Gonzalo R. Lafora: Spanish neuropsychologist and neuropathologist

Enrique Chaves-Carballo
Overland, Kansas, United States

 

Gonzalo Lafora, a balding man looking thoughtfully to the viewer's right
Portrait of Dr. Gonzalo R. Lafora (1886–1971). Reproduced with permission from Spanish Society of Neurology’s Museum and Historical Archives (MAH SEN).

Gonzalo Rodríguez-Lafora (1886–1971) was a Spanish neurologist best known for his description of intracytoplasmic inclusion bodies (Lafora bodies) in myoclonic epilepsy.

Lafora was born in Madrid on June 25, 1886. At the age of four, he moved to Puerto Rico when his father became a lieutenant colonel in the Spanish Army before the Spanish-American War.1,2,3 After a satisfactory scholastic career, Lafora studied medicine at the Central University of Madrid, graduated at the age of twenty-one, and then trained under the tutelage of well-known scientific leaders Ramón y Cajal, Luis Simarro, and Nicolás Achúcarro. He received further training in neuropsychiatry from European teachers in Berlin, Munich, and Paris, including Magnan, Pierre Marie, Dejerine, Oppenheim, Vogt, Kraepelin, and Alzheimer, strengthening his expertise in neuropathology.4

In 1910 he was recommended by his mentor Achúcarro and appointed director of the histopathology laboratory at the Government Hospital for the Insane (now St. Elizabeth Hospital) in Washington, D.C.2 During the two years he remained there, Lafora discovered the intraneuronal bodies found in familial myoclonic epilepsy. These were reported in 1911 in two papers, one of them co-authored with Bernhard Glueck.5,6 The authors described the clinical details of a seventeen-year-old young man who developed constant myoclonus, progressive dementia, bilateral papilledema, pain in both eyes, and deteriorating vision and hearing. At autopsy these were the findings:

The granule and pyramidal cells in layers 2 and 3 show striking alterations, the Nissl substance is lost, the nucleus is positioned eccentrically, the protoplasmic appendices lost, so that the cells appear round. In a great number of these cells, we find amyloid bodies, which merely fill the whole cell and compress the nucleus, so that it is semilunar shaped….The amyloid bodies are round, composed of various layers, which tend to show radial stripes…one can see needle-shaped crystals….In contrast to the expected we found the most alterations in the cortical layers 2 and 3, whereas Betz cells are mostly spared…these findings suggest some interesting considerations: are the intracellular bodies the cause or the consequence of myoclonic seizures? The lack of these bodies in Betz cells and in the ganglion cells of the anterior medullary column, the greater number in sensitive or sensory centers like the visual cortex, the quadrigeminal plate, and the dorsal horn of the medulla forces us to consider, that they are not products of tiring after convulsions. We would like to stress the remarkable circumstance that glial cells showed a very sparse reaction with respect to the amyloid-degenerated gangliocytes.2

Stretched, abnormal cells of varying colors from work of Gonzalo Lafora
Inclusion (Lafora) bodies described by Lafora in a case of myoclonic epilepsy. Reproduced from Lafora GR and Glueck B2 (1911). Public domain.

These intracellular “amyloid bodies” (later named Lafora bodies) were found mainly in the cerebral cortex, thalamus, globus pallidus, and substantia nigra, and are composed of polyglucosan elements (dense accumulations of malformed and insoluble glycogen molecules).7 The disease is caused by recessively inherited mutations in the EPM2A or EPM2 genes encoding the laforin carbohydrate-binding phosphatase and the malin E3 ubiquitin ligase.8

Myoclonic epilepsy is a fatal, autosomal recessive disorder characterized by refractory seizures (myoclonic, grand mal, and atypical absence), and progressive cognitive and visual loss, usually starting in adolescence and terminating in death in the thirties. There are three recognized types of progressive myoclonic epilepsy. In addition to the Lafora type, the Unverricht-Lundborg type is more common in Finland and has an earlier onset, mild mental symptoms, and variable survival. The Hartung type is autosomal dominant and lacks inclusion bodies.9 Other disorders accompanied by myoclonic epilepsy are neuronal ceroid lipofuscinosis (Batten’s disease), sialidosis type 1, and myoclonic epilepsy with ragged red fibers (MERRF).

Due to the political conflicts in pre-World War II Spain, Lafora emigrated to Mexico in 1938, where he remained for nine years and went into private practice as a neuropsychiatrist.1,5 Following his exile in Mexico, Lafora returned to Spain in 1947 to work as director of the neuropathology section of the Cajal Institute under his teacher and mentor Santiago Ramón y Cajal, who provided a small room on the third floor of his home in Madrid for Lafora’s investigations. According to López-Muñoz, “Lafora studied passionately the histopathology of senile and presenile psychoses, emphasizing the importance of fine and incipient cerebrovascular injuries in the genesis of senile alterations.” In addition, “Lafora had a broad range of interests in psychiatry including paranoid psychoses, auditory hallucinations, pathological jealousy, obsessive syndromes and sexual disorders. However, schizophrenia remained his main focus in which he tried to correlate neuropathological changes and psychotic symptoms.”10

Lafora was known by his disciples as “el maestro” (teacher or mentor). He was a true scientist, accepting only the truth as substantiated by meticulous research. As one of the founders of the Archives of Neurobiology, he resisted any attempt to insert personal views or comments not supported by the scientific method. According to Valenciano Gayá, “the fundamental characteristic of Lafora was his curiosity of all that occurred around him, from the most microscopic to the most macroscopic…. As a result, aside from medicine, he [was] a scholar in literature and philosophy, music and painting, ancient artifacts, and even cuisine.”11 Among his many disciples, Rey Ardid12 recalled:

Lafora spent his whole life teaching, and those of us who had the good fortune of working at his side were able to grasp the enormous span of knowledge that he possessed. He was a master, a great master…. He was a stoic man who shunned formalisms and constantly expressed sincerity. Without us ever asking, Lafora gave us everything and he devoted himself entirely to watching us grow, progress, and become successful in our own right.

To complement his lofty ideals, Lafora was described as tall and distinguished and was compared to Don Quixote. Llavero further described him as “tall, with a Nordic-like head, thin and upright like a candle[stick]…He was always ready to listen and never left anyone in mid-thought. He also knew nothing of punctuality. How could he as a scientist?”13 He walked using a walking stick, possibly related to having poliomyelitis at the age of two.3 He was exhaustive and persistent, often forgetting the most essential necessities of life and fueled only by some cigarettes and a few cups of coffee.14

Lafora published some 220 papers covering neurology, psychiatry, neuropsychology, and neuropathology.1 Among his many important contributions were studies on the histopathology of Alzheimer’s disease, cerebral malaria, treatment of syphilis, structure and function of the corpus callosum, Wernicke’s encephalopathy, poliomyelitis, von Recklinghausen’s disease, and “lethargic encephalitis.”3 His book on mental disorders in children (Los Niños Mentalmente Anormales) exemplifies his ability to gather in great detail all important aspects of a subject of interest.15 The book, published in Madrid as part of a series of manuals in science in education, consisted of 576 pages and twenty-seven chapters divided into four sections: 1) the normal child; 2) the abnormal child; 3) diagnosis of abnormal children; and 4) education of abnormal children. Each of these sections consisted of four to eleven chapters replete with useful information supported by numerous complete citations from the world literature. Section II dealt with “the abnormal child” and was the most extensive, ranging from “Methods for the examination and diagnosis of mentally abnormal children” (eleven chapters); “Methods for the psychological examination of children” (three chapters); “Speech disorders of abnormal children” (one chapter); and “Classification of mentally abnormal children” (one chapter). This manual must have required countless hours of research and is a testament to Lafora’s dedication to produce the most exhaustive scientific work on the subject. The book received an award from the Royal Academy of Medicine in 1919.

As director of the psychiatric clinic at the Provincial Hospital in Madrid, Lafora saw patients in the morning and in the afternoon examined at the Cajal Institute the brains of those who had died, as well as conducted other scientific studies.13 In addition, he organized a series of courses (as many as three each year) given by recognized personalities he invited to present the latest advances in psychiatry.

Lafora renewed publication in 1920 of the journal Archivos de Neurobiología. For this purpose, he formed an editorial board that represented every scientific and teaching personality in Spain. Nevertheless, the journal was product of his own soul and labor. Each editorial session was conducted in his office or in a parlor or dining room in his home. Lafora arrived with loads of journals, files, and newspaper clippings. He saved anything and everything of interest. He had a prodigious memory for everything he had read, but not for where he had placed an item, which at times required a thorough search among the piles of books and papers that accumulated in his home.14

His thirst for knowledge ran parallel to his desire to teach. He would attend scientific meetings, sitting in the front row so he could hear better and learn more. In addition to establishing Archivos de Neurobiología, Lafora founded the Spanish Neuropsychiatric Association and was a member of the Royal Academy of Medicine in Spain, the Royal Society of Medicine in London, The Neurological Society of Paris, the National Society of Germany, and honorary member of the National Academy of Medicine of Mexico.4

Lafora died in Madrid on December 28, 1971 at the age of eighty-five, remembered with admiration and gratitude as “el maestro.”

 

References

  1. Valenciano Gayá L. El doctor Lafora y su época. 1977, Madrid: Ediciones Morata, S.A.
  2. Nanduri AS, Kaushal N, Clusmann H, Binder DK. The maestro don Gonzalo Rodríguez-Lafora. Epilepsia 2008;49:943-947.
  3. Balcells M. Gonzalo Rodríguez Lafora (1886-1971). Neurosciences and History 2014;2:176-180.
  4. Ortiz-Hidalgo C. The man behind Lafora’s bodies. Am J Surg Pathol 1986;10:358-361.
  5. Lafora GR. Uber das Vorkommen amyloider Korperchen im Innern der Ganglienzellen: zugleich en Beitrag zum Studium der Amyloiden Substanz im Nervensystem. Virchows Arch Pathol Anat Physiol Clin Med 1911; 205:295-303.
  6. Lafora GR, Glueck B. Beitrag zur Histopathologie der myoklonischen Epilepsie. Zeitschrift fur die gesamte Neurologie und Psychiatrie 1911; 6:1-14.
  7. Myoclonic epilepsy of Lafora. Online Mendelian Inheritance in Man (OMIM). https:// omim.org/entry/254780 (accessed 6/1/2022).
  8. Turnbull J, DePaoli-Roach AA, Zhao X, et al. PTG deletion removes Lafora bodies and rescues the fata epilepsy of Lafora disease. PLOS Genetics. https://doi.org/10.1371/journal.pgen.1002037.
  9. Norio R, Koskiniemi M. Progressive myoclonic epilepsy; genetic and nosological aspects with special reference to 107 Finnish patients. Clin Genet 1979;15:382-398.
  10. López-Muñoz F, Molina JD, de Pablo S, Alamo C. Gonzalo R. Lafora: a pioneer of neuropsychiatry. Acta Neuropsychiatrica 2007; 19:254-255.
  11. Valenciano Gayá L. Para un estudio de la personalidad del Dr. Lafora. Arch Neurobiol (Madrid) 1972;35:159-166.
  12. Ardid RR. Lafora, docente. Arch Neurobiol (Madrid) 1972;35:171-172.
  13. Llavero F. Mi ultimo homenaje al maestro. Arch Neurobiol (Madrid) 1972;35:167-169.
  14. Gómez DG. Mi recuerdo de don Gonzalo. Arch Neurobiol (Madrid) 1972;35:177-182.
  15. Lafora GR. Los Niños Mentalmente Anormales (Mentally Abnormal Children). Madrid: Tipografía “La Lectura”, 1917.

 


 

ENRIQUE CHAVES-CARBALLO, M.D., retired physician, resides in Overland Park, Kansas.

 

Fall 2022  |  Sections  |  Neurology