A case history analysis of the “manic type” and the “melancholic type” of premorbid personality in affectively ill patients

Summary The use of case histories in examining the premorbid personality of affectively ill patients is especially useful in the case of patients with a predominantly manic course of the disorder, because this kind of affective illness is very rare. The concept of the manic type of premorbid personality is described in detail and contrasted with the concept of the melancholic type often found in patients with a purely depressive course of the illness.     

Intelligence and temperament as protective factors for mental health. A cross-sectional and prospective epidemiological study

The Sjöbring system of personality dimensions measuring intellectual capacity, activity, impulsivity and sociability was used to study possible salutogenic (i.e. causes of health) effects. The study comprised 590 subjects investigated in 1947, 1957, 1972 and 1988–1989 in the Lundby project, an epidemiological study in Sweden. Psychiatric diagnoses were made in 1947, 1957 and 1972. Mental health was estimated in 1988–1989 using the concept love well, work well, play well and expect well. The Sjöbring dimensions were clinically assessed in 1972. Both in the concurrent study in 1972 and in the prospective study in 1988–1989 super capacity (high intellectual function), super validity (high activity level) and super solidity (low impulsivity) were statistically associated with lower frequencies of certain psychiatric diagnoses and a higher frequency of positive mental health. These variables are proposed to increase coping capacity, and therefore increase stress resilience.     

The significance of cytoplasmic inclusions in late infantile and juvenile amaurotic idiocy

Summary The electron microscopic findings of cerebral biopsies from two siblings with late infantile-juvenile amaurotic idiocy are presented. One patient had a mixture of fingerprint and multilamellar inclusions, often in the same cytosome. The second patient had only fingerprint inclusions.Electron microscopic findings in autopsied tissues from two other cases of late infantile-juvenile amaurotic idiocy with multilamellar cytosomes are also presented. Evolution of the multilamellar cytosomes into lipofuscin was not observed. We concluded that cases of late infantile-juvenile amaurotic idiocy with multilamellar and fingerprint inclusions should be distinguished from cases with lipofuscin.The present investigation was supported by Research Grants NS 05572-08, 1 T01 NS 05712-01 and RR 75.     

Primary intracranial germ cell tumours

Summary A histological study has been made of a retrospective series of 17 primary intracranial germ cell tumours found in a collection of 3550 intracranial neoplasms (incidence of 0.48%). All, except for two differentiated teratomas (one extracerebral in a neonate and another in the lateral ventricle), were situated in the midline in persons aged 5 to 37 years (13 males, 4 females). 12 tumours were located in or originated from the (para)pineal region, two of them also invaded the hypothalamus, while three germinomas occupied the retrochiasmal (supra/intrasellar) region without pineal involvement. There were 11 rather pure tumours (7 germinomas, 4 teratomas of various differentiation) and six mixed neoplasms (2 germinomas with teratoid areas, 3 embryonal carcinomas containing elements of endodermal sinus tumour, choriocarcinoma and germinoma, and one teratocarcinoma with endodermal sinuses). Only one case showed prominent features of endodermal sinus tumour, but characteristic elements of this type were present in four other mixed tumours. All germinomas and germinomatous parts of mixed neoplasms showed an inflammatory reaction of varying intensity, in 6 cases associated with multinucleated giant cells, which may be related to the prognosis of these tumours (one patient with hypothalamic germinoma is alive 6 years after radiotherapy). The close structural similarities between the various types of intracranial and gonadal dysgerminomas and their frequent combination within the same tumour support the concept of a common histogenesis of germ cell tumours regardless of their site of origin. Difficulties of classification may arise from the rather frequent occurrence of mixed germ cell neoplasms.Dedicated to E. Frauchiger, on the occasion of his 70th anniversary.     

Familial glioma: occurrence within the “familial cancer syndrome” and systemic malformations

Summary The family pedigree across eight generations is presented with an association of osteochondrodysplasia, other skeletal abnormalities, familial glial tumours in a father and his son, colonic and other adenomatous disease, and pigment changes. This family cluster of diseases is considered to be a dysontogenetic process with blastomatous features and grouped within the phakomastoses. A review of the literature indicates that some familial gliomas show additional malformations, thus resembling phakomatoses. Others are found to be members within a familial cancer syndrome. A trait of hereditary glioma apart from these syndromes is difficult to identify, especially if only sibships are considered which are likely to share common environmental factors.     

Golgi-like demonstration of “dark” neurons with an argyrophil III method for experimental neuropathology

Summary A silver method is proposed for the selective, well-contrasted and reproducible demonstration of dark neurons in frozen, vibratome and paraffin sections cut at a thickness of 5 to 200 m from aldehyde-fixed brains. The Golgi-like staining of the dendrites enables asorting of dark neurons according to characteristic neuron classifications. The staining procedure includes an esterification with 1-propanol, a treatment with diluted acetic acid and development. The esterification strongly increases the argyrophilia of both dark neurons and mitochondria. Unwanted co-staining of mitochondria is suppressed by the acetic acid treatment, while a special developer is used to render the staining controllable. The applicability of the method to experimental neuropathology is demonstrated by Golgi-like staining of dark neurons in rat brains exposed, before transcardial perfusion-fixation and delayed autopsy, to various pathological conditions including ischemia, hypoglycemia, trauma, status epilepticus, deafferentation and poisoning with kainic acid, colchicine and sodium azide, respectively.     

A study of the capacity of myelinated and unmyelinated nerves to induce experimental allergic neuritis

Summary The capacity of myelin-free Schwann cells to induce EAN was investigated. Human foetal peripheral nerve and human adult abdominal vagus nerve, both containing little or no myelin, failed to induce EAN when injected intradermally (together with Freund's adjuvant) into rabbits. In contrast, human adult sciatic nerve, which is heavily myelinated, induced characteristic signs and histopathology of EAN. Thus in the myelin-free antigens Schwann cell plasma membrane, from which myelin is apparently derived, failed to induce EAN. Reasons for this paradox are discussed.     

Phospholipids of the cerebrospinal fluid in the course of subacute sclerosing leukoencephalitis

Summary Phospholipid fractions and total phospholipids were examined in the cerebrospinal fluid of a 6-year-old girl suffering from subacute sclerosing leukoencephalitis. The examination was repeated in monthly intervals over a period of 5 months. Total phospholipids were found to be considerably higher than in control patients of about the same age. During the time of observation we found an inverse relationship between lecithin and lysolecithin and between cephalin and lysocephalin.List of Abbreviations CSF Cerebrospinal fluid - EEG Electroencephalogram (-graphy) - PEG Pneumencephalogram (-graphy) - SSLE Subacute sclerosing leukoencephalitis - PL Phospholipid(s) - PLP Phospholipid phosphorus - O Origin - LL Lysolecithin - SM Sphingomyelin - L Lecithin - LC Lysocephalin (including lysophosphatidylethanolamine, lysophosphatidylserine and lysophosphatidylinositol) - C Cephalin (including phosphatidylinositol, phosphatidylserine, phosphatidylethanolamine) - Pl Phosphatidylinositol - PS Phosphatidylserine - PE Phosphatidylethanolamine     

Meningiomas with a non-meningotheliomatous component

Summary Seven cases of meningiomas with pseudopsammoma bodies have previously been described in the literature. Two additional cases are presented. Electron microscopy of the cells surrounding the pseudopsammoma bodies reveals an ultrastructure different from that of the meningotheliomatous cells. It is concluded that meningotheliomatous meningiomas with pseudopsammoma bodies are mixed tumours, including a non-meningotheliomatous component, the origin and significance of which is uncertain.     

Characterization of amyloid deposits in biopsies of 15 patients with “sporadic” (non-familial or plasma cell dyscrasic) amyloid polyneuropathy

Summary Review of the clinical and laboratory findings of 39 patients with amyloid polyneuropathy (AP) showed 12 cases to be hereditary and 12 to be associated with plasma cell dyscrasia (PCD). The remaining 15, termed sporadic AP, had neuropathy clinically indistinguishable from the other two groups but without a clinicopathologically identified PCD or positive family history. In an attempt to identify the type of amyloid in sporadic AP, the immunoreactivity of amyloid deposits was investigated using specific antisera raised against the following different chemical types of amyloid fibril proteins: variable regions of amyloid light chains (A) and (A), amyloid protein AA, and prealbumin. It was found that the amyloid in sporadic AP had A antigenic determinants in ten cases, A in one and prealbumin in three; in one case, the A nature of amyloid was confirmed biochemically on the extracted amyloid fibrills. Thus, the most common type of AP in our population appears to be the sporadic form. In sporadic AP, the amyloid is most commonly of immunoglobulin light chain origin, even in the absence of overt PCD, and it can be rapidly categorized immunocytochemically to determine therapeutic directions or provide genetic guidance.     

Post-traumatic epidural hematoma in two patients with long-standing “arrested” hydrocephalus

The occurrence of a post-traumatic epidural hematoma in two patients with long-standing arrested hydrocephalus is reported. There was a relatively long interval between the head injury and the onset of symptoms. The large hematoma was accommodated by the decrease in size of the markedly dilated ventricles. This report stresses the possibility of the presence of an epidural hematoma in the management of head injury in patients with long-standing arrested hydrocephalus.     

Focal ependymal differentiation in the choroid plexus of human newborn brain confirmed by immunohistochemistry with monoclonal antibodies

Summary Ependymal proliferation [Ependymzotten, G. Becker, Beitr Pathol Anat Allg Pathol 103:457–477 (1939)], found in choroid plexus of newborns, can be made easily visible by immunostaining with antiglial fibrillary acidic protein (GFAP) antibodies. The expression of both GFAP and cytokeratin is an unusual feature of these structures.     

Zur Frage des Off-On-Effektes bei Levodopa-Behandlung des Parkinsonismus

Zusammenfassung Tagesschwankungen der Leistungsfähigkeit bei Parkinsonkranken unter langdauernder Levodopabehandlung sind als sogenanntes Off-On-Phänomen bekannt. Reduzierter Proteingehalt in der Nahrung soll diesen Effekt bei Kranken, die nur mit L-Dopa allein behandelt werden, beheben können, nicht aber bei denjenigen, die eine Behandlung mit L-Dopa Dekarboxylasehemmer erhalten (Cotzias et al.). Die Hypothese von Cotzias beruht auf der Annahme, daß eine Transportkonkurrenz zwischen L-Dopa und Aminosäuren zu den Hirnganglien besteht.Um diese Ergebnisse zu prüfen, wurde bei 23 Parkinsonkranken mit Off-On-Phänomen der Einfluß einer proteinarmen Nahrung untersucht.Alle Patienten waren 5–8 Jahre mit L-Dopa vorbehandelt und erhielten zumindest in den letzten 3 Jahren eine Kombinationsbehandlung mit Dopa/Dekarboxylasehemmer. Der Eiweißgehalt der Nahrung wurde auf 25 g pro Tag beschränkt (weniger als 0,5 g pro kg Gewicht) und dies für eine Zeit von 1–4 Monaten.In 6 Fällen konnte eine deutliche Besserung mit Verminderung des Off-On festgestellt werden, in 1 Fall kam es zum völligen Verschwinden des Phänomens. Eine auffallende Besserung der allgemeinen Leistungsfähigkeit konnte in weiteren 5 Fällen beobachtet werden und eine objektive Besserung der Symptome, aber nur während der Off-Periode, festgestellt werden. Die restlichen 12 Fälle haben nicht angesprochen. Bei allen Patienten mit Hyperkinesie wurde eine Steigerung des Symptoms während der Diätperiode beobachtet. Eine Abhängigkeit von Diät zum Alter, Schwere, Dauer der Krankheit und der Dopabehandlung konnte nicht festgestellt werden. Der mögliche Mechanismus des Off-On-Phänomens sowie einige Vorschläge es zu beeinflussen werden dargestellt.

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The off-on phenomenon during treatment of Parkinson's disease with Levodopa

Summary The fluctuation in daily performance of Parkinson patients on long-term L-dopa therapy is known as the so called off-on phenomenon. Cotzias et al. found that a low protein diet is able to control this phenomenon in patients taking L-dopa alone but not in those receiving a combination of L-dopa and decarboxylase inhibitor. The author's hypothesis was based on the competition between the alimentary aminoacids and L-dopa for transport to the brain ganglia.In our attempt to prove the findings of Cotzias group we tested the influence of a low protein diet on 23 Parkinson patients manifesting the off-on phenomenon. All had been pretreated with L-dopa for 5–8 years and taking dopa DI for a minimum of 3 years. The protein intake was limited to 25 g/day (which is less than 0.5 g/kg body weight) for 1–4 months.In 6 cases there was a marked improvment with reduction of the off-on effect, and in one it disappeared completely.A distinct improvement of general capability was seen in the other 5 cases, and an objective improvement of the symptoms was noted, exept during the off period. No response could be observed in the remaining 12 cases. All cases with hyperkinesia showed an augmentation of this symptom during the use of the diet. The diet restriction was not found to be correlated with age, stage, duration of illness or duration of dopa treatment. The possible mechanism of the off-on phenomenon and some suggestions to influence it, are presented.

     

The fine structure of cerebral capillaries in “overgrown” neural tissue

Summary Cerebral capillaries in overgrown neural tissue of chick embryo brains ranging in age from 5–18 days of incubation were studied by means of electron microscopy. The vessels in the abnormal tissue showed more extensive and prolonged interdigitations and overlapping of adjacent endothelial cells than did those in normal control brains. In the abnormal neural tissue the appearance and distribution of endothelial cell organelles was similar to that in normal tissue; however, the Golgi complex was less highly developed, and there was an increased amount of coated vesicles in the capillaries of the abnormal brains.     

Über eine durch grüne Meerkatzen (Cercopithecus aethiops) übertragene,zu Gliaknötchenencephalitis führende Infektionskrankheit (“Marburger Krankheit”)

Zusammenfassung Die August/September 1967 in Marburg aufgetretene, durch grüne Meerkatzen aus Uganda (Cercopithecus aethiops) auf Menschen übertragene schwere Infektionskrankheit (Marburger Krankheit) hat in den tödlich verlaufenden Fällen unter dem Bilde einer subakuten komatösen Encephalitis zu einer Gliaknötchenencephalitis panencephaler Ausbreitung geführt. In den perakuten Verläufen mit nur eintägiger Bewußtlosigkeit fanden sich hingegen lediglich Hinweise auf eine hämorrhagische Diathese im Zentralnervensystem (Syndrom malin").Vergleichende neuropathologische Hinweise auf andere Formen von Gliaknötchenencephalitiden im Umkreis des Fleckfiebers, typhöser und paratyphöser Erkrankungen, der zahlreichen Arboviren-Encephalitiden und der sporadischen einheimischen Gliaknötchenencephalitis und die Frage möglichen Strukturwandels encephalitischer Prozesse nach Überimpfung auf Affen werden erörtert.

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An infections disease transmitted by cercopithecus aethiops (Marburg disease) with glial nodule encephalitis

Summary Report is given on the neuropathological findings in lethal cases of a severe exanthematous infectious disease which occurred in August to September 1967 in Marburg (Germany) and which was transmitted to man by green long-tailed monkeys from Uganda (cercopithecus aethiops). Two lethal cases showed typical clinical signs of a subacute comatous encephalitis. The histological picture was that of a panencephalitis with glial nodules (Gliaknötchenencephalitis) and slight perivasal lymphocytic infiltration. A similar but less marked glial process in combination with focal haemorrhages in the cerebral white matter and corpus callosum was found in a case without inconsciousness and neurological signs. Slight diapedeses were seen in cases which had been unconscious only for one day.The authors compare these neuropathological findings with other forms of glial nodule encephalitis i.e. in typhoid fever, typhous and paratyphous diseases, numerous arthropodborn encephalitides and in the glial nodule encephalitis occuring sporadically in middle Europa. The question of a possible change of the structure of the encephalitic process after animal passage is discussed.

Herrn Prof. Dr. h. c.Hugo Spatz anläßlich seines 80. Geburtstages in Verehrung gewidmet.     

„Fingerprint inclusions” in muscle fibres in dystrophia myotonica

Summary Fingerprint inclusions were observed in numerous muscle fibres of 3 cases of dystrophia myotonica studied by electron microscopy in two different laboratories. They consist of parallel or concentric palisades of short electron dense linear elements. Identical fingerprint inclusions were reported in two other clinical conditions and cannot therefore be regarded as specific for a particular muscle disease. Their origin and significance remain obscure.     

Die Bedeutung der diskontinuierlichen Zonierung des Immunglobulinbereiches für die Diagnose neurologischer Erkrankungen

Zusammenfassung 1. 340 Patienten, welche bei der agarelektrophoretischen Auftrennung der Liquorproteine eine diskontinuierliche Zonierung im Bereiche der -Globuline zeigten, wurden bezüglich Verteilung dieser clonalen -Zonen auf die verschiedenen neurologischen Erkrankungen untersucht.2. Bei der MS und den anderen entzündlichen neurologischen Erkrankungen findet sich eine Häufung der schnell wandernden Zone ₂ und der mittelschnell wandernden Zonen ₃ und ₄.3. Bei den Discushernien und den zentralnervös-nichtentzündlichen Erkrankungen ist die Zonenverteilung ziemlich flach und undifferenziert, wobei hier wie auch bei Tumoren und Polyneuritiden der relativ hohe ₀-Anteil auffällt als ein Phänomen, das bei zentralnervös-entzündlichen Prozessen nur selten anzutreffen ist. In den wenigen Tumorfällen mit -Zonierung scheint die ₄-Position deutlich zu überwiegen.4. In der Hälfte aller MS-Liquoren mit -Zonierung ist das Totalprotein, in einem Sechstel das Total--Globulin (rel%) normal, und nur bei zwei Dritteln finden sich Plasmazellen. Die elektrophoretische Feststellung von -Zonierung ist in der neurologischen Labordiagnostik folglich ein wichtiges Hilfskriterium.5. Mit zunehmendem Anstieg des -Globulin-Gehaltes im Liquor läßt sich bei MS-Patienten, nicht aber bei allen Krankheitsgruppen, eine Zunahme der Häufigkeit der -Zonierung nachweisen.6. Das Auftreten von -Zonierung ist bei den zentralnervös-entzündlichen Krankheiten und der MS sechsmal häufiger als bei den zentralnervös-nichtentzündlichen Krankheiten.7. -Zonierung scheint beim Gesunden, bei psychiatrischen Erkrankungen, Myopathien, bei gewissen Tumoren (Neurinomen) und metabolisch bedingten Polyneuritiden nicht vorzukommen.

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The significance of discontinuous zonation of electrophoretically separated globulins for the diagnosis of neurological diseases

Summary 1. 340 patients in whom discontinuous zonation of the globulin region was observed after electrophoretic separation of the CSF proteins were examined to see how the distribution of these clonal zones is correlated with different neurological diseases.2. In multiple sclerosis (MS) and other inflammatory diseases of the CNS, zones are most frequently found in the medium positions: ₂, ₃ and ₄.3. In disk hernias and the noninflammatory diseases of the CNS, the dispersion of zone frequency is rather undifferentiated. In these conditions and in tumors of the CNS and polyneuritis, the relatively high proportion of ₀ zones is a conspicuous feature; it is scarcely encountered in inflammatory processes of the CNS. The rare cases of tumors with zonation show a preponderance of the ₄ zone.4. The total protein content is normal in half of all MS fluids with zonation; in one sixth the relative amount of total globulin is also normal, whereas plasma cells are demonstrable in only two thirds. The electrophoretic evaluation of zonation is, therefore, an important tool in neurological laboratory work.5. Increased amounts of globulin in CSF are accompanied by an increased frequency of zonation in some diseases, such as MS, but not in tumors or vascular processes.6. The incidence of zonation is about 6 times higher in MS than in noninflammatory diseases of the CNS.7. zonation seems not to be present in healthy persons, in psychiatric diseases, myopathies, some tumors (neurinoma) and polyneuritis of metabolic-toxic etiology.

     

Immunohistological study of senile brains by using a monoclonal antibody recognizing β amyloid precursor protein: significance of granular deposits in relation with senile plaques

Summary Immunochemical analyses revealed that a monclonal antibody Am-3 recognized amyloid precursor protein (APP) in senile plaques extracted from Alzheimer's brain, but did not recognize amyloid protein. Immunohistochemically, however, the staining pattern of Am-3 in frozen section of Alzheimer's brain was almost the same with that of rabbit polyclonal antibody to amyloid peptide which could recognize both amyloid protein and APP. In other words, APP was present in senile plaques of various types, cerebrovascular amyloid and granular deposits. The granular deposits were 5–10 m in size and laminarily distributed in the 1st, 3rd and 4th layers of cerebral cortex. They were especially abundant in 1st and 4th layers where senile plaques were usually fewer in number. Although the distribution in the cerebral cortex was different between the senile plaques and the granular deposits, the number of the granular deposits was well correlated with that of senile plaques. The granular deposits were negative in Congo-red birefringence, but contained amyloid protein as well as APP fragment judging from positive staining by both Am-3 and polyclonal antibody to synthetic amyloid peptide. Thus, they could be regarded as pre-amyloid.     

Elektronenmikroskopie der Hämangioblastome des ZNS und der angioblastischen Meningiome

Summary 4 hemangioblastomas of the cerebellum, 1 of the choroid plexus, 1 of the spinal cord, and 3 angioblastic meningiomas of the brain were investigated with the electron microscope. They all show a similar histological arrangement of vessels, intervascular cells (Zwischenzellen), and the intercellular space. The vessels of the tumors regardless where they originate from are identical in their appearance. They differ from autochthonous vessels by the irregular form of the endothelium and the presence of pores. The Zwischenzellen of hemangioblastomas are not so uniform as those of angioblastic meningiomas. Corresponding to differences in the nucleus/cytoplasma ratio, the development of the ER and the number of cytofilaments as well as the content of lipid droplets hemangioblastomas can be subdivided in 4 types. Nevertheless they constitute a cytological unity. In 3 hemangioblastomas mast cells were found. glial cells mixed up with tumor cells are present only in the border of tumorous and nervous tissue. The extracellular space is filled either with a protein-rich exsudate or with collagen fibrils. — The electron microscopic findings support the histological identity of hemangioblastomas and angioblastic meningiomas. The relation of Zwischenzellen to the vessel walls, their similarity to endothelial cells, and their tendence to form basement membranes indicate that they derive from blastomatous vessels.

Meinem verehrten Lehrer, Herrn Prof. Dr. Gerd Peterz, zum 8. Mai 1971 zugeeignet.     

Juvenile Parkinson's disease and its response to L-dopa therapy

Summary Four youngsters, between the ages of 13–27 years, presented dystonic foot. Two to three years following the appearance of the dystonic foot, cogwheel rigidity and tremor appeared on the dystonic foot side. Treatment with low doses of levodopa/carbidopa consistently reversed the symptoms.On-off phenomena appeared in the first years of treatment and persisted for the entire period of 5 to 15 years of illness. No parkinsonian signs were present when the dystonic foot appeared. Based on our observations and on a review of the literature, we conclude that responsiveness to low doses of L-dopa is the major maker of juvenile Parkinson's disease.