Highlights of AAN 2021

Emerging Science Session: Half of Kids with Inflammatory Syndrome after COVID-19 have Neurologic Symptoms

Presenter: Omar Abdel-Mannan, MD, of University College London in the United Kingdom and a member of the American Academy of Neurology.

Half of the children who developed the serious condition associated with COVID-19 called multisystem inflammatory syndrome in children (MIS-C) had neurologic symptoms or signs when they entered the hospital, according to preliminary research presented at the American Academy of Neurology’s 73rd Annual Meeting. Those symptoms included headaches, encephalopathy and hallucinations.

“With this new inflammatory syndrome that
develops after children are infected with the
coronavirus, we are still learning how the
syndrome affects children and what we need
to watch out for,”said study author Omar Abdel-Mannan, MD, of University College London in the United Kingdom and a member of the American Academy of Neurology. “We found that many children experienced neurologic symptoms involving both the central and peripheral nervous system.”

For the study, researchers reviewed the records of all children under age 18 admitted to Great Ormond Street Hospital in London between April 4, 2020, and September 1, 2020, who met the criteria for multisystem inflammatory

syndrome in children.

There were 46 children with an average age of 10. New- onset neurological symptoms were reported in 52.2% of the children, including twenty-four had headaches, 14 had encephalopathy, six had voice abnormalities or hoarseness,

six had hallucinations and five had ataxia, or impaired coordination. In addition, three

children had problems with their peripheral nerves and one child had seizures.

   



The children with neurologic symptoms were more likely to need a ventilator and drugs to help stabilize their blood circulation than the children without neurologic symptoms. However, there were no differences in terms of demographics, inflammatory markers, management or short-term outcomes between the two groups.

“Although PIMS-TS patients with neurologic involvement are initially sicker, our center’s preliminary follow-up data up to six months post discharge from hospital demonstrates that most of these children make an almost complete functional recovery, which is reassuring,” said Abdel-Mannan.

The researchers will soon begin a multicenter research study that will involve longitudinal clinical and cognitive assessments and advanced neuroimaging. The objective will be to determine whether all children with PIMS-TS, or only those with neurologic symptoms, are at risk of chronic longer-term neurocognitive and psychiatric outcomes.

 

Reference: Abdel- Mannan O, etal. Neurologic and radiographic findings associated with pediatric inflammatory multisystem syndrome temporarily associated with SARA-CoV-2 (PIMS-TS) in children. Presented at: American Academy of Neurology Annual Meeting; April 17-22, 2021 (virtual meeting).



Remote Screening for Cognitive Impairment

Principal Investigator: Richard Gershon, PhD, Vice Chair for Research, and Professor, Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine.

Presenter: Sarah Pila, PhD, research assistant professor, Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine.

“One option may be to give this kind of test as an initial screen. It could potentially be self- administered – which is really the goal in this current project – or perhaps in a telemedicine environment in which a patient takes it on their phone under a doctor’s supervision to make certain that the patient is taking it themselves.”

Early detection of cognitive impairment due to neurodegenerative disease may be achieved using a mobile application dubbed the Mobile Toolbox Battery (MTB), according to a study presented at the 2021 American Academy of Neurology (AAN) Annual Meeting, April 17-22, by Sarah Pila, PhD, research assistant professor, Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine.

Cognitive Impairment (CI) is estimated to affect more than 16 million people (Centers for Disease Control and Prevention, 2011). About 5.8 million Americans are living with dementia, severe cognitive decline, most often due to Alzheimer’s Disease, with a projected increase to 13.8 million people aged 65 and older by 2050 (Alzheimer’s Association, 2020). There is a clear need for early detection of cognitive impairment due to neurodegenerative brain disease as well as to differentiate it from more benign, age- associated changes. However, there are currently few sensitive assessment tools to meet this need and fewer yet that can be easily and widely deployed across the lifespan, in different research settings, and with diverse participants.

MTB provides a complete research platform for app creation, study management, and data collection for participants 20-85 years old. Available for both iOS and Android devices, we envision the MTB being used in fully remote or follow-up remote studies. The initial core tests within MTB were designed to measure comparable cognitive skills to those in the well-established NIH Toolbox Cognition Battery, often utilized for in-person research.

Among investigators is senior author Richard Gershon, PhD, vice chair, research, Northwestern University Feinberg School of Medicine, who, with his colleagues, developed the MTB to safely, remotely, and effectively collect data from assessments that measure executive function, language, memory, and processing speed in adults. Assessments included in the battery are the Flanker, Face-Name (FNAME); Memory for Sequence (MFS); Picture Sequence Memory (PSM); and Vocabulary, Number Match, Spelling, and Dimensional Charge Card Sort (DCCS) tests.

Gershon emphasised to learn more about future applications of the MTB and its potential as an initial screening tool for cognitive impairment. He also stressed the importance of making sure the patient is not distracted while taking the assessment.

   

Given the COVID-19 global pandemic and its associated stay-at- home orders, it is now more important than ever that researchers have access to well-designed cognitive assessments that can be administered entirely remotely.

Reference: Pila S, Novak M, Weintraub S, et al. The Mobile Toolbox (MBT): A Completely Remote Platform for Cognitive Research. Presented at 2021 American Academy of Neurology Annual Meeting; April 17-22. Abstract P7.086.



Case Report: Painful leg spasms in patient with hemifacial spasms and Vitamin D and vitamin B12 deficiency

Presenter: Julius Anang, MD, PhD, FRCPC. St. Boniface Clinic, Winnipeg, Manitoba, Canada. Objective:

 Report a case of lower limb spasms in a patient with hemifacial spasms, vitamin B12 and D deficiency

Background:

 Demyelination resulting from vitamin B12 or D or combined deficiencies represents a secondary HFS etiology in addition to vascular compression. Vitamin B12 deficiency can cause myelopathy, neuropathy and dementia, but can have more discrete neuromuscular manifestations including cramps.

Case Report:

  A 65-year old female with a history of hemifacial spasms, type 2 diabetes mellitus and chronic low back pain presented to the emergency department with an 8- month history of painful bilateral calf and thigh muscles spasms with a nocturnal preponderance.

  She was treated with diazepam and referred to the outpatient neurology clinic. Upon evaluation in the clinic, her examination was remarkable for frequent mild to moderate right upper and lower facial spasms.

  Gait was antalgic with palpable tenderness along the left lateral thigh. Her MRI brain and MR angiogram of the Circle of Willis and carotids showed a branch of the right MCA in close proximity to the cisternal right facial nerve without definite contact. Her facial spasms had responded well to botulinum toxin injections.

  Laboratory investigations revealed vitamin B12 (212 pmol/) and D (19 nmol/l) deficiencies as well as increased serum parathormone (89 ng/l) but normal serum and ionized calcium levels.

  Full resolution of the lower limb spasms was reported within 4 weeks of initiation of vitamin B12 1000 mcg daily supplementation with normalization of serum levels to 625 pmol/l at 6 weeks.

  Vitamin D3 supplementation was also initiated. There was no obvious change in the severity or frequency of the hemifacial spasms.
It is important to consider vitamin deficiencies especially vitamin B12 in patients presenting with leg spasms and cramps. This is a treatable and reversible etiology compared with other cramping syndrome which are often refractory to therapy.





Acute-Onset Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) in a well-controlled diabetic patient without complications

Presenter: G. Kiri, MS, University of South Florida, Tampa; L. Montoya, MD, Neurology P.A. Port Charlotte, FL.

Background:

 This is a report on a rare case of acute-onset chronic inflammatory demyelinating polyneuropathy (CIDP) developing in a well-controlled diabetic patient who had no complications (including diabetic neuropathy).

Design and Methods:

  61-year-old male found unresponsive was admitted to the hospital and diagnosed with diabetic ketoacidosis (Type II DM). He was stabilized and discharged with mild paresthesia from which he recovered post-hospitalization.

  At his first neurologic outpatient visit, he complained of increasing mild numbness and paresthesia in both feet over the prior month and was unresponsive to gabapentin. He had significant weight loss and was unable to ambulate without assistance.

  He had weakness in his left hand and could not extend the 4th and 5th digits and showed decreased motor activity in both lower extremities (hip: 3/5 thigh: 3-/5; leg: 3/5) with decreased sensation in the distal regions. His labs and HbA1c (6.3) were normal.

  His electromyograph showed acute severe distal axonal polyneuropathy without evidence of demyelination or motor neuron disease. LP showed significant elevated protein without pleocytosis (244 mg/dL) and brain CT was normal. His differential was GBS or AIDP.

  The patient was given IVIg 1g/kg/day for 2 days and received physical, occupational, and speech therapy. He showed improvement for the next 3 months. Then he relapsed and his neurological exam showed worsening weakness which confirmed a diagnosis of CIDP.

  He was again treated with IVIg 1g/kg/day for 2 days. A month later, he showed some improvement and was started on azathioprine (50 mg/day up-titrated to 150 mg/day). He continues to get better and 5 months later, he showed significant motor function improvement (hip: 5/5 thigh: 5/5; leg: 3/5). One year later, he is walking independently.
Acute-onset CIDP should be considered as a differential in well- controlled diabetic patients presenting with paresthesia and significant limb weakness and no diabetic complications (including neuropathy).





Using EEG Alpha States to Understand Learning During Alpha Neurofeedback Training for Chronic Pain

Presenter: K. Patel, School of Medicine, University of Manchester; N. Trujillo-Barreto, J. Henshaw, J. Taylor, A. Jones, M. Sivan.

Objective:

 To quantify the EEG changes during Alpha-neurofeedback (α-NFB) for chronic pain in terms of dynamic changes in alpha states.

Background:

  Alpha-neurofeedback (α-NFB) is a novel therapy which trains individuals to volitionally increase their alpha power to improve pain.

  Learning during NFB is commonly measured using static parameters such as mean alpha power.

  Considering the biphasic nature of alpha rhythm (high and low alpha), dynamic parameters describing the time spent by individuals in high alpha state and the pattern of transitioning between states might be more useful.
Design and Methods:

  Four chronic pain and four healthy participants received five NFB sessions designed to increase frontal alpha power. Changes in pain resilience were measured using visual analogue scale (VAS) during repeated cold-pressor tests (CPT).

  Changes in alpha state static and dynamic parameters such as fractional occupancy (time in high alpha state), dwell time (length of high alpha state) and transition probability (probability of moving from low to high alpha state) were analysed using Friedman’s Test and correlated with changes in pain scores using Pearson’s correlation.
Results:

  There was no significant change in mean frontal alpha power during NFB. There was a trend of an increase in fractional occupancy, mean dwell duration and transition probability of high alpha state over the five sessions in chronic pain patients but not in healthy participants.

  Significant correlations were observed between change in pain scores and fractional occupancy (r=-0.45, p=0.03) and transition probability from a low to high state (r=- 0.47, p=0.03) in chronic pain patients but not in healthy participants.

  

There is a differential effect between patients and healthy participants in terms of correlation between change in pain scores and alpha state parameters. Parameters providing a more precise description of the alpha power dynamics than the mean may help understand the therapeutic effect of neurofeedback on chronic pain.



NorthShore Neuropathy Impairment Scale (NSNIS): A Validation of an Electronic Medical Record (EMR) Based Neuropathy Scale

Presenter: A. C. Barboi, MD, Department of Neurology, Northshore University Healthsystem, Evanston, IL; N. Aunaetitrakul, O. B. Kincaid, M. M. Shanks, R. Frigerio, H. Moulthrop, D. M. Maraganore.

Objective:

 Validation of an electronic medical record (EMR) based neuropathy scale. Background:

  We developed a structured clinical documentation support (SCDS) toolkit that standardizes polyneuropathy patient data collection to conform to Best Practices for evaluating patients with polyneuropathies.

  Part of this project was to design a practical, EMR embedded neuropathy scale, that can be easily used in all newly diagnosed polyneuropathy cases.
Design and Methods:

  Logistic regressions used total NorthShore Neuropathy Impairment Scale (NSNIS) scores, age, and sex as predictors for a diagnosis of polyneuropathy. Training and testing of the logistic regressions utilized a 75/25 split.

  Categories to predict were: diagnosis of polyneuropathy, pattern of involvement (large vs. small fiber), presence of autonomic symptoms, anatomic distribution (polyneuropathy, radiculopathy, mononeuropathy), etiology (acquired, hereditary, idiopathic), clinical course (progressive, relapsing, uniphasic), neurophysiological mechanism (axonopathy, myelinopathy, uncertain).
Results:

  The NSNIS was used in 2,215 new patients evaluated for a diagnosis of polyneuropathy. Out of these, the diagnosis of polyneuropathy was established in 1,182. The NSNIS is highly predictive for a diagnosis of polyneuropathy (AUC 0.717).

  For pattern of involvement, the NSNIS performed better in cases of large fiber polyneuropathy (AUC 0.81) compared to cases with small fiber polyneuropathy (AUC 0.63), although it performed better in patients with autonomic symptoms (AUC 0.768).

  Prediction of anatomic distribution of findings was as follows: isolated polyneuropathy (AUC 0.713), added radiculopathy (AUC 0.778), added mononeuropathy (AUC 0.713).

  When looking at potential etiologies, the NSNIS was more predictive of a hereditary cause (AUC 0.848) compared to idiopathic (AUC 0.566) and acquired etiologies (AUC 0.657).

  NSNIS performed equally well in axonopathies (AUC 0.718) compared to primary myelinopathies (AUC 0.708).

 

NSNIS is easy to use with our SCDS toolkit and is moderately predictive for a diagnosis of polyneuropathy in our patient population.

Disclaimer: This matter/content is distributed for the use of educational purpose to update the knowledge of the Registered Medical Practitioner only. The content of this input is sourced from sessions, abstracts and posters of AAN Annual Virtual Meeting, 17th April to 22nd April, 2021, and the objective is to provide latest research updates in neurology and to encourage medical practitioners to be a part of this conference remotely. The information is not intended to replace medical advice offered by the physicians. For more information please visit http://www.aan.com/virtual meeting.