Michał K. Owecki

Maksymilian Rose (1883–1937)

began his own research on the cytology of neurons in the cerebral cortex. Some of his works from that period of time covered such topics as cytoarchitectonic parcellation of forebrain of reptiles and birds [2]. Yet, it was On the histological principle of divisions of the cerebral cortex that earned him international attention [3]. Consequently, in 1925, he was appointed by Professor Oskar Vogt, the prospective director of the neurology department at Kaiser Wilhelm Institute in Berlin for Anthropology, Human Heredity and Eugenics. Rose remained there three busy years as a Member of the Institute’s Scientific Board. In 1926, he served on the editorial board of “Journal für Psychologie und Neurologie”, a leading neurological journal in Germany at that time, and in 1927, on Vogt’s request, he was appointed as its editorin-chief. At the same time, he worked on two atlases on cerebral cortex cytology and cytoarchitectonics [4, 5]. He also proved the division of the retrosplenial cortex into the granular and agranular part [6] and provided a detailed cytoarchitectonic analysis of the insula [7]. In 1928, Rose moved to the University of Warsaw, despite strong protests of his German colleagues, Walther Spielmeyer and Oskar Vogt. There he completed his habilitation thesis and two years later, in 1930, he founded the first Polish Brain Research Institute. In the newly established centre Rose introduced a modern neuropathological staining technique—the Cajal’s method. In 1931, Rose was appointed as the chair at the Psychiatry Department of the University of Vilnius to succeed Stanisław Władyczko, a prominent figure in central European psychiatry. In interwar Poland, only very few Poles of Jewish origin succeeded in attaining the position of a full professor; thus Rose decided to leave Warsaw, transferring the Brain Research Institute with him. In Vilnius he continued his broad scientific research, successfully joining it with his teaching duties and directing the neurological clinic. He The year 2017 marks the 80th anniversary of the death of Maksymilian Rose, one of the pioneers of brain cytoarchitectonics. Rose was born on May 19, 1883 into a Jewish low-income family in Przemyśl, Galicia, a Polish territory annexed by the Habsburg Empire (Austro-Hungary). After completing his secondary education in the small town of Wadowice, he studied medicine at the Jagiellonian University (JU), graduating with distinction in 1908. Next he took up a position at Cracow’s University Neurology and Psychiatry Department where he worked as an assistant of Professor Jan Pilz until 1910. The young professional quickly gained his new superior’s recognition, which enabled him to be trained in the best neurological centres of the time in Western Europe. Therefore, Rose spent the following two years abroad, continuing his education at various renowned clinics in Switzerland and Germany. In Berlin, he studied under Herman Oppenheim and Theodor Ziehen, the leading neurologists and psychiatrists in the German Empire. Shortly thereafter he moved to the Rheinau psychiatric clinic and, in 1912, to Professor Robert Gaupp’s clinic in Tübingen, where he worked on cytoarchitectonics under Professor Korbinian Brodmann who played a decisive role in shaping his further research interests [1]. After returning to Cracow in 1913, Rose was accepted for a position at the JU Descriptive Anatomy Unit where he

Co‐occurrence of Jalili syndrome and muscular overgrowth

Jalili syndrome is a rare disorder inherited in an autosomal recessive pattern manifesting as a combination of cone‐rod dystrophy including progressive loss of visual acuity, color blindness, photophobia, and amelogenesis imperfecta with hypoplastic, immature, or hypocalcified dental enamel. It is caused by mutations in CNNM4, which encodes the ancient conserved domain protein 4. Here we report three brothers with Jalili syndrome and muscle overgrowth of the legs. Myopathic changes were found in needle electromyography. Mutational analysis showed in all three brothers a novel likely pathogenic homozygous missense substitution in exon 1 (c.1076T>C, p.(Leu359Pro)) of CNNM4. Both parents were carriers for the variant. In order to exclude other causative variants that could modify the patients’ phenotype we performed exome sequencing and MLPA analysis of the DMD gene in Patient 1. These analyses did not identify any additional variants. Our results expand the mutational spectrum associated with Jalili syndrome and suggest that mild myopathy with muscle overgrowth of the legs could be a newly identified manifestation of the disorder.

Analysis of PRKN Variants and Clinical Features in Polish Patients with Parkinson’s Disease

The etiology of Parkinson’s disease (PD) is still unclear, but mutations in PRKN have provided some biological insights. The role of PRKN mutations and other genetic variation in determining the clinical features of PD remains unresolved. The aim of the study was to analyze PRKN mutations in PD and controls in the Polish population and to try to correlate between the presence of genetic variants and clinical features. We screened for PRKN mutations in 90 PD patients and 113 controls and evaluated clinical features in these patients. We showed that in the Polish population 4% of PD patients had PRKN mutations (single or with additional polymorphism) while single heterozygous polymorphisms (S167N, E310D, D394N) of PRKN were present in 21% of sporadic PD. Moreover, 5% PD patients had more than one PRKN change (polymorphisms and mutations). Detected PRKN variants moderately correlated with PD course and response to L-dopa. It also showed that other PARK genes (SNCA, HTRA2, SPR) mutations probably may additionally influence PD risk and clinical features. PRKN variants are relatively common in our Polish series of patients with PD. Analysis of the PRKN gene may be useful in determining clinical phenotype, and helping with diagnostic and prognostic procedures in the future.

Substantia nigra hyperechogenicity in Polish patients with Parkinson’s disease

BACKGROUND Hyperechogenicity of the substantia nigra (SN) measured by transcranial sonography (TCS) is a characteristic feature observed in patients with Parkinsons disease (PD). To our knowledge, no SN hyperechogenicity data are available for Polish population. Moreover most of studies come from few centres, which used the one type of ultrasound device. The main aim of the study was to investigate the association between PD and SN hyperechogenicity measured by sonographic machine, not assessed so far. MATERIALS AND METHODS In this study cross-sectional study SN hyperechogenicity was evaluated in 102 PD patients and 95 control subjects. Midbrain was visualised by Aloka Prosound 7 ultrasound device. SN area measurement, the relation to the clinical features of PD, inter- and intra-observer reliability were evaluated. RESULTS We confirmed that SN echogenicity is significantly increased in PD patients compared to control subjects (p < 0.001). The area under curve for PD patients vs. controls was 0.93. Receiver operating characteristic analysis indicated a cut-offs for SN echogenicity at 0.19 cm² with accuracy equal to 90%, specificity - 86% and sensitivity - 93.7%. The SN hyperechogenicity was not related to PD clinical findings. Reliability was good if an experienced sonographer performed the SN measurements. CONCLUSIONS This study shows that the SN abnormality observed by TCS isa specific feature, which can be helpful in the process of PD diagnosing.

Mutations of the SNCA gene and alpha-synuclein level in the patients with diseases of the extrapyramidal system

Parkinsons disease (PD) is one of the most common degenerative diseases of the extrapyramidal system and the incidence of this disease increases several times with age. It is believed currently that the cause of PD are environmental and genetics factors. An important genetic factors associated with disclosure of PD are SNCA gene mutations and polymorphisms of the region NACP-Rep1 promoter of SNCA, which may affect on the level of alpha-synuclein (ASN). The aim of the study was analysis of G88C mutation and the NACP-Rep1 region in the promoter of SNCA gene and the study of ASN level. The study was conducted on 78 individuals of the Polish population: 40 patients with diagnosed PD (18W and 22M, the average age 65 years), 4 patients with diagnosed multiple system atrophy (3W and 1M, the average age 59 years), 9 patients with diagnosed parkinsonism (5W and 4M, the average age 55 years) and 25 control volunteers without neurological symptoms and dementia (18W and 7M, the average age 57 years). G88C mutation in the SNCA gene was analyzed by performing PCR-RFLP reaction, polymorphism of the NACP-Rep1 promoter region of SNCA gene was evaluated using PCR reaction and capillary electro-phoresis. The ASN level in blood plasma was determined by ELISA. The result of the conducted studies was the exclusion of the presence of the familiar grounds of PD, which are connected with the G88C mutation in the SNCA gene, both among 53 patients with diseases of the extrapyramidal system and 38 control volunteers. Moreover, it was shown that in the Polish population the allele 0, +1, +2, +3 and the haplotypes 0/+1, 0/+2, +1/+1, +1/+2, +2/+2 and +2/+3 of the SNCA promoter region can appear with a various frequency among patients with analyzed disorders of the extra-pyramidal system. It was also shown that both the al-lele 0 and +1 and the haplotypes +2/+2 and +2/+3 of the promoter region SNCA gene can influence differently the disclosure of PD. It was also proved that level of ASN both among the patients with PD and with parkinsonism depends from the haplotype of the promoter region SNCA gene. The advancement and duration of the disease among patients with PD can have an impact on the level of ASN. It seems that polymorphism of the NACP-Rep1 in the promoter region of SNCA gene influence on the level of ASN among patients with diseases of the ex-trapyramidal system.

Psychopatologia chorób układu nerwowego w wieku podeszłym

Streszczenie Choroby naczyniowe i zwyrodnieniowe ośrodkowego ukladu nerwowego nalezą do jednych z najczestszych problemow zdrowotnych wieku podeszlego. Zaburzenia funkcji poznawczych, afektu i zachowania, a takze objawy wytworcze stanowią nieodlączny element obrazu klinicznego wiekszości spośrod tych chorob. Objawy psychopatologiczne wywierają istotny wplyw na decyzje terapeutyczne, są tez źrodlem dodatkowego cierpienia dla osob chorych oraz ich bliskich i opiekunow, nierzadko przesądzając o konieczności instytucjonalnej opieki nad pacjentem. Znajomośc i prawidlowe rozpoznanie charakteru objawow psychopatologicznych pozwala na rozpoczecie adekwatnej terapii, ktora daje szanse poprawy jakości zycia zarowno samego pacjenta, jak i jego opiekunow. W artykule przedstawiono manifestacje kliniczną zaburzen psychicznych wystepujących w przebiegu powszechnych dla wieku podeszlego chorob ośrodkowego ukladu nerwowego.

Jean-Alexandre Barré (1880–1967)

War I (1914–1918). The war brought new challenges for the medical staff of the time: millions of soldiers suffered severe psychological and somatic injuries of new types and on a scale never experienced before. Barré began his military service as a member of a front-line ambulance unit, but was later directed, fortunately, to hospital work within a neurological unit of the Sixth Army in the northern region of France. This relocation not only radically improved his chances of surviving the war, but also gave rise to a successful collaboration with Georges Guillain (1876–1961), the chief physician at the Sixth Army’s neurology center at the time. In 1917, Barré was assigned to the military neurological center in Nantes and afterwards, in 1918, with the end of the war, he gained a position as Director of the Neuropsychiatric Military Center in the Eastern Region of France. Throughout the war years, Barré effectively combined his military duties and care of injured soldiers with his scientific interests: hundreds of wounded men were not only the subject of his medical attention, but also the inspiration for in-depth clinical analysis. In cases of suspected hysteria as a way of avoiding army service, Barré warned against hastily attributing the symptoms observed to psychological causes and recommended a careful neurological examination of each patient. In close collaboration with Guillain, he studied the clinical presentation and course of numerous cases of peripheral and central nervous system traumatic lesions. The two men’s research work on wounded soldiers resulted in improved neurological examination techniques and contributed new insights to localizing symptomatology, in particular of spinal cord injuries. Their observations supported the conception of the early surgical management of spinal cord trauma and accompanying vertebral fractures. However, a high mortality rate due to bacterial infections remained an impassable obstacle for Barré and his colleagues in that pre-antibiotic era [2]. Jean-Alexandre Barré (Fig. 1) was a French neurologist, now mostly known for an early description of acute immunemediated inflammatory polyneuropathy, a heterogeneous neurological condition classified and grouped under the eponym Guillain-Barré syndrome. A skillful and perceptive clinician, he was also the author of the Barré test, a diagnostic maneuver still sometimes used in everyday neurological practice. Barré was born on May 25, 1880, in Nantes in France. He studied medicine at the University of Nantes and, following his graduation, began his medical career at a hospital in his hometown as an intern, with the idea of becoming a surgeon. In 1901, he completed his compulsory military service and, 5 years later, moved to Paris, where he successfully applied for an internship. It was during that time that he met Joseph Babiński (1857–1932), a masterful clinician of Polish origin, who introduced Barré to the fascinating world of neurology. Meeting Babiński influenced Barré’s life: he abandoned his surgical plans and began his neurological career. He completed his medical training under the guidance of Dr Alexandre-Achille Souques (1860–1944) and Professor Pierre Marie (1853–1940). Barré’s interests at that time were focused on syphilis and the skeletal changes caused by the disease. In 1912, he obtained his doctorate degree for an original thesis entitled “Osteoarthropathies in spinal syphilis. A critical study and a new conception” [1]. In the following years, Barré continued his neurological work as assistant to Babiński until the outbreak of World

George Huntington (1850–1916)

To the memory of Magdalena P. and all my patients with Huntington’s disease that I was unable to help as I wished. The nineteenth century was a time when specializations evolved from general medicine. General physicians, out of necessity dealing with the majority of their patients’ health problems, sometimes made important observations relevant to particular emerging specializations. For instance, a single article might unintentionally become an unquestioned and significant contribution to the development of a specific field of medicine. A good example in this context is George Huntington, the American family doctor after whom Huntington’s disease (or Huntington’s chorea) is named. George Huntington (Fig. 1) was born on April 9, 1850, in East Hampton on Long Island, New York, to a family with a rich medical tradition. He represented the third generation of physicians: his father, George Lee Huntington (1811–1881), had continued the medical practice opened by his own father, Abel Huntington (1777–1858). George Junior graduated from the Clinton Academy in his native town and, in 1868, began his medical studies at the College of Physicians and Surgeons at Columbia University in New York. In 1871, he qualified in medicine, with an inaugural dissertation on opium, at the age of 21. Shortly afterwards, he moved to Pomeroy in Ohio, where he began work as a family doctor [1]. On February 15, 1872, young Huntington traveled to the neighboring town of Middleport, Ohio. As it would turn out, the destination of that trip of a few miles was much farther: to a permanent place in the history of medicine. In front of the local medical society at the Meigs and Mason Academy of Medicine, a 22-year-old family doctor from a small town in the East of the United States, only 1 year after completing his medical graduation, with little clinical experience, gave a speech “On chorea”. Huntington must have been surprised by the significant difference he had noticed when comparing Sydenham’s chorea during his studies with those cases of chorea seen at his father’s practice. This probably explains why he chose to speak on chorea as a kind of welcome introduction to his new medical colleagues [2]. In his lecture, Huntington presented the clinical characteristics of chorea but, paradoxically, he dedicated the majority of the speech to discussing the symptomatology of Sydenham’s disease. Only in the final paragraphs did he specify the clinical features of the type of chorea later named after him: its hereditary nature, the onset occurring at “adult or middle life”, the predisposition to developing psychiatric symptoms, and a tendency to suicide. He also pointed out the steady progression of the disease, without any remission. At that time, he considered this form of chorea to be exclusive to Long Island and restricted “fortunately [to] a few families”; this was probably the reason he finished his lecture claiming that he only presented a “medical curiosity” with little practical significance. Time has shown how wrong he was in this opinion. The applause that followed the lecture prompted him to send his manuscript to The Medical and Surgical Reporter in Philadelphia, where it was printed only 8 weeks later, on April 13, 1872 [3]. This scientific report was noticed and published in the same year in the form of an abstract in the German medical press by Adolf Kussmaul (1822–1902) and Carl Nothnagel (1841–1905) in Jahresbericht or the Yearbook of Important Medical Writing for the Year 1872. Thus, was George Huntington’s name introduced into European medical literature [4]. The increasing recognition of the disease and, hence, growing interest in it contributed to further medical case reports that presented its clinical symptomatology consistent with Huntington’s own perception. In fact, the accurate and comprehensive characterization of chorea presented by George Huntington has become one of the classical descriptions of neurological diseases, and the reason the disease, in a period of eponyms, was named after this modest American physician. Several years later, in 1887, the designation “Huntington’s chorea” was coined by Huber [5]. But no man is an island. George Huntington had no patients of his own * Michał K. Owecki michal.owecki@wp.pl

Kazimierz Orzechowski (1878 – 1942)

Kazimierz Orzechowski, a Polish neurologist, coined the term ‘opsoclonus’ to refer to unpredictable involuntary, horizontal and vertical oscillations of the eyes occurring in some neurological disorders [1]. While today the term is associated primarily with the opsoclonus–myoclonus syndrome, first described in 1962, it is still frequently used in its original meaning, as confirmed by 38,618 articles in the PubMed database (on 30 October 2017). Kazimierz Orzechowski was born into a noble family in the town of Przemyśl in the Austrian Partition (since the end of the eighteenth century to 11 November 1918 Poland was partitioned by Austria, Prussia and Russia) on 5 February 1878. After graduating from secondary school, he went to Lvov (also in the Austrian Partition), where he studied medicine. Having obtained a doctor’s diploma in 1902, he worked for several months as an intern in a local hospital, but soon went to Vienna to learn about the emerging subject of neurology. He was admitted as an intern to the Second Medical Clinic of the University of Vienna which was run by Edmund von Neusser (1852–1912). At the same time, he worked at the Clinic for Psychiatry and Nervous Diseases which was led by Richard von Krafft-Ebing (1840–1902) and, after his sudden death, by Julius Wagner-Jauregg (1857–1940), a pioneer in the study of the effects of thyroid diseases on the nervous system. A year later, in 1904, he moved to the Neurological Institute which was founded and run by Heinrich Obersteiner (1847–1922), a prominent neuroanatomist and neuropathologist, at the University of Vienna. There he carried out his first histological examination of neoplasms in the subarachnoid space and presented results at the meetings of the Psychiatric Society in Vienna. In 1907, he also worked at a clinic led by Lothar von Frankl-Hochwart (1862–1914), who conducted innovative research on pituitary disorders, the pathogenesis of tetany and brain tumours. In February 1909, rich in knowledge and skills, he returned to Lvov to head a much-neglected department of mental diseases at the city hospital. In a short time, he transformed it into a well-organised neurological department with an adjacent clinic. In 1910, he received a postdoctoral degree (called in German-speaking countries ‘habilitation’) in the anatomy of the nervous system and was appointed as an assistant professor of neuropathology without the right to remuneration. He also conducted all histological examinations at the department, trained other doctors in this field and took an active part in the meetings of the Lvov Medical Society. After the outbreak of World War I, he became a neuroscience consultant at the Red Cross Hospital in Lvov and headed the department of nervous system diseases for some time. After the end of this war, he was appointed as an associate professor of neurology at the University of Lvov (Fig. 1). At the beginning of the twentieth century, Lvov was the most important medical centre on the territory of Poland (still partitioned) since all local doctors were graduates or former employees of the University of Vienna. No wonder then that, after Poland regained its independence in November 1918, newly established or reactivated Polish universities sought candidates for chairs and clinics there. In the spring of 1920, being a full professor, Orzechowski was appointed as organiser and head of the Department and Clinic of Neuroscience at the University of Warsaw. The newcomer from Lvov faced open hostility from Warsaw neurologists, the followers of Edward Flatau (1868–1932), who were convinced that the prestigious clinic should be entrusted to one of them. After the death of Flatau in 1932, Orzechowski took over his legacy and became the head of the Department of Neurobiology at the Nencki Institute of Experimental Biology and the Neurosurgical Department at the Trauma Institute in Warsaw. For the rest of life, he remained as the most influential figure in Polish neurology. He founded the Warsaw Neurological Society, later transformed into the Polish Neurological Society, and became its president. He also established its * Anita Maria Magowska anitamagowska@yahoo.com

Henri Meige (1866–1940)

his Jewish patients an irrepressible need to wander continuously, “from city to city, from clinic to clinic” in a search for “an efficacious remedy”. However, at the same time, he also noted these patients’ tendency to withdraw swiftly from any proposed therapy with new medications which were allegedly much more effective. Diagnosing “an obsession with constant traveling” or a compulsive unsteadiness in his patients, Meige reached the conclusion that this was a kind of putatively congenital and race-specific disease touching the Jewish population, and that racial factors were responsible for their inability to settle in a certain place or become part of a certain nation. Words that, in the context of the future Holocaust, are abhorrent. Fortunately, Meige’s doctoral analysis is not what represents his considerable contribution to neurology [2]. In 1894, Meige left Salpêtrière and followed his new mentor, Édouard Brissaud, to continue his neurological work at the Saint-Antoine Hospital in Paris. Meige’s interest at that time was focused on acromegaly and the skeletal changes caused by the disease. In 1895, with Brissaud’s cooperation, Meige accurately concluded that gigantism in teenagers and acromegaly in adults shared the same pathogenesis and was actually the same disease entity, although with a different age of onset [3]. Later, in collaboration with Eugene Feindel, Meige took up a subject that Georges Gilles de la Tourette had dealt with a decade or so earlier. In 1885, Tourette precisely reported the case of the Marquise de Dampierre, who was touched by a disease presenting with a composition of vocal and motor tics. Her illness began in childhood and the tics increased in number and severity over time. Although Tourette was awarded the honour of having the syndrome named after him, he proposed an explanation of the disease pathogenesis that reflected the spirit of the time: tics were a consequence of inherited nervous system degeneration due Henri Meige was a French neurologist now known for the eponymous “Meige’s syndrome”, which is a neurological condition characterized by blepharospasm and orofacial dystonic movements. Born on February 11, 1866 in Moulins-sur-Allier in France, into a family with a rich medical tradition, Meige represented the fourth generation of doctors. He graduated from high school in his hometown, moved to Paris to study medicine and, following his graduation, qualified for a position at Salpêtrière Hospital. His medical training was conducted under the guidance of Jean-Martin Charcot, the Head and the Chair of the Clinic of Nervous System Diseases at Salpêtrière. Meige had the advantage of being one of Charcot’s last interns and, until the end of his life, Meige remained under the great influence of his master’s genius. A few years after Charcot’s death, Meige wrote a short monograph, glorifying not only Charcot’s artistic interests, but also the artistry of his clinical skills and unmistakable diagnostic accuracy; the book was re-edited in 1925 [1]. In 1893, the year of Charcot’s death, Meige obtained his doctorate with a thesis entitled “The Study of Certain Neuropathological Travelers: The Wandering Jew at the Salpêtrière”. Meige prepared his doctoral dissertation under Charcot’s tutelage, basing it on his and Charcot’s observations of Jews hospitalized at the Salpêtrière. However, he also incorporated some conclusions derived from non-academic papers on “wandering Jews”; part of which comprised hideously anti-Semitic trends. Meige noticed in