September 3, 2019History of Medicine
Frederic Henry Lewey (born Friedrich Heinrich Lewy, January 28, 1885- October 5, 1950) was a prominent Jewish German-born American neurologist. He is best known for the discovery of Lewy bodies, which are a characteristic indicator of Parkinson's disease and dementia with Lewy bodies. Lewy was born in Berlin, Germany on January 28, 1885. He trained in Berlin and Z?rich and graduated from Berlin in 1910. He immigrated to the U.S. in 1933, and died in Haverford, Pennsylvania on October 5, 1950, aged 65. Lewy worked in Alois Alzheimer's Munich laboratory and was contemporary with Hans Gerhard Creutzfeldt (1885-1964), Alfons Maria Jakob (1884-1931) and Ugo Cerletti (1877-1963). He later fled Nazi Germany and moved to the United States.
Frederic Lewy was the first to discover the abnormal protein deposits (later called Lewy body inclusions) in the early 1900s. In 1912, studying Parkinson's disease (paralysis agitans), he described findings of these inclusions in the vagus nerve, the nucleus basalis of Meynert and other brain regions. He published a book, The Study on Muscle Tone and Movement. Including Systematic Investigations on the Clinic, Physiology, Pathology, and Pathogenesis of Paralysis agitans, in 1923 and except for one brief paper a year later, never mentioned his findings again.
In 1961, Okazaki et al. published an account of diffuse Lewy-type inclusions associated with dementia in two autopsied cases. Dementia with Lewy bodies was fully recognized and described in an autopsied case by Japanese psychiatrist and neuropathologist Kenji Kosaka in 1976; he first proposed the term Lewy body disease four years later, based on 20 autopsied cases. DLB was thought to be rare until it became easier to diagnose in the 1980s after the discovery of alpha-synuclein immunostaining that highlighted Lewy bodies in post mortem brains. Kosaka et al. described thirty-four more cases in 1984, which were mentioned along with four UK cases by Gibb et al. in 1987 in the journal Brain, bringing attention of the Japanese work to the Western world. A year later, Burkhardt et al. published the first general description of diffuse Lewy Body Disease.
With Japanese, UK, and US researchers finding in the 1990s that DLB was a common dementia, there were nonetheless no diagnostic guidelines, and each group was using different terminology. The different groups of researchers began to realize that a collaborative approach was needed if research was to advance. The DLB Consortium was established, and in 1996, the term dementia with Lewy bodies was agreed upon and the first criteria for diagnosing DLB were elaborated. Two 1997 discoveries highlighted the importance of Lewy body inclusions in neurodegenerative processes: a mutation in the SNCA gene that encodes the alpha-synuclein protein was found in kindreds with Parkinson's disease, and Lewy bodies and neurites were found to be immunoreactive for alpha-synuclein. Thus, alpha-synuclein aggregation as the primary building block of the synucleinopathies was established.
Between 1995 and 2005, the DLB Consortium issued three Consensus Reports on DLB. DLB was included in the fourth text revision of the DSM (DSM-IV-TR, published in 2000) under Dementia due to other general medical conditions. In the 2010s, the possibility of a genetic basis began to emerge. The Fourth Consensus Report was issued in 2017, giving increased diagnostic weighting to RBD and 123I-MIBG myocardial scintigraphy.