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Irish Institute of Clinical Neuroscience Neurology Update Meeting

By Paul Mulholland - 01st Jan 2025

parkinson's patient with doctor

Reference: January 2025 | Issue 1 | Vol 11 | Page 4


The complex Parkinson’s patient

The 2024 Neurology Update Meeting, organised by the Irish Institute of Clinical Neuroscience, took place in the Canal Court Hotel, Newry, Co Down, on 11 October, under the directorship of Dr Ferghal McVerry.

Dr McVerry, Consultant Neurologist at Altnagelvin Hospital, Co Derry, opened proceedings by welcoming guests, chairpersons, delegates, and sponsors to the meeting. A special word of thanks was extended to Dr Junie Koay and Dr Antoinette O’Connor who both agreed to speak at short notice.

The first lecture was delivered by Dr Laura Best, Consultant Neurologist at the Royal Victoria Hospital, Belfast. The title of Dr Best’s talk was ‘The complex Parkinson’s disease (PD) patient: When to consider advanced therapies’.

Dr Best advised attendees to refer early for advanced therapies if they think patients might benefit.

“If you take too long doing the pragmatic approach … you might miss the boat,” Dr Best said.

“Some of these patients do remarkably well with advanced therapies. And it can have a life-changing effect. It can have a massive improvement on quality of life for them and their carers. So, I think the take home message of my talk is, if you are not winning, it usually means they need something else. And refer early rather than late.”

Dr Best said, in her experience, clinicians have been referring patients earlier for advanced therapies in recent years. Medication options have also improved over this period.

In her talk, Dr Best referred to the EPSILON study, which investigated the efficacy of opicapone in enhancing the clinical benefit of levodopa in patients in earlier stages of PD, without end-of-dose motor fluctuations. The trial found that the Unified Parkinson’s Disease Rating Scale (UPDRS) III scores for patients in the active group were reduced by 6.5 points at 24 months. After a one-year open label extension, opicapone did not increase the development of motor fluctuations, according to the study.

“Opicapone has been out on the market now for the past few years,” Dr Best said. “And I suppose there has been some wariness around it – there certainly are some side effects. But what we are seeing is that the trials are now showing that these newer drugs that are coming out are more beneficial.”

She also pointed out that foslevodopa-foscarbidopa was recently approved by the National Institute for Health and Care Excellence (NICE) in the UK. The medication is administered subcutaneously, preferably in the abdomen, avoiding a 5cm radius area from the navel.

“But it is also thinking about these other medications, these add-ons, other ways of delivery and avoiding the types of complications that come with late onstage PD, such as gastric outlet syndrome, and better ways of delivering medication that can bypass those obstacles.”

In addition, Dr Best said there have been notable developments in the delivery of deep-brain stimulation (DBS) over the past decade. “DBS has been around for about 30 years. It’s not new,” she said. “But what has happened, particularly over the past 10 years, is there has been a massive improvement in the software and in the nature of the leads themselves.

“So, it used to be your traditional lead just had four contacts, and you just programmed off that. We now have multi-directional leads, so if the placement of the lead isn’t perfect, we can minimise the stimulation away and minimise side effects. We are now moving into, I think, the next big thing, which is adaptive neuro-stimulation.”

Appropriate patient selection for DBS is vital. “Young patients do very, very well with DBS,” Dr Best said. “There is an age restriction of course, usually around 70. There can’t be any cognitive decline evident. So, they have to get a quite big work-up before they come to DBS, but it is life changing and I think we should be considering it more and we should be considering it earlier than we currently are and making more people eligible for it.”

Updates in peripheral nerve vasculitis

It is important for clinicians to perform a systemic examination of patients presenting with apparent cases of isolated peripheral nerve vasculitis, the Neurology Update Meeting 2024 heard.

Dr Junie Koay, Consultant Neurologist, National Hospital of Neurology and Neurosurgery, London, UK, delivered a lecture entitled: ‘Peripheral nerve vasculitis: Update and future directions’.

Dr Koay said examination is needed to ascertain whether there is wider systemic involvement. “That will potentially open up different treatments that are available,” she said.

The diagnosis of vasculitic neuropathy relies on a patient’s medical history, clinical examination, and supporting laboratory tests. Dr Koay said basic tests include a urinalysis to ascertain whether there is renal involvement and a chest x-ray to assess the lungs.

“More in-depth investigations can then be conducted if you find a suggestive picture on bloods or the history, for example,” she said, adding that collaboration with other specialties is also key, both in terms of diagnosis and treatment.

The standard treatment for the condition is cyclophosphamide and glucocorticoids. However, Dr Koay highlighted that newer treatments have come on stream, such as complement inhibitors and anti-eosinophilic medications.

“They are available if you fulfil particular criteria,” she said.

Dr Koay said peripheral nerve vasculitis responds well to treatment, particularly when diagnosed early.

“Because it’s an inflammatory disease, it is very treatable. The time to diagnosis is important because the longer you go without a diagnosis the more there is this ongoing inflammatory and nerve death from ischaemia. So, if you can stop that process and control it, then you allow recovery.”

New era on horizon for Alzheimer’s treatment

The emergence of disease-modifying therapies for Alzheimer’s disease (AD) has ushered in an “exciting” period for the treatment of the condition, according to Dr Antoinette O’Connor, Consultant Neurologist, Tallaght University Hospital, Dublin. However, she said it is essential that patients are appropriately selected as these therapies become available.

Dr O’Connor delivered a lecture on the diagnosis and management of dementia at the Neurology Update Meeting 2024.

In her talk, Dr O’Connor stressed the value of early diagnosis and outlined recent developments in the field. She said “there has been a huge amount of progress” in the area of diagnosis, with the ability to test for and monitor cerebrospinal fluid biomarkers.

“Also, there is a lot of innovation in the field of blood biomarkers,” Dr O’Connor said. “And that’s really exciting because they are more accessible, they are cheap, they are easily repeatable. They are not available clinically yet and there will need to be proper regulation and research about how they are implemented clinically. But they are definitely coming.”

In terms of treatment, she stated that the advent of disease-modifying therapies is “very exciting”.

“Removing amyloid has been consistently related to the slowing of cognitive decline,” Dr O’Connor said. “For a long time, we have just had symptomatic therapies. But now we can actually have disease modification and that is exciting.”

She said the future promises greater biomarker-supported diagnosis and molecular-specific therapies.

Dr O’Connor said treatments targeting “additional elements” of AD pathophysiology, such as neuroinflammation and tau accumulation, will likely be needed to achieve a “more profound” impact on outcomes.

In her lecture, she pointed out that the treatment of AD could eventually mirror therapeutic developments in the field of multiple sclerosis (MS).

“With MS, many years ago, there weren’t disease-modifying therapies,” Dr O’Connor said. “Now we have many disease-modifying therapies. And they’ve really evolved. The first agents for MS are not often used now, or are rarely first-line, and we have all these other effective therapies. With these agents [for AD], the hope is in the future that we refine their mechanism, refine their delivery, and get even more targeted and effective therapies.”

However, Dr O’Connor stressed that patients need to be carefully selected for the new therapies.

“Like all medications, they come with side effects. We need to make sure that people are appropriately selected, that there is not an excessive risk of side effects. Also, that the people are appropriate in that they are eligible to benefit.”

She added that patients who are not eligible for the new treatments still need to receive adequate support and management of their condition.

Raising awareness of autoimmune nodopathies

The guest lecture at the Neurology Update Meeting 2024 was delivered by Prof Simon Rinaldi, Clinical Director at the Oxford Autoimmune Neurology Diagnostic Laboratory, UK.

Prof Rinaldi’s lecture was entitled ‘Bridging the gap: Dissecting the autoimmune nodopathies’. The talk covered the history of clinical and experimental data in relation to the area. It highlighted the relevance of nodal/paranodal antibodies in the differential diagnosis of acute, severe, or atypical inflammatory neuropathies.

Prof Rinaldi stressed that the node is an important target for antibodies in autoimmune neuropathies. He said the detection of antibodies targeting nodal and paranodal cell-adhesion molecules defines a group of distinct conditions that are important to recognise.

Prof Rinaldi said work in the field has advanced significantly over the past decade.

“There are now lots of labs doing the testing, there’s lots more information coming through,” he explained. “And it’s really grown over the past 10 years, expanding the number of antibodies we know about, expanding how much we know about the clinical syndromes, and how they’re treated.”

In his lecture, Prof Rinaldi acknowledged there is debate about how widespread testing should be and when testing should be conducted. He stressed it should be borne in mind that these conditions are clinically and pathologically different and have a divergent treatment response profile compared to Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy (CIDP).

“I have one opinion, which is if you are going to treat someone for Guillain-Barré syndrome or CIDP, you should probably think about these antibodies and test for them,” he said. “Because if you find them, it’s going to change your thinking about what agents you use and in what order.

“Other people would say, ‘why don’t you just treat first and then if it doesn’t go as expected, then you test the antibodies’. And the reason I go against that is one, that you may have spent a lot of money on immunoglobulin that is not going to do anything. And two, you may have made those tests more difficult to interpret, if you have already started treatment before you do them.”

Prof Rinaldi described autoimmune nodopathies as “treatable disorders”, with rituximab being “the most sustained and overall effective” medication.

“On the other side of that, recovery is actually about the ability of the peripheral nervous system to regenerate and repair,” he said. “Probably the earlier you can get in and turn off the damaging process the more chance there is of a full recovery. But, actually, some of those deficits can become potentially permanent if they are long-standing, if they are severe. I think that’s again why early diagnosis is potentially important. Because if you can stop this process before lots of damage accrues, outcomes, I think, will be better.”

In terms of future directions, Prof Rinaldi said research is being conducted to further refine the individual syndromes, which have distinct characteristics. For example, IgG1 pan-neurofascin antibodies are associated with a particularly severe form of autoimmune neuropathy.

Patients typically present with acute, immobilising sensorimotor neuropathy, accompanied by cranial nerve involvement and long-term respiratory insufficiency. In the chronic phase of the disease, antibodies targeting nodal and paranodal proteins are predominantly of the IgG4 subclass, which is generally linked to a less aggressive but persistent course.

“So those pan-neurofascin patients probably have a distinct pathological process based more around acute complement activation and specific autoantibody involvement compared to the rest, with IgG4,” he explained.

“And there may also be different origins in terms of the B cells responsible.” He said work is required to examine both the induction phase and the effector phase.

“We are trying to refine the immunology of the induction phase: Where do the antibodies come from, why do patients develop them. Then think about the effector end and what are the antibodies doing. Targeting the effector end is probably targeting more of the acute side of things, let’s stop this as quickly as possible. Targeting the induction phase is more about sustained remission and sustained response, and I think we need to address both of those in parallel.”

Microvascular decompression for neuralgia

The final session of the Neurology Update Meeting 2024 began with a talk on microvascular decompression (MVD). The talk was given by Mr Jonathan Poots, Consultant Neurological Surgeon, Royal Victoria Hospital, Belfast.

MVD is a surgical procedure aimed at relieving abnormal pressure on a cranial nerve, which can cause conditions like trigeminal neuralgia, glossopharyngeal neuralgia, or hemifacial spasm. Mr Poots pointed out that multiple specialties, not only surgeons, are involved in the management of these conditions.

In relation to trigeminal neuralgia, he said that a standard neurological examination might find “very mild” sensory loss. The condition usually responds, at least initially, to carbamazepine.

“The character of the pain may change with the use of neuropathic pain medications and have more of a constant character,” Mr Poots said.

He explained that patients with predominantly constant or burning pain or facial numbness are not good candidates for MVD. It is also important that patients are “physiologically young” and can tolerate the procedure. As a general rule, patients should be under 70 years of age. The precise location of the pain is another consideration.

Mr Poots described MVD as a “satisfying operation”, with a number of positive aspects. He highlighted how it is predictable and a relatively short procedure (three hours). The development of microsurgical techniques has also improved its efficacy.

Side effects are rare, but they can be severe. They can include bleeding/haematoma, cerebrospinal fluid leak, and ipsilateral hearing loss, among others.

Generally, patients can return home days after the surgery and are able to go back to work within three to four weeks.

The duration of benefit from the procedure is 10 years, with approximately 70 per cent of patients having “an excellent outcome”.

“MVD offers the only chance for a non-destructive procedure and a more durable result,” according to Mr Poots.

The next lecture was given by Dr John Craig, Consultant Neurologist, Royal Victoria Hospital, Belfast, and was titled ‘Managing uncertainty in seizure disorders’.

The final talk of the Neurology Update Meeting 2024 was on the subject of paraproteinaemic neuropathies and was delivered by Dr Aisling Carr, Consultant Neurologist, University College London Hospitals, UK.

Each lecture on the day generated much discussion, showcased the notable progress of this sub-specialty, and underscored the important role of a multidisciplinary approach in optimising outcomes.

Feedback from evaluation forms was also positive, according to the Irish Institute of Clinical Neuroscience.

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