Clemson Scientist Receives $442,000 Grant to Study Molecular Causes of Autism and Epilepsy

Clemson University scientist David Feliciano recently received a three-year, $442,000 grant from the National Institutes of Health to study how alterations to a complex pathway in the developing brain cause a constellation of neurological disorders, including the simultaneous presence of autism and epilepsy. The project will test the hypothesis that a transporter of amino acids in the brain regulates the “mammalian target of rapamycin” (mTOR) pathway in newborn neurons during fetal and early postnatal development of the cerebral cortex, the outer layer of the brain responsible for integrating sensory information with thought processing.

“The research funded by this grant will be devoted to forming a greater understanding of the upstream signals that turn the mTOR pathway on and off during development,” said Feliciano, an assistant professor in the College of Science. “We already know that too much or too little mTOR pathway activity can cause neurological diseases. But no one has yet to show whether amino acids play a critical role in brain development during the perinatal period.”

A vast array of changes must successfully occur to create a healthy, fully functioning brain. But deviations in mTOR pathway activity can inhibit these developments, and to further complicate matters, clinicians currently don’t possess reliable methods of measuring this activity.

Alterations in the mTOR pathway — whether due to mutations in genes or environmental factors — are linked to neurodevelopmental malformations that might contribute to autism, epilepsy and intellectual delay.

Epilepsy does not Impact Likelihood of Pregnancy

Women with epilepsy, without previous infertility and related disorders, who were attempting to get pregnant were as likely to conceive as their counterparts without epilepsy, according to findings recently published in JAMA Neurology.

“Prior studies report lower birth rates for women with epilepsy but have been unable to differentiate between biological and social contributions,” Page B. Pennell, MD, department of neurology at Brigham and Women’s Hospital and Harvard Medical School, and colleagues wrote. “To our knowledge, we do not have data to inform [women with epilepsy] seeking pregnancy if their likelihood of achieving pregnancy is biologically reduced compared with their peers.”

Researchers recruited, then analyzed data from 197 women — 89 with epilepsy, 108 women without epilepsy — who did not use tobacco and had not been previously diagnosed with infertility or a disorder that lowered their chances of conceiving.

Pennell and colleagues found that 60.7% of the women with epilepsy became pregnant vs. 60.2% of the control group and no epilepsy factors were significant. In addition, after controlling data for age, BMI, education level, employment status, ethnicity, marital status, prior pregnancy and race, researchers found that intercourse activity, ovulatory rates and median time to pregnancy did not differ between the groups. Also, 81.5% of the pregnancies in both groups resulted in live births.

Study: Social Context as a Risk Factor for Psychopathology in Children with Epilepsy

Epilepsy is the number one neurological disorder in children in western society. Childhood epilepsy is highly comorbid with psychopathology. Although neurological and biological factors may partially explain the increased risk of psychopathology in children with epilepsy, social contextual factors are also important to understanding development of psychopathology in children with epilepsy.

The current paper examines the development of children with epilepsy utilizing Bronfenbrenner’s micro-, meso-, exo-, and macrosystem social contexts. Negative interpersonal interactions within the microsystems and the ripple effect of social context at the other levels may contribute to increased risk for psychopathology.

Single-Center Long-Term Results of Vagus Nerve Stimulation for Epilepsy: A 10-17 Year Follow-Up Study

PURPOSE: The paper presents a long-term follow-up study of VNS patients, analyzing seizure outcome, medication changes, and surgical problems.

METHOD: 74 adults with VNS for 10 to 17 years were evaluated yearly as: non-responder – NR (seizure frequency reduction <50%), responder – R (reduction???50% and <90%), and 90% responder – 90R (reduction???90%). Delayed R or 90R (??4?years after surgery), patients with antiepileptic medication changes and battery or complete system replacement were identified. Statistical analysis of potential outcome predictors (age, seizure duration, MRI, seizure type) was performed.

RESULTS: The rates of R and 90R related to the patients with outcome data available for the study years 1, 2, 10, and 17 were for R 38.4%, 51.4%, 63.6%, and 77.8%, and for 90R 1.4%, 5.6%, 15.1%, and 11.1%. The absolute numbers of R and 90R increased until years 2 and 6. Antiepileptic therapy was changed in 62 patients (87.9%). There were 11 delayed R and four delayed 90R, with medication changes in the majority. At least one battery replacement was performed in 51 patients (68.9%), 49 of whom R or 90R. VNS system was completely replaced in 7 patients (9.5%) and explanted in 7 NR (9.5%). No significant predictor of VNS outcome was found.

CONCLUSIONS: After an initial increase, the rate of R (seizure reduction ??50% and <90%) and 90R (seizure reduction???90%) remains stable in long-term follow-up. The changes of antiepileptic treatment in most patients potentially influence the outcome. Battery replacements or malfunctioning system exchange reflect the patient’s satisfaction and correlate with good outcomes.

Study: Clinical and Electrocorticographic Response to Antiepileptic Drugs in Patients Treated with Responsive Stimulation

CONCLUSIONS: Significant quantitative changes in ECoG data recorded by the RNS System were observed in patients who experienced an additional clinical response to a new AED. While there was variability across patients in the changes observed, the results suggest that quantitative ECoG data may provide useful information when assessing whether a patient may have a favorable clinical response to an AED.

OBJECTIVE: The objective of this study was to explore whether chronic electrocorticographic (ECoG) data recorded by a responsive neurostimulation system could be used to assess clinical responses to antiepileptic drugs (AEDs).

METHODS: Antiepileptic drugs initiated and maintained for ?3?months by patients participating in clinical trials of the RNS® System were identified. Such “AED Starts” that produced an additional ?50% reduction in patient-reported clinical seizure frequency were categorized as clinically beneficial, and the remaining as not beneficial. Electrocorticographic features recorded by the RNS® Neurostimulator were analyzed during three periods: 3?months before the AED Start, first month after the AED Start, and the first 3?months after the AED Start.

RESULTS: The most commonly added medications were clobazam (n?=?41), lacosamide (n?=?96), levetiracetam (n?=?31), and pregabalin (n?=?25). Across all four medications, there were sufficient clinical data for 193 AED Starts to be included in the analyses, and 59 AED Starts were considered clinically beneficial. The proportion of AED Starts that qualified as clinically beneficial was higher for clobazam (53.7%) and levetiracetam (51.6%) than for lacosamide (18.8%) and pregabalin (12%). Across all AED Starts for which RNS ECoG detection settings were held constant, the clinically beneficial AED Starts were associated with a significantly greater reduction in the detection of epileptiform activity (p?<?0.001) at 1 (n?=?33) and 3?months (n?=?30) compared with AED Starts that were not beneficial at 1 (n?=?71) and 3?months (n?=?60). Furthermore, there was a significant reduction in interictal spike rate and spectral power (1-125?Hz) associated with a clinically beneficial response to an AED Start at 1 (n?=?32) and 3?months (n?=?35) (p?<?0.001). These reductions were not observed at either 1 (n?=?59) or 3?months (n?=?60) for AED Starts that were not clinically beneficial.

Recruiting Patients with a Recent Diagnosis of PML or Stroke for a Non-Invasive Brain Stimulation Study

You may be eligible for a research study being conducted at Beth Israel Deaconess (Boston, MA) and Northwestern University (Chicago, IL). This study is for adults who were recently (less than 1 year ago) diagnosed with Progressive Multifocal Leukoencephalopathy (PML) or a stroke.

During this study we will use a technique called transcranial magnetic stimulation (TMS) and another called electroencephalography (EEG). TMS is a noninvasive way of stimulating the brain and EEG is a way to measure your brain activity.

The study involves one to three visits which last about 3-4 hours long.

To be a part of this study, you should:

  • Have been diagnosed with PML (as determined by your referring clinician) less than a year ago or
  • Have been diagnosed with a stroke (as determined by your referring clinician) less than a year ago.
  • Be 18-75 years of age.

 

If you qualify to take part in the study, all study related visits and testing are performed at no cost to participants.

Parking and travel will be reimbursed for each study visit and you will be compensated for your participation.

If you are interested, or to learn more, please contact Pierre Boucher at:
pbouche1@bidmc.harvard.edu
617-667-0254

What are the goals of this study?

Epilepsy is a common complication of many acquired brain injuries such as stroke, brain infections, and traumatic brain injury. However, any one person’s likelihood of acquiring epilepsy after a brain injury is usually low, and there are no tests to help identify which individuals are particularly likely to develop seizures. As a result, research to help prevent acquired epilepsy in patients has been difficult. Furthermore, there are no approved treatments that directly affect the brain processes involved in the development of epilepsy.

We will utilize a noninvasive brain stimulation technique, Transcranial Magnetic Stimulation (TMS), in combination with electroencephalography (EEG) to evaluate brain excitability, and thereby the risk of developing epilepsy, in patients with an acquired brain infection called Progressive Multifocal Leukoencephalopathy (PML).

Adults who have been diagnosed with a prior stroke or PML (with or without a prior diagnosis of seizures or epilepsy) may be eligible for this study.

What are the possible outcomes of this study?

Using TMS-EEG, we will determine whether patients with PML and epilepsy have increased brain excitability relative to PML patients without epilepsy and healthy controls at the presumed seizure focus.

What are the outcome measures collected in this study?

Primary outcome measure: The amount of brain excitability at the seizure focus as measured with TMS-EEG.

What are the exclusion criteria for this study?

  • Uncertainty regarding the diagnosis of PML or stroke
  • Uncertainty regarding whether patient has ever suffered epileptic seizures (only for PML or stroke patients without a confirmed diagnosis of Epilepsy or seizures) or significant uncertainty if a stroke patient suffered an acute symptomatic seizure
  • Any confirmed diagnosis or condition known to cause non-epileptic seizures
  • Suspicion for or a history of psychogenic nonepileptiform spells
  • Cerebral palsy; history of severe head injury; current intracranial pathology or lesion from a known genetic disorder (e.g., NF1, tuberous sclerosis) or from acquired neurologic disease (e.g. tumor) OTHER than PML or stroke
  • Any evidence of increased intracranial pressure
  • Any unstable medical condition
  • Prior brain surgery (excluding brain biopsy)
  • Pregnancy. All female participants of child bearing age are required to have a pregnancy test
  • Any metal in the brain, skull or head (not including dental work)
  • Any medical devices (i.e. cardiac pacemaker, deep brain stimulator, medication infusion pump, cochlear implant, vagal nerve stimulator) unless otherwise approved by the responsible MD

 

Are there any risks to participating in this study? If so, what are they and what are the chances they will occur?

This study involves the use of TMS targeting the seizure focus in combination with EEG to investigate cortical excitability in patients with epilepsy, or at risk for developing seizures due to PML or stroke. TMS has been widely used since 1984, and is FDA-approved (and widely used) for treatment of refractory depression, migraines, and for presurgical mapping. TMS is generally very well tolerated. The risks and side effects of TMS include the following:

More Common Side Effects:

  • Pain:
    • TMS can cause muscles of the scalp, neck, or face to twitch. This feeling may range from strange to uncomfortable and could lead to scalp pain, muscle tension or headache.  As many as 20-40% of those having TMS experience headaches – that is 4 in 10 participants. Headache or tension from TMS will usually be relieved with a single dose of acetaminophen (Tylenol®) or ibuprofen.

 

Less Common or Rare Side Effects:

  • Seizures (are less common for participants who have seizures and are rare for those who do not):
    • TMS has in rare instances caused a seizure when used in research studies in subjects without a history of prior seizures. However, the risk of seizure is very low (less than 1 in 1000 participants and in less than 1 in 100,000 TMS sessions), and seizures have occurred primarily in participants with risk factors for suffering a seizure on that particular day (e.g. because of heavy alcohol use the night prior to the TMS session.)
    • If you do have seizures, it is possible that you could experience a seizure during TMS, although the risk is less than 2% for patients with known epilepsy. Typically, the type of seizure a patient experiences while undergoing TMS is identical to those he or she usually experiences.
    • Most seizures experienced during TMS occurred prior to the development of current safety guidelines, which are in place to minimize the risk of seizures and will be used in this study. TMS has never caused a prolonged seizure (known as status epilepticus) or a worsening of a participant’s prior seizure disorder.

Rare Side Effects:
* There is less than a 2% chance of the occurrence of the following rare side effects.

  • Hearing Problems
    • The TMS procedure includes a loud clicking noise throughout. It is possible that you could experience a temporary change in your hearing.  There is one report in the literature of someone who’s hearing protection fell out who experienced permanent hearing loss from TMS.  You will wear earplugs during the TMS to reduce the noise to prevent the risk of hearing problems.  We will ask you to let us know immediately if:
      • your ear plug loosens
      • your ear plug becomes detached
      • your ear plug falls out
    • You will be promptly referred for auditory assessment if you experience hearing loss, ringing in the ear, or ear fullness following completion of the TMS.
    • You may also have ringing in your ear due to the loud clicking sound during the TMS.
  • Syncope (Fainting):
    • It is possible that you could faint during the TMS.  This happens in less than 1% of people.  Fainting can happen if you are anxious, nervous or have not eaten. You should immediately tell the study staff if you feel:
      • dizzy
      • lightheaded
      • that you might pass out
    • If you have the above symptoms, the TMS will be stopped. You will be monitored until you are feeling better.
  • Memory
    • TMS can very rarely cause changes in memory, attention and other cognitive (thinking) functions which may last for several minutes to several hours. However, none of these effects have been reported to be lasting, they are very mild, and they seem to be extremely rare.
  • Pregnancy
    • The effects of TMS on a developing fetus are unknown.  If you are a woman capable of getting pregnant, you will be required to take a pregnancy test before TMS will be given.

 

TMS does not use ionizing radiation. Although TMS has been used worldwide since 1984, there may be complications that are not yet known.

Will I be compensated for this study?

Subjects will be compensated $40/hr for their time. This information is subject to change, so please contact the Pierre Boucher for more information: Pbouche1@bidmc.harvard.edu.

Is transportation assistance available?

Yes, transportation assistance is available.

Are there limitations in transportation assistance?

Travel costs up to $500/session and hotel costs up to $200 for one night (for out-of-town participants) will be covered. This information is subject to change, so please contact the Pierre Boucher for more information: Pbouche1@bidmc.harvard.edu.

Will my information remain private?

Information learned from your participation in this study and from your medical record may be reviewed and photocopied by the Food and Drug Administration (FDA) and/or other federal and state regulatory agencies, and by the device manufacturer (Nexstim, Inc and MagPro) manufacturer, accreditation agencies, the Committee on Clinical Investigations, the Human Subjects Protection Office and others involved in research administration of the Beth Israel Deaconess Medical Center with protection of confidentiality so far as permitted by applicable law.  Information resulting from this study and from your medical record may be used for research purposes and may be published; however, you will not be identified by name in such publications.

What is required of me?

You will have at least 1 visit for a TMS-EEG session. This visit will take approximately 5 hours. During this time, you will receive single pulses of TMS administered every 4-6 seconds, with simultaneous EEG monitoring. Depending on your individual history, you may be asked to return for 1-2 additional TMS-EEG sessions within the two years following the initial visit.

What is my role in the study? Am I a healthy volunteer or a patient volunteer?

Your role in the study is to be a patient volunteer, to help us develop better tests to predict and diagnose seizures in patients at high risk for developing acquired epilepsy.

What are my chances of being in the placebo group?

There is no placebo group in this study; all participants will receive active stimulation.

Will the study directly benefit me?

We do not anticipate that this study will benefit you directly. Results of the study will not be returned to participants directly.

Will the study benefit others?

Yes. This study will help us understand more about the changes in brain excitability that occur in patients with acquired epilepsy, and how those changes occur over time. This knowledge may help us develop better tools to diagnose patients with epilepsy, identify subjects with a high risk of developing seizures after a brain injury, and provide a measure to follow to predict how individual patients will respond to medical therapy.

What discomforts are involved?

See question 1 about risks of TMS above.

What is the total time involved?

Each session will take about 5 hours. Depending on your personal history, you may be asked to participate in 1-3 sessions (so 12-15 hours max).

Are there other inconveniences?

No, there are no other inconveniences.

What is the enrollment timeframe for this study?

This study is currently underway and enrolling. It is estimated that patients will continue to be enrolled until October 2019.

What are the enrollment site(s) for this study?

Beth Israel Deaconess (Boston, MA) and Northwestern University (Chicago, IL).

Recruiting Patients with Epilepsy or First Seizure for a Non-Invasive Brain Stimulation Study

You may be eligible for a research study being conducted at Beth Israel Deaconess (Boston, MA) and Northwestern University (Chicago, IL). This study is for adults who are diagnosed with epilepsy or have recently had a first seizure, and who are on an anti-seizure drug regimen or are planning to start one.

During this study we will use a technique called transcranial magnetic stimulation (TMS) and another called electroencephalography (EEG). TMS is a noninvasive way of stimulating the brain and EEG is a way to measure your brain activity.

The study involves two five hour visits.

To be a part of this study, you should:

  • Be diagnosed with epilepsy or have recently had a first seizure (as determined by your referring clinician).
  • Be on an anti-seizure medication regimen or planning to start one.
  • Be 18-85 years of age.

 

If you qualify to take part in the study, all study related visits and testing are performed at no cost to participants.

Parking and travel will be reimbursed for each study visit.

You will be compensated for your participation.

If you are interested, or to learn more, please contact Pierre Boucher at:
pbouche1@bidmc.harvard.edu
617-667-0254

What are the goals of this study?

The overall goal of this study is to develop better tools to diagnose epilepsy and predict the likelihood of future seizures, localize where the seizures come from, and predict the response to antiepileptic medications. We intend to characterize brain circuitry and excitability in individuals with epilepsy or who have recently had their first seizure.

Adults who are diagnosed with epilepsy and who are on an anti-seizure drug regimen or are planning to start one, and adults who have recently suffered a first seizure (regardless of whether they are planning to start medications), may be eligible for this study.  During this study we will use a technique called transcranial magnetic stimulation (TMS) and another called electroencephalography (EEG). TMS is a noninvasive way of stimulating the brain and EEG is a way to measure your brain activity.

What are the possible outcomes of this study?

We will investigate the levels of brain excitability in individuals with epilepsy or who have recently had their first seizure and will assess how these excitability levels are related to prior and subsequent seizures.

What are the outcome measures collected in this study?

Primary outcome measure: The amount of brain excitability as measured with TMS-EEG.

What are the exclusion criteria for this study? 

  • Uncertainty regarding the diagnosis of PML or stroke
  • Uncertainty regarding whether patient has ever suffered epileptic seizures (only for PML or stroke patients without a confirmed diagnosis of Epilepsy or seizures) or significant uncertainty if a stroke patient suffered an acute symptomatic seizure
  • Any confirmed diagnosis or condition known to cause non-epileptic seizures
  • Suspicion for or a history of psychogenic nonepileptiform spells
  • Cerebral palsy; history of severe head injury; current intracranial pathology or lesion from a known genetic disorder (e.g., NF1, tuberous sclerosis) or from acquired neurologic disease (e.g. tumor) OTHER than PML or stroke
  • Any evidence of increased intracranial pressure
  • Any unstable medical condition
  • Prior brain surgery (excluding brain biopsy)
  • Pregnancy. All female participants of child bearing age are required to have a pregnancy test
  • Any metal in the brain, skull or head (not including dental work)
  • Any medical devices (i.e. cardiac pacemaker, deep brain stimulator, medication infusion pump, cochlear implant, vagal nerve stimulator) unless otherwise approved by the responsible MD

 

Are there any risks to participating in this study? If so, what are they and what are the chances they will occur?

This study involves the use of TMS in combination with EEG to investigate cortical excitability in patients with epilepsy, or at risk for developing seizures. TMS has been widely used since 1984, and is FDA-approved (and widely used) for treatment of refractory depression, migraines, and for presurgical mapping. TMS is generally very well tolerated. The risks and side effects of TMS include the following:

More Common Side Effects:

  • Pain:
    • TMS can cause muscles of the scalp, neck, or face to twitch. This feeling may range from strange to uncomfortable and could lead to scalp pain, muscle tension or headache.  As many as 20-40% of those having TMS experience headaches – that is 4 in 10 participants. Headache or tension from TMS will usually be relieved with a single dose of acetaminophen (Tylenol®) or ibuprofen.

 

Less Common or Rare Side Effects:

  • Seizures (are less common for participants who have seizures and are rare for those who do not):
    • TMS has in rare instances caused a seizure when used in research studies in subjects without a history of prior seizures. However, the risk of seizure is very low (less than 1 in 1000 participants and in less than 1 in 100,000 TMS sessions), and seizures have occurred primarily in participants with risk factors for suffering a seizure on that particular day (e.g. because of heavy alcohol use the night prior to the TMS session.)
    • If you do have seizures, it is possible that you could experience a seizure during TMS, although the risk is less than 2% for patients with known epilepsy. Typically, the type of seizure a patient experiences while undergoing TMS is identical to those he or she usually experiences.
    • Most seizures experienced during TMS occurred prior to the development of current safety guidelines, which are in place to minimize the risk of seizures and will be used in this study. TMS has never caused a prolonged seizure (known as status epilepticus) or a worsening of a participant’s prior seizure disorder.

 

Rare Side Effects:

* There is less than a 2% chance of the occurrence of the following rare side effects.

  • Hearing Problems
    • The TMS procedure includes a loud clicking noise throughout. It is possible that you could experience a temporary change in your hearing.  There is one report in the literature of someone who’s hearing protection fell out who experienced permanent hearing loss from TMS.  You will wear earplugs during the TMS to reduce the noise to prevent the risk of hearing problems.  We will ask you to let us know immediately if:
      • your ear plug loosens
      • your ear plug becomes detached
      • your ear plug falls out
      • You will be promptly referred for auditory assessment if you experience hearing loss, ringing in the ear, or ear fullness following completion of the TMS.
    • You may also have ringing in your ear due to the loud clicking sound during the TMS.
  • Syncope (Fainting):
    • It is possible that you could faint during the TMS.  This happens in less than 1% of people.  Fainting can happen if you are anxious, nervous or have not eaten. You should immediately tell the study staff if you feel:
      • dizzy
      • lightheaded
      • that you might pass out
    • If you have the above symptoms, the TMS will be stopped. You will be monitored until you are feeling better.
  • Memory
    • TMS can very rarely cause changes in memory, attention and other cognitive (thinking) functions which may last for several minutes to several hours. However, none of these effects have been reported to be lasting, they are very mild, and they seem to be extremely rare.
  • Pregnancy
    • The effects of TMS on a developing fetus are unknown.  If you are a woman capable of getting pregnant, you will be required to take a pregnancy test before TMS will be given.
  • TMS does not use ionizing radiation. Although TMS has been used worldwide since 1984, there may be complications that are not yet known.

 

Will I be compensated for this study? 

Subjects will be compensated $40/hr for their time. This information is subject to change, so please contact the Pierre Boucher for more information: Pbouche1@bidmc.harvard.edu.

Is transportation assistance available? 

Yes, transportation assistance is available.

Are there limitations in transportation assistance? 

Travel costs up to $500/session and hotel costs up to $200 for one night (for out-of-town participants) will be covered. This information is subject to change, so please contact the Pierre Boucher for more information: Pbouche1@bidmc.harvard.edu.

Will my information remain private?

Information learned from your participation in this study and from your medical record may be reviewed and photocopied by the Food and Drug Administration (FDA) and/or other federal and state regulatory agencies, and by the device manufacturer (Nexstim, Inc and MagPro) manufacturer, accreditation agencies, the Committee on Clinical Investigations, the Human Subjects Protection Office and others involved in research administration of the Beth Israel Deaconess Medical Center with protection of confidentiality so far as permitted by applicable law.  Information resulting from this study and from your medical record may be used for research purposes and may be published; however, you will not be identified by name in such publications.

What is required of me?

You will have at least 1 visit for a TMS-EEG session. This visit will take approximately 4-5 hours. During this time, you will receive single pulses of TMS administered every 4-6 seconds, with simultaneous EEG monitoring. Depending on your individual history, you may be asked to return for 1-2 additional TMS-EEG sessions within the two years following the initial visit

What is my role in the study? Am I a healthy volunteer or a patient volunteer?

Your role in the study is to be a patient volunteer, to help us develop better tests to predict and diagnose seizures in patients at high risk for developing acquired epilepsy.

What are my chances of being in the placebo group?

There is no placebo group in this study; all participants will receive active stimulation.

Will the study directly benefit me?

We do not anticipate that this study will benefit you directly. Results of the study will not be returned to participants directly.

Will the study benefit others?

Yes. This study will help us understand more about the changes in brain excitability that occur in patients with acquired epilepsy, and how those changes occur over time. This knowledge may help us develop better tools to diagnose patients with epilepsy, identify subjects with a high risk of developing seizures after a brain injury, provide a measure to follow to predict how individual patients will respond to medical therapy, and ultimately guide treatment.

What discomforts are involved?

See question 1 about risks of TMS above.

What is the total time involved?

Each session will take about 4-5 hours. Depending on your personal history, you may be asked to participate in 1-3 sessions (so 12-15 hours max).

Are there other inconveniences?

No, there are no other inconveniences.

What is the enrollment timeframe for this study?

This study is currently underway and enrolling. It is estimated that patients will continue to be enrolled until October 2019.

What are the enrollment site(s) for this study?

Beth Israel Deaconess (Boston, MA) and Northwestern University (Chicago, IL).

Study: Adaptive Nocturnal Seizure Detection Using Heart Rate and Low-Complexity Novelty Detection

PURPOSE: Automated seizure detection at home is mostly done using either patient-independent algorithms or manually personalized algorithms. Patient-independent algorithms, however, lead to too many false alarms, whereas the manually personalized algorithms typically require manual input from an experienced clinician for each patient, which is a costly and unscalable procedure and it can only be applied when the patient had a sufficient amount of seizures. We therefore propose a nocturnal heart rate based seizure detection algorithm that automatically adapts to the patient without requiring seizure labels.

METHODS: The proposed method initially starts with a patient-independent algorithm. After a very short initialization period, the algorithm adapts to the patients’ characteristics by using a low-complex novelty detection classifier. The algorithm is evaluated on 28 pediatric patients with 107 convulsive and clinical subtle seizures during 695?h of nocturnal multicenter data in a retrospective study that mimics a real-time analysis.

RESULTS: By using the adaptive seizure detection algorithm, the overall performance was 77.6% sensitivity with on average 2.56 false alarms per night. This is 57% fewer false alarms than a patient-independent algorithm with a similar sensitivity. Patients with tonic-clonic seizures showed a 96% sensitivity with on average 1.84 false alarms per night.

CONCLUSION: The proposed method shows a strongly improved detection performance over patient-independent performance, without requiring manual adaptation by a clinician. Due to the low-complexity of the algorithm, it can be easily implemented on wearables as part of a (multimodal) seizure alarm system.

Survey of Physician Attitudes towards Psychogenic Nonepileptic Seizures and Driving

CONCLUSION: Psychogenic nonepileptic seizures are common across neurology, psychiatry, and primary care, and most physicians find assessing driving risk in such individuals highly warranted yet difficult. Developing such assessment guidelines and recommendations is of great need for clinicians.

BACKGROUND: Physicians from various disciplines encounter patients presenting with psychogenic nonepileptic seizures (PNES) as part of their routine clinical practice. Recommendations towards assessing fitness to drive and reporting are clearer for conditions such as neurocognitive disorders and epilepsy, but such guidelines do not exist for patients with PNES. Here, we assess physicians’ attitudes towards driving for patients diagnosed with PNES.

METHODS: Electronic questionnaires were sent to Neurology and Family Medicine physicians practicing at Creighton University Medical Center and Psychiatry physicians practicing at Creighton-Nebraska Psychiatry Residency Program to assess their opinion regarding driving risk when encountering PNES.

RESULTS: The survey request was sent to 125 physicians, of which close to 60% completed the survey. Eighty-eight percent of participants encountered PNES in their clinical practice, and 69.1% agreed it was a difficult problem to assess, with only 8.3% endorsing a belief that these patients should drive without restrictions. Ninety-three percent felt having guidelines would help them assess the driving risk in this population.

Historical Review Article: The Montreal Procedure: The Legacy of the Great Wilder Penfield

Wilder Penfield pioneered the early practice of brain surgery. In binding together the disciplines of neurosurgery, neurology, neuropathology, psychology, and related basic sciences, Penfield transformed our understanding of the field of neuroscience.

He brought to the operating room the meticulous techniques of Sherrington, combined with methods of stimulation described by Foerster, which he complemented with expert knowledge of the neurocytology of nervous tissue. While developing surgical treatments for epilepsy, Penfield began to map the brain. He established the “Montreal procedure” for the surgical treatment of epilepsy. His scientific contributions on neurostimulation were transformative in their time and continue to resonate today.

This article reviews the life of Wilder Penfield and summarizes key scientific contributions. Specifically, we detail the Montreal procedure.