More than 250 participants and speakers bring updates on Parkinson’s disease, migraines, and more.

Marianne de Visser

Rajeev Ojha

Rajeev Ojha and Marianne de Visser

I was fortunate to be invited to the First International Congress of Nepalese Academy of Neurology May 18-19 in Kathmandu, Nepal. Sessions on major neurological disorders, such as stroke, movement disorders, demyelinating disorders, epilepsy, headache, and cognitive neurology filled two conference days. There were also sessions on neuromuscular disorders and general neurology. Plus, there were posters and oral communications presented by early-career neurologists and residents. Dr. Rajeev Ojha, co-author of this report, was instrumental as one of the organizers of the congress, and he invited me to participate in the congress.

When I was on stage for my talk, I conveyed a message from WFN President, Prof. Wolfgang Grisold, in which he congratulated the president of the Nepalese Academy of Neurology on this unique event. It was a splendidly organized congress in a beautiful hotel in the center of Kathmandu, thanks to the assistance of the upcoming neurological generation and volunteers from the medical school. There were more than 250 participants and many speakers from abroad, including India, Malaysia, the Netherlands, Spain, and the United States.

Prof. Marianne de Visser giving a lecture during the neuromuscular session of congress on the second day.

During breaks between the sessions, there was plenty of time for networking. We were able to discuss how training in neurology and neurological care was organized in Nepal. The standard of care in Nepal is impressive considering that according to the World Bank it is a low- and middle-income country. MRI and endovascular interventions are readily available. However, the cost of thrombolysis and mechanical thrombectomy is high, and the insurance service is not available to most of the general public.

Prof. Shen-Yang Lim, co-lead of monogenic portal development and underrepresented populations for the East Asia branch of the Global Parkinson´s Genetics Program (GP2), congratulated Nepal on being connected to the GP2, which is a collaborative research program to understand the genetic architecture of Parkinson´s Disease. Dr. Avinash Chandra from Nepal highlighted how oral abortive treatments for migraine, such as rizatriptan and sumatriptan, have been available for a few years and recently zolmitriptan has been made available in nasal spray.  On the other hand, local speaker Dr. Niraj Gautam spoke about the unavailability of monoclonal antibodies used in the treatment of multiple sclerosis in Nepal. Prof. Lekha Pandit, from India, and Prof. Xavier Montalban, from Spain, presented an excellent diagnosis update and a discussion about the management of multiple sclerosis, respectively.

Right Honorable Vice President of Nepal, Mr. Ram Sahaya Prasad Yadav, congratulating first Nepalese neurologist Prof. Dinesh Bikram Shah during the inauguration ceremony of First Nepalese International Congress 2024.

The organizing committee included a neuromuscular session in the program. I selected myositis as a topic. Another speaker in that session was Prof. Nalini Atchayaram, from India, who gave a presentation on Hirayama disease, a disorder that should not be missed because it is treatable by surgery and may mimic ALS. She cited studies composed of hundreds of patients with this disease who, if diagnosed early, usually had excellent outcomes.

The other speakers gave excellent presentations on the diagnostic approach of muscular dystrophy (Dr. Saraswati Nashi, also from India) and on ocular myasthenia gravis (Prof. Rabindra Shrestha, from Nepal). Part of the congress was dedicated to an amazing cultural event with dancing and singing by local dancers in traditional costumes from different regions across Nepal.

All in all, this was an extremely inspiring and memorable congress that also put early career neurologists in the spotlight. During the breaks, many neurologists were willing to share the history of neurology becoming a separate discipline in Nepal and how they managed to establish three training centers across Nepal. There is an urgent need for training more neurologists (currently four residents per annum), since Nepal currently has 35 neurologists for a population of 31 million inhabitants.

I am indebted to the organizers of the congress, in particular to NAN President Prof. Kumar Oli and Secretary General Prof. Rabindra Shrestha. To my esteemed colleague and co-author, Rajeev Ojha, and to everyone who made my first visit to Nepal an incredible experience, I would like to express my sincere gratitude. •

Marianne de Visser, MD, PhD, FEAN, is a neurologist at Amsterdam University Medical Center in the Netherlands, and emeritus professor of neuromuscular diseases. Rajeev Ojha, MD, DM, FEBN, is a lecturer in the department of neurology at Tribhuvan University Institute of Medicine in Kathmandu, Nepal.

Partnerships could lead to new treatments and improved patient care.

Christina Briscoe Abath, MD, EdM, and Keryma Acevedo, MD

Keryma Acevedo, MD

Christina Briscoe Abath, MD, EdM

Although it has gone by many other names, infantile epileptic spasms syndrome (IESS) has been described since 1841. It is the most common infantile-onset epilepsy syndrome, and first-line treatments are over 40 years old. Steroids (prednisolone or ACTH) have been used since the 1950s, and vigabatrin has been used since the 1980s. The newest effective treatment for some children, epilepsy surgery, has been prescribed for epileptic spasms since 1990.¹ There has been consensus about the initial treatment for over a decade, as well as recognition that the lead time to standard treatment affects long-term developmental outcomes.^2,3 Treatment initiation of first-line therapy is considered a priority for the clinical team.

Despite this, most children in the world continue to have long delays in diagnosis. Although present in most settings, these delays are not equally distributed. In a large series from Bangladesh, the median lead time to a standard therapy was 5 months.⁴ Even in Boston (U.S.), the average lead time to standard therapy was 29 days.⁵ In the U.S., BIPOC (Black, Indigenous, and People of Color) infants, and those whose caregivers speak another language, are more likely to have delays to neurology referral.^6,7

Just as disturbing, not all children who are correctly diagnosed will receive appropriate treatment despite consensus about standard therapies. At quaternary care centers in the U.S. with pediatric epileptologists, Black/Non-Hispanic children and those with public insurance are less likely to receive a standard treatment course.⁸

In many countries, standard therapies are not always readily available. In Chile, for example — despite access to pediatric neurologists and similar delays to diagnosis as in Boston — challenges with access to standard treatments in the public system mean that between 2015-2022, only 67% of children received a standard treatment course.⁵ Moreover, anti-seizure medications (ASMs) for IESS are not covered by the National Epilepsy Plan, resulting in an extremely heavy economical overload for families.^9,10

On top of these issues, ACTH and vigabatrin have not been consistently available, and prednisolone has not been incorporated in the country’s list of approved drugs. This means that prednisolone is not available for purchase in Chile, resulting in families needing to go to Perú or other countries to buy the medication if indicated by their clinical team.¹¹ Efforts are underway to address these challenges with the Ministry of Health.

Hypsarrhythmia, initially described by Gibbs and Gibbs in 1952 (spelled as hypsarhythmia), is the classical interictal background pattern found in children with infantile epileptic spasms syndrome (IESS). It is high voltage, chaotic, and has embedded multifocal epileptiform abnormalities. Hypsarrhythmia may be state dependent, and only present in sleep. While no longer required for IESS diagnosis, when present it can suggest a diagnosis when accompanied by history concerning for epileptic spasms in children of the appropriate age (1-24 months).

Partnering Together for Solutions

New therapies and research to understand mechanisms of disease for IESS are certainly needed, since only around half of children will respond to the first standard therapy and only around 70% will respond to early sequential or dual therapy.^12,13 For this, significant increases in research for pediatric epilepsy are needed, given significant disparities in funding.¹⁴ The U.S. National Institutes of Health (NIH) spent approximately $68 per person with epilepsy in 2023 ($232 million for 3.4 million individuals in the U.S.).^15,16 In contrast, ALS receives $9,512 per person, Alzheimer’s $583 per person, and Parkinson’s disease $270 per person.¹⁶ Inadequate funding for drug research and development may be one reason why there have been no new first-line medications approved for IESS since the 1980s.

However, the percentage of children who do respond means that most children will still benefit from what we currently know and can apply appropriately.¹³ Given the high morbidity and mortality of IESS — with a 5-10% chance of response to a non-standard therapy — standard therapies are most likely cost-effective for public systems. Research should be done to support this supposition. We do know that epilepsy surgery is cost-effective for epilepsy, though cost-effectiveness specifically for epileptic spasm surgery has not been specifically assessed to our knowledge.^17,18

Intervention is needed at every level of health systems to effectively address these gaps in diagnosis and therapy. In May 2022, the Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders (IGAP) was unanimously approved at the 75th World Health Assembly, providing an invaluable tool to advocate for treatment and access around the world.^19,20

Joint efforts are needed to improve the standard of care for IESS, including early diagnosis, training general practitioners and pediatricians about adequate referral for suspicious clinical events, education of parents of children at high risk for IESS (Down Syndrome, Tuberous Sclerosis, Hypoxic Ischemic Encephalopathy), and access to standard treatments.

Families of children who have been affected by IESS are uniquely motivated to address these challenges. Partnering with these families to advocate for awareness and access to therapies is also needed. At a micro level, social media campaigns can promote epileptic spasm awareness. At the middle level, medical and other professional schools should incorporate pediatric epilepsy education (more common than other conditions that receive more attention). At a macro level, health systems should prioritize access to cost-effective epilepsy medication and therapies (including epilepsy surgery).

Much remains to be done around the world. In the U.S., one of the authors (CB) has been fortunate to start to work with the Infantile Spasms Action Network, parents of children with IESS, and other neurologists who are passionate about closing the equity gaps. We have created a module for primary care providers to recognize epileptic spasms and are working on a series of grassroots initiatives (a children’s book and a stuffed bear with EEG electrodes) to promote pediatric epilepsy awareness in Spanish, French, and English.

In Chile, the Chilean League Against Epilepsy (LICHE) is a non-profit organization that has several pharmacies distributed around the country that not only provide social benefits and discounts in ASMs, but also act as an intermediary to import medications to collaborate in the management of epilepsies, partnering with patients and their neurologists. As a PAHO/WHO Collaborating Centre, LICHE is committed with advocacy and education for patients, their families, caregivers and the community.

We believe collaboration, funding, and advocacy will be essential to making progress for children with IESS around the world. Please reach out to us with ideas, comments, and questions at:  christina.briscoeabath@childrens.harvard.edu and kacevedo@uc.cl. •

Christina Briscoe Abath, MD, EdM, is incoming instructor of neurology, Boston Children’s Hospital. Keryma Acevedo, MD, is associate professor, Section of Neurology, Division of Pediatrics, Pontificia Universidad Católica de Chile, and president of the Chilean League Against Epilepsy

References

1. Chugani HT, Shewmon DA, Shields WD, et al. Surgery for Intractable Infantile Spasms: Neuroimaging Perspectives. Epilepsia. 1993;34(4):764-771. doi:10.1111/j.1528-1157.1993.tb00459.

2. O’Callaghan FJK, Lux AL, Darke K, et al. The effect of lead time to treatment and of age of onset on developmental outcome at 4 years in infantile spasms: Evidence from the United Kingdom Infantile Spasms Study. Epilepsia. 2011;52(7):1359-1364. doi:10.1111/j.1528-1167.2011.03127.

3. Pellock JM, Hrachovy R, Shinnar S, et al. Infantile spasms: A U.S. consensus report. Epilepsia. 2010;51(10):2175-2189. doi:10.1111/j.1528-1167.2010.02657.

4. Abath CB, Chandra Saha N, Hoque SA, et al. Clinical characteristics of children with infantile epileptic spasms syndrome from a tertiary-care hospital in Dhaka, Bangladesh. Heliyon. 2023;9(3):e14323. doi:10.1016/j.heliyon.2023.e14323.

5. Briscoe Abath C, Vega S, Castro Villablanca F, Moya J, Garrido C, Hadjinicolaou A, Marin J, Munoz C, Soto C, Quintanilla C, Singh A, Margarit C, Andrade L, Leal L, Santana Almansa A, Gupta N, Acevedo K, Harini C. Proyecto Recaida: multi-center collaboration for infantile epileptic spasms syndrome relapse prediction and prognosis. American Epilepsy Society Conference 2023. Published December 2023. Accessed January 15, 2024. https://aesnet.org/abstractslisting/proyecto-recaida-multi-center-collaboration-for-infantile-epileptic-spasms-syndrome-relapse-prediction-and-prognosis.

6. Hussain SA, Lay J, Cheng E, Weng J, Sankar R, Baca CB. Recognition of Infantile Spasms Is Often Delayed: The ASSIST Study. The Journal of Pediatrics. 2017;190:215-221.e1. doi:10.1016/j.jpeds.2017.08.009.

7. Briscoe Abath C, Gupta N, Hadjinicolaou A, et al. Delays to Care in Infantile Epileptic Spasms Syndrome: racial and ethnic inequities. Epilepsia. n/a(n/a). doi:10.1111/epi.17827.

8. Baumer FM, Mytinger JR, Neville K, et al. Inequities in Therapy for Infantile Spasms: A Call to Action. Annals of Neurology. 2022;92(1):32-44. doi:10.1002/ana.26363.

9. Jr JE. Seizures and Epilepsy. OUP USA; 2013.

10. Engel J. What can we do for people with drug-resistant epilepsy?: The 2016 Wartenberg Lecture. Neurology. 2016;87(23):2483-2489. doi:10.1212/WNL.0000000000003407.

11. Ramani PK, Briscoe Abath C, Donatelli S, et al. Initial combination versus early sequential standard therapies for Infantile Epileptic Spasms Syndrome-Feedback from stakeholders. Epilepsia Open. 2024;9(2):819-822. doi:10.1002/epi4.12895.

12. Knupp KG, Leister E, Coryell J, et al. Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort. Epilepsia. 2016;57(11):1834-1842. doi:10.1111/epi.13557.

13. Mytinger JR, Parker W, Rust SW, et al. Prioritizing Hormone Therapy Over Vigabatrin as the First Treatment for Infantile Spasms. Neurology. 2022;99(19):e2171-e2180. doi:10.1212/WNL.0000000000201113.

14. Meador KJ, French J, Loring DW, Pennell PB. Disparities in NIH funding for epilepsy research. Neurology. 2011;77(13):1305-1307. doi:10.1212/WNL.0b013e318230a18f.

15. Epilepsy Data and Statistics | CDC. Published March 30, 2023. Accessed January 15, 2024. https://www.cdc.gov/epilepsy/data-research/facts-stats/?CDC_AAref_Val=https://www.cdc.gov/epilepsy/data/index.html.

16. RePORT. Accessed January 15, 2024. https://report.nih.gov/funding/categorical-spending#/.

17. Widjaja E, Li B, Schinkel CD, et al. Cost-effectiveness of pediatric epilepsy surgery compared to medical treatment in children with intractable epilepsy. Epilepsy Research. 2011;94(1):61-68. doi:10.1016/j.eplepsyres.2011.01.005.

18. Ngan Kee N, Foster E, Marquina C, et al. Systematic Review of Cost-Effectiveness Analysis for Surgical and Neurostimulation Treatments for Drug-Resistant Epilepsy in Adults. Neurology. 2023;100(18):e1866-e1877. doi:10.1212/WNL.0000000000207137.

19. Grisold W, Freedman M, Gouider R, et al. The Intersectoral Global Action Plan (IGAP): A unique opportunity for neurology across the globe. Journal of the Neurological Sciences. 2023;449. doi:10.1016/j.jns.2023.120645.

20. Wilmshurst JM. ICNA and the Global Regional Initiative Program: Aligning with IGAP towards providing child neurology services where they are most needed. Developmental Medicine & Child Neurology. n/a(n/a). doi:10.1111/dmcn.15836.

Neurologists from around the world converge in Almaty.

By Aida Kondybayeva

The VI International Educational Forum: Neurology Update in Kazakhstan, took place May 17-18, 2024, at the DoubleTree by Hilton Hotel in Almaty, Kazakhstan. The forum has become an annual tradition for neurologists not only from various regions of Kazakhstan but also from Kyrgyzstan, Azerbaijan, and Uzbekistan, gathering more than 700 doctors online and in person. The forum was supported by the Asfendiyarov Kazakh National Medical University and the Central City Clinical Hospital of Almaty.

The forum featured world-renowned neurologists, including:

• Paul Boon, MD, PhD, FEAN, president of the European Academy of Neurology, Belgium;
• Andrei Alexandrov, MD, professor of neurology at the University of Arizona, United States;
• Thanh Nguyen, MD, FRCPc, FSVIN, FAHA, president of the Society of Vascular and Interventional Neurology, United States;
• Dieter Ritmacher, PhD, vice dean for research and postgraduate education, professor of neurosciences, at the Nazarbayev University School of Medicine in Astana, Kazakhstan;
• Valery Feigin, MD, PhD, professor, National Institute for Stroke and Applied Neurosciences, School of Clinical Sciences at the Auckland University of Technology in New Zealand;
• Celia Oreja-Guevara, MD, vice chair and senior neurologist of the department of neurology at the University Hospital San Carlos, associate professor of neurology at the Universidad Complutense, and head of the Multiple Sclerosis Center at the University Hospital San Carlos in Madrid, Spain;
• Ugur Uygunoglu, MD, professor, department of neurology at Istanbul University, Cerrahpasa School of Medicine;
• Natalia Khachanova, department of neurology and clinical neurophysiology at the Pirogov National Medical and Surgical Center, and neurologist of the MS department of City Clinical Hospital No. 24.

The forum also featured a number of Kazakh speakers, including:

• Prof. Zhannat Idrisova, Asfendiyarov Kazakh National Medical University;
• Prof. Gulnar Kabdrakhmanova, Marat Ospanov West Kazakhstan Medical University;
• Ruslan Belyaev, Karaganda Medical University;
• Aida Kondybayeva, MD, PhD, Asfendiyarov Kazakh National Medical University;
• Karlygash Kuzhibayeva, head of the Center for Multiple Sclerosis, Autoimmune, and Orphan Diseases of the Nervous System, in Almaty;
• Tatyana Kaymak, neurologist at “SanClinic” in Semey; Adil Bisembaev, Private Clinic Almaty.

Next year, the International Educational Forum: Neurology Update in Kazakhstan 2025, will be held on
April 25-26.

We look forward to seeing you in Almaty in 2025! •

Aida Kondybayeva, MD, PhD, FEAN, is head of the Scientific and Educational Center for Neurology and Applied Neuroscience at Asfendiyarov Kazakh National Medical University, and chair of the Educational Committee at Kazakhstan National Association of Neurologists “Neuroscience” and Institutional Delegate at the European Academy of Neurology from Kazakhstan.