German Neuropathologist Research Articles

The Gut Microbiota-Brain Axis: A New Frontier in Alzheimer's Disease Pathology.

Dr. Aloysius Alzheimer, a German neuropathologist and psychiatrist, recognized the primary instance of Alzheimer's disease (AD) for a millennium, and this ailment, along with its related dementias, remains a severe overall community issue related to health. Nearly fifty million individuals worldwide suffer from dementia, with Alzheimer's illness contributing to between 60 and 70% of the instances, estimated through the World Health Organization. In addition, 82 million individuals are anticipated to be affected by the global dementia epidemic by 2030 and 152 million by 2050. Furthermore, age, environmental circumstances, and inherited variables all increase the likelihood of acquiring neurodegenerative illnesses. Most recent pharmacological treatments are found in original hypotheses of disease, which include cholinergic (drugs that show affective cholinergic system availability) as well as amyloid-accumulation (a single drug is an antagonist receptor of Nmethyl D-aspartate). In 2020, the FDA provided approval on anti-amyloid drugs. According to mounting scientific data, this gut microbiota affects healthy physiological homeostasis and has a role in the etiology of conditions that range between obesity and neurodegenerative disorders like Alzheimer's. The microbiota-gut-brain axis might facilitate interconnection among gut microbes as well as the central nervous system (CNS). Interaction among the microbiota-gut system as well as the brain occurs through the "two-way" microbiota-gut-brain axis. Along this axis, the stomach as well as the brain develop physiologically and take on their final forms. This contact is constant and is mediated by numerous microbiota-derived products. The gut microbiota, for instance, can act as non-genetic markers to set a threshold for maintaining homeostasis or getting ill. The scientific community has conducted research and found that bowel dysbiosis and gastrointestinal tract dysregulation frequently occur in Alzheimer's disease (AD) patients. In this review, the effects of the microbiota- gut-brain axis on AD pathogenesis will be discussed.

Franz Nissl's multiple contributions

Franz Alexander Nissl (1860–1919) was a German neuropathologist and a fine clinician. While studying at the Ludwig Maximilian University of Munich (Munich, Germany), under the neuroanatomist Aloys von Gudden (1824–86), Nissl won an award for his medical doctoral thesis (The pathological changes in the nerves cells of the cerebral cortex, in our own translation from the original German title). The work described in this thesis provided the basis for the development of Nissl's staining technique, which would become crucial for studying the brain.

The Marvel of Language: Knowns, Unknowns, and Maybes

The Marvel of Language: Knowns, Unknowns, and Maybes Susan McKay Amid our delight in the beauties of literature, our satisfaction in our writing (scholarly, technical, or creative), and the gratification and challenge inherent in our teaching, we often end up giving little attention to language, the faculty which makes all of those endeavors possible and which is the very foundation of our work as language professionals. I would like to use the opportunity of this keynote address to share with you what I see as some of the marvels of language, as I have observed them over the decades of my study and teaching of languages and linguistics. What Kinds of Things Are Linguistically Knowable? For centuries and even millennia, many minds–great and ordinary–have observed that man alone speaks, that language is a panhuman feature that both identifies and unites us. Linguists, and before them philologists, grammarians, philosophers, scribes, and translators, have worked both independently and collaboratively to devise rigorous methodologies for the analysis and description of language. Under objective study and analysis, many of language’s elements have been amenable to discovery. A few of the key things that are linguistically knowable are: • Language is an abstract and complex system of rules. • These rules, or operating principles, are organized internally into subsystems, which are themselves made up of smaller and smaller subsystems. • A vast and intricate web of connections links the rules both within and across systems and subsystems. • These rules reside and operate in the minds of the language’s speakers. • The functioning of these rules is in many ways effortless and unconscious. These properties, and many others, are things we know as linguists. [End Page 49] They have emerged from decades of inquiry and constitute what we think of as some of the fundamental properties of language; they are among what I call the design features of human language. Yet the marvel that is language remains a mystery to us in significant ways, due in no small measure to the limits of what is knowable linguistically. For many crucial properties of language, linguists depend on the research of scholars from other disciplines whose conceptions of and about language often do not correlate with what linguists think of as “knowns.” Let us consider three of those complex and deeply important questions that surpass the field of linguistics itself, and let us try to integrate a linguistic perspective into the views and findings of other disciplines. I will mention a few key aspects of each topic, and then conclude each of the three sections with a summary of “knowns,” “unknowns,” and “maybes.” I. Language and the BraIn: Where is language and how does it operate in the brain? Our knowledge of language as seated in the brain began with the study of focal brain damage, that is, injuries to specific areas in the brain, and any concomitant changes in language ability. Wars in the last half of the 19th century–the American Civil War in the 1860s and the Franco-Prussian War in the 1870s–resulted in many head wounds from sabers, cannon shot, and musket balls, accompanied by many forms of language impairment, collectively known as aphasia. In 1861, French surgeon Paul Pierre Broca found that damage in part of the left frontal lobe (specifically, the left inferior frontal gyrus) was accompanied by impaired speech production. That region of the brain came to be called “Broca’s area.” Building on Broca’s published findings, Carl Wernicke, a German neuropathologist and surgeon during the Franco-Prussian War, traced impairment in language comprehension to some of the wounds he treated in another part of the brain—located further back than Broca’s area—a small part of the left temporal lobe (specifically, the left posterior superior temporal gyrus), which became known as “Wernicke’s area.” In the 20th century, the importance of Broca’s and Wernicke’s areas for language was confirmed by many studies of strokes and other brain injuries. For instance, detailed aphasia studies conducted [End Page 50] in France in the 1930s greatly expanded our understanding of which aspects of language were involved with the two physiological areas. Electro-encephalograms...

Hans Joachim Scherer and His Impact on the Diagnostic, Clinical, and Modern Research Aspects of Glial Tumors.

The historical descriptions of glial tumors are often poorly understood and interpreted. The gross and histological depictions of glial tumors are often credited to Virchow, and while the first true histological description is truly his, gross descriptions can be traced back to the beginning of the 1800s, with their classification and histogenesis attributed to Percival Bailey and Harvey Cushing. Without any question, the most prominent and under-credited researcher in the field of glioma pathobiology was the German neuropathologist Hans Joachim Scherer. Despite the limited armamentarium available to him, his systematic approach led to conclusions, some of which have now been molecularly explained today while some are still being widely researched. Scherer defined pseudopalisadic necrosis as a pathognomonic feature of glioblastoma multiforme (GBM), as well as secondary features due to tumor growth, known collectively as secondary Scherer figures, for example, neuronal and vascular satellitosis, tract and subpial aggregation. All these features are key points in the modern histological diagnosis of glial tumors. Other contributions by Scherer include the definition of glomeruloid vascular proliferation and his conclusion that they are caused by vascular factors released by the tumor, decades before vascular endothelial growth factor and its receptors were discovered and their role in glioma evolution was established. Furthermore, he concluded that GBMs can arise de novo (primary) or from a preceding lower-grade glioma (secondary). All his contributions find their place in all modern aspects of glioma research, with some giving a simple explanation of the phenomena observed in glial tumors.

A Collection of Brain Sections of “Euthanasia” Victims: The Series H of Julius Hallervorden

Julius Hallervorden, a distinguished German neuropathologist, admitted on several occasions that he had received some five hundred brains of “euthanasia” victims from the Nazi killing centres for the insane. He investigated the brains in the summer of 1942; however, their traces were subsequently lost. The present study shows, that the Series H, which was part of the Hallervorden collection of brain sections in the Max Planck Institute for Brain Research, comprises the brain sections of the above mentioned five hundred euthanasia victims. The provenance of 105 patients could be reconstructed and 84 are for sure euthanasia victims. Most of them were killed in Bernburg or in Sonnenstein-Pirna. Hallervorden used the brain sections of Series H until 1956 for his studies and never publicly regretted this abuse of the brains of euthanasia victims.

«A most strange instance of illness in several siblings»--first description of a rare neurological disease in 1830?

Was district medical officer Jensen the first doctor to describe patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN) in Volda in 1830? A case series of four siblings with the same disease written by district medical officer Peter Jensen (1799-1832) in Aalesund in 1830, was published in the Norwegian medical journal Eyr in 1832. The children, who were healthy almost up to school age, developed dystonic involuntary movements and deformities in all extremities, lost their ability to speak and were emaciated before they died at around the age of nine years. Further information about the family and a fifth affected child has been found in the parish records. The clinical picture is consistent with Pantothenate Kinase-Associated Neurodegeneration (PKAN), a rare condition with basal ganglia iron deposition, described in 1922 by the German neuropathologists Julius Hallervorden (1882-1965) and Hugo Spatz (1888-1969). The disease was formerly called Hallervorden-Spatz syndrome, but because of the medical activities undertaken by these two researchers before and during the Second World War, this eponym is no longer recommended.

Die Einbeziehung von Minderjährigen in die nationalsozialistischen Medizinverbrechen - dargestellt am Beispiel der brandenburgischen Landesanstalt Görden

The article shows, through a study of the Berlin-Brandenburg region, that children and juveniles who were subjected to the killings of diseased and disabled, or mentally retarded persons during the Third Reich did not only fall victim to the operations of the "Reichsausschuss" ("Reich Commission for Registration of Severe Disorders in Childhood"). Many were also included in the gas chamber killings of the "T4"-action and in various decentralized killing actions. To gain scientific knowledge, the brains of many of these patients were examined by German neuropathologists. It will be shown that the purpose of the killings was not the painless ending of individual suffering, but that they constituted a means of freeing the public from so-called "ballast existences", whose lives were only prolonged if they could be of scientific use.

Neuropathology in Germany during World War II: Julius Hallervorden (1882–1965) and the Nazi programme of ‘euthanasia’

In Germany, during World War II, more than 120,000 handicapped children and adults were murdered for the convenience of the State. To gain scientific knowledge, the brains of many of these patients were examined by German neuropathologists. Some 698 of these specimens were examined in the Kaiser-Wilhelm-Institut für Hirnforschung in Berlin-Buch by Julius Hallervorden, whose career is reviewed together with that of his superior, Hugo Spatz. Hallervorden also oversaw the examination of cases of mental handicap by W-J Eiche at a laboratory at the Hospital Brandenburg-Gorden. Also in Berlin was Berthold Ostertag, neuropathologist at the Rudolf-Virchow-Hospital, who examined cases from the Children's Ward at Wiesengrund. Smaller but significant numbers of brains were examined in Munich, Heidelberg, Hamburg and Schleswig. Some brains of similar origin were examined in Vienna and in Lubliniecz. Jürgen Peiffer has estimated that German neuropathologists examined 2097 brains arising from the Nazi Programme of 'Euthanasia'.

Movement disorders: Parkinson's disease dominates

We did a 5 year follow-up study of 49 patients who had a mean age of 55 at the time of surgery, no dementia or major ongoing psychiatric illness, and severe levodopa-related motor complications. The benefit on levodopa-responsive motor features during off periods was sustained and dyskinesias were substantially decreased—partly because the dose of dopaminergic drugs was reduced by 59% throughout the study. Tolerance to stimulation did not develop. However, symptoms that do not normally respond to levodopa (eg, dysarthria, postural instability, and freezing of gait) gradually worsened. Cognitive function was stable during the first 3 years; between the third and the fifth year, three patients became demented. Therefore, subthalamic nucleus stimulation provides a sustained benefit on the motor complications of chronic levodopa therapy but does not stop disease progression. With time, many symptoms of PD become non-responsive to therapy with both levodopa and stimulation, probably in relation to the development of mainly non-dopaminergic cerebral lesions. Therapy for nigrostriatal dopamine deficiency does not treat many features that may be just as disabling as the dopamine-responsive symptoms. Braak and colleagues 2 studied the cerebral distribution of α -synucleinimmunopositve Lewy bodies or neurites, the pathological hallmark of PD. They compared the brains of patients with clinically diagnosed of PD with those of healthy people. The authors confirmed that PD is caused by progressive, multisystem neurodegeneration with a predictable sequence. Lesions first occur in the dorsal motor nucleus of the glossopharyngeal and vagal nerves and anterior olfactory nucleus; the lesions then ascend from the medulla oblongata to the midbrain (in particular the pars compacta of the substantia nigra). Cortical involvement follows, beginning with anteromedial temporal mesocortex then a few areas of the neocortex. These findings explain non-motor and levodopa-resistant symptoms and why cognitive impairment occurs late in PD whereas defects in smell and dysautonomia can be detected even at a presymptomatic phase. Glial-cell-derived neurotrophic factor (GDNF), has protective and restorative effects on midbrain dopaminergic neurons in non-human-primate models of Parkinson’s disease. Intraventricular bolus injections of GDNF in 50 patients with PD were not effective because insufficient quantities of GDNF diffused through the ventricular wall and reached the dopaminergic nigrostriatal targets. Gill and coworkers reported on the direct delivery of GDNF into the putamen—the brain area with the most severe dopamine depletion—in five patients with PD. The effects on parkinsonism, openly assessed, were highly beneficial. After 1 year, there was a 39% improvement in the off-treatment motor score and a 61% improvemnt in the activity of daily living score of the unified PD rating scale. Drug-induced dyskinesias were reduced by 64%. Fluorine-18-labelled dopamine uptake was increased in the putamen, which suggests a direct effect of GDNF on dopamine function. This study needs to be confirmed in controlled trials. New ways to release GDNF in the brain are needed to avoid complications related to the implants and the periodic refilling of the pump. The discovery of five genes since 1997 has provided important insight into the pathogenesis of PD. The ubiquitine proteasome system is integral to protein handling and detoxification. Mutations of parkin (PARK2), the most common cause of early onset PD, UCHL1 (PARK5), and the recently discovered DJ-1 (PARK7) 4 lead to a dysfunction of this system, which may contribute to the accumulation and aggregation of the α -synuclein protein (PARK1). However, the pathogenetic network seems complex because DJ-1 is thought to be an antioxidant, and mutations in NR4A2 affect another signalling pathway. In non-familial PD, genes and environment probably interact to give rise to the disease. In clinical practice, these discoveries provide great hope for the discovery of neuroprotective treatments. Hayflick and colleagues 5 looked for pantothenate kinase 2 mutations in patients with classic or atypical autosomal recessive Hallervorden–Spatz syndrome. The classic form presents with dystonia, dysarthria, and rigidity, begins in childhood, and has a rapid progression that culminates in early death. Pigmentary retinopathy is common and iron deposition in the medial globus pallidus is evident on T2weighted MRI (the so called “eye-of-the-tiger” sign). The atypical form of the syndrome has a late onset and slow progression. Mutations in the pantothenate kinase gene were found in all 49 families with the classic form, and 17 of 49 families with atypical disease. All patients with the mutation and none without had the “eye-of-the-tiger” sign. Hayflick and colleagues suggested that the name of the syndrome should be changed—given these findings and the unethical activities of the two German neuropathologists during World War II—and propose “pantothenate kinaseassociated neurodegeneration” (PKAN) for disease caused by the mutation and “neurodegeneration with brain iron accumulation” for the remainder. They also speculated that pantothenate (vitamin B5) could ameliorate symptoms.

Response

Response

100 years of collaboration between Japanese and German neuropathologists.

100 years of collaboration between Japanese and German neuropathologists.

Alzheimer Disease, Down Syndrome and their Relationship

The first detailed description of Down's syndrome is attributed to the English physician John Langdon Down in 1886. In 1907 the German neuropathologist Alois Alzheimer published a report of progressive intellectual, deterioration in a middle aged patient, and a subsequent necropsy identified the presence of plaques and intensely staining fibrils. The term Alzheimer's disease was subsequently applied by Kraepelin (1910) to describe a presenile dementia characterised by what were then believed to be unique histopathological findings. It was not until 1948 that George A Jervis first recognised a genuine association between Alzheimer's disease and Down's syndrome. However, his findings languished in relative …

Some morbid-anatomical aspects of mental deficiency.

Clown: … Nay, I'll never believe a madman till I see his brains.Substantial contributions to clinical medicine have come from the many accounts of abnormalities in the brains of mental defectives, our knowledge of certain conditions such as epiloia, amaurotic family idiocy and microcephaly being largely based on them. But, in the main, these reports have concerned cases selected for some special interest and few workers have attempted to relate morbid-anatomical changes to the general problem of mental deficiency. The most complete description, chiefly histological, of lesions in the brains of idiots is that of Schob (1930), who summarized in his valuable contribution the wide experience of German neuropathologists. The brains of 120 unselected cases were later studied by Berry (1938), the results being published in an atlas illustrating, case by case, the differences between normal and mentally defective individuals. More recently, Christensen and Vestergaard (1949) presented a short account of a routine autopsy series of 46 mental defectives, finding some structural abnormality in every one of these cases. Other researches covered more restricted aspects of the problem and some of these will be referred to below.

TOPOGRAPHIC DISTRIBUTION OF PLAQUES IN THE SPINAL CORD IN MULTIPLE SCLEROSIS

THE PRESENT work is an attempt to define the topographic distribution of plaques in the spinal cord in multiple sclerosis, thus contributing to the solution of the old and important question of the possible relation of vascular territories to the formation of plaques. Ever since Rindfleisch1(1863) first gave an account of the topography and morphology of plaques there has been constant controversy concerning this problem, which has not yet been definitely solved. Its significance has been realized for many years, and it is possible to say as did Rossolimo2(1904) that it is a question of eminent importance to the understanding of the pathogenesis of multiple sclerosis. Prominent German neuropathologists (Pette,31928; Hallervorden,41940) have stated the opinion that no evidence has been given of a relation of vascular territories to the localization of plaques. Hallervorden4stated that plaques are related neither to arterial

From the life of a German medical society

On the pages of our journal there was a message (in 1908) about the emergence of a scientific society in Germany, the main goal of which is to promote the success of neuropathology - the society of German neuropathologists Geseleschaft Deutscher Nervenrzte. Its founder and inspirer must be considered a well-known Berlin professor, H. Oppenheim. In mid-September 1907, the first meeting and opening of this society took place in Dresden. 139 people gathered; 22 reports were made and immediately there was a discussion of the charter, which is remarkable for its remarkable brevity and clarity, set forth in just 17 paragraphs.