International Congress in The Capital of Scandinavia

The 18th International Congress of Parkinson’s Disease and Movement Disorders was hosted this year in the beautiful city of Stockholm, Sweden on June 8-12, 2014. As the city known for hosting the Nobel Prize winners, Stockholm was the perfect location for delegates to learn about the latest research, and perspectives in the field of Movement Disorders and to network and collaborate with colleagues. Everyone’s participation made for several highlights during the week:

• 4,500 total people registered (including press and exhibitors)
• 86 countries represented
• 100 travel grants awarded by MDS
• 196 faculty members participated in the Scientific Sessions
• 1,558 posters accepted
• 34 late-breaking posters accepted
• 17 MDS study group abstracts accepted
• 4 therapeutic plenary sessions
• 9 plenary sessions
• 24 parallel sessions
• 8 teaching courses
• 24 video sessions and skills workshops
• 16 guided poster tours
• 28 companies exhibited
• 23 representatives from the press attended

Under the direction of Dr. Victor Fung, the Congress Scientific Program Committee (CSPC) made every effort to ensure that the science for the 18th International Congress was diverse and educational.  The 2014 Scientific Program incorporated therapeutic plenary sessions, plenary and parallel sessions, teaching courses, video sessions, skills workshops, controversies, blue ribbon highlights, poster sessions and guided poster tours.  There were 13 sessions focused on this year’s theme of “Emerging and Experimental Therapies,” which gave participants an educational and comprehensive overview on the subject.

A unique session was introduced this year to the Scientific Program called, “Late-Breaking Clinical and Scientific Topics Relevant to Movement Disorders.” This parallel session was designed to help participants understand and appreciate the latest clinical and scientific discoveries relevant to movement disorders, as well as understand the role of new clinical discoveries for basic science and understand the role of new basic science discoveries for clinical progress.

Also of note was the Movement Disorders Grand Rounds Parallel Session. In this interactive session, volunteer patients with a known complex movement disorder were presented to one of four movement disorder “experts.” This year’s experts included Bastiaan Bloem (Netherlands); David John Burn (United Kingdom); Beom Jeon (Korea) and Claudia Trenkwalder (Germany). The patient’s history and clinical findings (including video of the movement disorder) were presented by the expert, who then reviewed the history with the patient and highlighted and demonstrated the neurological signs to the audience. The expert’s job is to generate a differential diagnosis and management plan which can be critiqued by his/her fellow experts, the audience and the chairs. The final diagnosis and learning point were then presented after the expert and audience discussion was finished. The session showed how a movement disorders expert takes a clinical history and performs a movement disorders examination of a patient to generate a diagnosis and a management plan.

The always popular video challenge was held on Wednesday night with Masters of Ceremony Anthony Lang and Kapil Sethi. A world-renowned panel of Movement Disorders experts including Victor Fung (Australia); Orlando Barsottini (Brazil); Daniel Healy (Ireland); Björn Holmberg (Sweden) and David Riley (U.S.) guided participants through unique Movement Disorder cases. The cases were presented by representatives from Movement Disorder Centers around the world and discussed by the Panel of Experts. Awards were given for the most interesting and challenging cases. The goal of this session was for attendees to learn from a series of unusual, very interesting patients and see how senior experts approach these types of challenging cases.

At the opening ceremony, President Matthew Stern distributed the following awards:

Honorary Member Awards:

• Anthony Lang, OC, MD, FRCPC, Toronto, ON, Canada
• William Weiner, MD, Baltimore, MD, U.S., President’s Distinguished Service Award:
• Esther Cubo, Burgos, Spain

The International Parkinson and Movement Disorder Society (MDS) would like to extend their gratitude to faculty, supporters, exhibitors and delegates for traveling to Stockholm and for helping make the 18th International Congress of Parkinson’s Disease and Movement Disorders another successful meeting.

Mark your calendars!  MDS is already planning for the 19th International Congress in San Diego, California, June 14-18, 2015.  Please visit our website for details regarding 2015 Congress at www.mdscongress2015.org or contact the International Secretariat at congress@movementdisorders.org with any
questions.

By John D. England, MD

John D. England, MD

The Journal of the Neurological Sciences (JNS) is a broad-based journal which publishes articles from a wide spectrum of disciplines, ranging from basic neuroscience to clinical cases.  In an upcoming issue of JNS, we will be acknowledging our peer reviewers.  The individuals whose names appear in the list have provided peer reviews of manuscripts which were submitted to JNS during the past year. This elite group of individuals from around the world includes some of the best and brightest minds in neuroscience and clinical neurology. They receive no remuneration for their work for the journal and take time from their busy schedules to review our articles.  All of the associate editors and I thank them for their indispensable work.  The journal would not survive without their expert advice. I express my most sincere gratitude to all of the reviewers.  They inform and enlighten all of us in the editorial office and help to make JNS a journal of the highest quality.

In our ongoing attempt to enhance accessibility of JNS articles to members of the World Federation of Neurology (WFN), we have selected two “free – access” articles, which are profiled in this issue of World Neurology.

In this issue, we feature two paired articles regarding the diagnostic accuracy of the famous Babinski sign:

1. Despite its legendary status, controversy exists regarding the diagnostic accuracy and usefulness of the Babinski sign in determining pyramidal tract dysfunction. Much of the variability in the assessment of the diagnostic accuracy of the Babinski sign is due to studies which do not follow simple but important methodological standards.  The paper by S.P. Isaza Jaramillo, et al. is exceptional in this regard. This paper describes a simple but methodologically rigorous study to ascertain the diagnostic accuracy of the Babinski sign for identifying pyramidal tract disease. One hundred and seven (107) patients with limb weakness were assigned a random identification number for blinding purposes. Two neurologists elicited a plantar response in each patient in a standardized manner.  The examination was performed in a blind and independent manner, and each examination was filmed to quantify intra-observer variability. The reference standard for diagnosis of pyramidal tract dysfunction was provided by a senior neurologist who examined every patient independently and had available the patient’s history, complete neurological examination, laboratory and neuroimaging results. Compared to the reference standard, the Babinski sign had a very high specificity of 99 percent (CI 97.7-100), but moderately low sensitivity of 50.8 percent (CI 41.5-60.1) in identifying pyramidal tract dysfunction.  These findings indicate that a Babinski sign elicited in a standardized manner by an experienced practitioner has high diagnostic accuracy for identifying pyramidal tract disease.  However, in view of the low sensitivity, the absence of a Babinski sign does not rule out pyramidal tract dysfunction. Jaramillo SPI, Uribe CSU, Jimenez FAC, Cornejo-Ochoa W, Restrepo JFA, Roman GC.  Accuracy of the Babinski sign in the identification of pyramidal tract dysfunction.  J Neurol Sci 2014;343:66-68.
2. In an editorial in the same issue of JNS, Austin Sumner provides an historical perspective on the Babinski sign and discusses the more recent controversy concerning its diagnostic usefulness. He concludes that the “confidence traditionally placed by clinicians on this simple test is justified” with the caveat that its absence does not rule-out pyramidal tract disease. Sumner AJ.  The Babinski sign.  J Neurol Sci 2014;343:2.

The Importance of Measuring Thyroid Function in the Expectant Mother

By Gustavo C. Román, M.D.

Encouraging news for the prevention of autism emerged from the results of a research study conducted by an international collaborative team conformed by Prof. Gustavo C. Román, MD, from the Methodist Neurological Institute (Houston, Texas) and researchers from the Generation R Study at Erasmus University Medical Centre in Rotterdam, The Netherlands, including Akhgar Ghassabian, MD, PhD; Jacoba J. Bongers-Schokking, MD, PhD; Vincent W.V. Jaddoe, MD, PhD; Albert Hofman, MD, PhD; Yolanda B. de Rijke, PhD; Frank C. Verhulst, MD, PhD;  and Henning Tiemeier, MD, PhD. The results point to the deficiency of maternal thyroid function during the first trimester of pregnancy as a significant factor in the causation of autism in the child.  Pregnant women with deficient thyroid hormone are nearly four times likelier to produce autistic children than women with normal thyroid function.  The study was published in the prestigious journal Annals of Neurology¹.

The research was conducted in a cohort of more than 4,000 Dutch mothers and their children, and it supports the view that autism can be caused by lack of maternal thyroid hormones T4, also called thyroxine, and T3, which is crucial to the migration of fetal brain cells during embryo development, early in pregnancy. The most common cause of thyroid hormone deficiency is a lack of dietary iodine, given that T4 contains four atoms of iodine. There are also environmental contaminants and dietary factors that affect thyroid function².

According to Prof. Román, the hypothesis linking thyroid and autism originated from his early experiences as a neurologist in the Andes of South America where the deficiency of iodine in table salt results in high prevalence of goiter and congenital problems in children including high rates of deafness, borderline mental retardation and, in the most severe cases, endemic cretinism. (See Figure 1.)  Román recently described this topic in detail³.

Iodine deficiency remains common throughout the world; including industrialized countries where it was believed to be eradicated by the use of iodinated salt.  This could explain the upward trend in the incidence of autism observed in these countries.  Another factor is the lack of determination of T4, T3 and urinary iodine levels in expectant mothers early in pregnancy, and the use of prenatal vitamin supplements lacking the extra supplementary iodine needed during pregnancy and lactation.

The complex gene network regulated by thyroid hormone during brain development is being deciphered with the use of experimental animal models⁴ and should provide a better understanding of the complex problem of autism spectrum disorders.

References

1. Román GC, Ghassabian A, Bongers-Shokking JJ, et al. Association of gestational maternal hypothyroxinemia and increased autism risk. Ann Neurol 2013; 74: 733–742.  doi: 10.1002/ana.23976 (E-pub 2013 Aug 13). Chang K, Shin JI. (Letter to the Editor) Association of gestational maternal hypothyroxinemia and increased autism risk: The role of Brain-Derived Neurotrophic Factor. Ann Neurol 2014;75:971–972. doi: 10.1002/ana.24143  Román GC, Ghassabian A, Bongers-Shokking JJ, et al. (Reply)  Ann Neurol 2014;75:971-972. doi: 10.1002/ana.24141

2. Román GC. Autism: transient in utero hypothyroxinemia related to maternal flavonoid ingestion during pregnancy and to other environmental antithyroid agents. J Neurol Sci 2007; 262: 15–26

3. Román GC. Nutritional Disorders in Tropical Neurology. Chapter 30, Vol. 114 (3rd series), Handbook of Clinical Neurology, Neuroparasitology and Tropical Neurology. Edited by HH Garcà­a, HB Tanowitz, and OH Del Brutto. Elsevier BV: Amsterdam, 2013: 381-404

4. Berbel P, Navarro D, Román GC:  An evo-devo approach to thyroid hormones in cerebral and cerebellar cortical development: Etiological implications for autism. Frontiers in Endocrinology 2014, ISSN: 1664-2392

25^th SUMMER STROKE SCHOOL

Lecturers and participants of the 25th Summer Stroke School.

This year in Dubrovnik, under the auspices of the Department of Medical Sciences – Croatian Academy of Sciences and Arts, our traditional 25th Summer Stroke School was held from June 9-13. The event was organized by Inter-University Centre in Dubrovnik, Croatian Stroke Society, Zagreb Institute for the Culture of Health, School of Medicine University of Zagreb, Central and Eastern European Stroke Society and the Applied Research Group on Delivery and Care of the World Federation of Neurology.

Directors of Summer Stroke School are: Prof. Vida Demarin (Croatia), Prof. Roman Haberl (Germany), Prof. Kurt Niederkorn (Austria), Prof. Tatjana Rundek (U.S.) and Prof. Zlatko Trkanjec (Croatia). The course brought together top experts from all over the world:  Natan Bornstein (Israel), David Russell (Norway), Moise Desvarieux (U.S.), Yoshikazu Yonei (Japan) who, together with  above mentioned course directors, shared their knowledge and experience with participants during the whole week, both from clinical work as well as from their rich scientific life.

The aim of this course is to contribute to the global fight against stroke, by increasing the knowledge, exchanging experiences and supporting the cooperation among the 60 participants from all over the world, from Albania, Bosnia and Herzegovina, Serbia, Macedonia, and Slovenia as well as from distant Kazakhstan, Zambia and Japan. Also, participants had the unique opportunity to exchange national data on stroke and discuss specific problems that are unique in some countries and together try to solve problems related to stroke, be they medical, economic or other nature.

During the week, participants presented interesting cases of stroke patients; there have been a total of 32 lectures and 30 presentations of interesting cases by the participants themselves.  It was a fruitful and unforgettable experience for all of us.

Development, Opportunity, Hope and Challenges

By Amadou Gallo Diop and Riadh Gouider

Figure 1. Evolutions, by the time, of economy data and number of neurologists and facilities in Sub-Saharan Africa (South Africa and Maghreb not included).

At the end of 2014, 15 new young neurologists will contribute to increase the number of rare specialists in Sub-Sahara-African countries. These new cohorts have been trained in Dakar, Abidjan and Addis-Ababa. They originate from Benin, Burkina Faso, Cameroon, Comoros, Ivory Coast, Ethiopia, Mali, Mauritania, Niger, Rwanda, Senegal and Togo. Their professors are from African universities with the support (by short visiting professorship collaboration) of French and North American colleagues. The four-year content of their training program was very broad, similar to any courses worldwide and composed of all aspects of neurology, including neuro-anatomy, neurophysiology, basic neuroscience, semiology, pathologies and strategies of care. Courses focus on the most prevalent neuro-conditions in the African continent and how to adapt ideal management to the local socio-economic realities. Practical training was obtained with clinical outpatient and inpatient tasks, under the auspices of assistant and senior professors. In neurological departments, but also in other services such as cardiology, psychiatry, internal medicine, pediatrics and some ground visits and duties in provinces or suburban areas. That type of course is applied to selected MDs who intend to specialize in neurology since two decades in Africa. Before the 1990’s, African neurologists were, in majority trained abroad in ex-colonizing countries i.e. France, UK, Belgium, Portugal, Germany, Russia or Switzerland.

The good news is that in 50 years, from 1974 – 2014, the number of neurologists has multiplied by more than 30 while the population has multiplied by three in Sub-Saharan Africa. It’s crucial and very interesting to see that the same situation is noted regarding the economy. One can see that the Growth Development Product has followed the same dramatic evolution, rising from $461 billion in the 70’s to up to $1,500 in 2008. The continent faces the third fastest GDP growth after the “Dragons” and Petrol-Middle-East Region as shown in Figure 1 (courtesy furnished by Pr Perucca, Pdt of the ILAE). The same remark can be done about diagnostic facilities (EEG, EMG, and neuro-imaging facilities). That let us see that when the general economic situation improves, the “neuro-conditions” improve in term of human and material resources. This is encouraging and is a reason for being more optimistic.

A training course in neurology and epileptology in Dakar, with trainees and faculty coming from different continents.

But there is still so much to achieve. While WHO recommendations is to reach at least the ratio of one neurologist for 50,000 people in a state, the fact in Sub-Saharan Africa is, in the “best” case, one for 500,000 (Ivory Coast and Senegal). In Ethiopia, the ratio was one for 10 million people 10 years ago; it is now one for 5 million. All the French-speaking countries have now at least one neurologist. Few countries have just one neurologist. Nowadays, only very rare sub-African countries do not have even one single neurologist (Cape Verde Islands, Gambia, Equatorial Guinea, Guinea-Bissau, Liberia, Sao Tome and Principe). One can remark that the majority of them are Portuguese-speaking states. Many countries have tenfold more native neurologists in North America, Europe or the Gulf countries than locally. In 15 years, few immigrant neurologists still residing abroad are initiating annual or bi-annual short-term periodic come-back-home for teaching and supporting somehow research, equipment and care.

It’s also very encouraging to see that the number of training courses has dramatically increased these last years. If we consider all training courses dedicated to the nervous system and co-organized by Pan-African Association of Neurological Sciences (which will soon become African Academy of Neurology), Society for Neurosciences in Africa, and almost a dozen of international bodies (WFN, IBRO, EFNS (now EAN), ILAE and IBE, AAN, SFN, WSO, PAUNS, HIS, ICNA, MDS) their number and quality is increasing. They occur every year in English or French.

But the challenges are still huge. The Sub-Saharan Region of Africa still needs many more neurologists for filling the gap. Every professor who has ever lectured in Africa is amazed by how motivated and thirsty for learning the trainees are. Many volunteers come and spend a few days with young MDs specializing in neurology and neurosciences for theoretical lessons and clinical activities. The ultimate goal is to increase, by massive training, the number of neurologists in Sub-Saharan Africa. Let us share this formula from Sam Kinyangui (cited by Charles Newton, Kenya) and which could be our common vision about Neuro-Training in Sub-Saharan Africa: “Attract, Train, and Retain.” At this moment, several universities have set up curricula for training in neurology: Dakar since 50 years, Abidjan since 20 years and more recently: Addis Ababa, Cotonou, Kinshasa, Lome, Yaounde and some Nigeria’s cities which university teaching hospitals are training grounds. They do not partake in the final diploma because the two awarding bodies are The West African Post Graduate Medical College, and the National post Graduate Medical college, if we refer to Pr Ogun, Nigeria. Four to six new trained neurologists from new training sites (Lome, Cotonou, Yaoundé) will graduate from 2015 and 2016. Individually, or under the auspices of bilateral academic cooperation or the umbrella of international neuro-institutions, the short visiting professorships, in cooperation with local faculty, should be encouraged by any mean (finances, teaching materials and slides, neuro examination means and books).

BOOK REVIEW

Oxford University Press, 2014.

This book reviews the history of the first 50 years of the WFN which was officially founded in 1957. One question immediately comes to mind: Why 1957? There may be a debate about the “date of birth” of neurology, but everybody agrees that it was firmly established as a discipline by the first part of the 20th century or even before that time. In subsequent years, there were several meetings attended by international members, even though the two World Wars forced the cancellation of some of these meetings. Why then did we have to wait until 1957 to see the foundation of WFN?  One probable reason is that international collaboration, like international travel, was much less common than it later became. It took the strength and charisma of one man, Ludo van Bogaert, to carry through the creation of the federation. Note that in its early years, WFN was “worldly” only in name: Asia, Africa and Oceania were barely represented. Yet it was certainly quite international. A picture in the first pages of the book shows that of 10 delegates participating in an early WFN organizational meeting, one was from Cuba, one from Iran while a third was a neurosurgeon representing India. Iran and India were the only two Asian countries present in the initial years of WFN. In its first years, WFN survived mainly thanks to a grant from the US-based National Institutes of Health (NIH).

In this nicely presented volume, Dr. Aarli who has actively participated in the activities of WFN for many years, including a term as president, describes the state of neurology before 1957 and narrates how WFN took shape, evolving gradually into today’s structure and organization. He then describes in varying amounts of detail the organization of the Research Committee and the Research Groups, at first called “Problem Commissions.” Subsequent pages of the volume provide details about the regional neurological associations and the relationship with the World Health Organization. The volume continues with a chapter which further illustrates the close ties of neurology with world events. The Indian neurologist Noshir Wadia went to jail and Jun Kimura (Kyoto, Japan) almost went to jail. Both were absolutely innocent:  Wadia had been kidnapped and jailed by the police of the Portuguese dictator Salazar in retribution of India having annexed the tiny enclave of Goa; and the charges of embezzlement brought against Kimura were completely unjustified. Both Wadia and Kimura played important roles in developing neurology and neuroscience in their respective countries and within the WFN. The book concludes with a review of the International Congresses that took place since 1957, first every four years and now every two years. A short but exciting epilogue is written by Vladimir Hachinski who, as president until 2013, perfectly embodied the motto Continuity and Change. This epilogue provides an interesting view into the future of WFN now under the helm of Raad Shakir.

One of the interesting features of Dr. Aarli’s narrative is the glimpses it provides into the features and developments of the world at large during those years. It reminds us of how much things have changed in this relatively short space of less than 60 years. For instance, we hear about the relations between the German Neurological Societies when a wall divided the Federal Republic and its Eastern counterpart, the German Democratic Republic. The relations ranged from nonexistent to acrimonious. We witness the very gradual entry of African countries into the WFN as they became independent in the early 60’s. In one of the most thrilling parts of the book, we read about the “slow boat to China.” Dr. Aarli built on the efforts of his predecessors, John Walton and Jun Kimura, and managed a diplomatic exploit. That is certainly what it took to reach the point where delegates from the People’s Republic of China, the Hong Kong Neurological Society and the Taiwanese Neurological Society agreed to sit together. A picture showing the presidents of the three societies posing next to Dr. Aarli illustrates that truly historic moment.

Dr. Aarli reminds us of that decentralization was always a theme of WFN, but different players interpreted the concept differently. On one hand, decentralization could provide a more equitable division of labor among the WFN members and thus Ludo van Bogaert and Pearce Bailey vigorously advocated it from the beginning. Others such as Hans Hoff from Austria and Russell DeJong from the USA feared that it could lead to fragmentation of the Federation. Regional societies now exist, but they have evolved in different fashions. The Asian Oceanian Association (AOAN) has attracted countries such as Mongolia and Myanmar to join both AOAN and WFN, but we are not told much about the Congresses of AOAN, which are held every two years. Similarly not much is said about the Pan Arab Union of Neurological Societies (PAUNS), which had its first meeting in Cairo in 1975. Recent PAUNS meetings have taken place in Damascus in 2010 and in Sharm el-Sheikh in 2013. In Europe, on the other hand, the regional society has developed considerably. The earliest European association known initially as Pan European included mostly neurologists from what was known as Eastern Europe and it did not have much prestige until it evolved into the European Federation of Neurological Societies (EFNS) in 1991. The other European scientific society, the European Neurological Society (ENS) was created in 1986 and its first meeting organized by Gérard Saïd (Kremlin-Bicàªtre) and Pierre Rondot (Sainte-Anne) took place in Nice in 1988 with P.K. Thomas as first president. ENS was modeled on the American Neurological Association (ANA) and conceived as a body of scientists elected because of their merit and not their nationality.  The two societies have merged in the spring of 2014 into the European Academy of Neurology (EAN). It is presided by Günther Deuschl and will have its first meeting in Berlin in 2015. This process is in great part due to the determination of the presidents (particularly Franz Gerstenbrand, Jes Olesen, Jacques DeReuck and Richard Hughes for EFNS and Gustave Moonen, Josè
Ferro and Claudio Bassetti for ENS) and also to the creation of the Journal, the European Journal of Neurology (François Boller and Per Soelberg Sörensen, founding editors; Anthony Shapira current editor) which will be the official organ of the EAN. Under the auspices of Gustavo Roman and others, an effort is under way to develop an American Federation of Neurological Societies.

As can be expected, the development of WFN was far from being always smooth. Dr. Aarli displays the full extent of his elegant diplomacy when he discusses some of the rougher moments of the WFN: “conflicts, problems” and “the usual suspects” are alluded to in ways that will be well understood by WFN insiders. He refers to a real or narrowly avoided catastrophe as “an unforeseen event.” And all the players are hardworking, true leaders full of ideals and integrity. Of course this is true in most cases. However, it is amusing to read the descriptions of some of the same people given elsewhere, for instance the admirable and highly readable book “A Fragmented Memoir: Life and the Teeming Brain” (Bacchante Books, 2013, by John Moossy.) Moossy, a neurologist and neuropathologist, former editor-in-chief of the Journal of Neuropathology and Experimental Neurology lived through many of these events including a  one year stay at  van Bogaert’ Bunge Institute. Moossy freely distributes high praises to some such as van Bogaert himself and the late Charles Poser, also a very important player in the creation and evolution of WFN. On the other hand, he does not hesitate to use much sharper words for people who played a dominant role in the development of WFN, but who he did not like as much. It is not clear whether Giancarlo Guazzi, an important collaborator of van Bogaert from 1958 to 1968, played any role in the early years of the WFN. Actually Guazzi is not mentioned in the book, but he is indirectly alluded to when we are told that van Bogaert received a Honoris Causa Doctorate in Siena (unfortunately misspelled), Guazzi’s alma mater.

In conclusion, this book is a great tribute to a great organization. This reviewer fully shares the words of Lord Walton who writes in his preface: “Posterity will be very grateful to Prof. Aarli for this historical work of scholarship.”

By Kiran Thakur, MD

Kiran Thakur

Before the introduction of the measles vaccine in the United States in 1963, more than 500,000 cases of measles and at least 500 measles-associated deaths were reported annually^1,2. Although measles elimination was declared in 2000, importations of cases from endemic areas of the world continue to occur, leading to secondary measles cases and outbreaks. This year, the United States is experiencing a record number of confirmed measles cases, with 592 cases and 18 outbreaks reported to the Centers for Disease Control’s (CDC’s) National Center for Immunization and Respiratory Diseases (NCIRD) between Jan. 1 and Aug. 29, 2014³. (See Figure 1.) Recent increases in the incidence of measles in the United States are attributed to the importation of measles virus through travel to other countries, including the Philippines, where there is a large, ongoing measles outbreak. Approximately 20 million cases of measles occur each year globally, and importations into the United States continue to pose a risk for measles cases and outbreaks. This is also coupled with greater rates of transmission because of unvaccinated or incompletely vaccinated United States citizens, a significant portion of which are children⁴.

The large number of cases this year emphasizes the need for health care providers to have a heightened awareness of the potential for measles and the importance of vaccination to prevent infection, in particular in young children and travelers who are susceptible to severe infection. Health care providers should maintain a high level of suspicion for measles among febrile patients who present with rash, cough, coryza, and/or conjunctivitis. Patients should be asked about recent travel abroad and/or contact with returning travelers, and their vaccination status.

Figure 1. United States (U.S.) measles cases by year.

In particular, neurologists should be aware of the early and late neurological manifestations of the infection. Although neurological symptoms and signs have not been reported among the 592 cases in the United States reported this year, neurologists should be aware of the potential early and late central nervous system (CNS) complications of the infection. CNS manifestations are indeed rare, but devastating when they occur. The most common CNS manifestation of measles infection is acute measles encephalitis (AME) occurring in approximately 0.1 percent of cases⁵. In AME, the virus replicates within neurons and triggers a lymphocytic infiltration within the brain parenchyma and meninges⁶. AME typically occurs during the exanthem phase of the systemic illness, but can rarely precede the onset of rash. Cerebrospinal fluid (CSF) typically shows a lymphocytic pleocytosis and mildly elevated protein⁷. Treatment for AME is largely supportive and prognosis is guarded as approximately 20 percent of patients die, with at least one quarter of survivors developing permanent neurologic sequelae⁸. Post-measles encephalomyelitis (PME) occurs in approximately one in 1,000 patients, occurring within two weeks of the onset of rash and is characterized by seizures and focal neurological deficits. Periventricular demyelination, induction of immune responses to myelin basic protein, and absence of measles virus in the brain suggest that PME is an autoimmune disorder triggered by measles virus infection⁹. Other CNS complications that occur months to years after acute infection are measles inclusion body encephalitis (MIBE) and subacute sclerosing panencephalitis (SSPE), both of which are caused by persistent measles virus infection. MIBE is a rare, but fatal complication associated with progressive neurological deterioration that affects individuals with defective cellular immunity and typically occurs months after infection. SSPE is a rare delayed complication of measles that occurs in about one in 10,000–100,000 patients and is characterized by seizures and progressive deterioration of cognitive and motor function followed by death 5–15 years after measles virus infection¹⁰. On histopathology, neurons, oligodendrocytes, astrocytes and microvascular endothelial cells are infected¹¹. SSPE most often occurs in people infected with measles virus before two years of age.

Rates of CNS manifestations due to measles infection have dramatically declined since the introduction of the measles vaccine, though with the resurgence of measles outbreaks around the world, and the increase in refusal of vaccines in resource-rich nations, the risk of these complications is now heightened. As travel to worldwide destinations becomes more accessible, neurologists should be aware of the potential neurological effects of acquired infections abroad, including measles and other neurotropic infections. Clinicians should also be aware of the increasing susceptibility to infection in those who are not vaccinated, including young children.

References:

1. Campbell H, Andrews N, Brown KE, et al: Review of the effect of measles vaccination on the epidemiology of SSPE. Int J Epidemiol 36: 1334-1348, 2007 4

2. Hinman AR, Orenstein WA, Papania MJ: Evolution of measles elimination strategies in the United States. J Infect Dis 189(suppl 1):S17-S21, 2004

3. http://www.cdc.gov/measles/hcp/index.htm Accessed September 4th, 2014

4. Verla-Tebit E, Zhu X, Holsinger E, et al. Predictive value of immunization records and risk factors for immunization failure in internationally adopted children. Arch Pediatr Adolesc Med 2009;163:473-479

5. Schneider-Schaulies J, Meulen V, Schneider-Schaulies S. Measles infection of the central nervous system. Journal of Neurovirology 2003;9: 247–252

6. Johnson RT, Griffin DE, Hirsch RL, et al: Measles encephalomyelitis—clinical and immunologic studies. N Engl J Med 310:137-141, 1984

7. Johnson RT, Griffin DE, Hirsch RL, et al: Measles encephalomyelitis—clinical and immunologic studies. N Engl J Med 310:137-141, 1984

8. Perry RT, Halsey NA: The clinical significance of measles: A review. J Infect Dis 2004;189(suppl 1):s4-s16

9. Johnson RT, Griffin DE, Hirsch RL, et al. Measles encephalomyelitis—clinical and immunologic studies. N Engl J Med 1984; 310: 137–41.

10. Bellini WJ, Rota JS, Lowe LE, et al. Subacute sclerosing panencephalitis: more cases of this fatal disease are prevented by measles immunization than was previously recognized. J Infect Dis 2005; 192: 1686–93.

11. Allen IV, McQuaid S, McMahon J, et al. The significance of measles virus antigen and genome distribution in the CNS in SSPE for mechanisms of viral spread and demyelination. J Neuropathol Exp Neurol 1996;55:471–480.

By Girish Modi

Girish Modi

According to data from the World Health Organization (WHO), almost   75 million people worldwide have been infected by the HIV virus. About 36 million people are estimated to have died as a result of being infected. At the end of 2012, globally 35.3 million [32.2–38.8 million] people were living with HIV. In the young, economically active adult population (15 – 49 years) 0.8 percent are living with HIV.

Sub-Saharan Africa bears the brunt of this burden and remains the most severely affected. In Sub-Saharan Africa, one in every 20 adults are HIV infected accounting for 71 percent of the people living with HIV worldwide.

In South Africa, the total number of persons living with HIV increased from an estimated 4 million in 2002 to 5.26 million by 2013. For 2013, an estimated 10 percent of the total population is HIV positive. Also, 17 percent of South African women in their reproductive ages are HIV positive.

These statistics are important to help understand the impact they have had on the practice of clinical medicine in Sub-Saharan Africa and for us here in South Africa. In the teaching public hospitals in South Africa, 40-60 percent of medical admissions are in some way linked to HIV infection. In the non-teaching rural hospitals, these figures are much higher.

Naturally, neurology has been affected and to a large extent has borne the brunt of this epidemic. Neurological involvement in HIV is described to affect 40-75 percent of HIV infected patients admitted to the medical wards in a tertiary care setting¹. In a prospective study of 506 in-patients at the Helen Joseph Hospital, Johannesburg, South Africa, 75 percent of patients had some clinical neurological involvement, and in 11 percent neurological disease was the sole presenting feature. The neurological presentation of the patient is dependent and to an extent determined by the immunological state of the patient.

Seizures and Epilepsy in HIV

Seizures in HIV can occur at any stage of the infection and have been described in patients with presumed acute HIV induced seroconversion illnesses through to advanced disease or AIDS.

Incidence data on seizures in HIV infection has mostly been focused on new onset seizures (NOS). All the studies have been hospital-based and most are retrospective. The incidence ranges from 2-20 percent. The differences in incidence can be explained by the different inclusion and exclusion criteria in the studies and the specific groups surveyed. The relatively low incidence of two percent was from a study in New York where patients with provoked seizures were excluded.  The high incidence of 20 percent came from Bangalore in India where the study population group was pre-selected in that all their patients had a pre-existing neurological disorder.

In terms of seizure types, in these study populations, generalized seizures were  by far the commonest occurring in 58-100 percent of patients. This high proportion may be due to the under-reporting of focal origin seizures that cause immediate secondary generalization or inaccurate details from eyewitnesses. Focal seizures may in some patients indicate the presence of an underlying focal brain lesion but they have also been described in patients with diffuse disease. Status epilepticus also occurs in this population group and has been described in 8-18 percent of patients.

In terms of causes, NOS in HIV positive persons can be categorized or grouped into:

• Focal brain lesions (FBL)
• Meningitis
• Metabolic causes
• No identifiable cause (NIC)

The majority of patients with NOS have a specific underlying cause for their seizure.

The most commonly identified causes are focal brain lesions (FBLs) and meningitis. FBLs occur in 30-50 percent of patients. FBLs can be infectious; neoplastic; demyelinating or due to cerebrovascular disease.  Toxoplasmosis has been identified as the commonest infectious cause of FBLs in patients with HIV and occurs in up to 88 percent of patients presenting with NOS in most of the studies that have been published. However, in populations where tuberculosis is endemic, this has been found to be the commonest cause of FBL in HIV patients with NOS. CNS lymphoma is recognized as the second most common cause of FBL and has been reported in up to 11 percent of patients. Other reported causes of FBL include Progressive Multi-focal Leukoencephalopathy (PML); neurocysticercosis and strokes.

Meningitis has been described in 10-22 percent of patients presenting with NOS.  Cryptococcal meningitis is the most frequent cause of meningitis except again in regions where tuberculosis is endemic.

The other aetiologies that need to be considered include metabolic abnormalities; medication side-effects and HIV-Associated Dementia (HAD).

In 6-46 percent of patients, NIC can be found for the seizure presentation and it is presumed that primary cerebral HIV infection is responsible. In keeping with this, SPECT scan studies have shown focal temporal lobe abnormalities.

Numerous abnormal electroencephalographic (EEG) findings have been reported in HIV-infected individuals presenting with seizures. The abnormalities have been both focal and generalized and are most commonly non-specific e.g. generalized slowing. Non-specific abnormalities have been well described in asymptomatic HIV-positive individuals and their significance in this setting is uncertain. Focal abnormalities on EEG do not necessarily signify an underlying focal lesion.

Seizures recurrence risk as expected from the potential causes listed above is high and therefore treatment even with a new onset first seizure requires medical intervention. Valproate has been described to increase viral replication but it has also been shown to be beneficial in HIV infected seizure patients and is therefore widely used. Phenytoin and carbamazepine induce the hepatic p450 system and interact with anti-retrovirals adversely and are therefore not recommended. Gabapentin, Levetiracetam and Lamotrigine do not have such interactions are preferred in the setting of HIV and seizures. Availability in resource limited regions is an issue with these anti-epileptics.

In an acute setting, standard epilepsy protocols should be adhered to. Long-term anti-epileptic therapy needs to be initiated in the majority of patients but this can be a difficult decision. Evidence-based guidelines (American Academy of Neurology) have been formulated for patients that require both HAART and anti-epileptics. The guidelines do not however specify when anti-epileptics should be initiated or how long they should be continued for.

Epilepsy and HIV remains a daunting neurological challenge.