To detect a possible correlation between the neurology and duration of Creutzfeldt-Jakob disease (CJD) and cerebral pathology, we studied 22 autopsy cases by histological and immunohistochemical methods. The duration of disease ranged between I and 15 months with an average of 5.2 months. Only in 11 cases was the EEG typical for CJD. Morphologically the changes varied from minimal spongy changes to severe neuronal loss and brain atrophy. For the three cortical regions examined semiquantitatively, there was no correlation between the severity of spongiform changes and the duration of disease or the pattern of neurological symptoms. The study shows that more extensive sampling for the detection of regional heterogeneity of changes is mandatory in spongiform encephalopathies, and that complicating changes such as intermittant infections may play a role for the survival time as well. Moreover, genetic determinants, prion protein polymorphisms and the mode of exposure have to be considered as possible modulating factors.

Zur Abklärung einer Korrelation zwischen neurologischen Befunden, zeitlichem Verlauf und zerebraler Pathologie bei Creutzfeldt-Jakob-Erkrankung (CJD) untersuchten wir 22 Autopsiefälle. Die Erkrankungsdauer lag zwischen 1 und 15 Monaten. Nur in 11 Fällen lag ein CJD-typisches EEG vor. Die zerebrale Pathologie reichte von minimalen spongiformen Veränderungen bis zu schwersten neuronalen Ausfällen und fortgeschrittener Hirnatrophie. Hinsichtlich dreier semiquantitativ untersuchter Rindenregionen bestand keine Korrelation zwischen Schweregrad und Ausprägung spongiformer Veränderungen einerseits und Erkrankungsdauer und neurologischer Symptomatik andererseits. Die Untersuchungen belegen, dass auch bei spongiformen Enzephalopathien umfangreichere Probenentnahmen zu Abklärung regionaler Heterogenität der Hirnveränderungen notwendig sind und dass Allgemeinveränderungen wie interkurrente Infekte hinsichtlich der Überlebenszeit nicht außer Acht gelassen werden können. Daneben müssen aber auch genetische Determinanten, Prionproteinpolymorphismen und der Expositionsmodus als mögliche modulierende Faktoren berücksichtigt werden.

Muscle & NerveVolume 20, Issue 5 p. 625-627 Short Report Characteristic morphologic manifestation of cadasil, cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, in skeletal muscle and skin Hans H. Goebel MD, Corresponding Author Hans H. Goebel MD Department of Neuropathology, Mainz University Medical Center, Langenbeckstrasse 1, D-55131 Mainz, GermanyDepartment of Neuropathology, Mainz University Medical Center, Langenbeckstrasse 1, D-55131 Mainz, GermanySearch for more papers by this authorRichard Meyermann MD, Richard Meyermann MD Department of Neuropathology, Eberhard-Karls University, Tübingen, GermanySearch for more papers by this authorRegina Rosin MD, Regina Rosin MD Department of Neurology, Eberhard-Karls University, Tübingen, GermanySearch for more papers by this authorWolfgang Schlote MD, Wolfgang Schlote MD Department of Neuropathology, Edinger Institute, Johann Wolfgang-Goethe University, Frankfurt, GermanySearch for more papers by this author Hans H. Goebel MD, Corresponding Author Hans H. Goebel MD Department of Neuropathology, Mainz University Medical Center, Langenbeckstrasse 1, D-55131 Mainz, GermanyDepartment of Neuropathology, Mainz University Medical Center, Langenbeckstrasse 1, D-55131 Mainz, GermanySearch for more papers by this authorRichard Meyermann MD, Richard Meyermann MD Department of Neuropathology, Eberhard-Karls University, Tübingen, GermanySearch for more papers by this authorRegina Rosin MD, Regina Rosin MD Department of Neurology, Eberhard-Karls University, Tübingen, GermanySearch for more papers by this authorWolfgang Schlote MD, Wolfgang Schlote MD Department of Neuropathology, Edinger Institute, Johann Wolfgang-Goethe University, Frankfurt, GermanySearch for more papers by this author First published: 07 December 1998 https://doi.org/10.1002/(SICI)1097-4598(199705)20:5<625::AID-MUS17>3.0.CO;2-VCitations: 19AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Lechner-Scott J, Engelter S, Steck AJ, Dellas S, Tolnay M, Probst A: A patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) confirmed by sural nerve biopsy. Stroke 1995; 26: 235–236. 2 Ragno M, Tournier-Lasserve E, Fiori MG, Manca A, Patrosso MC, Ferlini A, Sirocchi G, Trojano L, Chabriat H, Salvi F: An Italian kindred with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Ann Neurol 1995; 38: 231–236. 3 Ruchoux M-M, Chabriat H, Bousser M-G, Baudrimont M, Tournier-Lasserve E: Presence of ultrastructural arterial lesions in muscle and skin vessels of patients with CADASIL. Stroke 1994; 25: 2291–2292. 4 Ruchoux M-M, Guerouaou D, Vandenhaute B, Pruvo J-P, Vermersch P, Leys D: Systemic vascular smooth muscle cell impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Acta Neuropathol (Berl) 1995; 89: 500–512. 5 Schröder JM, Sellhaus B, Jörg J: Identification of the characteristic vascular changes in a sural nerve biopsy of a case with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Acta Neuropathol (Berl) 1995; 89: 116–121. 6 Tournier-Lasserve E, Joutel A, Melki J, Weissenbach J, Mark Lathrop G, Chabriat H, Mas L, Cabanis EA, Baudrimont M, Maciazek J, Bach MA, Bousser MG: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12. Nat Genet 1993; 3: 256–259. Citing Literature Volume20, Issue5May 1997Pages 625-627 ReferencesRelatedInformation

Despite many sensational and intimidating reports in the mass media, transmissible spongiform encephalopathies (prion disease) are not contagious in the usual sense. Successful transmission requires both specific material (an affected individual's tissue, from or adjacent to CNS) and specific modes (mainly penetrating contact with the recipient). Nevertheless, specific safety precautions are mandatory to avoid accidental transmission and to decontaminate any infectivity. Autopsy is essential for definite diagnosis of these disorders. Recommendations are given here for performance of the autopsy, for neuropathology service and appropriate decontamination; they are based on the current literature and on precautions taken in most laboratories with experience in handling tissue from transmissible spongiform encephalopathies. In particular, special care must be taken to avoid penetrating wounds, possible contamination should be kept to a minimum, and potential infectious material must be adequately decontaminated by specific means.

The brainstems of ten patients with Alzheimer's disease were examined with specific silver impregnations for beta-amyloid deposits, neurofibrillary tangles, neuropil threads and neuritic plaques. The results show a selective and focal involvement of brainstem nuclei, which are diffusely connected to the cortex or are neuronally connected with other damaged subcortical and cortical regions. Therefore, it is concluded that neuronal connectivity plays an important role in the pathogenesis of Alzheimer's disease lesions. This may be due to the intraneuronal transport of beta-amyloid precursor protein. There was a local association between neurofibrillary tangles and neuropil threads, but not between beta-amyloid structures on the one hand and neurofibrillary structures on the other hand. Neuritic plaques were rarely found.

In meningiomas the proliferation index determined with Ki-67 antibody is usually regarded as a reliable criterion of the biological behavior of this tumor entity, as far as it is based on cell proliferation activity. Since its first description by Gerdes et al. in 1983 [3], several studies on the proliferation rate of brain tumors have reported Ki-67 labeling indices (LI) of about 1% or even less than 1% in benign meningiomas, i.e., tumors without any atypical histological findings [2,5,8],

The understanding of delayed hippocampal death as a therapeutic window for post-ischemic treatment of the brain has led to numerous investigations focusing upon underlying cellular mechanisms and pharmacological potentials in gerbils and rats. Nevertheless, studies on the occurrence of delayed neuronal death in the human brain have been singular and dealt with only small files of patients. To complement these limited data, in the present study 26 adult patients with a history of a single cardiac arrest were included. Following successful resuscitation, individual survival ranged from less than 1 h to 186 days (\(\overline x \)= 11 days). The severity of the resultant ischemic injury in hippocampus CA1, among Purkinje cells, or in frontal neocortex, respectively, was quantified by direct counting of necrotic neurons. Additionally, hippocampal specimens were immunostained for neuron-specific enolase. The data obtained demonstrate the occurrence of delayed neuronal death in human hippocampus and, in a minor form, in cerebellar Purkinje cells. This is in contrasts to the immediate manifestation of ischemic neuronal necrosis in the neocortex. Unlike previous findings in experimental animals and in humans, the delay of CA1 cell death could be defined as lasting about 7 days following cardiac arrest. Moreover, the immunohistochemical results indicate delayed neuronal recovery in CA1, which in the time course reciprocally corresponds to delayed manifestation of hippocampal neuronal death. Interpretation of the results must consider the lack of information about the exact individual duration of cardiac arrest and resuscitation, as well as missing data concerning pre-ischemic physiological variables.

The results of neuroradiological grading of 30 oligodendrogliomas were correlated to conventional histology and a proliferation index, which was determined by the monoclonal antibody Ki-67. A good correspondence of neuroradiological criteria and the proliferation index was given in 90% of the cases and demonstrates the value of the radiological method, to detect early stages of malignant transformation. Disagreement between neuroradiology and conventional histology could be observed more frequently than differences from the grading made by Ki-67-values.

In 1940, he worked as a pathologist in the German Air Force.In the meantime, he maintained his connections with the Berlin-Buch Brain Research Institute, where he received a degree of docent in neuropathology in 1942 with his thesis "Zur Histopathologie der neuralen Muskelatrophie und der hypertropischen Neuritis und Neurofibromatose" under the auspices of Robert R6ssle.During the final years of World War II, he did research on brain and spinal cord trauma at an Air Force hospital in Bad Ischl, Austria.Before the end of the war, Krficke was active trying to save the neuroanatomy and neuropathology collection of the K-W-Institute, transferring part of it to the Dillenburg Castle in Hessen.His efforts ensured the reorganization of the

The process of Giant Axonal Neuropathy (GAN) is not restricted to the peripheral nerves, but also involves the central nervous system. In a 25 year old man with normal hair, abundant axon swellings and spheroids were observed in the spinal cord, brain system, and cerebral cortex. The findings in the sural nerve have already been published by Boltshauser et al. (1977). Accumulations of filaments in the axons and in the perineural cells were accompanied by Rosenthal fibres. The ultrastructural pattern of GAN differs clearly from that of Neuroaxonal Dystrophies.

Focal and widespread intense hyperplasia of piloid astrocytes was found in the brain of a 51 year old woman with multiple sclerosis and typical demyelinating lesions. The piloid astrocytosis was confined to older plaques in brain stem, cerebellum and periventricular white matter, but could not be found in telencephalic plaques distant from the ventricular system. The piloid astrocytes and accompanying glial fiber bundles were oriented in alternating direction, thus imitating structural characteristics of spongioblastomas. In the pons, an especially high density of astrocytosis was found with lobulated and giant nuclei and binuclear cells. One large demyelinated plaque in the central white matter of the cerebellum contained numerous Rosenthal fibers between the piloid astrocytes. By their intense glial fiber production, the piloid astrocytes took part of the formation of glial scars. The term spongiocyte is proposed for piloid astrocytes of this highly differentiated type, in order to separate them from the immature spongioblasts of gliogenesis. The pathogenetic mechanism is not clear. It is supposed that during intense reparative astrocytic proliferation the development of atypic reactions is favoured. A primary evocation of this type of reaction by the demyelinating factor itself must also be taken into consideration. The topographic predilection, in our case, of piloid astrocytosis to brain stem and cerebellum indicates a disposition of regions formed by the embryogenetic side plate to reactions of this type.

: Focal and widespread intense hyperplasia of piloid astrocytes was found in the brain of a 51 year old woman with multiple sclerosis and typical demyelinating lesions. The piloid astrocytosis was confined to older plaques in brain stem, cerebellum and periventricular white matter, but could not be found in telencephalic plaques distant from the ventricular system. The piloid astrocytes and accompanying glial fiber bundles were oriented in alternating direction, thus imitating structural characteristics of spongioblastomas. In the pons, an especially high density of astrocytosis was found with lobulated and giant nuclei and binuclear cells. One large demyelinated plaque in the central white matter of the cerebellum contained numerous Rosenthal fibers between the piloid astrocytes. By their intense glial fiber production, the piloid astrocytes took part of the formation of glial scars. The term spongiocyte is proposed for piloid astrocytes of this highly differentiated type, in order to separate them from the immature spongioblasts of gliogenesis. The pathogenetic mechanism is not clear. It is supposed that during intense reparative astrocytic proliferation the development of atypic reactions is favoured. A primary evocation of this type of reaction by the demyelinating factor itself must also be taken into consideration. The topographic predilection, in our case, of piloid astrocytosis to brain stem and cerebellum indicates a disposition of regions formed by the embryogenetic side plate to reactions of this type.

The response of previously severed rat optic fibers to a second transection after various time intervals was studied by light and electron microscopy. The optic nerve of adult animals was crushed retrobulbar and, after 6, 12, 28 or 48 h recrushed 2 mm distant from the first lesion. The changes in the axoplasm of myelinated fibers in the stumps distal to the two lesions, in reference to the perikarya of the cells (i.e. on the cerebral side of each lesion) were studied 6 or 12 h after the second lesion. In the nerves that had been severed 6 h after the first retrobulbar lesion, mitochondria, dense bodies, neurofilaments and endoplasmic reticulum accumulated in the axoplasm distal to the second lesion 6–12 h after the operation. These changes were identical to those seen in the corresponding distal stump of the primary lesion; they may represent a peritraumatic reactive change preceeding the process of Wallerian degeneration.

9 Std nach experimentellen traumatischen Läsionen am Rückenmark der Ratte wurden peritraumatisch in der grauen Substanz der Hinterhörner die Folgen einer Plasmaexsudation in das Gewebe elektronenmikroskopisch beobachtet. Es kommt zu plasmatischer Durchtränkung des Extracellularfugensystems bei Erhaltung der dicht gefügten Lagerung der Zellteile im Neuropil. Es folgen Einrisse der Zellmembranen und Eintritt von Plasmabestandteilen in die Zellfortsätze. Im Cytoplasma akkumulieren Blutplasmabestandteile in rundlichen membranumgrenzten Körpern, die aus dem endoplasmatischen Reticulum stammen. Fibrin wird in Form fein verteilter Fäden eingelagert. Zwischen Gefäßwänden und Neuropil finden sich Fibrinaggregate mit typischer Querstreifung. Die Zellfortsätze zerfallen schließlich, in den lockeren Nekrosebezirken restieren dichte Körper und Doppelmembranbruchstücke. Die plasmatische Infiltrationsnekrose (Scholz) unterscheidet sich somit nicht nur pathogenetisch, sondern auch feinstrukturell von den primär hypoxischen Gewebsschäden (Kolliquations- und Koagulationsnekrose). In der Umgebung der Nekrosezonen tritt ein kollaterales Ödem mit Schwellung der Zellfortsätze auf.

Fibrilläre Astrocytome bestehen nach elektronenmikroskopischer Untersuchung an menschlichem Biopsiematerial (zwei Fälle) aus astrocytären Zellelementen vom „reaktiven faserbildenden Typ“. Der Zelleib hat unterschiedliche Größe, plasmaarme kommen neben „gemästeten“ Astrocyten vor. Hauptbestandteil des Cytoplasmas sind 100 Å breite Filamente, die in den Zellfortsätzen besonders dicht angeordnet sind. Die Perikarya enthalten außerdem Mitochondrien von vorzugsweise runder Form und dichter Matrix, spärliche ergastoplasmatische Zisternen, freie Ribosomen in Rosettenform, vesiculäres Material und verschiedenartige dichte osmiophile Einschlüsse von Lipidcharakter. Die Fortsätze der Zellen bilden ein lockeres bis dichteres Flechtwerk („Gliopil“), das nie die enge, epitheliale Anordnung des Neuropils erreicht; stets sind freie, extracelluläre Räume vorhanden. Feine lamelläre filamentarme Ausläufer der Zellen bilden mehrschichtige, stapelartige oder konzentrische Formationen, meist um präexistente Oligodendrocyten und Nervenfasern.

Der N. opticus von erwachsenen weissen Ratten wurde 5 mm retrobulbär scharf durchtrennt. Nach 24–48 Std. findet man im Axoplasma aufgetriebener Faserstümpfe distal der Läsion vesico-tubuläre endoplasmatische Reticula, Filamente, Anhäufungen von Mitochondrien und dense bodies” sowie Schichtenkörper, die aus schalenartig gewölbten Doppellamellen bestehen und die im Axoplasma der Opticusfasern normalerweise nicht vorkommen. Die Lamellen entstehen durch Fusion sackartig sich ausweitender Anteile des endoplasmatischen Reticulum. Bei der Anreicherung der Mitochondrien spielen wahrscheinlich stumpfwärts gerichtete Axoplasmabewegungen ursächlich eine Rolle; daneben bestehen Anhaltspunkte für eine abschnittweise Querteilung der Organellen. Die dense bodies” repräsentieren besondere Zustandsformen der Mitochondrien, die während reaktiver Vorgänge in neuronalem Cytoplasma vorkommen. Die Mitochondrien neigen zu schalenförmiger Apposition aneinander unter Verdünnung und Abflachung ihrer Mittelteile und verschiedenartiger Transformation der Cristae. Schichtenkörper können durch Apposition derartig sich umwandelnder Mitochondrien an Umfang zunehmen. Während der Formänderungen bieten die Mitochondrien keine Anzeichen einer Nekrobiose. Im Anschluss an diese primären, reaktiven Vorgänge setzen nach dem 2. Tag im Axoplasma regressive Veränderungen ein, die den Beginn der sekundären Degeneration kennzeichnen. The optic nerve was transsected at about 5 mm from its point of entry into the bulbus oculi. After 24–48 hours, the stump on the distal side of the lesion was found to contain swollen axonal end bulbs. They were studied with the electron microscope after osmium tetroxide fixation and embedding in Vestopal W. Mitochondria, dense bodies, vesicotubular endoplasmic reticulum and filaments are seen to be accumulated in the axoplasm. In addition, large spherical lamellar bodies, normally not occurring in the axoplasm, were observed in considerable numbers among these organelles. They consist of double layer plates in the form of spheres, regularly arranged one upon the other. These plates are formed by fusion of vesicles and tubules of the neighboring axoplasmic reticulum. The central space inside the spherical bodies communicates with the surrounding axoplasm. Some mitochondria are attenuated and transformed to cupped disks which associate one with another. Occasionally they are apposed at the surfaces of the lamellar bodies and contribute to their enlargement. It is supposed that the accumulation of axoplasmic mitochondria in the distal stump is mainly caused by movements of the stump axoplasm in the direction of the lesion. The striking increase of small round mitochondrial profiles is probably, in addition, a result of segmentation of the long-distended mitochondria. The dense bodies are considered not as necrotizing mitochondria, but as a special form of these organelles occurring in the course of neuroplasmic reactions to various injuries. Within the first 2 days after transsection, the axoplasm of distal stumps reveals no phenomenon of necrobiosis, though separated from the pericaryon of the cell. Subsequently, increasing density of accumulated organelles and ground cytoplasm indicates that secondary degeneration begins to superpose the primary changes of reactive type.