Targeted ultrasound might sound like something a Bond villain would use to incinerate a Swiss canton, but, in reality, it could be the next big, breakthrough Parkinson's treatment. On today's episode, the Movers & Shakers gather in the Notting Hill pub to discuss this new therapy and are joined in that undertaking by returning guest Professor Ludwic Zrinzo, an expert in both this technique as well as its main rival, Deep Brain Stimulation (so expert that he had the honour of performing Gillian's procedure). Is this a less invasive alternative to DBS? Or are we some way away from this being offered on the NHS?
Each week Rory Cellan-Jones guides us between the laughs and moans in the pub. To read about Rory's visit to watch targeted ultrasound in action click here.
Guest Biography
Professor Ludvic Zrinzo
Prof Zrinzo is head of the UCL functional neurosurgery unit. He specialises in the surgical management of chronic neurological disease including Parkinson's disease, dystonia, tremor, headache (cluster headache and other autonomic cephalalgias) as well as the surgical management of treatment refractory mental disorders, including Tourette's syndrome, obsessive compulsive disorder (OCD) and major depression. In addition to stereotactic ablation and deep brain stimulation (DBS) he also specialises in disorders of the cranial nerves, including microvascular decompression (MVD) procedures for trigeminal neuralgia and hemifacial spasm.
Prof Zrinzo completed undergraduate medical studies in Malta, before moving to London to train in neurosurgery (Atkinson Morley Hospital, Royal London Hospital, Great Ormond Street Hospital, The National Hospital for Neurology and Neurosurgery and Old church Hospital). He was awarded an MSc in clinical neuroscience with distinction from the UCL Institute of Neurology, London and completed two fellowships in stereotactic and functional neurosurgery, at Queen Square and at UCLA, Los Angeles, USA.
Prof Zrinzo's research interests have been directed towards continued improvement in the surgical care of Parkinson's with particular emphasis on improving safety, accuracy and efficacy of surgery. He is the author of numerous peer-reviewed publications, abstracts and several book chapters and his work has received several international awards.
For more information visit UCLH.
Listen to Ian King's audio clip here
Focussed Ultrasound The new kid on the block?
By Prof Keyoumars Ashkan
People say medicine isn’t just a natural science but an art. I would add that medicine is more than that; it is also a social science. Medicine practised well has to address the social context of the disease; after all, humans are social entities and societal elements can cause, aggravate, prevent and heal diseases. If we agree that medicine and sociology move hand in hand, then the essence of medicine itself might not be free of social influences, one such influence being the concept of fashion and mode of the day.
In the field of functional neurosurgery, perhaps, nowhere this can be better seen than in the escalating interest in the use of focused ultrasound (FUS). Magnetic resonance guided focused ultrasound, first introduced for functional neurosurgery in the U.K. in 2016 is a technique where under the safety of real time MRI guidance, ultrasound beams are focused on a target in the brain to lesion (burn) it, thus producing a functional effect. The procedure is performed with the patient awake, allowing neurological assessment of the patient throughout the procedure, thus enhancing its safety and efficacy. In the U.K. NICE approved this in 2018 specifically to lesion thalamus, an important relay nucleus deep inside the brain, to treat unilateral tremor. Since then, FUS has achieved remarkable interest, indeed raising the question in certain functional neurosurgical circles, if this should replace deep brain stimulation (DBS) as the first line surgical modality of choice for movement disorders such as Parkinson disease (PD) and tremor.
To recap, DBS in its current form, was popularised through the works of Prof AL Benabid in 1980s for medically refractory movement disorders and secured NICE approval in 2003. The procedure involves insertion of electrodes into the target nuclei in the brain which are then empowered by an implantable pulse generator. The electricity thus delivered to the brain causes modulation of the brain circuits which then translates into functional improvement. The procedure can be performed awake, again increasing its safety and efficacy.
At this point a brief review of the history is warranted. Up to the introduction of DBS, lesioning in its various forms was indeed practiced for decades to treat movement disorders. But what DBS brought to the field were clear advantages over the lesioning. To touch base on a few:
1. Lesioning in its essence entails destruction and burning of neural tissue. Insertion of DBS electrodes on the other hand, is generally considered to be non-destructive. Clearly, complications at a rate of less than 1%, such as bleeds, can occur with DBS but these are rare and no significant or permanent neural destruction commonly happens with DBS. This is a consideration for all patients but particularly in the growing brain such as in children with dystonia.
2. Lesioning, again by definition, is non reversible. This is a major concern if mis-targeting happens. For example, if a lesion is made too lateral during thalamotomy, then the internal capsule could be damaged, potentially leading to permanent weakness and paralysis. The risks are less with DBS; although a laterally placed DBS electrode may well not produce any clinical benefit, it is also unlikely to cause major harm since it can be left in place but not activated.
3. Lesioning is typically a one-off event unless the patient is prepared to undergo multiple surgical procedures with the added risks. This is a problem in long term since many of the neurological disorders are progressive. Thus, lesioning is not conducive to titration against patient symptoms. DBS, however, is ideal here. DBS system can readily be programmed externally, nowadays in 1000s of configurations and even remotely with the patient sitting at home, thus personalising the therapy to the patient over time.
4. This point about personalised medicine warrants further elaboration. The emerging DBS systems are now able to record the brain activity as a biomarker of the disease status which can then be fed-back and used to adjust the stimulation parameters. This can happen in real-time as the status of the disease changes throughout the day and the DBS system can automatically self-adjust in a closed loop fashion to personalise and optimise the therapy. The technology is already available in the U.K. although not all functionalities are as yet activated and further work is needed to clearly define various biomarkers for different symptoms.
5. Because of the lower risks, especially with respect to gait and speech, DBS can be performed bilaterally at the same surgical setting, which is important given that most movement disorders are bilateral. There are, however, major concerns with respect to performing bilateral lesions, although staged lesioning with the 2 procedures spaced 6-12 months apart (and only after confirming safety of the first procedure) is now considered by some clinicians.
6. Currently in the U.K., FUS lesions are only indicated for tremor whilst DBS can be used to treat a large spectrum of PD symptoms as well as other movement disorders such as dystonia.
So given all the above, why has FUS gained so much popularity so quickly? Is FUS really now the new state of the art neurosurgical procedure of choice for movement disorders over DBS?
I can’t help but thinking societal factors and medical “fashion” has a major role in play here!
Please don’t get me wrong! I am a big fan of FUS. Indeed, well over a decade ago our functional neurosurgery team at King’s was the first in the U.K. to apply for funding to secure a FUS device; alas we were not successful. Notwithstanding this, I regularly refer patients to the FUS team at Imperial, which is by far the most experienced FUS service in the U.K. In my previous role as the President of the British Society for Stereotactic and Functional Neurosurgery, I wholeheartedly supported the development of the FUS service in Liverpool. The units at Imperial and Liverpool remain the only 2 NHS FUS services in England providing first class care to the patients in the north and south of the country.
My support for FUS, however, is not because I believe FUS is superior to DBS but because not all patients are candidates for DBS. DBS is a long and complex procedure and not all patients maybe fit enough to undergo this. DBS requires cooperation of the patient for post-operative programming and adjustments; not all patients might be able to engage with this, although the recent ability to program DBS remotely is helping to address this issue. A small minority of patients may have issues with recurrent infections or inability to tolerate the DBS hardware; again FUS lesions are ideal here. Next, socio-politico-economic factors may influence availability of DBS for certain national populations and again lesions are a good alternative. And of course, last but not least is the matter of patient choice which for personal reasons may favour one modality over another.
With respect to FUS lesions versus lesions made through other modalities, such as radio frequency or gamma knife, for me this is a no brainer! Radio frequency lesioning requires insertion of a probe into the brain whilst FUS lesions can be made without a skin incision, thus lowering the risks. Compared to gamma knife lesions, FUS does not involve ionising radiation and allows awake surgery, again a clear advantage. Simply said, if a medically refractory patient is not a good candidate for DBS, it must not be assumed that the patient should be deprived of surgical treatment. Lesions have a long history and should definitely be considered. If one is to lesion, then the new and fascinating technique of FUS is arguably the safest and best modality we have at the present.
In fact one of the biggest privileges we have in the 21st century is the range of modalities we have at hand to help our patients combat their disease. The choice, however, needs to be governed by careful multi-disciplinary medical judgement and remain free of influences of new modes and fashions.
Professor Ashkan is the lead for Functional and Oncological Neurosurgery at King's College Hospital. His clinical practise covers the 4.5 million population of Southeast London and Kent, translating into around 300 operations per year. He is the Co-Chair of the Neuroscience Research Delivery Unit at King’s. He is an Elected Council Member of the Society of British Neurological Surgeons and the Immediate Past President of the British Society for Stereotactic and Functional Neurosurgery. He led the Glioma Genomics England Clinical Interpretation Partnership Section of the100K Genomes Project and was the Chair of the Neurosurgical Special Interest Group of the International Parkinson and Movement Disorder Society.
Prof Ashkan's main clinical and research interests include deep brain stimulation, basal ganglia anatomy and physiology, intra-operative imaging and physiology, image guided surgery, gliomas, immunotherapy, brain mapping, brain tumour genomics and radiomics, minimally invasive neurosurgery, radiosurgery, new and novel therapies and patient reported outcome measures. He has won over 20 undergraduate and postgraduate prizes and scholarships. He has attended/ chaired/ presented papers in over 270 national and international meetings and published over 650 full papers, abstracts and book chapters. To date he has been Chief/ Principal Investigator in over 30 major studies/ trials. He is the Associate Editor of the British Journal of Neurosurgery. In 2018 he was voted Clinician of the Year nominated by the Brain Tumour Charity and in 2021 he was the runner-up for the UK Ground-Breaking Pioneer Award. His surgery to remove a brain tumour whilst the patient played the violin attracted the global audience and put neurosurgery at the forefront of public mind.
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