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By Eamonn Brady MPSI Parkinson's Disease Parkinson's disease is a chronic (long-term) disorder of caused by the degeneration of dopamine generating cells in the mid-section of the brain. The reason for this degeneration in Parkinson’s patients still remains largely unknown. It mainly affects the way the brain co-ordinates movements of the muscles in various parts of the body. Symptoms gradually worsen over time. The main symptoms of Parkinson's disease are stiffness, shaking (tremor) and slowing of movement. There is no cure but treatment can slow down its progression and can provide good relief of symptoms for several years in most patients. Modern treatment options means that people with Parkinson’s can have a normal or near normal life expectancy. Profile of patients According to the Parkinson’s Association of Ireland, approximately 9000 people in Ireland are affected by Parkinson’s. Parkinson’s usually develops in people over the age of 50 and is rare in people under 50. It affects about 5 in 1,000 people in their 60s about 40 in 1,000 people over 80. Men are one and a half times more likely to get Parkinson’s than women; the reason for this is unknown. Parkinson’s does not seem to have a genetic link so it does not appear to run in families. There is some evidence that there is a small risk of a hereditary link in those who develop it under 50. There is some evidence that smoking increases risk of Parkinson’s. Causes The substantia nigra region of the brain is the area affected. The substantia nigra controls muscles in the body by sending messages via nerves in the spinal cord to the rest of the body. Messages are passed between brain cells, nerves and muscles via chemicals called neurotransmitters. Dopamine is the main neurotransmitter produced by the brain cells in the substantia nigra. With Parkinson’s, cells in the substantia nigra become damaged and die over time. As the cells die, the amount of dopamine produced is gradually reduced. Symptoms The brain cells and nerves normally help to produce smooth, co-ordinated movements of muscles. The gradual reduction of dopamine causes the three main symptoms of Parkinson’s, slowness of movement, stiffness and tremor. The symptoms of Parkinson’s often occur in one side initially (eg) tremor in one leg or one hand, loss of ability to swing your arm or leg on one side. It is worth noting that a reduced sense of smell may be one of the initial symptoms in early Parkinson’s. Slowness of movement (bradykinesia). This causes difficulty performing simple and legs tending not to swing as easily. Page Stiffness of muscles (rigidity) is when the muscles become tense with the arms 1 everyday activities like walking, climbing a stairs or getting out of a chair. Many people mistake this as a normal part of aging which means diagnosis is delayed in many cases. Diagnosis often does not occur until other symptoms like tremor of stiffness occur. With time, normal walking becomes difficult and Parkinson’s patients often develop a 'shuffling' type of walk with difficulty in starting, stopping, and turning. By Eamonn Brady MPSI Tremor is common symptom of Parkinson’s. For many people it is the symptom that leads them to seek treatment and thus allow diagnosis. However not all patients with Parkinson’s have tremor. About 30% of Parkinson’s patients do not suffer from tremor initially but it always develops as the condition progresses. It usually affects the fingers, thumbs, hands, and arms, but can affect any part of the body. It is most noticeable when resting. Tremors tend to worsen when anxious or emotional and tends to reduce when using your hands or picking up an object or moving the affected area. The speed in which symptoms become worse varies from person to person. It can take several years before symptoms become bad enough to affect routine tasks and quality of life. In many cases one side of the body may be more affected than the other initially but with time both sides are usually affected equally. As the condition develops and more dopamine receptors are destroyed, other symptoms develop. These include difficulty with balance and posture and an increased tendency to fall. Further symptoms include inability to perform facial expressions like smiling or frowning; reduced blinking; difficulty with fine movements such as using a scissors, tying shoelaces, opening and closing buttons, zipping up and difficulty with writing (handwriting tends to become smaller). There can be a slowdown in speech leading to a monotone voice and swallowing difficulties can develop leading to pooling of saliva in the mouth. Tiredness, aches and pains are other possible symptoms. Other symptoms which occur in some people as the condition develops include: Bladder symptoms including incontinence Constipation Sweating Sexual difficulties. Alterations in sense of smell Sleeping problems (can be disturbed sleep at night or excessive sleep during the day) Hallucinations Weight loss Pain Depression Anxiety Page There is no specific test to diagnose Parkinson’s. Diagnosis is based the typical symptoms. It may be difficult for diagnosis initially with many people not being diagnosed for years after developing the condition as symptoms are mild and may be mistaken as a normal part of aging. Parkinson’s is sometimes confused with other conditions that have some “Parkinson” type symptoms. Parkinson symptoms may occur in people suffering from neurological disorders such as Alzheimer's disease, Huntington's disease, Wilson's disease, spinocerebellar ataxias and CreutzfeldtJakob disease (better known as “mad cow disease”). Other conditions that can occasionally display symptoms similar to Parkinson’s include brain injury, brain 2 Diagnosis By Eamonn Brady MPSI infections (such as encephalitis), hyperthyroidism, brain tumour, liver disease, stroke, carbon monoxide poisoning and heavy metal (such as manganese) poisoning. Some medication can cause side effects that resemble symptoms of Parkinson’s. A form of Parkinson’s which is reversible sometimes develops from some drugs such as chlorpromazine and haloperidol, which are prescribed for patients with psychiatric conditions. Some anti-sickness medication (metoclopramide) and epilepsy medication (valproate) may also cause Parkinson type symptoms. Reducing the dose of these medications generally eases or stops the Parkinson type symptoms. A neurologist or a doctor specialising in elderly care usually makes the diagnosis of Parkinson’s. While a scan of the brain cannot determine if Parkinson’s is present it is sometimes used to differentiate Parkinson’s from other conditions that cause Parkinsonism features. Link between Parkinson's disease and dementia The thinking part of the brain is not affected by Parkinson’s so dementia is not a usual early feature. However, Parkinson’s increases the risk of developing dementia. Approximately 40% of patients with Parkinson’s develop dementia but dementia typically does not develop until 10 years or more after the first Parkinson symptoms occur.3 If dementia occurs, it generally develops in Parkinson patients over 70. The cholinesterase inhibitors rivastigmine (Exelon®), donepezil (Aricept®) and galantamine (Reminyl®) have been shown in studies to have a modest benefit in cognitive function and in the reduction of hallucinations and psychosis in patients with Parkinson related dementia. Rivastigmine appears to be most effective for Parkinson’s related dementia with donepezil to a lesser extent. Treatment While there is no cure for Parkinson’s, treatments can ease symptoms and slow progression. If diagnosis is early, medication is often started before symptoms become troublesome to slow progression. Medication Page Levodopa Levodopa tends to give a good improvement in symptoms. Levodopa is converted to dopamine in the brain. The dose is started low but tends to be increased to control symptoms. Levodopa is always used in combination with another medicine to prevent side effects (either benserazide or carbidopa). Benserazide and carbidopa 3 Scottish Intercollegiate Guidelines Network (SIGN) which is an influential health guidance authority in the UK recommend starting with a dopamine agonist (ie. levodopa) with a dopa-decarboxylase inhibitor or a monoamine-oxidase inhibitor. There are other anti-Parkinson medicines available but they are not used as often as the three types of medication described above but they can be used in addition to these to improve response. Levodopa is considered the most effective Parkinson treatment and is central to any pharmalogical treatment regime. It can take 8 to 10 weeks from the start of treatment before the patient notices improvement in symptoms. By Eamonn Brady MPSI prevent levodopa being converted to dopamine before it reaches the brain thus reducing side-effects. Levodopa combined with benserazide is called cobeneldopa (Madopar®) and levodopa combined with carbidopa is called cocareldopa (Sinemet®). Side effects from Levodopa tend to be rare at low doses. Nausea is the most common side effect. Other side effects which may occur include vomiting, dizziness and low blood pressure; however these often ease after a few days of use and are minimised by starting with lower doses. Levodopa can occasionally cause compulsive behaviour in some people (eg) urge to gamble, spend money. The effect of Levodopa tends to wear off over time, usually over a period of 3 to 5 years. Problems that occur with time include 'on-off' effects; thus alternating between being 'on' (being able to move freely), and being 'off' (not being able to move) in quick succession. Another side effect can be dyskinesia which is uncontrollable jerky movements which can be disabling, tiring and painful. Levodopa can cause other movement disorders such as head nodding, jerking and twitches. Movement disorders caused by Levodopa appear to come on quicker in younger patients (under 60) than older patients. Keeping the levodopa dose at the lowest that is effective to control Parkinson’s symptoms is the best way to reduce risk of movement disorders. Page Despite being slight less effective than Levodopa, one potential advantage of them as compared with levodopa is that their use is associated with at least a 50% lower risk of dyskinesia (involuntary movements) and other movement type side effects in the first four to five years of treatment, particularly among patients receiving dopamine-agonists on their own. Many doctors prescribe dopamine agonists as the first choice to delay the starting of levodopa as levodopa generally only works well for about five years, thus the longer you can hold off using levodopa, the longer it takes to get to the stage when it wears off. A dopamine agonist may be tried in combination with levodopa as the condition gets worse. Apomorphine is an alternative dopamine agonist that is used in combination with levodopa; it is administered as a subcutaneous injection. It is only used when the condition is no longer controlled by the main drugs used for Parkinson’s such as leovodopa and is reserved for patients with severe 'off' episodes and immobility. As its effect wears off after about an hour, frequent injections are therefore needed, thus it is sometimes given as a continuous infusion. In trials comparing levodopa and dopamine agonists, symptoms of Parkinson’s improved with levodopa by about 40 to 50% as compared with approximately 30% with dopamine agonists. 4 Dopamine agonists Dopamine agonists mimic dopamine. There are several types. Ropinirole (Requip®), pramipexole (Mirapexin®) and rotigotine (Neupro® patch) are used most commonly. Bromocriptine (Parlodel®), cabergoline or pergolide are used less often because of the risk of side effects which include thickening of heart valves and thickening or scarring of lung tissue. Initial side-effects are similar to levodopa (nausea, vomiting and dizziness) however side-effects tend to ease within a few days or weeks. Drowsiness can also occur. Like Levodopa, compulsive behaviour can be a sideeffect; compulsive behaviour is more of a problem with dopamine agonists than levodopa. Dopamine agonists should be avoided in the treatment of patients with dementia because dopamine agonists can produce hallucinations. By Eamonn Brady MPSI Monoamine oxidase-B inhibitors Sometimes used as alternative to levodopa for early Parkinson’s. They include selegiline (Eldepryl®) and rasagiline (Azilect®). They work by inhibiting or blocking the effect of monoamine-oxidase-B (MAOB) in the brain, a chemical that prevents the breakdown of levodopa and dopamine. Blocking the effect of MAO-B means the effect of dopamine lasts longer. Most Parkinson’s sufferers require levodopa eventually when the disease gets worse. MAO-B inhibitors are sometimes used as the first treatment after diagnosis as it can delay the requirement for levodopa for months or years. MAOBs are often used in combination with levodopa as the condition progresses. Other medication used for Parkinson's disease Catechol-O-methyltransferase (COMT) inhibitors have become available in the last 20 years. Entacapone (Comtess® and also an ingredient in Stalevo®) is a COMT. COMT inhibitors are often given in combination to levodopa as it slows the breakdown of levodopa by the body so a higher percentage of levodopa can get to the brain to work. A COMT inhibitor is often added to levodopa when levodopa is not controlling symptoms sufficiently alone or where the effect of levodopa wears off. This is why Stalevo® has grown in popularity in recent years. Other medicines are sometimes used to help relieve symptoms. These medicines aim to correct the chemical imbalance in the brain. Examples include beta-blockers, amantadine and anticholinergic drugs. However they are only a temporary or add on therapy as levodopa or dopamine agonists are the mainstay and the most effective therapies available for Parkinson’s. Non drug treatment options Page Surgery Surgery was not traditionally part of Parkinson’s treatment and is not still commonly used as a form of treatment and techniques are still in the early days of development. Surgery will not cure Parkinson’s but may help ease symptoms when medicines are not working well. An example of a surgical procedure for Parkinson’s is chronic deep brain stimulation, a technique that involves putting a pulse generator (like a heart pacemaker) in the chest wall. Fine cables are placed under the skin; they connect to electrodes placed in the brain. The electrodes stimulate parts of the brain affected by Parkinson’s and can help to ease symptoms. Clinical trials are still underway for this therapy as long-term safety of this surgery is not certain. Deep brain stimulation is not yet available in Ireland and you must travel to the UK for treatment with this technique under the HSE. 5 Therapies A physiotherapist can advise and help with movement. They will concentrate on posture, walking and exercises, thus maximising the length the person can move and manage independently. An occupational therapist can advise on areas that will make the person’s day to day living easier to manage and will advise on home adaptations and devices which can simplify tasks that become difficult due to the condition. A speech and language therapist can help if difficulties with speech, swallowing or saliva occur; these difficulties normally only occur later on in the condition. By Eamonn Brady MPSI General advice Stay as active as possible Exercise regularly as much as you are able. Exercise may not be possible as the condition progresses. Walking and movement may be slower than before, but walking regularly can help loosen up stiff muscles and will help maintain and improve balance which will make falls less likely. Constipation Constipation is common with Parkinson’s as the nerves which allow the bowels to move freely are not functioning as well. Prevention includes staying well hydrated and eating plenty of fruit and veg and high fibre foods. Exercise can also improve constipation. Laxatives may be required as the disease progresses. Side effects of medication Familiarise yourself with any possible side effects of medication so you can recognise them early and deal with them promptly if they occur. Speak to your doctor and pharmacist about possible side effects and ‘Patient Information Leaflets’ that come with the medicines are an important source of information. You should inform your doctor or pharmacist of any side effects. For example, hallucinations, confusion and mental changes are possible side-effects of some medicines used to treat Parkinson’s. Driving Your doctor can advise you if driving is still possible. Depending on the severity of symptoms and the medicines that you are taking, driving may still be possible following a medical assessment. Depression Depression is thought to occur in approximately 40% of patients with depression. Page Psychosis Psychosis may occur in up to 30% of patients with Parkinsons. It often presents as hallucinations which are usually visual together with delusions and agitation or occasionally aggressive behaviour. Paranoia may occur particularly towards partners and family members. Psychosis is thought to be due to the loss of dopamine receptors in the substantia nigra region of the brain. Older “typical” antipsychotics such as chlorpromazine (Clonactil®, Largactil®) and haloperidol (Serenace®) can worsen symptoms of Parkinson’s including movement and should be avoided. The newer “atypical” antipsychotic agents such as quetiapine (Seroquel®) and clozapine are better tolerated and often effective in controlling psychosis. Close monitoring of the white cell count is important with clozapine because of a 1% chance of a serious condition called agranulocytosis (a loss of the white blood cells which reduces the ability to fight infection). Acetylcholinesterase inhibitors such as the anti-Alzheimer’s drugs rivastigmine (Exelon®), donepezil (Aricept®) and galantamine (Reminyl®) may also be beneficial in reducing hallucinations and delusions in Parkinson patients. 6 The main reason for depression is the massive impact Parkinson’s can have on day to day living and life expectancy. Depression can cause symptoms similar to Parkinson’s and which may make it look like Parkinson’s is getting worse when actually it is not (such as lack of energy and becoming slower). By Eamonn Brady MPSI Practical tips Limit caffeine intake as caffeine can act as a diuretic and increase the frequency of urination. Decrease fluids to either two hours before bedtime, after dinner or earlier; this will reduce waking up at night to use the bathroom. Sleep deprivation can exacerbate symptoms of Parkinson's. At night, a portable urinal and or bedpan can be an alternative to getting out of bed to make trips to the bathroom which can be difficult. Using a shower stall is much easier and much safer than a shower/tub combination. The shower area should be fitted with at least two handrails. It is easier to get up from a high chair than from a low couch. Consider using Velcro fasteners instead of buttons; carrying a walking stick when out can increase confidence if unsteadiness is a problem. Use an electric toothbrush and razor to make brushing your teeth and shaving easier. There are many utensils designed for people living with disability which can make everyday chores like eating, preparing food easier, grooming and cleaning easier. Examples include reaching devices, electric jar openers, modified cups and utensils for ease of holding and use, the list is limitless. Ask your occupational therapist or pharmacist for more details. Longer term outlook Symptoms tend to get worse with time but the speed of progression may vary significantly from person to person. Many do not need treatment initially as symptoms may be relatively mild. Most Parkinson’s sufferers have a period of relatively mild symptoms. When symptoms become worse, medication can give several years of good or reasonable control of the symptoms. It is difficult to predict how quick the condition will progress. Some people may only have mild symptoms 20 years after diagnosis with other being disabled after only 10 years. Parkinson’s Association of Ireland The Parkinson’s Association of Ireland provides support for Parkinson’s patients, their families, carers and healthcare professionals. They operate a Freephone number (1800 359 359, Monday to Friday 9am to 9pm), they have a nurse on staff, provide free information leaflets and organise regular information evenings around Ireland. They also operate 14 branches around Ireland which operate on a local basis and are run by volunteer committees. The closest branch to Westmeath is the East Midlands branch; you can contact Marian Deely from the Midlands East branch at 045 435023. If you or a loved one is affected by Parkinson’s, they can be a great source of information and support. References Page 7 1. Mutch WJ, Dingwall-Fordyce I, Downie AW et al. Parkinson’s disease in a Scottish City. British Medical Journal. 1986; 292, 534–536 2. Wooten GF, Currie LJ, Bovbjerg VE, Lee JK, Patrie J. Are men at greater risk for Parkinson’s disease than women? Journal of Neurology, Neurosurgery & Psychiatry. 2004;75:637-9 3. Davie, C.A. A review of Parkinson’s disease. British Medical Bulletin. April 2008; 86: 109–127 By Eamonn Brady MPSI Page 8 4. Hughes AJ, Daniel SE, Ben-Shlomo Y et al. The accuracy of diagnosis of Parkinsonian syndromes in a specialist movement disorder service. Brain. 2002; 125, 861–870 5. Emre M, Aarsland D, Albanese A et al. Rivastigmine for dementia associated with Parkinson’s disease. New England Journal of Medicine. 2004; 351, 2509–2518 6. Ravina B, Putt M, Siderowf A et al. Donepezil for dementia in Parkinson’s disease: a randomised, double blind, placebo controlled, crossover study. Journal of Neurology, Neurosurgery & Psychiatry. 2005; 76, 934–939 7. Nutt JG, Wooten GF, Diagnosis and initial management of Parkinson’s disease. Clinical Practice. New England Journal of Medicine. 2005; 353;10217 8. Pritchett AM, Morrison JF, Edwards WD, Schaff HV, Connolly HM, Espinosa RE. Valvular heart disease in patients taking pergolide. Mayo Clinical Proceedings. 2002;77:1280-6 9. Lees AJ, Katzenschlager R, Head J, Ben Shlomo Y. Ten-year follow-up of three different initial treatments in de-novo PD: a randomized trial. Neurology 2001;57: 1687-94 10. Rascol O, Brooks DJ, Korczyn AD, De Deyn PP, Clarke CE, Lang AE. A fiveyear study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa. New England Journal of Medicine. 2000;342: 1484-91 11. Holloway RG, Shoulson I, Fahn S, et al. Pramipexole versus levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. Archives of Neurology. 2004;61:1044-53 12. Braak H, Bohl JR, Muller CM et al. Stanley Fahn Lecture 2005: The staging procedure for the inclusion body pathology associated with sporadic Parkinson’s disease reconsidered. Movement Disorders. 2006; 21, 2042– 2051 13. Naimark D, Jackson E, Rockwell E et al. Psychotic symptoms in Parkinson’s disease patients with dementia. Journal of the American Geriatric Society. 1996; 44, 296–299.