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Challenges of stroke management in resource-limited settings: A case-based reflection

Yohane G. Gadama1, Gloria Mwangalika2, Louis B. Kinley3, Beth Jackson1, Henry C. Mwandumba2,4, Jane Mallewa5, Tom Solomon6, Rob Simister7, Laura Benjamin6,7, Maria I. Vargas8, Joseph Kamtchum-Tatuene2,6, Tamara Phiri5


1. Department of Medicine, Queen Elizabeth Central Hospital, Blantyre, Malawi

2. Malawi–Liverpool–Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi

3. Department of Radiology, Queen Elizabeth Central Hospital, Blantyre, Malawi

4. Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom

5. Department of Medicine, College of Medicine, University of Malawi, Blantyre, Malawi

6. Liverpool Brain Infections Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom

7. Hyper-acute Stroke Unit, University College of London Hospital, London, United Kingdom

8. Department of Neuroradiology, Geneva University Hospital, Geneva, Switzerland

Correspondence: Dr Joseph Kamtchum-Tatuene (tatuene@liverpool.ac.uk)


 Abstract

A 19-year-old man presented with a one-year history of headache, generalized body weakness, progressive memory loss and disorientation. One month prior to admission, there was aggravation of the weakness of the right upper limb with new onset difficulty to masticate food, speech impairment, apathy, and urinary incontinence. On clinical examination, the patient had a motor aphasia and a right-sided hemiparesis with increased muscle tone and hyperreflexia. A non-contrast brain CT-scan revealed large ischaemic strokes extending beyond the classical vascular territories. The cerebrospinal fluid analysis showed a mildly increased protein level. The electrocardiogram revealed an irregular sinus bradycardia. The remainder of the cardiovascular and laboratory workup was unremarkable. Considering a working diagnosis of central nervous system vasculitis, the patient was treated with acetylsalicylic acid, prednisolone, and physiotherapy. However, a sudden death occurred a few weeks later. Based on this case, we discuss the challenges of stroke management in resource-limited settings, provide practical tips for general practitioners, reflect on the potential avenues for short and long term action and introduce the budding collaboration platform between the University College of London, the University of Liverpool, the Queen Elizabeth Central Hospital and the Malawi-Liverpool-Wellcome Trust Clinical Research Programme.


Introduction

Stroke is the most common cause of disability and the second most common cause of death worldwide, after ischaemic heart diseases.1 In Malawi, it is the 6th biggest killer after infectious diseases.2 Although more common in the elderly, stroke also affects young adults and recent data suggest an increasing incidence of ischaemic stroke in young adults, with significant adverse socioeconomic consequences.3 Furthermore, stroke in young adults (those younger than 45 years of age) is often initially misdiagnosed by inexperienced clinicians because of its unexpectedness, leading to lost opportunities for intervention.4,5 In high-income countries, stroke is labelled as cryptogenic in up to one-third of cases.6–8 The challenge of appropriate diagnosis and management of stroke is even greater in low-income countries where there is a dearth of basic equipment, trained personnel, and specific drugs. In this paper, through a case managed at Queen Elizabeth Central Hospital (QECH) in Blantyre, we discuss the challenges of stroke management in resource-limited settings, provide practical tips for general practitioners, and reflect on the potential avenues for short- and long-term action.

QECH, which is Malawi’s largest referral hospital, does not house a stroke unit; therefore, all stroke cases are managed within the internal medicine department. The hospital has a Magnetic Resonance Imaging (MRI) department, the construction of which was funded by the Blantyre Malaria Project.9 However, computed tomography (CT) is only accessible in Lilongwe, the capital city, which is over 350 km away. There are in-house radiologists but neurology, neurosonology, and neuroradiology expertise is only provided sporadically by visiting researchers.

Case presentation

A 19-year-old man presented with a one-year history of persistent headache of variable intensity, associated with generalized body weakness, progressive memory loss and disorientation with the patient being unable to find his way back home whenever he went out of the house. One month prior to admission, there was an aggravation of the weakness of the right upper limb with new onset difficulty to masticate food, speech impairment, excessive sleepiness, and urinary incontinence. During the course of the disease, the patient had been hospitalized several times and treated for meningitis, cerebral malaria or psychosis without clear evidence for these diagnoses. There was no fever, no seizures, no vomiting, and no visual symptoms. There was no history of hypertension, diabetes mellitus, or consumption of tobacco, alcohol or drugs.

On clinical examination, the patient was found apathetic with a Glasgow Coma Scale score of 14 (eye opening to verbal command). He had a motor aphasia with right-sided hemiparesis, increased muscle tone and brisk reflexes without clonus or Babinski’s sign.

A non-contrast brain CT-scan revealed multiple large hypodense lesions extending beyond the classical vascular territories and involving the lenticular nucleus and the frontal operculum on the right, the insula and the frontal lobe on the left and both putamen and temporal lobes. The lesions were suggestive of recurrent ischaemic strokes and the one in the left frontal lobe seemed more recent and associated with a mild haemorrhagic transformation (Figure 1).

fig 1

The full blood count, the liver function tests, the random blood sugar and the HIV and syphilis serological tests were unremarkable. The cerebrospinal fluid analysis revealed a mild increase of the protein level (0.66 g/L; normal range: 0.2–0.4) but a normal white blood cell count (1/mm3; normal range: 0–5). The carotid-vertebral ultrasound was unremarkable. The transcranial Doppler could not be performed because there was no temporal window. The electrocardiogram revealed a sinus bradycardia (56 beats per minute) with supraventricular extrasystoles. The transthoracic cardiac ultrasound showed a mild dilatation of the right atrium but there was no valvulopathy, no myxoma, and no intracardiac thrombus. There was no sign of right-to-left shunt, even after microbubble injection at rest (the patient could not perform the Valsalva manoeuvre).

Considering a working diagnosis of recurrent strokes secondary to central nervous system vasculitis, the patient was started on oral low dose Aspirin (75 mg/day) and Prednisone (60 mg/day). He was also offered some physiotherapy. A brain MRI (0.35 Tesla) without contrast performed 2 weeks after admission did not show any additional lesion. He was discharged with a schedule for a close neurological follow-up. However, the patient’s parents reported his sudden death two weeks later.

Discussion

The patient described in this report was diagnosed with recurrent strokes but the young age, the atypical presentation (chronic headache and alteration of cognitive functions with focal neurological symptoms only appearing at a later stage), the absence of cardiovascular risk factors (diabetes mellitus, hypertension, obesity, smoking, dyslipidaemia), the absence of HIV infection, and the limited accessibility of brain imaging techniques led to recurrent misdiagnosis with ensuing failure to initiate adequate preventative therapy. At first sight, given the distribution of lesions in space (bilateral with cortical involvement) and in time (lesions of different ages), one could think of cardioembolism as the primary mechanism of the ischaemic lesions. However, their size, confluence, and extension beyond classical vascular territories tends to speak against this hypothesis and would rather suggest either a primary or secondary central nervous system vasculitis, a coagulopathy, or a metabolic or mitochondrial encephalopathy.

Besides radiological findings, other arguments in favour of a primary central nervous system vasculitis would be the presence of a chronic headache which is the most common symptom, the insidious progression of the disease, the presence of cognitive impairment which is the second most common symptom, the absence of constitutional symptoms (fever, weight loss, night sweating) as would be seen in systemic vasculitides, and the high protein level in the cerebrospinal fluid.10,11 A coagulopathy seems less probable in the absence of past or present thrombotic events in other organs or episodes of abnormal bleeding but a definitive conclusion would request a comprehensive assessment of the coagulation profile. The negative family history, the absence of myopathy, and the normal psychomotor development do not support the diagnosis of mitochondrial encephalopathy but genetic tests would be needed to formally rule out a sporadic case with atypical presentation. Thus, given the limited investigation resources, the final cause of the recurrent strokes remains uncertain. The irregular bradycardia found on admission could be related the lesions of the left insula. Association between insular lesions and arrhythmias have been consistently demonstrated with left insular lesions most often causing bradycardia.12 These perturbation of the cardiac rhythm are a candidate culprit for the patient’s sudden death in the absence of a pacemaker.

MMJ_29_2_Gadama CR_Table 1a_170808.pages

MMJ_29_2_Gadama CR_Table 1b_170808.pages

MMJ_29_2_Gadama CR_Table 1c_170808.pages

MMJ_29_2_Gadama CR_Table 2_170808.pages

This case illustrates a few of the numerous diagnostic and therapeutic challenges related to stroke diagnosis and management in resource-limited settings as summarized in Table 1. A few practical messages could be formulated for clinicians on the frontline. First, stroke could occur at all ages and should not be considered as a disease of the elderly. In children and young adults, the clinical presentation is often atypical with chronic headache, seizures and neurobehavioral symptoms.13 Hence, a thorough neurological examination must always be performed to look for discrete signs pointing toward a structural brain lesion, notably speech disturbance, sensory deficit, abnormal or asymmetric muscle tone or reflexes and the threshold for brain imaging should be low. The identification of the aetiology of stroke in young adults is more challenging because on one hand, classical cardiovascular risk factors are usually absent and on the other hand, the numerous alternative causes are rare conditions that are difficult to diagnose in low-to-middle income countries. In order to draw the best of the limited resources at disposal, clinicians should use a stepwise approach based on epidemiological data and specific clinical clues presented in Table 2. Advice should be sought from a physician with expertise in stroke medicine whenever possible, especially for patients with recurrent and/or cryptogenic strokes.

 

While waiting for a substantial improvement of their economic condition, some simple solutions could be implemented to improve stroke care in low-to-middle income countries like Malawi. These include raising population awareness about stroke symptoms and risk factors using well-designed communication strategies,14 investing in telemedicine for teaching and cases management,15,16 and strengthening the partnership with high-income countries for the financial, logistic and training support. There are ongoing discussions between the University College of London Hospital, the University College of London and the University of Liverpool on one side, and the Queen Elizabeth Central Hospital and the Malawi-Liverpool-Wellcome Trust Clinical Research Programme on the other side, in order to design a collaborative platform to address some of these challenges in the short term.17 The actions implemented will aim to improve clinical care through the creation of a stroke unit as well as support local stroke research and staff training.

Acknowledgements

The authors are grateful to the patient and his parents for granting the permission to use their medical information for teaching and scientific publication.

Competing interests

All authors declare that they have no competing interests related to this work.

References

1.WHO. Top 10 causes of death – Fact sheet N°310 Geneva: WHO Press; 2017 [updated January 2017; cited 2017 04 July ]. Available from: http://www.who.int/entity/mediacentre/factsheets/fs310/en/index.html#.

2.Mahawish KM, Heikinheimo T. Stroke in Malawi–what do we know about it and how should we manage it? . Malawi Med J 2010;22(1):24-28.

3.Bejot Y, Delpont B, Giroud M. Rising Stroke Incidence in Young Adults: More Epidemiological Evidence, More Questions to Be Answered. J Am Heart Assoc 2016;5(5).

4.Sultan S, Elkind MS. The growing problem of stroke among young adults. Curr Cardiol Rep 2013;15(12):421.

5.Griffiths D, Sturm J. Epidemiology and etiology of young stroke. Stroke Res Treat 2011;2011:209370.

6.Calvet D. [Ischemic stroke in the young adult]. Rev Med Interne 2016;37(1):19-24.

7.Saver JL. Cryptogenic Stroke. N Engl J Med 2016;375(11):e26.

8.Li L, Yiin GS, Geraghty OC, et al. Incidence, outcome, risk factors, and long-term prognosis of cryptogenic transient ischaemic attack and ischaemic stroke: a population-based study. Lancet Neurol 2015;14(9):903-913.

9.Mwendera CA, de Jager C, Longwe H, Hongoro C, Mutero CM, Phiri KS. Malaria research in Malawi from 1984 to 2016: a literature review and bibliometric analysis. Malar J 2017;16(1):246.

10.Bhattacharyya S, Berkowitz AL. Primary angiitis of the central nervous system: avoiding misdiagnosis and missed diagnosis of a rare disease. Pract Neurol 2016;16(3):195-200.

11.Salvarani C, Brown RD, Jr., Hunder GG. Adult primary central nervous system vasculitis. Lancet 2012;380(9843):767-777.

12.Oppenheimer S. Cerebrogenic cardiac arrhythmias: cortical lateralization and clinical significance. Clin Auton Res 2006;16(1):6-11.

13.Singhal AB, Biller J, Elkind MS, et al. Recognition and management of stroke in young adults and adolescents. Neurology 2013;81(12):1089-1097.

14.Nansseu JR, Atangana CP, Petnga SN, Kamtchum-Tatuene J, Noubiap JJ. Assessment of the general public’s knowledge of stroke: A cross-sectional study in Yaounde, Cameroon. J Neurol Sci 2017;378:123-129.

15.Bediang G, Perrin C, Ruiz de Castaneda R, et al. The RAFT Telemedicine Network: Lessons Learnt and Perspectives from a Decade of Educational and Clinical Services in Low- and Middle-Incomes Countries. Front Public Health 2014;2:180.

16.Noubiap JJ, Kamtchum-Tatuene J, Nganou-Gnindjio CN, Jingi AM. The Cardio-PadTM project: progress and remaining challenges. Cardiovasc Diagn Ther 2017;7(1):98-101.

17.Benjamin LA. Sharing expertise in stroke in Malawi Liverpool: University of Liverpool; 2017 [updated 11 May 2017; cited 2017 17 June]. Available from: https://news.liverpool.ac.uk/2017/05/11/sharing-expertise-stroke-malawi/.

18.Duarte MM, Geraldes R, Sousa R, Alarcao J, Costa J. Stroke and Transient Ischemic Attack in Takayasu’s Arteritis: A Systematic Review and Meta-analysis. J Stroke Cerebrovasc Dis 2016;25(4):781-791.

19.Morris NA, Matiello M, Lyons JL, Samuels MA. Neurologic complications in infective endocarditis: identification, management, and impact on cardiac surgery. Neurohospitalist 2014;4(4):213-222.

20.Wang D, Liu M, Lin S, et al. Stroke and rheumatic heart disease: a systematic review of observational studies. Clin Neurol Neurosurg 2013;115(9):1575-1582.

21.Benjamin LA, Bryer A, Emsley HC, Khoo S, Solomon T, Connor MD. HIV infection and stroke: current perspectives and future directions. Lancet Neurol 2012;11(10):878-890.

22.Benjamin LA, Corbett EL, Connor MD, et al. HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults: A case-control study. Neurology 2016;86(4):324-333.

23.Gutierrez J, Albuquerque ALA, Falzon L. HIV infection as vascular risk: A systematic review of the literature and meta-analysis. PLoS One 2017;12(5):e0176686.

24.Cowan LT, Alonso A, Pankow JS, et al. Hospitalized Infection as a Trigger for Acute Ischemic Stroke: The Atherosclerosis Risk in Communities Study. Stroke 2016;47(6):1612-1617.

25.Miller EC, Elkind MS. Infection and Stroke: an Update on Recent Progress. Curr Neurol Neurosci Rep 2016;16(1):2.

26.Minassian C, Thomas SL, Smeeth L, Douglas I, Brauer R, Langan SM. Acute Cardiovascular Events after Herpes Zoster: A Self-Controlled Case Series Analysis in Vaccinated and Unvaccinated Older Residents of the United States. PLoS Med 2015;12(12):e1001919.

27.Piel FB, Steinberg MH, Rees DC. Sickle Cell Disease. N Engl J Med 2017;376(16):1561-1573.

28.Switzer JA, Hess DC, Nichols FT, Adams RJ. Pathophysiology and treatment of stroke in sickle-cell disease: present and future. Lancet Neurol 2006;5(6):501-512.

29.Tuinenburg A, Mauser-Bunschoten EP, Verhaar MC, Biesma DH, Schutgens RE. Cardiovascular disease in patients with hemophilia. J Thromb Haemost 2009;7(2):247-254.

30.Miller EC, Gatollari HJ, Too G, et al. Risk Factors for Pregnancy-Associated Stroke in Women With Preeclampsia. Stroke 2017;48(7):1752-1759.

31.Cheng YC, Ryan KA, Qadwai SA, et al. Cocaine Use and Risk of Ischemic Stroke in Young Adults. Stroke 2016;47(4):918-922.

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