A molecular basis for interactions between the immune and neuroendocrine systems

Homeostatic and psychologic alterations associated with infections and tumors are very interesting yet poorly understood pathophysiologic responses. Numerous anecdotal and indirect examples suggest that these responses occur through a link between the central nervous and immune systems (for review see Blalock, Bost, & Smith, 1985; Spector & Korneva, 1981; Maestroni & Pierpaoli, 1981; Felton et al., 1985; Jankovic, 1985). Interactions between the two systems are just now being described. One possible mechanism is direct modulation of the immune system by the sympathetic nervous system. This could occur in innervated immune organs such as spleen, thymus, and bone marrow (Felton et al., 1985). The evidence for this is that sympathectomy and lesioning of specific regions of the brain can be shown to both enhance and/or suppress immune responses (Miles et al., 1985; Roszman et al., 1985). Also, the firing rate of hypothalamic neurons is altered during an immune response (Besedovsky et al., 1977). Alternatively, hormonal involvement in immune reactions has been known for some time, in particular the immunosuppressive effects of glucocorticoids (for review see Cupps & Fauci, 1982). Recently, we and others found that neuroendocrine peptide hormones will modulate T and B lymphocytes plus other immunocyte responses (Besedovsky et al., 1977; Cupps & Fauci, 1982; Johnson et al., 1982; Wybran et al., 1979; Hazum, Chang & Cuatrecasas, 1979; O'Dorisio et al., 1981; Gilman et al., 1982; McCain et al., 1982; Mathews et al., 1983; Plotnikoff et al., 1985; Johnson et al., 1984). Furthermore, lymphocytes themselves can synthesize biologically active neuroendocrine hormones (Blalock & Smith, 1980; O'Dorisio et al., 1980; Smith & Blalock, 1981; Smith et al., 1983; Lolait et al., 1984; Ruff & Pert, 1984), as well as possess specific hormone receptors (Blalock et al., 1985; Johnson et al., 1982; Wybran et al., 1979; Hazum et al., 1979; O'Dorisio et al., 1981; Lopker et al., 1980; Payan, Brewster & Goetzl, 1984; Pert et al., 1985). Immune responses (Besedovsky, del Rey & Sorkin, 1981), thymic hormones (Healy et al., 1983), and lymphokines (Lotze et al., 1985; Woloski et al., 1985) have all been shown to exert hormonal effects. Thus, another method for communication between the immune and neuroendocrine systems seems to be through soluble factors such as neuroendocrine hormones. This review will concentrate on the latter topic, in particular on work this laboratory has done over the past few years to show the lymphocyte production and immunoregulatory actions of neuroendocrine hormones.     

Conducting exposure and response prevention treatment for contamination fears during COVID-19: The behavioral immune system impact on clinician approaches to treatment

The coronavirus disease 2019 (COVID-19) pandemic sparked significant anxiety regarding viral rates and means of transmission. Heightened concerns about contamination have prompted new hygienic strategies to vigilantly guard against infection, including hand washing immediately after touching foreign objects or suspected contaminants. This has presented a critical challenge for the delivery of exposure and response prevention (ERP) therapy to individuals with contamination fears due to Obsessive Compulsive Disorder (OCD), as providers must manage not only their clients’ attitudes and reactions but their own as well. In this investigation, self-identified anxiety and OCD treatment specialists (N = 139) provided demographic information, including their anxiety and OCD caseloads, and completed measures related to intolerance of uncertainty (IUS-SF; Carlton et al., 2007), beliefs about exposure therapy (TBES; Deacon et al., 2013), and emotional reactions to physical sensations (The Chills; Maruskin et al., 2012). We tested the hypothesis that intolerance of uncertainty and activation of the behavioral immune system (BIS; Schaller & Park, 2011), a mechanism theoretically activated by the prominent emergence of pathogens to protect against illness would predict attitudes toward exposure. The Chills Scale was used to assess BIS activation, a broad assessment of vasoconstriction responses associated with different emotional reactions, and includes a subscale (coldness) that evaluates vasoconstriction associated with defense against pathogens. Both coldness and OCD caseload, but not anxiety caseload or subscales of intolerance of uncertainty, emerged as significant predictors of clinicians’ beliefs about exposure; increases in OCD caseload were also related to decreases in negative beliefs about exposure. Findings are useful in determining methods for aiding clinicians in developing effective approaches to contamination fears during and post-pandemic that include addressing their own BIS-related concerns and mapping out means for social behavioral norms associated with engaging in exposure treatment.     

Does schizophrenia result from developmental or degenerative processes?

The debate as to whether schizophrenia is a neurodevelopmental or a neurodegenerative disorder has its roots in the latter part of the 19th century when authorities such as Clouston (1891) posited that at least some insanities were "developmental" in origin. These views were soon eclipsed by Kraepelin's (1896) concept of dementia praecox as a degenerative disease, and the latter view carried not only the day but also much of the 20th century. Then, in the 1980s several research groups again began to speculate that schizophrenia might have a significant developmental component (Feinberg, 1982-1983; Schulsinger et al., 1984; Murray et al., 1985; Murray and Lewis, 1987; Weinberger et al., 1987). What became known as the "neurodevelopmental hypothesis" received support from neuropathological studies implicating anomalies in early brain development such as aberrant migration of neurons. Unfortunately, these studies proved difficult, if not impossible, to replicate (Harrison, 1999). The pendulum, therefore, began to swing again, and in the latter part of the 1990s came renewed claims that the clinical progression of the illness was accompanied by continued cerebral ventricular enlargement and reduction in the volumes of certain brain structures. Nevertheless, since few doubt that there is a developmental component to schizophrenia, the question which we will address in this paper is whether schizophrenia is a) simply the final consequence of a cascade of increasing developmental deviance (Bramon et al., 2001), or b) whether there is an additional brain degeneration following onset of psychosis which is superimposed on the developmental impairment (Lieberman, 1999).     

Intraspinal opiates for treatment of intractable pain in the terminally ill cancer patient

The discovery of opiate receptors and then their endogenous ligands in 1974 (Snyder et al., 1974) has elucidated a vast pharmacology of opiates providing a basis for their diverse clinical applications. With the awareness of quality of life as a primary goal in terminal cancer patients, widespread attention has been drawn to the direct delivery of long-term intraspinal analgesics to cancer patients for who all medical pain control regimens have failed (Coombs & Saunders, 1974). Intraspinal administration of opiates and nonopiate analgesics is not only appealing on theoretical grounds but provides a minimally invasive method to insure otherwise unobtainable pain relief while eliminating obtundation and systemic side-effects associated with conventional therapy (Cobb et al., 1984; Harbaugh et al., 1982; Leavens et al., 1982; Malone et al., 1985; Onofrie et al., 1981; Poletti et al., 1981). Although intraspinal opiates have been used in the treatment of postoperative and benign-pain syndromes (Asari et al., 1981; Cousins & Mather, 1984), in our discussion we review the basic science, current techniques and possible future improvements in spinal analgesia in the control of chronic cancer pain.     

Neuromodulation of acute-phase responses to interleukin-6 in guinea pigs

It is now generally recognized that interleukin-6 (IL6) is one of the cytokines that mediate the various nonspecific host defense responses to infectious pathogens. Among its now well-demonstrated effects on systemic administration are fever and acute-phase proteinemia. These effects are also activated by the cytokine, IL1, and it has been shown that they are modulated in the preoptic-anterior hypothalamus (POA). This study was undertaken to determine whether this brain region similarly drives the febrile and proteinemic responses to IL6. We compared, therefore, these responses of conscious guinea pigs to human recombinant (hr)IL6 administered intravenously (IV) and into the POA. hrIL6 given IV was not pyrogenic at 1 microgram/kg, caused low-grade, dose-independent fevers (0.4 +/- 0.1 degree C) at 5-20 micrograms/kg, and dose-related fevers at 50 and 100 micrograms/kg (0.6 +/- 0.0 and 0.9 +/- 0.1 degree C, respectively). However, all doses of hrIL6 induced elevations in the plasma levels of ceruloplasmin (as an indicator of acute-phase proteins), albeit not in a dose-dependent manner. Indomethacin (10 mg/kg, injected intramuscularly 20 min before hrIL6) abolished the febrile response, but did not prevent the rise in plasma ceruloplasmin levels. Fever and ceruloplasminemia were also evoked by 50 and 100 ng of hrIL6 injected into the POA (1 microliter bilaterally), but not by 25 ng. These results indicate that the inductions of fever and plasma ceruloplasmin by IL6 are, like those of IL1, modulated in the POA, albeit the effective doses are much higher than those of IL1.     

The two major phosphoproteins in growth cones are probably identical to two protein kinase C substrates correlated with persistence of long-term potentiation

Regulation of neural protein kinase C (PKC) activity appears to directly affect the persistence of long-term potentiation (LTP; Akers and Routtenberg, 1985; Lovinger et al., 1985, 1986, 1987; Routtenberg et al., 1985, 1986; Akers et al., 1986; Linden et al., 1987), a model of neural plasticity (Bliss and Lomo, 1973). In addition, the in vitro phosphorylation of a brain-specific PKC substrate, protein F1 (Mr 47 kDa, pl 4.5), has been directly correlated with persistence of LTP (Lovinger et al., 1986). Because PKC has been implicated in neurite outgrowth and is present at high levels in growth cone-rich areas of fetal brain, we investigated and characterized PKC substrates in a preparation of isolated nerve growth cone fragments from fetal rat brain and compared them with PKC substrates found in adult rat hippocampus. Four major proteins in the growth cone preparation showed endogenous phosphorylation levels at least 10-fold greater than any other phosphoproteins. Three of these 4 phosphoproteins, termed pp40, pp46, and pp80 (Katz et al., 1985), were phosphorylated by exogenous PKC in a dose-dependent manner, indicating that PKC activity might be of particular importance relative to other kinases in growth cone function. The 2 most highly labeled PKC substrates, pp46 and pp80, comigrated on 2-dimensional gels with the adult hippocampal proteins F1 and "80k" (Mr 78-80 kDa, pl 4.0), respectively. In addition, similarities in charge heterogeneity, 2-dimensional phosphopeptide maps, and increased phosphorylation in the presence of exogenous PKC or PKC stimulators suggest that protein F1 and 80k are highly homologous to, if not identical to, pp46 and pp80, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blends of rostral and caudal scratch reflex motor patterns elicited by simultaneous stimulation of two sites in the spinal turtle

Simultaneous tactile stimulation of 2 sites on the body surface of a spinal turtle elicits complex blends of the scratch forms and motor patterns associated with each site. Our previous work has utilized 1-site stimulation to elicit distinct forms of the scratch reflex in the spinal turtle (Mortin et al., 1985; Robertson et al., 1985). Using this paradigm, stimulation of a site on the shell bridge anterior to the hindlimb elicits a rostral scratch reflex in which the dorsum of the foot rubs against the stimulated site; stimulation of a site near the tail elicits a caudal scratch reflex in which the heel or side of the foot rubs against the stimulated site (Mortin et al., 1985). During each scratch cycle, the monoarticular knee extensor muscle is active when the limb rubs against the stimulated site, and there is rhythmic alternation between hip protractor and hip retractor muscle activity (Robertson et al., 1985). In a rostral scratch, the monoarticular knee extensor muscle is active during the latter portion of hip protractor muscle activity; in a caudal scratch, the monoarticular knee extensor muscle is active near the end of hip retractor muscle activity. Pure-form motor patterns that are similar to those recorded from these muscles during movement can be recorded from the corresponding nerves in a spinal turtle immobilized with a neuromuscular blocking agent (Robertson et al., 1985). In this paper, we describe blend responses to simultaneous stimulation of 2 sites, one in the rostral scratch and the other in the caudal scratch receptive field. During these blends, the responding hindlimb rubs against both stimulated sites in one continuous movement sequence.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immune cytokines and regulation of body temperature, food intake and cellular immunity

Interleukin-1 (IL-1) and interferon alpha (IFN alpha), cytokines originally detected in immunological cells, now have been shown to produce nonimmunological host defense responses of central and peripheral origins. These cytokines are released from glial cells in the brain in pathological states. Local application of IL-1 beta and IFN alpha to thermosensitive neurons in the preoptic and anterior hypothalamus and glucose responsive neurons in the ventromedial hypothalamus in vivo and in vitro, altered the activity in appropriate ways to explain the cytokines-induced fever and anorexia, respectively. The responses to IL-1 beta, but not to IFN alpha, were blocked by sodium salicylate, suggesting the involvement of synthesis of prostaglandins. alpha MSH, an endogenous antipyretic and a possible antagonist of IL-1 beta at lymphocytes, specifically depressed the responses to IL-1 beta, but not those to IFN alpha. In contrast, the action of IFN alpha was reversibly blocked by naloxone, suggesting the opioid receptor mediation. Intracerebral injection of IFN alpha and beta-endorphin in the rat and mouse resulted in the suppression of cytotoxic activity of natural killer cells in the spleen by activation of brain opioid receptor, which was shown to be mediated predominantly by splenic sympathetic nerves. The results suggest a view that immune cytokines may provide afferent links for the regulatory circuits between the brain and the immune system.     

Mechanisms of CNS response to systemic immune challenge: the febrile response

The acute-phase reaction is the multisystem response to acute inflammation.  The central nervous system (CNS) mediates a coordinated set of autonomic, endocrine and behavioral responses that constitute the cerebral component of the acute-phase reaction. However, the mechanisms of immune signaling of the CNS remain controversial. Emerging evidence indicates that different parts of the acute-phase reaction are initiated by distinct mechanisms and in different brain regions. Cytokines produced as a result of local infections (for example, in the abdominal or thoracic cavities) might activate vagal sensory fibers, resulting in sickness behavior and fevers.  Additionally, circulating immune stimuli might activate meningeal macrophages and perivascular microglia along the borders of the brain, eliciting the local production of prostaglandins and responses such as fever, anorexia, sleepiness, and activation of the hypothalamo–pituitary–adrenal (HPA) axis.  The biological importance of these responses might favor the existence of multiple parallel CNS pathways that are engaged by cytokines.     

Membrane proteins of the nerve growth cone and their developmental regulation

The membrane polypeptides of growth cone fragments ("growth cone particles," GCPs) isolated from fetal rat brain by subcellular fractionation have been analyzed in further detail. The major polypeptides of salt-washed GCP membranes detected by 1-dimensional gel electrophoresis (Ellis et al., 1985b) resolve in 2-dimensional gels as a spot of 52 kDa that comigrates with beta-tubulin and reacts with anti-beta-tubulin; a 46 kDa, pl 4.3, polypeptide (pp46) that has no equivalent in the soluble fraction and is identical to one of the GCP's major phosphoproteins (Katz et al., 1985) and to GAP43 (Willard et al., 1985); a spot of 42 kDa that comigrates with actin; and a species of 34 kDa (p34) without soluble equivalent. The prominent 38 kDa doublet identified in 1-dimensional gels is difficult to resolve in 2-dimensional gels. The major phosphoproteins pp80ac, pp46, and pp40 (Katz et al., 1985), as well as p34 partition into the oil phase of Triton X-114 extracts, suggesting that they are integral membrane proteins, at least in our experimental conditions. The properties of pp46 reported here are in conflict with the highly hydrophilic amino acid sequence predicted for GAP43/B50/F1 (Basi et al., 1987; Karns et al., 1987). Growth-cone and presynaptic membrane proteins are compared as follows. After eye injection of 35S-methionine, GCPs and synaptosomes are isolated from the target areas of optic nerve of fetal and adult rats, respectively. Polypeptides are separated by 1- and 2-dimensional gel electrophoresis and the radiolabeled species identified fluorographically. The comparison of labeled GCP and synaptosome polypeptides shows that all 5 major Coomassie blue-stained polypeptides of GCP membranes (52, 46, 42, 38, 34 kDa) are intensely labeled after eye injection. However, in synaptosomes, these polypeptides are weakly labeled if at all; instead, an intensely labeled polypeptide of 28 kDa, and several additional species not seen in GCPs, have appeared. Therefore, the major growth cone membrane proteins are developmentally regulated, and the rates of synthesis and transport into the axonal ending of neuronal polypeptides change dramatically at the time of synaptogenesis.     

Vagal immune-to-brain communication: a visceral chemosensory pathway

The immune system operates as a diffuse sensory system, detecting the presence of specific chemical constituents associated with dangerous micro-organisms, and then signalling the brain. In this way, immunosensation constitutes a chemosensory system. Several submodalities of this sensory system function as pathways conveying immune-related information, and can be classified as either primarily brain barrier associated or neural. The vagus nerve provides the major neural pathway identified to date. The initial chemosensory transduction events occur in immune cells, which respond to specific chemical components expressed by dangerous micro-organisms. These immune chemosensory cells release mediators, such as cytokines, to activate neural elements, including primary afferent neurons of the vagal sensory ganglia. Primary afferent activation initiates local reflexes (e.g. cardiovascular and gastrointestinal) that support host defense. In addition, at least three parallel pathways of ascending immune-related information activate specific components of the illness response. In this way, immunosensory systems represent highly organized and coherent pathways for activating host defense against infection.     

The neurotrophic factor, n-hexacosanol, reduces the neuronal damage induced by the neurotoxin, kainic acid

The long-chain fatty alcohol, n-hexacosanol, has been shown to possess neurotrophic properties in vitro on rat CNS cultures (Borg et al., 1987) and to promote the survival of septal cholinergic neurons after experimental axotomy (Borg et al., 1990). Long-chain alcohols have also been shown to be synthesized and metabolised by rat brain during development (Bishop and Hayra, 1981; Natarajan et al., 1984). The present study was undertaken in order to find out if a nonproteic neurotrophic factor like n-hexacosanol may be able to reduce the neuronal damages induced by the excitatory amino acid, kainic acid. When administered chronically by intraperitineal injection, hexacosanol (1 mg/kg) protected the pyramidal neurons of the hippocampus from the neurotoxic degeneration induced by an intracerebroventricular infusion of kainic acid in rats; the extent of the damage was limited to a small part of the CA3 region. Morphometric analysis showed that 72% of the neurons that would have died following kainic acid injection were spared by hexacosanol. Moreover the increased locomotor activity induced by the neurotoxin was also inhibited by hexacosanol and the behavioral effect was statistically correlated to the extent of neuronal loss. The present study suggests a possible role for nonproteic neurotrophic compounds against neurotoxic damages on central neurons. Moreover the peripheral administration of hexacosanol may lead to a significant breakthrough in the treatment of exicotoxin-related human diseases.     

In situ immune response in brain and kidney during early relapsing fever borreliosis

Characterization of the host immune response during initial pathogenesis of relapsing fever neuroborreliosis would be a key to understanding Borrelia persistence and factors driving the inflammatory process. We analyzed immune cells in brain and kidney with the highly invasive B. crocidurae during the first two weeks of murine infection. In both organs, microglia and/or macrophages predominated while T-cell changes were minimal. Compared to kidney, brain neutrophils infiltrated more rapidly and B-cells were essentially absent. Our results indicate that during early neuroborreliosis, brain defense is comprised primarily of innate immune cells while adaptive immunity plays a minor role.     

Differentiation potential of a monoclonal antibody-defined neural progenitor cell population isolated from prenatal rat brain by fluorescence-activated cell sorting

We have studied the differentiation potential in vitro of a subpopulation of neural progenitor cells from BDIX-rat brain. These cells transiently express a cell surface determinant (CSD) specified by monoclonal antibody (Mab) RB13-2 (Kindler-R?hrborn, A. et al., Differentiation 30 (1985) 53-60), and recently identified as a set of O-acetylated gangliosides (Reinhardt-Maelicke, S. et al., submitted) also recognized by Mab D1.1 (Levine, J.M. et al., J. Neurosci., 4 (1984) 826-831) and partly by Mab JONES (Schlosshauer, B. et al., J. Neurosci., 8 (1988) 580-592), respectively. As analyzed by immunofluorescence, Mab RB13-2 binding brain cells (prenatal days 11-22; postnatal days 7 and 89) were localized in different areas of the proliferative ventricular layer of the prenatal cerebrum and in the external granular layer of the early postnatal cerebellum. No Mab RB13-2 positive brain cells were found in adult brain. Following their isolation by fluorescence activated cell sorting on prenatal day 18, the differentiation potential of Mab RB13-2 binding brain cells was studied by double-immunofluorescence analysis under different conditions of monolayer culture. In the presence of 10% fetal calf serum (FCS), these cells differentiated into glial fibrillary acidic protein (GFAP) positive flat astrocytes, whereas neurons (neurofilament-positive) and a smaller number of stellate astrocytes (GFAP-positive) developed in a chemically defined medium containing 0.5% FCS. Neural progenitor cells binding Mab RB13-2 may thus either retain more than one option for differentiation into specific cell types, or the expression of the CSD specified by Mab RB13-2 may be common to more than one subset of neural progenitor cells (with or without predetermined unidirectional differentiation pathways) whose survival and/or proliferative behavior could be differentially affected by microenvironmental conditions.     

Immunoregulators in the nervous system

The nervous system, through the production of neuroregulators (neurotransmitters, neuromodulators and neuropeptides) can regulate specific immune system functions, while the immune system, through the production of immunoregulators (immunomodulators and immunopeptides) can regulate specific nervous system functions. This indicates a reciprocal communication between the nervous and immune systems. The presence of immunoregulators in the brain and cerebrospinal fluid is the result of local synthesis--by intrinsic and blood-derived macrophages, activated T-lymphocytes that cross the blood-brain barrier, endothelial cells of the cerebrovasculature, microglia, astrocytes, and neuronal components--and/or uptake from the peripheral blood through the blood-brain barrier (in specific cases) and circumventricular organs. Acute and chronic pathological processes (infection, inflammation, immunological reactions, malignancy, necrosis) stimulate the synthesis and release of immunoregulators in various cell systems. These immunoregulators have pivotal roles in the coordination of the host defense mechanisms and repair, and induce a series of immunological, endocrinological, metabolical and neurological responses. This review summarizes studies concerning immunoregulators--such as interleukins, tumor necrosis factor, interferons, transforming growth factors, thymic peptides, tuftsin, platelet activating factor, neuro-immunoregulators--in the nervous system. It also describes the monitoring of immunoregulators by the central nervous system (CNS) as part of the regulatory factors that induce neurological manifestations (e.g., fever, somnolence, appetite suppression, neuroendocrine alterations) frequently accompanying acute and chronic pathological processes.     

Experimental studies on the interaction between sleep and the immune system in humans

Sleepiness and increased sleep pressure are typical symptoms of inflammation and infection. Moreover, it is a pre-scientific belief that sleep supports host defense. The present paper summarizes the experimental evidence regarding the interaction between sleep and the immune system in humans. Sleep-wake behavior is very sensitive to experimental host defense activation, for example, by bacterial endotoxin. When the injection of endotoxin is accompanied by fever and a prominent neuroendocrine activation, sleep continuity will be disturbed. When the production of inflammatory cytokines is stimulated by smaller amounts of endotoxin, but no fever and no neuroendocrine activation are apparent, the nonREM-sleep amount will increase. This is possibly due to changes in the biological activity of the tumor necrosis factor-alpha (TNF-alpha) system. Besides their important function in sleep regulation during acute immune response, cytokines also seem to be involved in physiological sleep regulation, although there still is not very much data on this issue. So far, it remains largely unknown whether or not sleep supports host defense. In humans, for example, acute sleep deprivation up to 55 hours has only minor effects on endotoxin-induced host responses. In contrast, there is preliminary and yet inconsistent evidence that sleep deprivation might impair antibody formation in response to viral challenges.     

Hypothalamic compensatory mechanisms in Parkinson's disease

Parkinson's disease (PD) is associated with loss of dopaminergic neurons of the nigrostriatal bundle and to a lesser extent of the mesolimbic and hypothalamic dopaminergic systems. Frank symptoms of the disease usually emerge when at least 70-80% of striatal dopamine (DA) content have been reduced, raising the possibility that the preclinical phase of the disease might be due to compensatory changes that permit residual dopaminergic neurons to subserve functions previously carried out by the entire projection. These neurochemical compensatory mechanisms are known to occur at a striatal level of the rate limiting enzymes of catecholamine synthesis as well as alterations in the sensitivity of the dopaminergic postsynaptic receptors (Zigmond et al., 1984; Bokobza et al., 1984). Compensatory mechanisms, although generally less well recognized, also occur in the hypothalamus and involve endocrine regulation, abnormal neuropeptide release and the emergence of several autonomic and sensory symptoms manifesting prior to or during the course of the disease. Such neurochemical and clinical adaptation mechanisms of the hypothalamus may help to explain the neurobiological events underlying the preclinical phase of Parkinsonism. Moreover, progressive failure of these hypothalamic adaptive mechanisms may be critical in the transition of the disease into the "malignant phase" (Danielczyk et al., 1980).     

Occipital Paroxysmal Discharges Suppressed By Eye Opening: Variability in Clinical and Seizure Manifestations in Childhood

Summary: The EEG in childhood epilepsy with occipital paroxysms (CEOP) was termed "distinctive" by Gastaut (1985) and Talwar et al. (1992) and "characteristic" by Herranz Tanarro et al. (1984), which suggests that the EEG is specific and diagnostic for CEOP. However, this hypothesis has been challenged (Newton and Aicardi, 1983; Beaumanoir and Grandjean, 1987). To test this, we reviewed 5,291 EEG reports made in 51/2 years in the only tertiary pediatric center in Newfoundland and Labrador. We identified 31 children who had one or more EEGs with occipital spike/sharp waves showing suppression of discharges with eye opening and normal background activity. Six had CEOP, 17 had benign nocturnal childhood occipital epilepsy, 5 had symptomatic epilepsy, 3 had unusual complex partial seizures (CPS), 4 had only provoked seizures, and 2 had no definite seizures. Overlap between seizure types was common. The EEG criteria for CEOP are not very specific.     

Work and psychiatric illness: The significance of the posthospitalization occupational environment for the course of psychiatric illnesses

Summary The value of the reintegration and rehabilitation of inpatients vocationally was studied. Certain of the vocational experiences (unemployment and stressful working conditions) of former psychiatric inpatients were examined, with attention being paid to their stabilizing or destabilizing effect on symptomatic behaviour. A cohort of 230 first-time admissions for treatment of various disorders were interviewed while hospitalized and 1 year later. A 20-item list prepared by INFAS was used for indexing stressful working conditions. Psychopathological states were assessed with the help of the Present State Examination of Wing et al. (1973). The results indicate that mentally ill persons (especially those with organic or affective disorders), when confronted with unemployment after discharge from hospital, will usually respond by developing new or worse syndromes. Stressful working conditions appear to have very different effects in schizophrenia and affective disorders, viz. deterioration and amelioration of psychopathological syndromes respectively.This Study was supported by the Deutsche Forschungsgemeinschaft (German Research Association), as part of special program no. 129.This report is part of a prospective study of predictors, prognoses and the courses of first-time admissions for psychiatric disorders. Summary accounts of the study have appeared elsewhere (e.g. Aschoff-Pluta et al. 1984, 1985; Bell et al. 1986, 1988; Blumenthal et al. 1985, 1986; Vogel et al. 1985, 1986, 1987, 1988; Vogel 1988).