AAN 2023 Day 1 - MindNext

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AAN

2023
Annual Meeting
Boston | April 22–27, 2023

DAY 1 & 2 UPDATE

Mn
AAN Annual Meeting
2023 Boston | April 22–27, 2023

Sl. No. Content Page No.

1 Stroke on Imaging -Now What? 1

2 Connect the dots in neuro-oncology 3

Impact of a Free Anti-seizure Medication Intervention on Anxiety and Depression


3 5
in People Living with Epilepsy in the Republic of Guinea
Distinguishing Features of MOG Positive and MOG Negative Pediatric Patients with
4 6
ADEM
Resident-Driven Quality Improvement Project to Improve Treatment of Status
5 7
Epilepticus
Long-term Efficacy of Satralizumab in Adults with Aquaporin-4-IgG-seropositive
6 (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD): Results from 8
SAkuraMoon
Efficacy subgroup analyses from the phase 3 CHAMPIONNMOSD trial in adults with
7 9
anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder
RNA profiles to distinguish multiple sclerosis (MS) and neuromyelitis optica (NMO)
8 10
in peripheral whole blood
A Study On The Quality Of Life And Psychiatric Comorbidities In Patients Of Juvenile
9 11
Myoclonic Epilepsy In A Tertiary Care Center In North India
Investigation of anxiety, depression, and adjustment disorder in mothers of children
10 12
with a seizure disorder in the Georgian population

11 Lesion-related epilepsy maps to a common brain network 13

Initial Clinical Experience with Thin-Film Polyimide Subdural Electrodes for Seizure
12 14
Monitoring

13 Two Distinct Networks are Affected by Mesial Temporal Lobe Epilepsy 15

Yield of Stereotactic Electroencephalography for evaluation of Drug Resistant Focal


14 16
Epilepsy: Single-Center Experience.
Ipsilateral Arm Movement related to Extratemporal Premotor Cortex Seizures
15 with Secondary Spread to the Limbic Network seen on Pre-Surgical Stereotactic 17
Electroencephalogram
Ictal Single Photon Emission Computed Tomography (SPECT) In Patients with Focal
16 Aware Seizure without Ictal Electroencephalographic Changes: A Single Center 18
Experience
Seizures in Dementia are Associated with Worse Clinical Outcomes, Higher
17 19
Mortality and Shorter Lifespans
AAN Annual Meeting
2023 Boston | April 22–27, 2023

1. Stroke on Imaging -Now What?


Saturday, April 22nd, 2023, Boston

This presentation was presented by Lori Jordan MD, PhD on Saturday, April 22nd at the AAN Annual
Meeting 2023 in Boston.

A 16-year-old athletic male who presented with a left MCA stroke. The patient arrived at the hospital
two hours after onset, and had a hyperdense MCA and NIHSS score of 13. The patient received IV tPA,
although thrombolytics are not effective for ICA/MCA long segment occlusion.

The AHA Guidelines 2019 state that for off-label use of mechanical thrombectomy, criteria include a
persistent disabling neuro deficit with NIHSS score greater than 6, radiographically confirmed large
artery occlusion, larger child due to contrast dye limitations with small size, treatment decision made
in conjunction with neurologists with pediatric stroke expertise, and an experienced endovascular
surgeon with expertise in thrombectomy in adult stroke patients and pediatric endovascular
procedures.

1
AAN Annual Meeting
2023 Boston | April 22–27, 2023

In this case, the patient underwent successful mechanical thrombectomy with stentreiver for a long
segment distal ICA and M1 large vessel occlusion on angiogram. The stroke remains idiopathic other
than patent foramen ovale (PFO).

The causes of ischemic stroke in US children include arteriopathy (30-50%), arterial dissection (25%),
cardioembolism (25-35%), sickle cell anemia (part of newborn screen in all 50 states), hypercoagulable
state, vasculitis, pregnancy, metabolic disorders, and idiopathic (5–15%). Diagnostic evaluation for
confirmed ischemic stroke includes CT/CTA, MRI Brain with “Stroke protocol with diffusion”, image of
brain and NECK vessels with CT Angiography or MR Angiography, echocardiogram for cardiac function
and undiagnosed CHD with bubble study for PFO, EKG/cardiac monitoring for cardiac arrhythmia, labs
for risk factors such as fasting lipid profile and Hemoglobin A1c, and coagulation evaluation (typically
for non-newborns) especially if cryptogenic or family history of thrombosis.

Regarding investigations, for cardioembolic causes, transthoracic echo (TTE) with bubble study
is recommended to assess cardiac function and for PFO. Four extremity dopplers for DVT are
recommended especially if the patient has a PFO on echo. Blood cultures are recommended if
there is any concern for endocarditis and strokes. COVID testing is recommended for all patients on
admission. Consideration of a 30-day Holter/event monitor is recommended for occult arrhythmia.

In our patient, nothing was found except PFO, which raises the question of whether to close the PFO.
However, pediatric data shows an increased frequency of PFO in children with cryptogenic stroke
(7 of 25, 28%) compared with children with stroke of known etiology (3 of 54, 5.6%) versus children
without stroke 11.5% in this cohort. Adult data suggests that in the 5 “double-disk” PFO closure
trials, the event rate for recurrent ischemic stroke over 5 years after randomization was 6.0% on
medical therapy versus 1.8% with device closure plus long-term antiplatelet therapy. Adult stroke
opinions suggest looking for 5 additional factors: presence of or disposition to venous thrombosis,
increased right-to-left shunt flow permanently or transiently, atrial septal aneurysm that increases
the risk of PFO, recipient brain artery or territory typical of embolism, and absence of risk factors for
atherosclerosis.

Take Home Points

» 20% of children will have a stroke when stroke is suspected.

» Lots of unusual causes of pediatric stroke.

» Think about common causes of pediatric stroke –arteriopathy, cardioembolic, sickle cell disease

» Detailed evaluations are need.

» Acute stroke care in children takes a team and a plan.

» Implementation of pediatric acute stroke protocols can be challenging but may prevent long-term
disability

2
AAN Annual Meeting
2023 Boston | April 22–27, 2023

2. Connect the dots in neuro-oncology


Saturday, April 22nd, 2023, Boston

This presentation was presented by Yasmin Khakoo, MD on Saturday, April 22nd at the AAN Annual
Meeting 2023 in Boston.

A 16-year-old girl who has been diagnosed with congenital melanocytic nevus and some smaller nevi.
She currently lives in Vail, Colorado.

The patient had been experiencing bitemporal headaches for several weeks along with photophobia.
She was on oral contraceptive pills (OCPs) at the time. During the examination, the patient was awake
but uncomfortable and had neck stiffness with Kernig’s sign. Her heart rate was 70 beats per minute
and blood pressure was 140/85. The patient had a medium-sized nevus and several smaller nevi on
her skin. Brisk reflexes were noted in her lower extremities compared to the upper extremities.

The differential diagnosis considered for her condition was increased intracranial pressure (ICP) due
to infection, venous sinus thrombosis, or altitude sickness.

Further testing showed positive somatic alterations in genes such as NRAS, CDKN1A, PIM1, CCND3,
VEGFA, SCG5, GREM1, SPRED1, among others.

3
AAN Annual Meeting
2023 Boston | April 22–27, 2023

Methylation profiling results

Melanocytic lesions of the CNS

The patient received craniospinal radiation therapy and immunotherapy, including ipilimumab and
nivolumab. Currently, she is doing well.

Future directions

» Targeted therapy: better CNS MEK inhibitors (binimetinib)

» Mast cell targets

» PD1: nivo/ipi

» Sosman abstract: ribociclib/everolimus?

» SHP2 inhibitors

» Better characterizing NCM radiographically and clinically

» Predicting which patients will develop CNS melanoma

» Raising awareness in the medical community

4
AAN Annual Meeting
2023 Boston | April 22–27, 2023

3. Impact of a Free Anti-seizure Medication Intervention on


Anxiety and Depression in People Living with Epilepsy in the
Republic of Guinea
Sunday, April 23rd, 2023, Boston

This paper was presented by Dylan R. Rice, Farrah J. Mateen, MD, PhD, and Nathanael Jong Lee, MD,
PhD on Sunday, April 23rd at the AAN Annual Meeting 2023 in Boston.

Little is known about mental health in PLWE in Sub-Saharan Africa and how seizure freedom could
improve outcomes.

The objective of this study was to quantify anxiety and depression in people living with epilepsy
(PLWE) in Guinea before and after anti-seizure medication (ASM) intervention.

PLWE were prospectively recruited in Conakry (March 2022) to receive free clinical consultations with
neurologists to implement/augment treatment regimens with free ASMs. Inclusion criteria were: >12
years old and >=2 unprovoked seizures. As part of a broader interview, participants reported seizure
frequency and completed scales screening for depression (PHQ-9) and anxiety (GAD-7). 90-day follow-
up assessed adherence to ASMs and re-assessed seizure frequency and mental health scales.

Of 148 participants enrolled (mean age=27.3 years, range 12–72; 45% female), 53.3% regularly took
ASMs. Average seizure frequency over the 30 days pre-enrollment was 3.2 (SD=5.9; 28% seizure-free
during this period).

Treatment regimens were modified for 95% of participants, mostly consisting of new levetiracetam
provision (n=115). At 90 days, retention was 78.4% (n=116). Average adherence was 87.0%. Average
seizure frequency over the prior 30 days was 1.5 (SD=5.7; 66% seizure-free during this period).

At baseline, average PHQ-9 score was 21.2 (95%CI [20.2,22.2]), indicating severe depressive
symptoms, and average GAD-7 score was 16.5 [15.6,17.4], indicating severe anxious symptoms. At
90-days, average PHQ-9 was 17.5 [16.4,18.5] and significantly lower than baseline (p<.001). Average
GAD-7 was 14.4 [13.6,15.3] and significantly lower than baseline (p=.002). Seizure frequency was not
correlated with PHQ-9 (p=.50) nor GAD-7 (p=.10) scores at baseline but was at 90-days (PHQ-9: r=.24,
p=.01; GAD-7: r=.22, p=.02).

High levels of anxiety and depression occur in PLWE in Guinea, underscoring the unmet
psychiatric needs in un- and under-treated epilepsy and the need for collaboration between
neurologists and psychiatrists. Medication intervention may positively impact mental health,
highlighting seizure control in addition to psychiatric intervention for this population.

5
AAN Annual Meeting
2023 Boston | April 22–27, 2023

4. Distinguishing Features of MOG Positive and MOG Negative


Pediatric Patients with ADEM
Sunday, April 23rd, 2023, Boston

This paper was presented by Cynthia X. Wang, MD, Benjamin M. Greenberg, MD, and Lana Harder,
PhD on Sunday, April 23 rd at the AAN Annual Meeting 2023 in Boston.

MOG antibody disease is an increasingly recognized etiology for acute disseminated encephalomyelitis
(ADEM). ADEM is a condition that predominately affects children and presents with multifocal
neurological symptoms and encephalopathy. Positive MOG antibodies strongly argues against later
development of multiple sclerosis or NMOSD. The distinguishing characteristics of ADEM, as defined
by MOG positive or negative status has not been well studied.

The objective of this study was to compare MOG positive and negative patients with ADEM as relates
to demographic features, neuroimaging and laboratory features, hospital course, treatments, and
relapse rate.

Children with the initial diagnosis of ADEM were consented to participate in a study of ADEM related
outcomes. Their demographic features, clinical presentation, laboratory and imaging results, and
clinical course are presented, highlighting differences in MOG positive and negative cohorts.

37 children in the study were assessed for MOG IgG. 18 children were MOG positive (49%) and 19
children were MOG negative (51%). Average age and race/ethnicity were similar between cohorts but
the MOG positive group showed equal male/female ratio while MOG negative cohort showed male
predominance (74%).

The MOG negative cohort had greater number of individuals with normal nucleated cells in CSF (0-5
cells/mm3) than MOG positive cohort: 7/19 (37%) vs 2/18 (11%). Neuroimaging features, need for
ICU stay and acute rehabilitation were similar between cohorts. A greater number of MOG positive
patients required ICP management (4/18 vs 1/19) and one MOG positive child died.

6/18 (33%) MOG positive patients had relapses compared to 3/19 (16%) MOG negative patients. 90%
of the 29 patients who had neuropsychological testing scored within the normal range.

MOG antibody disease is a common cause of ADEM though the characteristics of MOG
positive and negative ADEM patients have not been well described. This study compares
these populations from tertiary center’s cohort of ADEM patients enrolled in an ADEM study.

6
AAN Annual Meeting
2023 Boston | April 22–27, 2023

5. Resident-Driven Quality Improvement Project to Improve


Treatment of Status Epilepticus
Sunday, April 23rd, 2023, Boston

This paper was presented by Christopher Alan Houck, MD, Joseph C. Alario, DO, and Joseph Seemiller,
MD on Sunday, April 23rd at the AAN Annual Meeting 2023 in Boston.

The American Epilepsy Society Guidelines recommend benzodiazepines (BZ) as first line treatment for
seizures lasting greater than 5 minutes and loading antiseizure medications (ASM) in a 20–40-minute
window. Delay and underdosing the initial treatment of SE is associated with longer duration of
seizures, increased hospital stay, morbidity and mortality. The initial phase of our QI project found
that at our institution the main barriers were lack of knowledge of treatment guidelines for SE, timely
communication with pharmacy and nursing, and preparation of intravenous ASMs.

The objective of this study was to establish interventions that address barriers to improve the
treatment of status epilepticus (SE) at Geisinger Medical Center.

During study the following interventions were implemented: 1) educate prescribers in the neurology,
emergency medicine, and critical care departments regarding the approved institutional protocol
for SE and availability of an orderset with optimal dosing, 2) two-factor communication regarding
SE medication orders to nursing and education of nursing and pharmacy staff regarding target
administration times, 3) add ready-to-mix levetiracetam to nurse omnicells on high-volume floors, and
4) update the SE orderset to improve usability across multiple departments. They compared the use
of appropriate doses of ASMs and time to administration of ASMs before and after the interventions.
They analyzed data 9 months after the interventions.

About 71 patients were treated for SE during this time period. Use of high-dose BZ in SE increased
from 32% to 47%. Use of second line ASMs at appropriate SE doses increased from 77% to 86%.
The average BZ order-to-administration time was reduced from 10-14 minutes to 9 minutes and the
average second line ASM order-to-administration time was reduced from 86 minutes to 45 minutes.

This resident-driven QI project led to improvement in dosing and timing of administration of


BZ and second line ASMs. BZ dosing continues to be a major area for improvement.

7
AAN Annual Meeting
2023 Boston | April 22–27, 2023

6. Long-term Efficacy of Satralizumab in Adults with


Aquaporin-4-IgG-seropositive (AQP4-IgG+) Neuromyelitis Optica
Spectrum Disorder (NMOSD): Results from SAkuraMoon
Sunday, April 23rd, 2023, Boston

This paper was presented by Anthony Traboulsee, MD, Kazuo Fujihara, MD, and Jeffrey L. Bennett,
MD, PhD on Sunday, April 23 rd at the AAN Annual Meeting 2023 in Boston.

Satralizumab reduced the risk of protocol-defined relapse (PDR) and severe PDR vs placebo in the
double-blind periods (DBP) of two phase 3 trials in patients with NMOSD: SAkuraSky (satralizumab +
baseline immunosuppressants [IST]) and SAkuraStar (satralizumab monotherapy).

The objective of this study was to evaluate the long-term efficacy of satralizumab in patients with
AQP4-IgG+ NMOSD.

Patients who completed the DBPs and open-label extensions (OLEs) of SAkuraSky and SAkuraStar
were rolled-over into a single-arm, open-label study (SAkuraMoon [NCT04660539]) and continued
receiving satralizumab 120mg Q4W +/- IST; we evaluated all AQP4-IgG+ adults (≥18 years) who
received ≥1 dose of satralizumab during these studies (data cut-off: 31 January 2022).

PDRs in the DBPs were adjudicated by a Clinical Endpoint Committee; however, PDRs in the OLEs
and SAkuraMoon were determined by the investigator (iPDRs). We evaluated the annualized iPDR
rate (ARR), time to first iPDR, severe iPDR (≥2 point increase in the Expanded Disability Status Scale
[EDSS] score), and sustained EDSS worsening (EDSS increase of ≥2, ≥1, or ≥0.5 points for patients with
baseline scores of 0, 1–5, or ≥5.5, respectively, confirmed ≥24 weeks post-initial-worsening).

Overall, 106 AQP4-IgG+ adults were included. The median (range) duration of satralizumab exposure
was 5.0 (0.1–7.9) years. The overall adjusted ARR (95% CI) was 0.09 (0.06–0.12). When assessed
longitudinally, the ARR did not increase with additional years of exposure (Y1: 0.16 [0.09–0.27]; Y2:
0.10 [0.05–0.20]; Y3: 0.05 [0.01–0.15]; Y4: 0.07 [0.02–0.26]). At Week 240 (4.6 years), 72% (95% CI:
62–80%) of satralizumab-treated patients were free from iPDR, 91% (84–96%) were free from severe
iPDR, and 85% (75–91%) had no sustained EDSS worsening.

These results demonstrate that the efficacy of satralizumab observed in the DBPs is sustained
with long-term treatment. High proportions of patients remained free from relapse, severe
relapse, or worsening disability, with a consistently low ARR over 4.6 years of satralizumab
exposure.

8
AAN Annual Meeting
2023 Boston | April 22–27, 2023

7. Efficacy subgroup analyses from the phase 3 CHAMPION-


NMOSD trial in adults with anti-aquaporin-4 antibody-positive
neuromyelitis optica spectrum disorder
Sunday, April 23rd, 2023, Boston

This paper was presented by Michael Levy, MD, PhD, Carlo Pozzilli, and Jeffrey L. Bennett, MD, PhD on
Sunday, April 23 rd at the AAN Annual Meeting 2023 in Boston.

CHAMPION-NMOSD is a study of ravulizumab in adults with anti-aquaporin-4 antibody-positive


neuromyelitis optica spectrum disorder. Ravulizumab binds to the same complement component 5
epitope as eculizumab; however, its longer elimination half-life extends the dosing interval (every 8
versus 2 weeks).

This prespecified analysis of the CHAMPION-NMOSD global, open-label, multicenter, phase 3,


externally controlled study aimed to evaluate the efficacy of ravulizumab in clinically relevant patient
subgroups.

Patients (≥18 years) received a weight-based intravenous loading dose of ravulizumab (2400–3000
mg) on day 1, followed by maintenance doses (3000–3600 mg) on day 15 and once every 8 weeks
thereafter. Concurrent placebo treatment was precluded owing to the availability of eculizumab and
other treatments; the placebo arm from PREVENT was the external comparator. Prespecified efficacy
subgroup analyses of time to first adjudicated on-trial relapse (primary endpoint) were conducted
and safety outcomes were analyzed across subgroups.

At baseline, 30/58 ravulizumab-treated patients were receiving monotherapy and 28/58 concomitant
immunosuppressive therapy (IST): steroids (n=12), azathioprine (n=7), mycophenolate mofetil (n=6)
or other (n=3). No ravulizumab-treated patient experienced a positively adjudicated on-trial relapse.
Based on time to first adjudicated on-trial relapse, ravulizumab was superior to placebo in preventing
on-trial relapse in monotherapy (HR, 0.021; 95% CI: 0–0.176; relapse risk reduction [RRR], 97.9%;
p<0.0001) and IST groups (HR, 0.031; 95% CI: 0–0.234; RRR, 96.9%; p<0.0001). Significant differences
versus placebo were seen in patients who had previously received rituximab (n=20; RRR, 93.7%;
p=0.0078) or not (n=38; RRR, 98.1%; p<0.0001). Ravulizumab was superior to placebo in prespecified
subgroups by age, sex, race and geographic region. Overall safety profile was consistent with that of
ravulizumab across other approved indications.

The robust effect of ravulizumab on RRR was observed across all prespecified subgroups,
including ravulizumab monotherapy, concomitant IST use, age, sex, geographic region, and
prior rituximab use.

9
AAN Annual Meeting
2023 Boston | April 22–27, 2023

8. RNA profiles to distinguish multiple sclerosis (MS) and


neuromyelitis optica (NMO) in peripheral whole blood
Sunday, April 23rd, 2023, Boston

This paper was presented by Lukasz Wylezinski, PhD, Michael K. Racke, MD, and Charles F. Spurlock,
III, PhD on Sunday, April 23rd at the AAN Annual Meeting 2023 in Boston.

MRI imaging and antibodies against AQP4 have been used to differentiate MS from NMO. However,
early in the disease course, some patients do not have imaging or clinical characteristics that
distinguish the two disorders, particularly in AQP4 antibody negative patients. Currently, there are no
blood-based biomarkers that alone confirm the presence or absence of MS or NMO.

The aim of this study was to compare gene expression differences in the peripheral whole blood
of patients with multiple sclerosis (MS) versus neuromyelitis optica (NMO), including differences in
patients with NMO who are aquaporin-4 (AQP4) antibody positive (AQP4+) versus AQP4 negative
NMO (AQP4-).

Total RNA-sequencing was used to examine coding and non-coding RNA expression profiles, immune
repertoire composition, and biologic pathway activation. Whole blood from relapsing-remitting MS
patients (n=105), NMO patients (AQP4+ = 39, AQP4- = 14), and healthy controls (n=70) was collected
into PAXgene tubes. MS and NMO patient samples were obtained from the Accelerated Cure Project
and were not on disease-modifying treatment. MS and NMO patients were screened for myelin
oligodendrocyte glycoprotein (MOG) antibody status. Plasma neurofilament light chain (NfL) was
assessed to determine underlying disease activity.

Differentially expressed genes, unique immune repertoire, and biologic pathway signatures with the
greatest ability to differentiate among MS, NMO, and healthy controls were identified. Activation of
pathways associated with antimicrobial responses and neutrophil activation were more prominent
in NMO patients. Pathways associated with innate immune responses and type 1 interferons were
enriched in the comparison of AQP4+ and AQP4- NMO patients.

These findings suggest that RNA-sequencing data derived from peripheral whole blood can
identify the characteristic RNAs, immune repertoires, and pathways that distinguish MS from
NMO and NMO AQP4+ versus AQP4- individuals. These approaches could lead to novel RNA-
based biomarkers to identify patients with demyelinating diseases at their earliest stages
and direct therapeutic management.

10
AAN Annual Meeting
2023 Boston | April 22–27, 2023

9. A Study On The Quality Of Life And Psychiatric Comorbidities


In Patients Of Juvenile Myoclonic Epilepsy In A Tertiary Care
Center In North India
Sunday, April 23rd, 2023, Boston

This poster was presented by Cankatika Choudhury, DM, Neera Chaudhry, and Sanghamitra Laskar,
MD on Sunday, April 23rd at the AAN Annual Meeting 2023 in Boston.

Juvenile myoclonic epilepsy (JME) is exemplary of a well-defined age-related genetic epilepsy syndrome
representing 5-11 % of all epilepsy cases & 3-11 % of all adolescent epilepsy cases. 74% of JME patients
have at least one major marker of unfavorable social outcome. One of the contributing factors maybe
the distinct personality profile such as unsteadiness, lack of discipline and an indifference to their
disease. JME though usually well controlled, may adversely impact the Quality of Life.

The objectives of this study were to assess quality of life in patients with Juvenile Myoclonic Epilepsy
with special emphasis on social, psychological, relationships and vocational aspects of life and to
screen and classify psychiatric co morbidities in patients with Juvenile Myoclonic Epilepsy.

This was an observational cross – sectional study carried out over a period of 18 months in a tertiary
center at Delhi. Sample size was 50. Patients fulfilling the diagnostic criteria of Juvenile Myoclonic
Epilepsy according to ILAE criteria 2001 were included in the study. They underwent a structured
questionnaire to assess for the impact of JME on the Quality of Life. QOLIE-48 AD and QOLIE 31 P
was used for adolescent and adult population respectively. Then they underwent M.I.N.I 7.0.2. Those
testing positive for psychiatric disorders underwent DSM-5 categorization.

It was found two important determinants of reduced Quality of Life in the adolescent patients –
Physical Functioning [Mean score :57.36 ± 18.94] & Health perception [Mean score: 57.36 ± 18.94]
respectively. Quality of Life -31 P score [Mean score:62.29 ± 25.02] was fair in (37.21 %) of adults.
Academic underachievement was seen in 1(2%), 1(2%) public gatherings,2 (4%) expressed fear of
breaking marriage . Anxiety was found in (10%) and depression in (6%).

Anxiety and depression were the comorbid psychiatric disorders in the study population.
The concurrent presence of these comorbid conditions must be addressed to improve the
quality of life.

11
AAN Annual Meeting
2023 Boston | April 22–27, 2023

10. Investigation of anxiety, depression, and adjustment


disorder in mothers of children with a seizure disorder in the
Georgian population
Sunday, April 23rd, 2023, Boston

This poster was presented by Mariam Alavidze , Tinatin Tkemaladze, MD, PhD, and Marilyn Victoria
Ann Dias on Sunday, April 23rd at the AAN Annual Meeting 2023 in Boston.

Around fifty million people worldwide have a seizure disorder, making it one of the most common
neurological diseases globally. Studies have shown that caregivers of patients often experience
mental health issues. However, there are few studies about the risk factors contributing to mental
and adjustment disorders in mothers of children with seizures leading to chronic depression.

Study aimed to investigate the prevalence of depression, anxiety, and adjustment disorder in mothers
of children with seizure disorders and to find the risk factors contributing to developing these diseases.

A cross-sectional study was conducted. Fifty-nine mothers of children with seizures aged 0-18 years
were investigated in Georgia using questionnaires including information about sociodemographic,
financial, and personal issues, as well as Patient Health Questionnaire-9 (PHQ9), General Anxiety
Disorder-7 (GAD7), and Adjustment Disorder–New Module-7 (ADNM7).

Out of fifty-nine participants, fifty-five had one or more mental disorders. 37/59 had depression, 16/59
had adjustment disorder and 45/59 had GAD. The most common risk factor was financial issues. GAD
and depression had a strong association with lack of family support. Adjustment disorder was mainly
associated with patients’ mothers being aware of the disease before diagnosis. Stigma was primarily
associated with depression, while conflicts within the family were associated with depression and
adjustment disorder.

Results of the study suggest that the most common risk factors causing mental distress are
financial issues and lack of family support. This opens new avenues to develop preventive
and management strategies for these diseases.

12
AAN Annual Meeting
2023 Boston | April 22–27, 2023

11. Lesion-related epilepsy maps to a common brain network


Sunday, April 23rd, 2023, Boston

This poster was presented by Frederic Schaper, MD, PhD, Hal Blumenfeld, MD, PhD, and Natalia S.
Rost, MD on Sunday, April 23rd at the AAN Annual Meeting 2023 in Boston.

Focal epilepsy is commonly caused by brain lesions, but it remains unclear why some lesion locations
result in epilepsy while others do not. One possibility is that some brain regions or networks are more
vulnerable than others. Identifying the brain regions or networks related to epilepsy could inform
prognosis and guide interventions.

The aim of this study was to test whether lesions related to epilepsy map to a common brain network.

Lesion locations from patients with ischemic stroke-related epilepsy (n = 76) and control lesions (n
= 625) were mapped to a common brain atlas. Traditional lesion mapping methods were used to
test for associations between epilepsy and lesion location. Next, we computed the brain network
functionally connected to each lesion location using human brain connectome data (n = 1000).
Network connections associated with epilepsy were identified. Generalizability to other lesion types
was assessed using independent datasets of four different lesion etiologies (n = 772) and a leave-
one-dataset-out analysis. These connections were then used to generate a brain network map that
best encompasses lesion locations related to epilepsy. Finally, we tested whether thalamic deep brain
stimulation sites that improve seizure control were connected to this same network (n = 30).

It was found that lesions associated with epilepsy occurred in multiple heterogenous locations
spanning different lobes and vascular territories. However, these heterogenous lesion locations
were part of a common brain network defined by functional connectivity to the basal ganglia and
cerebellum (Vmax = 6.8, P < 0.001). Functional connectivity to these regions was associated with the
risk of epilepsy across different lesion types (χ2 = 205.3, P < 0.001) and with therapeutic response to
thalamic deep brain stimulation (r = 0.63, P < 0.005).

Lesion locations related to epilepsy map to a common brain network defined by functional
connectivity to the basal ganglia and cerebellum.

13
AAN Annual Meeting
2023 Boston | April 22–27, 2023

12. Initial Clinical Experience with Thin-Film Polyimide


Subdural Electrodes for Seizure Monitoring
Sunday, April 23rd, 2023, Boston

This poster was presented by Brigitte Reina, MD , George Wesley Culler, IV, MD, and Yinchen
Song on Sunday, April 23rd at the AAN Annual Meeting 2023 in Boston.

Subdural grid-and-strips are used routinely in pre-surgical evaluations for people with drug-resistant
epilepsy (DRE). Thin-film polyimide electrodes (NeuroOne Evo, 0.08mm) which have been approved
for clinical use, are thinner and better conform to brain convolutions than current market grids.

Two patients with DRE were presented in the study, who underwent pre-surgical evaluation with
traditional EEG as well as intracranial EEG (iEEG) monitoring using thin-film polyimide subdural
electrode grid-and-strip electrodes. Patient 1 had a prior left mesial temporal lobe ablation with
seizure recurrence. They underwent left temporal craniotomy with implantation of two subdural grids,
three strips and additional depth electrodes. IEEG demonstrated two habitual seizures arising from
anterior temporal subdural strips. Functional mapping identified the basal-temporal and Wernicke’s
speech areas. Left anterior temporal lobectomy was performed and he remains seizure free 9 months
post-resection. Patient 2 underwent bilateral stereoEEG electrode placement with coverage in the
frontal/temporal/insular regions and subdural strip electrodes. IEEG demonstrated seizure onset
from the left hippocampus and right hippocampal spikes. Given bilateral findings, they underwent
Responsive Neurostimulation System implantation.

The two patients underwent subdural electrode placements without complications. IEEG recordings
were comparable between NeuroOne Evo and traditional electrodes in terms of integrity, artifactual
content and signal recording characteristics. The thinner profile of the Evo grid tail facilitated dura
closure and reduced mass effect compared to traditional grids. By trimming material from the tip of
the subdural strip, the electrode was placed through a burr hole without difficulty. Recording from
these grids contributed to pre-surgical evaluation and led to surgical interventions.

Initial experience suggests that thin-film electrodes are a viable option for subdural iEEG that
could safely minimize intracranial mass effect/brain shift and improve surgical ease of use.

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AAN Annual Meeting
2023 Boston | April 22–27, 2023

13. Two Distinct Networks are Affected by Mesial Temporal


Lobe Epilepsy
Sunday, April 23rd, 2023, Boston

This poster was presented by Jonathan Michael Towne, Jose E. Cavazos, MD, PhD, and Vahid Eslami,
MD on Sunday, April 23rd at the AAN Annual Meeting 2023 in Boston.

The brain is organized into a robust set of canonical networks that are detectable across imaging
modalities and invariant to analytic method. The same functional architecture is reflected in
pathology, vis-à-vis the Network Degeneration Hypothesis. Imaging studies of MTLE often focus on
canonical network effects, reporting regional changes congruent with semiology. However, MTLE-
specific networks remain ill-defined.

The aim of this study was to define networks affected by mesial temporal lobe epilepsy (MTLE)
pathology.

A comprehensive literature search identified 45 structural and 29 resting-state-functional imaging


experiments, collectively reporting 588 coordinate-foci of pathology (n=1599 MTLE subjects). Patterns
of coordinate co-occurrence (within and across experiments) were computed using independent
component analysis (FSL-MELODIC.v3.14). Spatial cross-correlations (FSL.v6.0.4) were computed to
assess the stability of and overlap between network-patterns. Functional interpretations were obtained
by regional behavioral analysis (Mango.v4.1; http://rii.uthscsa.edu/mango/plugin_behavioralanalysis.
html) of healthy task-activation data (20,998 experiments; n=103,977) from the BrainMap database
(https://www.brainmap.org/). Effect modification was assessed (χ²-homogeneity).

Two stable (R=0.890) network-patterns were identified in the MTLE literature, bearing little
resemblance to canonical architecture (R<0.3). Network-patterns overlapped at the hippocampus/
MDN-thalamus but were otherwise spatially distinct (R=0.042). Network-1 (supramarginal, frontal/
precentral, fusiform, temporal, and occipital gyri) was associated with verbal (speech-action: Z=8.23;
speech-cognition: Z=6.85), motor (Z=6.06), and visual (Z=4.30) tasks. Network-2 (frontal, temporal
and cingulate cortical areas, pulvinar, anterior-nucleus, and contralesional-parahippocampus) was
associated with limbic (explicit-memory: Z=5.42; positive-emotion: Z=4.54) and executive-function
(attention: Z=4.65; reasoning: Z=3.15) tasks. No effect-modification was observed (p>0.05); structural
and functional data contributed equally to both networks.
This study identifies two distinct networks in MTLE. Seizure propagation along these networks
is congruent with ictal observations of communication deficits, stereotypic behaviors, and
visual hallucinosis (Network-1) as well as dyscognitive effects, transient amnesia, and pre-/
post-ictal social-emotional deficits (Network-2). These cortical networks may underlie
discrete behavioral phenomena manifested in MTLE; further investigation is required to
determine their precise functions as they relate to the peri-ictal continuum.

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AAN Annual Meeting
2023 Boston | April 22–27, 2023

14. Yield of Stereotactic Electroencephalography for evaluation


of Drug Resistant Focal Epilepsy: Single-Center Experience.
Sunday, April 23rd, 2023, Boston

This poster was presented by Cindy Luan, MD and Jaysingh Singh, MD on Sunday, April 23rd at the
AAN Annual Meeting 2023 in Boston.

A growing number of North American epilepsy centers are looking to offer intracranial evaluation for
epilepsy surgery. This invasive procedure can result in symptomatic and asymptomatic hemorrhage,
neurologic deficits, electrode malfunction, and failure to complete investigation.

This study aims to report initial experience with the effectiveness, safety, and outcomes following the
adoption of stereotactic electroencephalography (sEEG) technique for surgical evaluation of patients
with drug-resistant focal epilepsy.

This was a retrospective, single-center, observational study which reviewed every patient undergoing
Phase II monitoring at our center from 2019 to 2022. At our center, 21 patients underwent sEEG
monitoring, and 225 sEEG electrodes were implanted. Variables collected included demographic data,
Phase I data, type of coverage (unilateral vs. bilateral), length of in-hospital stay, rate of complications,
and seizure-free outcome using the ENGEL surgical outcome scale.

Among the 21 patients who were implanted, 7 (33.3%) were completely asymptomatic following
the procedure. The most common complication was a headache in 9 patients (42.8%), followed by
asymptomatic hemorrhage in 3 patients (14.2%). Only one patient (4.76%) experienced symptomatic
hemorrhage but required no surgical intervention. Other less common complications included
vasogenic edema at the surgical site, perceived cognitive slowing, visual hallucinations, and dislodged
electrodes requiring revision. One patient had a complete resolution of seizures following sEEG
implantation. The average duration of hospitalization was eight days, with a trend towards more
extended hospitalization in patients experiencing procedural complications. SEEG method confirmed
the epileptogenic zone in 15 patients (68%). Of these, 11 patients (50%) underwent surgical resection
or ablation, and four (18%) received neuromodulation. 72% (n=8/11) achieved seizure freedom (i.e.,
ENGEL-I outcome).

New surgical epilepsy centers can safely adopt sEEG while anticipating a relatively low rate
of debilitating complications from the procedure. The rate of complications documented in
this cohort is comparable to other established surgical epilepsy programs.

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AAN Annual Meeting
2023 Boston | April 22–27, 2023

15. Ipsilateral Arm Movement related to Extratemporal Premotor


Cortex Seizures with Secondary Spread to the Limbic Network
seen on Pre-Surgical Stereotactic Electroencephalogram
Sunday, April 23rd, 2023, Boston

This poster was presented by Gaurav Kathuria, MD and Tarek Zakaria, MD on Sunday, April 23rd at the
AAN Annual Meeting 2023 in Boston.

Patient is a thirty-four year old female with focal epilepsy refractory to medications and vagus nerve
stimulation (VNS). The semiology consisted of stereotyped rhythmic high amplitude flailing like
movement of right upper extremity, followed by behavioral arrest, lip smacking and head turn to
the left. On the scalp EEG, there were late changes in the right temporal region. MRI brain showed a
moderate sized arachnoid cyst in the left middle cranial fossa and mass effect on the temporal lobe
with hypoplasia and displacement of the left hippocampus. sEEG was performed with implantation in
the bilateral limbic network, frontal and parietal cortex. The seizures were found to originate in the
right premotor cortex in association with arm movement. This was followed by spread to the right
hippocampus when she had behavioral arrest and lip smacking. There was one instance where the
originating focus was in the right temporal region with no involvement of the right precentral cortex.

There is an unusual presentation of ipsilateral arm movement due to pre-central seizures and quick
spread of the extra temporal seizures to the limbic network. It is reported that parietal lobe, insular
and supplementary motor area (SMA) seizures can produce seizures with ipsilateral arm movement.
However, to our knowledge, this is the first case to report ipsilateral arm movement with premotor
cortex. This case shows the close connectivity between the extratemporal and temporal network. It
provides insight to the development of secondary multi-focal epileptic focus in cases with refractory
epilepsy.

sEEG is an emerging tool to understand the pathogenesis of epilepsy and correlate seizures
semiology and certain epileptic location. There can be occasional unusual presentations of
the seizure semiology so comprehensive sEEG coverage to all potential targets is necessary.
Optimal localization in refractory epilepsy is vital prior to any surgical intervention.

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AAN Annual Meeting
2023 Boston | April 22–27, 2023

16. Ictal Single Photon Emission Computed Tomography


(SPECT) In Patients with Focal Aware Seizure without Ictal
Electroencephalographic Changes: A Single Center Experience
Sunday, April 23rd, 2023, Boston

This poster was presented by Saniya Pervin, MD , Sally Valentina Mathias, MD, and Jordan Lee Clay,
MD on Sunday, April 23rd at the AAN Annual Meeting 2023 in Boston.

There is currently limited literature on the localization value of ictal SPECT tracer injection during
patient-reported typical focal aware seizures (auras) that lack electrographic changes. One study
reported that ictal SPECT studies in isolated auras lack reliability, with concordant localization with
the seizure onset zone obtained in 5%, and lateralization in 35% of cases. In another study, localizing
information of self-injection of ictal SPECT was better in three patients and obviated the need for
intracranial monitoring in one patient. We present a study in which tracer injection was administered
for patient-reported typical focal aware seizures, where the subsequent analysis of ictal and interictal
SPECT helped inform further management.

A retrospective review of cases who underwent ictal SPECT between 2020 to 2022 at University of
Kentucky hospital was performed. Cases with radiotracer injection during patient-reported auras
lacking electrographic changes were identified. Timing of injection from onset of reported aura,
hyperperfusion changes on ictal SPECT, and the outcome of imaging on further management of
refractory epilepsy were noted.

20 patients underwent ictal SPECT, of which 7 met our inclusion criteria. None of the 7 cases had
electrographic correlate with aura on scalp EEG. Time of tracer injection ranged from 1- 17 seconds
following onset of aura. The ictal SPECT changes correctly localized the seizure onset zone in five
patients. This was followed by intracranial monitoring and subsequent temporal lobectomy in
three patients, interventricular ablation of epileptogenic focus in one patient, and Responsive
Neurostimulation implant in one patient. One patient was managed medically, and one is ongoing
pre-surgical evaluation.

Ictal SPECT with radiotracer injection during typical focal aware seizures (patient reported
auras) without ictal electrographic changes is helpful in the localization of the seizure onset
zone. Additional studies with larger sample size and outcome information are needed to
assess accuracy of localization.

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AAN Annual Meeting
2023 Boston | April 22–27, 2023

17. Seizures in Dementia are Associated with Worse Clinical


Outcomes, Higher Mortality and Shorter Lifespans
Sunday, April 23rd, 2023, Boston

This poster was presented by Ifrah Zawar, MD, Jaideep Kapur, MD, PhD, and Mark S. Quigg, MD on
Sunday, April 23rd at the AAN Annual Meeting 2023 in Boston.
Dementia and seizures are both public health imperatives.Seizures occur in 10-64% of those with
dementia and accelerate cognitive decline.However,the impact of seizures on clinical and mortality
outcomes in dementia patients has not been studied.
The aim was to study impact of seizures on clinical and mortality outcomes in dementia patients.
Longitudinal data from 39 Alzheimer’s Disease Centers maintained by the National Alzheimer’s
Coordinating Center were analyzed from 9/2005-12/2021. Patients with cognitive impairment at
the initial visit were included. Cognitive, functional, and mortality outcomes among those with and
without seizures were compared.
At the initial visit, among 26,425 cognitively impaired patients, 374(1.4% point prevalence) had seizures.
Seizure patients were significantly younger(62.91vs 68.4years,p<0.001) at onset of cognitive decline.
In multivariate regression analysis,dominant Alzheimer’s disease(AD) mutation(OR:5.55,CI:2.39-
12.89,p<0.001),stroke(OR:3.17,CI:2.35-4.27,p<0.001), transient ischemic attack[TIA](OR:1.72,CI:1.21-
2.46,p=0.003), traumatic brain injury[TBI] (OR:1.92,CI:1.48-2.50,p<0.001), Parkinson’s disease
[PD] (OR:1.79,CI:1.07-2.98,p=0.025), depression(OR:1.61,CI:1.30-1.99,p<0.001) and lower
education(OR:0.97,CI:0.95-0.99,p=0.043) were associated with seizures.
Patients with seizures performed worse on mini-mental-status examination(18.50 vs 22.88,p<0.001)
and Clinical-Dementia-Rating Sum-of-boxes(7.95 vs 4.28,p<0.001); and had more physical
dependence(OR:2.52,CI:1.99-3.19,p<0.001) compared to those without seizures after adjusting for
age and dementia duration using generalized linear model.
Analysis of longitudinal mortality data showed that a higher proportion of seizure patients had died
(OR:1.56,CI:1.27-1.91,p<0.0001),and they were younger at death(72.99 vs 79.72years,p<0.001).
Multivariate survival analysis using Cox regression was conducted to study age at death and seizure
status.We adjusted the model for sex,disease duration, stroke,TIA,TBI, depression,education and
dominant AD mutation.Despite adjustment,patients with seizures were at a higher risk of dying at a
younger age(hazard ratio:1.76,CI:1.49-2.08,p<0.001).

Study shows that dementia patients with seizures have worse cognition and higher mortality rates
at a younger age compared to dementia patients without seizures.Dementia patients with early
onset of dementia, dominant AD mutation,stroke,TIA,TBI,PD,depression, and/or lower education
are more likely to have seizures.Dementia patient with these risk factors may be routinely
considered for EEG for early identification and treatment of seizures to improve outcomes.

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