Colorized scanning electron micrograph of a cell showing morphological signs of apoptosis, infected with SARS-COV-2 virus particles (orange), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland.

NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community

NIH Press Release

For the millions of people living with a rare disease, the novel coronavirus disease COVID-19 presents challenges, from potential reduced access to needed medical care to possible heightened anxiety and stress. A new online survey launched by the National Institutes of Health-supported Rare Diseases Clinical Research Network (RDCRN) aims to find out how the COVID-19 pandemic is impacting individuals with rare diseases, their families and their caregivers. Results will help the rare disease research community shed light on the needs of people with rare diseases during the COVID-19 pandemic and other potential health crises, in addition to informing future research efforts.

The RDCRN, led by NIH’s National Center for Advancing Translational Sciences (NCATS), in collaboration with nine other NIH Institutes and Centers, currently is made up of 20 recently funded clinical research consortia focused on better understanding how rare diseases progress and developing improved approaches for diagnosis and treatment. Scientists from different disciplines at hundreds of clinical sites around the world work together with about 140 patient advocacy groups to study more than 200 rare diseases, including immune system disorders, heart, lung and kidney disorders, brain development diseases and more.

“As a leader in fostering innovative, collaborative clinical research to improve the lives of individuals  with rare diseases, the RDCRN is uniquely positioned to carry out a survey like this,” said Anne Pariser, M.D., director of the NCATS Office of Rare Diseases Research, which oversees the RDCRN. “The network has the necessary infrastructure, disease expertise, and access to patients through patient organizations to find answers to important questions.”

Though individually rare, affecting only a few hundred to several thousand people, rare diseases collectively affect an estimated 30 million people in the United States. Many rare diseases are life-threatening, and about half of those affected are children.

The research survey, developed and led by the RDCRN Data Management and Coordinating Center at Cincinnati Children’s Hospital Medical Center, is one of the first efforts nationwide to quantify the impact of a health crisis on the rare disease community. It is seeking responses from at least 5,000 people with a rare disease or caring for someone who has a rare disease. The survey will be distributed online to participants. In addition, some RDCRN-funded scientists plan to incorporate survey results into natural history studies, which follow patients to chart the progression and course of a disease. The survey is open to anyone with a rare disease, along with family and caregivers, and is not limited to the diseases studied within the RDCRN.

The impetus for the survey began through conversations among network researchers and patient advocacy organizations. Patients, families and caregivers were worried about how COVID-19 might affect them.

“People affected by a rare disease, and families and caregivers, initially asked how to avoid the virus,” said RDCRN Program Director Tiina Urv, Ph.D. “Then they became concerned about access to medicines and maintaining medical care during the pandemic, and the status of clinical trials. They were concerned about meeting the medical challenges that they face every day. We were hearing enough anecdotally that we wanted to get a clearer picture of the problem.”

As consortia scientists and clinicians engaged with patient groups and patients, sharing information and advice, a plan came together over several weeks to conduct a scientific research study to gauge the impact of COVID-19 on those in the rare disease community.

Questions in the research survey focus on a range of topics, from a patient’s ability to get proper care for a rare disease or condition to mental and emotional health. The survey asks what their concerns are as a person with a rare disease, or as family members and caregivers. Groups of people with different rare diseases and the community will have different needs and concerns, whether it is how to get needed medications or physical therapy to navigating an emergency room in a medical crisis.

“We hope the study questionnaire will help us better estimate the proportion of rare disease patients who have been diagnosed with COVID-19, and find out how they are affected whether or not they had COVID-19,” said project principal investigator Maurizio Macaluso, M.D., Dr.P.H. at Cincinnati Children’s. “This survey provides an opportunity for the rare disease community to get timely data on the challenges they face.”

The researchers also think the survey data may help them tease out answers to many other questions. For example, do some subgroups of people with rare disease fare better or worse with the virus? Are certain individuals more prone to infection because of their underlying rare condition or disease?

Ultimately, the researchers hope the survey will help determine how the RDCRN can respond to the rare disease community’s concerns by providing information and advice through its network of medical experts and patient advocacy groups.

“This survey is a great example of how the consortia and patient groups are working together as a network to make a difference for the entire rare disease community,” Urv said.

For more information on the RDCRN COVID-19 survey, including how to participate, go to To learn more about the RDCRN, see

In addition to NCATS, other NIH funding for the RDCRN comes from the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Neurological Disorders and Stroke, the National Heart, Lung, and Blood Institute, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Dental and Craniofacial Research, the National Institute of Mental Health and the Office of Dietary Supplements.

About the National Center for Advancing Translational Sciences (NCATS): NCATS conducts and supports research on the science and operation of translation — the process by which interventions to improve health are developed and implemented—to allow more treatments to get to more patients more quickly. For more information about NCATS and its programs, visit

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

University of Alabama Birmingham Dr. Sandipan Pati stands smiling in a nice blue suit.

Extra Benefit from Epilepsy Neurostimulators – Reducing Coexisting Neuropsychiatric Symptoms

People with drug-resistant epilepsy also can have deleterious neuropsychiatric symptoms like anxiety, depression, psychosis and impaired memory. These have negative impacts on quality of life, and there is an unmet need to improve therapy for such patients. Diagnosing and monitoring such neurobehavioral symptoms is challenging because their presentation can overlap with seizures.

Sandipan Pati, M.D., and his colleagues at the University of Alabama at Birmingham now report cases of five patients who found better treatments for those symptoms using data collected — while the patients were at home — from implanted neurostimulators placed in their brains to control their epileptic seizures. This is an extra benefit from the implanted Responsive Neurostimulator Systems, due to the system’s ability to record brain electrocorticography data initiated when a patient senses an anxiety or panic attack.

This data is key to showing whether the neuropsychiatric comorbidity began before, during or after an epileptic seizure. This guides medication or therapy changes that can reduce the negative symptoms caused by attacks that initiate outside of seizures, including psychogenic nonepileptic seizures. The only other way to get this useful information is video-electroencephalography in an inpatient clinic, with stays that typically last three to five days.

“Treating these patients can be challenging, and one reason for this is that sometime seizures can mimic anxiety and panic attacks, or psychosis,” Pati said. “Seizure-induced anxiety or psychosis is treated with anti-seizure medications, while ‘pure’ psychosis is treated with anti-psychotic medications. This study will be attractive for patients, as anxiety or depression is a common problem in epilepsy, and patients get frustrated as they think we are always focused on treating seizures and not depression.”

How Often Do Doctors Discuss Drug Withdrawal with their Seizure-Free Patients with Epilepsy?

Among patients with epilepsy, almost 70% become seizure-free with the current antiseizure drugs (ASDs) within 20 years following seizure onset. Of those who have been seizure-free for many years, around 70% remain seizure-free after withdrawal of ASDs.

The purpose of this study was to determine the extent to which seizure-free patients with epilepsy in Norway discuss drug discontinuation with their physician.

An online questionnaire was used; among the respondents were 186 adult patients who had been seizure-free for at least five years and were still using ASDs. Of these, 60 patients (32%) reported that they had discussed the question of drug withdrawal with their treating physician. Those patients who reported being involved in treatment decisions were more likely to have discussed ASD withdrawal.

In conclusion, it is the research team’s opinion that discontinuation of drug treatment in patients with long-term seizure freedom is discussed far too seldom and that many patients may be living with an unnecessary drug burden.

A blonde woman in a lab coat is conducting genetic research in the lab.

CURE Discovery: Researchers use “Big Data” to Identify a Protein that Protects Against Epileptogenesis

Key Points


  • Dr. Avtar Roopra and his team used a “big data” approach to understand how an injured brain may develop epilepsy. To do so, the team analyzed a vast amount of data to identify a protein called EZH2, which determines when thousands of genes are “turned on” or “turned off.”
  • The research team found that inhibiting EZH2 activity increased the frequency and severity of seizures in rodent models of acquired epilepsy, suggesting that EZH2 protects against the development of seizures and may be a potential new therapeutic target.
  • Because of this CURE-funded work, Dr. Roopra was able to secure a grant from the National Institutes of Health (NIH) to continue his promising study on EZH2.

Deep Dive

There are many antiepileptic drugs (AEDs) commercially available, but they only treat the seizures rather than cure or even prevent epilepsy. To develop curative or preventative AEDs, researchers must first understand the biological mechanisms underlying epileptogenesis, the process by which an initial “insult” to the brain, such as a head injury or even a period of recurrent seizures, leads to epilepsy.1 A particularly critical stage of epileptogenesis is called the latent period, a poorly understood span of time between the initial insult and the onset of epilepsy.1 Dr. Roopra’s CURE-funded project set out to better understand what happens in the brain during this period.2

Key Terms DefinedThe researchers turned to a potentially powerful method, which involves identifying possible proteins, known as transcription factors, that activate (“turn on”) or suppress (“turn off”) specific genes. Some transcription factors control thousands of genes and are therefore known as “master” regulators. Unfortunately, finding these master regulators can be a challenging task given the large quantity of genomic data to analyze.

Dr. Roopra’s work overcame these challenges through a collaboration with Dr. Raymond Dingledine’s team at Emory University. They collected data from numerous laboratories and worked together to construct a large database of detailed gene expression profiles3 of brain cells from different rat models of acquired epilepsy, collected at multiple time points during the latent period.4 Dr. Roopra’s team then developed a high-powered computer algorithm5 to identify potential master regulators from this database.

Gene Expression ProfileUsing these tools, Dr. Roopra and his team uncovered evidence for increased levels of EZH2 in these samples.2 In addition, when the team inhibited EZH2 activity in rodent models of acquired epilepsy, the frequency and severity of daily seizures increased significantly, suggesting that EZH2 serves to dampen seizure activity during the latent period. 2

This discovery could lead to the development of novel treatments that could potentially cure or even prevent epilepsy rather than offer only symptomatic treatment of the seizures.

Since completing his CURE-funded grant, Dr. Roopra and his co-investigators have parlayed their initial results to obtain a much larger grant from the NIH to further explore the role of EZH2 in the generation of epilepsy. CURE is proud to have played a part in propelling Dr. Roopra’s groundbreaking work to the next stage. Such success highlights the importance of funding innovative ideas that one day will lead to developing treatments with “no seizures, no side effects” for every person with epilepsy.

Literature Cited

1Lukawski, K. et al. Mechanisms of epileptogenesis and preclinical approach to antiepileptogenic therapies. Pharmacol. Rep. 2018; 70(2): 284-293.
2 Khan, N. et al. A systems approach identifies Enhancer of Zeste Homolog 2 (EZH2) as a protective factor in epilepsy. PLoS One 2019; 14(12): e0226733.
3 Casamassimi, A. et al. Transcriptome profiling in human diseases: new advances and perspectives. Int. J. Mol. Sci. 2017; 18(8): 1652.
4 Dingledine. R. et al. Transcriptional profile of hippocampal dentate granule cells in four rat epilepsy models. Sci. Data 2017; 4: 170061
5 Roopra, A. MAGIC: A tool for predicting transcription factors and cofactors driving gene sets using ENCODE data. PLoS Comput. Biol. 2020; 16(4): e1007800.

Your support makes this research possible. Our researchers’ important work continues through the current public health crisis and beyond, thanks to generous donors who, like us, envision a world without epilepsy.

Epilepsy in Older People

Globally, as populations age there will be challenges and opportunities to deliver optimal health care to senior citizens. Epilepsy, a condition characterized by spontaneous recurrent seizures, is common in older adults (aged  > 65 years) and yet has received comparatively little attention in this age group.

In this Review, researchers evaluate the underlying causes of epilepsy in older people, explore difficulties in establishing a diagnosis of epilepsy in this population, discuss appropriate antiseizure medications, and evaluate potential surgical treatment options. We consider cognitive, psychological, and psychosocial comorbidities and the effect that epilepsy might have on an older person’s broader social or care network in high-income versus middle-income and low-income countries.

We emphasize the need for clinical trials to be more inclusive of older people with epilepsy to help inform therapeutic decision making and discuss whether measures to improve vascular risk factors might be an important strategy to reduce the probability of developing epilepsy.

Poverty, Insurance, and Region as Predictors of Epilepsy Treatment Among US Adults

Disparities in epilepsy treatment have previously been reported. In the current study, researchers examine the role of socioeconomic status, health insurance, place of residence, and sociodemographic characteristics in past-year visit to a neurology or epilepsy provider and current use of antiseizure medications.

Multiple years of data were compiled from the National Health Interview Surveys, Sample Adult Epilepsy Modules. The sample (n = 1655) included individuals 18 years and older who have been told by a doctor to have epilepsy or seizures. Independent variables included number of seizures in the past year, health insurance, poverty status, education, region, race/ethnicity, foreign-born status, age, and sex/gender.

Accounting for recent seizure activity and other factors, uninsured and people residing outside of the Northeast were less likely to see an epilepsy provider, and people living in poverty were less likely to use medications, relative to their comparison groups. However, no racial/ethnic and nativity-based differences in specialty service or medication use were observed.

Further research, including longitudinal studies of care trajectories and outcomes, are warranted to better understand healthcare needs of people with epilepsy, in particular treatment-resistant seizures, and to develop appropriate interventions at the policy, public health, and health system levels.

Study Shows No Risk of Seizures from COVID-19

The aim of this study was to clarify the incidence and risk of acute symptomatic seizures in people with coronavirus disease 2019 (COVID-19). This multicenter retrospective study enrolled people with COVID-19 from 18 January to 18 February 2020 at 42 government-designated hospitals in Hubei province, the epicenter of the epidemic in China; Sichuan province; and Chongqing municipality.

Data were collected from medical records by 11 neurologists using a standard case report form. A total of 304 people were enrolled, of whom 108 had a severe condition. None in this cohort had a known history of epilepsy. Neither acute symptomatic seizures nor status epilepticus was observed. Two people had seizure-like symptoms during hospitalization due to acute stress reaction and hypocalcemia, Eighty-four (27%) had brain insults or metabolic imbalances during the disease course known to increase the risk of seizures.

There was no evidence suggesting an additional risk of acute symptomatic seizures in people with COVID-19. Neither the virus nor potential risk factors for seizures seem to be significant risks for the occurrence of acute symptomatic seizures in COVID-19.

Metabolic Syndrome in People with Epilepsy

Background: Little is known about the association of metabolic syndrome (MetS) and quality of life (QoL) in people with epilepsy (PWE). We evaluate the trends of MetS in PWE across various age groups. We also evaluate the association of MetS and QoL in PWE.

Methods: Clinical and seizure data were collected in 173 people with controlled epilepsy. Physical fitness was assessed by using the six-minute walk test and one-minute step test. Self-reported SF-12 questionnaire, a 12-item, patient-reported survey of patient health, was used to derive physical (PCS) and mental (MCS) component scores.

Results: The average age of the study population was 25.85 ± 9.62 years, and MetS was observed in 91 (52.6%). Obesity was seen in 153 (88.4%). Average distance walked in the six-minute walk test was 385.55 ± 71.52 m. Mean PCS and MCS were 45.95 ± 7.92 and 45.72 ± 10.40, respectively. A greater number of women had MetS (47.6% vs. 62.6%; p = 0.049) and women in the study population had lower high-density lipoprotein (HDL) (44.34 ± 11.60 vs. 38.65 ± 10.13 mm Hg). Except for the variables that define MetS, none of the clinical characteristics were associated with MetS. Across age groups, prevalence of MetS was consistently at 50.0% although prevalence of hypertension showed a linear increase with age. While low HDL was seen highest (61.5%) in individuals less than 20 years age, impaired fasting blood sugar (FBS) was highest in PWE aged > 40 years.

Conclusion: Metabolic syndrome is seen in more than half of people with epilepsy, and this increased prevalence is not associated with the number of antiepileptic medicines. While the prevalence of metabolic syndrome was stable at 50.0% across all age groups, individual components have varying prevalence across age groups hence, suggesting their varied contribution across age groups.

Pregnancy After Valproate (Depakote®) Withdrawal – Fetal Malformations and Seizure Control

Objective: To assess the outcomes in women with epilepsy in relation to fetal malformation and epileptic seizure control during pregnancy when valproate (VPA) intake was ceased, or the drug’s dose was reduced before pregnancy.

Methods: Statistical analysis of data collected in the Australian Pregnancy Register between 1999 and 2018 concerning 580 pregnancies previously treated with VPA, with the VPA dose reduced or the drug withdrawn prior to pregnancy in 158 cases.

Results: Although the available data have limitations, fetal malformation rates in the pregnancies studied were lower in the VPA changed pregnancies (4.5%) than in the VPA unchanged comparator pregnancies (10.9%), and were only 2.7% where VPA intake was ceased before pregnancy. Seizure-affected pregnancies were more frequent in the VPA changed pregnancies than in the VPA unchanged ones (46.2% vs 30.8%). Convulsive seizure-affected pregnancies also were increased, but the difference was not statistically significant.

Significance: Prepregnancy reduction in valproate dosage reduced the hazard of fetal malformations, whereas ceasing intake of the drug decreased the hazard to one similar to that which applies in the general population, but at a cost of decreased control of epileptic seizures during the pregnancies studied. Further investigations are needed to see whether such findings apply more widely in women with epilepsy.

Trends in Documented Cannabis Use Disorder Among Hospitalized Adult Epilepsy Patients in the United States

Objective: Patients with epilepsy are at increased risk for mental health and substance abuse disorders. Given ongoing contemporary societal controversies about medicinal and recreational cannabis use, we aimed to ascertain recent nationwide prevalence, trends, and psychiatric diagnoses associated with cannabis use disorders (CUD) among epilepsy patients.

Results: Of all hospitalized patients with epilepsy, 3.19 % had CUD., CUD was higher in males, people of color, those aged 18?44 years, those with lower incomes, and those hospitalized during more recent years. CUD was more likely to be present in epilepsy patients with depression, bipolar disorder, and tobacco use disorder. In contrast, alcohol use disorder  was associated with lower odds of CUD. Overall, CUD prevalence more than doubled among epilepsy patients (2.18 % in 2006 to 4.41 % in 2014). Among patients with PTSD, CUD prevalence increased over fivefold, and it nearly tripled in those with tobacco use disorder.

Significance: Documented cannabis use disorder has doubled among hospitalized patients with epilepsy in the United States over the last decade and is especially more prevalent in specific demographic and mental health disorder groups. Increased awareness and potential screening for cannabis use disorder in high-risk epilepsy patients may be warranted, given the risk for potential complications.