Somatosensory evoked potentials in patients with thalamic lesions

Summary Somatosensory evoked potentials (SEPs) were recorded in 20 patients with thalamic lesions confirmed by CT (10 with infarction, 10 with haemorrhage). The changes in SEP configuration are discussed in their relationship to clinical symptoms. Four types of SEP abnormality produced by thalamic lesion are distinguished: (1) FF type, (2) N20/P23 dissociation type, (3) N18/N20 false shift type, and (4) reduced early component type. It was shown that clinically similar lesions might produce different SEP patterns.     

Venous hypertension and craniosynostosis

Introduction This article addresses the relevance of venous hypertension to children born with, in particular, the syndromic forms of craniosynostosis. The development of the human cerebral venous system is summarised and the patterns of anomalous venous drainage seen in children with complex forms of craniosynostosis associated with raised intracranial pressure are described.Aetiology The aetiology of these abnormal patterns is discussed under the general headings of The constriction theory, A primary role for FGFR mutations and Persistence of the foetal pattern of intracranial venous drainage.Venous hypertension (along with hydrocephalus, cranio-cerebral disproportion and airway obstruction) has an important role in the aetiology of raised intracranial pressure in severely affected children.Treatment The inter-relationship between these factors is explained and then the treatment of those children whose raised intracranial pressure is considered to be due predominantly to venous hypertension is described.     

Potential role of transforming growth factor-β1 in terminating the immune response in patients with Guillain-Barré syndrome

T-cell activation and proinflammatory cytokines seem to be important in promoting the disease activity in Guillain-Barré syndrome (GBS). Transforming growth factor-1 (TGF-1) is a multifunctional peptide with potent immunosuppressive activity, and can therefore be considered a putative disease-limiting cytokine. We determined levels of soluble TGF-1 in the serum of 12 patients with GBS in serial investigations during the course of the disease, in 12 patients with other non-inflammatory neurological diseases (OND), and in 12 healthy control subjects. Levels of biologically active and total TGF-1 were significantly increased in patients with GBS compared with patients with OND and healthy controls. During the course of GBS, levels of TGF-1 peaked in the plateau phase before onset of recovery. During the recovery phase levels of TGF-1 decreased but still exceeded significantly the levels in patients with OND and healthy controls. The differences were more marked with biologically active than with total TGF-1. The temporal relationship between increased serum levels of TGF-1 and the end of the progressive phase indicates that TGF-1 has a role in terminating the pathological immune response in GBS. These findings suggest that TGF-1 may be important in recovery from GBS.     

Amelioration of the cerebrovascular amyloidosis in a transgenic model of Alzheimer’s disease with the neurotrophic compound Cerebrolysin™

Summary. Increased production and reduced clearance of amyloid (A) plays a central role in the pathogenesis of Alzheimers disease (AD). We have recently shown that the neurotrophic peptide mixture Cerebrolysin (Cbl) has the ability of improving synaptic functioning and reducing amyloid deposition in a transgenic (tg) animal model of Alzheimers disease (AD). Since in AD, potentially toxic A aggregates accumulate not only around neurons but also in the blood vessels, then it is important to investigate whether bioactive compounds such as Cbl might have the capacity to ameliorate the age-related cerebral amyloid angiopathy (CAA) in tg models. To this end, tg mice expressing mutant human amyloid precursor protein (APP) under the Thy1 promoter were treated with Cbl or saline alone starting at 7 or 12 months of age for a total of three months. Neuropathological analysis with an antibody against A showed that Cbl decreased amyloid deposition around the blood vessels in a time dependant manner. These effects were accompanied by a reduction in perivascular microgliosis and astrogliosis and increased expression of markers of vascular fitness such as CD31 and ZO-1. No lymphocytic infiltration was observed associated with A in the vessels. Consistent with these findings, ultrastructural analysis showed that while in tg mice treated with saline alone there was an abundant accumulation of amyloid fibers in the vascular wall accompanied by thickening of the basal membrane and endothelial cell damage, in Cbl-treated mice there was considerable reduction in the subcellular alterations of endothelial and smooth muscle cells with preservation of basal membranes and intercellular junctions. Taken together, these results suggest that Cbl treatment might have beneficial effects in patients with cognitive impairment due to cerebrovascular amyloidosis by reducing A accumulation and promoting the preservation of the cerebrovasculature.     

Hyperkinetic children: Early indicators of potential school failure

Hyperkinetic children are identified as a population-at risk upon admission to kindergarten. The etiology of hyperkinetic behavior is controversial. Organic driveness, hyperkinetic behavior disorder, postencephalitic behavior, brain damage with behavioral and conceptual deficit, Strauss syndrome, have all been used to label essentially similar symptom constellations. Bypassing the area of controversy, a study is reported that demonstrates that children who were identified as hyperkinetic (using behavioral criteria developed in an earlier study) were (1) absent from school more frequently, and (2) did remarkably less well on standardized tests of school readiness than their peers rated nonhyperkinetic. The implications are discussed and suggestions made for the development of intervention programs.An earlier version of this paper was presented at the Annual Meeting of the American Orthopsychiatric Association, March, 1967.     

Immunohistochemical study on the distribution of α and β subunits of S-100 protein in brain tumors

Summary The immunohistochemical distribution of and subunits of S-100 protein (S-100, S-100, respectively) in 138 cases of human brain tumors was investigated by the avidin-biotin immunoperoxidase method. Brain tumors can be divided into four groups: group 1 [S-100 (+) and/or S-100 (+)]; astrocytoma, glioblastoma, ependymoma, subependymoma, oligodendroglioma, choroid plexus papilloma, gangliocytoma, meningioma, chordoma, malignant melanoma. Group 2 [S-100 (+) and S-100 (-)]; pineoblastoma, pituitary adenoma, craniopharyngioma, rhabdomyosarcoma. Group 3 [S-100 (-) and S-100 (+)]; acoustic Schwannoma. Group 4 [S-100 (-) and S-100 (-)]; medulloblastoma, malignant lymphoma, germinoma. The S-100 immunoreactivity pattern in brain tumors was similar to those obtained using conventional anti-S-100 protein sera. In the first group of brain tumors both the number of positively stained tumor cells and the staining intensity were generally greater for S-100 than for S-100 with a few exceptions including one gemistocytic astrocytoma, one subependymoma, one malignant melanoma, and some cases of glioblastomas. As to the relationship between malignancy and S-100 protein in glioma, S-100 immunoreactivity decreased according to degree of malignancy, while that of S-100 varied, suggesting a heterogeneity of tumor cells in glioblastomas. Immunostaining for S-100 and S-100 might become a useful diagnostic procedure in brain tumors and may give us more detailed and precise data of S-100 protein in brain tumors.     

Die Polarität von Tiefe und Intensität in der Psychiatrie

Zusammenfassung Die Erlebnisse von großer manifester Wucht und Intensität pflegen eine begrenzte, meistens nur wenig nachhaltige Wirksamkeit auf die als tragender Grund und als ganzheitliche Bedingung allem Erleben zugrunde liegende Persönliehkeitsstruktur auszuüben, während die strukturell sehr bedeutsamen Tiefengefühle in der Regel als unaufdringlich und nur wenig intensiv erlebt werden. Es wird versucht, diese in der Normalpsychologie nachgewiesene polare Beziehung auf ihre Anwendbarkeit für psychiatrische Fragestellungen zu prüfen.In bezug auf die typischen Abwandlungen, denen der Mensch im Rahmen der Alternsvorgänge ausgesetzt ist, wird die Frage erörtert, inwieweit diese im Sinne einer zunehmenden Entfaltung der Persönlichkeit in der Tiefendimension gedeutet werden dürfen, die auf Kosten der Intensität aktuell ablaufender seelischer Vorgänge und Zustände vor sich geht. Analoge Differenzierungen erweisen sich als durchführbar im Hinblick auf den zu beobachtenden Wandel der abnormen psychogenen Reaktionen von den massiven Erscheinungen der klassischen Hysterie zu den gegenwärtig vorherrschenden intimen, gleichsam unterschwelligen Formen. Es zeigt sich, daß die: letzteren Reaktionsformen meistenfalls durch Tiefenerlebnisse ausgelöst werden und eine erheblichere Therapieresistenz aufweisen als die im allgemeinen durch intensive Erlebnisse bewirkten Reaktionen von hysterischem Gepräge.Die endo-reaktive Dysthymie erweist sich beim Vergleich mit der typischen cyclothymen Depression als eine Krankheitsform mit Tiefendimension. Bei einer Differenzierung der schizophrenen Psychosen im Sinne der gleichen Polarität darf man die schleichend verlaufenden, zu fortschreitender Entleerung der Persönlichkeit führenden Hebephrenien dem Pole der Tiefe und die stürmisch verlaufenden, aber oft keine stärkere Defektsymptomatik bewirkenden periodischen Katatonien dem der Intensität zuordnen, während den paranoiden Formen eine Zwischenstellung zukommt.Herrn Professor Kurt Kolle zum 60. Geburtstag in Verehrang gewidmet.     

Neuroectodermal tumors of the peripheral and the central nervous system share neuroendocrine N-CAM-related antigens with small cell lung carcinomas

Summary The current study describes the presence of neuroendocrine antigens of peripheral and central neural tumors using eight monoclonal antibodies raised to small cell lung carcinoma (SCLC), which recognize neural/neuroendocrine or neural antigens, as defined by their reaction pattern in normal tissues and tumors. At least five of them recognize different epitopes of the neural cell adhesion molecule (N-CAM). It was found that all of 12 neuroblastomas, 2 ganglioneuroblastomas and 4 ganglioneuromas as well as 23 central primitive neuroectodermal tumors, 13 astrocytomas and 4 ependymomas share neural/neuroendocrine antigens (as defined by the anti-N-CAM antibodies Moc-1,-21,-32,-52 and-191) with SCLC. The neural/neuroendocrine antigen defined by Moc-171 was also found in all peripheral tumors, but only in further differentiated central tumors. Non-N-CAM related neural antigens (as defined by Moc-51 and-172) were found only in better-differentiated peripheral and central tumors, but they could be demonstrated in all three medulloblastoma cell lines studied. In addition, the antigen defined by Moc-51 was demonstrated in an immunoblot of a neuroblastoma cell line. Antibodies recognizing epithelia antigens of SCLC and other epithelia and their tumors (Moc-31 and-181) were non-reactive. It was concluded that these findings give further support for a relation between neural and neuroendocrine tumors and that some of the antibodies may be useful for the detection of differentiation in neural tumors. Antibodies with an epithelia recognition pattern may serve to distinguish neural from neuroendocrine tumors.Supported by NIH grant CA 36245 W.M.M. was a Fullbright scholar     

Extraocular muscles light microscopy and ultrastructural features

Summary Thirty extraocular muscles (EOM) from 20 patients were evaluated by light microscopy (LM), electron microscopy (EM), and enzyme histochemistry (EZH). Twenty-one EOM were obtained from 13 patients with strabismus, 9 EOM from 4 patients undergoing eye surgery for other reasons and from 3 autopsy cases. One m thick sections revealed marked variation in muscle fibre shape and size and in myofibrillar structure; also noted were small, hypertrophied, whorled, and ringbinden fibres. Dense and granular material in the central portion of some fibres and sarcomere disruption in 2–3 m sections was observed. EZH revealed the absence of the classical mosaic pattern usually found in skeletal muscles. ATPase studies were inconsistent and did not correlate with the expected reciprocal activity of NAD-H diaphorase, particularly on the large fibres.Ultrastructural features consisted of vacuoles within myofilament bundles, smearing of Z bands, and nemaline rods. Occasional myelin figures and lipid-like droplets were observed in subsarcolemmal spaces, associated with scattered clusters of glycogen granules. Abnormal mitochondria and subsarcolemmal inclusions of dense and granular material were conspicuous. Leptomeric profiles, Zebra bodies, or striated bodies were noted in 8 EOM's, and an Hirano body was found in 1. The intramuscular nerves contained structures resembling Luse bodies in 7 cases.These observations suggest that EOM from individuals with and without strabismus possess unique structural characteristics suggestive of developmental and morphological disarrangement of contractile elements. Some of these changes might play a role in the pathogenesis of strabismus and in the development of clinical symptoms.These features are significantly different from striated skeletal muscle. Therefore the criteria used in the pathological evaluation and diagnosis of skeletal muscle disorders cannot be unequivocally applied to EOM investigations. These data establish the necessity to determine histological norms, ultrastructural patterns, and develop new enzyme histochemistry criteria for the evaluation of EOM. Only then can an acceptable comparison of EOM and skeletal muscle be made.     

Comparison of integrin adhesion molecules expressed by primary brain lymphomas and nodal lymphomas

The expression of 17 adhesion molecules was immunohistochemically examined in 5 primary cerebral lymphomas (PCL) and in 5 histologically similar nodal lymphomas (NL) to evaluate their possible involvement in selective targeting of lymphoma cells to the brain. PCL and NL tumor cells showed very similar expression patterns: they were consistently positive for ₃, ₄ and ₁ integrin chains; negative for ₂, ₆, ₃ and ₄ integrin chains; and heterogeneous for ₅, _L, _M, _X, ₂ and ₇ integrin chains, as well as for intercellular adhesion molecule-1 (ICAM-1) and the selectin LECAM-1. Loosely infiltrating PCL showed lower levels of the _L2 integrin than compact cell clusters. Vessels stained for ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1). We conclude that the adhesion molecules implicated in the extravasation of non-neoplastic leukocytes (₄₁/VCAM-1 and _L2/ICAM-1) are also expressed by both PCL and NL. The adhesion molecules examined are apparently not selective mediators of lymphoma cell homing to the brain, but at least _L2 integrin might be related to the infiltration pattern of PCL within the brain parenchyma.Supported by the Sander Foundation     

Does social deprivation during gestation and early life predispose to later schizophrenia?

Summary We employed a case-control study design to investigate whether schizophrenic patients differed from non-psychotic psychiatric patients in terms of place of birth and paternal occupation. Cases were first-contact schizophrenic patients ascertained from the Camberwell Cumulative Psychiatric Case Register. Controls were the next (non-psychotic) patient on the Register matched for age and sex. In comparison with controls, cases were more likely to have: (1) been born in the deprived innercity Camberwell catchment area (odds ratio 2.3), and (2) had fathers who had manual as opposed to non-manual occupations (odds ratio 2.1). The results were compatible with the notion that socio-economic deprivation during gestation and early life predisposes to later schizophrenia.     

Analytic work with LSD 25

Summary In this paper, work with LSD 25 as an aid to analysis has been described. Of particular interest, has been theseeming unpredict-ability and arbitrariness of experiences elicited by the drug, and an attempt has been made at finding the determining factor in emerging material. This appears to be the selection of complementary and compensatory unconscious contents; selected in accordance with Jung's idea of the psyche as a self-regulating system, striving toward wholeness.Clinical material has been grouped in five categories, in which different aspects of complementation are illustrated. Some questions of transference and resistance in connection with LSD treatment have been discussed; and ideas about typical mechanisms in certain categories of neuroses, as suggested by the patient's response to the drug, have been put forward.This report is based on a paper read at a meeting of the (British) Society of Analytical Psychology in 1957.     

Assessment of complicance-related attitudes in psychiatry

Summary In a study of 118 psychiatric patients two questionnaires of similar content that are supposed to predict compliance with pharmacotherapy in psychiatry were examined, COSS and KK-Skala. These questionnaires assess the patient's attitudes towards his illness, pharmacotherapy, and the physician. Patient compliance was judged by the treating physicians. The results of discriminant analyses indicated that about two thirds of the patients were correctly classified into compliant and moderately or not compliant (as judged by the physicians) by means of COSS and KK-Skala, respectively. It is a matter for further research whether these results reflect in fact moderate associations between patient attitudes and compliant behavior or are due to limitations of the questionnaires and of the study design.     

Cortical regulation of subcortical dopamine systems and its possible relevance to schizophrenia

Summary A unique model of DA system regulation is presented, in which tonic steady-state DA levels in the ECF act to down-regulate the response of the system to pulsatile DA released by DA cell action potential generation. This type of regulation is similar in many respects to the phenomenon proposed to mediate the action of norepinephrine on target neurons; i.e., an increase in the signal-to-noise ratio as measured by postsynaptic cell firing (Freedman et al., 1977; Woodward et al., 1979). However, in this model the signal and the noise are neurochemical rather than electrophysiological. Furthermore, the noise (tonic DA in the ECF) actually down-regulates the signal (phasic DA release) directly, and thereby provides a signal of its own that affects the system over a longer time-course. Therefore, the difference between signal and noise may also depend on the time frame under which such determinations are made.     

Quantitative analysis of “synaptic” ribbon profiles in the pineal complex of male and female Pirbright-White guinea pigs

Summary Previous studies have pointed in the direction of sex differences as well as regional differences in the pineal gland of guinea pigs. In the present investigation these aspects were studied at the electron-microscopic level by quantitating different types of synaptic bodies, intrinsic to pinealocytes. The two major types of synaptic organelles, ribbons and spherules, did not exhibit regional or sex differences. Synaptic structures intermediate in appearance to ribbons and spherules were significantly larger in number in males in the distal region of the pineal gland, compared to females. As previous studies have shown that ribbon and spherule numbers undergo characteristic changes depending on the functional state of the pineal gland, it is concluded that, as far as the synaptic organelles are concerned, no clear-cut sex or regional differences appear to exist in the guinea pig pineal gland.     

Diagnosing Depression in African Americans

Since the 1970s, articles have noted the increased presence of psychotic symptoms among depressed African Americans, the presence of diagnostic bias identified when structured clinical interviews are used, and the identification of misdiagnosis of affective illness among chronically, mentally ill, African Americans. This paper reviews this literature and describes three alternative presentations of depressive illness among African Americans that differ from the DSM IV criteria for Major Depressive Disorder: the stoic believer, the angry, evil one with a personality change, and the John Henry doer. Clinicians are encouraged to recall these presentations of depression when evaluating African American patients.     

Psychometric properties of the parental bonding instrument in a spanish sample

Summary The Parental Bonding Instrument was translated into Spanish and administered to a sample of 205 Spanish primiparae 3 days after childbirth. Reliability, factorial structure and predictive validity for affective disorders were evaluated. The Spanish version of the PBI has psychometric features similar to those described in other cultures. However, the results suggest that in future research the predictive power of the Control factor in affective disorders might be improved by splitting it into two subfactors: Overprotection and Restraint.     

An electronmicroscopical study of a case of atypical cerebral lipidosis

Summary Histological and electron microscopical findings in a cerebral biopsy from a 16 year old boy are presented. He developed dementia from the age of 10 and grand mal from the age of 13. The histological picture was one of neuronal lipid storage disease, and the electron microscopy, while confirming this, was not clearly characteristic of any of the previously reported lipidoses. Apart from a few zebra bodies (characteristics of gargoylism) the neurons contained masses of material (here called granular vesicles) which resembled the pericyte deposits of gargoylism, though these are very rare in the neurones of that disease. It was therefore not possible to assign a presumptive classification to this case, as there was no clinical evidence of gargoylism.

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Zusammenfassung Histologische und elektronenoptische Befunde einer Hirnbiopsie eines 16jährigen Knaben werden mitgeteilt. Klinisch bot er eine progressive Demenz seit dem 10. sowie Grand Mal-Anfälle ab dem 13. Lebensjahr. Histologisch ergab sich das Bild einer neuronalen Lipoidspeichererkrankung. Elektronenoptisch wurde dieser Befund zwar bestätigt, doch ergaben sich keine für die bisher berichteten Formen von Lipoidspeichererkrankung charakteristische Veränderungen. Außer wenigen Zebrakörpern (Merkmale des Gargoylismus) enthielten die Neurone massenhaft Material (als granuläre Vesikeln bezeichnet), das an die Deposite in den Perizyten bei Gargoylismus erinnert, obwohl sie äußerst selten bei dieser Erkrankung in den Neuronen angetroffen werden. Da klinisch keine Hinweise auf einen Gargoylismus bestanden, war eine eindeutige Klassifizierung dieses Falles nicht möglich.

     

Ultrastructure of peripheral nerve in metachromatic leucodystrophy

Summary An electron microscopical study of two consecutive nerve biopsies from a patient with metachromatic leucodystrophy (sulphatide lipidosis) was made. The ultrastructural changes observed consisted of: a) irregular whorls of myelin. The myelin in the whorls showed a thickened, sometimes doubled, intraperiod line, which was barely visible in compact myelin; b) inclusion bodies up to 1 in diameter in the cytoplasm of Schwann cells. These had a lamellar structure, with stacked membranes 60 Å apart; c) a loose pattern of the myelin in some nerve fibers, with loss of the intraperiod line, and d) presence of abnormally dense mitochondria with thickened cristae in Schwann cells. It is suggested that: a) the whorl formation and the ultrastructural abnormalities of the myelin in the whorls may be due to impaired myelin synthesis, and b) that the inclusion bodies may represent the accumulation of cerebroside sulfate in micellar aggregates. The loose pattern of myelin is considered artifactural until proven otherwise.

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Zusammenfassung Zwei aufeinanderfolgende Nervenbiopsien bei einem Patienten mit metachromatischer Leukodystrophie (Sulfatid-Lipoidose) wurden elektronenoptisch untersucht. Die beobachteten ultrastrukturellen Veränderungen bestehen in: a) unregelmäßigen Wirbelbildungen (whorls), in welchen das Myelin Verdickungen, manchmal Verdopplung des Zwischenstreifens (intraperiod line) aufweist, was im kompakten Myelin kaum sichtbar ist. b) Einschlußkörperchen mit einem Durchmesser bis zu1 im Cytoplasma der Schwann-Zellen. Diese weisen lamelläre Struktur mit einem Membranabstand von 60 Å auf. c) ein lockeres (loose) Myelinmuster mit Verlust des Zwischenstreifens in einigen Nervenfasern und d) Auftreten von abnorm dichten Mitochondrien mit verdicktem Cristae in Schwann-Zellen. Es wird angenommen, daß a) die Wirbelbildungen und die ultrastrukturellen Myelinabnormitäten in den Wirbeln einer gestörten Myelinsynthese entsprechen und b) daß die Einschlußkörperchen die Anhäufung von Cerebrosidsulfat in micellaren Verbänden darstellen. Das lockere Myelinmuster wird vorläufig als artifiziell angesehen.

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This investigation was supported in part by Public Health Service Research Grant No. FR-86 from the N.I.H. Division of Research Facilities and Resources.     

Intuition VI. The psychodynamics of intuition

Summary The psychodynamics of intuition are considered from the viewpoints of psychoanalysis and structural analysis.⁸ An example is offered to illustrate the fact that ethical as well as logical thinking can interfere with the intuitive process. Defenses against scopophilia, the need to be alert, and oral receptivity seem to give rise to a resistance against the whole topic. Conversely, intuitive faculties are probably most readily available to individuals who have successfully sublimated scopophiliac, paranoid, and oral receptive tendencies. Sources of error, and the role of the intellect in clinical intuition, are discussed.