CME INDIA Presentation by Dr R Ramnarayan,M.Ch, FRCS, IFAANS, Consultant Functional Neurosurgeon, Chennai. Author email: r.ramnarayan65@gmail.com / r.ramnarayan@rediffmail.com.

Parkinson’s Disease

Parkinson’s disease is a disease which affects the movements of the body. So, it is called a movement disorder. It is usually a disease of aging but in India younger people are getting affected more and more.

Exact cause not known

• It happens due to a loss of nerve cells in the area of the brain called the substansia nigra. The nerve cells of Substansia nigra produce a chemical substance called dopamine. This dopamine is essential for the normal coordinated and smooth movements of the body. When the cells in the substansia nigra get reduced, the amount of dopamine also gets reduced. This causes difficulty in movements and causes the manifestations of Parkinson’s disease.
• The onset is a slow process and manifestations start only when about 80% of the cells are destroyed.
• The exact cause of Parkinson’s disease is not yet clear but several like genetic factors and hereditary factors, exposure to some toxins like pesticides and other pollutants have been blamed.
•  Parkinson’s disease is more common as people age and seen more in men. Reduction of blood supply due to age and other reasons like atherosclerosis have also been found but these may not always cause the typical Parkinson’s disease.

Parkinson’s signs and symptoms may include

1. Tremor which is a shaking of the hands and usually starts on one starts on one side and then goes to the other. The tremor is described as a pill rolling tremor and occurs only at rest.
2. Slowness also called bradykinesia.
3. Rigidity or stiffness of the body.
4. Loss of balance and falling.
5. Loss of blinking and facial expressions.
6. Disturbances in speaking and writing.

There may be other symptoms usually at the later stages like

1. Difficulty in thinking and remembering.
2. Depression and emotional changes including anxiety. Some patients develop hallucinations because of drug side effects.
3. Swallowing problems and drooling of saliva and later in the disease problems with chewing causing choking and frequent aspiration into the lungs.
4. Sleep problems especially as turning in bed can be difficult.
5. Difficulty in controlling urine causing incontinence and severe constipation.

Consume caffeine (found in coffee), get Parkinson’s disease less

• Prevention is a very good strategy for any disease but it is not always possible in Parkinson’s disease. The reason is that the exact cause is unknown.
• Some research has shown that regular aerobic exercise might reduce the risk of Parkinson’s disease.
• Other research has shown that people who consume caffeine (found in coffee) get Parkinson’s disease less often than those who don’t drink it.
• Currently there is not enough evidence to suggest drinking caffeinated beverages to protect against Parkinson’s.

Diagnosis of Parkinson’s disease

• The diagnosis of Parkinson’s disease is usually by clinical methods based on medical history, a review of symptoms and signs and a neurological examination.
• No specific test exists to diagnose Parkinson’s disease.
• An MRI should be done to rule out other causes.
• In selected cases, specific investigations like dopamine transporter scan (DaT scan) or PET scan may be done for proper diagnosis.
• Some major hospitals routinely perform a DOPA challenge test but this may not always be necessary.
• Many patients do get confirmed diagnosis only over a period of time.

Any chance of cure?

• Parkinson’s disease can’t be cured, but treatment can help control your symptoms, often dramatically.
• In some more advanced cases, surgery may be advised.
• Many supportive measures like lifestyle changes, especially on-going aerobic exercise and physical therapy that focuses on balance and stretching also is important.
• A speech-language pathologist may help improve speech problems.
• Many drugs are available which help in the treatment and help manage problems with walking, movement and tremor.
• These medications increase or substitute for dopamine and dopamine is the deficient chemical in the brain.
• Drugs produce significant improvement of symptoms after beginning Parkinson’s disease treatment. But over time, however, the benefits of drugs frequently diminish or become less consistent. The most common drugs used in Parkinson’s disease include:
  1. Levodopa-carbidopa.
  2. Dopamine agonists (agonist means supportive drug) like pramipexole, ropinirole and rotigotine given as a patch). Apomorphine is a short-acting injectable dopamine agonist used for quick relief.
  3. MAO inhibitors like selegiline.
  4. Catechol O-methyltransferase (COMT) inhibitors like Entacapone.
  5. Anticholinergics. Like trihexyphenidyl.
  6. Amantadine for short term benefits.
• As already mentioned, drugs are very effective in early cases and when the symptoms are mild. But over time say in about 5 to 6 years, the efficacy of the drugs slowly starts coming down. So the dosages of the drugs need to be increased.
• This will cause side effects to start appearing. The common side effects include drug induced movement disorders (dyskinesia), hallucinations etc. So, the patient enters into a devil and deep sea like situation. If the dosage is increased, side effects appear and if dose is reduced Parkinson features appear. It is in these types of patients that surgery is given as the next option.

The surgery that is done is called Deep brain stimulation (DBS).

• In deep brain stimulation (DBS), surgeons implant electrodes into a specific part of your brain. The electrodes are connected to a generator implanted in your chest near your collarbone that sends electrical pulses to your brain and may reduce your Parkinson’s disease symptoms.
• The surgery is a pin hole procedure done under local anesthesia and patient can go home the very next day. DBS is most often offered to people with advanced Parkinson’s disease who have unstable response to drugs. DBS can stabilize medication fluctuations, reduce or halt involuntary movements (dyskinesia), reduce tremor, reduce rigidity, and improve slowing of movement. DBS is effective in controlling erratic and fluctuating responses to levodopa or for controlling dyskinesia that doesn’t improve with medication adjustments.
• DBS helps in improving those symptoms which are improved by high dose levodopa (DOPA challenge test). The exception is tremor predominant Parkinson’s disease where levodopa does not improve tremor much but DBS practically abolishes the tremor.
• As the disease progresses, the battery current needs to be adjusted which is done as an OPD procedure. The risks of DBS include infections, strokes or brain hemorrhage and rarely breakdown of the implants used. But the total risk is less than 1% in centers where the surgery is done routinely.
• Although DBS may provide sustained benefit for Parkinson’s symptoms, it doesn’t keep Parkinson’s disease from progressing. Also, surgery will not benefit all patients with Parkinson’s disease. Detailed, internationally very well-established assessments are done which will help to select the correct patient who will benefit from DBS for Parkinson’s disease.

From a surgical point of view, Parkinson’s disease can be divided into three stages.

• In the first stage which is 5 to7 years from onset of symptoms, drugs do very well to control.
• the symptoms and patients can have a good quality of life.
• The second stage is next where either the effect of the drugs starts coming down or because of higher dosage given, the side effects start appearing. It is in this stage that surgery is offered to patients.
• The third stage is when the patient is very crippled with recurrent falls, difficulty in swallowing and chewing and other symptoms.
• Unfortunately, neither drugs nor surgery helps in this stage. But studies have shown that surgery, if done in the second stage, can delay the appearance of the third stage by many years.

In the later stages of the disease, falling down becomes more frequent.

In fact, a small push or bump can cause patient to lose balance and fall and hurt himself. Especially if the patient is on drugs like aspirin or clopidogrel for heart problems, they can end up having bleeding into the brain which can even be fatal. The following suggestions may help:

• Make a U-turn instead of pivoting your body over your feet.
• Distribute your weight evenly between both feet, and don’t lean.
• Avoid carrying things while you walk.
• Avoid walking backward.

Parkinson’s Plus Syndrome

There are a group of disorders called Parkinson plus syndromes which mimics Parkinson’s disease but caused by other diseases like progressive supranuclear palsy, Multisystem atrophy etc. Here the drugs used in the treatment for Parkinson’s disease do not work well neither does surgery.

CME INDIA Learning Points

Audio message by Dr Ujjawal Roy,DM Neuro, Ranchi:

• In patients in whom conventional therapy has been exhausted and cannot be optimized, three main device-assisted therapies should be considered:
  • Continuous subcutaneous infusion of apomorphine.
  • Intra-intestinal infusion of levodopa-carbidopa gel (LCIG).
  • Deep-brain stimulation (DBS).
• Deep brain stimulation (DBS) is a functional neurosurgical procedure that can be used to treat motor fluctuations, dyskinesia, and tremor. It has also been shown to improve HRQoL (Health related quality of life).
• DBS is associated with a decreased risk for recurrent falls and delays the onset of psychosis in patients with Parkinson’s disease.
• DBS did not affect the development of dementia.
• DBS is regarded as the second therapeutic breakthrough in Parkinson’s therapy after the LDOPA drug therapy.
• It involves placing electrodes in certain areas of the brain that are connected to a stimulator implanted subcutaneously in the thoracic or abdominal area through a neurosurgical procedure. The system, often referred to as “brain pacemaker,” generates and delivers electrical impulses that change the function of stimulated sections of the brain.
• The beneficial effects of subthalamic DBS on motor functioning in patients with Parkinson’s disease has been shown in numerous well-designed, randomized controlled trials.
• The effects of the procedure on other key disease milestones in the long-term course of Parkinson’s have not fully been evaluated in a controlled manner. 
• Oral levodopa, the initial gold-standard therapy for PD, is still the most effective and widely used therapeutic option in the treatment of this neurodegenerative disorder.
• Levodopa use eventually results in the development of motor fluctuations and levodopa-induced dyskinesia (LID).
•  Nearly 40% of PD patients develop LID after 4 to 6 years of levodopa treatment.

CME INDIA Tail Piece

• Key messages for diagnosis of Parkinson’s disease are as follows (Courtesy movement disorder society):

1. There are two different diagnostic criteria for the clinical diagnosis of Parkinson’s disease.
2. The first and most important feature of Parkinson’s disease is bradykinesia: tremor without bradykinesia is not enough for the diagnosis of parkinsonism or Parkinson’s disease.
3. Patients correctly diagnosed with Parkinson’s disease should have a clear effect of their antiparkinsonian medications if the dose is sufficient. However, some motor symptoms such as tremor can result from a combination of dopaminergic and nondopaminergic brain lesions, which may contribute to variable response to levodopa across patients.

• Key messages for treatment of Parkinson’s disease (initial stages) are as follows:

1. When choosing medication, individual approach is required based on symptoms and preference.
2. Start low and go slow until reaching good clinical benefit.
3. Medications with a more continuous stimulation profile, such as dopamine agonists or MAO-B inhibitors, are preferred in initial stages if appropriate for the clinical profile of the patient.
4. Levodopa should not be avoided at all costs, even in initial stages. Consider levodopa if other medications are not indicated or not effective.

Further Reading:

1. https://doi.org/10.1155/2020/9131474 Update on the Management of Parkinson’s Disease for General Neurologists.

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