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.     

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.     

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.     

Delirium and isolated angiitis of the central nervous system: a case report and review

Central nervous system (CNS) vasculitis is a rare entity, especially when it occurs in isolation; it is seen more commonly as part of a multisystem vasculitis. Common presenting symptoms include persistent headache, encephalopathy, and multifocal signs. We discuss the case of a 68-year-old female who presented twice in 1 month with confusion and choreaform movements. Extensive workup was negative for a connective tissue disease or other conditions in the differential, including neurosarcoidosis, Creutzfeldt-Jakob disease, and neurosyphilis. The only significant findings were elevated erythrocyte sedimentation rate, inflammatory signs in the CNS, and diffuse slowing of the electroencephalogram. A presumptive diagnosis of isolated angiitis of the central nervous system (IACNS) was made and the patient was successfully treated with steroids. She recovered fully with no residual symptoms. The diagnosis of IACNS is often difficult given there are no definitive laboratory investigations or pathognomonic presentation. However, a series of signs, symptoms, and laboratory findings have been proposed that are helpful in making the diagnosis. To our knowledge, IACNS presenting primarily with delirium has not been previously reported in the literature. The diagnosis of IACNS is purely speculative for this case, as the gold standard for diagnosis, a leptomeningeal cortical biopsy, was not performed.     

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.     

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.     

Discrepancies between premorbid and current IQ as a function of progressive mental deterioration

The declining cognitive functioning typically found in patients with Alzheimer's disease presents an opportunity to study that decline. The changing magnitude of ever widening discrepancies between premorbid estimators of IQ and observed IQ increases as severity of the disease increases. Premorbid IQs estimated by these scores (the National Adult Reading Test-Revised, the reading tests of the Revised and Third Editions of the Wide Range Achievement Test, and a demographically based regression index for the Wechsler Adult Intelligence Scale-Revised) had relatively similar discrepancies from obtained WAIS-R Full Scale IQs in samples of normal elderly (n = 30), and elderly patients diagnosed with mild (n = 30) and moderate Alzheimer's disease (n = 30) dementia. The discrepancies became larger, regardless of premorbid estimator, as disease severity progressed from none to mild to moderate across the samples.     

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.     

Evaluation of a behaviour analysis and treatment of progressive myoclonus epilepsy, type Unverricht-Lundborg: a case study

This case study evaluates the clinical effectiveness of a psychological treatment within a behaviour medicine approach to epilepsy of a subject with progressive myoclonic epilepsy. The pattern of seizure behaviour was identified in the behaviour analysis. Self-management skills were taught to the client and in vivo exposure was subsequently used in a desensitization process. The main findings in this study were that the debilitating effects of the myclonic jerks can be reduced and functioning level improved when fear of seizures is reduced. These results indicate that psychological treatment can increase the level of functioning in clients with progressive myoclonic epilepsy.     

Cognitive and behavioral functioning in Coffin-Siris syndrome and epilepsy: a case presentation

The authors characterized the cognitive, adaptive, and behavioral sequelae of Coffin-Siris (CS) syndrome and epilepsy in a 7.5-year-old child. Little is known about the early neurobehavioral presentation of CS. Clinical features consistent with this genetic anomaly include underdeveloped tips and nails of the fifth fingers, extended infranasal depression, and craniofacial abnormalities. MRI findings often reveal callosal agenesis. The authors conducted a neuropsychological evaluation and obtained parental ratings of behavioral and adaptive functioning. Attentional abilities were limited. As assessed by the Mullen Scales of Early Learning, receptive language abilities (age equivalent [AE]: 3-3) were relatively stronger than expressive skills (AE: 1-4). Adaptive functioning was low across all domains (Vineland Adaptive Behavior Composite AE: 1-9). On the Behavior Assessment for Children (BASC-2), social skills dysfunction, stereotyped and self-stimulatory behaviors, restricted interests, ritualistic play, and inappropriate object usage were noted. No significant mood disturbances were endorsed. Study findings indicate a diffuse pattern of neurobehavioral deficits in a child with CS and epilepsy. Further clinical assessment and research should include multidimensional assessment techniques, including evaluation of adaptive behavior, in an effort to capture the full range developmental sequelae in children with CS.     

"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.     

Characteristics of body excursion during a static upright posture in elderly people with central nervous system disorders and with other disorders from the viewpoint of body-excursion parameters

This study aimed to compare characteristics of body excursion of healthy elderly and elderly people with disorders. The participants were 38 healthy elderly who were at home (Healthy Elderly group) and 24 elderly people with disorders. The latter consisted of two groups: 12 in the Central Nervous System Disorders group with vestibular organ or central nervous system disorders, and 12 in the Other Disorders group with other system disorders. 34 parameters were selected from six domains: distance, distribution of amplitude, area, velocity, power spectrum, and vector. When compared with the Healthy Elderly group, the Central Nervous System Disorders group was judged abnormal on many parameters and showed large and quick body excursion characteristics, particularly in left-right excursion. The Other Disorders group showed different characteristics in the size of the left-right excursion and velocity of the front-back excursion. However, compared with the Central Nervous System Disorders group, very few people in the Other Disorders group were judged abnormal, and they showed slower velocity for front-back excursion.     

The progressive heritage of guidance: a view from the left

As one part of a larger progressive movement, the guidance and counseling movement has typically supported progressive programs in the schools and in society as a whole. While most counselors point with pride to such a progressive heritage, a case can be made that the effect of progressivism is to prop up existing structures and resist fundamental change in societal institutions. In this article the author discusses four ideals that are commonly held by the progressive and the counseling movements, pointing out some of the destructive effects these ideals have on societal change efforts. The four ideals discussed are: (a) an emphasis on access to opportunity (pluralism), (b) an emphasis on pragmatism, (c) an emphasis on adjustment, and (d) an emphasis on individualism.     

The mutual influence of insulin and environmentally-conditioned central nervous system performance on the regulation of carbohydrate metabolism

Investigating the effects of insulin on carbohydrate metabolism and on the central nervous system (C.N.S.) under conditions of rest and of stress in dogs and in rats, using the conditional reflex method and measuring the nitrogen and phosphate brain metabolites and the blood sugar differences, the author found that cerebral glucose metabolism is dependent upon insulin, and that if glucose supplies are adequate, insulin stimulates C.N.S. performance within 15–20 minutes. The C.N.S. and blood sugar reactivity depend upon the environmental situation: the conditional stimuli for stress increase glycemia. Animals under stress went into shock even though their glycemic levels were relatively high, whereas those at rest did not go into shock or sometimes reacted with slight symptoms of somnolence even at a lower glycemic level. In experimental hyperglycemia the level rises even more during stress, with ensuing coma, especially with larger doses of insulin. An increase of inhibition with reduced learning precedes the glycemic irregularities. Thus, insulin directly influences the central nervous system.     

Strength of the nervous system and augmenting-reducing: Paradox lost

Two conflicting viewpoints were identified regarding the relationship between sensation seeking and subjective response to stimulation: (a) that sensory augmenters are high sensation seekers compared with sensory reducers (the view of Zuckerman and Buchsbaum); and (b) that it is the reducer rather than the augmenter who is the high sensation seeker (the view of Petrie and Vando). Proponents of the first approach measure Augmenting-Reducing through the use of the average cortical-evoked response, while advocates of the second position use Petrie's version of the Kinaesthetic Figural Aftereffects Test or Vando's Reducer-Augmenter Scale. It is argued that the disagreement is semantic and results from the differences in method of measurement. It is further argued that most, if not all, of the research findings may be accommodated within the framework of strength-of-the-nervous-system theory which distinguishes between two dimensions,sensitivity andfunctional endurance. The implications for future research are pointed out.