PALS Support Group Meeting February 5th 2006

Speakers:
Prof. Marwan Hariz, Neurosurgeon, Dr. Pat Limousin, Neurologist, National Hospital for Neurology & Neurosurgery, Institute of Neurology,
Queen Square, London


· Prof. Hariz worked in Sweden with Prof. Laitinen, who pioneered stereotactic pallidotomy for Parkinson’s
· Dr. Limousin worked with Prof. Alim Benabid and Prof. Pollak in Grenoble. They were the pioneers of Deep Brain Stimulation for Parkinson’s.

Parkinson’s disease : The Neurosurgeon’s and the Neurologist’s Opinion

In conversation with Prof Marwan Hariz and Dr Pat Limousin, before the meeting, I asked what they would see as future therapies for Parkinson’s. Prof. Hariz firstly commented on stem cell therapy, saying that “stem cell therapy as a routine operation will not come” in his lifetime. He said that if we could figure out why we get Parkinson’s, then we could perhaps figure out how to avoid getting it. He also felt that growth factors might be the way forward.

Dr. Limousin felt that, with Deep Brain Stimulation, the use of more than one lead on each side might become more commonplace – one lead in each Subthalamic nucleus and each Globus Pallidus for example.

Prof. Hariz started the presentation by making the point that “We are not the experts. We learn from the experts – the patients and the carers”.

Dr. Limousin quickly detailed James Parkinson’s description of Parkinson’s in 1817, and simply explained that Parkinson’s resulted from a lack of dopamine. She went on to explain the route that an instruction being sent to a limb to move took, i.e. there were consequences following upon a lack of dopamine: In PD, there was a “problem in the connections” that made movement “more difficult”.

The main treatment is still medication. Sinemet’s absorption can be slowed down especially by food. It is absorbed from the duodenum, and protein can slow its journey to the brain through the blood brain barrier.

In early stages, the medication (Sinemet) produces a stable response,, but later on, fluctuations occur, often with sudden onset of “Offs”.

If the medication is helping you to lead a relatively normal life, then no operation will be offered, but if the ups and downs become problematical then you should consider an operation.

History of Surgery for Parkinson’s Looking at the origins of surgery for Parkinson’s, Prof. Hariz said that James Parkinson, who observed that patients with what he called the “shaking palsy”, who had strokes, often no longer had tremor on the same body side, and some surgeons even created artificial strokes to try and control tremor. As one would expect, the rate of complications was very high.

The advent of stereotactic surgery in 1947, along with the creation of the brain atlas, meant that the patient’s head could be held rigid in a frame, and the target in the brain could be identified with greater precision, taking into account the variations between the brain atlas and the individual patients’ brains. Micro electrode recording allowed the distinctive pattern of each part of the brain to be identified, while having the patient awake meant that you had visual reinforcement to assist in locating the target.

An alternative to lesioning arrived with High Frequency Deep Brain Stimulation, pioneered by Pollak, Benabid and Limousin. They started with the Thalamus, using DBS as treatment for tremor. The electrodes were 1.3mm in diameter, four on a lead, and 1.5 mm apart. Microsurgery.

The Operation

In the operating theatre, the Surgeons, Neurologist, nurses and patient all have a part to play. The frame is positioned under local anaesthetic, with the head shaven. The calculations to pinpoint the target area are done by two different surgeons, using different methods, to ensure maximum accuracy and rule out any chance of error. The operation is performed with the patient awake, and the patient’s condition is constantly evaluated during the surgery. The leads and extensions are run under the skin under general anaesthetic and connected to the pacemaker. Prof. Hariz stressed that the end point was the same no matter what variation there was in how the whole procedure was completed – with the patient awake or asleep, or a delay between implanting the leads and the implantation of the pulse generator. That end point was the improvement of the patient’s condition through the use of Deep Brain Stimulation.

The aim of the programming of the pulse generator (aka neurostimulator; pacemaker) is to achieve the best programming parameters for the patient whilst avoiding negative side effects.

Thalamic Stimulation

For tremor
· Medications stay the same
· Switch off the machine at night.

If the operation was for the tremor of Parkinson’s then over time other symptoms might become a problem. When done unilaterally, it presents few problems, even for 80 year olds.

Pallidal/Subthalamic Stimulation

A pallidotomy was usually done unilaterally – only on one side,and primarily to help alleviate dyskinesias. Bilateral Pallidal Stimulation can be offered for advanced disease in the elderly where DBS of the Sub thalamic nucleus is more suited to the younger candidate.

Both urged caution in the selection of patients for surgery, and said that patient expectation should be realistic. Some people after operation have difficulty in adjusting to their new situation.

They offer these operations with local anaesthetic, and without micro electrode recording, and both were in agreement that this allowed the neurosurgeon to get the most positive identification of the correct target area. They start to programme immediately and the patient has to come back now and then during the first month when the swelling goes down to increase the level of stimulation.

In the presentation, they said that this operation can only improve some symptoms and will not result in perfection, and so it is wise not to have one’s expectations too high.

Pallidal Stimulation

This helps mainly dyskinesia (involuntary movements) but does not allow for a reduction in medication. Its effect against the “Off” phenomenon is variable. They felt that this operation suited the over 70s.

STN Stimulation

This works on a whole range of symptoms, including tremor, slowness, stiffness, gait, and freezing, and allows a reduction in the medication. This operation has a variable effect on speech, and is considered more risky for the over 70s. She urged caution in those over 70, citing a reduced effectiveness of DBS of the STN in this age group.

Who can benefit?

These operations will help those with “relatively severe forms of Parkinson’s”, said Dr. Limousin. The right time for such an operation is when the medications are not providing full coverage, but still showing some effect. The candidate should be in good general health and have reasonable expectations. He should not have major depression or severe memory problems. Look for the operation a bit earlier if impaired or working.

They said that, for them, the complications that may arise are very few, because of careful patient selection, but include a 2% chance of infection. Memory problems may become worse (especially if there before surgery), speech problems and psychiatric problems (including depression and hallucinations). General risks of surgery should also be acknowledged, including thrombosis.

Other Target Sites

Promising early reports about a new target area, the Pedunculopontine nucleus (PPN), which is currently under research, are emerging. Low frequency stimulation is being used, thus ensuring that the pulse generator lasts for longer. *

GDNF

MRI scans prove the usefulness of GDNF (Glial Derived Neurotrophic Factors). The original trial in Bristol** data suggested that regeneration was occurring, but a second, multi-centre trial showed no effect, and was cut short.

Patients with more advanced Parkinson’s, have they any alternatives?

A patient with fluctuations, but too early to consider surgery, what are the options? One option is to consider the use of apomorphine, a fast-acting dopamine agonist, delivered either via an injection or a pump, to shorten off periods.(See below)

Another option is Duodopa (above, right), which is suitable for those advanced stage patients in trouble with the apomorphine pump. This drug (and the delivery system) drastically reduced both Offs and dyskinesias. Side effects are rare, but you need an experienced team

Patients with DBS, and Dentistry – No ultrasound to be used

Diathermy/ultrasound may prove fatal and so is to be avoided. This also includes ultrasound teeth cleaning.

For more on Prof. Hariz, his team, and the operations offered, see http://www.parkinsonsappeal.com/

Editor: In the Pipeline

There is a rechargeable pulse generator now nearly at the point of being ready for marketing (Medtronic news). This would last nine years before having to be replaced. There is a pulse generator that can be reprogrammed over a telephone line in the making, which will hopefully be available in the next two or three years. Another future possibility - contacts shaped to suit each differently shaped target area!! And finally, a wireless miniature pacemaker that could be set in under the scalp!

*In Frenchay Hospital Mr. Gill reports that it seems to have a good effect on gait and balance, which are sometimes not helped by surgery in the other target area, while being an increasing problem for many patients as Parkinson’s progresses.