Infection is an independent risk factor for both ischemic and hemorrhagic stroke

By Jerome H. Chin, MD, PhD, MPH

Jerome H. Chin, MD, PhD, MPH

Stroke is the third-leading cause of premature death globally as measured in years of life lost¹.  Demographic and epidemiologic changes, including population growth and aging, urbanization and unhealthy diets are driving a rise in the incidence of stroke in low- and middle-income countries (LMIC)². Due to inadequate primary health care services to screen for and treat the most common stroke risk factors, particularly hypertension and diabetes, the age-standardized incidence rates of stroke in LMIC exceed those in high-income countries². In addition, strokes due to atrial fibrillation and rheumatic heart disease contribute a significant share of the stroke burden in LMIC as a result of both diagnostic and therapeutic resource limitations for these conditions.

Figure. HIV-associated stroke: (a) middle cerebral artery infarct; 25-year-old HIV-infected male, CD4+ cell count = 42 cells/mm3; (b) bilateral basal ganglia infarcts; 25-year-old HIV-infected female, unknown CD4+ cell count.

HIV infection has recently emerged as an independent risk factor for both ischemic and hemorrhagic stroke^3-8. Two cohort studies conducted in the United States reported an elevated risk of ischemic stroke in HIV-infected individuals compared to non-HIV-infected individuals^4,5. Lower CD4+ cell counts or higher HIV RNA levels were associated with an increased risk of stroke. Cohort studies from Canada and the United States have reported an association of HIV infection with an increased risk of intracerebral hemorrhage^6,7. A community-based case-control study performed in Tanzania found HIV infection to be an independent risk factor for stroke (ischemic and hemorrhagic combined) with an adjusted odds ratio of 5·61⁸. Only 40 percent of the 200 stroke cases had a CT scan. The pathogenic mechanisms responsible for the increased risk of stroke associated with HIV infection are multiple and may include chronic inflammation and immune activation leading to endothelial dysfunction and subsequent vasculopathy^3,9. Both small-vessel (e.g. lacunar) and large-vessel strokes are observed in HIV-infected individuals (figure) in addition to intracerebral hemorrhages.

Thirty-five million people are living with HIV worldwide¹⁰. The population-attributable risk of stroke due to HIV infection will depend on the prevalence of HIV infection in a particular region or country. Given the higher prevalence of HIV infection in sub-Saharan Africa compared to other regions, a substantial number of incident strokes in sub-Saharan Africa may be the result of HIV infection. However, reliable figures for stroke incidence, mortality and comorbidities are difficult to obtain in most countries of sub-Saharan Africa due to inadequate stroke surveillance and vital registration data. The above-mentioned epidemiologic studies provide support for the inclusion of HIV antibody testing in the diagnostic evaluation of patients with acute stroke in all regions of the world. Furthermore, stroke prevention should now be considered another potential benefit of the early initiation of antiretroviral therapy in HIV-infected individuals through both a reduction in HIV-associated vasculopathy as well as through the prevention of HIV transmission to their uninfected partners.

References

1. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385:117-171.
2. Krishnamurthi RV, Feigin VL, Forouzanfar MH, et al. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet Glob Health. 2013;1(5):e259-e281. doi:10.1016/S2214-109X(13)70089-5.
3. Cole JW, Chin JH. HIV infection: a new risk factor for intracerebral hemorrhage? Neurology. 2014;83:1690-1.
4. Marcus JL, Leyden WA, Chao CR, et al. HIV
   infection and incidence of ischemic stroke, AIDS. 2014;28:1911–1919.
5. Chow FC, Regan S, Feske S, Meigs JB, Grinspoon SK, Triant VA. Comparison of ischemic stroke incidence in HIV-infected and non-HIV-infected patients in a U.S. health care system. J Acquir Immune Defic Syndr. 2012;60:351-358.
6. Chow FC, He WS, Bacchetti P, et al. Elevated rates of intracerebral hemorrhage in individuals from a U.S. clinical care HIV cohort. Neurology. 2014;83:1705–1711.
7. Durand M, Sheehy O, Baril JG, LeLorier J, Tremblay CL. Risk of spontaneous intracranial hemorrhage in HIV infected individuals: a population-based cohort study. J Stroke Cerebrovasc Dis. 2013;22:e34–e41.
8. Walker RW, Jusabani A, Aris E, et al. Stroke risk factors in an incident population in urban and rural Tanzania: a prospective, community-based, case-control study. Lancet Glob Health. 2013;1:e282–e288.
9. Benjamin LA, Bryer A, Emsley HCA, Khoo S, Solomon T, Connor MD. HIV infection and stroke: current perspectives and future directions. Lancet Neurol. 2012;11:878–90.
10. UNAIDS, The Gap Report, available at: http://www.unaids.org/en/resources/campaigns/2014/2014gapreport/gapreport/ Accessed January 25,  2015.

The European Board Examination in Neurology is a joint development of the UEMS Section of Neurology and the European Academy of Neurology. It is considered to be a tool for the assessment of European neurological education and to boost its European standards.

It is supervised by the examination committee of the UEMS/EBN and also observed by the EAN representing the European neurological scientific societies and the World Federation of Neurology.

The exam was held in 2009 for the first time, and since then 130 candidates have passed the exam. Beginning in 2015, the title “Fellow of the European Board of Neurology” will be conferred to European and non-European candidates.

The next UEMS/EBN examination will be organized one day prior to the 1st Congress of the European Academy of Neurology (EAN) on Friday, June 19, 2015, in Berlin, Germany. (http://www.eaneurology.org/)

The European Board Examination in Neurology is a substantial step forward in the further harmonization and in the raising of the standards in European neurology. The cooperation with the scientific neurological societies is an important scientific input and a guarantee of continuous updates of the current knowledge of a European neurologist.

The European Examination in Neurology is a proof of excellence: Taking the examination shows the candidate’s commitment to lifelong learning. Even without legal recognition, this is known and recognized within the profession throughout Europe and the rest of the world, thus encouraging the mobility of specialists in neurology and giving an additional distinguishing mark to the individual candidate.

The deadline for application is the May 1, 2015. (http://www.uemsneuroboard.org/ebn/)

There is a reduced fee for candidates from low- and lower-middle income countries (see http://data.worldbank.org/about/country-and-lending-groups#Low_income) and for those who follow the early-bird registration procedure.

The examination consists of the following parts:

• 80 MCQs (multiple choice questions)
• 50 EMQs (extended matching question)
• A short essay on a neurology-related public health or ethics-related topic to be orally discussed with the examiners.
• A critical appraisal of a neurological topic to be discussed with the examiners.

Results of these four parts of the examination will be combined to one final mark.

We are happy to note that the number of participants taking the European Board Exam in Neurology is increasing year by year, and we aim to develop an exam that will be taken by all neurology trainees, particularly those who wish to extend their experience beyond the borders of their own country.

Any questions and comments can be sent to uems-sbn@medacad.org

Professor Dr. Jan Kuks: Chair of the examination committee: j.b.m.kuks@umcg.nl

Professor Dr. Wolfgang Grisold: UEMS/EBN past chair of the examination committee wolfgang.grisold@wienkav.at

Dr Walter Struhal: WFN website and social media, w.struhal@aesculapian.net

CONTACT address:

Mag.Gabrielle Lohner: uems-sbn@medacad.org

Section of Neurology –European Board of Neurology
c/o Vienna Medical Academy
Alser Strasse 4, 1090 Vienna
AUSTRIA
T (+43 1) 405 13 83 – 32
F (+43 1) 407 82 74
www.uems-neuroboard.org

Fellowship program builds skills for health practitioners

By Jo Wilmshurst, MD

Doctors trained in the management of child neurology conditions are lacking in Africa^1,2. Epilepsy is one of the major disease burdens in the continent and training in this area is even more scarce. EEG interpretation in children is very different to that for adults and grave errors can occur in patient management when misinterpretations occur.

The African Paediatric Fellowship Program (APFP) is a project developed by the Department of Paediatrics and Child Health at the Red Cross War Memorial Children’s Hospital, under the University of Cape Town in South Africa, to build skills capacity of health practitioners from Africa. The center is the largest dedicated children’s hospital in sub-Saharan Africa. Children are managed across primary to quaternary levels of care with the spectrum of diseases prevalent in Africa.

Figure 1. Some of the 2014 APFP fellows attending the end-of-year discussion group. Dr. Kija, child neurology trainee from Tanzania, is fourth from the left. Represented in the group are doctors training in areas from pediatric urology to pediatric rheumatology from areas in Africa inclusive of Uganda, Zambia, Kenya, Ghana, Zimbabwe and Malawi. The group remains as a cohesive support network and stay in contact after completion and following their return home.

The APFP formed collaborations with tertiary centers across Africa and has assisted their identification of strategic training requirements based on their countries’ key health care needs. Structured training occurs at the pediatric units through the University of Cape Town. More than 65 specialists have completed, or are completing in 2015, the training program in diverse pediatric areas, referred from 33 centers in 12 different African countries. There has been a 98 percent retention rate of trainees returning to work in their home country since 2008. The program is evolving with training arms supporting nursing and ancillary services. The trainee becomes the trainer in his or her home center, and a key opinion leader equipped to lobby for changes to health care policy (Figure 1).

The grant provided by the WFN to support neurology training in 2013 has enabled the focused training for six general pediatricians from different centers in Nigeria, and three further trainees from Zimbabwe, who manage large caseloads of children with neurodisabilities and epilepsy. The University of Cape Town rolled out in 2015 a post-graduate diploma in “basic electrophysiology interpretation and the management of children with epilepsy.” This requires one-on-one training with a focus on areas relevant to the African context. The aim of the post-graduate diploma is to establish safe practice and not to train accredited epileptologists. In Africa, most child health practitioners who manage children with neurologic disorders must address the comprehensive needs of the child inclusive of the other health issues, such as co-infections, nutritional deficits, and social challenges (Figures 2 a, b).

At the current time in most African settings, it is not viable to work as an epileptologist without addressing these other health care issues (Figures 3 a, b). However as a result of more cost-effective neurophysiology equipment, and through equipment donations, there are an increasing number of EEG machines that are potentially being operated and interpreted by health practitioners with no pediatric training. This training program was devised out of the needs that this situation created. The audit of the preliminary findings of a pilot study on the impact of the training course while it was being established is in press. The audit confirmed that access to a basic handbook improved EEG interpretation skills, but that the optimal outcomes were seen in those doctors who had additional one-on-one training.

a.) Children attending the neurology clinic at Red Cross War Memorial Children’s Hospital, enjoying a donation of new reading books. b.) One of the neurology patients occupied in puzzle play in the waiting area.

Between 2013 and 2014, three doctors from Nigeria, Tanzania and Ghana entered the APFP for formal training to become accredited child neurologists. Tanzania has no accredited child neurologists and Ghana has two. These trainees, in addition to completing the full post-graduate clinical master’s degree in child neurology, also are completing research in areas relevant to the context they work in. The doctor from Tanzania is heading a prospective study to review the effects on bone mineral density in children on antiepileptic drugs in the African setting. Vitamin D supplementation is not part of standard care of these patients and it is hoped that the findings from this study will lead to data to support lobbying for this intervention to be part of standard practice. The doctor from Ghana will complete a study assessing the neurobehavioral influences on children from antiretroviral therapy. The doctor from Nigeria has completed a large prospective study assessing the efficacy of attaining sleep EEGs in children using melatonin.

In the next training cycle it is hoped that there will be funding to support applicants from Sierra Leone, Zimbabwe, Uganda, Kenya, Sudan and Zambia.

The training curriculum, while in line with international templates, also accommodates approaches novel to Africa, such as the neurological care for children with tuberculous meningitis, HIV, malaria and neurocysticercosis. The perinatal complication rates remain high in Africa with significant numbers of neonates suffering hypoxic ischaemic encephalopathy. Other neuroinsults are seen from the effects of central nervous system infections and motor vehicle accidents. The training must accommodate these areas in depth as well. The returning trainee must often function in all areas from social welfare to rehabilitation, the training is adjusted for this.

a.) Mothers attending the Queen Elizabeth Hospital, Blantyre, in Malawi, taken during an APFP site visit in 2013. This is the main teaching hospital in the country, which has one pediatric neurologist for the total population. b.)
Child-care workshop for children with motor disabilities at the Child Rehabilitation Unit, Harare Hospital, Zimbabwe, taken during the APFP site visit to the referring units in the country in 2014.

Prevention and early intervention is one of the major aims for this project and all trainees in the program are facilitated in the knowledge gained during their training and assess its relevance to their home setting, how to introduce these skills to the optimal benefit to child health care and how these interventions can extend across all levels of health care—from primary to tertiary.

On the trainee’s return to their home center they maintain contact with their supervisor, and site visits are scheduled as needed to provide local input into service development and local training (Figure 3 a, b). Research collaborations also continue. These trainees are having a real impact in their home centers and are becoming voices in Africa lobbying to promote child health. One of the child neurology trainees who completed training in 2009 and returned to Kenya now sits on the national Kenyan pediatric body, assists selection of ongoing APFP trainees referred from the country, and is also on the Pediatric Commission for the International League Against Epilepsy. This trainee is part of a team developing its own subspecialty training program for East African doctors. This is viewed as a major future aim of the APFP. In order to grow and to fulfill the health care needs for the continent, more training sites are needed. It is important these remain within Africa with training relevant to the diseases of the region. There is much to learn from the approaches many innovative African centers undertake to cope with the challenges of scare resources.

While training experience in overseas centers offers obvious gains in skills development, the local relevance of the training may be questionable and the risk of the “brain drain” is high. A number of overseas specialists have opted to spend time working, training and lecturing in African centers. This is a superb way to assist skills development in African centers. Building on these relationships with regular visits develops sustained skills where often none existed before.

References

1. Wilmshurst JM, Badoe E, Wammanda RD, Mallewa M, Kakooza-Mwesige A, Venter A, Newton CR. Child neurology services in Africa. J Child Neurol. 2011 Dec; 26(12):1555-63.
2. Wilmshurst JM, Cross JH, Newton C, Kakooza AM, Wammanda RD, Mallewa M, Samia P, Venter A, Hirtz D, Chugani H. Children With Epilepsy in Africa: Recommendations From the International Child Neurology Association/African Child Neurology Association Workshop. J Child Neurol. 2013; 28 633-644