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Morphine effects in brainstem-transected cats: II. Behavior and sleep of the decerebrate cat.

Previous studies have shown that opiates suppress both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Furthermore, during the induced insomnia period, characteristic species-specific behaviors occur which are associated with high voltage slow waves in the EEG. This paper investigates the lower brainstem mechanisms involved in the generation of these effects, and describes the action of single morphine doses (0.5, 2.0 or 3.0 mg/kg, i.p.) on the behavior and REM sleep of chronic decerebrate cats. The effects of morphine in the decerebrate cat followed a 3-stage time course similar to that seen in intact cats: (1) autonomic manifestations (3-8 min postdrug); (2) a quiet state (10-60 min postdrug) with behavioral signs of NREM; and (3) a state of activated behavior (1-6 h postdrug), including motor activity and variations in muscle tone. The decerebrate cats also showed a dose-dependent suppression of REM sleep. The present results indicate that: (1) the lower brainstem provides the basic mechanisms for the behavioral deactivation-activation and the autonomic effects of the drug; (2) hypnogenic and synchronizing influences arising from the brainstem might induce the high voltage, slow burst EEG produced by opiates; (3) REM sleep suppression originates only partially in the lower brainstem; (4) the subsidiary action of the prosencephalon seems to be required for the full expression of the drug's effect on behavior and the EEG.

Animals↗

Apparent life-threatening events in infants: high risk in the out-of-hospital environment.

STUDY OBJECTIVE: The purpose of this study is to define the prevalence and significance of apparent life-threatening events among infants in the out-of-hospital setting. METHODS: This was a retrospective, cohort, outcome study of infants for whom a caregiver activated the emergency medical services (EMS) system. For purposes of the study, an apparent life-threatening event was defined as an episode of apnea, skin color change, or change in muscle tone. Study data characteristics included initial physical appearance, work of breathing, circulation skin signs, pulse rate, respiratory rate, and overall concern for the chief complaint as interpreted by EMS personnel. RESULTS: Sixty (7.5%) of 804 infants encountered by EMS during the study period met our criteria for apparent life-threatening event. Mean age was 3.1+/-3.3 months, and 55% were boys. Of the infants with apparent life-threatening event, 50 (83.3%) infants appeared to be in no distress, 8 (13.3%) infants were in mild distress, and 2 (3.3%) infants were in moderate distress. General physical appearance, work of breathing, circulatory signs, respiratory rate, and pulse rate were not clinically abnormal in the study group as a whole. Critical conditions associated with apparent life-threatening event included pneumonia or bronchiolitis (12%), seizure (8%), sepsis (7%), intracranial hemorrhage (3%), bacterial meningitis (2%), dehydration (2%), and severe anemia (2%). Limitations of the study included retrospective design and inability to follow up study patients beyond hospital discharge. CONCLUSION: An apparent life-threatening event in an infant can present without signs of acute illness and is commonly encountered in the EMS setting. It is often associated with significant medical conditions, and EMS personnel should be aware of the clinical importance of an apparent life-threatening event. Infants meeting criteria for an apparent life-threatening event should receive a timely and thorough medical evaluation.

Anemia↗

Hyperekplexia-like syndromes without mutations in the GLRA1 gene.

Hyperekplexia (MIM: 149400), or startle disease, is an autosomal dominant neurological disorder characterized by an extreme generalized stiffness immediately after birth, normalizing during the first years of life. Other features of this disorder are excessive startle reactions to unexpected, particularly auditory, stimuli together with a short period of generalized stiffness during which voluntary movements are impossible. Linkage analysis mapped a gene for this disorder to chromosome 5q33-q35. Subsequently, mutations in the GLRA1 gene encoding the alpha 1-subunit of the glycine receptor proved to be causally related to the disease. In the present study, mutation analysis of all exon and flanking intron sequences of this gene was performed in sporadic patients and their parents. Moreover, a branch of the original Dutch hyperekplexia family with a very severely affected individual was screened for an additional mutation in the GLRA1 gene. Except for two polymorphisms, of which one results in an amino acid change, no potentially disease causing mutations were found in the alpha 1-subunit of the glycine receptor. Together with haplotype analysis these results exclude a recessive inheritance or new mutation etiology in these hyperekplexia-like syndrome and emphasize that hyperekplexia-like syndromes can be caused by other genetic factors. The involvement of other genes encoding subunits of the functional glycine receptor complex has not been excluded.

Adult↗

A case of lithium intoxication with downbeat vertical nystagmus.

Lithium carbonate has recently been used in the treatment of manic diseases. However, since the marginal range between therapeutic and toxic doses is very narrow, close attention should be paid to the development of adverse reactions in its application. Lithium intoxication is manifested by neurological symptoms. Neurotological tests were performed on a patient with lithium intoxication that occurred in the course of psychiatric treatment of mania. The observed sequelae included marked downbeat vertical nystagmus and truncal ataxia. The main lesions in the present case were considered to be located in the cerebellum. Close observation, including neurotological tests, is of greatest importance because in cases of lithium intoxication the development of cerebellar as well as brainstem disorders must not be overlooked.

Cerebellar Ataxia↗

Malignant hyperthermia and myotonic disorders.

Advances in physiology and molecular genetics have promoted greater understanding of the various clinical manifestations of muscle disorders. For example, myotonia or profound weakness may be observed in sodium channel disease (e.g., paramyotonia congenita or hyperkalemic periodic paralysis), depending on the specific channel defect or with slight changes in membrane potential. Observed effects of anesthetic techniques have been essential to elucidating the primary muscular nature of myotonia. Commonly used anesthetic medications have potentially lethal (e.g., MH) or serious (e.g., myotonic dystrophy) adverse effects. Conversely, lidocaine or propofol may have therapeutic benefit for patients with skeletal muscle sodium channel disorders. Additional investigation is required to improve our understanding of how age, gender, or other factors determine the phenotypic expression of malignant hyperthermia. Future research holds the promise for more accurate pre-anesthetic identification of persons with heritable myopathies, especially those who are asymptomatic. Enhanced awareness of multiple organ system involvement in myotonic dystrophy is essential for planning perioperative care. Patients with periodic paralysis require that we know factors that incite or inhibit the development of their attacks. Advances in bench research and detailed clinical studies will further improve our ability to provide optimal care for patients with muscle disorders.

Animals↗

Behavioral effects of exposure to endosulfan and methyl parathion in adult rats.

Endosulfan (ES) and methyl parathion (MP) are widely used in Latin America, and simultaneous exposure to both products is documented. This exposure may have effects on the nervous system because their targets include the GABAergic and cholinergic systems, which are main modulators of neuronal excitability in the cortex and hippocampus. We tested whether low-level, repeated exposure of adult rats to commercial formulations containing ES and MP disrupts spatial learning in the water maze. Five groups of eight animals received subcutaneously appropriate dilutions of the commercial formulations to yield the following treatments during 10 days: saline, 25 mg/kg ES, 2 mg/kg MP (MP(2)), 25 mg/kg ES plus 1 mg/kg MP (ES+MP(1)) and 25 mg/kg ES plus 2 mg/kg MP (ES+MP(2)). In addition, markers of neurological function, renal and hepatic damage were explored as potential consequences of exposure. In the absence of overt toxicity, the groups exposed to the ES plus MP showed significantly longer escape latencies, higher number of failures to reach the platform and more time in the periphery of the tank than the control and single-exposed groups. This finding shows that commercial formulations of ES and MP have marginal effects when administered individually but can produce behavioral alterations when given in combination.

Acetylcholinesterase↗

Startle disease--hyperekplexia (two sibling cases).

Two sisters aged 12 and 13 applied to our hospital with complaints of jerking tonic contraction triggered by sudden noise. Diffuse bilaterally polyspike-wave discharges appeared on waking electroencephalography and during that time a startle-induced tonic contraction was seen. Their neurological examinations and neuro-radiological imaging were normal except for hyperreflexia. We presented these cases because of being rare.

Acoustic Stimulation↗

Genetic factors in the response to neuroleptics in schizophrenia: a psychopharmacogenetic study.

A psychopharmacogenetic strategy was used to investigate a genetic heterogeneity model of schizophrenia. This model consisted of various genetic subtypes represented by patients classified hypothetically according to the types and genealogical (Mendelian) patterns of illnesses in first-degree relatives. The effect of neuroleptics on these subtypes (drug x genetic subtype interactions) were tested for evidence of post-treatment responses which discriminated between them. The findings revealed that schizophrenics who had depressed relatives tended to exhibit (1) depression and more severe pseudoparkinsonism irrespective of types of neuroleptics, and (2) greater remission of paranoid-hostility symptoms when treated with neuroleptics of the aliphatic-piperadine type. Schizophrenics who had schizophrenic relatives failed to show these responses. Interpretation of these findings emphasized the recognition of these responses as arising from neuroleptic-induced alterations of defective neurologic-neurochemical systems underlying this subtype and as "pharmacogenetic criteria" by which it can be discriminated.

Adolescent↗

Electrical stimulation of the brain in Wilson-Konovalov hepatocerebral dystrophy (a neuromorphological and neurophysiological analysis).

Stereotaxic surgery was performed in 27 patients. Complete elimination of or significant reductions in hyperkinesia were obtained in 17 cases; five patients died. There was no correlation between the severity of clinical manifestations of hepatocellular dystrophy and the relatively normal quantitative measures of cortical and subcortical biopotentials, which were produced on a background of microstructural changes affecting neurons in these regions. It is suggested that qualitative significance of these biopotentials is that they carry an excess pathological spike activity resulting in hyperkinesia. This is supported by the fact that hyperkinesia was suppressed after surgical destruction of the ventrolateral nucleus of the thalamus and subthalamic structures.

Adolescent↗