Yann Péréon

Unique drawings by Duchenne de Boulogne

Guillaume Duchenne de Boulogne (1806–75) is renowned not only for his contributions to the fi eld of muscular diseases, but also for pioneering the use of photography in medical books. Despite his fondness of photography, Duchenne was also a keen illustrator and used his fi ne drawing skills to portray In the evaluation of new-onset seizures in pregnant and post-partum women, the authors state that patients “should undergo thorough investigation, usually including MRI sequences”. This statement could be taken to mean that all such patients require MRI for diagnosis, which is practically impossible in a resourcelimited setting. Instead, the utility of CT venography should have been emphasised, at least for post-partum CVST. Multidetector CT venography has equal sensitivity to magnetic resonance venography for diagnosis of CVST. Multidetector CT venography also provides better anatomical visualisation of the dural sinuses and cerebral veins than does magnetic resonance venography of various strengths. Although Edlow and colleagues have described all the clinical features of CVST, we emphasise the importance of papilloedema as a clinical sign because it often provides the fi rst clinical clue of a possible CVST, especially in patients who present in the emergency ward with new-onset seizures without any focal neurological defi cit. Finally, CVST can present as isolated psychiatric abnormality and can be misdiagnosed as post-partum psychosis or depression.

Palmo-Plantar hyperkeratosis, intellectual disability, and spastic paraplegia in two maternal half brothers: further evidence for an X-linked inheritance.

In 1983, Fitzsimmons et al. reported four brothers with an unrecognized disorder characterized by intellectual disability, spastic paraplegia, and palmo‐plantar hyperkeratosis (OMIM 309500). In this report, we describe a family in which two males, maternal half‐brothers, had learning disabilities. Both patients also showed spasticity in the lower limbs and palmo‐plantar hyperkeratosis. The mother of the affected boys had learning difficulties but did not show any dermatological symptoms. This report confirms that the association of features reported by Fitzsimmons et al. is a distinct entity and further suggests an X‐linked mode of inheritance.

Paralysis with muscle atrophy.

What has been the greatest achievement of your career? What stands out most for me is that over the years I’ve been able to develop great relationship with junior and senior leaders across disciplines in neuroscience and beyond. Through these connections, I’ve developed a clear vision of where I want our scientifi c discoveries to go and how I can contribute. My challenge now is to bring the vision to life.

The first illustrations of neurons by Camillo Golgi

In 1906, the sixth Nobel Prize in Physiology or Medicine was awarded to Camillo Golgi (1843–1926) and Santiago Ramon y Cajal (1852–1934) in recognition of their work on the structure of the nervous system. The name of Golgi is eponymous with the cytoplasmic organelle that he discovered (the Golgi apparatus) and a type of cerebellar cell (the Golgi cells). But Golgi’s most impressive contribution was perhaps his method of histological silver-staining, the black reaction (la reazione nera), described in 1873 at the Abbiategrasso Hospital in Milan, Italy. This method initiated a new era in the description of the microscopic anatomy of the nervous system. Golgi studied at the University of Pavia, Italy, which was famous for its school of anatomy, led by Giovanni Battista Morgagni and Antonio Scarpa. He became interested in the study of nervous system cells through his teacher and friend Giulio Bizzozero, a pathologist who had been a student of Rudolf Virchow at the Charite Hospital at the University of Medicine in Berlin, Germany. Golgi used the black reaction to study the cerebellum, the olfactory bulb, the hippocampus, and the spinal cord. His fi ndings raised fundamental questions about the structure–function relationships in neuronal circuits. Golgi championed the so-called reticular theory, which envisaged the nervous system as a single, continuous network. The notion was challenged by Ramon y Cajal’s widely accepted neuron theory. Between 1875 and 1885, Golgi published eight masterpieces entitled “Sulla fina anatomia degli organi centrali del sistema nervoso”, with 24 colour plates drawn by himself, in the Rivista sperimentale di Freniatria e di medicina legale, a specialist Italian journal. These articles describe some of the most important work on the structure of the nervous system published at that time. They contain much better plates than those included in the books that reprinted these articles in 1886 and 1894 (a German translation), and again in Golgi’s Opera Omnia in 1903. At the time, reprinting preserved neither the beauty of the original plates nor the details of fine anatomical nervous structures. More than a century after its initial publication, Golgi’s work is always of considerable historical scientific interest. We had the opportunity to find in a small bookstore in Rome, Italy, all the issues of Rivista sperimentale di Freniatria e di medicina legale with the eight articles by Golgi and the original coloured plates. These plates are extremely rare, as very few copies of these issues were printed. The figure displays one of these beautiful plates, and the remainder are presented in the appendix. The plate reproduced here illustrates the connections between multiple Golgi cells in a sample of cerebellar convolution (vertical section) from a neonatal cat. As translated from Golgi’s original legend, “the design is particularly intended to show the shape, arrangement, ramification rules, positions, and links between ganglionic cells existing within the granular layer”. Golgi’s histological samples were thick, and such thickness can affect the functional description of neurons and fibres. Cells were therefore drawn from slightly different microscopic depths of fi eld. Axons and dendrites are presented in a single image, although extending across multiple layers. Indeed, Golgi’s drawing was specifically made to show shapes, ramification laws, dispositions, localisation, and relationships of the large ganglionic cells of the granular layer. Protoplasmic prolongations branch dichotomously in a very different way than do those of Purkinje cells. The most distal extensions of the branches often reach the molecular layer peripheral limit. Figure: Plate VIII—The spatial relationships between multiple Golgi cells

G.P.156

Hereditary Fibrosing Poikiloderma (HFP) with tendon contracture and pulmonary fibrosis has been described in a South-African family with autosomal dominant inheritance by Khumalo et al. in 2006. Recently, we confirmed the existence of this new syndrome by reporting four additional cases and identified the causative gene called FAM111B (NM_198947.3) by whole exome sequencing. Here we report the clinical and molecular data of seven independent patients: four males and three females (ages 3–38). Key features consist of: (i) congenital poikiloderma, hypotrichosis, hypohidrosis; (ii) muscle contractures in particular triceps surae and/or biceps brachii muscle contractures; (iii) progressive muscular weakness with a proximal and distal pattern and (iv) progressive pulmonary fibrosis. Muscle MRI showed extensive fatty infiltration confirmed by muscle biopsy. Histological examination of skeletal muscle revealed a partial loss of muscle tissue associated with extensive fibrofatty tissue infiltration regardless of age. There was no indication of denervation, necrosis, or inflammation. Microscopy of the skin showed a sclerodermiform aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two mutations were shared respectively by three and two patients). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain of function or dominant negative mutations resulting in FAM111B enzymatic activity changes. Functional studies are ongoing to better understand the pathophysiology of this entity. In conclusion, HFP with tendon contracture, myopathy and pulmonary fibrosis, a phenotypically recognisable syndrome, is caused by autosomal dominant mutations in FAM111B gene. These findings provide genetic evidence for a new pathogenetic pathway for muscle impairment.