Adults with cerebral palsy about twice as likely to develop cardiovascular and chronic respiratory diseases, RCSI study

Adults with cerebral palsy are about twice as likely to develop cardiovascular disease and chronic respiratory disease compared to adults without cerebral palsy, according to a new study led by RCSI (Royal College of Surgeons in Ireland) and Brunel University London.The study compared 1,700 adults with cerebral palsy and 5,000 adults without cerebral palsy to identify how many developed non-infectious diseases, such as asthma or stroke. The research is published in the current edition of NEUROLOGY. 

Patients with cerebral palsy were overall 75% more likely to have a non-communicable disease. After adjusting for other variables, the study found that adults with cerebral palsy were around twice as likely to develop cardiovascular disease and chronic respiratory disease, such as asthma, but not more likely to develop diabetes or cancer.

Adults with cerebral palsy were specifically 2.6 times more likely to develop heart failure, 5.5 times more likely to have a stroke, 2.2 times more likely to develop asthma, 1.6 times more likely to develop hypertension and 2.3 times more likely to develop ischaemic heart disease.

Globally, approximately 17 million people have cerebral palsy. Although cerebral palsy was historically considered a paediatric condition, the majority of children with cerebral palsy now survive into adulthood and many adults with cerebral palsy have a near normal life expectancy.

Cerebral palsy is not a progressive condition. However, at least a quarter of young adults report that their ability to walk gets worse, which may contribute to the development of chronic health conditions.

“Until recently, we did not know much about the consequences of ageing with cerebral palsy. Our findings highlight the need for further research into the management of non-communicable diseases in this population,” said Jennifer Ryan, the study’s lead author and StAR Research Lecturer at RCSI and Senior Lecturer at Brunel University London.

“Recent clinical guidelines for adults with cerebral palsy in the UK recommended that pathways need to be developed that allow adults with cerebral palsy access to a multidisciplinary team. However, adults with cerebral palsy in Ireland lack access to co-ordinated multidisciplinary support.”

Being able to access health professionals, such as physiotherapists, orthopaedic surgeons and neurologists with knowledge of cerebral palsy early, may slow deterioration in the patient’s function and prevent development of secondary conditions with age.

Dr Neil O'Connell, co-author, physiotherapist and senior lecturer at Brunel University London said:

"Our results clearly emphasise the importance of reframing how cerebral palsy is traditionally viewed; to recognise that it is not simply a condition of childhood. Health services should be designed and delivered with the aim of supporting people with cerebral palsy to be healthy and active throughout their lives."

The study was funded by the Brunel University London Research Catalyst Fund, and it involved collaborators from Brunel University London, University of Michigan-Medicine, London School of Hygiene and Tropical Medicine, Aberdeen Royal Infirmary, Hospital Clinico San Carlos, University of Surrey and Queen Mary University London.

Queen Máxima visits Congress of the European Academy of Neurology

The Congress of the European Academy of Neurology (EAN) in Amsterdam received a royal visit today: H.M. Queen Máxima of the Netherlands attended the major scientific event at RAI Amsterdam, in which over 6,000 people are participating.

Queen Máxima attended a lecture on “Outcome measures in neurology” – the overarching theme of the EAN 2017 Congress. This important field deals, inter alia, with objective and patient reported indicators for the impact of neurological conditions on the patients’ well-being. It also helps to decide on the effectiveness of treatments. The Queen also met with leading representatives of the EAN and the Dutch neurological community, as well as patients suffering from neurological diseases. The EAN Congress deals with all neurological diseases of which headache, sleep disorders, dementia, stroke, epilepsy, Parkinson’s disease, multiple sclerosis are the most common ones.

                                                

“The EAN is very honoured by Queen Máxima’s visit and is delighted with the interest she showed in the topics we are discussing at the congress,” said EAN President Prof Guenther Deuschl. “In fact, there is hardly another discipline that is developing as rapidly as neurology. And this fast pace is urgently required given the growing disease burden. Data from the European Brain Council indicates that a total of 220.7 million people in Europe suffer from at least one neurological disease – that is more than the populations of Germany, France and Great Britain combined.” 

Headaches, with 152.8 million affected, top the list of the most common neurological disorders, followed by sleep disorders (44.9 million), strokes (8.2 million) and dementia (6.3 million). “Sufficient funding for brain research activities and adequate care for neurological patients must therefore be given high priority throughout Europe.” The EAN President also emphasized the excellent standing of neurology in the Netherlands as one of the 47 member countries of EAN.

Neurology congress in Amsterdam: Outcomes measurements are becoming ever more important

 Outcomes measurements are increasingly important in neurology from the perspective of practitioners as well as patients or the payers of health services. How can one objectively determine and plausibly prove whether a given therapy brings about the desired improvement, makes a useful clinical difference or delays the progression of a disease? Is the treatment in reasonable proportion to the patient benefits involved and to the financial cost? The 3rd Congress of the European Academy of Neurology (EAN) in Amsterdam is focused on this overarching focal theme, discussing it in several scientific sessions. 

For EAN Programme Committee Chairman Prof Paul Boon (Ghent University, Belgium and Kempenhaeghe, The Netherlands), the possible advantages for patients have priority when it comes to outcomes in neurology: “Of course, the clinical explanation of the disease mechanism revealed through such indicators is very important but patients obviously focus on other aspects.” After being diagnosed with epilepsy or migraine, they are usually keen to know the following: Will the therapy work? Will my seizures or headache attacks stop? Do the medications have undesirable side effects? How many pills do I need to take and when in order to achieve an optimum effect? “Outcomes measurements enable us to answer questions like these. In the process, we can find out how the disease will affect the patient in the future and see how our treatment is working,” explained Prof Dr Bernard Uitdehaag (VUmc MS Center Amsterdam), chair of the local organizing committee of the congress and chair of one of the EAN sessions on this topic.

Progress in measurement methods

Progress is being made in neurology in the development of assessment methods that are easy to handle, and can contribute to objective and precise outcomes measures. This is, however, not yet the case for all diseases. For slowly progressing neuromuscular diseases, for instance, existing outcomes measurements are still cumbersome and burdensome with regard to the patients’ restriction of motion and quality of life. By contrast, there have long been outcomes measurements for common diseases such as epilepsy and migraine. For example, the number of seizures or headache attacks is recorded. Prof Boon: “Recently, the measurements have become more differentiated. For example, we record days free of complaints. For patients, this metric is more meaningful than the total number of seizures.” With epilepsy, outcomes measurements are also assessed with EEG, which is then analysed using special software. Prof Boon: “This approach lets us detect certain indicators much more effectively than with customary methods.” 

For instance, in order to measure a possible decline of the condition of multiple sclerosis patients, a simple test has been established as a standard procedure: patients are asked to insert pegs in a board with nine holes and subsequently take them out one by one. If they need 20 per cent longer than last time, this difference proves that the disease has deteriorated clinically.

Measuring outcomes for dementia 

Researchers from Amsterdam have developed a questionnaire for Alzheimer’s patients which helps to detect dementia at an early stage. Further outcomes measurements for Alzheimer’s can be done with an amyloid PET scan. In this procedure, a low-radiation substance is injected, enabling amyloid plaques in the brain to be seen.  This protein is a typical biomarker for Alzheimer’s. Examinations of cerebrospinal fluid can also allow conclusions to be drawn about the progression of neurodegeneration in dementia. 

Combined methods yield more information

A combination of examination methods is increasingly relied upon in outcomes measurements. Prof Uitdehaag advised to use multidimensional outcomes measurements for heterogeneous diseases such as multiple sclerosis. “It is very revealing to harness the patient’s perspective together with e.g. imaging methods. An MRI scan can indicate a stable condition even though the patient is complaining about a change for the worse. Conversely, the patient can feel great while the MRI result indicates that problems are likely to occur in the near future.”

Side effects count as part of the overall outcomes 

In the treatment of neurological diseases, certain medications can provoke side effects such as difficulties in concentration or memory loss. Until a few years ago, these side effects were simply put up with, especially by older patients. Prof Boon emphasized that these attitudes are changing more and more, adding: “Side effects are recorded and taken seriously as part of outcomes measurements.” To an increasing extent, therapies are individually tailored to patients so outcomes, too, must be subject to a differentiated analysis. Prof Uitdehaag: “It no longer suffices to compare patient groups with each other in sweeping ways. Even if many people do respond to a certain treatment, it may not be effective for a given individual.” As therapies become more individualized, the challenge grows to record exactly what is being done, what benefits this action has and whether the treatment is beneficial for this specific patient.

Cost-benefit analysis 

As cost pressure on public health care budgets mounts, the field of neurology is also increasingly confronted with demands to give evidence of therapy outcomes so the costs of a given treatment can be weighed against its benefits. Prof Boon: “Payers in the European healthcare systems are showing an increasing interest in outcomes-related reimbursement concepts. In other words, they are willing to assume costs if the effectiveness of a treatment can be verified. In the process, new therapies are compared against conventional ones to find out which ones are worth the price being charged. The more varied the possible treatment options for a disease, the more relevant outcomes measurement becomes,” the expert concluded. 

Eisai epilepsy data presented at the American Academy of Neurology (AAN) annual meeting‏

 Data show that seizure control improves regardless of age, sex and ethnicity in drug-resistant patients with primary generalised tonic-clonic (PGTC) seizures treated with once-daily adjunctive Fycompa^®(perampanel) at doses up to 8mg per day.]  These data are one of a number of perampanel and Inovelon^® (rufinamide) abstracts presented this week at the American Academy of Neurology (AAN) Annual Meeting Vancouver, Canada.

The results show that a change in seizure frequency from baseline is greater with perampanel than with placebo across all groups and similar for placebo between age, sex, and ethnicity. Data are obtained from a double-blind, placebo-controlled Phase III study in 162 patients with idiopathic generalised epilepsy (IGE) (81 each on either perampanel or placebo) who have confirmed PGTC seizures.

“These data confirm that adjunctive perampanel provides effective management of seizures in all groups of IGE patients studied with primary generalised tonic-clonic seizures,” comments Bernhard Steinhoff, Medical Director and Executive Chief Physician, Kork Epilepsy Centre, Germany.

Post-hoc analysis of this Phase III study of adjunctive perampanel for primary tonic-clonic seizures across age, sex and ethnicity shows similar median percent change from baseline in primary generalised tonic-clonic seizure frequency for age (age <18y nbsp="" span="">-88.0%; age ≥18−<65y nbsp="" span="">-74.4%), sex (males, -53.3%; females, -83.0%) and ethnic groups (White, -65.5%; Asian/Pacific, -79.1%).  The 50% responder rate is also similar across age (age <18y 53.8="" age="" span="">-<65y 54.3="" 58.8="" 66.2="" 68.2="" 71.7="" acific="" and="" asian="" ethnic="" females="" groups="" hite="" males="" sex="" span="">

Perampanel has shown efficacy in, and is indicated for the adjunctive treatment of partial-onset seizures with or without secondarily generalised seizures in adult and adolescent patients from 12 years of age with epilepsy; and for the adjunctive treatment of primary generalised tonic-clonic seizures in adult and adolescent patients from 12 years of age with idiopathic generalised epilepsy. 

Abstract P2.024 17 April 08:30-17:30 PDT Krauss et al[iii]

Data presented from this Phase III study in PGTC seizures explores the relationship between perampanel exposure, primary generalised tonic-clonic seizure outcomes, and treatment-emergent adverse events (TEAEs) in patients with uncontrolled primary generalised      tonic-clonic seizures. Response rate increases, and responder probability is predicted to increase with increased perampanel exposure.  Concomitant use of enzyme-inducing anti-epileptic drugs (EIAED) reduces perampanel exposure, and perampanel exposure is higher in patients with hostility/aggression-related TEAEs than in those without, although the concentrations overlap substantially.³

Abstract P2.045 17 April 08:30-17:30 PDT French J et al

Data from an external review was used for the first time to ensure the appropriate classification of trial participants⁴ withprimary generalised tonic-clonic seizures in the Phase III perampanel PGTC trial. An independent group review eliminated almost a third (29.9%) of patients, initially considered eligible, from inclusion in perampanel’s pivotal study 332.  Without this review the interpretability of results may otherwise be compromised.⁴  

Abstract P2.044 17 April 08:30-17:30 PDT Tsong et al 

With the advent of newer medications for primary generalised tonic-clonic seizures the standard of care (SOC) has changed over time while trial designs remain similar over time, according to a systematic literature review of published data during 1989-2014 of different anti-epileptic drug (AED) trials versus placebo for adjunctive treatment of primary generalised tonic-clonic seizures. The latest trial, the perampanel Phase III study 332⁵ includes a standard of care that is weighted to the most recently approved drugs for primary generalised tonic-clonic seizures such as topiramate, lamotrigine, levetiracetam, and valproate.  

Abstract P5.405 20 April 08:30-19:00 PDT Perucca et al

In patients with partial seizures, results of an extension study shows that treatment with perampanel for three or four years significantly improves seizure control, and is well tolerated as an adjunctive treatment At three years’ exposure to perampanel, median seizure reduction is 61.98% and at four years’ exposure is 70.63%.  The largest median percent decrease during the last year of treatment occurs in patients with secondarily generalised seizures at baseline – at three years, seizure reduction is 87.96% and at four years is 100%.

“We are proud to share these data on the use of perampanel to manage partial-onset seizures and primary generalised tonic-clonic seizures, both seizure types with life-limiting outcomes where treatment with perampanel can make a real difference, Eisai is committed to the exploration of effective treatments for people affected by epilepsy,” comments Neil West, Vice President, Global Neurology Business Unit, Eisai EMEA.

Abstract P2.056 17 April 08:30-17:30 PDT Striano et al[viii] Abstract P2.043 17 April 08:30-17:30 PDT Ng et al

A sub-group analysis of another Phase III trial shows that rufinamide demonstrates favourable efficacy as adjunctive treatment for adults with Lennox-Gastaut syndrome (LGS), a severe and rare form of childhood-onset epilepsy, which affects nearly 208,000 people in Europe.  Median change from baseline in seizure frequency was -31.5% for rufinamide (n=21) versus +22.1% for placebo (n=21), this represents a statistically significant difference in favour of rufinamide (p=0.008).

Further data reported at AAN 2016⁹ in 138 people with LGS aged 4-37, shows no evidence of tolerance to rufinamide during short-term and long-term treatment.    Larger median decreases in both total and tonic-atonic seizure frequency for rufinamide versus placebo are evident as early as two weeks and over the course of treatment for rufinamide (total: -20.6%−-43.1%; tonic-atonic: -22.8%−-50.3%) than for placebo (total: 1.3%−-1.5%; tonic-atonic: -1.3%−1.0%), which suggests a fast onset of action and lack of short-term tolerance to rufinamide.

Rufinamide efficacy continues up to three years.  Over the course of open-label treatment from 3-36 months, progressive median decreases in seizure frequency for total seizures are -31.6% to -79.3% and for tonic-atonic seizures are -41.9% to-76.1%.⁹

Rufinamide is currently indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in children four years and older. Effective Lennox-Gastaut Syndrome management and compliance to treatment is of key importance to patients, as the condition is characterised by a high number of seizures - up to 70 seizures a day.  The condition often persists into adulthood and most people with this condition will have developmental delay, mental retardation, and moderate to severe learning disabilities, in addition to physiological and behavioural problems.

The development of perampanel and rufinamide demonstrates Eisai’s commitment to the therapeutic area of epilepsy and further exemplifies the company’s contribution to addressing the diversified needs of and increasing the benefits provided to patients and their families as shown by its human health care mission.

World Congress of Neurology to take place in Santiago de Chile

The Chilean capital Santiago will host the XXII World Congress of Neurology (WCN 2015), the world's biggest and most important neurology event. About 3.500participants are expected to attend this major scientificmeeting which will be held at the Casa Piedra, Centro de Eventos, Congresos y Exhibiciones, from October 31 to November 5, 2015. More than 220 renowned invited speakers from all fields of neurology will lecture on latest developments in their fields of expertise.
 
The WCN 2015 is organized by the World Federation of Neurology (WFN) together with the Sociedad de Neurología Psiquiatría y Neurocirugía de Chile. 
 
The timely Congress motto is “Changing Neurology Worldwide”. The Congress provides an impressive overview of the achievements of modern neurology, a medical discipline which will gain more importance not just in view of demographic developments. 
 
“According to the World Health Organisation, neurological disorders are responsible for between 4.5 and 11 per cent of all illnesses, depending on whether you are looking at low- or high-income economies. This is far higher than the number of respiratory ailments, gastrointestinal disorders or malignant tumours. And the burden is set to increase dramatically in the years to come”, says WFN President Dr Raad Shakir. 
 
“Many people all over the world have either no access or only inadequate access to neurological care. We must therefore be very vocal in our support for more global cooperation in research as well as training and continuing education”, according to WFN Secretary General Prof Wolfgang Grisold.
 
Against the background of an increase in neurological diseases on the global scale the World Congress of Neurology will feature important topics such asdementia, stroke, headache, epilepsy, multiple sclerosis, pain management, genetics in neurology, gender-related issues, sleep disorders, neuromuscular disorders or neuro-oncology. 
 
„Chile and many countries in Latin America are leaving behind the health problems of underdevelopment, and are facing the diseases of aging. We are developing techniques in genetics, neuro-radiology or rehabilitation”, Congress President? Dr Renato Verdugounderlines. “It is the right time to have a World Congress of Neurology in Chile.”