Relation between the increase in the diffusional permeability of the blood-central nervous system barrier and other changes during the development of experimental allergic encephalomyelitis in the lewis rat

The reduction in the effectiveness of the blood-brain and blood-spinal cord barriers, previously seen in rats at the height of the acute episode of experimental allergic encephalomyelitis, has now been measured at various stages in the development of the disease up to 60 days after inoculation with guinea pig spinal cord in complete Freund's adjuvants. The marker of extracellular space, radioactively labelled mannitol, only crosses the blood-central nervous system barriers very slowly by passive diffusion in normal rats. An abnormal penetration of this marker into the central nervous system began to develop during the second week after inoculation, appearing first in the lower spinal cord, where it also reaches the highest level during the acute phase of the attack. The leak begins before either the clinical signs become evident or cuffing is seen around blood vessels in stained sections. As the clinical signs are disappearing, from about 15 days onwards, the permeability of the barrier returns steadily to its normal low value, starting in the spinal cord, especially the caudal part. The timing of the reduction in the effectiveness of the blood-central nervous system barrier in relation to other clinical and histological changes suggests that it may play a part in the development of the lesion. The relation between the timing of these changes in EAE and that in the development of a new lesion in (exacerbation of) multiple sclerosis is discussed.     

Retinal perivasculitis with neurological involvement. A case report with pathological findings

The clinical and neuropathological findings in a case of retinal periphlebitis with cerebral involvement are described. Neurological involvement in retinal periphlebitis is uncommon and so far the pathology has been described in only one case.     

Successful flooding treatment of a noise phobia in an eleven-year-old

An 11-yr-old boy with a severe phobia for loud noises was treated in two sessions of flooding treatment following the failure of in vivo desensitization. The boy has remained free of phobic behaviour over a 25-month follow-up period.     

Sensory experience as a trigger in Gilles de la Tourette's syndrome

The case to be reported presented with multiple motor tics. During the course of therapy, directed along behavioural lines, a model of the nature of the movements emerged which was later found to be strikingly similar to that described by Bliss (1980). The patient (J) complained of a “horrible” sensation, similar to an “itch”, which always preceded the tic movements and which could be removed by movement. Occasionally, by supreme effort, the “itch” would be resisted and movement avoided. These sensations could thus be viewed as a trigger for the movements. The implications of such an analysis for current conceptualisations of, and intervention with, motor tics are discussed.     

A brief correction procedure for the management of high rate spitting in a profoundly retarded girl

This study demonstrates the effectiveness of a brief correction procedure in decelerating a high rate anti-social behaviour (spitting) in a profoundly retarded girl. A simple correction procedure seemed as effective as a more elaborate procedure incorporating positive practice elements, and gains were sustained with some variability over an extended period of time. No reliable increases in collateral behaviours were noted to result from the deceleration in spitting.     

A case of absolute ejaculatory incompetence treated without extra-vaginal ejaculation

In a case of absolute ejaculatory incompetence, a covert self-modelling procedure was used to overcome inhibition of ejaculation. This was combined with instructions on modification of position and techniques of intercourse in order to increase penile stimulation. The patient achieved normal functioning without being required to pass through the usual intermediary stage of extra-vaginal ejaculation by masturbation. The improvement was maintained fifteen months after termination of treatment.     

Nonconvulsive psychogenic attacks investigated for temporal lobe epilepsy

Slater and Roth recognize the occasional diagnostic problem due to the “overlap between the symptomatology of temporal lobe epilepsy and neurotic disturbance…”¹ Harper and Roth² compared the clinical features of patients with phobic anxiety-depersonalization syndrome with temporal lobe epileptics and found that the psychogenic group had significantly more family histories of neurosis, childhood and adult phobias, anxiety and depressive syndromes, hypochondriacal symptoms, and personality traits of immaturity and dependence. This study examined this subject using rating scales.     

Cellular hypersensitivity to gangliosides and myelin basic protein in multiple sclerosis

Peripheral blood lymphocytes from patients with multiple sclerosis (MS), other neurological diseases and healthy controls were investigated for the presence of cell-mediated hypersensitivity to brain gangliosides and myelin basic protein using an active E-rosette assay. Sensitivity to myelin basic protein and gangliosides was found in MS patients in acute relapse and with progressive disease, whereas no sensitivity was found in MS patients in remission. Patients with other neurological diseases showed no response to gangliosides, but sensitization to myelin basic protein was found in a patient with leucoencephalopathy and in 4 of 6 stroke patients. Healthy controls did not respond to either antigen. In MS patients a positive correlation was seen between lymphocyte responses to myelin basic protein and to gangliosides. The data suggest that in comparison to gangliosides, myelin basic protein is a weaker stimulator of active rosette-forming cells. Moreover, cellular hypersensitivity to myelin basic protein is not MS-specific and may be present as a consequence of brain damage. However, cellular hypersensitivity to gangliosides appears to be more specific to MS and may be important in the pathogenesis of the disease.     

Serum creatine phosphokinase (CPK) activity in monozygotic twins discordant for schizophrenia: Heritability of serum CPK activity

Recent studies with normal monozygotic and dizygotic twins have established that serum creatine phosphokinase (CPK) activity in man is under genetic control (Meltzer, Dorus, and Davis, in preparation). This is of interest because of the reports that serum CPK activity is increased in many acutely psychotic patients, provided that they are studied in the first days after the onset of gross psychotic symptoms and throughout hospitalization.^1–12 The increases range from slightly above the 95% upper limits of normal to 50–75 times the limits for each race-sex group. Furthermore, 25%–30% of the first degree relatives of psychotic patients have slight but persistent increases in serum CPK activity.^2,3,7 These increases occur significantly more frequently in relatives of psychotic patients who have themselves had increases in serum CPK activity (Meltzer and Moretti, in preparation). Prior to the studies with normal twins which established that serum CPK activity is under some genetic control, we had the opportunity to study serum CPK activity in twins discordant for schizophrenia. These results will be reported here.     

Distribution of radioactivity from topically applied [H3]acetylcholine in relation to seizure.

A study was performed to determine if topically applied acetylcholine (ACh) could reach infragranular cortical layers by the time epileptiform activity appeared in intact and bilaterally chronically undercut cat cortex. At various times after bilateral application of neostigmine and [H³]ACh, the brain was frozen with liquid nitrogen. The cortex was sectioned parallel to the surface, placed in liquid sicntillation vials, and curves of radioactivity estimated as ACh vs. cortical depth constructed. In 2 min activity is found in white matter with maximum amounts of activity in all layers of the cortex reached in 3 to 5 min, the time when seizure begins when it occurs. It is concluded that topically applied ACh is not restricted to supragranular layers and probably acts throughout the cortical depth to induce seizure. Seizure occurred in nine of 24 foci, eight of which were in chronically undercut preparations. With these bilateral foci, seizure began earlier ($\text{x}\text{= 4.8}\text{min}$) than seizure from unilateral foci ($\text{x}\text{= 8.7}\text{min}$). However, no difference in depth distribution was found between seizure and nonseizure foci or between intact and chronically undercut cortex. Therefore, depth distribution alone is not sufficient to explain the seizure propensity of chronically undercut cortex.     

Depression and Incidence of Frailty in Older People From Six Latin American Countries

ObjectiveFrailty and depression are highly comorbid conditions, but the casual direction is unclear and has not been explored in low- and middle-income countries. The aim of this study was to investigate the potential impact of depression on incident frailty in older people living in Latin America.MethodsThis study was based on a population-based cohort of 12,844 people aged 65 or older from six Latin American countries (Cuba, Dominican Republic, Mexico, Venezuela, Puerto Rico, and Peru), part of the 10/66 cohort study. Two types of frailty measures were used: a modified Fried frailty phenotype and a multidimensional frailty criterion, which included measures from cognition, sensory, nutrition, and physical dimensions. Depression was assessed using EURO-D and International Classification of Diseases, Tenth Revision criteria. A competing risk model was used to examine the associations between baseline depression and incidence of frailty in the 3–5 years of follow-up, accounting for sociodemographic and health factors and the competing event of frailty-free death.ResultsDepression was associated with a 59% increased hazard of developing frailty using the modified Fried phenotype (subdistribution hazard ratio [SHR]: 1.59; 95% confidence interval [CI]: 1.40, 1.80) and 19% for multidimensional frailty (SHR: 1.19; 95% CI: 1.06, 1.33) after adjusting for sociodemographic factors, physical impairments, and dementia. The associations between depression and the multidimensional frailty criteria were homogenous across all the sites (Higgins I² = 0%).ConclusionDepression may play a key role in the development of frailty. Pathways addressing the association between physical and mental health in older people need to be further investigated in future research.     

Acetylcholine epilepsy: Relationship of surface concentration,chronicity of denervation,and focus size

Experiments were performed on intact and chronically undercut cat suprasylvian gyrus attempting to determine a critical minimum size of cortical aggregate for acetylcholine (Ach) induced epileptiform activity. Cortical seizure foci of different sizes, 4 × 4 mm, 2 × 2 mm, and 1 × 1 mm were made with filter papers wetted to contain equal fluid volumes with equimolar amounts of Ach per unit area for each experiment. Concentrations of Ach varied from 0.5% (3.4 nmoles/mm²) to 4% (28 nmoles/mm²). The following results were obtained: The probability of seizure increased with increasing focus size and with increasing amount of Ach per mm² of filter paper. Seizure occurred reliably with small (1 × 1 mm) foci in intact animals with 28 nmoles of Ach, whereas only 6.8 nmoles was required in chronically undercut preparations of 31 days or more. Average time to seizure onset was 8.75 min and was not statistically different for different size foci. No minimum cortical aggregate size necessary for Ach induced seizure could be established with this method. The size may vary under differing stimulus conditions but the results suggest that a volume with linear dimensions of 1 mm or less would be large enough.     

Complement abnormalities in polymyositis

Eight of 19 cases of polymyositis were found to have positive anticomplementary assays with concomitant evidence of complement activation in 6 of these cases. The presence of circulating soluble immune complexes is suggested. These complexes may have a primary role in the pathogenesis of the disease     

Endorphin research in schizophrenic psychoses

The discovery of the endorphins has opened up a new dimension for research into the biological determinants of schizophrenic behavior. However, it would be premature to advance an endorphin hypothesis on the pathogenesis of schizophrenic psychoses at this time. Technical difficulties have so far been an obstacle in the study of the human central endorphin metabolism. The therapeutic aspect of endorphin research shows some interesting features. Opiate (endorphin) antagonists certainly do not seem to be universal antipsychotics, but undoubtedly it is worthwhile to continue the search for subgroups that are susceptible to these compounds. The reverse of this strategy has also been applied: administration of endorphins to schizophrenic patients. Of the three compounds used in this context, β-endorphin, a synthetic met-enkephalin derivative and DTγE, the latter is the most interesting. It is a naturally occurring fragment of γ-endorphin which lacks morphinomimetic effects and has certain pharmacological as well as clinical properties in common with the traditional neuroleptics. This compound may well open up entirely new perspectives for the treatment of schizophrenic psychoses.