Gabrielle Lévy and the Roussy-Lévy syndrome.

In 1934, Gabrielle Lévy died at the age of 48. She became well known for an article she published on a hereditary polyneuropathy in cooperation with Gustav Roussy, resulting in the eponym Roussy-Lévy syndrome. Not much is known about this extraordinary neurologist/neuropathologist. Her family declared that she died from the disease she was studying. She was a pupil of Pierre Marie, with whom she worked at the Salpêtrière in Paris and wrote on war neurology. In cooperation with Marie, she published a number of articles on postencephalitic syndromes, which also became the subject of her 1922 thesis. Three years later, she became associate physician at the Paul-Brousse Hospital in Paris, where the study of brain tumors became one of the subjects of her scientific work. Remarkably, Lévy was first author in a few of her many articles, although Roussy confirmed that she often initiated the study and even wrote the main part. In this article her career is considered in the context of the struggle of women physicians to improve their position during the early-twentieth century. She probably died from a brain tumor or a postencephalitic syndrome.

The seminal role played by Pierre Marie in Neurology and Internal Medicine / O papel essencial de Pierre Marie na neurologia e na medicina interna

The authors review the most important contributions of Pierre Marie to the elucidation and description of several neurological diseases, such as Charcot-Marie-Tooth’s disease and hereditary cerebellar ataxia, as well as his contributions to Internal Medicine, including his pioneering studies on acromegaly, ankylosing spondylitis, and hypertrophic pulmonary osteoarthropathy. His works led to incontestable advances in the medical sciences that transcended his time.

Os autores revisaram as mais importantes contribuições de Pierre Marie para a elucidação e a descrição de várias doenças neurológicas, tais como a doença de Charcot-Marie-Tooth e a ataxia cerebelar hereditária, bem como na medicina interna, incluindo os seus estudos pioneiros na acromegalia, espondilite anquilosante e osteo-artropatia hipertrófica pulmonar. Os seus trabalhos promoveram uma crescimento incontestável das ciências médicas que transcenderam o seu tempo.

The seminal role played by Pierre Marie in Neurology and Internal Medicine.

The authors review the most important contributions of Pierre Marie to the elucidation and description of several neurological diseases, such as Charcot-Marie-Tooth's disease and hereditary cerebellar ataxia, as well as his contributions to Internal Medicine, including his pioneering studies on acromegaly, ankylosing spondylitis, and hypertrophic pulmonary osteoarthropathy. His works led to incontestable advances in the medical sciences that transcended his time.

Charcot Marie Tooth disease (CMT): historical perspectives and evolution.

Prior to Charcot and Marie's and Tooth's reports, patients with peroneal muscular atrophy had been described by Virchow, Eulenburg, Friedreich, Osler, and others. In February 1886, Charcot and Marie published their original description of five patients who had what they called Progressive Muscular Atrophy. They surmised that the lesion could be in the spinal cord. Three months later, Tooth presented his M.D. degree thesis entitled "Peroneal Type of Progressive Muscular Atrophy", to the University of Cambridge, UK. Tooth localized the pathology to the peripheral nerves. Dyck and Lambert (Arch Neurol 18:619-625, 1968) classified several CMT kinships based on differences in modes of inheritance, natural history, biochemical features, nerve conduction velocity, and pathologic characteristics. This article will focus on historical landmarks and major discoveries pertinent to the disease since its original description through the second half of the twentieth century.

[Current issues in hereditary neuropathies]. / Actualités dans les neuropathies héréditaires.

This short review highlights five studies published in 2012 in the field of Charcot-Marie-Tooth disease (CMT) and transthyretin familial amyloid neuropathies (TTR-FAN). Regarding CMT, an Australian pediatric study shows the high prevalence of impaired speech perception and hearing disability in children with CMT1 or CMT2 with normal or near normal audiometry (Rance et al., 2012). In a second study, the clinical and electrophysiological characteristics of 14 patients with CMT4C due to mutations in SH3TC2 gene are described (Yger et al., 2012). The 3 clinical hallmarks of CMT4C patients in this French cohort are the high prevalence of scoliosis, the proximal motor weakness and the cranial nerves involvement. Concerning TTR-FAN, the first data from French and international registries are reported (Adams et al., 2012; Coelho et al., 2013) and a phase II trial describes the results of taurourodeoxycholic acid and doxycycline treatment (Obici et al., 2012).

Experimental therapeutics in hereditary neuropathies: the past, the present, and the future.

Hereditary neuropathies represent approximately 40% of undiagnosed neuropathies in a tertiary clinic setting. The Charcot-Marie-Tooth neuropathies (CMT) are the most common. Mutations in more than 40 genes have been identified to date in CMT. Approximately 50% of CMT cases are accounted for by CMT type 1A, due to a duplication within the peripheral myelin protein 22 gene (PMP22). Mutations in the gap junction beta 1 gene (GJB1), the myelin protein zero gene (MPZ), and the mitofusin 2 gene (MFN2) account for a substantial proportion of other genetically definable CMT. Some 15% of demyelinating CMT and 70% of axonal CMT await genetic clarification. Other hereditary neuropathies include the hereditary sensory and autonomic neuropathies, the familial amyloid polyneuropathies, and multisystem disorders (e.g., lipid storage diseases and inherited ataxias) that have peripheral neuropathy as a major or minor component. This review surveys the challenges of developing effective therapies for hereditary neuropathies in terms of past, present, and future experimental therapeutics in CMT.

Clinical and electrophysiological aspects of Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous group of disorders sharing the same clinical phenotype, characterized by distal limb muscle wasting and weakness, usually with skeletal deformities, distal sensory loss, and abnormalities of deep tendon reflexes. Mutations of genes involved in different functions eventually lead to a length-dependent axonal degeneration, which is the likely basis of the distal predominance of the CMT phenotype. Nerve conduction studies are important for classification, diagnosis, and understanding of pathophysiology. The subdivision into demyelinating CMT1 and axonal CMT2 types was a milestone and is still valid for the majority of patients. However, exceptions to this partition are increasing. Intermediate conduction velocities are often found in males with X-linked CMT (CMTX), and different intermediate CMT types have been identified. Moreover, for some genes, different mutations may result either in demyelinating CMT with slow conduction, or in axonal CMT. Nerve conduction slowing is uniform and diffuse in the most common CMT1A associated with the 17p12 duplication, whereas it is often asymmetric and nonhomogeneous in CMTX, sometimes rendering difficult the differential diagnosis with acquired inflammatory neuropathies. The demyelinating recessive forms, termed CMT4, usually have early onset and run a more severe course than the dominant types. Pure motor CMT types are now classified as distal hereditary motor neuronopathy. The diagnostic approach to the identification of the CMT subtype is complex and cannot be based on the clinical phenotype alone, as different forms are often clinically indistinguishable. However, there are features that may be of help in addressing molecular investigation in a single patient. Late onset, prominent or peculiar sensory manifestations, autonomic nervous system dysfunction, cranial nerve involvement, upper limb predominance, subclinical central nervous system abnormalities, severe scoliosis, early-onset glaucoma, neutropenia are findings helpful for diagnosis.

Charcot revisited: the case of Bruegel's chorea.

Since Jean-Martin Charcot's time, Pieter Bruegel has been invoked as a famous contributor to the iconography of chorea. This is based not on a picture by Bruegel himself but on a 19th century engraving declared by Charcot to depict St Vitus' dance or chorea germanorum, a form of mass hysteria. A search through the art history literature did not find chorea or St Vitus' dance as a subject of any of Bruegel's works. However, the picture presented by Charcot appeared to be based on a composition that features a pilgrimage of patients suffering from St John's disease or falling sickness, one of the many names applied to epilepsy. This study traces the history of Charcot's allusions to Bruegel's picture and explores the little-known works--drawings, engravings, and paintings--based on Bruegel's composition in the context of chorea, epilepsy, and hysteria. The conclusion of this study is that while Charcot ignored the precise details of Bruegel's composition, his overall interpretation was correct. Beyond any specific diagnosis, Bruegel's work remains universal, giving a unique and compelling picture of human suffering and of the plight of devoted caregivers.

Pierre Marie: gifted intellect, poor timing and unchecked emotionality.

Pierre Marie was a prominent member of the French neurological world of the early twentieth century. Having been trained by the celebrated physician, J-M Charcot, Marie remained influenced by his teacher throughout his career. Because of this influence, his career can be logically divided into three phases: first, the early years under the direct mentorship of Charcot (1878-1893); secondly, the aftermath of Charcot's death when Marie left his teacher's institution, the Salpêtrière hospital and established himself at the Bicêtre hospital in southern Paris (1893-1918); and finally, Marie's return to the Salpêtrière to assume the original Charcot chaired professorship, albeit as an aged man (1918-1925). This essay examines Marie's career with an emphasis on documentation of the combined attributes of a gifted intellect as well as a heated emotionality. In the context of his time, these elements prompted Marie to enter into controversies and medico-political battles that advanced neurological knowledge, but likely disadvantaged him in his career successes.