Abnormal course of spinal posterior roots and tracts associated with brain malformations

Summary An unusual mode of the spinal posterior nerve root entrance and of the course of ascending tracts in the hyperplastic gray matter of the posterior horn was observed in three newborn babies. This sensory pathway malformation was combined with severe but unspecific brain anomalies. The common associated brain anomaly was agenesis of the corpus callosum.Dedicated to Professor Dr. Hans Jacob for his 80th birthday     

Neuropathological findings of a patient with pyruvate dehydrogenase E1α deficiency presenting as a cerebral lactic acidosis

Summary Neuropathological findings are reported of a 6-month-old female child with a cerebral lactic acidosis. A mutation in the pyruvate dehydrogenase (PDH) E1 gene was found. Gross examination of the brain revealed a severe thinning of the cerebral parenchym, a marked hydrocephalus sparing the aqueduct and fourth ventricle, agenesis of the corpus callosum and heterotopic noduli of gray matter in subependymal regions. Microscopical examination showed heterotopic inferior olives, absent pyramids and focal neuroglial overgrowth into meninges. In addition some heterotopia of Purkinje cells and dysplasia of the dentate nuclei were observed. There was a marked vascular proliferation with many thin-walled, congestive vessels in the cerebral and cerebellar white matter, and to a lesser extent in the striatum. To our knowledge these cerebellar and vascular abnormalities have not been reported before in patients with cerebral lactic acidosis. The combination of these neuropathological findings might be characteristic for PDH deficiency and more specifically for its E1 subtype. Neuropathological examination could lead to the retrospective diagnosis of PDH E1 deficiency in those cases where biochemical investigations were not or incompletely performed. This may have potential implications for genetic counseling.     

Mental Hygiene of the Special Schools Teachers in Kerman,Iran

The goal of this research is to identify and study the mental hygiene and its related factors (individual, family, organizational) in the Kerman special schools teachers. 266 teachers of the special schools of the cities of the province Kerman were chosen as the research sample. The necessary data were obtained by questionnaire which its validity and reliability were determined. The statistical analysis of the research findings (by Spearman coefficient test) Man-Whithey and Kruskal wallis tests showed that there was a positive and meaningful relationship between Level of education, service of record the number of the members of teachers family, income, dwelling-place, economic power, acceptance of the teachers job in their family, leadership style, suitable educational possibilities, suitable educational space, job satisfaction with the mental hygiene of the teachers. The results of the research also showed that the Kerman special schools teachers enjoyed a relatively desirable mental hygiene.     

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.     

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.     

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     

Fluctuating parkinsonism: a pilot study of single afternoon dose of levodopa methyl ester

Thirty-four patients with idiopathic fluctuating Parkinson's disease and early afternoon delayed on or severely resistant off periods, in spite of long-term antiparkinsonian therapy, were studied. The first afternoon levodopa administration was substituted with an equimolar dosage of the liquid formulation levodopa methyl ester (LDME). The major end-points for efficacy were latency to on and duration of on periods. The patients were divided into five subgroups according to their baseline treatment and they were evaluated monthly for 6 months using the Unified Parkinson's Disease Rating Scale. The patients completed weekly self-evaluation using an on-off chart. LDME was well tolerated by all the patients. A statistically significant reduction in latency to on was observed in all patients. The clinical effect of LDME remained stable during the treatment period (repeat measures ANOVA). The more rapid clinical effect of LDME and its stable and predictable antiparkinsonian activity represents a new and useful approach for treating patients with complicated Parkinson's disease.     

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.     

Deposition of β/A4 protein along neuronal plasma membranes in diffuse senile plaques

Summary The origin of the extracellular -amyloid protein (/A4) found in senile plaques and the cellular mechanisms responsible for its deposition in cerebral tissues are still an unresolved issue in Alzheimer's disease. In this study we analyzed in detail the distribution of various epitopes of /A4 in relation to local cellular elements in diffuse plaques of the hippocampal region. We also correlated our findings with the presence and distribution of non-/A4 epitopes of the amyloid precursor protein (APP) and with synaptophysin immunoreactivity in the cortical neuropil. Discontinuous /A4-immunoreactive deposits were found along dendrites, and around the soma of neurons included in the plaques. Furthermore, increased synaptophysin reactivity with slightly dilated synaptophysin-immunolabeled presynaptic terminals were found in diffuse plaques. APP epitopes could not be found in diffuse plaques. However, some of the APP antibodies, mainly those to the C-terminal portion of APP, and antibodies to /A4 recognized clusters of flat vesicular profiles (0.6–1.4 m in width and 2–3 m in length) in the neuropil of cortical areas where plaques had developed. Our findings are compatible with a neuronal origin of /A4 in diffuse plaques and with a primary release of /A4 at synaptic sites along the immunostained neurites. They also suggest that diffuse plaques might be preceded by minute lesions of the neuropil where /A4 is not yet released from the precursor molecule.     

Über die sogenannte „zentrale Tonusdifferenz“ mit Nystagmusbereitschaft nach einer Seite

Zusammenfassung An Hand von 71 sowohl otologisch als auch neurologisch-psychiatrisch untersuchten Fällen wird zur Frage der sog. zentralen Tonusdifferenz Stellung genommen.1. In 40% der Beobachtungen waren als Ursache des einseitigen Nystagmusüberwiegens Schäden im Labyrinth bzw. im Bereich des 1. vestibulären Neurons anzunehmen.2. Bei 35% der Untersuchten war sowohl eine periphere als auch zentrale Verursachung möglich. Überwiegend handelt es sich um Patienten mit einem klinischen Halswirbelsäulensyndrom. Der funktionelle Charakter der Störung wird diskutiert.3. In 25% unserer Fälle lagen sicher zentrale Schäden vor, jedoch fand sich mit 2 Ausnahmen kein Anhalt für die Annahme einer Hirnstammläsion als Ursache der Nystagmusbereitschaft nach einer Seite.Therapieversuche werden erwähnt.Der Begriff zentrale Tonusdifferenz wird als mißverständlich abgelehnt und betont, daß dem einseitigen Nystagmusüberwiegen keineswegs ein Hinweischarakter auf eine Hirnstammcontusion zukommt. Die Nystagmusbereitschaft nach einer Seite kann von jedem Abschnitt des vestibulären Systems ausgelöst werden.Teilergebnis eines Forschungsauftrages des Bundesministeriums für Arbeit.     

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.

     

Obsessive-Compulsive Disorder in Popular Magazines

To examine what the general public is learning about Obsessive-Compulsive Disorder (OCD) through popular magazines, all articles listed in the Reader's Guide to Periodical Literature under the topic headings of obsessive-compulsive behavior or obsessive-compulsive disorder between 1983 and 1997 were read and rated. Only 31 of the 107 articles under these headings dealt explicitly with OCD, and these were found to be reasonably accurate in their presentations of symptoms, causes, and treatments. Many of the other articles under the target headings, however, focused on incidents of stalking of famous people by obsessed fans. The implications of the content patterns of these articles for understanding and misunderstanding of OCD are discussed.     

Akinetic mutism due to glioma of the midline

Summary The case described presents all clinical features for the definition of the true akinetic mutism syndrome. The anatomical examination revealed a polymorphous glioblastoma involving the structure of the midline, and particularly the rostral region of the gyrus cinguli, corpus callosum and the septal areas.     

Effects of thyroid status on presynapticα2-adrenoceptor function andβ-adrenoceptor binding in the rat brain

Summary The effect of thyroid status on noradrenergic synaptic function in the mature rat brain was examined by measuring presynaptic2- and post-synaptic-adrenoceptors.Repeated triiodothyronine (T₃) administration to rats (100g/kg×14 days: hyperthyroid) caused an 18% increase in striatal-adrenoceptors as shown by [³H]-dihydroalprenolol binding with no change in membranes from cerebral cortex or hypothalamus. In contrast, hypothyroidism (propyl-thiouracil, PTU×14 days) produced significant 12% and 30% reductions in striatal and hypothalamic-adrenoceptors respectively with no change in the cerebral cortex. Presynaptic2-adrenoceptor function was measured in the two dysthyroid states using the clonidine-induced hypoactivity model. Experimental hyperthyroidism increased the degree of clonidine-induced hypoactivity, and suggests increased presynaptic2-adrenoceptor function compared with control rats, whereas hypothyroidism suppressed presynaptic2-adrenoceptor function. These results show firstly that changes in thyroid status in the mature rat may produce homeostatic alterations at central noradrenergic synapses as reflected by changes in pre- and postsynaptic adrenoceptor function. Secondly, there appear to be T₃-induced changes in-adrenoceptors in the striatum where changes in dopaminergic neuronal activity have previously been demonstrated.     

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.     

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.     

The Proustian itinerary from sensation to memory

Information processing streams that proceed through the sensory unimodal and multimodal areas of the cerebral cortex, and hence the limbic system, bring from perception to memory. This itinerary through the neural networks underlying perception and cognition is briefly outlined through famous passages from Marcel Proust's Swann's Way, in which the flavour of the petites madeleines triggers vivid recollection.La mémoire est nécessaire pour toutes les opérations de la raison     

Astrocytes in hemangioblastomas of the central nervous system and their relationship to stromal cells

Summary Thirteen cases of CNS hemangioblastoma were examined with the immunoperoxidase technique for glial fibrillary acidic protein (GEAP) to determine if there were astrocytic elements among the stromal cells of these tumors.In six cases, including two leptomeningeal hemangioblastomas, none of the stromal cells were positive on GFAP stain. Seven cases, however, showed variable presence of GFAP positive cells, including clusters of heavily lipidized cells deep within cerebellar hemangioblastomas. These GFAP positive cells were indestinguishable by other stains from interstitial or stromal cells.Thus, it appears that in at least some hemangioblastomas of the CNS parenchyma, a few or many stromal cells are lipidized astrocytes. All stromal cells, however, cannot be of astrocytic origin, as proposed by Jakobiec et al. (1976), in view of our six cases where no GFAP-positive cells were found in the tumors.It is suggested that cells identified as stromal cells of hemangioblastomas on light microscopy are a heterogeneous group of cells including astrocytic as well as other elements and that they resemble each other on ordinary stains because of the equalizing effect of cell lipidization.     

Die ZNS-Veränderungen bei den olivo-ponto-cerebellaren Atrophien

Zusammenfassung Es wird über 20 Autopsiefälle und einen klinisch beobachteten Geschwisterfall von olivo-ponto-cerebellarer Atrophie (OPCA) berichtet. Es handelte sich um 6 familiäre, darunter 2 dominante, Formen und 15 sporadische Fälle. Letztere waren durch ein durchschnittlich höheres Erkrankungsalter und seltenere spinale Ausfälle gekennzeichnet. Extrapyramidale Syndrome wurden bei 8 Probanden verzeichnet. Morphologisch fanden sich neben der typischen Atrophie der cerebellopetalen Systeme (Brückenfuß, untere Oliven, Kleinhirnhemisphären) in allen Fällen atrophisierende Läsionen wechselnden Grades in anderen Neuronen-system (Nebenlokalisationen): Außer fast konstanter Schädigung der Z. compacta nigrae und des Putamen bestanden häufig Läsionen im Thalamus (Centrum medianum), in der Z. reticularis nigrae und in Hirnstammkernen. Die Hälfte der Fälle bot höhergradige Großhirnrindenatrophie. Spinale Strang- und Kerndegenerationen traten nicht nur bei allen hereditären, sondern auch in einem Teil der sporadischen Formen auf. Ein reiner Fall von OPCA wurde nicht beobachtet. Zwischen den sporadischen und hereditären Formen ergaben sich keine grundsätzlichen morphologischen Unterschiede. Auf das konstante Auftreten variabler Nebenlokalisationen bei der OPCA als einem Prototyp der kombinierten Systematrophien des ZNS wird hingewiesen.

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CNS lesions in olivo-ponto-cerebellar atrophies

Summary 20 autopsy cases and one clinical case of siblings with olivopontocerebellar atrophies (OPCA) are reported. They include 6 familial cases, two of them of dominant transmission, and 15 sporadic cases. The latter type was characterized by a higher mean age at the onset of the disease and by a more frequent incidence of spinal symptoms. Extrapyramidal symptoms were reported in 8 cases. The morphological examination revealed, in addition to the typical atrophy of the cerebellopetal systems (basis of the pons, inferior olives, and cerebellar hemispheres), further atrophic lesions of different intensity involving various neuron systems (associated lesions) in all cases examined. Substantia nigra and putamen were almost consistently affected, the thalamus (centrum medianum) and the reticular part of the substantia nigra frequently. Severe cerebral cortical atrophy was seen in almost half the cases. Losses of neurons and fibres of the spinal cord occurred in all hereditary cases and in some of the sporadic ones. Pure cases of OPCA were not observed in this sample. Morphologically there were no essential differences between hereditary and sporadic forms of OPCA. The regular occurrence of associated lesions in this group of combined systemic degenerations of the CNS is emphasized.

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Herrn Prof. Dr. G. Peters zum 8. 5. 1971 in Verehrung zugeeignet.     

“Echoing approval”: A new speech disorder

We report the cases of two patients presenting a peculiar speech disorder, which we have named echoing approval, in which the patients echo, in replying to questions in a dialogue with short phrases, the positive or negative syntactical construction of a question, or its positive or negative intonation, but without any repetition of whole or part of sentences. When asked about their symptoms, the patients replied 80% of the time with yes, yes, that's right, or exactly to positive questions and no, no or absolutely not to negative questions, regardless of their actual symptoms and oblivious to self-contradiction. In addition, when the examining doctor was speaking to a medical colleague in the patient's presence and using medical terminology that the patient did not understand, he/she agreed or disagreed with any sentence and technical word uttered in a way entirely dependent on the syntax or intonation used. To distinguish this speech disorder from echolalia or verbal perseverations, with which it may be superficially confused, we suggest that it be called echoing approval, as it may be part one of the manifestations of the environment-dependency syndrome. This clinical picture was found to be associated with features of transcortical motor aphasia and frontal lobe signs. One patient had a bilateral callosofrontal malignant glioma and the other a probable multiple system atrophy with global deterioration, pre-eminent frontal release signs, diffuse leukoencephalopathy and multiple lacunes. On the basis of these clinical deficits and neuroimaging features, we are unable to delineate the common, or minimal, lesioned network required for this symptomatology to occur, especially in the absence of a series of patients, and with such a difference in both the location and causes of the lesions. However, bilateral frontosubcortical dysfunction was pre-eminent in the clinical picture in both patients, even though more diffuse brain pathology was seen in one, and it might be speculated that dysfunction of the bilateral orbitofrontal and frontomesial motor frontosubcortical circuits might be involved in the aetiology of this peculiar speech disorder.