Neuropathological findings in muscle-eye-brain disease (MEB-D)

Summary Congenital muscular dystrophy (CMD) associated with cerebro-ocular dysplasia named muscle-eye-brain disease (MEB-D) is described in two sisters. Progressive hypotonia, mental retardation and severe visual failure appeared immediately after birth. Pathological examination demonstrated muscular dystrophy, hydrocephalus, type II lissencephaly and defective eye development of foetal origin. The great similarity of the clinical and neuropathological picture of both sisters is in agreement with an autosomal recessive inheritance. Neuropathological distinction between Fukuyama-CMD and MEB-D is a more severe and earlier cerebral developmental defect and the association with ocular dysplasia in MEB-D.This investigation is part of the research program Disorders of the Neuro-muscular System of the University of Nijmegen     

“Sporadic” prealbumin-related amyloid polyneuropathy: report of two cases

Summary Two sporadic cases of amyloid polyneuropathy are reported. There was no family history or plasma cell dyscrasia. Both showed sensorimotor and autonomic polyneuropathy with onset in the seventh decade. Amyloid deposits in both cases reacted with anti-human prealbumin sera but not with antisera to human AA and anti-human immunoglobulin light-chain amyloids, including A and A. One patient had the abnormal serum prealbumin and abnormal DNA sequence found in type I familial amyloid polyneuropathy (FAP) (Japanese type). Investigations in sporadic amyloid polyneuropathy should include immunohistochemistry, using antisera to the different amyloid proteins, and the radioimmunoassay and recombinant DNA techniques for diagnosis of FAP.     

Kritische Anmerkungen über die Gedankeneingebung

Zusammenfassung Gedankeneingebung ist eines der Symptome ersten Ranges im Sinne von Kurt Schneider. Schon früher hatte Karl Jaspers eine feinere Trennung vollzogen: Er unterschied zwischen der Gedankeneingebung in einem engeren Sinne und gemachten Gedanken. Indessen haben die meisten deutschen und englischen Autoren die Jasperschen Kriterien dieser Unterscheidung verschmolzen und dadurch den Gebrauch des Terminus ausgeweitet. Auch Kurt Schneider und Weitbrecht sprachen von Gedankeneingebung, gemachten Gedanken und Gedankenbeeinflussung, als ob diese Phänomene identisch seien. Demgegenüber bietet die Jaspersche Differenzierung eine Trennschärfe bei der Erfassung psychopathologischer Symptome, auf die nicht verzichtet werden sollte. Logischerweise und aus praktischen Gründen läßt sich diese Differenzierung auf alle gemachten oder Beeinflussungserlebnisse ausdehnen, so daß man vier Aspekte solcher Phänomene unterscheiden kann. Einige differential-diagnostische Überlegungen hinsichtlich der Gedankeneingebung werden abschließend kurz besprochen.Professor H. -H. Meyer zum 65. Geburtstag herzlich zugeeignet.     

Die Hamburger Schätzskala für Psychische Störungen nach Herzoperationen (HRPD)

Zusammenfassung An einer Stichprobe von 99 herzoperierten Patienten wurde zur Erfassung, Beschreibung und Klassifikation früh-postoperativer psychischer Störungen aus dem psychopathologischen Befundbogen des AMP/AMDP-Systems eine Kurzform (HRPD) entwickelt. Weitgehend mit Hilfe einer klassischen Itemanalyse wurde eine Auswahl von 36 Symptomen vorgenommen.Eine Faktorenanalyse dieser Kurzform ergab 8 Merkmalsfaktoren bzw. Syndromskalen: Desorientierung, Konzentrations-/Denkstörungen, paranoid-halluzinatorische Symptomatik, Angstsymptomatik, gehemmt-depressive Symptomatik, Hostilität, Kontrollverlust sowie Selbstaufgabe.Clusteranalytisch wurden 6 psychopathologisch verschiedene Patientengruppen gefunden: unauffällig, fast unauffällig, leichte psychoorganische Symptomatik mit Affektstörungen, schwere psychoorganische Symptomatik mit Kontrollverlust, Hostilität mit paranoid-halluzinatorischer und psychoorganischer Symptomatik, sowie delirante Symptomatik.Ein Vergleich der Ergebnisse der HRPD mit Syndrombeschreibungen anderer AMP/AMDP-Untersucher ergab zum Teil gute Übereinstimmungen, zum Ted aber auch deutliche Unterschiede, die am ehesten durch die besondere Situation herzoperierter Patienten bedingt sein dürfte.Vorform in englischer Sprache: HRPD = Hamburg Rating Scale for Psychic Disturbances     

A simplified radioimmunological method for the determination of human β-endorphin in cerebrospinal fluid

Summary Human -endorphin-like immunoreactive substances ( _h -EI) in human cerebrospinal fluid (CSF) were determined radioimmunologically. The cross reactivity of the antibodies to human -endorphin ( _h -E) amounted to 40% for human -lipotropin ( _h -LPH) whilst it was less than 1% for leu-and metenkephalin, - and -endorphin, fraction I and II [5], substance P and -MSH. Prior to radioimmunological determination, an adsorbtion of _h -EI from CSF with silicic acid was carried out and followed by a desorbtion, using a mixture of aceton/hydrochloric acid. This method was chosen because the ratio of _h -LPH to _h -E in the desorbat can be shifted in favour of _h -E owing to the variation in recoveries r ( =33%, =64%). On the one hand, this enables a more specific determination of _h -E and, on the other hand, and separation of any peptidase than may be present [9]. An adsorbtion/desorbtion of 2 ml CSF suffices to prove the presence of 20–150 pg/ml (6–48 fmol/ml) of _h -EI.The CSF of 28 patients with various neurological diseases was examined and 24 of them had concentrations of 20–70 pg/ml _h -EI. The remaining four, which had concentrations less than 20 pg/ml, came from meningitis patients undergoing corticoid therapy.A purchasable RIA kit was tested for its determination of _h -E and was found to be unsuitable.

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Zusammenfassung Beta-human-Endorphin-like immunreaktive Substanzen ( _h -EI) im menschlichen Liquor (CSF) wurden radioimmunologisch bestimmt. Die Kreuzreaktivität des von uns eingesetzten Antikörpers gegen Beta-human-Endorphin ( _h -E) zum Beta-human-Lipoprotein ( _h -LPH) betrug 40%, während sie zu Leu- und Met-Enkephalin, Alpha- und Gamma-Endorphin, Fraktion I und II nach Terenius [10], Substanz P und Alpha-MSH geringer war als 1%. Vor der radioimmunologischen Bestimmung wurde eine Adsorption von _h -EI aus CSF an Kieselsäure mit anschließender Desorption mittels eines Gemisches aus Aceton/Salzsäure durchgeführt. Diese Methode wurde gewählt, weil sich dadurch das Verhältnis von _h -LPH zu _h -E im Desorbat zugunsten von _h -E aufgrund der unterschiedlichen Recoveries R ( =33%, =66%) verschob. Damit wird einerseits eine erhöhte Spezifität bei der Bestimmung von _h -EI und andererseits eine Abtrennung von eventuell vorhandenen Peptidasen erreicht. Eine Adsorption/Desorption aus 2 ml CSF genügt, um _h -EI von 20–150 pg/ml (6–48 fmol/ml) nachzuweisen.Patienten (n=28) mit verschiedenen neurologischen Erkrankungen wiesen Werte von 20–70 pg/ml auf. Vier Liquores unter 20 pg/ml stammten von Meningitis-Patienten, welche unter einer Corticoidtherapie standen.Ein käuflicher RIA-Kit wurde auf seine Eignung zur Bestimmung von _h -E untersucht und verworfen.

     

Low temperature in the golden hamster accelerates the gonadal atrophy induced by short photoperiod but does not affect the daily pattern of melatonin secretion

Summary Male golden hamsters were exposed to short photoperiod at either 20C or 5C. After 4 weeks a complete gonadal inhibition was observed in animals kept at 5C while in animals kept at 20C such an inhibition was much less. No significant difference in the pattern of pineal and plasma melatonin concentrations was observed between hamsters kept at 20C and 5C. If in the golden hamster pineal melatonin secretion is implicated in the transduction of the photoperiodic information, it is probably not implicated in the transduction of thermal information.     

AMP-rated psychopathology in chronic alcoholics

Summary In a group of 39 alcoholics within a withdrawal process, the psychical situation was rated using AMP scales (Angst et al. 1969). Cluster analysis of the items rendered the following five-cluster solution: (1) aggressive-depressive patients, (2) less impaired persons, (3) slowed persons with diminished contact, (4) emotionally inadequate persons, (5) appealing depressive persons. These results are discussed with respect to other data from clinical history and diagnostic findings.Supported by Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 115, Teilprojekt C21     

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.     

Morphological demonstration of the first phase of polyomavirus replication in oligodendroglia cells of human brain in progressive multifocal leukoencephalopathy (PML)

Summary Ultrastructural characteristics of adsorption, penetration and intracellular transport of polyomavirus is demonstrated in oligodendrocytes in PML. The findings are compared with those obtained by virological examinations of polyomavirus infections described in cell cultures. The morphology of the eclipse phase and the site of the beginning of virus assembly are also described. The vacuolization of the cytoplasm is considered to be the consequence of the production of viral protein and nucleic acid. The cytoplasmic virions surrounded by membrane in the early and late phases of replication are considered to be infective virions, while those in the cytoplasm in a free state, aligned along membrane fragments or arranged in crystals are classified as virus progenies.The first demonstration of polyoma virions between the separated lamellae of the myelin sheath of a viable axon is presented; their presence, however, is not considered to play a direct pathogenetic role in demyelination.     

Lost in the shuffle: The influence of patient classification scheme on views about the relationship between refusal of medication and involvement in important hospital-based outcomes

The approach used to classify patients into refuser subgroups can influence conclusions about the relationship between refusal of antipsychotic medication and involvement in important hospital-based outcomes such as the need for seclusion and restraint. Use of a cross-sectional taxonomy led to conclusions which were somewhat negatively biased against refusers. In contrast, use of a longitudinal taxonomy which reflects changes in formal informed consent behaivor over time, suggests that it is not refusal, per se, but changes in informed consent status that appear to be associated with problematic behavior. In fact, consistent-refusers tended to be the least troublesome of the three informed consent status groups studied. Researchers are encouraged to use patient classification schemes which consider patterns of formal informed consent behavior over time when examining the relationship between refusal and involvement in important outcomes.     

Apolipoprotein E co-localizes with newly formed amyloid β-protein (Aβ) deposits lacking immunoreactivity against N-terminal epitopes of Aβ in a genotype-dependent manner

Different types of amyloid -protein (A)-containing plaques occur in brains of Alzheimers disease (AD) patients. Diffuse plaques seen during early stages of AD differ from neuritic plaques in later stages both with respect to the length of the A peptides and the presence of other proteins, e.g., apolipoprotein-E (apoE). Since apoE is involved in A transport and clearance, and the 4-allele of the apolipoprotein-E gene (APOE) is a major risk factor for sporadic AD, it is plausible to speculate that apoE plays a pathophysiological role in the initiation of A deposition. To address the issue of whether binding of apoE to A is involved in initial A deposition, we studied the human medial temporal lobe of 60 autopsy cases encompassing the full spectrum of AD-related pathology. In temporal lobe regions, which become involved for the first time at a given stage of -amyloidosis, all plaques represent newly formed plaques, and these were studied with immunohistochemical methods. ApoE was present in 36 cases, and was frequently co-localized with newly formed A deposits detectable with anti-A₄₂ but not with antibodies raised against N-terminal epitopes of A. In 10 additional cases, immunoreactivity against apoE was completely lacking in newly formed plaques, which, at the same time, displayed immunoreactivity against N-terminal epitopes of A. The failure of N-terminal epitopes of A to co-localize with apoE in newly formed plaques indicates that these deposits presumably contain apoE-A complexes, in which the N-terminal epitopes of A are often concealed after complexing with apoE, thus preventing subsequent binding of antibodies. Moreover, apoE-positive newly formed plaques were seen more frequently in APOE 4/4 cases than in non-APOE 4/4 individuals, thereby underlining the potentially crucial role of apoE for the development of A deposits.     

Zur Morphologie und Pathogenese spinaler Läsionen bei Verletzungen der Halswirbelsäule

Zusammenfassung An einer Serie von verifizierten Rückenmarksschäden nach Gewalteinwirkung auf die Halswirbelsäule werden die wichtigsten morphologischen Befunde und ihre formale Pathogenese erörtert. Neben lokalen Kompressions- und Quetschungsnekrosen sowie spinalen Contusionen am Ort der Gewalteinwirkung sind die Nebenläsionen in den Nachbarsegmenten sowie die cranial und caudal vom Lokalherd auftretenden multisegmentalen stiftförmigen Zentralläsionen von Bedeutung, die auch als Fernschäden ohne direkte räumliche Beziehung zur Lokalverletzung sowie ohne manifeste Wirbelaffektion entstehen können. Bei den erst nach mehrtägiger Überlebensdauer nachweisbaren zentromedullären Läsionen, welche den bekannten Cysten mit nekrotischem Inhalt entsprechen, handelt es sich um eigenartige Partialnekrosen ohne Abbau- und Organisationstendenz, die einer reaktionslosen Verflüssigung anheimfallen und am ehesten atypischen Ödemnekrosen vergleichbar sind. Pathogenetisch stehen neben den mechanischen Faktoren vor allem primäre und sekundäre spinale Zirkulations-störungen zur Diskussion, wobei auf die aus den mitgeteilten Befunden morphologisch abzuleitende Bedeutung venöser Durchblutungs- und Abflußstörungen für die Entstehung der spinalen Nebenläsionen und Fernschäden nach Halswirbeltrauma hingewiesen wird.

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Summary In a series of verified spinal cord lesions caused by cervical spine injuries, the most important morphological findings as well as their formal pathogenesis are discussed. Beside local compression and crushing necroses as well as spinal contusions immediately at the side of the impact also Nebenläsionen in the neighbouring segments as well as multisegmental pencil-like central lesions several segments above and below the site of injury are of great importance. These may also occur as remote lesions without direct spatial relation to the local injury and without significant vertebral affection. The centro-medullar lesions to be disclosed only after a survival of several days corresponding to the well known cysts with necrotic content are particular partial necroses having no tendency to reduction and organisation. They undergo a non-reactive liquefaction and can be best compared with atypical edema necroses. As to their pathogenesis beside mechanical factors above all primary and secondary disturbances of spinal cord circulation are to be discussed. The importance of disturbances of venous circulation and drainage is emphasized for the pathogenesis of the spinal neighbouring and remote lesions after cervical spine injuries.

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Mit 7 Textabbildungen

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Auszugsweise vorgetragen auf dem 9. Kongreß der Internationalen Gesellschaft für Orthopädische Chirurgie und Traumatologie, am 1.–7. 9. 1963 in Wien.     

Psychopathology and language behavior in schizophrenics

Summary Verbal samples of 30 schizophrenics were analyzed using the Social Alienation—Personal Disorganization (Schizophrenic) Scale developed by Gottschalk and Gleser (1969). The psychopathological status of all patients had been assessed in a semistandardized interview (Present State Examination, Wing et al., 1974). A relatively close relationship was found between productive or plus symptoms and syndromes of psychosis and the scores on the content analytic scale. On the other hand, no significant relationship existed with the minus symptomatology and no relationship with the residual syndrome and the neurotic syndromes. The Schizophrenic Scale may allow a sufficiently reliable estimate of the degree of psychosis. There was no significant effect attributable to sociodemographic factors and to the course of illness (disregarding the duration of the present hospitalization).     

Types of authority and two problems of psychiatric wards

This paper concerns the relationship between authority structures and two problems reported in the literature as common to milieu or therapeutic community wards. Psychiatric wards with rational-legal and charismatic authority structures are found more likely to experience mood and morale swings on the part of patients and staff and to spend excessive time and energy changing ward rules.     

Comparison of the effects of dopamine D 1 and D 2 receptor antagonists on rat striatal,limbic and nigral dopamine synthesis and utilisation

Summary The effects of dopamine (DA) antagonists upon DA synthesis and utilisation in the rat striatum, olfactory tubercle and substantia nigra have been studied. The concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the rate of depletion of DA afterin vivo inhibition of tyrosine hydroxylase by H 44/68, and the accumulation of L-DOPA afterin vivo inhibition of 1-aromatic amino acid decarboxylase by NSD 1015 were measured in the study. Haloperidol (0.23mol/kg i. p.), sulpiride (293mol/kg i. p.) and remoxipride (5.6mol/kg i. p.) increased both DA synthesis and utilisation in the striatum and olfactory tubercle. A lower dose of sulpiride (45mol/kg i. p.) increased DA synthesis and utilisation in the olfactory tubercle alone. None of the compounds, at the doses used, affected either DOPAC and HVA concentrations or the rate of utilisation of DA in the substantia nigra. Sulpiride (293mol/kg i. p.) and remoxipride, however, produced a modest rise in nigral DA synthesis. The dopamine D 1-selective antagonist SCH 23390 had only modest effects on striatal, limbic and nigral DA synthesis and utilisation at the doses tested (0.078 and 0.36mol/kg i. p.).     

Effect ofd,l-α-aminoadipate on the mediobasal hypothalamus and endocrine function in the rat

Summary Using the glutamate analog,d,l--aminoadipic acid (d,l-AA), experiments were conducted to examine the nature, extent, and specificity of its toxicity in the mediobasal hypothalamus and to determine its effect on endocrine homeostasis. Neonatal rats received daily injections ofd,l-AA (4 g/kg BW) on postnatal days 5–10 and were killed at various post-treatment intervals. Sex-matched littermates were given equimolar amounts of NaCl and served as controls. Treated rats killed 18 days post injection weighed slightly less than controls and had reduced testicular, ovarian, and uterine weights, but the differences were not statistically significant. Ind,l-AA treated rats serum and pituitary levels of TSH and PRL were comparable to control values. Pituitary content of LH ('s and 's) and FSH ('s), however, was lower (P<0.05) ind,l-AA treated rats than in controls, but serum levels were not significantly different. Distinct cytopathologic changes were evident in the arcuate nucleus and median eminence ofd,l-AA-treated rats killed at 2 and 6 h post injection only. By 12 h evidence of acute damage had largely disappeared. Both glial and ependymal cells underwent edematous swelling and necrosis, but neurons were largely unaffected. Evidence of reactive changes, such as gliosis, infiltration of microglia, and removal of debris, however, were not very conspicious. A random sample of mediobasal hypothalami of rats killed 18 days post injection failed to show any detectable lesion or residual effects of earlier pathology. Age at the time of exposure to the gliotoxin was found to be an important variable affecting both extent and duration of injury. The most deleterious effects were observed when the gliotoxin was administered in the form of a single injection on postnatal day 5 only. The results suggest that normal neuronal activity and endocrine homeostasis, specifically gonadotropin, may be irreversibly altered as a consequence of transient disruption of the glial compartment.Supported by grants from the Medical Research Council of Canada, the St. Boniface General Hospital, and Mrs. James A. Richardson Research Foundations     

Visual pattern evoked responses and blink reflexes in assessment of MS diagnosis

Summary VEPs were measured after pattern reversal in 135 MS patients and 30 control subjects. Neurological findings were documented in a standard manner. An extensive ophthalmological examination of all subjects was part of the study. The latency of P₂ was abnormally delayed in 82% of the definite, in 60% of the probable and in 65% of the possible MS groups respectively. The VEP was more often delayed in relation to ophthalmological disturbances. Changes in the MS classification had to be made in more than 10% of the patients, due to delay of VEP latency. These were patients with a spinal form of MS, which is known to create diagnostic problems.Optically and electrically evoked blink reflexes were recorded in 107 MS patients. All patients with mesencephalic lesions had delayed responses of the optically evoked reflex. 74% of the patients with caudal brainstem lesions had delayed latencies of the components of the electrically evoked blink reflex. The blink reflex was delayed in 18 additional patients without brainstem signs. The possibility of delineating clinically silent brainstem lesions by investigating blink reflexes is discussed.Supported by the Deutsche Forschungsgemeinschaft (Dr. Fischer Bosch-Stiftung).     

Attitudes toward mental health professionals in a hospital-based community mental health center

This study examined the attitudes of several diverse subject groups in a large medical center toward various mental health professionals. The groups consisted of: 1) general hospital staff; 2) professional mental health workers; and 3) psychiatric in-patients. Subjects evaluated a selection of 11 professional health related role titles (clinical psychologist, physician, psychiatrist, etc.) and the categories me and mental patient by marking a series of 19 seven-step rating scales, each composed of bipolar anchoring adjectives. Additionally, a familiarity rating for each of the role titles was obtained. An understanding and a value cluster were derived from the 19 adjectives along with an overall favorability-unfavorability score for each role title. It was expected that subjects would value mental health professional roles more strongly than they would indicate an understanding of these same roles. Secondly, it was expected that the hospital setting itself, the subject's role within that setting, and the degree of familiarity with the role being rated would have a significant impact on the subject's attitude. Results generally supported the above expectations. Overall ratings of the professional groups were consistently high, with less difference between the health designations (physician, nurse) and the psych designations than has been previously reported in the literature.     

Zum Problem der sogenannten Simultanagnosie

Zusammenfassung Bei einem Patienten mit einem vorzugsweise lobär verlaufenden hirnatrophischen Prozeß wurden die Störungen der Gesamtauffassung bildlich dargestellter Situationen (Simultanagnosie), die er neben Wortfindungsschwierigkeiten, Paraphasien, Dysgraphie, Dyskalkulie und Merkschwäche bot, einer Analyse unterzogen. Die gestörte Intellektualität der Wahrnehmung zeigte sich als ein Darniederliegen ihrer sinngerichteten Aktivität. Der Patient war nicht in der Lage, Strukturen in eine Wahrnehmungsgegebenheit zu bringen, war unfähig, eine Gestalt aufzubauen. Durch Störungen des Übersehens hatte die Überschaubarkeit des Wahrnehmungsfeldes gelitten. Bei schneller Absättigung des Sinnfindungsbedürfnisses kam es zum sinngemäßen Illusionieren innerhalb kurzschlüssig hergestellter Sinneinheiten. Die durch das Zurücktreten der Gestalt gegenüber der Physiognomie des Gegenstandes gekennzeichneten Zeichnungen des Patienten wurden den raumagnastischen Gestaltungsstörungen zugeordnet. Die Bedeutung der Störungen für das Leben des Patienten erhellen sein Verzicht auf Wahrnehmung und seine Unsicherheit gegenüber einer eindringlicher gewordenen, nicht mehr dahingestellten Welt.     

Acid maltase deficiency in non-identical adult twins

Summary Acid maltase deficiency is described in non-identical adult twins. The onset of the disease can be traced into late infancy; the clinical picture is one of severe muscular dystrophy; respiratory insuficiency was the cause of death in one case. The autopsy showed the central nervous system, heart and liver to be spared. Glycogen filled vacuoles are found in skin, mesenchymal cells, small nerves and skeletal muscles. The light microscopic study of 9 different muscles showed extremely variable involvement ranging from normal appearance to overt vacuolization. A 6–20% residual acid -glucosidase activity was found in visceral organs, cultured fibroblasts and in some skeletal muscles. No satisfactory explanation can be given why this generalized acid -glucosidase deficiency produces a selective involvement of skeletal muscles. If compared with infantile AMD (Pompe's disease) our cases have a much higher residual acid -glucosidase activity and show the presence of an antigenically detectable protein.From our study and from a similar report in the literature (de Barsy et al., 1975), it appears that a combined approach of light microscopy, electron microscopy and biochemical analysis (determination of acid -glucosidase) is necessary to make a diagnosis of AMD in adults.Dr. Th. de Barsy is a Research Fellow of the Fonds National de la Recherche Scientifique.