single case study on stroke

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Neurotherapy for stroke rehabilitation: A single case study

1995, Biofeedback and Self-Regulation

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Chapter 7:  10 Real Cases on Transient Ischemic Attack and Stroke: Diagnosis, Management, and Follow-Up

Jeirym Miranda; Fareeha S. Alavi; Muhammad Saad

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Case 1: Management of Acute Thrombotic Cerebrovascular Accident Post Recombinant Tissue Plasminogen Activator Therapy

A 59-year-old Hispanic man presented with right upper and lower extremity weakness, associated with facial drop and slurred speech starting 2 hours before the presentation. He denied visual disturbance, headache, chest pain, palpitations, dyspnea, dysphagia, fever, dizziness, loss of consciousness, bowel or urinary incontinence, or trauma. His medical history was significant for uncontrolled type 2 diabetes mellitus, hypertension, hyperlipidemia, and benign prostatic hypertrophy. Social history included cigarette smoking (1 pack per day for 20 years) and alcohol intake of 3 to 4 beers daily. Family history was not significant, and he did not remember his medications. In the emergency department, his vital signs were stable. His physical examination was remarkable for right-sided facial droop, dysarthria, and right-sided hemiplegia. The rest of the examination findings were insignificant. His National Institutes of Health Stroke Scale (NIHSS) score was calculated as 7. Initial CT angiogram of head and neck reported no acute intracranial findings. The neurology team was consulted, and intravenous recombinant tissue plasminogen activator (t-PA) was administered along with high-intensity statin therapy. The patient was admitted to the intensive care unit where his hemodynamics were monitored for 24 hours and later transferred to the telemetry unit. MRI of the head revealed an acute 1.7-cm infarct of the left periventricular white matter and posterior left basal ganglia. How would you manage this case?

This case scenario presents a patient with acute ischemic cerebrovascular accident (CVA) requiring intravenous t-PA. Diagnosis was based on clinical neurologic symptoms and an NIHSS score of 7 and was later confirmed by neuroimaging. He had multiple comorbidities, including hypertension, diabetes, dyslipidemia, and smoking history, which put him at a higher risk for developing cardiovascular disease. Because his symptoms started within 4.5 hours of presentation, he was deemed to be a candidate for thrombolytics. The eligibility time line is estimated either by self-report or last witness of baseline status.

Ischemic strokes are caused by an obstruction of a blood vessel, which irrigates the brain mainly secondary to the development of atherosclerotic changes, leading to cerebral thrombosis and embolism. Diagnosis is made based on presenting symptoms and CT/MRI of the head, and the treatment is focused on cerebral reperfusion based on eligibility criteria and timing of presentation.

Symptoms include alteration of sensorium, numbness, decreased motor strength, facial drop, dysarthria, ataxia, visual disturbance, dizziness, and headache.

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Emotional Freedom Techniques for Stroke Rehabilitation: A Single Case Study

Finding Me with EFT, Labrador, Queensland, Australia

School of Psychology, Bond University, Queensland 4229, Australia

† These authors contributed equally to this work.

Academic Editor: Gerhard Litscher

Special Issue: Mind-Body Approaches that are Revolutionizing the Health Field

Received: June 17, 2021 | Accepted: October 13, 2021 | Published: October 26, 2021

OBM Integrative and Complementary Medicine 2021 , Volume 6, Issue 4, doi: 10.21926/obm.icm.2104038

Recommended citation: Fuller SA, Stapleton P. Emotional Freedom Techniques for Stroke Rehabilitation: A Single Case Study. OBM Integrative and Complementary Medicine 2021 ; 6(4): 038; doi:10.21926/obm.icm.2104038.

© 2021 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License , which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.

A 37-year-old female with a history of complex trauma, anxiety and depression was treated with Emotional Freedom Techniques (EFT) supplemented with guided imagery within the first 24 hours of having a stroke that affected the right side. CT scans indicated a haemorrhage and brain clot. Surgery was delayed as another seizure was expected. Interventions occurred during COVID-19 restrictions. The patient then engaged in 90 minutes of EFT every day over the course of a week while in hospital. After seven days she was discharged, and there were significant reductions in depression, anxiety and pain, and mobility returned. Upon discharge the patient had evident improvement in balance and coordination and successfully completed a driving test within the weeks that followed. Subsequent CT scans reveal very little scaring or evidence of the stroke, blood pressure remained stable, and no medication was warranted. This case study presents the practitioner’s perspective of the sessions provided.

Graphical abstract

Stroke; emotional freedom techniques; tapping; guided imagery; visualization; cerebral; single case; depression; anxiety; trauma

1. Introduction

1. Rudberg AS, Berge E, Laska AC, Jutterström S, Näsman P, Sunnerhagen KS, et al. Stroke survivors’ priorities for research related to life after stroke. Top Stroke Rehabil. 2021; 28: 153-158. [ CrossRef ]

2. Barthels D, Das H. Current advances in ischemic stroke research and therapies. Biochim Biophys Acta Mol Basis Dis. 2020; 1866: 165260. [ CrossRef ]

3. Rutten-Jacobs LC, Maaijwee NA, Arntz RM, Van Alebeek ME, Schaapsmeerders P, Schoonderwaldt HC, et al. Risk factors and prognosis of young stroke. The future study: A prospective cohort study. Study rationale and protocol. BMC Neurol. 2011; 11: 109. [ CrossRef ]

4. Rutten-Jacobs LCA. Long-term prognosis after stroke in young adults. Nijmegen: Radboud University; 2014.

5. Cotoi A, Teasell R. Evidence-based review of stroke rehabilitation. London: EBRSR Research Group; 2018.

6. Nedeltchev K, der Maur TA, Georgiadis D, Arnold M, Caso V, Mattle HP, et al. Ischaemic stroke in young adults: Predictors of outcome and recurrence. J Neurol Neurosurg Psychiatry. 2005; 76: 191-195. [ CrossRef ]

7. Marini C, Russo T, Felzani G. Incidence of stroke in young adults: A review. Stroke Res Treat. 2010; 2011: 535672. [ CrossRef ]

8. Marini C, Totaro R, De Santis F, Ciancarelli I, Baldassarre M, Carolei A. Stroke in young adults in the community-based L’Aquila registry: Incidence and prognosis. Stroke. 2001; 32: 52-56. [ CrossRef ]

9. Waje-Andreassen U, Naess H, Thomassen L, Eide GE, Vedeler CA. Arterial events after ischemic stroke at a young age: A cross-sectional long-term follow-up of patients and controls in western Norway. Cerebrovasc Dis. 2007; 24: 277-282. [ CrossRef ]

10. Waje-Andreassen U, Thomassen L, Jusufovic M, Power KN, Eide GE, Vedeler CA, et al. Ischaemic stroke at a young age is a serious event-final results of a population-based long-term follow-up in Western Norway. Eur J Neurol. 2013; 20: 818-823. [ CrossRef ]

1.1 Post Stroke Mood Issues in Young Stroke Patients

11. Saikaley M, Iruthayarajah J, Harnett A, Salter K, Foley N, Mehta S, et al. Post stroke depression (Chapter 18). In: Evidence-based review of stroke rehabilitation. London: EBRSR Research Group; 2018.

12. Jones F, Gage H, Drummond A, Bhalla A, Grant R, Lennon S, et al. Feasibility study of an integrated stroke self-management programme: A cluster-randomised controlled trial. BMJ Open. 2016; 6: e008900. [ CrossRef ]

13. Kootker JA, Rasquin SM, Lem FC, van Heugten CM, Fasotti L, Geurts AC. Augmented cognitive behavioral therapy for poststroke depressive symptoms: A randomized controlled trial. Arch Phys Med Rehabil. 2017; 98: 687-694. [ CrossRef ]

14. Visser MM, Heijenbrok-Kal MH, van ‘t Spijker A, Lannoo E, Busschbach JJ, Ribbers GM. Problem-solving therapy during outpatient stroke rehabilitation improves coping and health-related quality of life: Randomized controlled trial. Stroke. 2016; 47: 135-142. [ CrossRef ]

15. Raglio A, Zaliani A, Baiardi P, Bossi D, Sguazzin C, Capodaglio E, et al. Active music therapy approach for stroke patients in the post-acute rehabilitation. Neurol Sci. 2017; 38: 893-897. [ CrossRef ]

16. Gezer H, Karaahmet OZ, Gurcay E, Dulgeroglu D, Cakci A. The effect of aerobic exercise on stroke rehabilitation. Ir J Med Sci. 2019; 188: 469-473. [ CrossRef ]

17. Topcuoglu A, Gokkaya NK, Ucan H, Karakuş D. The effect of upper-extremity aerobic exercise on complex regional pain syndrome type I: A randomized controlled study on subacute stroke. Top Stroke Rehabil. 2015; 22: 253-261. [ CrossRef ]

18. Konecny P, Elfmark M, Horak S, Pastucha D, Krobot A, Urbanek K, et al. Central facial paresis and its impact on mimicry, psyche and quality of life in patients after stroke. Biomed Pap. 2014; 158: 133-137. [ CrossRef ]

1.2 Emerging Psychological Interventions

19. Hackett ML, Anderson CS, House A, Halteh C. Interventions for preventing depression after stroke. Cochrane Database Syst Rev. 2008; 3: CD003689. [ CrossRef ]

20. Forster A, Brown L, Smith J, House A, Knapp P, Wright JJ, et al. Information provision for stroke patients and their caregivers. Cochrane Database Syst Rev. 2012. Doi: 10.1002/14651858.CD001919.pub3. [ CrossRef ]

21. Knapp P, Young JO, House AL, Forster AN. Non-drug strategies to resolve psycho-social difficulties after stroke. Age Ageing. 2000; 29: 23-30. [ CrossRef ]

22. Redfern J, McKevitt C, Wolfe CD. Development of complex interventions in stroke care: A systematic review. Stroke. 2006; 37: 2410-2419. [ CrossRef ]

23. Kirkevold M, Bragstad LK, Bronken BA, Kvigne K, Martinsen R, Hjelle EG, et al. Promoting psychosocial well-being following stroke: Study protocol for a randomized, controlled trial. BMC Psychol. 2018; 6: 12. [ CrossRef ]

24. Lanza M. Psychological impact of stroke: A recovering nurse's story. Issues Ment Health Nurs. 2006; 27: 765-774. [ CrossRef ]

25. Church D. The EFT manual. Fulton: Energy Psychology Press; 2013.

26. Church D. Clinical EFT as an evidence-based practice for the treatment of psychological and physiological conditions. Psychology. 2013; 4: 645-654. [ CrossRef ]

27. Church D, Yount G, Brooks AJ. The effect of emotional freedom techniques on stress biochemistry: A randomized controlled trial. J Nerv Ment Dis. 2012; 200: 891-896. [ CrossRef ]

28. Stapleton P, Crighton G, Sabot D, O'Neill HM. Reexamining the effect of emotional freedom techniques on stress biochemistry: A randomized controlled trial. Psychol Trauma. 2020; 12: 869-877. [ CrossRef ]

29. Bach D, Groesbeck G, Stapleton P, Sims R, Blickheuser K, Church D. Clinical EFT (Emotional Freedom Techniques) improves multiple physiological markers of health. J Evid Based Integr Med. 2019; 24: 2515690X18823691. [ CrossRef ]

30. Church D, Yount G, Rachlin K, Fox L, Nelms J. Epigenetic effects of PTSD remediation in veterans using clinical emotional freedom techniques: A randomized controlled pilot study. Am J Health Promot. 2018; 32: 112-122. [ CrossRef ]

31. Clond M. Emotional freedom techniques for anxiety: A systematic review with meta-analysis. J Nerv Ment Dis. 2016; 204: 388-395. [ CrossRef ]

32. Church D, Stapleton P, Yang A, Gallo F. Is tapping on acupuncture points an active ingredient in Emotional Freedom Techniques? A systematic review and meta-analysis of comparative studies. J Nerv Ment Dis. 2018; 206: 783-793. [ CrossRef ]

33. Nelms JA, Castel L. A systematic review and meta-analysis of randomized and nonrandomized trials of clinical emotional freedom techniques (EFT) for the treatment of depression. Explore. 2016; 12: 416-426. [ CrossRef ]

34. Sebastian B, Nelms J. The effectiveness of emotional freedom techniques in the treatment of posttraumatic stress disorder: A meta-analysis. Explore. 2017; 13: 16-25. [ CrossRef ]

35. Wolpe J. The practice of behavior therapy. 2nd ed. New York: Pergamon Press; 1973.

Figure 1 Side of the hand EFT Acupoint. Copyright granted Peta Stapleton, 2019.

Figure 2 EFT Acupoints. Copyright granted Peta Stapleton, 2019.

1.3 The Present Study

36. McLeod J. Case study research in counselling and psychotherapy. London: SAGE Publications; 2012.

1.4 Approach

While research through narrative may typically focus on communication styles between patient and practitioner, or personal illness experiences, this case study was not pre-designed. The nature of young stroke occurs without warning, and it was only in the months following the incident did the EFT practitioner shape and process her therapy notes to share the story. Thus, a strict interpretive and phenomenological tradition has not been utilised here, although the practitioner’s commentary is presented.

2.1 Participant Information

The patient was a 37-year-old female with a history of complex trauma, anxiety and depression. She had been receiving a disability pension due to her high anxiety, complex PTSD and severe depression. Her typical tolerance to stressful situations was extremely low. She had previously had two near-fatal car accidents and other life-threatening experiences resulting in a phobia related to hospitals and confinement.

The patient suffered a haemorrhagic stroke that affected the right side. Surgery addressed the bleed and a brain clot. Because no cause could be medically identified, the patient was not prescribed any medication during her eight-day admission other than paracetemol.

2.2 Practitioner Information

The first author was next of kin (her mother) and also a certified EFT practitioner and because of this was able to have daily contact through the hospital. The interventions were delivered via telephone due to her daughter being in isolation.

2.3 Overview of the Sessions

Sue-Anne outlines the nature of the neurological event (for the purpose of this narrative):

“My daughter was behind the wheel of the car when she had a stroke at the property gate of her home. It left her paralysed down her right side and understandably, terrified. She was unsure how long she lay on the road beside her car until someone found her. She was unable to move”.

Scans at the local country hospital revealed a brain bleed (haemorrhage) and blood clot. She was immediately flown to another State for emergency neurological assessment. Quarantine restrictions due to COVID-19 resulted in her being in isolation. The patient was prepared for surgery to stem the bleed, although the timing was uncertain due to the external lockdown.

Because of her daughter’s traumatic history and low tolerance of medical services Sue-Anne shares her concerns as a mother:

“I feared she might not have the will to live. I was feeling trapped, as I couldn’t be at her bedside and overwhelmed by the thought of her being alone. I made the decision to be emotionally present and support her with my somatic training approaches. I consciously began to ‘hold space’ for her healing and highest good. In the past I have felt overwhelmed by my children’s challenges. This time was different; I had a sense of certainty as I had committed to my own personal peace procedure years prior (a process in EFT) and had a strong sense of inner peace.”

Sue-Anne is a trained Neuro Linguistic Programming and EFT practitioner and began to use these approaches for her own personal overwhelm and worry. She shares the next step once her daughter had surgery:

“Thankfully, once she (her daughter) was assigned a bed, she agreed to work with me as she did not know what else to do. Her mind was already spinning with anxiety, she was rehearsing how much worse her life was going to be if she was confined to a wheelchair. Some years prior she was given a dose of the incorrect medication while hospitalised and suffered a negative reaction to the point of becoming paralysed by fear. She remembered the relief from our tapping experience then and agreed to work with me daily, via FaceTime, to ease her emotional distress.”

At this point the hospital staff assisted her daughter with accessing Facetime on her cell phone, with Sue-Anne, she began tapping on presenting issues. The frequency was daily, often twice a day for 90 minutes at a time.

While her daughter did not have pain, her body felt numb and heavy. The lifeless weight of her right side, from head to toe terrified her and this was potentially her future reality. Tapping sessions focussed on these aspects and presenting issues.

Sue-Anne describes the general pattern of their sessions on Facetime:

“Our sessions usually began with tapping and breathing to bring my daughter to a felt-sense of body state regulation. Some days we tapped on a story title, this helped to keep her safe (e.g., “‘My life keeps getting worse”). I simply worked with whatever was the most urgent matter at the time. Sometimes I guided her mindfully to focus on interesting aspects of her room or the sound of my voice to help with grounding, as she had a habit of spacing out.

Each session focussed on calming her nervous system by focusing on her breath and tapping on the specific presenting issue that session. I didn’t include body sensations or emotions until the SUDS level dropped. An example was “Even though I can’t believe it, I’m here now doing the best I can. Reminder phrase, I can’t believe it”.

Other reminder phrases that were used included:

“I can’t find the words”, and “This is too much for me”.

Once the SUDS dropped below 5 out of 10 we tapped on felt body sensations and emotions. For example, “Pounding heart, all this worry, tight jaw, thumping headache, all this numbness, tired and exhausted”.

Thankfully her speech was only mildly impacted, and we were able to notice marked improvements in her articulation fairly quickly.

It was important she was able to soothe herself with the EFT technique. She found it helpful to use it on herself in my absence, particularly to ease minor frustrations such as feeding herself with her less dominant hand and also craving a cigarette (which she could not have inside).”

Sue Anne highlights that because of her daughter’s previous negative experiences in the hospital setting, most interactions with medical staff were very triggering for her. Because of COVID-19 they were wearing protective clothing and their faces were covered (masks) and the lack of facial contact resulted in her feeling hypervigilant, nauseated and she could not sleep. Sue-Anne shares:

“She (daughter) began suffering flashbacks of traumatic unresolved memories in her sleep and during the day. Her brain was hyper alert as she scanned all the possible horrific, imagined, future events that may occur (including a potential seizure). However, if she felt, saw, heard or imagined anything distressing we tapped on it. On average we tapped for 90 minutes every day. She also applied the stress management technique to her negative thoughts in between our sessions. The idea of being aware of her thoughts was quite confronting at first, as she usually had a few strategies to avoid or suppress her feelings (e.g., cigarette smoking & alcohol consumption). A typical example setup statement was “Even though I have resistance to being aware of my thoughts, I have too many uncontrollable thoughts, I accept myself anyway.”

2.3.1 A Set Back

On the third day her daughter received the prognosis that she may never walk again from one specialist. Another gave some hope saying she had some chance of regaining a little mobility, however it would take at least six months of ‘hard work’ in the hospital Rehabilitation Unit.

Sue-Anne shares:

“The doctor’s report and prognosis were highly distressing and threatened to counteract my daughter’s progress. The words kept looping in her head. This news had struck a core wound of feeling ‘helpless’ and it derailed her. She was again contracted by fear. It reminded her of her old story, ‘Nobody helps me, I can’t be helped’”.

These reactions were targeted with EFT in the daily sessions and her daughter became more relaxed and coherent. She began questioning the possibility of a different outcome. This provided a profound pivotal moment and her daughter stated: “No -body knows what my body, mind and spirit are capable of, not even me. I’m going to believe I will walk again, and it won’t take six months.”

Because her daughter had a clear intention and a goal, Sue-Anne reported her confidence increased by the hour. Sue-Anne shares:

“It was delightful to witness the shift in her thinking. She began to express all the things in her life she had previously taken for granted. Her persona changed and she started to feel movement in her fingers and toes.”

2.3.2 Supplementary Interventions

It was at this time Sue-Anne introduced her daughter to active visualisation techniques which she reframed as a way to ‘play’ with her daughter’s over-active mind. After a session using EFT, her daughter was able to visualise her limbs moving. She imagined each movement, the thought of taking a step, the message being sent from her brain to her nervous system, bones and muscles.

Sue-Anne shares the process:

“The exercise of visualising green healing energy flooding her injured brain gave her a sense of excitement. Guided meditation allowed her shrink to the size of a particle and enter into her skull to locate the sites of her brain trauma. She imagined herself cleaning the injured tissue. She had seen the scans and x-rays, and these provided her with a clear picture of the affected sites. Using her imagination, she was able to lovingly perform imaginary surgery and remove the damaged tissue.”

This exercise also became the content for EFT set up statements. For example, they said “Even though my brain is inflamed and bruised, I accept how I feel about myself and my body”.

Can you imagine Sue-Anne’s surprise less than a week after hospitalisation when her daughter announced she had, ‘stood up,’ by herself! Her daughter had woken that day with a clear picture of herself standing unassisted and the words ‘I can do this!’ in her mind. She used the left side of her body to manoeuvre herself off the bed. The nurse came in to see her standing there. While she was not able to move from that position and initially felt completely off balance, she was beside herself with excitement.

From this point her daughter began shuffling slowly, and while she reported it was exhausting, she kept focusing on the image in her mind – of walking and driving again. She had one picture in her mind: that she was going to walk and drive again.

Sue-Anne’s daughter was flown back to the Rehabilitation Unit in her home State eight days after the stroke. The doctors confirmed she was making an outstanding recovery and they had no doubt she would walk again. Sue-Anne continued to work via Facetime addressing her daughter’s fears as they arose, particularly her flashbacks about driving.

Sue-Anne’s daughter was released from Rehabilitation after two weeks. Several weeks later she passed a test to be able to drive again. The following neural scans reveal very little scaring or evidence of the stroke. She has not been prescribed any medication. And her blood pressure remained stable. She was quick to reach out if she felt overly stressed or anxious however, these incidences became less and less frequent. Sue-Anne’s daughter was surprised when she noticed she was driving on the freeways without any anxiety, and instead felt calm and at ease.

At the time of this article (some three months post-stroke) Sue-Anne’s daughter’s right arm sometimes shakes if she becomes overly tired or physically pushes herself too far. However, the traumatic memory of the stroke appears to have been transformed. It is now simply a story about something that happened to her, and she has no compulsion to keep reliving it. In fact, there are aspects of the experience she cannot remember, as the memory appears to have been changed. Her daughter commented “It sometimes seems as if the whole stroke thing was a dream”.

Sue-Anne comments on the conclusion of this journey with her daughter: “I am forever grateful for the powerful tool of tapping. I was confident in meeting my child at the place of her pain, confusion and overwhelm. I am not so sure we would have achieved this degree of positive intervention and fast outcome if we had not had this life-changing, evidence-based tool at our fingertips. It certainly delivered hope and results in an extraordinary situation. In my heart, I believe we were instrumental in a miracle. Words cannot express my utter faith in these techniques to align the mind and body to the realm of the profound and the body’s innate wisdom to heal”.

2.3.3 Final Reflection

Sue-Anne reflected in the 12-months after the incident:

“I’m still mind boggled how she [daughter] managed to cut through all those distractions and addictions to create such outstanding Tapping results in what she would perceive as an alienating and hopeless situation. Plus, she had very little faith in the process as she was convinced, she was beyond help. The process created deep inner miracles. Her personality has had a makeover, she’s far more grounded in herself.”

Sue-Anne contemplated that while her daughter’s event was unexpected and difficult, she was in wonder of how impactful and life-changing EFT was for her, perhaps because it was delivered in the 10-day window. She expressed hope that describing the narrative would help to raise awareness in the traditional fields of how techniques such as EFT may support the healing process.

3. Discussion

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40. Frankfurt M, Luine V. The evolving role of dendritic spines and memory: Interaction(s) with estradiol. Horm Behav. 2015; 74: 28-36. [ CrossRef ]

41. Sudhof TC. Neuroligins and neurexins link synaptic function to cognitive disease. Nature. 2008; 455: 903-911. [ CrossRef ]

42. Dorostkar MM, Zou C, Blazquez-Llorca L, Herms J. Analyzing dendritic spine pathology in Alzheimer’s disease: Problems and opportunities. Acta Neuropathol. 2015; 130: 1-19. [ CrossRef ]

3.1 Limitations and Further Opportunities

It is acknowledged that the intervention in this case was delivered by the client’s mother. Although she was a certified EFT practitioner, it does raise ethical questions of bias and potential transference. Furthermore, the intervention was delivered via Facetime and the client did have a brain injury, possibly affecting the validity of the sessions. However, given the nature of the pandemic at the time, and the inability of another trained practitioner to visit in person, her mother as next of kin was the only approved person for contact. In this case it was possibly the most appropriate way to support the client. Finally, often narratives and personal experiences as a research strategy are focused on the participants’ stories, but in this case the lived experience and context was provided by the practitioner. Future research in this area would benefit from the patient’s narrative, as well as a structured EFT intervention program for stroke patients, quantitative data examining the patient’s psychological symptomatology and biomarker outcomes.

3.2 Conclusions

Acknowledgments.

The authors acknowledge the patient for sharing her story and outcomes in this case study.

Author Contributions

S.F. delivered the intervention and documented the qualitative notes. P.S. wrote the main paper.

Competing Interests

Both authors may derive remuneration for presenting on the topic of EFT because of their level of expertise.

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Single-Case Design, Analysis, and Quality Assessment for Intervention Research

Michele a. lobo.

1 Biomechanics & Movement Science Program, Department of Physical Therapy, University of Delaware, Newark, DE, USA

Mariola Moeyaert

2 Division of Educational Psychology & Methodology, State University of New York at Albany, Albany, NY, USA

Andrea Baraldi Cunha

Iryna babik, background and purpose.

The purpose of this article is to describe single-case studies, and contrast them with case studies and randomized clinical trials. We will highlight current research designs, analysis techniques, and quality appraisal tools relevant for single-case rehabilitation research.

Summary of Key Points

Single-case studies can provide a viable alternative to large group studies such as randomized clinical trials. Single case studies involve repeated measures, and manipulation of and independent variable. They can be designed to have strong internal validity for assessing causal relationships between interventions and outcomes, and external validity for generalizability of results, particularly when the study designs incorporate replication, randomization, and multiple participants. Single case studies should not be confused with case studies/series (ie, case reports), which are reports of clinical management of one patient or a small series of patients.

Recommendations for Clinical Practice

When rigorously designed, single-case studies can be particularly useful experimental designs in a variety of situations, even when researcher resources are limited, studied conditions have low incidences, or when examining effects of novel or expensive interventions. Readers will be directed to examples from the published literature in which these techniques have been discussed, evaluated for quality, and implemented.

Introduction

The purpose of this article is to present current tools and techniques relevant for single-case rehabilitation research. Single-case (SC) studies have been identified by a variety of names, including “n of 1 studies” and “single-subject” studies. The term “single-case study” is preferred over the previously mentioned terms because previous terms suggest these studies include only one participant. In fact, as will be discussed below, for purposes of replication and improved generalizability, the strongest SC studies commonly include more than one participant.

A SC study should not be confused with a “case study/series “ (also called “case report”. In a typical case study/series, a single patient or small series of patients is involved, but there is not a purposeful manipulation of an independent variable, nor are there necessarily repeated measures. Most case studies/series are reported in a narrative way while results of SC studies are presented numerically or graphically. 1 , 2 This article defines SC studies, contrasts them with randomized clinical trials, discusses how they can be used to scientifically test hypotheses, and highlights current research designs, analysis techniques, and quality appraisal tools that may be useful for rehabilitation researchers.

In SC studies, measurements of outcome (dependent variables) are recorded repeatedly for individual participants across time and varying levels of an intervention (independent variables). 1 – 5 These varying levels of intervention are referred to as “phases” with one phase serving as a baseline or comparison, so each participant serves as his/her own control. 2 In contrast to case studies and case series in which participants are observed across time without experimental manipulation of the independent variable, SC studies employ systematic manipulation of the independent variable to allow for hypothesis testing. 1 , 6 As a result, SC studies allow for rigorous experimental evaluation of intervention effects and provide a strong basis for establishing causal inferences. Advances in design and analysis techniques for SC studies observed in recent decades have made SC studies increasingly popular in educational and psychological research. Yet, the authors believe SC studies have been undervalued in rehabilitation research, where randomized clinical trials (RCTs) are typically recommended as the optimal research design to answer questions related to interventions. 7 In reality, there are advantages and disadvantages to both SC studies and RCTs that should be carefully considered in order to select the best design to answer individual research questions. While there are a variety of other research designs that could be utilized in rehabilitation research, only SC studies and RCTs are discussed here because SC studies are the focus of this article and RCTs are the most highly recommended design for intervention studies. 7

When designed and conducted properly, RCTs offer strong evidence that changes in outcomes may be related to provision of an intervention. However, RCTs require monetary, time, and personnel resources that many researchers, especially those in clinical settings, may not have available. 8 RCTs also require access to large numbers of consenting participants that meet strict inclusion and exclusion criteria that can limit variability of the sample and generalizability of results. 9 The requirement for large participant numbers may make RCTs difficult to perform in many settings, such as rural and suburban settings, and for many populations, such as those with diagnoses marked by lower prevalence. 8 To rely exclusively on RCTs has the potential to result in bodies of research that are skewed to address the needs of some individuals while neglecting the needs of others. RCTs aim to include a large number of participants and to use random group assignment to create study groups that are similar to one another in terms of all potential confounding variables, but it is challenging to identify all confounding variables. Finally, the results of RCTs are typically presented in terms of group means and standard deviations that may not represent true performance of any one participant. 10 This can present as a challenge for clinicians aiming to translate and implement these group findings at the level of the individual.

SC studies can provide a scientifically rigorous alternative to RCTs for experimentally determining the effectiveness of interventions. 1 , 2 SC studies can assess a variety of research questions, settings, cases, independent variables, and outcomes. 11 There are many benefits to SC studies that make them appealing for intervention research. SC studies may require fewer resources than RCTs and can be performed in settings and with populations that do not allow for large numbers of participants. 1 , 2 In SC studies, each participant serves as his/her own comparison, thus controlling for many confounding variables that can impact outcome in rehabilitation research, such as gender, age, socioeconomic level, cognition, home environment, and concurrent interventions. 2 , 11 Results can be analyzed and presented to determine whether interventions resulted in changes at the level of the individual, the level at which rehabilitation professionals intervene. 2 , 12 When properly designed and executed, SC studies can demonstrate strong internal validity to determine the likelihood of a causal relationship between the intervention and outcomes and external validity to generalize the findings to broader settings and populations. 2 , 12 , 13

Single Case Research Designs for Intervention Research

There are a variety of SC designs that can be used to study the effectiveness of interventions. Here we discuss: 1) AB designs, 2) reversal designs, 3) multiple baseline designs, and 4) alternating treatment designs, as well as ways replication and randomization techniques can be used to improve internal validity of all of these designs. 1 – 3 , 12 – 14

The simplest of these designs is the AB Design 15 ( Figure 1 ). This design involves repeated measurement of outcome variables throughout a baseline control/comparison phase (A ) and then throughout an intervention phase (B). When possible, it is recommended that a stable level and/or rate of change in performance be observed within the baseline phase before transitioning into the intervention phase. 2 As with all SC designs, it is also recommended that there be a minimum of five data points in each phase. 1 , 2 There is no randomization or replication of the baseline or intervention phases in the basic AB design. 2 Therefore, AB designs have problems with internal validity and generalizability of results. 12 They are weak in establishing causality because changes in outcome variables could be related to a variety of other factors, including maturation, experience, learning, and practice effects. 2 , 12 Sample data from a single case AB study performed to assess the impact of Floor Play intervention on social interaction and communication skills for a child with autism 15 are shown in Figure 1 .

An example of results from a single-case AB study conducted on one participant with autism; two weeks of observation (baseline phase A) were followed by seven weeks of Floor Time Play (intervention phase B). The outcome measure Circles of Communications (reciprocal communication with two participants responding to each other verbally or nonverbally) served as a behavioral indicator of the child’s social interaction and communication skills (higher scores indicating better performance). A statistically significant improvement in Circles of Communication was found during the intervention phase as compared to the baseline. Note that although a stable baseline is recommended for SC studies, it is not always possible to satisfy this requirement, as you will see in Figures 1 – 4 . Data were extracted from Dionne and Martini (2011) 15 utilizing Rohatgi’s WebPlotDigitizer software. 78

If an intervention does not have carry-over effects, it is recommended to use a Reversal Design . 2 For example, a reversal A 1 BA 2 design 16 ( Figure 2 ) includes alternation of the baseline and intervention phases, whereas a reversal A 1 B 1 A 2 B 2 design 17 ( Figure 3 ) consists of alternation of two baseline (A 1 , A 2 ) and two intervention (B 1 , B 2 ) phases. Incorporating at least four phases in the reversal design (i.e., A 1 B 1 A 2 B 2 or A 1 B 1 A 2 B 2 A 3 B 3 …) allows for a stronger determination of a causal relationship between the intervention and outcome variables, because the relationship can be demonstrated across at least three different points in time – change in outcome from A 1 to B 1 , from B 1 to A 2 , and from A 2 to B 2 . 18 Before using this design, however, researchers must determine that it is safe and ethical to withdraw the intervention, especially in cases where the intervention is effective and necessary. 12

An example of results from a single-case A 1 BA 2 study conducted on eight participants with stable multiple sclerosis (data on three participants were used for this example). Four weeks of observation (baseline phase A 1 ) were followed by eight weeks of core stability training (intervention phase B), then another four weeks of observation (baseline phase A 2 ). Forward functional reach test (the maximal distance the participant can reach forward or lateral beyond arm’s length, maintaining a fixed base of support in the standing position; higher scores indicating better performance) significantly improved during intervention for Participants 1 and 3 without further improvement observed following withdrawal of the intervention (during baseline phase A 2 ). Data were extracted from Freeman et al. (2010) 16 utilizing Rohatgi’s WebPlotDigitizer software. 78

An example of results from a single-case A 1 B 1 A 2 B 2 study conducted on two participants with severe unilateral neglect after a right-hemisphere stroke. Two weeks of conventional treatment (baseline phases A 1, A 2 ) alternated with two weeks of visuo-spatio-motor cueing (intervention phases B 1 , B 2 ). Performance was assessed in two tests of lateral neglect, the Bells Cancellation Test (Figure A; lower scores indicating better performance) and the Line Bisection Test (Figure B; higher scores indicating better performance). There was a statistically significant intervention-related improvement in participants’ performance on the Line Bisection Test, but not on the Bells Test. Data were extracted from Samuel at al. (2000) 17 utilizing Rohatgi’s WebPlotDigitizer software. 78

A recent study used an ABA reversal SC study to determine the effectiveness of core stability training in 8 participants with multiple sclerosis. 16 During the first four weekly data collections, the researchers ensured a stable baseline, which was followed by eight weekly intervention data points, and concluded with four weekly withdrawal data points. Intervention significantly improved participants’ walking and reaching performance ( Figure 2 ). 16 This A 1 BA 2 design could have been strengthened by the addition of a second intervention phase for replication (A 1 B 1 A 2 B 2 ). For instance, a single-case A 1 B 1 A 2 B 2 withdrawal design aimed to assess the efficacy of rehabilitation using visuo-spatio-motor cueing for two participants with severe unilateral neglect after a severe right-hemisphere stroke. 17 Each phase included 8 data points. Statistically significant intervention-related improvement was observed, suggesting that visuo-spatio-motor cueing might be promising for treating individuals with very severe neglect ( Figure 3 ). 17

The reversal design can also incorporate a cross over design where each participant experiences more than one type of intervention. For instance, a B 1 C 1 B 2 C 2 design could be used to study the effects of two different interventions (B and C) on outcome measures. Challenges with including more than one intervention involve potential carry-over effects from earlier interventions and order effects that may impact the measured effectiveness of the interventions. 2 , 12 Including multiple participants and randomizing the order of intervention phase presentations are tools to help control for these types of effects. 19

When an intervention permanently changes an individual’s ability, a return to baseline performance is not feasible and reversal designs are not appropriate. Multiple Baseline Designs (MBDs) are useful in these situations ( Figure 4 ). 20 MBDs feature staggered introduction of the intervention across time: each participant is randomly assigned to one of at least 3 experimental conditions characterized by the length of the baseline phase. 21 These studies involve more than one participant, thus functioning as SC studies with replication across participants. Staggered introduction of the intervention allows for separation of intervention effects from those of maturation, experience, learning, and practice. For example, a multiple baseline SC study was used to investigate the effect of an anti-spasticity baclofen medication on stiffness in five adult males with spinal cord injury. 20 The subjects were randomly assigned to receive 5–9 baseline data points with a placebo treatment prior to the initiation of the intervention phase with the medication. Both participants and assessors were blind to the experimental condition. The results suggested that baclofen might not be a universal treatment choice for all individuals with spasticity resulting from a traumatic spinal cord injury ( Figure 4 ). 20

An example of results from a single-case multiple baseline study conducted on five participants with spasticity due to traumatic spinal cord injury. Total duration of data collection was nine weeks. The first participant was switched from placebo treatment (baseline) to baclofen treatment (intervention) after five data collection sessions, whereas each consecutive participant was switched to baclofen intervention at the subsequent sessions through the ninth session. There was no statistically significant effect of baclofen on viscous stiffness at the ankle joint. Data were extracted from Hinderer at al. (1990) 20 utilizing Rohatgi’s WebPlotDigitizer software. 78

The impact of two or more interventions can also be assessed via Alternating Treatment Designs (ATDs) . In ATDs, after establishing the baseline, the experimenter exposes subjects to different intervention conditions administered in close proximity for equal intervals ( Figure 5 ). 22 ATDs are prone to “carry-over effects” when the effects of one intervention influence the observed outcomes of another intervention. 1 As a result, such designs introduce unique challenges when attempting to determine the effects of any one intervention and have been less commonly utilized in rehabilitation. An ATD was used to monitor disruptive behaviors in the school setting throughout a baseline followed by an alternating treatment phase with randomized presentation of a control condition or an exercise condition. 23 Results showed that 30 minutes of moderate to intense physical activity decreased behavioral disruptions through 90 minutes after the intervention. 23 An ATD was also used to compare the effects of commercially available and custom-made video prompts on the performance of multi-step cooking tasks in four participants with autism. 22 Results showed that participants independently performed more steps with the custom-made video prompts ( Figure 5 ). 22

An example of results from a single case alternating treatment study conducted on four participants with autism (data on two participants were used for this example). After the observation phase (baseline), effects of commercially available and custom-made video prompts on the performance of multi-step cooking tasks were identified (treatment phase), after which only the best treatment was used (best treatment phase). Custom-made video prompts were most effective for improving participants’ performance of multi-step cooking tasks. Data were extracted from Mechling at al. (2013) 22 utilizing Rohatgi’s WebPlotDigitizer software. 78

Regardless of the SC study design, replication and randomization should be incorporated when possible to improve internal and external validity. 11 The reversal design is an example of replication across study phases. The minimum number of phase replications needed to meet quality standards is three (A 1 B 1 A 2 B 2 ), but having four or more replications is highly recommended (A 1 B 1 A 2 B 2 A 3 …). 11 , 14 In cases when interventions aim to produce lasting changes in participants’ abilities, replication of findings may be demonstrated by replicating intervention effects across multiple participants (as in multiple-participant AB designs), or across multiple settings, tasks, or service providers. When the results of an intervention are replicated across multiple reversals, participants, and/or contexts, there is an increased likelihood a causal relationship exists between the intervention and the outcome. 2 , 12

Randomization should be incorporated in SC studies to improve internal validity and the ability to assess for causal relationships among interventions and outcomes. 11 In contrast to traditional group designs, SC studies often do not have multiple participants or units that can be randomly assigned to different intervention conditions. Instead, in randomized phase-order designs , the sequence of phases is randomized. Simple or block randomization is possible. For example, with simple randomization for an A 1 B 1 A 2 B 2 design, the A and B conditions are treated as separate units and are randomly assigned to be administered for each of the pre-defined data collection points. As a result, any combination of A-B sequences is possible without restrictions on the number of times each condition is administered or regard for repetitions of conditions (e.g., A 1 B 1 B 2 A 2 B 3 B 4 B 5 A 3 B 6 A 4 A 5 A 6 ). With block randomization for an A 1 B 1 A 2 B 2 design, two conditions (e.g., A and B) would be blocked into a single unit (AB or BA), randomization of which to different time periods would ensure that each condition appears in the resulting sequence more than two times (e.g., A 1 B 1 B 2 A 2 A 3 B 3 A 4 B 4 ). Note that AB and reversal designs require that the baseline (A) always precedes the first intervention (B), which should be accounted for in the randomization scheme. 2 , 11

In randomized phase start-point designs , the lengths of the A and B phases can be randomized. 2 , 11 , 24 – 26 For example, for an AB design, researchers could specify the number of time points at which outcome data will be collected, (e.g., 20), define the minimum number of data points desired in each phase (e.g., 4 for A, 3 for B), and then randomize the initiation of the intervention so that it occurs anywhere between the remaining time points (points 5 and 17 in the current example). 27 , 28 For multiple-baseline designs, a dual-randomization, or “regulated randomization” procedure has been recommended. 29 If multiple-baseline randomization depends solely on chance, it could be the case that all units are assigned to begin intervention at points not really separated in time. 30 Such randomly selected initiation of the intervention would result in the drastic reduction of the discriminant and internal validity of the study. 29 To eliminate this issue, investigators should first specify appropriate intervals between the start points for different units, then randomly select from those intervals, and finally randomly assign each unit to a start point. 29

Single Case Analysis Techniques for Intervention Research

The What Works Clearinghouse (WWC) single-case design technical documentation provides an excellent overview of appropriate SC study analysis techniques to evaluate the effectiveness of intervention effects. 1 , 18 First, visual analyses are recommended to determine whether there is a functional relation between the intervention and the outcome. Second, if evidence for a functional effect is present, the visual analysis is supplemented with quantitative analysis methods evaluating the magnitude of the intervention effect. Third, effect sizes are combined across cases to estimate overall average intervention effects which contributes to evidence-based practice, theory, and future applications. 2 , 18

Visual Analysis

Traditionally, SC study data are presented graphically. When more than one participant engages in a study, a spaghetti plot showing all of their data in the same figure can be helpful for visualization. Visual analysis of graphed data has been the traditional method for evaluating treatment effects in SC research. 1 , 12 , 31 , 32 The visual analysis involves evaluating level, trend, and stability of the data within each phase (i.e., within-phase data examination) followed by examination of the immediacy of effect, consistency of data patterns, and overlap of data between baseline and intervention phases (i.e., between-phase comparisons). When the changes (and/or variability) in level are in the desired direction, are immediate, readily discernible, and maintained over time, it is concluded that the changes in behavior across phases result from the implemented treatment and are indicative of improvement. 33 Three demonstrations of an intervention effect are necessary for establishing a functional relation. 1

Within-phase examination

Level, trend, and stability of the data within each phase are evaluated. Mean and/or median can be used to report the level, and trend can be evaluated by determining whether the data points are monotonically increasing or decreasing. Within-phase stability can be evaluated by calculating the percentage of data points within 15% of the phase median (or mean). The stability criterion is satisfied if about 85% (80% – 90%) of the data in a phase fall within a 15% range of the median (or average) of all data points for that phase. 34

Between-phase examination

Immediacy of effect, consistency of data patterns, and overlap of data between baseline and intervention phases are evaluated next. For this, several nonoverlap indices have been proposed that all quantify the proportion of measurements in the intervention phase not overlapping with the baseline measurements. 35 Nonoverlap statistics are typically scaled as percent from 0 to 100, or as a proportion from 0 to 1. Here, we briefly discuss the Nonoverlap of All Pairs ( NAP ), 36 the Extended Celeration Line ( ECL ), the Improvement Rate Difference ( IRD) , 37 and the TauU and the TauU-adjusted, TauU adj , 35 as these are the most recent and complete techniques. We also examine the Percentage of Nonoverlapping Data ( PND ) 38 and the Two Standard Deviations Band Method, as these are frequently used techniques. In addition, we include the Percentage of Nonoverlapping Corrected Data ( PNCD ) – an index applying to the PND after controlling for baseline trend. 39

Nonoverlap of all pairs (NAP)

Each baseline observation can be paired with each intervention phase observation to make n pairs (i.e., N = n A * n B ). Count the number of overlapping pairs, n o , counting all ties as 0.5. Then define the percent of the pairs that show no overlap. Alternatively, one can count the number of positive (P), negative (N), and tied (T) pairs 2 , 36 :

Extended Celeration Line (ECL)

ECL or split middle line allows control for a positive Phase A trend. Nonoverlap is defined as the proportion of Phase B ( n b ) data that are above the median trend plotted from Phase A data ( n B< sub > Above Median trend A </ sub > ), but then extended into Phase B: ECL = n B Above Median trend A n b ∗ 100

As a consequence, this method depends on a straight line and makes an assumption of linearity in the baseline. 2 , 12

Improvement rate difference (IRD)

This analysis is conceptualized as the difference in improvement rates (IR) between baseline ( IR B ) and intervention phases ( IR T ). 38 The IR for each phase is defined as the number of “improved data points” divided by the total data points in that phase. IRD, commonly employed in medical group research under the name of “risk reduction” or “risk difference” attempts to provide an intuitive interpretation for nonoverlap and to make use of an established, respected effect size, IR B - IR B , or the difference between two proportions. 37

TauU and TauU adj

Each baseline observation can be paired with each intervention phase observation to make n pairs (i.e., n = n A * n B ). Count the number of positive (P), negative (N), and tied (T) pairs, and use the following formula: TauU = P - N P + N + τ

The TauU adj is an adjustment of TauU for monotonic trend in baseline. Each baseline observation can be paired with each intervention phase observation to make n pairs (i.e., n = n A * n B ). Each baseline observation can be paired with all later baseline observations (n A *(n A -1)/2). 2 , 35 Then the baseline trend can be computed: TauU adf = P - N - S trend P + N + τ ; S trend = P A – NA

Online calculators might assist researchers in obtaining the TauU and TauU adjusted coefficients ( http://www.singlecaseresearch.org/calculators/tau-u ).

Percentage of nonoverlapping data (PND)

If anticipating an increase in the outcome, locate the highest data point in the baseline phase and then calculate the percent of the intervention phase data points that exceed it. If anticipating a decrease in the outcome, find the lowest data point in the baseline phase and then calculate the percent of the treatment phase data points that are below it: PND = n B Overlap A n b ∗ 100 . A PND < 50 would mark no observed effect, PND = 50–70 signifies a questionable effect, and PND > 70 suggests the intervention was effective. 40 The percentage of nonoverlapping (PNDC) corrected was proposed in 2009 as an extension of the PND. 39 Prior to applying the PND, a data correction procedure is applied eliminating pre-existing baseline trend. 38

Two Standard Deviation Band Method

When the stability criterion described above is met within phases, it is possible to apply the two standard deviation band method. 12 , 41 First, the mean of the data for a specific condition is calculated and represented with a solid line. In the next step, the standard deviation of the same data is computed and two dashed lines are represented: one located two standard deviations above the mean and the other – two standard deviations below. For normally distributed data, few points (less than 5%) are expected to be outside the two standard deviation bands if there is no change in the outcome score due to the intervention. However, this method is not considered a formal statistical procedure, as the data cannot typically be assumed to be normal, continuous, or independent. 41

Statistical Analysis

If the visual analysis indicates a functional relationship (i.e., three demonstrations of the effectiveness of the intervention effect), it is recommended to proceed with the quantitative analyses, reflecting the magnitude of the intervention effect. First, effect sizes are calculated for each participant (individual-level analysis). Moreover, if the research interest lies in the generalizability of the effect size across participants, effect sizes can be combined across cases to achieve an overall average effect size estimate (across-case effect size).

Note that quantitative analysis methods are still being developed in the domain of SC research 1 and statistical challenges of producing an acceptable measure of treatment effect remain. 14 , 42 , 43 Therefore, the WWC standards strongly recommend conducting sensitivity analysis and reporting multiple effect size estimators. If consistency across different effect size estimators is identified, there is stronger evidence for the effectiveness of the treatment. 1 , 18

Individual-level effect size analysis

The most common effect sizes recommended for SC analysis are: 1) standardized mean difference Cohen’s d ; 2) standardized mean difference with correction for small sample sizes Hedges’ g ; and 3) the regression-based approach which has the most potential and is strongly recommended by the WWC standards. 1 , 44 , 45 Cohen’s d can be calculated using following formula: d = X A ¯ - X B ¯ s p , with X A ¯ being the baseline mean, X B ¯ being the treatment mean, and s p indicating the pooled within-case standard deviation. Hedges’ g is an extension of Cohen’s d , recommended in the context of SC studies as it corrects for small sample sizes. The piecewise regression-based approach does not only reflect the immediate intervention effect, but also the intervention effect across time:

i stands for the measurement occasion ( i = 0, 1,… I ). The dependent variable is regressed on a time indicator, T , which is centered around the first observation of the intervention phase, D , a dummy variable for the intervention phase, and an interaction term of these variables. The equation shows that the expected score, Ŷ i , equals β 0 + β 1 T i in the baseline phase, and ( β 0 + β 2 ) + ( β 1 + β 3 ) T i in the intervention phase. β 0 , therefore, indicates the expected baseline level at the start of the intervention phase (when T = 0), whereas β 1 marks the linear time trend in the baseline scores. The coefficient β 2 can then be interpreted as an immediate effect of the intervention on the outcome, whereas β 3 signifies the effect of the intervention across time. The e i ’s are residuals assumed to be normally distributed around a mean of zero with a variance of σ e 2 . The assumption of independence of errors is usually not met in the context of SC studies because repeated measures are obtained within a person. As a consequence, it can be the case that the residuals are autocorrelated, meaning that errors closer in time are more related to each other compared to errors further away in time. 46 – 48 As a consequence, a lag-1 autocorrelation is appropriate (taking into account the correlation between two consecutive errors: e i and e i –1 ; for more details see Verbeke & Molenberghs, (2000). 49 In Equation 1 , ρ indicates the autocorrelation parameter. If ρ is positive, the errors closer in time are more similar; if ρ is negative, the errors closer in time are more different, and if ρ equals zero, there is no correlation between the errors.

Across-case effect sizes

Two-level modeling to estimate the intervention effects across cases can be used to evaluate across-case effect sizes. 44 , 45 , 50 Multilevel modeling is recommended by the WWC standards because it takes the hierarchical nature of SC studies into account: measurements are nested within cases and cases, in turn, are nested within studies. By conducting a multilevel analysis, important research questions can be addressed (which cannot be answered by single-level analysis of SC study data), such as: 1) What is the magnitude of the average treatment effect across cases? 2) What is the magnitude and direction of the case-specific intervention effect? 3) How much does the treatment effect vary within cases and across cases? 4) Does a case and/or study level predictor influence the treatment’s effect? The two-level model has been validated in previous research using extensive simulation studies. 45 , 46 , 51 The two-level model appears to have sufficient power (> .80) to detect large treatment effects in at least six participants with six measurements. 21

Furthermore, to estimate the across-case effect sizes, the HPS (Hedges, Pustejovsky, and Shadish) , or single-case educational design ( SCEdD)-specific mean difference, index can be calculated. 52 This is a standardized mean difference index specifically designed for SCEdD data, with the aim of making it comparable to Cohen’s d of group-comparison designs. The standard deviation takes into account both within-participant and between-participant variability, and is typically used to get an across-case estimator for a standardized change in level. The advantage of using the HPS across-case effect size estimator is that it is directly comparable with Cohen’s d for group comparison research, thus enabling the use of Cohen’s (1988) benchmarks. 53

Valuable recommendations on SC data analyses have recently been provided. 54 , 55 They suggest that a specific SC study data analytic technique can be chosen based on: (1) the study aims and the desired quantification (e.g., overall quantification, between-phase quantifications, randomization, etc.), (2) the data characteristics as assessed by visual inspection and the assumptions one is willing to make about the data, and (3) the knowledge and computational resources. 54 , 55 Table 1 lists recommended readings and some commonly used resources related to the design and analysis of single-case studies.

Recommend readings and resources related to the design and analysis of single-case studies.

Quality Appraisal Tools for Single-Case Design Research

Quality appraisal tools are important to guide researchers in designing strong experiments and conducting high-quality systematic reviews of the literature. Unfortunately, quality assessment tools for SC studies are relatively novel, ratings across tools demonstrate variability, and there is currently no “gold standard” tool. 56 Table 2 lists important SC study quality appraisal criteria compiled from the most common scales; when planning studies or reviewing the literature, we recommend readers consider these criteria. Table 3 lists some commonly used SC quality assessment and reporting tools and references to resources where the tools can be located.

Summary of important single-case study quality appraisal criteria.

Quality assessment and reporting tools related to single-case studies.

When an established tool is required for systematic review, we recommend use of the What Works Clearinghouse (WWC) Tool because it has well-defined criteria and is developed and supported by leading experts in the SC research field in association with the Institute of Education Sciences. 18 The WWC documentation provides clear standards and procedures to evaluate the quality of SC research; it assesses the internal validity of SC studies, classifying them as “Meeting Standards”, “Meeting Standards with Reservations”, or “Not Meeting Standards”. 1 , 18 Only studies classified in the first two categories are recommended for further visual analysis. Also, WWC evaluates the evidence of effect, classifying studies into “Strong Evidence of a Causal Relation”, “Moderate Evidence of a Causal Relation”, or “No Evidence of a Causal Relation”. Effect size should only be calculated for studies providing strong or moderate evidence of a causal relation.

The Single-Case Reporting Guideline In BEhavioural Interventions (SCRIBE) 2016 is another useful SC research tool developed recently to improve the quality of single-case designs. 57 SCRIBE consists of a 26-item checklist that researchers need to address while reporting the results of SC studies. This practical checklist allows for critical evaluation of SC studies during study planning, manuscript preparation, and review.

Single-case studies can be designed and analyzed in a rigorous manner that allows researchers strength in assessing causal relationships among interventions and outcomes, and in generalizing their results. 2 , 12 These studies can be strengthened via incorporating replication of findings across multiple study phases, participants, settings, or contexts, and by using randomization of conditions or phase lengths. 11 There are a variety of tools that can allow researchers to objectively analyze findings from SC studies. 56 While a variety of quality assessment tools exist for SC studies, they can be difficult to locate and utilize without experience, and different tools can provide variable results. The WWC quality assessment tool is recommended for those aiming to systematically review SC studies. 1 , 18

SC studies, like all types of study designs, have a variety of limitations. First, it can be challenging to collect at least five data points in a given study phase. This may be especially true when traveling for data collection is difficult for participants, or during the baseline phase when delaying intervention may not be safe or ethical. Power in SC studies is related to the number of data points gathered for each participant so it is important to avoid having a limited number of data points. 12 , 58 Second, SC studies are not always designed in a rigorous manner and, thus, may have poor internal validity. This limitation can be overcome by addressing key characteristics that strengthen SC designs ( Table 2 ). 1 , 14 , 18 Third, SC studies may have poor generalizability. This limitation can be overcome by including a greater number of participants, or units. Fourth, SC studies may require consultation from expert methodologists and statisticians to ensure proper study design and data analysis, especially to manage issues like autocorrelation and variability of data. 2 Fifth, while it is recommended to achieve a stable level and rate of performance throughout the baseline, human performance is quite variable and can make this requirement challenging. Finally, the most important validity threat to SC studies is maturation. This challenge must be considered during the design process in order to strengthen SC studies. 1 , 2 , 12 , 58

SC studies can be particularly useful for rehabilitation research. They allow researchers to closely track and report change at the level of the individual. They may require fewer resources and, thus, can allow for high-quality experimental research, even in clinical settings. Furthermore, they provide a tool for assessing causal relationships in populations and settings where large numbers of participants are not accessible. For all of these reasons, SC studies can serve as an effective method for assessing the impact of interventions.

Acknowledgments

This research was supported by the National Institute of Health, Eunice Kennedy Shriver National Institute of Child Health & Human Development (1R21HD076092-01A1, Lobo PI) and the Delaware Economic Development Office (Grant #109).

Some of the information in this manuscript was presented at the IV Step Meeting in Columbus, OH, June 2016.

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• Clinical course of a 66-year-old man with an acute ischaemic stroke in the setting of a COVID-19 infection
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• http://orcid.org/0000-0002-7441-6952 Saajan Basi 1 , 2 ,
• Mohammad Hamdan 1 and
• Shuja Punekar 1
• 1 Department of Stroke and Acute Medicine , King's Mill Hospital , Sutton-in-Ashfield , UK
• 2 Department of Acute Medicine , University Hospitals of Derby and Burton , Derby , UK
• Correspondence to Dr Saajan Basi; saajan.basi{at}nhs.net

A 66-year-old man was admitted to hospital with a right frontal cerebral infarct producing left-sided weakness and a deterioration in his speech pattern. The cerebral infarct was confirmed with CT imaging. The only evidence of respiratory symptoms on admission was a 2 L oxygen requirement, maintaining oxygen saturations between 88% and 92%. In a matter of hours this patient developed a greater oxygen requirement, alongside reduced levels of consciousness. A positive COVID-19 throat swab, in addition to bilateral pneumonia on chest X-ray and lymphopaenia in his blood tests, confirmed a diagnosis of COVID-19 pneumonia. A proactive decision was made involving the patients’ family, ward and intensive care healthcare staff, to not escalate care above a ward-based ceiling of care. The patient died 5 days following admission under the palliative care provided by the medical team.

• respiratory medicine
• infectious diseases
• global health

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/ .

https://doi.org/10.1136/bcr-2020-235920

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SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a new strain of coronavirus that is thought to have originated in December 2019 in Wuhan, China. In a matter of months, it has erupted from non-existence to perhaps the greatest challenge to healthcare in modern times, grinding most societies globally to a sudden halt. Consequently, the study and research into SARS-CoV-2 is invaluable. Although coronaviruses are common, SARS-CoV-2 appears to be considerably more contagious. The WHO figures into the 2003 SARS-CoV-1 outbreak, from November 2002 to July 2003, indicate a total of 8439 confirmed cases globally. 1 In comparison, during a period of 4 months from December 2019 to July 2020, the number of global cases of COVID-19 reached 10 357 662, increasing exponentially, illustrating how much more contagious SARS-CoV-2 has been. 2

Previous literature has indicated infections, and influenza-like illness have been associated with an overall increase in the odds of stroke development. 3 There appears to be a growing correlation between COVID-19 positive patients presenting to hospital with ischaemic stroke; however, studies investigating this are in progress, with new data emerging daily. This patient report comments on and further characterises the link between COVID-19 pneumonia and the development of ischaemic stroke. At the time of this patients’ admission, there were 95 positive cases from 604 COVID-19 tests conducted in the local community, with a predicted population of 108 000. 4 Only 4 days later, when this patient died, the figure increased to 172 positive cases (81% increase), illustrating the rapid escalation towards the peak of the pandemic, and widespread transmission within the local community ( figure 1 ). As more cases of ischaemic stroke in COVID-19 pneumonia patients arise, the recognition and understanding of its presentation and aetiology can be deciphered. Considering the virulence of SARS-CoV-2 it is crucial as a global healthcare community, we develop this understanding, in order to intervene and reduce significant morbidity and mortality in stroke patients.

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A graph showing the number of patients with COVID-19 in the hospital and in the community over time.

Case presentation

A 66-year-old man presented to the hospital with signs of left-sided weakness. The patient had a background of chronic obstructive pulmonary disease (COPD), atrial fibrillation and had one previous ischaemic stroke, producing left-sided haemiparesis, which had completely resolved. He was a non-smoker and lived in a house. The patient was found slumped over on the sofa at home on 1 April 2020, by a relative at approximately 01:00, having been seen to have no acute medical illness at 22:00. The patients’ relative initially described disorientation and agitation with weakness noted in the left upper limb and dysarthria. At the time of presentation, neither the patient nor his relative identified any history of fever, cough, shortness of breath, loss of taste, smell or any other symptoms; however, the patient did have a prior admission 9 days earlier with shortness of breath.

The vague nature of symptoms, entwined with considerable concern over approaching the hospital, due to the risk of contracting COVID-19, created a delay in the patients’ attendance to the accident and emergency department. His primary survey conducted at 09:20 on 1 April 2020 demonstrated a patent airway, with spontaneous breathing and good perfusion. His Glasgow Coma Scale (GCS) score was 15 (a score of 15 is the highest level of consciousness), his blood glucose was 7.2, and he did not exhibit any signs of trauma. His abbreviated mental test score was 7 out of 10, indicating a degree of altered cognition. An ECG demonstrated atrial fibrillation with a normal heart rate. His admission weight measured 107 kg. At 09:57 the patient required 2 L of nasal cannula oxygen to maintain his oxygen saturations between 88% and 92%. He started to develop agitation associated with an increased respiratory rate at 36 breaths per minute. On auscultation of his chest, he demonstrated widespread coarse crepitation and bilateral wheeze. Throughout he was haemodynamically stable, with a systolic blood pressure between 143 mm Hg and 144 mm Hg and heart rate between 86 beats/min and 95 beats/min. From a neurological standpoint, he had a mild left facial droop, 2/5 power in both lower limbs, 2/5 power in his left upper limb and 5/5 power in his right upper limb. Tone in his left upper limb had increased. This patient was suspected of having COVID-19 pneumonia alongside an ischaemic stroke.

Investigations

A CT of his brain conducted at 11:38 on 1 April 2020 ( figure 2 ) illustrated an ill-defined hypodensity in the right frontal lobe medially, with sulcal effacement and loss of grey-white matter. This was highly likely to represent acute anterior cerebral artery territory infarction. Furthermore an oval low-density area in the right cerebellar hemisphere, that was also suspicious of an acute infarction. These vascular territories did not entirely correlate with his clinical picture, as limb weakness is not as prominent in anterior cerebral artery territory ischaemia. Therefore this left-sided weakness may have been an amalgamation of residual weakness from his previous stroke, in addition to his acute cerebral infarction. An erect AP chest X-ray with portable equipment ( figure 3 ) conducted on the same day demonstrated patchy peripheral consolidation bilaterally, with no evidence of significant pleural effusion. The pattern of lung involvement raised suspicion of COVID-19 infection, which at this stage was thought to have provoked the acute cerebral infarct. Clinically significant blood results from 1 April 2020 demonstrated a raised C-reactive protein (CRP) at 215 mg/L (normal 0–5 mg/L) and lymphopaenia at 0.5×10 9 (normal 1×10 9 to 3×10 9 ). Other routine blood results are provided in table 1 .

CT imaging of this patients’ brain demonstrating a wedge-shaped infarction of the anterior cerebral artery territory.

Chest X-ray demonstrating the bilateral COVID-19 pneumonia of this patient on admission.

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Clinical biochemistry and haematology blood results of the patient

Interestingly the patient, in this case, was clinically assessed in the accident and emergency department on 23 March 2020, 9 days prior to admission, with symptoms of shortness of breath. His blood results from this day showed a CRP of 22 mg/L and a greater lymphopaenia at 0.3×10 9 . He had a chest X-ray ( figure 4 ), which indicated mild radiopacification in the left mid zone. He was initially treated with intravenous co-amoxiclav and ciprofloxacin. The following day he had minimal symptoms (CURB 65 score 1 for being over 65 years). Given improving blood results (declining CRP), he was discharged home with a course of oral amoxicillin and clarithromycin. As national governmental restrictions due to COVID-19 had not been formally announced until 23 March 2020, and inconsistencies regarding personal protective equipment training and usage existed during the earlier stages of this rapidly evolving pandemic, it is possible that this patient contracted COVID-19 within the local community, or during his prior hospital admission. It could be argued that the patient had early COVID-19 signs and symptoms, having presented with shortness of breath, lymphopaenia, and having had subtle infective chest X-ray changes. The patient explained he developed a stagnant productive cough, which began 5 days prior to his attendance to hospital on 23 March 2020. He responded to antibiotics, making a full recovery following 7 days of treatment. This information does not assimilate with the typical features of a COVID-19 infection. A diagnosis of community-acquired pneumonia or infective exacerbation of COPD seem more likely. However, given the high incidence of COVID-19 infections during this patients’ illness, an exposure and early COVID-19 illness, prior to the 23 March 2020, cannot be completely ruled out.

Chest X-ray conducted on prior admission illustrating mild radiopacification in the left mid zone.

On the current admission, this patient was managed with nasal cannula oxygen at 2 L. By the end of the day, this had progressed to a venturi mask, requiring 8 L of oxygen to maintain oxygen saturation. He had also become increasingly drowsy and confused, his GCS declined from 15 to 12. However, the patient was still haemodynamically stable, as he had been in the morning. An arterial blood gas demonstrated a respiratory alkalosis (pH 7.55, pCO 2 3.1, pO 2 6.7 and HCO 3 24.9, lactate 1.8, base excess 0.5). He was commenced on intravenous co-amoxiclav and ciprofloxacin, to treat a potential exacerbation of COPD. This patient had a COVID-19 throat swab on 1 April 2020. Before the result of this swab, an early discussion was held with the intensive care unit staff, who decided at 17:00 on 1 April 2020 that given the patients presentation, rapid deterioration, comorbidities and likely COVID-19 diagnosis he would not be for escalation to the intensive care unit, and if he were to deteriorate further the end of life pathway would be most appropriate. The discussion was reiterated to the patients’ family, who were in agreement with this. Although he had evidence of an ischaemic stroke on CT of his brain, it was agreed by all clinicians that intervention for this was not as much of a priority as providing optimal palliative care, therefore, a minimally invasive method of treatment was advocated by the stroke team. The patient was given 300 mg of aspirin and was not a candidate for fibrinolysis.

Outcome and follow-up

The following day, before the throat swab result, had appeared the patient deteriorated further, requiring 15 L of oxygen through a non-rebreather face mask at 60% FiO 2 to maintain his oxygen saturation, at a maximum of 88% overnight. At this point, he was unresponsive to voice, with a GCS of 5. Although, he was still haemodynamically stable, with a blood pressure of 126/74 mm Hg and a heart rate of 98 beats/min. His respiratory rate was 30 breaths/min. His worsening respiratory condition, combined with his declining level of consciousness made it impossible to clinically assess progression of the neurological deficit generated by his cerebral infarction. Moreover, the patient was declining sharply while receiving the maximal ward-based treatment available. The senior respiratory physician overseeing the patients’ care decided that a palliative approach was in this his best interest, which was agreed on by all parties. The respiratory team completed the ‘recognising dying’ documentation, which signified that priorities of care had shifted from curative treatment to palliative care. Although the palliative team was not formally involved in the care of the patient, the patient received comfort measures without further attempts at supporting oxygenation, or conduction of regular clinical observations. The COVID-19 throat swab confirmed a positive result on 2 April 2020. The patient was treated by the medical team under jurisdiction of the hospital palliative care team. This included the prescribing of anticipatory medications and a syringe driver, which was established on 3 April 2020. His antibiotic treatment, non-essential medication and intravenous fluid treatment were discontinued. His comatose condition persisted throughout the admission. Once the patients’ GCS was 5, it did not improve. The patient was pronounced dead by doctors at 08:40 on 5 April 2020.

SARS-CoV-2 is a type of coronavirus that was first reported to have caused pneumonia-like infection in humans on 3 December 2019. 5 As a group, coronaviruses are a common cause of upper and lower respiratory tract infections (especially in children) and have been researched extensively since they were first characterised in the 1960s. 6 To date, there are seven coronaviruses that are known to cause infection in humans, including SARS-CoV-1, the first known zoonotic coronavirus outbreak in November 2002. 7 Coronavirus infections pass through communities during the winter months, causing small outbreaks in local communities, that do not cause significant mortality or morbidity.

SARS-CoV-2 strain of coronavirus is classed as a zoonotic coronavirus, meaning the virus pathogen is transmitted from non-humans to cause disease in humans. However the rapid spread of SARS-CoV-2 indicates human to human transmission is present. From previous research on the transmission of coronaviruses and that of SARS-CoV-2 it can be inferred that SARS-CoV-2 spreads via respiratory droplets, either from direct inhalation, or indirectly touching surfaces with the virus and exposing the eyes, nose or mouth. 8 Common signs and symptoms of the COVID-19 infection identified in patients include high fevers, severe fatigue, dry cough, acute breathing difficulties, bilateral pneumonia on radiological imaging and lymphopaenia. 9 Most of these features were identified in this case study. The significance of COVID-19 is illustrated by the speed of its global spread and the potential to cause severe clinical presentations, which as of April 2020 can only be treated symptomatically. In Italy, as of mid-March 2020, it was reported that 12% of the entire COVID-19 positive population and 16% of all hospitalised patients had an admission to the intensive care unit. 10

The patient, in this case, illustrates the clinical relevance of understanding COVID-19, as he presented with an ischaemic stroke underlined by minimal respiratory symptoms, which progressed expeditiously, resulting in acute respiratory distress syndrome and subsequent death.

Our case is an example of a new and ever-evolving clinical correlation, between patients who present with a radiological confirmed ischaemic stroke and severe COVID-19 pneumonia. As of April 2020, no comprehensive data of the relationship between ischaemic stroke and COVID-19 has been published, however early retrospective case series from three hospitals in Wuhan, China have indicated that up to 36% of COVID-19 patients had neurological manifestations, including stroke. 11 These studies have not yet undergone peer review, but they tell us a great deal about the relationship between COVID-19 and ischaemic stroke, and have been used to influence the American Heart Associations ‘Temporary Emergency Guidance to US Stroke Centres During the COVID-19 Pandemic’. 12

The relationship between similar coronaviruses and other viruses, such as influenza in the development of ischaemic stroke has previously been researched and provide a basis for further investigation, into the prominence of COVID-19 and its relation to ischaemic stroke. 3 Studies of SARS-CoV-2 indicate its receptor-binding region for entry into the host cell is the same as ACE2, which is present on endothelial cells throughout the body. It may be the case that SARS-CoV-2 alters the conventional ability of ACE2 to protect endothelial function in blood vessels, promoting atherosclerotic plaque displacement by producing an inflammatory response, thus increasing the risk of ischaemic stroke development. 13

Other hypothesised reasons for stroke development in COVID-19 patients are the development of hypercoagulability, as a result of critical illness or new onset of arrhythmias, caused by severe infection. Some case studies in Wuhan described immense inflammatory responses to COVID-19, including elevated acute phase reactants, such as CRP and D-dimer. Raised D-dimers are a non-specific marker of a prothrombotic state and have been associated with greater morbidity and mortality relating to stroke and other neurological features. 14

Arrhythmias such as atrial fibrillation had been identified in 17% of 138 COVID-19 patients, in a study conducted in Wuhan, China. 15 In this report, the patient was known to have atrial fibrillation and was treated with rivaroxaban. The acute inflammatory state COVID-19 is known to produce had the potential to create a prothrombotic environment, culminating in an ischaemic stroke.

Some early case studies produced in Wuhan describe patients in the sixth decade of life that had not been previously noted to have antiphospholipid antibodies, contain the antibodies in blood results. They are antibodies signify antiphospholipid syndrome; a prothrombotic condition. 16 This raises the hypothesis concerning the ability of COVID-19 to evoke the creation of these antibodies and potentiate thrombotic events, such as ischaemic stroke.

No peer-reviewed studies on the effects of COVID-19 and mechanism of stroke are published as of April 2020; therefore, it is difficult to evidence a specific reason as to why COVID-19 patients are developing neurological signs. It is suspected that a mixture of the factors mentioned above influence the development of ischaemic stroke.

If we delve further into this patients’ comorbid state exclusive to COVID-19 infection, it can be argued that this patient was already at a relatively higher risk of stroke development compared with the general population. The fact this patient had previously had an ischaemic stroke illustrates a prior susceptibility. This patient had a known background of hypertension and atrial fibrillation, which as mentioned previously, can influence blood clot or plaque propagation in the development of an acute ischaemic event. 15 Although the patient was prescribed rivaroxaban as an anticoagulant, true consistent compliance to rivaroxaban or other medications such as amlodipine, clopidogrel, candesartan and atorvastatin cannot be confirmed; all of which can contribute to the reduction of influential factors in the development of ischaemic stroke. Furthermore, the fear of contracting COVID-19, in addition to his vague symptoms, unlike his prior ischaemic stroke, which demonstrated dense left-sided haemiparesis, led to a delay in presentation to hospital. This made treatment options like fibrinolysis unachievable, although it can be argued that if he was already infected with COVID-19, he would have still developed life-threatening COVID-19 pneumonia, regardless of whether he underwent fibrinolysis. It is therefore important to consider that if this patient did not contract COVID-19 pneumonia, he still had many risk factors that made him prone to ischaemic stroke formation. Thus, we must consider whether similar patients would suffer from ischaemic stroke, regardless of COVID-19 infection and whether COVID-19 impacts on the severity of the stroke as an entity.

Having said this, the management of these patients is dependent on the likelihood of a positive outcome from the COVID-19 infection. Establishing the ceiling of care is crucial, as it prevents incredibly unwell or unfit patients’ from going through futile treatments, ensuring respect and dignity in death, if this is the likely outcome. It also allows for the provision of limited or intensive resources, such as intensive care beds or endotracheal intubation during the COVID-19 pandemic, to those who are assessed by the multidisciplinary team to benefit the most from their use. The way to establish this ceiling of care is through an early multidisciplinary discussion. In this case, the patient did not convey his wishes regarding his care to the medical team or his family; therefore it was decided among intensive care specialists, respiratory physicians, stroke physicians and the patients’ relatives. The patient was discussed with the intensive care team, who decided that as the patient sustained two acute life-threatening illnesses simultaneously and had rapidly deteriorated, ward-based care with a view to palliate if the further deterioration was in the patients’ best interests. These decisions were not easy to make, especially as it was on the first day of presentation. This decision was made in the context of the patients’ comorbidities, including COPD, the patients’ age, and the availability of intensive care beds during the steep rise in intensive care admissions, in the midst of the COVID-19 pandemic ( figure 1 ). Furthermore, the patients’ rapid and permanent decline in GCS, entwined with the severe stroke on CT imaging of the brain made it more unlikely that significant and permanent recovery could be achieved from mechanical intubation, especially as the damage caused by the stroke could not be significantly reversed. As hospitals manage patients with COVID-19 in many parts of the world, there may be tension between the need to provide higher levels of care for an individual patient and the need to preserve finite resources to maximise the benefits for most patients. This patient presented during a steep rise in intensive care admissions, which may have influenced the early decision not to treat the patient in an intensive care setting. Retrospective studies from Wuhan investigating mortality in patients with multiple organ failure, in the setting of COVID-19, requiring intubation have demonstrated mortality can be up to 61.5%. 17 The mortality risk is even higher in those over 65 years of age with respiratory comorbidities, indicating why this patient was unlikely to survive an admission to the intensive care unit. 18

Regularly updating the patients’ family ensured cooperation, empathy and sympathy. The patients’ stroke was not seen as a priority given the severity of his COVID-19 pneumonia, therefore the least invasive, but most appropriate treatment was provided for his stroke. The British Association of Stroke Physicians advocate this approach and also request the notification to their organisation of COVID-19-related stroke cases, in the UK. 19

Learning points

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is one of seven known coronaviruses that commonly cause upper and lower respiratory tract infections. It is the cause of the 2019–2020 global coronavirus pandemic.

The significance of COVID-19 is illustrated by the rapid speed of its spread globally and the potential to cause severe clinical presentations, such as ischaemic stroke.

Early retrospective data has indicated that up to 36% of COVID-19 patients had neurological manifestations, including stroke.

Potential mechanisms behind stroke in COVID-19 patients include a plethora of hypercoagulability secondary to critical illness and systemic inflammation, the development of arrhythmia, alteration to the vascular endothelium resulting in atherosclerotic plaque displacement and dehydration.

It is vital that effective, open communication between the multidisciplinary team, patient and patients relatives is conducted early in order to firmly establish the most appropriate ceiling of care for the patient.

• Cannine M , et al
• Wunderink RG
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Contributors SB was involved in the collecting of information for the case, the initial written draft of the case and researching existing data on acute stroke and COVID-19. He also edited drafts of the report. MH was involved in reviewing and editing drafts of the report and contributing new data. SP oversaw the conduction of the project and contributed addition research papers.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests None declared.

Patient consent for publication Next of kin consent obtained.

Provenance and peer review Not commissioned; externally peer reviewed.

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Neurotherapy for stroke rehabilitation: A single case study

• Published: September 1995
• Volume 20 , pages 211–228, ( 1995 )

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• George R. Rozelle 1 &
• Thomas H. Budzynski 1  

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A 55-year-old male subject was treated with a two-tiered neurotherapy approach for a period of six months beginning approximately one year after a left-side CVA. Medical evaluation revealed left posterior temporal/parietal infarctions secondary to occlusion of the left internal carotid artery. The patient complained of hesitant speech with word finding difficulty and paraphasia, difficulty focusing his right eye, lack of balance and coordination, poor short-term memory, poor concentration, anxiety, depression, and tinnitus. A quantitative electroencephalograph (QEEG) analysis revealed increased left-side 4–7-Hz activity and alpha persistence on eye opening. Two neurotherapy approaches were used beginning with electroencephalographic entrainment feedback (EEF). This was followed by neurofeedback to inhibit 4–7 Hz and increase 15–21 Hz over sensorimotor and speech areas. At the conclusion of treatment there were significant reductions in slow-wave activity. Improvement was evident in speech fluency, word finding, balance and coordination, attention, and concentration. Depression, anxiety, and tinnitus were greatly reduced.

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Anabasis, Sarasota, Florida, and Center for Behavioral Medicine, University of West Florida, 2477 Stickney Point Road, Suite 319-B, 34231, Pensacola, Sarasota, Florida, USA

George R. Rozelle & Thomas H. Budzynski ( Visiting Scholar/Scientist )

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This study was made possible through a grant from Margaret S. Buzzelli to support the study of Innovations in the Restoration and Development of the Sense of Self at Anabasis. The authors wish to acknowledge the contribution of Timothy Hallinan, Ph.D., for providing neuropsychological testing; Phyllis Joseph, M.S., C.C.C., and Nelda Foster, Speech Language Pathologist, for providing speech evaluations; and Philip Reed and Tom Allen, who provided invaluable technical assistance. Preparation of this manuscript was supported in part by grant No. NS-29855 from The National Institute of Neurological Disorders and Stroke.

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Rozelle, G.R., Budzynski, T.H. Neurotherapy for stroke rehabilitation: A single case study. Biofeedback and Self-Regulation 20 , 211–228 (1995). https://doi.org/10.1007/BF01474514

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DOI : https://doi.org/10.1007/BF01474514

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Virtual reality and haptics as a training device for movement rehabilitation after stroke: a single-case study

Affiliation.

• 1 Mednet, Göteborg, Sweden. [email protected]
• PMID: 15295748
• DOI: 10.1016/j.apmr.2003.09.020

Objective: To investigate whether training in a virtual environment with a haptic device will improve motor function in the left hemiparetic arm of a stroke subject.

Design: Single case, A-B-A design.

Setting: University hospital research laboratory.

Participant: A man in his late fifties (right handed), with a right-hemisphere lesion that caused a deficit in the left upper extremity.

Intervention: The subject trained with a 3-dimensional computer game during a 4-week period that consisted of twelve 90-minute sessions.

Main outcome measures: Three tests (Purdue pegboard test, dynamometer hand-grip strength, upper-extremity test) and a subjective interview were used to evaluate motor performance.

Results: Improvements were found in fine manual dexterity, grip force, and motor control of the affected upper extremity. The subject reported that there was a change in his day-to-day use of the upper extremity and that he was able to use it in activities that were previously impossible for him.

Conclusions: Training with virtual reality and haptics can promote motor rehabilitation.

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