Degeneration of brainstem respiratory neurons in dementia with Lewy bodies.

BACKGROUND: Respiratory dysfunction, including sleep disordered breathing, is characteristic of multiple system atrophy (MSA) and may reflect degeneration of brainstem respiratory nuclei involved in respiratory rhythmogenesis and chemosensitivity, including the pre-Bötzinger complex (preBötC), nucleus raphe pallidus (RPa), and nucleus raphe obscurus (ROb). However, impaired ventilatory responses to hypercapnia have also been reported in dementia with Lewy bodies (DLB), suggesting that these nuclei may also be affected in DLB. OBJECTIVES: To determine whether there is involvement of the preBötC, RPa, and ROb in DLB. DESIGN: We applied stereological methods to analyze sections immunostained for neurokinin-1 receptor and tryptophan hydroxylase in neuropathologically confirmed cases of DLB, MSA, and controls. RESULTS: Reduction of neuronal density occurred in all three nuclei in DLB, as well as in MSA. The magnitude of neuronal depletion in ROb was similar in DLB and MSA (49% versus 56% respectively, compared to controls, P < 0.05), but neuronal loss in the preBötC and RPa was less severe in DLB than in MSA (40% loss in preBötC of DLB, P < 0.05 and 68% loss in MSA, P < 0.0001, compared to controls; 46% loss in RPa of DLB, P < 0.05 and 73% loss in MSA P < 0.0001, compared to controls). CONCLUSIONS: Medullary respiratory nuclei are affected in dementia with Lewy bodies but less severely than in multiple system atrophy. This may help explain differences in the frequency of sleep disordered breathing in these two disorders.

Measurements of RF heating during 3.0-T MRI of a pig implanted with deep brain stimulator.

PURPOSE: To present preliminary, in vivo temperature measurements during MRI of a pig implanted with a deep brain stimulation (DBS) system. MATERIALS AND METHODS: DBS system (Medtronic Inc., Minneapolis, MN) was implanted in the brain of an anesthetized pig. 3.0-T MRI was performed with a T/R head coil using the low-SAR GRE EPI and IR-prepped GRE sequences (SAR: 0.42 and 0.39 W/kg, respectively), and the high-SAR 4-echo RF spin echo (SAR: 2.9 W/kg). Fluoroptic thermometry was used to directly measure RF-related heating at the DBS electrodes, and at the implantable pulse generator (IPG). For reference the measurements were repeated in the same pig at 1.5 T and, at both field strengths, in a phantom. RESULTS: At 3.0T, the maximal temperature elevations at DBS electrodes were 0.46 °C and 2.3 °C, for the low- and high-SAR sequences, respectively. No heating was observed on the implanted IPG during any of the measurements. Measurements of in vivo heating differed from those obtained in the phantom. CONCLUSION: The 3.0-T MRI using GRE EPI and IR-prepped GRE sequences resulted in local temperature elevations at DBS electrodes of no more than 0.46 °C. Although no extrapolation should be made to human exams and much further study will be needed, these preliminary data are encouraging for the future use 3.0-T MRI in patients with DBS.

Standardized sign-out improves completeness and perceived accuracy of inpatient neurology handoffs.

OBJECTIVES: As residency programs adjust to new duty hour restrictions, the use of cross-coverage systems requiring handoffs will rise. Handoffs are vulnerable to communication failures when unstructured. Accordingly, we implemented a standardized sign-out process on our inpatient neurology services and assessed its effect on completeness and perceived accuracy of handoffs. METHODS: Residents spent the first half of their rotations utilizing unstructured sign-out. They transitioned to a structured sign-out system (using the situation-background-assessment-recommendation format) during the second half of their rotations. We analyzed survey responses before and after implementation to evaluate for an effect. RESULTS: Residents utilizing structured sign-out were significantly more likely to share test results with patients/families prior to shift changes (p = 0.037), update our electronic service list (p = 0.045), and feel all important data were being transmitted (p = 0.041). Overall satisfaction (scale 1-10) increased from 6.2 ± 1.6 to 7.4 ± 1.3 (p = 0.002). CONCLUSIONS: Our findings demonstrate that standardized sign-out improves the completeness and perceived accuracy of handoffs. Such improvement has the potential to improve patient safety and quality of care.

Striatal opioid peptide content in an animal model of spontaneous stereotypic behavior.

Stereotypic behaviors are associated with a broad spectrum of developmental, psychiatric, and genetic disorders. Several lines of evidence indicate that these abnormal repetitive behaviors may be expressed as a consequence of imbalanced activity along the direct and indirect processing pathways of the basal ganglia. Because the activity of these two pathways is modulated, in part, by the neuropeptides dynorphin and enkephalin, we sought to determine whether spontaneous and persistent stereotypy is associated with alterations in striatal neuropeptide content. Specifically, the present study employed radioimmunoassay to measure dynorphin-A and leu-enkephalin content in the dorsolateral striatum of deer mice exhibiting different levels of spontaneous stereotypic jumping. The results indicate significantly decreased leu-enkephalin content and significantly increased dynorphin/enkephalin content ratios in high-stereotypy mice relative to low-stereotypy mice. Moreover, analyses revealed a significant negative correlation between striatal enkephalin content and frequency of stereotypy as well as a significant positive correlation between the dynorphin/enkephalin content ratio and frequency of stereotypy in these mice. These data are consistent with the hypothesis that spontaneous stereotypic behavior is expressed as a consequence of relative hyperactivity along cortico-basal ganglia-cortical feedback circuits involving the direct (facilitative) pathway, but suggest that primary perturbations to the indirect (inhibitory) pathway give rise to such imbalanced activity.

Behavior-related alterations of striatal neurochemistry in a mouse model of stereotyped movement disorder.

Motor stereotypy is a common component of several developmental, genetic, and neuropsychiatric disorders. In animals, these behaviors can be induced or attenuated via pharmacological manipulation of specific neural loci comprising cortico basal ganglia-cortical feedback circuits, including the striatum. The present study employed the deer mouse model of spontaneous and persistent stereotypy to assess the involvement of several endogenous neurotransmitters and neuromodulators in mediating the expression of the stereotypic behaviors (i.e., repetitive hindlimb jumping) exhibited by these mice. This was accomplished by employing a microdialysis sampling system coupled on-line to capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection apparatus. Given the 13-s temporal resolution for analyte measurement afforded by this system, discrete behavior-related alterations in striatal neurochemical concentrations were detected. Rearing behavior was found to be associated with significant and selective elevations of striatal glutamate (Glu) and aspartate (Asp) concentrations. Moreover, rearing was found to most frequently precede repetitive jumping. The results also indicated that alterations in striatal serine (Ser) concentrations were involved in the modulation of locomotor activity. The present findings support a role of the striatal glutamatergic system in the mediation of spontaneous stereotypic behavior and suggest a potential neuronal mechanism by which transition to stereotypy occurs in these mice. Moreover, the present findings demonstrate the usefulness of the microdialysis system employed in studying the neurochemical substrates of rapidly transitioning behavior.

Effects of intrastriatal administration of selective dopaminergic ligands on spontaneous stereotypy in mice.

Abnormal repetitive behaviors are often associated with specific developmental, genetic, and neuropsychiatric disorders. Repetitive motor behaviors, often referred to as stereotypies, have been studied extensively as they can be readily induced by certain drugs (e.g., amphetamine). Recent work has shown, however, that such drug-induced models of stereotypy may not accurately reflect the neurobiological perturbations responsible for the spontaneous manifestation of these behaviors. The present study employed the deer mouse model of spontaneous and persistent stereotypy to evaluate the capacity of several selective dopaminergic agonists (apomorphine, SKF81297, and quinpirole) to exacerbate levels of spontaneously emitted stereotypic topographies when administered intrastriatally. Additionally, the effects of intrastriatal administration of the D(2)R antagonist raclopride on the expression of spontaneous stereotypic jumping were evaluated. No induction or exacerbation of stereotypy was observed following administration of the selective D(1)- or D(2)- receptor agonists, and the mixed agonist apomorphine induced hyperlocomotion and excessive grooming but failed to exacerbate spontaneous stereotypy. Thus, a dissociation was observed between spontaneously emitted and drug-induced stereotypy, suggesting significant limitations to the use of dopamine agonist-induced stereotypy as a model of clinical stereotyped movement disorder. Furthermore, an unexpected and statistically significant (P<.05) potentiation of locomotor activity was observed following intrastriatal raclopride administration, suggesting major alterations to the modulatory characteristics of the striatal dopaminergic system in these spontaneously stereotypic animals.

Selective blockade of spontaneous motor stereotypy via intrastriatal pharmacological manipulation.

Abnormal repetitive behavior, including stereotypy, is often observed in conjunction with developmental, neuropsychiatric, and genetic disorders. The present work employed the deer mouse model of spontaneous and persistent stereotypy to identify basal ganglia involvement in the mediation of these abnormal behaviors. To evaluate the hypothesis that stereotypy is expressed in these mice due to alterations in the activity of cortico-basal ganglia motor circuits, intrastriatal pharmacological manipulations aimed at attenuating the spontaneously emitted stereotypy were performed. Bilateral striatal infusion of the NMDA or dopamine D(1) receptor antagonists MK-801 or SCH23390, respectively, produced a substantial reduction in levels of stereotypic jumping without inhibiting nonstereotypic motor behavior. These findings support the hypothesis that environmentally related stereotypy is expressed as a consequence of elevated feedback activity occurring along motor circuits of the basal ganglia.

Dissociation between spontaneously emitted and apomorphine-induced stereotypy in Peromyscus maniculatus bairdii.

Stereotyped behavior is repetitive, topographically invariant motor activity that lacks an obvious function. We have previously characterized the spontaneous and persistent stereotypies that occur in deer mice housed in standard laboratory cages. Providing these animals with enriched environments markedly reduces their vulnerability to develop stereotypic behavioral repertoires, thus enabling us to generate behaviorally distinct (stereotypic and nonstereotypic) mice of the same species. As stereotypic behaviors are readily induced by systemic administration of a dopamine (DA) agonist, the present study tested whether apomorphine would induce stereotypies in environmentally enriched (nonstereotypic) deer mice that were topographically similar to the stereotypies that are spontaneously emitted by standard-caged (stereotypic) deer mice. The effects of apomorphine were also evaluated in the standard-caged (stereotypic) deer mice. DA agonist-induced behaviors in nonstereotypic mice included stereotypies that were largely topographically distinct from spontaneously emitted stereotypies; apomorphine failed to produce statistically significant elevations in two of the three stereotypic behaviors typical of standard-caged deer mice. Furthermore, there was no evidence of increased DA receptor sensitivity in stereotypic mice. Thus, environmentally related stereotypy is distinct from systemically administered DA agonist-induced stereotypy, and is not exacerbated by such drug treatment. The results obtained do provide support, however, for a limited involvement of the DA system in the mediation of these behaviors.