Stiff-person syndrome: autoimmunity and the central nervous system

Stiff-person syndrome (SPS) is a rare disease of severe progressive muscle stiffness in the spine and lower extremities with superimposed muscle spasms triggered by external stimuli. Patients with SPS are often referred for psychiatric evaluation and the psychiatrist may be the first to diagnosis SPS. Psychosocial stressors often precede the first manifestations of the disease; depression, anxiety, and alcohol abuse are comorbid illnesses. The identification of an association with antibodies to glutamic acid decarboxylase (GAD) was invaluable for definitively establishing a pathological basis for the disease; antibodies to amphiphysin and gephyrin are also found in cases of SPS but at much lower frequencies. Whether the antibodies inhibit GAD activity in vivo, target GAD-expressing neurons for immune-mediated destruction, are part of a wider immune process, or are merely a marker for destruction of GAD-expressing neurons by an independent neurodegenerative process is not yet clear. Both electromyography and the detection of GAD antibodies are useful in establishing a diagnosis of SPS. Treatment of SPS includes the use of immunomodulating therapies (plasmapheresis and intravenous immunoglobulins) and symptomatic treatment with benzodiazepines and baclofen. The use of tricyclic antidepressants and rapid withdrawal from therapy should be avoided.     

Adrenergic pharmacology: focus on the central nervous system

Norepinephrine and epinephrine are involved in the control of several important functions of the central nervous system (CNS), including sleep, arousal, mood, appetite, and autonomic outflow. Catecholamines control these functions through activation of a family of adrenergic receptors (ARs). The ARs are divided into three subfamilies (alpha1, alpha2, and beta) based on their pharmacologic properties, signaling mechanisms, and structure. ARs in the CNS are targets for several therapeutic agents used in the treatment of depression, obesity, hypertension, and other diseases. Not much is known, however, about the role of specific AR subtypes in the actions of these drugs. In this paper, we provide an overview of adrenergic pharmacology in the CNS, focusing on the pharmacologic properties of subtype-selective AR agonists and antagonists, the accessibility of these drugs to the CNS, and the distribution of ARs in different areas of the brain.     

Learning disabilities and central nervous system involvement.

The relation of damage to the central nervous system to learning disabilities remains a continuing issue. This study explored how learning disable children fare on the Visual Retention Test. Analysis of correct scores and errors for the 24 children responding to Administration A would ordinarily suggest a primary relationship (t = 2.60, p less than .02; t = 4.01, p less than .001, respectively). However, since extensive medical and case history material yielded no evidence of cerebral injury or disease and since the impact of short-term memory (Administration D) led to no further performance decrement (t less than 1.00), additional research must determine a more precise understanding of perceptual dysfunction and the role of short-term memory in regard to learning disabilities.     

Aspects of biochemical differentiation in the central nervous system

A demonstration of cell-specific patterns of development in the immature CNS is provided by examples of characteristic, cellspecific time-courses of enzyme development in different classes of brain cells isolated in highly purified form by bulk-separation from the cerebral and cerebellar cortex of the growing rat. The enzymatic analysis was carried out at the level of the nerve and glial cell lysosomes and mitochondria, two subcellular organelles crucial to the economy of all cells. The findings reveal rather similar developmental patterns for the lysosomal hydrolase N-acetyl-β-D-glucosaminidase in neurons and glial cells of the cerebral cortex as well as in two different cerebellar nerve cell types, the Purkinje and the granule cell. However, significant differences in the post-natal chronology of development of the mitochondrial enzyme α-glycerophosphate dehydrogenase were noted between cortical nerve and glial cells, the glial enzyme exhibiting 6-fold higher levels of activity than the neuronal one throughout the first month of postnatal life. The findings emphasize the feasibility as well as the necessity of studies aimed at the elucidation of the cell-specific aspects of the biochemistry of developing nerve and glial cells.     

Environmental complexity and central nervous system development and function

Environmental restriction or deprivation early in development can induce social, cognitive, affective, and motor abnormalities similar to those associated with autism. Conversely, rearing animals in larger, more complex environments results in enhanced brain structure and function, including increased brain weight, dendritic branching, neurogenesis, gene expression, and improved learning and memory. Moreover, in animal models of CNS insult (e.g., gene deletion), a more complex environment has attenuated or prevented the sequelae of the insult. Of relevance is the prevention of seizures and attenuation of their neuropathological sequelae as a consequence of exposure to a more complex environment. Relatively little attention, however, has been given to the issue of sensitive periods associated with such effects, the relative importance of social versus inanimate stimulation, or the unique contribution of exercise. Our studies have examined the effects of environmental complexity on the development of the restricted, repetitive behavior commonly observed in individuals with autism. In this model, a more complex environment substantially attenuates the development of the spontaneous and persistent stereotypies observed in deer mice reared in standard laboratory cages. Our findings support a sensitive period for such effects and suggest that early enrichment may have persistent neuroprotective effects after the animal is returned to a standard cage environment. Attenuation or prevention of repetitive behavior by environmental complexity was associated with increased neuronal metabolic activity, increased dendritic spine density, and elevated neurotrophin (BDNF) levels in brain regions that are part of cortical-basal ganglia circuitry. These effects were not observed in limbic areas such as the hippocampus.     

Rasmussen's syndrome: intractable epilepsy and progressive neurological deterioration from a unilateral central nervous system

Rasmussen's syndrome (chronic encephalitis with epilepsy) is a rare neurological disorder of unknown cause characterized by severe epilepsy, hemiplegia, dementia, and inflammation of the brain, and progressive functional and structural destruction of a single cerebral hemisphere. While one mechanism underlying the pathogenesis of Rasmussen's encephalitis has been hypothesized to be mediated by production of excitotoxic GluR3 autoantibodies to the a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor, other neuropathological etiologies have also been indicated. Proposed therapies have included antiepileptics, steroids, antiviral agents, alpha-interferon, and immunoglobulin. The mainstay of therapy is surgical hemispherectomy. To date, no medical therapies have permanently halted neurologic deterioration.     

MR imaging of fetal central nervous system abnormalities

Ultrasound is the screening modality of choice for fetal imaging. However, when additional information regarding fetal anatomy or pathology is needed, fast MR imaging is increasingly being used as a correlative imaging modality. Performances of high quality sonographic and MR examinations as well as interpretation by individuals familiar with prenatal diagnosis are important factors for optimal parental counseling. MR imaging frequently adds additional information regarding fetal central nervous system anomalies beyond that available with ultrasound. This information commonly changes patient counseling, and at times patient management.     

Peer review, third-party payment, and the analytic situation: a case report

The complexities of insurance coverage and peer review as they intrude into the analytic situation were discussed. The basic question was raised of whether becoming acceptable to major health providers through the peer-review program is truly a compromise of the analytic pact and a threat to the future of psychoanalysis. Practical as well as technical considerations facing the analyst when he is confronted with having to write a report to the patient's insurance company were elucidated. Countertransference feelings were emphasized. A detailed case illustration was presented to demonstrate that peer review, as it relates to third-party payment, need not compromise an analysis.     

Rapid associative learning: Conditioned bradycardia and its central nervous system substrates

It has become clear from the study of different response systems during classical conditioning that some responses are acquired quite rapidly and others show a much slower rate of acquisition. The most often studied rapidly acquired responses have been classically conditioned autonomic changes (e.g., heart rate); the slowly acquired responses most often studied are skeletal responses, such as the eyeblink or leg flexion response. Although there are various other differences between rapidly acquired and slowly acquired responses, we have suggested that the most important difference is the possibility that they represent different stages of the learning process. In the present review I describe research in our laboratory that has focused on conditioned bradycardia as a model system of a rapidly acquired associative system and contrast it with the more slowly acquired Pavlovian conditioned eyeblink response. I also describe the generality of conditioned bradycardia and discuss the differential role of subdivisions of the prefrontal cortex as a substrate for mediating this response. Finally, I briefly discuss the other brain areas involved in conditioned bradycardia, and its functional significance as it relates to the learning process.     

Hypertonic central nervous system complications from the viewpoint of the pathologist

Based on 2130 autopsies with a hypertension it is reported on the hypertensive CNS-lesions. The frequency of encephalomalacia was 12%. By 9.7% was founded brain haemorrhages. The relapse rate of haemorrhages was about 5%. The encephalomalacia existed by way of secondary finding in 24.7%, and the haemorrhage in 2.2%. The investigations showed an important arteriosclerosis by 39.8% in haemorrhages and by 51.6% in brain infarct. It was remarkable by the hypertensive brain haemorrhages a dominant right hemisphere.     

Functional effects of neural grafting in the mammalian central nervous system

Grafts of fetal and nonfetal brain tissues have been successfully implanted into the mammalian central nervous system (CNS). The functional effects of neural grafting in the CNS of rodents and nonhuman primates in a variety of situations are reviewed. Research areas discussed included the effects of dopamine-rich grafts in animal models of Parkinson's disease and acetylcholine-rich grafts in animals with lesions of the cholinergic pathways to the neocortex and hippocampus. Graft effects also are examined in aged animals and genetic mutants. In addition, the effects of neural grafts on circadian rhythmicity, reproductive functions, and conditioned taste aversion are discussed. The beneficial functional effects of neural grafts and the possible mechanisms and implications for these effects are discussed, including the possibility that the CNS exhibits a regional biochemical specificity that influences the outcome of neural graft procedures.     

The functional state of the central nervous system in chemical stress

The psychosocial and physical factors, including chemical ones, which affect the human organism are considered by some authors to be stress factors which affect the functional state (FS) of the central nervous system (CNS). We calculated correlations among the clinical, psychological/psychometric, and quantitative electropsychological (QEEG) variables of the functional changes of the CNS in chemical stress. These data were based on occupational contact with lead as experienced by 402 workers, with styrene by 96, with shale-oil products by 252, with organic solvents by 77 workers, and a control group of 145 workers in different age groups. The QEEG data of 77 patients were analyzed to determine the chronic neurotoxic effects of industrial chemical substances by diagnosing the functional changes at the syndrome level. We concluded that occupational chemical factors impact the functional state of the CNS. During chemical stress -activity and total cerebral bioelectrical activity (BA) decreases. The use of psychometric/ psychological and QEEG methods makes it possible to diagnose the changes of the CNS as hypersthenic, hyposthenic, and organic psychosyndromes.     

Listeriosis of the central nervous system in children beyond the neonatal period

Observations on three children with neurolisteriosis (one case of meningitis, two cases of meningoencephalitis, each Serovar 4 b), show that even after the neonatal period, listeriosis must not be ignored in the process of diagnosis and therapy. It is the bacteriological examination of the cerebrospinal fluid, together with the blood culture, and not clinical symptoms and serology that guarantee a timely diagnosis and therapy (ampicillin and gentamicin).     

"Slow virus" infections and degenerative diseases of the central nervous system]

Slow virus infections of the central nervous system are produced by both conventional and unconventional viruses. Diseases of the central nervous system which are produced by unconventional viruses are discussed. They are kuru and the Creutzfeldt-Jacob disease. Mention is also made of the fact that these disease may be transmitted to animals which allows an infectious genesis to be assumed. The author also discusses the clinical symptomatology, the results of anatomical and pathological examinations, and the mechanism of transmission of the disease from one human being to another. Slow virus infection as a cause of other neurological diseases is also dealt with by the author in her present paper.     

Sympathetic nervous system and pain: a clinical reappraisal

The target article discusses various aspects of the relationship between the sympathetic system and pain. To this end, the patients under study are divided into three groups. In the first group, called "reflex sympathetic dystrophy" (RSD), the syndrome can be characterized by a triad of autonomic, motor, and sensory symptoms, which occur in a distally generalized distribution. The pain is typically felt deeply and diffusely, has an orthostatic component, and is suppressed by the ischemia test. Under those circumstances, the pain is likely to respond to sympatholytic interventions. In a second group, called "sympathetically maintained pain" (SMP) syndrome, the principal symptoms are spontaneous pain, which is felt superficially and has no orthostatic component, and allodynia. These symptoms, typically confined to the zone of a lesioned nerve, may also be relieved by sympathetic blocks. Since the characteristics of the pain differ between RSD and SMP, the underlying kind of sympathetic-sensory coupling may also vary between these cases. A very small third group of patients exhibits symptoms of both RSD and SMP. The dependence or independence of pain on sympathetic function reported in most published studies seems to be questionable because the degree of technical success of the block remains uncertain. Therefore, pain should not be reported as sympathetic function independent until the criteria for a complete sympathetic block have been established and satisfied.