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VSHP June Newsletter 
Message from Outgoing President Scott Anderson

As my year as VSHP President comes to a close, I would like to thank you all for allowing me to represent our org anization. VSHP advocated with a strong voice at the state and national level for a number of important issues this year, i  ncluding expanding pharmacist and pharmacy technician scope of practice, enhancing pharmacy technician training, as well as taking a patient-centric stance on drug importation and disposal. I have been proud to sign as the representative of our membership to support these issues and I am proud of the progress we're making and the results we've achieved.

The past few months have presented a multitude of unexpected challenges for health system pharmacy. VSHP remains committed to supporting our members - from providing resources for managing COVID-19 responses, to hosting a residency platform presentation program, as well as developing a number of virtual continuing education webinars, VSHP is encouraging our members to continue learning and collaborating in a time of social distancing. Given the dynamic situation regarding group gatherings, VSHP is also developing strategies and contingency plans to ensure we will continue providing value to our membership, but we're definitely looking forward to when we can all come together again in person to collaborate and network with our colleagues.

I'd like to close by thanking all the outgoing VSHP Board members for their service, and welcoming the incoming Board members to their roles. Additionally, I'd like to recognize and thank all the committee chairs and our executive director Steve Glass for their efforts over the past year, and in particular send a big thank you to Cindy Williams for her leadership and support of all things VSHP as she finishes her three years on the Executive Board. A volunteer organization like ours gains its strength from its volunteers, and VSHP is privileged to have so many members willing to sacrifice their time to support the mission of educating, advocating, and collaborating across the Commonwealth. If you would like to expand your involvement with VSHP, please consider joining a committee, becoming a mentor, submitting an education session proposal, applying for a grant, donating to the PAC, or running for the Board of Directors next year - participation in VSHP has been the most enriching time I've spent in my professional life, and I believe it will be for you as well!
Scott Anderson
VSHP Immediate Past-President

Virginia Board of Pharmacy Update

The Virginia Board of Pharmacy (the Board of BOP) convened a virtual meeting on June 16, 2020 (virtual meetings of government bodies during the COVID-19 public health emergency have been allowed by the Governor and General Assembly). All Board members were present.

Licensees can obtain CE credit for participating in the Board meeting; review the agenda packet and email Board staff for more information. The agenda packet can be found here.

Public Hearings and Adoption of Minutes

Delivery of Dispensed Prescriptions; Labeling (pp. 10-22). A public hearing was held specifically on this matter, which was extended from previous public comment periods and Board meetings. CVS testified in support. VPhA testified in opposition. VSHP testified with the following statement: "VSHP would like the Board to consider and provide context to the various situations of alternate delivery sites and potential impact to patient safety and pharmacist-patient relationships in its decision-making on this matter."

The full Board meeting was then called to order, and the agenda and minutes from the previous Board meeting were approved, as amended.

Covetrus Maine testified to reiterate their comments from the previous Board meeting in regard to Credentials for Nonresident Pharmacies Dispensing Only for Animals (see below).

VPhA made public comment including asking that the petition to Allow Remote Order Processing by Pharmacy Technicians Outside of a Pharmacy be referred to the pharmacy technician expansion of duties work group created by HB 1304 and SB 830. VSHP concurs with that position and also testified to support the regulatory amendment that would allow for live or real-time CE credit applied for a pharmacist providing services without compensation to low income individuals receiving health services through a local health department or a free clinic, and to support the consideration to extend the timeframe for change of PIC from 14 to 30 days within the context of pharmacy acquisition.

Board members had several questions for Natalie Nguyen, VSHP Legislative Chair, regarding the PIC transition issue. Nguyen provided answers about the application to health system pharmacies and the relevant situations and dynamics at hospitals.

Walgreens commented on the two-year PIC requirement and change timeframe, stating that there are many factors taken into consideration when the company names a PIC (such as previous experience with the company). The two-year requirement is already a concern, and the process is an additional concern. Some locations need a PIC quickly.

MedMen Enterprise spoke in favor of PharmaCann's pharmaceutical processor corrective action plan. MedMen is now the owner of PharmaCann, which had obtained the provisional permit to operate in HSA III (Southwest Virginia).

DHP Director's Report

Department of Health Professions (DHP) Director David Brown spoke about the recent developments on police reform and racial inequality, COVID-19 updates, and the executive actions taken to provide flexibility to the healthcare workforce to combat the pandemic in Virginia. The duration of pharmacy related waivers during the emergency declaration is under discussion by staff, who are considering recommending their effect through the end of this calendar year, but need to discuss with the Board Chairman.


Update on Regulatory/Policy Actions Resulting from 2020 General Assembly and the Report of Regulatory Actions (pp. 23-26). Elaine Yeatts, DHP Senior Policy Analyst, noted that the pharmacist scope protocols are to be adopted at the September Board meeting, and that the brown/white bagging proposed final regulations are now at the office of the Secretary of Health and Human Resources for review. Recall that the Board accepted VSHP's comments requesting an exemption of the proposed regulations on brown/white bagging for patients receiving hemophilia treatment.

Adopt Exempt Regulations for Pharmaceutical Processors (pp. 27-69). These proposed actions are exempted from the regular rulemaking process in order to expedite conforming regulations to current law, primarily to update the definition of CBD/THC-A oil to cannabis oil as passed in legislation this year - Adopted.

Consider Petition for Rulemaking to Amend 18VAC110-20-276 to Allow Remote Order Processing by Pharmacy Technicians Outside of a Pharmacy (pp. 70-80). A letter from NACDS seeking additional modifications, beyond the submitted petition, to pharmacy technician duties was displayed on the screen for the Board to read and will be made available to the public electronically. The practice requested in the petition is happening now under emergency COVID-19 waivers. The pharmacy technician expansion of duties work group will not meet until 2021. The Board voted to deny the petition and refer the matter to the Regulation Committee.

Consider Adoption of Fast-track Regulation to Allow Volunteer CE to Satisfy Live CE Requirement (pp. 81-83). Staff recommended adding new language to allow for a maximum of 2 hours of delivery of volunteer pharmacy services in accordance with current regulations, for a total of 6 hours of volunteer CE - Adopted.

Adoption of Emergency Regulations for Limited-Use License and Permit for Non-Profit Facilities (pp. 84-89) - The Board discussed the definition of "non-profit" and the potential use of a limited-use license and permit by different kinds of non-profits. The Board voted to defer adoption and request that counsel and staff conduct additional research for presentation at the next Board meeting.

Adopt Guidance Document 110-49 Credentials for Nonresident Pharmacies Dispensing Only for Animals (pp. 90-92) - Approved.

Adopt Guidance Document 110-48 Verification Sources for a Pharmaceutical Processor (pp. 93-96). In addition to the proposed document, the Board voted to change the definition of CBD/THC-A oil to conform to the new definition of "cannabis oil" (referenced above) to be consistent with other document references - Approved.

Adopt draft Guidance Document for use of telemedicine by registered practitioners of cannabis oil (this proposed document was not included in the board agenda packet and will be made available to the public electronically). The document complies with federal telemedicine guidelines as mandated by state law, requiring secure two-way audio-visual interaction - Approved.

Amend Guidance Documents 110-4, 110-8, 110-9, 110-16, 110-20, 110-22, 110-27, 110-35 (pp. 97-151). These updates are a result of periodic review and contain technical and "clean-up" updates and references - Approved in a block except for 110-4 (see below).

Guidance Document 110-4 was discussed separately as staff provided an updated version regarding CE, which will be made available electronically - Approved as amended.

Repeal Guidance Documents 110-14, 110-19, 110-32, and 110-40 (pp. 152-158). References in these Guidance Documents are now in law or regulation, which make the documents no longer necessary - Approved.

Request to Amend Guidance Document 110-39 Guidance for Continuous Hours Worked by Pharmacists and Breaks (pp. 159-160). The Board has received complaints of confusion and conflicts when a pharmacist is on break but the pharmacy is still open to patients, so the pharmacist often does not have an uninterrupted break. The Board discussed patient access vs. pharmacist wellness and patient safety. The Board voted to refer the matter to the Regulation Committee.

Request for Guidance for Granting Exception to Minimum Two Years' Experience for PIC Eligibility (pp. 161-163). The Board discussed that various factors are taken into consideration when authority is delegated to the Executive Director (ED) and Board Chairman to ensure safety and operational continuity. A motion was made to accept the proposed guidance for due process and delegate authority to the ED and Chairman to grant exceptions, consistent with Board bylaws (staff to develop final language) - Adopted.

Request to Amend Regulation to Extend Change of PIC Timeframe from 14 to 30 Days (pp. 164-166). The Board had discussion around the need for PIC to PIC transition, PIC training, periodic inventory timeline, and needs in various contexts and settings. A few members proposed 21 instead of 30 days. The Board voted to refer the matter to the Regulation Committee.

Consideration for Requiring CE on a Specific Topic in 2021 (pp. 167-168). The Board discussed various possible topics but decided to defer to next year.

Verbal Update on Action Item from December 2019 Board Meeting regarding Virginia Immunization Information System . Staff reached out to the Virginia Department of Health (VDH) and wrote an article that was included in the March licensee newsletter. Any future COVID-19 vaccination will be required to be reported. Registration in the information system is encouraged now.

Election of Chairman and Vice Chairman . The Board elected Kris Ratliff as Chairman and Cheryl Nelson as Vice Chairman.

Chairman's Report. Chairman Warriner expressed her thanks and farewell as she completes her final term on the Board.

Report on Board of Health Professions . The BHP meeting was canceled so no report.

Reports on Licensure Program (pp. 170) and Inspection Program (pp. 171-181). Refer to the reports provided in the agenda packet.

Report on Pharmaceutical Processors (p. 182). Columbia Care in Portsmouth and Green Leaf Medical in Richmond have been awarded final permits. Dharma in Bristol has underdone inspection. 2500 patients have registered.

Report on Disciplinary Program (pp. 183-209). Disciplinary proceedings were suspended in March, April and May due to the COVID-19 public health emergency. A large backlog of cases is expected when proceedings resume.

Executive Director's Report (p. 210). Caroline Juran stated that if the Governor does not make timely Board appointments, Warriner and Thornbury, who are completing their 8-year terms, may need to continue to serve until replacements are appointed. Juran said she has been invited to give a presentation on July 7, 2020 to a legislative committee on drug pricing.

Review of the inspection report for PharmaCann's pharmaceutical processor location, PharmaCann's submitted corrective action plan, and PharmaCann's application for a pharmaceutical processor permit (p. 169). The Board went into closed session to discuss this matter. When it came out of close session, the Board reported that PharmaCann has 90 days to correct their inspection, and that the Board will be issuing an RFA for the license.

ADA examination accommodation requests - After going into closed session, the Board reported that all requests were approved.

The next Board meeting is scheduled for September 9, 2020 at 9:00AM. The next Regulation Committee meeting is scheduled for November 12, 2020 at 9:00AM.

3rd Annual VSHP Residency Forum

This year's forum will be held virtually on Friday, July 24, 2020 from 1p-4p

The forum is open to active VSHP members at no cost.  Last year, over 50% of the residents in Virginia attended the forum.  Residency Program Directors are also invited to attend. 

Tentative Agenda:
o   Welcome and VSHP Discussion- Matt Jenkins, Current VSHP President
o   Keynote- Janet Silvester
o   Financial Planning- Jonathan Lafrenaye
o   IRB Overview- Kathy Koehl
o   Time Management

Please share the attached information with your incoming residents and other members of your team.  We hope to "see" you there.

To join VSHP

ASHP Files Amicus Brief to Safeguard Residency Funding 

ASHP has filed an amicus brief in support of a hospital in its case against the Centers for Medicare & Medicaid Services (CMS) regarding residency funding disallowances. CMS had disallowed several years of the hospital's residency funding. Challenges to funding threaten the viability of pharmacy residency programs. 
ASHP previously met with CMS to discuss residency program audits and the Medicare Administrative Contractors' application of new and inconsistent interpretations of residency program regulations. ASHP has followed up several times with the agency and hopes to work collaboratively with CMS to resolve the issue and safeguard residency program funding.
In this case, a win for the hospital would likely force CMS to remedy the hospital's disallowance and the current residency audit issues. ASHP will keep members updated on the litigation and will continue to push CMS to cease disallowances until the agency publishes clear and consistent residency program guidance.

VSHP Leadership Profile
Cat Floroff
What is your current leadership position in VSHP?
Chair of the VSHP Grants Committee
What benefits do you see in being active in a professional association such as VSHP?  
I really enjoy giving back to the profession. I has always been a passion of mine and especially important in these unprecedented times. I also appreciate networking and learning from other pharmacy leaders throughout the state. You never know what opportunities will arise until you get involved!
What initially motivated you to get involved in VSHP?
I was active as a student pharmacist and appreciated all the time other pharmacists and mentors dedicated to helping me grow in the organization. I wanted to make sure I stayed committed to helping others outside of my healthcare organization, especially now that I have been out of school and practicing for some time now.
Where did you go to pharmacy school?
Where have you trained or worked?  
MUSC PGY1 and PGY2 critical care 2013-2015
Clinical Specialist - Internal Medicine, Sentara Norfolk General Hospital, 2015-2017
Clinical Coordinator, Sentara Leigh Hospital, 2017-2018
Team Coordinator, Sentara Norfolk General Hospital, 2018-2019
Describe your current area of practice and practice setting:
Pharmacy Management
What advice would you give to student pharmacists?
Never turn down an opportunity. Choose courage over comfort. Practice your values. Make productive contributions through knowledge, skills and good work habits. Build on your humility, catalyze your commitment, and always have a vision. Lately, find a mentor if you haven't already. Your mentor doesn't need to be in any official capacity but find someone who will always be willing to give advice and guide you.
What pharmacy related issues keep you up at night?
We are now living in a world where we are in post anticipated COVID-19 surge of patients that never materialized in most of Virginia... this has led to a significant drop in patient volumes in hospitals across the country. Even if patient volumes return to projected rates, most institutions will still be below revenue expectations. This means we will have to make every effort to become more efficient in use of resources and more cost efficient in how we provide care safely while meeting operational demands. What keeps me up at night is answering the "how" and what difficult decisions may lie ahead.
Do you have any special interests or hobbies outside of work?
I love doing Cross Fit
I will always have the Hallmark channel on during the holidays
What is your favorite place to vacation?
Key West
What 3 adjectives would people use to best describe you?
Hard working

New Drug Update: Brexanolone
Carley T. Sadler, VCU School of Pharmacy PharmD Candidate, 2021
Ericka L. Crouse, PharmD, BCPP, BCGP, FASHP, FASCP, VCU School of Pharmacy
In March of 2019 the FDA approved the first drug for the treatment of postpartum depression (PPD). 1 Brexanolone (Zulresso™) is an intravenous infusion that works as a positive allosteric modulator of synaptic and extra-synaptic GABA A receptors. 1,2 What makes brexanolone distinguishable as a treatment for PPD is its structure; unlike currently available depression treatments, brexanolone is a synthetic version of the naturally occurring hormone allopregnanolone. 2 In a study published in 2001 by the American College of Obstetricians and Gynecologists it was found that allopregnanolone levels were significantly lower in women who were experiencing symptoms of PPD compared to women lacking mood disturbances (p< 0.001). 3 This information is promising for the use of brexanolone to replete allopregnanolone levels, reducing the severity of PPD in mothers.
            Brexanolone is formulated as a clear solution in a single dose vial. 2 It currently is available in only one strength, 100 mg/20mL (5mg/mL) and should be prepared in a "polyolefin, non-DEHP, nonlatex bag". 2 The prepared infusion bags can only be used for 12 hours when infused at room temperature, therefore the average patient will require five bags to span the full 60 hour infusion. 2 Once made, the bags can be stored at refrigerator temperature for 96 hours. 2 Infusion bags are made by withdrawing the entire contents of the brexanolone vial (20 mL) and injecting it directly into the infusion bag. 2 It should then be diluted with 40 mL of Sterile Water for Injection, and then further diluted with 40 mL of 0.9% Sodium Chloride Injection for a total infusion volume of 100 mL and a final concentration of brexanolone 1 mg/mL. 2
Administration of brexanolone should be done using a "programmable peristaltic infusion pump" to ensure the correct dose is given and should have its own dedicated line; infusion bags should not be mixed with any other medication. 2 Brexanolone infusion must be monitored as there is a black box warning for "excessive sedation and sudden loss of consciousness". 1,2 Patients should have their pulse oximetry monitored and should be supervised while with their child. 2 In an attempt to reduce the risk of serious events associated with this warning, there is a Risk Evaluation and Mitigation Strategy (REMS) in place for brexanolone; with this being said, access to the medication is restricted to those certified in the Zulresso™ (brexanolone) REMS. 2,4
            Table 1: Dosing for brexanolone is titrated over a 60-hour period as follows: 2
Infusion hour
Infusion rate
0 to 4 hours
Begin infusion at 30 mcg/kg/hr
4 to 24 hours
Increase to 60 mcg/kg/hr
24 to 52 hours
Increase to 90 mcg/kg/hr
52 to 56 hours
Decrease to 60 mcg/kg/hr
56 to 60 hours
Decrease to 30 mcg/kg/hr
If patients are unable to tolerate the 90 mcg/kg/hr dosage during hours 25 to 52 the dosage can be reduced back to 60 mcg/kg/hr. 2 If the patient becomes overly sedated at any time the infusion should be stopped until the sedation is resolved. 2 It can then be resumed at the same or lower dose at the clinician's discretion. 2 Should the patient become hypoxic during the infusion, the infusion should be stopped and not resumed at any point. 2 Brexanolone does not need to be hepatically or renally dose adjusted; however, it should not be used in individuals with eGFR of < 15 mL/minute/1.73 m 2. 2 It does not have any contraindications. 2
            Side effects related to brexanolone include excessive sedation mentioned above as well as dry mouth, passing out, and skin flushing. 1,2 Special care should be used in those who are currently on opiates or other CNS depressants. 1,2 The risk of suicidal thoughts while on brexanolone is unknown; however, since brexanolone is considered an antidepressant, although not a monoamine, the risk of suicidal thoughts must be evaluated when making treatment decisions. 2 It is worth noting that brexanolone is a Schedule IV controlled substance; however, the risk of abuse while in a monitored environment is low. 2 Clinicians should still weigh the risks versus benefits of using brexanolone in individuals who have a substance abuse history. 2 Since brexanolone is tapered before discontinuation, signs and symptoms of withdrawal are not expected. 2 Brexanolone is passed through breastmilk; however, the dose that is transferred to the infant is low, and the oral bioavailability of the medication in infants is also believed to be low, as it is less than 5% in adults. 2 There is currently no data on the outcomes of infants who ingest breastmilk containing brexanolone so patients are encouraged to discuss the risks versus benefits of using the medication while breastfeeding. 2
            The research currently available on brexanolone is optimistic. Two randomized, double-blind, placebo-controlled, phase 3 trials were completed at 30 different clinical research centers and psychiatric units in the United States involving women aged 18-45 years old who were at the most 6 months post-partum. 5 In order to qualify for the study, the women had to have a Hamilton Rating Scale for Depression (HAM-D) score of ≥26 points (severe depression) to be enrolled into study 1 and 20-25 points (moderate depression) to be enrolled in study 2. 5 Study 1 (n=138) consisted of dividing women into three equally dispersed arms to be administered either a placebo for 60 hrs, brexanolone 90 mcg/kg/hr, or brexanolone 60 mcg/kg/hr. 5 Study 2 (n=108) was divided into only two arms consisting of placebo over 60 hrs or brexanolone 90 mcg/kg/hr. 5 The primary outcome was the change in HAM-D score from baseline at 60 hrs. 5 Study 1 results showed statistically significant 19.5 point reduction in HAM-D score from baseline in the brexanolone 60 mcg/kg/hr group (placebo difference −5.5 [95% CI −8.8 to −2.2], p=0.0013) and a statistically significant 17.7 point reduction in the brexanolone 90 mcg/kg/hr group (placebo difference −3.7 [95% CI −6.9 to −0.5], p=0.0252) compared to a 14.0 point reduction in the placebo group. 5 Study 2 results showed a statistically significant 14.6 point reduction in HAM-D score from baseline in the brexanolone 90 mcg/kg/hr group (placebo difference −2.5 [95% CI −4.5 to −0.5], p=0.0160) compared to a 12.1 point reduction in the placebo group. 5 Considered statistically significant, brexanolone reduced HAM-D scores 2 to 3 points more than placebo. A limitation of these studies is that the primary outcome was based on change in HAM-D score rather than the Edinburgh Postnatal Depression Scale, which is used to screen for PPD with symptoms felt in the past 7 days. 6 The most common adverse events seen across both studies for brexanolone included headache, dizziness, and somnolence. 5 There were 4 serious adverse events across both studies which included suicidal ideation, intentional overdose attempt during follow up, altered state of consciousness, and syncope. 5
            One barrier to patients receiving this medication will be the REMS requirement. If an institution is not certified to administer the medication, the patient will not have access to brexanolone. 2,4 Another large barrier to treatment will be the cost. According to the drug's manufacturer, Sage Therapeutics, Inc., the medication's listing price will be $7,450 per vial, with a total treatment cost of about $34,000 per patient. 7
            Brexanolone has a unique place in therapy as it is the first drug approved for the treatment of PPD. Cited as "the most common medical complication of childbirth", one can only hope that brexanolone can serve as a possible step in the right direction for the treatment of PPD. 1 This medication seems to be a possible option for a wide range of individuals as there are no contraindications to its use; contrary to this, the barriers posed to both institutions, REMS requirements, and patients receiving the medication may minimize the use of the drug in therapy. Mothers receiving this infusion will require close monitoring. Patients and institutions alike will have to weigh the pros and cons to brexanolone's use when making decisions.

  1. Sage Therapeutics. Sage Therapeutics Announces FDA Approval of ZULRESSO™ (brexanolone) Injection, the First and Only Treatment Specifically Indicated for Postpartum Depression. Sage Therapeutics. https://investor.sagerx.com/news-releases/news-release-details/sage-therapeutics-announces-fda-approval-zulressotm-brexanolone. Published March 19, 2019. Accessed September 24, 2019.
  2. Zulresso [package insert]. Cambridge, MA: Sage Therapeutics; 2019.
  3. Nappi RE, Petraglia F, Luisi S, et al. Serum allopregnanolone in women with postpartum "blues." Obstet Gynecol. 2001, 97:77-80. doi:10.1016/S0029-7844(00)01112-1
  4. Sage Therapeutics. Zulresso REMS. Zulresso. https://www.zulressorems.com/#Public. Published 2019. Accessed September 24, 2019.
  5. Meltzer-Brody S, Colquhoun H, Riesenberg R, et al. Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet. 2018, 392:1058-70. doi:10.1016/S0140-6736(18)31551-4
  6. Edinburgh Postnatal Depression Scale. Available at: https://www.aap.org/en-us/advocacy-and-policy/aap-health-initiatives/practicing-safety/Documents/Postnatal%20Depression%20Scale.pdf Accessed 4/28/20. Originally published by: Cox JL, Holden JM, Sagovsky R in Br J Psychiatry 1987.
  7. Sage Therapeutics Form 8-K. United States Securities and Exchange Commission. https://www.sec.gov/Archives/edgar/data/1597553/000119312519079860/d721324d8k.htm. Published March 19, 2019. Accessed September 24, 2019.
Approaches to the Treatment of Acute Disseminated Encephalomyelitis
Ashley Eden, PharmD; PGY1 Pharmacy Resident Sentara Healthcare
Acute disseminated encephalomyelitis (ADEM) is a rare immune mediated demyelinating disorder with an incidence of 0.3 to 0.6 cases per 100,000 years. According to the American Academy of Neurology, it is defined as a new onset of polyfocal neurologic symptoms including encephalopathy with imaging that displays demyelination of the brain and often the spinal cord. ADEM typically presents as a monophasic course with reversible white matter lesions, however there is potential for a relapse to occur. 1
Clinical Presentation
Signs and symptoms can vary based off of the affected location of the central nervous system. Symptom onset is rapid reaching maximum effects within 2 to 5 days. 1 Patients may experience altered mental status, acute hemiparesis, and ataxia 2. Symptoms may also include dysarthria, aphasia, seizures, and extrapyramidal effects. 3
The white matter of the brain is most often affected, however lesions may present in the cortical gray matter and basal ganglia as well.The myelin sheath becomes damaged with little to no effect on the axon or soma. 2 The mechanism triggering an autoimmune disorder leading to demyelination is unclear. A proposed mechanism is a cell-mediated response or antibody production due to a cross reaction with myelin autoantigens such as myelin basic protein or myelin oligodendrocyte protein. Another potential mechanism is increased permeability of the central nervous system (CNS) as a result of inflammation and circulating immune complexes that may occur after an infection or a vaccination. 3

Risk Factors
The highest prevalence has occurred in childhood, however ADEM can occur in all ages. About 50-75% of cases occur following an infection and less than 5% of reported cases have occurred following a vaccination based off of a time to event association. 4 The majority of infections present as a respiratory or gastrointestinal illness. However, in about one third of cases a preceding event is not found. 2

Diagnostic Criteria
There is a lack of specific labs to diagnose ADEM. It can present similar to other demyelinating disease states such as multiple sclerosis and therefore is a diagnosis of exclusion. The process involves obtaining a magnetic resonance imaging (MRI) of the brain and spinal cord, ruling out an infectious etiology as the cause, a cerebrospinal fluid (CSF) analysis, and clinical signs/symptoms.The erythrocyte sedimentation rate and C-reactive protein may be elevated as makers of inflammation. The CSF leukocyte, total IgG, and myelin basic protein may be elevated. 4 MRI lesions typically appear large with ill-defined borders and can achieve partial or complete resolution following treatment. 5 Diagnostic criteria is based off of recommendations from a pediatric consensus group as the majority of available literature is from pediatric cases. 1 An new attack occurring after the initial onset or relapse may be reflective of multiphasic ADEM, multiple sclerosis, or neuromyelitis optica spectrum disorder. 4
Table 1: ADEM Diagnostic Criteria 1
A first polyfocal clinical CNS event with an inflammatory demyelinating cause
Brain MRI abnormalities consistent with demyelination within the acute phase (3 months)
No new clinical or MRI findings 3 months or more after clinical onset

There are no randomized controlled trials for the treatment of ADEM. Recommendations are based off of observational studies, case reports, and expert opinion. The American Academy of Neurology recommends corticosteroids as first line treatment, followed by IV immunoglobulin (IVIG) as second line therapy in patient's refractory to corticosteroids or in combination. Plasma exchange is recommended for patients unresponsive to treatment with severe ADEM. 1
Table 2: Treatment Recommendations 1
IV methylprednisolone 30 mg/kg/day (maximum of 1 g/day) for 5 days followed by an oral prednisone taper over 4-6 weeks with a starting dose of 1-2 mg/kg/day
IV immunoglobulin
2 g/kg over 2-5 days
Plasma exchange
7 exchanges every other day

The mechanism of action of IVIG in ADEM is unclear. However, IVIG may result in immunomodulatory effects by binding to antibodies or antigens that mimic myelin basic protein. Plasma exchange may be beneficial in ADEM by removing antibodies that lead to demyelination. 4
The largest study available in ADEM is a retrospective cohort of 228 patients, 122 being children. The study analyzed clinical features of ADEM and long term outcomes. Treatment was determined at the discretion of the neurologist and the median follow up time was 24 months. The majority of patients presented with a preceding systemic infection or vaccination 4 weeks prior to the initial presentation. A minor respiratory tract infection (27%) or a nonspecific infection (15%) were most frequently reported. Ten patients reported having received a vaccination and 7 of the 10 patients had a concomitant infection. Steroid therapy was first line in 188 patients and escalated to IVIG (37 patients) or plasma exchange (17 patients) if refractory. Patients who received plasma exchange could have received both steroids and IVIG prior. A favorable outcome was defined as achieving a modified Rankin score of 2. Patients refractory to steroids that required plasma exchange or IVIG had a lower chance of a favorable outcome (66% vs. 85%, p=0.009). A favorable outcome was achieved for 28 of the 41 (68%) patients who received IVIG or plasma exchange as second line treatment. A monophasic course occurred in 156 patients while 55 patients experienced at least one release. The majority of relapses (85%) occurred within 2 years of the initial presentation. This study reflects a common occurrence of an infectious etiology prior to disease onset, the potential for relapse, and displays that an initial response to corticosteroids may increase the rate of a favorable outcome. This study has several limitations as treatment regimens were not clearly defined, follow up periods were not consistent, and a lack of uniform testing. However, this is the largest study to date. 6

The role of IVIG was assessed in a cohort study of patients with severe ADEM refractory to steroids. First line therapy in 65 patients was IV methylprednisolone 500 mg to 1000 mg daily until a maximum dose of 6 to 8 g was achieved. In 21 patients steroids were ineffective, and 19 patients received IVIG 0.4 g/kg/day for 5 days as second line therapy. Five patients had contraindications to steroids and received IVIG 0.4 g/kg/day for 5 days as first line therapy. A clinical evaluation occurred at 18-24 months and was categorized as good (normal walking or unilateral assistance, normal or mild bladder dysfunction, normal or mildly compromised cognitive function) or bad (walking with double assistance or wheelchair use, severe bladder dysfunction and cognitive dysfunction). Overall, IVIG was effective as second line treatment in 10 of 19 (53%) patients and effective as first line treatment in 3 of 5 (60%) patients. Steroid refractory patients most often had peripheral nervous system damage (89%) and myelitis (95%). Based off the study results IVIG's role may be in patients with myelitis and both central and peripheral system involvement. Overall, in patient's refractory to steroid treatment, IVIG may be an effective option. 7

A retrospective review was conducted in patients with central nervous system demyelination to assess the effects of plasma exchange in patients refractory to steroids. The most common diagnosis in the study consisted of relapsing multiple sclerosis (n=22, 37.3%), neuromyelitis optica (n=10, 16.9%), and ADEM (n=10, 16.9%). The primary outcome was to determine if improvement in the target neurologic deficient was achieved and defined by moderate (definite improvement in function such as walking or usage of extremity) or marked improvement (major improvement in function). Patients received a median of 7 exchanges (range of 2 to 20). Follow-up occurred over a median of 222 days. Overall, 26 of 59 (44.1%) patients met criteria for moderate or marked improvement. Of patients with ADEM, 4 of 10 (40%) achieved marked improvement, none had moderate improvement, and 1 had mild improvement (no gain in neurologic function). Plasma exchange resulted in clinical improvement and may be an effective option. Limitations include lack of long term outcomes due to limited follow up information and few patients with ADEM enrolled. 8

ADEM is a rare and rapidly progressive disease reaching its maximum effects within approximately 2 to 5 days. 1 Limited literature is available regarding treatment recommendations. About 50-75% of patients are able to achieve full recovery in one to six months following the onset of symptoms.The duration and severity of demyelination and inflammation may have an effect on the clinical outcome. 2 Further research is recommended to gain a better understanding of the disease state and approaches to treatment.

  1. Pohl D, Alper G, Van Haren K, et al. Acute Disseminated Encephalomyelitis Updates on an inflammatory CNS syndrome. American Academy of Neurology. 2016; 87 (Suppl 2) S38-S45
  2. Brenton J. Acute Disseminated Encephalomyelitis: Clinical Presentation, Pathophysiology, Diagnosis, and Treatment. Neuroinflammation. 2018. DOI: 10.1016/B978-0-12-811709-5.00017-X
  3. Anilkumar A, Foris L, Tadi P. Acute Disseminated Encephalomyelitis. NCBI Bookshelf. 2019.
  4. Noorbakhsh F, Johnson R, Emery D, et al. Acute Disseminated Encephalomyelitis: Clinical and Pathogenesis Features. Neurologic Clinics. 2008. 759-780
  5. Narula S, Hopkins S, Hacohen Y, et al. Acute disseminated encephalomyelitis. International Neurology Second Edition. 2016. 372-375
  6. Koelman D, Chahin S, Mar S, et al. Acute disseminated encephalomyelitis in 228 patients. American Academy of Neurology. 2016. 2085-2092.
  7. Ravaglia S, Piccolo G, Ceroni M, et al. Severe steroid-resistant post-infectious encephalomyelitis. Journal of Neurology. 2007. 254:1518-1523. DOI 10.1007/s00415-007-0561-4
  8. Keegan M, Pineda A, McClelland R, et al. Plasma exchange for severe attacks of CNS demyelination: Predictors of response. American Academy of Neurology. 2002;58:143-146
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Clinical Writing Opportunities for APPE Students

As a new year of APPE rotations begin, writing a clinical article for the VSHP newsletter is a great way for students to get publication experience. As preceptors we can co-author these articles with our students, engage them in the writing process, and enhance their rotation experiences. Topics can be anything related to hospital-system pharmacy. Examples include (but are not limited to): new drug updates, national policy updates for hospital pharmacy, guideline updates, therapeutics reviews, and clinical controversies. Articles are generally 1-3 pages in length, and can include tables and figures. Interested member and students should email Steve Glass, contact@vshp.org for more details.

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