Fast neurotransmitter identity of MCH neurons: Do contents depend on context?

Hypothalamic melanin-concentrating hormone (MCH) neurons participate in many fundamental neuroendocrine processes. While some of their effects can be attributed to MCH itself, others appear to depend on co-released neurotransmitters. Historically, the subject of fast neurotransmitter co-release from MCH neurons has been contentious, with data to support MCH neurons releasing GABA, glutamate, both, and neither. Rather than assuming a position in that debate, this review considers the evidence for all sides and presents an alternative explanation: neurochemical identity, including classical neurotransmitter content, is subject to change. With an emphasis on the variability of experimental details, we posit that MCH neurons may release GABA and/or glutamate at different points according to environmental and contextual factors. Through the lens of the MCH system, we offer evidence that the field of neuroendocrinology would benefit from a more nuanced and dynamic interpretation of neurotransmitter identity.

Serum anti-GM2 and anti-GalNAc-GD1a IgG antibodies are biomarkers for acute canine polyradiculoneuritis.

OBJECTIVES: A previous single-country pilot study indicated serum anti-GM2 and anti-GA1 anti-glycolipid antibodies as potential biomarkers for acute canine polyradiculoneuritis. This study aims to validate these findings in a large geographically heterogenous cohort. MATERIALS AND METHODS: Sera from 175 dogs clinically diagnosed with acute canine polyradiculoneuritis, 112 dogs with other peripheral nerve, cranial nerve or neuromuscular disorders and 226 neurologically normal dogs were screened for anti-glycolipid antibodies against 11 common glycolipid targets to determine the immunoglobulin G anti-glycolipid antibodies with the highest combined sensitivity and specificity for acute canine polyradiculoneuritis. RESULTS: Anti-GM2 anti-glycolipid antibodies reached the highest combined sensitivity and specificity (sensitivity: 65.1%, 95% confidence interval 57.6 to 72.2%; specificity: 90.2%, 95% confidence interval 83.1 to 95.0%), followed by anti-GalNAc-GD1a anti-glycolipid antibodies (sensitivity: 61.7%, 95% confidence interval 54.1 to 68.9%; specificity: 89.3%, 95% confidence interval 82.0 to 94.3%) and these anti-glycolipid antibodies were frequently present concomitantly. Anti-GA1 anti-glycolipid antibodies were detected in both acute canine polyradiculoneuritis and control animals. Both for anti-GM2 and anti-GalNAc-GD1a anti-glycolipid antibodies, sex was found a significantly associated factor with a female to male odds ratio of 2.55 (1.27 to 5.31) and 3.00 (1.22 to 7.89), respectively. Anti-GalNAc-GD1a anti-glycolipid antibodies were more commonly observed in dogs unable to walk (OR 4.56, 1.56 to 14.87). CLINICAL SIGNIFICANCE: Anti-GM2 and anti-GalNAc-GD1a immunoglobulin G anti-glycolipid antibodies represent serum biomarkers for acute canine polyradiculoneuritis.

Assessing the state of consciousness for individual patients using complex, statistical stimuli.

Patients with prolonged disorders of consciousness (PDOC) are often unable to communicate their state of consciousness. Determining the latter is essential for the patient's care and prospects of recovery. Auditory stimulation in combination with neural recordings is a promising technique towards an objective assessment of conscious awareness. Here, we investigated the potential of complex, acoustic stimuli to elicit EEG responses suitable for classifying multiple subject groups, from unconscious to responding. We presented naturalistic auditory textures with unexpectedly changing statistics to human listeners. Awake, active listeners were asked to indicate the change by button press, while all other groups (awake passive, asleep, minimally conscious state (MCS), and unresponsive wakefulness syndrome (UWS)) listened passively. We quantified the evoked potential at stimulus onset and change in stimulus statistics, as well as the complexity of neural response during the change of stimulus statistics. On the group level, onset and change potentials classified patients and healthy controls successfully but failed to differentiate between the UWS and MCS groups. Conversely, the Lempel-Ziv complexity of the scalp-level potential allowed reliable differentiation between UWS and MCS even for individual subjects, when compared with the clinical assessment aligned to the EEG measurements. The accuracy appears to improve further when taking the latest available clinical diagnosis into account. In summary, EEG signal complexity during onset and changes in complex acoustic stimuli provides an objective criterion for distinguishing states of consciousness in clinical patients. These results suggest EEG-recordings as a cost-effective tool to choose appropriate treatments for non-responsive PDOC patients.

[Smoking Cessation with E-Cigarettes? - Ad Hoc Statement of the German Respiratory Society (DGP)]. / Tabakentwöhnung mit E-Zigarette?

The German Respiratory Society (DGP) turns against the e-cigarette as a means for harm reduction because of potential health risk and dangers to young people. The aerosol of e-cigarettes contains toxic ingredients that have been shown to be damaging to the lungs, the cardiovascular system and the immune system and are potentially carcinogenic. Studies on e-cigarettes as a means of smoking cessation are not very convincing, in order to favor e-cigarettes over nicotine replacement therapy, which have been tried and tested for many years, or other drugs that reduce the desire to smoke.

Early gamma-oscillations as correlate of localized nociceptive processing in primary sensorimotor cortex.

Recent studies put forward the idea that stimulus-evoked gamma-band oscillations (GBOs; 30-100 Hz) play a specific role in nociception. So far, evidence for the specificity of GBOs for nociception, their possible involvement in nociceptive sensory discriminatory abilities, and knowledge regarding their cortical sources is just starting to grow. To address these questions, we used electroencephalography (EEG) to record brain activity evoked by phasic nociceptive laser stimuli and tactile stimuli applied at different intensities to the right hand and foot of 12 healthy volunteers. The EEG was analyzed in the time domain to extract phase-locked event-related brain potentials (ERPs) and in three regions of interest in the time-frequency domain (delta/theta, 40-Hz gamma, 70-Hz gamma) to extract stimulus-evoked changes in the magnitude of non-phase-locked brain oscillations. Both nociceptive and tactile stimuli, matched with respect to subjective intensity, elicited phase locked ERPs of increasing amplitude with increasing stimulus intensity. In contrast, only nociceptive stimuli elicited a significant enhancement of GBOs (65-85 Hz, 150-230 ms after stimulus onset), whose magnitude encoded stimulus intensity, whereas tactile stimuli led to a GBO decrease. Following nociceptive hand stimulation, the topographical distribution of GBOs was maximal at contralateral electrode C3, whereas maximum activity following foot stimulation was recorded at the midline electrode Cz, compatible with generation of GBOs in the representations of the hand and foot of the primary sensorimotor cortex, respectively. The differential behavior of high-frequency GBOs and low-frequency 40-Hz GBOs is indicating different functional roles and regions in sensory processing.NEW & NOTEWORTHY Gamma-band oscillations show hand-foot somatotopy compatible with generation in primary sensorimotor cortex and are present following nociceptive but not tactile stimulation of the hand and foot in humans.

Evidence for a magnocellular disadvantage in early-onset schizophrenic patients: a source analysis of the N80 visual-evoked component.

BACKGROUND: Visual impairments in schizophrenia have been suggested to be partly caused by early processing deficits of the magnocellular (M) pathway. This might include disturbed interactions between the M and parvocellular (P) pathways and especially impaired M priming, which can disturb highlighting of relevant information. Such disorders may result from neurodevelopmental irregularities, which are assumed to be substantially involved in schizophrenia. This study sought to test the hypothesis that M priming is impaired in schizophrenia. In order to elucidate this neurodevelopmental aspect, we investigated patients with different ages of schizophrenia onset. This provided a useful design to integrate visual information processing in a neurodevelopmental model of schizophrenia. METHOD: Nine stimulus conditions were used to investigate the M- and P-pathways and their interaction in a pattern reversal VEP paradigm. N80 generators were analyzed using source localization (Brain Electrical Source Analysis software: BESA). Forty schizophrenia patients (early-onset=19; adult-onset=21) were compared with age- and gender-matched healthy controls (early-onset controls=19; adult-onset controls=21). Hypotheses were tested using a bootstrap resampling procedure. RESULTS: The N80 component was represented by a single dipole located in the occipital visual cortex. The bootstrap analysis yielded significant differences between early-onset schizophrenia patients and controls. We found lower amplitudes in response to mixed M-P conditions and normal amplitudes in response to isolated P- and M-biased stimulation. Concerning the latencies, significant differences were found between adult-onset subjects and their controls, with prolonged latencies for schizophrenia patients. CONCLUSIONS: The early VEP component N80 evoked by mixed M-P conditions is assumed to be a correlate of M priming and showed reduced amplitude in early-onset schizophrenic patients but not in adult-onset patients. These findings point towards an M priming deficit in early-onset patients and are compatible with a neurodevelopmental hypothesis of schizophrenia, probably reflecting asynchronies in brain maturational abnormalities occurring at different ages of illness onset.

[Implementing in-patient smoking cessation interventions. Basic characteristics of smoking patients in a lung health department]. / Implementierung von Maßnahmen zur Tabakentwöhnung im Krankenhaus. Basisdaten eines pneumologischen Patientenkollektivs.

BACKGROUND: Hospitals have a unique key role in promoting smoking cessation. However, cessation interventions are uncommon in clinical routine despite their proven effectiveness. For planning a tailored intervention for hospitalised patients we examined the characteristics of smokers in our department for lung diseases. METHODS AND PATIENTS: From July to September 2009 we evaluated the smoking status of all admitted patients. The smoking status was validated by measuring the CO-Hb. Smokers admitted for the first time on one of our regular wards received a comprehensive questionnaire. Patients with a duration of stay of 2 days or less and patients with substantial cognitive or linguistic limitations were excluded. Clinical data was collected from the participating smokers. RESULTS: 25% of all admitted patients were smokers. The participation rate was almost 90% of the eligible smokers. Our questionnaire was very well accepted und provided multitude helpful information for a following cessation counselling. Up to 3 or 4 smokers per day should be anticipated for a cessation intervention at an 80-bed-hospital. At least one counselling contact could be enabled. Although 75% of participants had experienced at least one unsuccessful quit attempt, only a minority used any support or help for cessation so far. CONCLUSIONS: Specific questionnaires to evaluate the smoking history of patients in hospitals are very suitable and facilitate a subsequent bedside-counseling. To come up with their key role in promoting smoking cessation more hospitals as yet should implement cessation interventions.

[Smoking cessation programmes at hospitals with departments for lung diseases]. / Tabakentwöhnung an pneumologischen Akutkliniken.

BACKGROUND AND OBJECTIVES: Tobacco smoking is the main preventable risk factor resulting in multiple diseases and premature death. In particular, the airways and the lungs are affected by the effects of smoking. Hospitals have considerable potential to advance smoking cessation. However, so far there have only been a few data on availability and effectiveness of smoking cessation programs in hospitals. This study aimed to assess such programs in general hospitals with a special department for lung disease in South West Germany. METHODS: 40 hospitals with at least one pulmonary specialist were identified. This doctor was subsequently interviewed by a telephone call. 39 hospitals participated, one could not be reached by telephone. RESULTS: Although most of the interviewed specialists confirmed the importance of smoking cessation in the field of pneumology only 3 hospitals had own activities for promoting smoking cessation. Another 7 hospitals cooperated with other institutions. Accompanying pharmacotherapy was not practised regularly. The main reasons for a lack of smoking cessation activities in the hospitals were due to the lack of personnel, time and money. CONCLUSION: Our study highlights the tremendous difficulties facing general hospitals when trying to implement a smoking cessation program. Changes in the economic frameworks, and further examination of appropriate measures for brief interventions in the hospital setting are necessary.

Interaction among the components of multiple auditory steady-state responses: enhancement in tinnitus patients, inhibition in controls.

Amplitude and phase of steady-state signals recorded in response to amplitude-modulated (AM) sine tones vary over time, suggesting that the steady-state response (SSR) reflects not only stimulus input but also its interaction with other input streams or internally generated signals. Alterations of the interaction between simultaneous SSRs associated with tinnitus were studied by recording the magnetic field evoked by AM-tones with one of three carrier and one of three modulation frequencies. Single AM-tones were presented in single presentation mode and superpositions of three AM-tones differing in carrier and modulation frequency in multiple presentation mode. Modulation frequency-specific SSR components were recovered by bandpass filtering. Compared with single mode, in multiple mode SSR amplitude was reduced in healthy controls, but increased in tinnitus patients. Thus, while in controls multiple response components seem to reciprocally inhibit one another, in tinnitus reciprocal facilitation seems to predominate. Reciprocal inhibition was unrelated to the phase coherence among SSR components, but was correlated with the frequency of phase slips, indicating that the lateral interaction among SSR components acts in a quasi-paroxysmal manner and manifests itself in terms of a random train of phase reset events. Phase slips were more frequent in patients than controls both in single and multiple mode. Together, these findings indicate that lateral or surround inhibition of single units in auditory cortex is reduced and suggest that in-field inhibition is increased in tinnitus.

Parent based language intervention for 2-year-old children with specific expressive language delay: a randomised controlled trial.

OBJECTIVE: The aim of this randomised controlled trial was to evaluate the effectiveness of a short, highly structured parent based language intervention group programme for 2-year-old children with specific expressive language delay (SELD, without deficits in receptive language). METHODS: 61 children with SELD (mean age 24.7 months, SD 0.9) were selected between October 2003 and February 2006 during routine developmental check-ups in general paediatric practices, using a German parent-report screening questionnaire (adapted from the MacArthur Communicative Development Inventories). Standardised instruments were used to assess the language and non-verbal cognitive abilities of these children and of 36 other children with normal language development (reference group; mean age 24.6 months, SD 0.8). 58 children with SELD were sequentially randomly assigned to an intervention group (n = 29) or a 12-month waiting group (n = 29). In the intervention group, mothers participated in the 3-month Heidelberg Parent-based Language Intervention (HPLI). All children were reassessed 6 and 12 months after pretest. Assessors were blind to allocation and previous results. RESULTS: 47 children were included in the analysis. At the age of 3 years, 75% of the children in the intervention group showed normal expressive language abilities in contrast to 44% in the waiting group. Only 8% of the children in the intervention group versus 26% in the waiting group met the criteria for specific language impairment (t score < or =35). CONCLUSIONS: By applying the short, highly structured HPLI in children with SELD, the rate of treatment for language impairment at the age of 3 years can be significantly reduced.

Low-dose hydrocortisone in the evening modulates symptom severity in restless legs syndrome.

BACKGROUND: Circadian symptom manifestation in the evening and night is one of the main characteristics of restless legs syndrome (RLS). Although the inverse temporal course of corticosteroid rhythm and RLS symptom severity is obvious, this relationship has yet to be studied. We investigated the effect of late-evening application of exogenous cortisol (hydrocortisone) on sensory leg discomfort (SLD), one of the main complaints of patients with RLS. METHODS: Ten untreated patients with idiopathic RLS participated in the study. Change of SLD was rated on a visual analogue scale during the 60 minutes resting period of the so-called Suggested Immobilization Test. Patients received either hydrocortisone 40 mg or placebo (saline) IV in random order in a double-blind crossover design, with 1 week between the experiments. RESULTS: Severity of SLD was lower during hydrocortisone infusion than during placebo (p = 0.032). Though blind to the experimental condition, 5 of the 10 patients experienced improvement in symptoms during hydrocortisone administration, but no patient felt an amelioration during the placebo condition. CONCLUSIONS: Our data indicate a probable physiologic relationship between evening and early night hour restless legs syndrome symptom increase and low cortisol level.

Surgical therapy of peripheral nerve lesions: current status and new perspectives.

The severe functional deficits in patients suffering from traumatic peripheral nerve damage underline the necessity of an optimal therapy. The development of microsurgical techniques in the sixties contributed significantly to the progress in nerve repair. Since then, no major clinical innovation has become established. However, with an increased understanding of cellular and molecular mechanisms underlying nerve regeneration, various tubulization concepts have been developed which yield possible alternatives to direct suturing and to autologous nerve grafting in cases of short nerve defects. The vast knowledge gathered in the field of nerve regeneration needs to be further exploited in order to develop alternative therapeutic strategies to nerve autografting, which can result in donor-site defects and often lead to inappropriate results. Considering the encouraging results from preclinical studies, innovative nerve repair strategies are likely to improve the outcome of reconstructive surgical interventions. This paper outlines, in addition to the fundamentals of nerve regeneration, the current treatment options for defects of peripheral nerves. This article also reviews the developments in the use of alternative nerve guides and demonstrates new perspectives in the field of peripheral nerve reconstruction.

Combined EEG and MEG analysis of early somatosensory evoked activity in children and adolescents with focal epilepsies.

OBJECTIVE: The study aimed to evaluate differences between EEG and MEG analysis of early somatosensory evoked activity in patients with focal epilepsies in localizing eloquent areas of the somatosensory cortex. METHODS: Twenty-five patients (12 male, 13 female; age 4-25 years, mean 11.7 years) were included. Syndromes were classified as symptomatic in 17, idiopathic in 2 and cryptogenic in 6 cases. 10 patients presented with malformations of cortical development (MCD). 122 channel MEG and simultaneous 33-channel EEG were recorded during tactile stimulation of the thumb (sampling rate 769 Hz, band-pass 0.3-260 Hz). Forty-four hemispheres were analyzed. Hemispheres were classified as type I: normal (15), II: central structural lesion (16), III: no lesion, but central epileptic discharges (ED, 8), IV: lesion or ED outside the central region (5). Analysis of both sides including one normal and one type II or III hemisphere was possible in 15 patients. Recordings were repeated in 18 hemispheres overall. Averaged data segments were filtered (10-250 Hz) and analyzed off-line with BESA. Latencies and amplitudes of N20 and P30 were analyzed. A regional source was fitted for localizing S1 by MRI co-registration. Orientation of EEG N20 was calculated from a single dipole model. RESULTS: EEG and MEG lead to comparable good results in all normal hemispheres. Only EEG detected N20/P30 in 3 hemispheres of types II/III while MEG showed no signal. N20 dipoles had a more radial orientation in these cases. MEG added information in one hemisphere, when EEG source analysis of a clear N20 was not possible because of a low signal-to-noise ratio. Overall N20 dipoles had a more radial orientation in type II when compared to type I hemispheres (p=0.01). Further N20/P30 parameters (amplitudes, latencies, localization related to central sulcus) showed no significant differences between affected and normal hemispheres. Early somatosensory evoked activity was preserved within the visible lesion in 5 of the 10 patients with MCD. CONCLUSIONS: MEG should be combined with EEG when analyzing tactile evoked activities in hemispheres with a central structural lesion or ED focus. SIGNIFICANCE: At time, MEG analysis is frequently applied without simultaneous EEG. Our results clearly show that EEG may be superior under specific circumstances and combination is necessary when analyzing activity from anatomically altered cortex.

Strain differences in the branching of the sciatic nerve in rats.

The sciatic nerve in the rat is the site most often used for peripheral nerve regeneration studies. The length of sciatic nerve available for research, however, depends on the point at which the sciatic nerve divides into the peroneal and tibial nerves. In the present study, the hind limbs of 150 adult male rats of five different strains (Sprague-Dawley, Fischer 344, Wistar-Han, Lewis and Nude) were analysed with regard to femur length, the point at which the sciatic nerve divides into the tibial and peroneal nerves, and where these are surrounded by the same epineurium, and the point at which they are encased in individual epineurial sheaths. The results indicate that the lengths of sciatic nerve are fairly constant in all strains of rats. In absolute terms, they amount to about one-third of the length of the femur for stretches of undivided sciatic nerve, and up to nearly half of the femur length for stretches where the tibial and peroneal nerves are already present, but are still enclosed by the same epineurium. In 61.7% of the hind limbs examined in Fischer rats, however, no sciatic nerve could be seen as such, but only in the form of its successors surrounded by the separate epineuria. This makes it highly advisable not to use male adult Fischer rats in peripheral nerve regeneration studies with the sciatic nerve as the point of focus.

Additional neuromagnetic source activity outside the auditory cortex in duration discrimination correlates with behavioural ability.

In magneto- and electroencephalographic experiments on an oddball paradigm we compared the components of the auditory evoked fields and potentials of "attend" with "nonattend" conditions in 17 subjects. The former consisted of the performance of a duration discrimination task, where we observed augmented activity for the auditory sustained response. A multiple source analysis showed this effect mainly stemming from a third source outside the auditory cortices. The dipole moment of this specific activation was increased by 150% under the attend condition. Having anatomical 3D MRI data sets of 12 subjects the likely location of the third source was shown to be within the area of the precuneus or the posterior cingulate gyrus, which, along with its waveform, suggests it to be a CNV equivalent. Further, the dipole moment is correlated significantly to the subjects' psychometrically derived discriminative abilities.

Is frontal lobe involved in the generation of auditory evoked P50?

This study examined the functional substrate of P50 suppression. Auditory evoked potentials (AEPs) and magnetic fields (AEFs) were recorded from healthy subjects simultaneously and analyzed using spatio-temporal source analysis. The resulting equivalent dipole model for the AEP consisted of one source in the auditory cortex (AC) of each hemisphere and an radially oriented medial frontal source, both with maximum AEP activity around 50 ms. The frontal source was functionally separated from the AC sources since it peaked significantly later and showed significantly larger P50 amplitude suppression. P30m showed neither suppression nor substantial frontal activity. In sum, this study relates P50 suppression to reduction of AC source activity and is the first to yield direct evidence for frontal involvement in P50 suppression.

Interaction of tactile input in the human primary and secondary somatosensory cortex--a magnetoencephalographic study.

Interaction of simultaneous tactile input at two finger sites in primary (SI) and secondary somatosensory cortex (SII) was studied by whole-head magnetoencephalography. Short pressure pulses were delivered to fingers of the right and left hand at an interstimulus interval of 1.6 s. The first phalanx of the left digit 1 and four other sites were stimulated either separately or simultaneously. We compared four sites with increasing distance: the second phalanx of left digit 1, left digit 5, and digits 1 and 5 of the right hand. The temporal evolution of source activity in the contralateral SI and bilateral SII was calculated using spatiotemporal source analysis. Interaction was assessed by comparing the source activity during simultaneous stimulation with the sum of the source activities elicited by separate stimulation. Significant suppressive interaction was observed in contralateral SI only for stimuli at the same hand, decreasing with distance. In SII, all digits of the same and the opposite hand interacted significantly with left digit 1. When stimulating bilaterally, SII source waveforms closely resembled the time course of the response to separate stimulation of the opposite hand. Thus, in bilateral simultaneous stimulation, the contralateral input arriving first in SII appeared to inhibit the later ipsilateral input. Similarly, the separate response to input at two unilateral finger sites which arrived slightly earlier in SII dominated the simultaneous response. Our results confirm previous findings of considerable overlap in the cortical hand representation in SII and illustrate hemispheric specialization to contralateral input when simultaneous stimuli occur bilaterally.

Variability of blood-brain ratios of phenylalanine in typical patients with phenylketonuria.

Blood-brain ratios (BBR) of phenylalanine (Phe) were determined by quantitative in vivo 1H magnetic resonance spectroscopy (1H-MRS) in 17 adult patients with early-treated phenylketonuria who were randomly selected from a sample of 75 adults. Measurements were performed in all patients during steady-state conditions. The BBR showed a unimodal distribution with a mean of 4.0 (range 3.3 to 4.5). Blood-brain ratios were comparable for subgroups of patients with genotypes classified as severe, moderate, or mild and for patients on different types of diets. Brain Phe concentrations showed a strong linear correlation with blood Phe values (r = 0.93, P < 0.001). There were no saturation effects for blood Phe values up to 1.8 mmol/L, and a local regression analysis did not confirm increasing BBR for increasing blood Phe values. The intellectual outcome (Wechsler Adult Intelligence Scale) was correlated with long-term dietary control (r = -0.65, P < 0.05), fluctuation of blood Phe values during treatment (r = -0.60, P < 0.05), and concurrent blood and brain Phe concentration. The severity of white matter changes visible on magnetic resonance images (MRI) was increased with high blood and brain Phe concentrations but failed to reach statistical significance. No correlation was found between BBR values, intelligence quotient, and MRI grade. Based on the assumption that BBR show intraindividual stability, the current data do not support the hypothesis that blood-brain barrier transport of Phe is a key explanatory factor for outcome variability in the vast majority of "typical" patients with phenylketonuria.

Managed care and children's behavioral health services in Massachusetts.

OBJECTIVE: The authors investigated changes in treatment patterns and costs of care for children after the implementation of the Massachusetts Medicaid carve-out managed care plan. METHODS: The authors hypothesized that after the introduction of managed care, per-child expenditures would be reduced, continuity of care would not improve, and per-child mental health expenditures would undergo larger reductions for disabled children, compared with children enrolled in the Aid to Families With Dependent Children program. Using data from Medicaid and the Massachusetts Department of Mental Health, the authors studied 16,664 Massachusetts Medicaid beneficiaries aged one to 17 years for whom reimbursement claims were submitted for psychiatric or substance use disorder treatment at least once during the two years before the introduction of managed care (1991 to 1992) or during the two years afterward (1994 to 1995). Multivariate analysis was used to estimate changes in probability of admission, and, among patients admitted, to identify factors accounting for variation in length of stay. To assess the variation in expenditures, we regressed the same variables, using the natural logarithm function to transform total mental health expenditures data and inpatient expenditures data to reduce skewness. RESULTS: After the introduction of managed care, per-child expenditures were lower, especially for disabled children, and the Department of Mental Health was used as a safety net for the most seriously ill children without increasing state expenditures. Continuity of care appeared to decline for disabled children. CONCLUSIONS: It is likely that a combination of factors related to the reported changes in patterns of care and expenditures were responsible for the overall per-child expenditures.