Cytoplasmic and axoplasmic density variations in relation to hyperactivity

Summary The density of the cytoplasm and axoplasm of the anterior horn cell in rats was determined by X-ray microradiography. The average density of the cytoplasm of more than 400 cells from control rats was 0.31 g/³, while that of over 600 cells from rats fed IDPN (- iminodipropionitrile) was 0.43 g/³.Hyperactivity developed during the first 5 weeks and was associated with a gradual increase in cytoplasmic density to 0.51 g/³.At 6 weeks there was a drop in density to 0.36 g/³ which coincided with the appearance of axonal balloons having a density of 0.17 g/³.During the 7–12th week on the diet, the cytoplasmic density showed a gradual increase to 0.59 g/³ and the balloons to 0.29 g/³.The volume of the nerve cells remained fairly constant. The density increases were discussed in relation to hypertrophy, dystrophy, and hyperactivity.

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Zusammenfassung Die Dichte des Cytoplasmas und Axoplasmas der Vorderhornzellen von Ratten wurde durch Röntgenmikroradiographie bestimmt. Die mittlere Dichte des Cytoplasmas von mehr als 400 Zellen der Kontrollratten war 0,31 g/³, während die mittlere Dichte von mehr als 600 Zellen der Ratten, die mit IDPN (- iminodipropionitrile) gefüttert waren, 0,43 g/³ war.Hyperaktivität entwickelte sich während der ersten 5 Wochen und war mit einer progressiven Zunahme der Cytoplasmadichte bis auf 0,51 g/³ verbunden.Nach 6 Wochen sank die Dichte auf 0,36 g/³. Diese Tatsache traf mit dem Auftreten der Axonauftreibungen zusammen, die eine Dichte von 0,17 g/³ hatten.Nach 7–12 Wochen zeigte die Cytoplasmadichte eine progressive Zunahme auf 0,59 g/³ und die der Auftreibungen eine Zunahme auf 0,29 g/³.Das Volumen der Nervenzellen blieb ziemlich konstant.Die möglichen Zusammenhänge zwischen Zunahme der Dichte, Hypertrophie, Dystrophie und Hyperaktivität werden dargestellt.

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Supported by U. S. Public Health Grant NB 1305.     

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.     

Electroconvulsive therapy in Parkinson's syndrome with “on-off” phenomenon

Summary During long-term treatment with L-dopa in Parkinson's syndrome on-off phenomenon develops in many cases, often entailing considerable therapeutic problems. Decreased sensitivity in postsynaptic striatal dopamine (DA) receptors has been shown to occur in parkinsonian patients during long-term treatment with L-dopa. This has been suggested as one possible mechanism for development of the on-off phenomenon. In contrast to L-dopa treatment electroconvulsions have been shown to increase sensitivity in the DA receptors, when administered to animals.The antiparkinsonian effect of electroconvulsive therapy (ECT) was investigated in five parkinsonian patients with on-off phenomenon, with or without concomitant signs of mental depression. ECT was administered according to praxis in treatment of mental depression. Drug therapy, including L-dopa, was maintained on previously adjusted doses during and after ECT.A marked improvement in the parkinsonian symptoms as well as in the on-off phenomenon occurred in three of the patients, persisting for several months. The other two patients showed only slight and transient improvement.It thus seems that ECT may be useful as a supplementary treatment in parkinsonian patients with on-off phenomenon. The antiparkinsonian effect of ECT is probably mediated by increased sensitivity in postsynaptic DA structures.     

A 3’-UTR polymorphism in the oxidized LDL receptor 1 gene increases Aβ40 load as cerebral amyloid angiopathy in Alzheimer’s disease

It is presently unclear whether polymorphic variations in the oxidized low-density lipoprotein receptor 1 (OLR1), or low-density lipoprotein receptor-related protein 1 (LRP1), genes act as risk factors for Alzheimers disease (AD). In the present study, we have investigated the extent of amyloid protein (A) deposition as cerebral amyloid angiopathy (CAA) or senile plaques (SP) in relationship to OLR1 +1071 and +1073 polymorphisms and LRP1 C766T polymorphism in patients with AD There was an increased A₄₀ load as CAA, but not as SP, in frontal cortex of AD patients carrying OLR1+1073 CC genotype, compared to those with CT, TT or CT+TT genotypes, but only in those individuals without apolipoprotein (APOE) 4 allele. No differences in total A or A₄₂ load as CAA or SP between OLR1+1073 genotypes was seen, nor were there any differences between OLR1+1071 and LRP1 genotypes for any measure of A. Present data suggests that homozygosity for the C allele for OLR1+1073 polymorphism, selectively in individuals without APOE 4 allele, may impair clearance of A, and particularly A₄₀, from the brain across the blood-brain barrier, leading to its diversion into perivascular drainage channels, thereby increasing the severity of CAA in such persons.     

A disease-specific psychosocial questionnaire for Parkinson’s disease caregivers

Abstract. Objective: To evaluate the Belastungsfragebogen Parkinson Angehörigen—kurzversion (BELA-A-k), a questionnaire for measuring psychosocial problems and need for help in Parkinsons disease (PD) caregivers. Methods: The Belastungsfragebogen Parkinson Angehörigen—kurzversion was translated into Dutch. It consists of 15 items with a Bothered by (Bb) and a Need for Help (NfH) score. The BELA-A-k was tested for cultural differences, relevance and feasibility in a pilot (n = 10). We determined the psychometric properties in a validation study (n = 50) and compared the BELA-A-k with the Sickness Impact Profile, the COOP/WONCA Functional Health Assessment Charts and the Loneliness Questionnaire (de Jong-Gierveld). All questionnaires were administered in person at home, in a prescribed order. Results: The BELA-A-k was completed by 60 PD-caregivers. The internal-consistency reliability coefficients for the total Bothered by (0.90) and Need for Help (0.92) scales were excellent. The internal consistency of the subscales exceeded the 0.70 standard except for the Bothered by and Need for Help Social functioning scale (Bb = 0.62; NfH = 0.65) and the Partner-bonding/Family scale (NfH = 0.69). Almost all BELA-A-k subscales correlated highly (P < 0.001) with the corresponding scales of the standard quality of life indices. Conclusion: The BELA-A-k is a relevant, reliable and valid measure for assessing psychosocial problems and need for help of PDcaregivers.     

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.     

Amyloid β peptide 1–42 highly correlates with capillary cerebral amyloid angiopathy and Alzheimer disease pathology

Recent studies reported both positive [Thal et al. (2003) J Neuropathol Exp Neurol 62:1287–1301] and negative [Tian et al. (2003) Neurosci Lett 352:137–140] correlations between cerebral amyloid angiopathy (CAA) and Alzheimers disease (AD) pathology. We have recently shown high correlations between neuritic AD pathology and amyloid peptide (A) deposits in the capillary/pericapillary compartment (CapCAA) with only low correlations to general CAA (non-capillary). We have now studied the relationship between CapCAA and AD pathology with respect to the distribution of A40 and 42 in the frontal cortex of 100 human postmortem brains from both male and female, demented and non-demented patients (mean age ± SD 84.3±9.3 years). Using polyclonal antibodies to A40 and 42, capillary and plaques positivity were assessed semiquantiatively on a four-point scale. A42 deposits in capillaries correlated highly with both A42 deposits in plaques and morphological AD criteria (CERAD, Braak stages, and NIA-Reagan-Institute criteria), while only a low correlation with CAA was observed. A40 deposits in capillaries differed morphologically from A42 ones: they were limited to capillary walls, were significantly less frequent in both capillaries and plaques compared to A42 (P<0.01), and showed a low correlation with morphological AD criteria (P<0.05) and general CAA (P<0.01). By contrast, A42 deposits were seen in the glia limitans rather than in capillary walls themselves, and showed high correlation with morphological AD criteria (P<0.01). These data indicate that CapCAA is characterized by A42 deposits in pericapillary spaces or in the glia limitans. A low correlation between CAA and CapCAA, but high correlations between morphological AD criteria and CapCAA suggest different pathomechanisms for both types of CAA, and a close relation between CapCAA and AD pathology (both neuritic and plaque type). These data support the concept of a neuronal origin of A via drainage from interstitial fluid from the central nervous system along basement membranes to capillaries.List of Abbreviations AD Alzheimer disease - A beta amyloid peptide - A 40/42 CapS score of deposits of A 1–40/42 in capillaries - A 40/42 C number of A 1–40/42 positive cortical vessels - A 40/42 PS score of deposits of A 1–40/42 in plaques - A 40/42 TS total score of A 1–40/42 deposits - A 40/42 Csev severity of A 1–40/42 affection of cortical vessels - A 40/42 CS A 1–40/42 cortical score - A 40/42 L percentage of A 40/42 positive leptomeningeal vessels - A 40/42 Lsev severity of A 40/42 affection of leptomeningeal vessels - A 40/42 LS A 40/42 leptomeningeal score - ACTS A cortical total score - ALTS A leptomeningeal total score - CAA cerebral amyloid angiopathy - CAATS CAA total score - CapCAA capillary CAA - CERAD Consortium to Establish a Registry of Alzheimers Disease - NFT neurofibrillary tangle - NIA National Institute of Aging - NIA-RI National Institute of Aging and Reagan Institute - NP neuritic plaque - SP senile plaque - TS total scoreAn erratum to this article can be found at     

Der Hirnstoffwechsel und die Häufigkeit cerebraler Durchblutungsstörungen beim organischen Psychosyndrom

Zusammenfassung Bei 200 Patienten mit den typischen Zeichen eines organischen Psychosyndroms wurden Hirndurchblutung, cerebraler Verbrauch von Sauerstoff und Glucose sowie der zur Oxydation gelangende Glucoseanteil bestimmt. In 170 Fällen (85%) war eine dieser Größen führend herabgesetzt, bei 28 Fällen (14%) lagen gesteigerte Werte vor, bei zwei Patienten (1%) waren die Befunde normal. Lediglich in 35 Fällen (17,5%) war eine Minderung der Hirndurchblutung der führende Befund. Bei 68% der von uns untersuchten Patienten waren Störungen des Hirnstoffwechsels mit einem zum Teil erheblichen cerebralen Energiedefizit vorherrschend. Das bedeutet, daß beim organischen Psychosyndrom viermal häufiger cerebrale Stoffwechselstörungen im Vordergrund stehen als cerebrale Durchblutungsstörungen. Damit werden auch die aus dem psychopathologischen Bild, dem EEG oder dem Pneumencephalogramm gestellten Diagnosen cerebrale Durchblutungsstörungen, cerebrovasculäre Insuffizienz, Cerebralsklerose oder Hirnarteriosklerose in ihrem Aussagewert zweifelhaft.

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Incidence of disorders of cerebral blood flow in the organic psychosyndrome

Summary Cerebral blood flow, consumption of oxygen and glucose, and the fraction of glucose subject to oxidation were measured in 200 patients. Either one of these parameters was critically reduced in 170 cases (85%), while being elevated in 28 (14%) and within normal limits in two others. Only in 35 cases (17.5%) was a diminished cerebral blood flow the main finding. In 68% of the patients of this study the prominent feature of the disturbed cerebral metabolism was an energy deficit assuming appreciable extents in some cases. From this it follows that in the organic psychosyndrome an impaired cerebral metabolism was the leading symptom four times more often than a diminished cerebral blood flow. Thus diagnoses like disturbed cerebral blood flow, cerebrovascular insufficiency, cerebral sclerosis, or brain arteriosclerosis which are usually based on either psychopathologic impression, EEG or pneumencephalogram become doubtful as to their conclusiveness.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Etic and emic criteria for non-psychotic mental disorder: a study of the CISR and care provider assessment in Harare

The paper describes the relationships between the Revised Clinical Interview Schedule (CISR) and the assessment of psychiatric status by primary care providers in Harare. Primary care clinic (PHC) and traditional medical practitioner (TMP) clinic attenders (n=302) were interviewed with the Shona Symptom Questionnaire, the CISR and the Explanatory Model Interview. The PHC nurses and TMP were interviewed to elicit diagnostic formulation using the WHO Health Staff Rating codes. Etic cases were those who scored 12 or more on the CISR and emic cases were those whom the care provider had assessed as having a mental disorder. In all, 52% of subjects were classified as etic cases and 59% as emic cases. Overall agreement between the two criteria was 55%. Three-quarters of care provider false-positives were accounted for by a failure to take into account the varying reasons for consultation, such as social or spiritual problems. Most of the false-negative groups were symptomatic subjects, though with fewer symptoms than those who were definite cases. One etic conceptphobia-was not considered as a mental disorder and appeared to lack concept validity in this setting.     

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.     

Hirnembolie und Psychose

Zusammenfassung Hirnembolisationen können in bestimmten Fällen als reine Psychosen verlaufen. Ist die Tatsache einer Embolisation nicht bekannt, so werden häufig sogar endogene Psychosen aus dem schizophrenen oder manisch-depressiven Formenkreis diagnostiziert.Herzerkrankungen und die Herzchirurgie gehen mit einem großen Embolierisiko einher. Mikroembolien spielen eine besondere Rolle bei der extrakorporalen Zirkulation, bei der signifikant öfter kardiogene Psychosen auftreten als bei geschlossenen Herzoperationen. Unmittelbar postoperativ treten nach Herzoperationen stuporös-akinetisch-parkinsonähnliche Zustandsbilder auf, die nach 3–5 Tagen abklingen. Hierbei handelt es sich mit großer Wahrscheinlichkeit um einen reversiblen embolischen Parkinsonismus bei Basalganglienapoplexie infolge von Mikroembolisation. Das spätere Auftreten depressiver und produktiv-psychotischer Syndrome, nach dem 3.–5. postoperativen Tag, wird ebenfalls im Zusammenhang mit Störungen im Bereich der Basalganglien gesehen. Für das Auftreten produktiv-psychotischer Syndrome ließ sich ein signifikanter Zusammenhang mit einer erblichen Belastung für endogene Psychosen in der Familien- und Eigenanamnese nachweisen.Auf der psychopathologischen Ebene kann man hier nicht zwischen endogenen und exogenen Psychosen unterscheiden. In diesem Zusammenhang haben psychopathologische Syndrome mit neurologischen Syndromen das Gemeinsame, daß die Art eines bestimmten Symptoms von der Akuität und dem Ausmaß der Hirnschädigung, der Hirnlokalisation und von hereditären Faktoren bestimmt wird.

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Cerebral embolism and psychosis with special reference to cardiac surgery

Summary Cerebral embolism can manifest itself in certain cases as pure psychosis. In the absence of neurological symptoms it might be mistaken for schizophrenia or manic-depressive psychosis.Cardiac disease and cardiac surgery involve a high risk of embolism. Microembolism plays a special role with extracorporal circulation. There is a significant increase of postoperative psychosis in cases with E.C.C. in comparison to closed heart surgery. Immediately postoperatively there occurs what has been described as the catastrophic reaction or immobilization syndrome. This reaction is in fact an akinetic, parkinsonian-like state for which there is good evidence that it is due to transient microembolism of the basal ganglia (striatum apoplexy). After its disappearance around the 3rd–5th day cardiac psychoses (cardiac delirium) may manifest themselves.Patients who develop these late psychoses have a significantly higher correlation with endogenous psychoses in their family histories. On the psychopathological level—in the absence of disturbances of consciousness and orientation—it is not possible to differentiate between exogenous and endogenous psychosis. A special type of psychopathological reaction is dependent, as in neurological disease, on the severity of brain damage, its localization and on hereditary factors.

     

Pseudosystematische Läsionen bei „atypischen” Encephalitiden

Zusammenfassung Im topischen Ausbreitungsmuster des entzündlichen Gewebssyndroms atypischer Encephalitiden der SSLE- und Panencephalitisgruppe können pseudosystematische Läsionen in Hirnstamm und Kleinhirn mit Ausgang in Systematrophien imitierende Substrate auftreten. Diese Läsionen sind einerseits durch sekundäre Entmarkungsvorgänge der ponto-cerebellaren Neurone infolge primärer Affektion der interfasciculären Oligodendroglia bedingt, die sich in deren schwerem Kerneinschlußbefall manifestiert. Die quantitative Variationsbreite des prädilektiven Hirnstammbefalls bei SSLE, die durch elektive Entmarkung der ponto-cerebellaren Neurone formale Ähnlichkeiten mit der olivo-ponto-cerebellaren Atrophie ergeben kann, wird an zwei einschlägigen Beobachtungen demonstriert. Anderseits handelt es sich bei den pseudosystematischen Läsionen um inkomplette bis subtotale Gewebsnekrosen als unmittelbare Folge lokal akzentuierter Entzündungsvorgänge ohne nachweisbare Einschlußkörpererkrankung der Oligodendroglia. Die Ätiologie des encephalitischen Syndroms und die Ursache seiner speziellen systemaffinen Prädilektionstopik sind unbekannt. Bei einer als Kleinhirn-Hirnstammsyndrom mit oculo-facialen Myoklonien verlaufenden subakuten Encephalitis fand sich eine pseudosystematische Akzentuierung des Entzündungsprozesses mit Markschädigung und Sklerose im Kleinhirn-Bindearm-Rubersystem bei geringer Endhirnbeteiligung. Bei längerem Verlauf können diese entzündlichen Sekundärschäden zu pseudosystematischen Atrophien und Sklerosen führen, die formale Ähnlichkeiten mit endogenen Systemdegenerationen aufweisen. Bei einer chronischen Panencephalitis mit knötchenförmigem Hirnstammbefall fand sich eine ponto-cerebellare Atrophie und Sklerose mit sekundärer Olivenatrophie und spinalen Strangdegenerationen, welche das Bild einer spino-olivo-ponto-cerebellaren Atrophie imitierte. Die Beziehungen dieser als subakute Encephalitis des Hirnstamms und Kleinhirns herausgestellten Sonderform atypischer Encephalitiden unbekannter Ätiologie zu den postencephalitischen Atrophien als prozeßhafte Nachkrankheiten gesicherter Virusinfektionen des ZNS sowie zu chronischen Systemerkrankungen des tierischen Nervensystems infolge langsam wirkender oder latenter Virusinfektionen werden diskutiert.

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Summary Within the topical pattern of the inflammatory process of atypical encephalitides of the SSLE and panencephalitis group pseudosystemic lesions of brain stem and cerebellum may occur which can terminate in substrates similar to system atrophies. These lesions may result from secondary demyelination of the pontocerebellar neurons caused by primary affection of the interfascicular oligodendroglia that manifests itself in a significant inclusion body disease of the oligos. The quantitative variability of the predilective affection of brain stem and pontine basis in SSLE which, by elective demyelination of the ponto-cerebellar neurons, may reveal formal similarities to olivo-ponto-cerebellar atrophy, is demonstrated in two relevant cases. On the other hand, these pseudosystemic lesions represent incomplete to subtotal necroses as direct sequelae of the locally accentuated inflammatory process without significant inclusion bodies in the oligodendroglia or neurons. The etiology of the encephalitic syndrome and the causes of its system-bound predilective pattern are unknown. In a case of subacute encephalitis clinically presenting a cerebellar-mesencephalic syndrome with oculo-facial myoclonies, there was pseudosystemic accentuation of the inflammatory process associated with demyelination and sclerosis of the cerebellum-brachium conjunctivum-ruber system and minor affection of telencephalon. In prolonged course these inflammatory sequelae may result in pseudosystemic atrophies and scleroses showing formal similarities to endogenous system degenerations of the CNS. In a case of chronic panencephalitis with nodular brain stem affection, there was a ponto-cerebellar atrophy with secondary olivary atrophy and degeneration of spinal tracts closely imitating the picture of spino-olivo-ponto-cerebellar atrophies. The relations of this special type of atypical sporadic encephalitides of unknown etiology, preliminarily denominated as subacute encephalitis of brain stem and cerebellum, to chronic postencephalitic atrophies which represent process-like sequelae of verified or suspected virus infections of the CNS and to chronic system degenerations of the nervous system in animals caused by slow and latent virus infections are discussed.

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Im Auszug vorgetragen auf der wiss. Tagung der Österr. Arbeitsgemeinschaft f. Neuropathologie in Bad Goisern, am 23. Mai 1966.     

Clinical and Human Resource Planning for the Downsizing of Psychiatric Hospitals: The British Columbia Experience

Riverview Hospital, B.C.'s only and Canada's largest remaining provincial psychiatric hospital began a formal planned downsizing process in 1992. This initiative was an important element in the Province's strategic plan to shift to a more community-focused mental health system and to bring tertiary psychiatric services closer to home by redeveloping Riverview Hospital on three sites. The paper summarizes the literature pertaining to the downsizing of psychiatric hospital services in relation both to clinical and human resource planning. It describes the mental health system in B.C. and the service system context in which this exercise is occurring. It is based on the first three years of experience in identifying the major challenges and the strategies developed to meet these challenges. It draws some conclusions about the effectiveness of these strategies and it speculates about the likely future challenges as the downsizing process continues.     

Amakiro: A Ugandan puerperal psychosis?

Summary 31 childbearing Ugandan women were interviewed, and their beliefs about the causes, symptoms and treatment of the traditional puerperal illness amakiro were studied. The variety of such beliefs had been established by 20 preliminary interviews, and a semi-structured interview subsequently developed. All interviews were carried out in the vernacular language by a male medical student from the same tribe as the sample women. The results showed that, despite proximity to a modern teaching health centre, the majority of the women were familiar with the illness and could readily identify its symptoms. Thus 28 women knew of the illness, and 12 women had known of a particular person with amakiro. Wanting to eat the baby was a symptom of amakiro described by 22 (78.6%) of those women who had heard about the illness. Promiscuity of the pregnant woman and not using herbal baths during pregnancy were the causes most frequently described. These results are discussed in relationship to traditional beliefs about legitimacy and some similarities noted with the psychology of Western women.     

Use of plasma levels for antiepileptic drug monitoring in clinical practice

A multi-center survey of antepileptic treatment was conducted in Italy on 245 previously untreated (new) patients with epilepsy and 355 patients treated for more than three months (old patients). Therapeutic drug monitoring (TDM) of antiepileptic drugs was evaluated in the context of routine clinical conditions, in relation to individual therapeutic problems and mode of treatment. Plasma levels (PL) were determined in 75% of new patients and 78% of old patients, with wide intercenter variability. TDM was done at 69% of the follow-up attendences for new patients and at 34% for old patients, but was apparently unrelated to specific therapeutic problems, such as poor disease control or adverse drug reactions. Plasma drug concentration measurements were made more often among patients on polytherapy. The age of the patient and the time elapsing since diagnosis did not seem to affect request patterns significantly. From these findings it appears that TDM is largerly influenced by factors unrelated to the common recommendations in the literature. In addition, the use of TDM in clinical practice reflects the limitations of the available techniques.

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Sommario In uno studio multicentrico condotto su 245 casi di epilessia di nuova diagnosi (trattati da meno di 3 mesi) e su 355 casi di epilessia di vecchia diagnosi (trattati da almeno 3 mesi)l'uso dei livelli plasmatici dei farmaci anticonvulsivanti è stato valutato in relazione alle modalità di trattamento e a problemi specifici indicati dai clinici. La percentuale di richieste di livelli plasmatici era del 75% e riguardava il 69% delle visite di follow-up nei pazienti di nuova diagnosi. Le percentuali erano rispettivamente del 78% e del 34% per i pazienti di vecchia diagnosi. In entrambi i casi vi era una marcata variabilità tra centri nelle percentuali di prescrizioni. Le richieste di livelli plasmatici erano più numerose nei pazienti in politerapia. Per contro, il monitoraggio dei farmaci antiepilettici non risultava influenzato dalla presenza di specifici problemi, quali il non completo controllo della crisi o la presenza di segni di tossicità farmacologica, né dall'età del paziente o dal tempo intercorso dalla formulazione della diagnosi. Da tutto ciò deriva che l'utilizzo dei livelli plasmatici dei farmaci antiepilettici nella pratica clinica è influenzato da fattori che spesso non riflettono le norme di comportamento comunemente suggerite dalla letteratura. Risultano inoltre ampiamente confermati i limiti delle metodiche attualmente in uso.

     

Transcranial doppler CO2 test for the detection of hemodynamically critical carotid artery stenoses and occlusions

Summary Cerebral CO₂-reactivity was tested by transcranial Doppler sonography (Doppler CO₂ test) in 232 patients. Time averaged flow velocity in the middle cerebral artery at the 40 mm Hg blood PCO₂ level was taken as a reference point, and the relative increase of flow in hypercapnia of 46.5 mm Hg pCO₂ was defined as Normalized Autoregulatory Response (NAR). A total of 82 patients with no evidence of cerebrovascular disease gave normal values for NAR (23.2 ± 5.2 SD). In 150 patients with 233 stenoses and occlusions of the internal carotid artery NAR was significantly decreased in highergrade stenoses (P = 0.01 for 80% diameter reduction, P < 10^–6 for 90% or more). In such stenoses, patients with NAR < 14 had suffered more frequently (P < 0.01) from ipsilateral transient ischemic attacks and/or stroke during the previous 6 months than patients with normal NAR. Preoperative NAR < 14 always improved to normal values following carotid surgery, while preoperative NAR > 19 remained unchanged (60 cases). The transcranial Doppler CO₂ test is thought to be a reliable noninvasive method to detect hemodynamically critical carotid stenoses and occlusions. This may be of interest in selecting patients for superficial temporal artery-middle cerebral artery bypass and carotid surgery. For practical use 4 categories of NAR are suggested.     

Peripheral chromatolysis after transection of mouse facial nerve

Summary Adult male mice, after transection of the facial nerve near the stylomastoid foramen, were sacrificed at predetermined intervals by the two-step perfusion fixation with a modified Heidenhain's Susa solution and subsequently autopsied after a delay of at least four hours.The normal population of neurons consists of one small form with small basophil granules and one large with numerous coarse granules.The initial change demonstrable in the large neuron 12 hours post-operatively is the loosening of cytoplasmic basophil material which proceeds to a disappearance peripherally at the 24-hour stage; simultaneously an increased staining of the non-particulate cytoplasm takes place. The disintegration of basophil material reaches a maximum 9 days post-operatively and from 12 through 49 days post-operatively occurs an increasingly prominent restoration of basophil material near the nuclear membrane. At the 49-day stage the number of recovered large neurons is small and many are lost. At the 9-and 12-days post-operative stages appears a dark abnormal neuron of questionable origin. Histiocyte reaction is apparent by an increasing number of mitotic figures along vascular walls from the 2nd day to the 9th day; the invasion of microglia cells occurs from the 3rd day and clusters of microglia from the 9th day.The sequential changes in the small neuron are somewhat similar to those in the large type. In its recovered forms, it exceeds the large in number, but is abnormal in color and poorly supplied with basophil material.A concurrent study of the rabbit facial nucleus discloses two types of neurons which after axotomy react differently but mimic at a slower rate the sequence in mice.The cardinal feature of acute retrograde cell changes is the inability of the cytoplasm to store properly its basophil material, as first manifested by a loosening of texture with an early disappearance along the cell periphery and then by haphazard deposition of granular material.With 2 Figures in the Text     

I,you, me,and autism: An experimental study

The nature of autistic individuals' abnormalities in the use of personal pronouns has been a topic of considerable speculation but little systematic investigation. We tested groups of CA- and verbal MA-matched autistic and nonautistic mentally retarded children and young adults on a series of tasks that involved the comprehension and use of the personal pronouns I, you, and me. All subjects were able to comprehend these pronouns within the test situations, and there were few instances of pronoun reversal. However, autistic subjects were significantly less likely to employ the pronoun me in a visual perspective-taking task (when instead they tended to say: I can see the ...), and lower ability subjects were more likely to use their own proper names rather than personal pronouns in certain photograph-naming tasks. There were also circumstances in which autistic subjects were less likely than controls to employ the pronoun you to refer to the experimenter. A high proportion of these autistic subjects were reported to have current difficulties with personal pronouns in their everyday life, and we discuss some alternative interpretations of the results.This research was supported by a Project Grant from the Medical Research Council to the first two authors. We thank the pupils and staff of the Helen Allison School, Gravesend; Dedisham School, Horsham; Great Stony School, Chipping Ongar; and Priory School, Croydon for their help and support with this study.     

Über angeborene Mischgeschwülste des Kleinhirns

Zusammenfassung Es wird über neun umschriebene Geschwülste der hinteren Schädelgrube berichtet, die feingeweblich aus zwei verschiedenen, in Feldern und Zügen angeordneten Gewebsanteilen bestehen. Die Zellen der Felder sind kleine, körnerzellähnliche Elemente mit runden, stark chromatinreichen Kernen. Die Zellen der Züge sind größere Elemente mit rund-ovalen, kommaartigen, chromatinarmen Kernen. In den Zügen läßt sich regelmäßig ein ausgedehntes Reticulinfasernetz nachweisen. Die Felder sind dagegen reticulinfrei, sie bestehen aus einer feinfaserigen neuroectodermalen Grundsubstanz. Charakteristikum dieser Tumoren ist, daß das Mengenverhältnis der zwei Gewebsanteile von Fall zu Fall und sogar innerhalb des gleichen Falles stark variieren kann, so daß die Beobachtung von nur einzelnen Geschwulstpartien oft nicht erlaubt, die gesamte Struktur des Tumors zu erfassen und zu falschen Diagnosen führt.Diese als angeborene Mischtumoren des Kleinhirns bezeichneten Geschwülste sind feingeweblich von den Mischgewächsen des Unterwurmes Ostertags zu trennen. Sie zeigen hingegen gewisse Ähnlichkeiten mit dem sogenannten umschriebenen Arachnoidealsarkom des Kleinhirns (Foerster u. Gagel), von dem sie aber ebenfalls zu trennen sind.Die formale Genese dieser Geschwülste wird unter Berücksichtigung histogenetischer, feingeweblicher und lokalisatorischer Aspekte diskutiert. Sie werden als Kombinationstumoren angesehen mit einer mesodermalen Züge- und einer neuroectodermalen Felder-Gewebskomponente. Ihre dysembryogenetische Natur bzw. ihr früher Entstehungszeitpunkt wird durch das Vorkommen von Kleinhirnmißbildungen bestätigt. Schließlich werden ihre Beziehungen zu den Geschwülsten der sogenannten Medulloblastomgruppen erörtert.

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Summary Nine circumscribed tumors of the posterior cerebral fossa are described; histologically, they were characterized by two different types of tissue components arranged in strands and fields. The parvicellular fields are of neuroectodermal origin, the mesodermal strands consist of large cells and are rich in reticulin containing fibers. One of the two components may considerably outgrow the other one and become responsible for quantitative alterations.These tumors show some resemblance with the so-called circumscribed arachnoidal sarcoma of Foerster-Gagel, but should not be confused with it. They are morphologically also different from Ostertag's mixed tumors of the posterior vermis.This group of tumors is generally combined with cerebellar malformations which underline their dysontogenetic nature or at least the early onset of their development. As to their formal genesis they may be compared with the congenital mixed tumors of other organs (kidney, liver), and therefore be classified as combination tumors according to Meyer.Finally, their relation to so-called medulloblastomas is discussed.

     

Intrafamilial phenotype variation in Friedreich's disease: possible exceptions to diagnostic criteria

Summary Three families are described which include members with typical Friedreich's disease (FD) and others who are ataxic but do not satisfy all the diagnostic criteria for that disease. In family A two patients have an early-onset, rapidly progressive FD, while two others have a late-onset, more benign form. In families B and C one member has typical FD, and another has a similar ataxic syndrome, except for preservation of knee jerks. Laboratory evaluation is consistent with the diagnosis of FD in all cases. FD diagnosis appears justified in secondary cases with late onset or preserved tendon reflexes, provided that the index case fulfils all diagnostic criteria. Whether the diagnosis of FD is tenable in sporadic atypical cases remains to be seen. Echocardiographic and neurophysiological examination may be valuable in classifying such cases.