adverse effects: confusion, postural hypotension (especially with selegiline). Mild efficacy. Interactions with SSRIs / pethidine and nasal decongestants (pseudoephedrine) Rasagiline may be used for patients intolerant of or unable to take other MAOBI's or where compliance is a concern
- Anticholinergics. Trihexyphenidyl (benzhexol): Avoid in older patients as can worsen cognition. Used in young patients where tremor predominates and side effects less. Use Benzhexol and titrate slowly. Adverse effects: dry mouth, urinary retention, constipation, blurred vision, impaired cognitive function. Rarely indicated in older patients due to risk of confusion, orphenadrine may occasionally be used. On-off phenomena are also seen when patients suddenly lose all function. Has been improved slightly with COMT inhibitors.
- Amantadine: has been used in advanced IPD for drug-induced dyskinesias. Use cautiously as can cause cognitive impairment
- Surgery - deep brain stimulation may be considered. An elective surgical procedure in which electrodes are implanted into certain brain areas such as the subthalamic nucleus or the Globus pallidus interna. These electrodes, or leads, generate electrical impulses that control abnormal brain activity. The electrode lead inserted through an opening in the skull and implanted into a specific brain area. This is connected to a pacemaker-like device called a pulse generator. Successful DBS allows a decrease in medication or makes a medication regimen more tolerable in these disorders. There are gains in movement and control.
- Specialist nurse support, Occupational therapy and physiotherapy. A multidisciplinary team approach is needed. Equipment and advice is useful. Speech and language may also need to give some help. See non-motor problems below.
- Be aware of Impulse control disorders(see entry) which may worsen with dopamine agonists in which there are abnormal behaviours.
First 24 hours in Hospital
- Ensure accurate medication reconciliation. Ensure all medication prescribed at the correct dose and time and facilitate patient self-administration whenever possible. Assess swallow early and ensure the provision of medication via alternative route ASAP if any concerns. Ensure contra-indicated medications are not prescribed. Sit out and mobilise early as appropriate. Involve physiotherapy early
- Risks of omitting Parkinson's medication: Deterioration of swallow - higher than normal risk of aspiration and aspiration pneumonia. Exacerbation of Parkinson's symptoms - motor (mobility, self-care, falls risk) and non-motor (pain, anxiety, lack of concentration and focus, slowness of thought). Deterioration in longer-term Parkinson's control - can result in a permanent reduction in mobility.
- Failure to prescribe can cause Neuroleptic Malignant Syndrome - pyrexia, fever, confusion, raised CPK, muscle rigidity, altered consciousness. Death - patients with Parkinson's have greater in-hospital mortality. Ensuring patients receive their usual medication and timely specialist review will reduce this risk
- It is vitally important that PD medication must be continued even if the patient is in a hospital or needs surgery and is fasting or unable to swallow.
- If no swallow then considers NG tube and use the online calculator to convert oral levodopa or dopamine agonist preparations into a madopar dispersible regime (Online calculator). If the patient is already taking a Rotigotine patch, this can continue.
- Parenteral route: If NBM then an alternative is to convert to rotigotine patch useful for patients with lengthy surgery and/or prolonged nil by mouth due to ileus, delayed gastric emptying, or nausea and vomiting. Use the online calculator to convert oral levodopa or dopamine agonist preparations into a rotigotine patch regime
Non Motor Issues
- Lower respiratory tract infection: Early physiotherapy, sitting out and mobilisation. Mobilise.
- Constipation: will affect medication absorption. Treat aggressively with a macrogol (polyethylene glycol) laxative. Ensure adequate hydration and encourage mobility.
- Urinary tract infection: Ensure constipation adequately treated. Ensure adequate hydration. Consider community-based anticipatory care pathway for future management if the cause of recurrent admissions
- Orthostatic hypotension: Ensure adequate hydration and salt intake. Rationalise anti-hypertensive medication. Consider compression hosiery (if not contra-indicated). Consider fludrocortisone. Consider Midodrine
- Urinary dysfunction: Refer patients with refractory or persistent bladder problems to a urologist as a comprehensive assessment is needed. Trospium is less likely to cause anticholinergic effects of confusion.
- Siallorhoea: Hyoscine patches can be used but only if the patient is not confused. The PD UK society suggests sucking clove sticks. Atropine 1% eye drops twice daily in the mouth can be used (unlicensed indication).
- Falls: Look for and treat any underlying orthostatic hypotension. Ensure early physio review. Consider bone health. Aim to optimise mobility. Conduct a full falls assessment (NICE CG21). Consider prescribing alendronic acid with calcium and vitamin D to reduce fracture risk where appropriate.
- Polypharmacy - be cautious as centrally-acting anti-emetics (such as metoclopramide, cyclizine, prochlorperazine), can worsen Parkinson's disease. Anticholinergics (such as oxybutynin, imipramine, amitriptyline), can worsen confusion
- Depression: A review concluded that amitriptyline was effective in treating depression in patients with PD although this had to be balanced against its anticholinergic side effects. Best choice: SSRIs, particularly sertraline. Severe dyskinesias consider amantadine: Relieves moderate dyskinesias. Rapid response. Effects mild and unsustained. Confusion with higher doses
- Dementia: Cholinesterase inhibitors have shown efficacy for the treatment of cognitive decline in PD. Rivastigmine (Specialist initiation only). May improve cognition, hallucinations & delusions but tremor may deteriorate.
- Psychosis: Patients with psychosis in Parkinson's disease should be considered for treatment with low-dose clozapine and undergo weekly monitoring for the first 18 weeks of treatment
followed by fortnightly monitoring for the first year and then monthly thereafter. Where weekly monitoring of blood is not possible on a consistent basis, low-dose
quetiapine should be considered as an alternative antipsychotic for the treatment of
patients with psychosis in Parkinson's disease
- Advance Planning: Should discuss the progression of Parkinson disease. Possible future adverse effects of medicines for Parkinson disease. Advance care planning, including orders for advanced decisions to refuse treatment and do not attempt resuscitation, and lasting power of attorney for finance and health and social care. Options for future management: What could happen at the end of life. Available support services; for example, personal care, equipment and practical support, financial support and advice, care at home and respite care.