Burkhard S. Kasper, Christian Thomas, Anne Albers, Ekkehard Kasper, Konrad Sandhoff
Free Neuropathol 4: 12 (2023)
On February 23rd 1936, a boy-child (“Kn”) died in an asylum near Munich after years of severe congenital dis-ease, which had profoundly impaired his development leading to inability to walk, talk and see as well as to severe epilepsy. While a diagnosis of “Little’s disease” was made during life, his postmortem brain investiga-tion at Munich neuropathology (“Deutsche Forschungsanstalt für Psychiatrie”) revealed the diagnosis of “amaurotic idiocy” (AI). AI, as exemplified by Tay-Sachs-Disease (TSD), back then was not yet understood as a specific inborn error of metabolism encompassing several disease entities. Many neuropathological studies were performed on AI, but the underlying processes could only be revealed by new scientific techniques such as biochemical analysis of nervous tissue, deciphering AI as nervous system lipid storage diseases, e.g. GM2-gangliosidosis. In 1963, Sandhoff & Jatzkewitz published an article on a “biochemically special form of AI” reporting striking differences when comparing their biochemical observations of hallmark features of TSD to tissue composition in a single case: the boy Kn. This was the first description of “GM1-Gangliosidosis”, later understood as resulting from genetically determined deficiency in beta-galactosidase. Here we present illus-trative materials from this historic patient, including selected diagnostic slides from the case “Kn” in virtual microscopy, original records and other illustrative material available. Finally, we present results from genetic analysis performed on archived tissue proving beta-galactosidase-gene mutation, verifying the 1963 interpre-tation as correct. This synopsis shall give a first-hand impression of this milestone finding in neuropathology.

Charles Duyckaerts, Thierry Maisonobe, Jean-Jacques Hauw, Danielle Seilhean
Free Neuropathol 2: 12 (2021)
Jean-Martin Charcot described what he called amyotrophic lateral sclerosis in his 12th and 13th lessons published in 1873 by Bourneville. He distinguished the symptoms that were related to the lesion of the anterior horn of the spinal cord and those that were due to the degeneration (that he named “sclerosis”) of its lateral column. He thought that “inflammation” progressed from the lateral column to the anterior horn (but the term inflammation is not to be taken in the current meaning): the lesion of the anterior horn was thus “deuteropathic”. An album containing drawings made by Charcot is kept in La Salpêtrière Neuropathology Department. Four drawings are pasted on one of its pages, showing the degeneration of the pyramidal tract. They constitute the original of the engravings illustrating Charcot’s 12th lesson. The illustration of the fascicular atrophy of the adductor pollicis presented in the album does not appear in the lessons, even though this alteration is widely discussed and linked to the lesion of the anterior horn, which was supposed to ensure the “nutrition” of the muscle. The technique used by Charcot and his interpretation of the microscopic pictures, as exposed in his lessons, are discussed.
Burkhard S. Kasper
Free Neuropathol 2: 11 (2021)
50 years ago back in 1971, David C. Taylor and colleagues from England reported on a small series of surgical epilepsy cases proposing a new type of tissue lesion as a cause of difficult-to-treat focal epilepsy: a localized malformation of cerebral cortex. The lesion is now known as focal cortical dysplasia (FCD) Type II or Taylor’s cortical dysplasia. FCD II is not rare, and today is a frequent finding in neurosurgical epilepsy specimens. Med-ical progress has been achieved in that the majority of FCD II is diagnosed non-invasively by magnetic reso-nance imaging today. Detailed studies on FCD revealed that the lesion belongs to a spectrum of mTOR-o-pathies, thereby confirming the authors´ initial hypothesis of a relationship to tuberous sclerosis. Here, se-lected original materials from Taylor´s series are presented as virtual slides, supplemented by original clinical records, in order to give a first-hand impression of this milestone finding in neuropathology of epilepsy.