Professor Jean Aicardi (1926-2015)

Jean Aicardi was arguably the greatest child neurologist of the modern era, an internationally renowned French child neurologist who wrote his textbooks in English. His name will live on in the two separate conditions that he described—Aicardi syndrome and Aicardi-Goutières syndrome (AGS). His name will also live on through his several textbooks, all written in English, and through his friends, colleagues, and pupils (over 100 fellows trained with him) throughout the world. Most of his work was done in Paris, but in later years he also held posts in Miami, Florida (as Visiting Scientist), at the Institute of Child Health (as Honorary Professor of Child Neurology), and in Great Ormond Street Hospital (Honorary Consultant Neurologist), London, UK.

Isabelle Rapin, in her report, “The International Child Neurology Association: the First 25 Years” wrote that Jean Aicardi was “one of the most peripatetic child neurologists the world has yet seen, thanks in part to his prowess in multiple languages and to the fact that his retirement from the Hôpital des Enfants Malades in Paris gave him the freedom to serve as Visiting Professor in London, Miami, Sydney and elsewhere and to visit all the continents one or more times during his presidency (of ICNA).”

Jean François Marie Aicardi was born on November 8, 1926, in Rambouillet, 50 km from Paris, the seventh of nine children. As a student at the Lycée Hoche in Versailles, he was “an average student with no burning interest in any particular subject, notably not maths.”¹ However, a vague attraction to biology led him to think of medicine as a career.

Despite many difficulties he seems to have become more and more excited by his medical education and finally earned the MD from the University of Paris for his thesis on convulsive disorders in the first year of life.

Jean Aicardi (3rd from the left in the front row) at the 1985 Baltimore workshop on Rett syndrome.He was inspired to do neurology by Professor Raymond Garcin and to do child neurology by Professor Stéphane Thieffry. After obtaining his MD he spent an inspirational year as research fellow at Harvard Medical School and the Children's Hospital Medical Center in Boston.

Not only did he get to know people like Cesare Lombroso, but most importantly, he also assimilated North American research methods and their rigor. Thereafter he rejoined Thieffry in Paris in what was to be the first child neurology unit in France and a unit of great productivity over many years, both at Hôpital des Enfants Malades and Hôpital Saint-Vincent DePaul.

However, it was only when Aicardi joined INSERM (Institut National de la Santé et de la Recherche Médicale - National Institute of Health and Medical Research) that his career was assured and he was able to write and to collaborate internationally. At INSERM he was Mâitre de Recherche 1969-1991 and Directeur de Recherche 1986-1991.

Aicardi's best known papers described his two new syndromes. Aicardi syndrome² and ³ consists of infantile spasms, eye defects—mainly chorioretinal lacunae (white holes) and agenesis of the corpus callosum—and is almost entirely confined to girls. AGS—described with Françoise Goutières,⁴ with whom he wrote over 60 papers between 1966 and 2007—is best known as an infantile encephalopathy, but has proved to be of extraordinary interest on a wider scale.

The seven genes⁵ (so far) for AGS are involved in pathways that converge on type 1 interferon, a protein involved in innate immunity. Thus it comes about that AGS resembles both congenital viral infections (including human immunodeficiency virus) and also autoimmune disorders in particular systemic lupus erythematosus.

Rett syndrome was another condition confined to females to which Aicardi made a major contribution.⁶ Actually, Rett syndrome was rediscovered in many countries in the early 1980s, but it was Bengt Hagberg, Jean Aicardi, and Karin Dias who really put it on the map.⁶ Then, everyone flocked to Baltimore for the 1985 Rett workshop, and the rest is history.

Aicardi's textbooks have been hugely popular, and both Diseases of the Nervous System in Childhood and Epilepsy in Children have run to three editions, as yet. He was also the founding editor and editor-in-chief of the journal Epileptic Disorders that includes videos of patients to accompany the written word.

His academic honors were numerous, but one should note especially Aicardi's receipt of the Hower Award from the Child Neurology Society in 1986. Of this award he said “I would first like to thank the Child Neurology Society for the honor that it has bestowed on me.I am aware of the prestige which is attached to the Hower Award, and I deeply value this distinction, especially as I realize that it is the first time the award has been given to a non-American child neurologist. In addition to honoring me, the Child Neurology Society wanted to demonstrate that neuro-pediatrics has no geographic, political or linguistic borders, and that the care of neurologically disabled children requires the efforts of all men and women of good will across lands and oceans.”⁷

Aicardi was a man without hubris. American child neurologist E. Steve Roach wrote recently “I was so impressed by how someone of his stature and accomplishment seemed so modest. I have come to believe, largely from this encounter, that truly accomplished people have no real need to tout themselves: a valuable life lesson for all of us.”

Jean married Jeanne early in his career, and they lived in a flat in Boulevard Beaumarchais, a flat that she made particularly beautiful. Sadly, Jeanne predeceased him.

References:

1. Aicardi J (2013) Jean Aicardi: my circuitous path to becoming a French child neurologist and epileptologist. J Child Neurol 28 (3):409-15. DOI: 10.1177/0883073812470212 PMID: 23400630.
2. J. Aicardi, J. Lefebvre, A. Lerique-Koechlin. A new syndrome: spasms in flexion, callosal agenesis, ocular abnormalities. Electroencephalogr Clin Neurophysiol, 19 (1965), pp. 609–610 (Abstract)
3. Aicardi J, Chevrie JJ, Rousselie F (1969) [Spasma-in-flexion syndrome, callosal agenesis, chorioretinal abnormalities]. Arch Fr Pediatr 26 (10):1103-20. PMID: 4314028.
4. Aicardi J, Goutières F (1984) A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis.Ann Neurol 15 (1):49-54. DOI:10.1002/ana.410150109 PMID: 6712192.
5. Crow YJ, Chase DS, Lowenstein Schmidt J, Szynkiewicz M, Forte GM, Gornall HL et al. (2015)Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.Am J Med Genet A 167A (2):296-312. DOI: 10.1002/ajmg.a.36887 PMID: 25604658.
6. Hagberg B, Aicardi J, Dias K, Ramos O (1983) A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases.Ann Neurol 14 (4):471-9. DOI: 10.1002/ana.410140412 PMID: 6638958.
7. Aicardi J (1987) The future of clinical child neurology.J Child Neurol 2 (2):152-9. PMID: 3598143.

Acknowledgements:
Article originally published by The Child Neurology Society (USA) and in Pediatric Neurology Volume 54, January 2016,DOI: 10.1016/j.pediatrneurol.2015.09.006

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