Iodine Extravasation Quantification on Dual-Energy CT of the Brain Performed after Mechanical Thrombectomy for Acute Ischemic Stroke Can Predict Hemorrhagic Complications.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage represents a potentially severe complication of revascularization of acute ischemic stroke. The aim of our study was to assess the capability of iodine extravasation quantification on dual-energy CT performed immediately after mechanical thrombectomy to predict hemorrhagic complications. MATERIALS AND METHODS: Because this was a retrospective study, the need for informed consent was waived. Eighty-five consecutive patients who underwent brain dual-energy CT immediately after mechanical thrombectomy for acute ischemic stroke between August 2013 and January 2017 were included. Two radiologists independently evaluated dual-energy CT images for the presence of parenchymal hyperdensity, iodine extravasation, and hemorrhage. Maximum iodine concentration was measured. Follow-up CT examinations performed until patient discharge were reviewed for intracerebral hemorrhage development. The correlation between dual-energy CT parameters and intracerebral hemorrhage development was analyzed by the Mann-Whitney U test and Fisher exact test. Receiver operating characteristic curves were generated for continuous variables. RESULTS: Thirteen of 85 patients (15.3%) developed hemorrhage. On postoperative dual-energy CT, parenchymal hyperdensities and iodine extravasation were present in 100% of the patients who developed intracerebral hemorrhage and in 56.3% of the patients who did not (P = .002 for both). Signs of bleeding were present in 35.7% of the patients who developed intracerebral hemorrhage and in none of the patients who did not (P < .001). Median maximum iodine concentration was 2.63 mg/mL in the patients who developed intracerebral hemorrhage and 1.4 mg/mL in the patients who did not (P < .001). Maximum iodine concentration showed an area under the curve of 0.89 for identifying patients developing intracerebral hemorrhage. CONCLUSIONS: The presence of parenchymal hyperdensity with a maximum iodine concentration of >1.35 mg/mL may identify patients developing intracerebral hemorrhage with 100% sensitivity and 67.6% specificity.

Electrophysiological properties of cat reticular thalamic neurones in vivo.

1. The electrophysiological properties of neurones of the reticular thalamic (RE) nucleus were studied in acutely prepared cats under urethane anaesthesia. 2. Two main types of neuronal firing were recorded. At the resting membrane potential (-60 to -65 mV) tonic repetitive firing was elicited when the cell was activated synaptically or by current injection. From membrane potentials more negative than -75 mV, synaptic or direct stimulation generated a burst of action potentials. 3. The burst of RE cells consisted of a discharge of four to eight spikes riding on a slowly growing and decaying depolarization. The discharge rate during the burst showed a characteristic increase, followed by a decrease in frequency. 4. The burst response behaved as a graded phenomenon, as its magnitude was modulated by changing the intensity of the synaptic volley or the intensity of the injected current. 5. Spike-like small potentials presumably of dendritic origin occurred spontaneously and were triggered by synaptic or direct stimulation. They were all-or-none, voltage-dependent events. We postulate that these spikes originate in several hot spots in the dendritic arbor, with no reciprocal refractoriness and may generate multi-component depolarizations at the somatic level. 6. Excitatory postsynaptic potentials (EPSPs) evoked by internal capsule stimulation consisted of two components, the late one being blocked by hyperpolarization. Such compound EPSPs were followed by a period of decreased excitability during which a second response was diminished in amplitude. 7. A series of depolarizing waves at the frequency range of spindle oscillations was triggered by internal capsule stimulation. The individual depolarizing waves constituting the spindle oscillation gradually decreased in amplitude when decreasing the intensity of the stimulation. 8. These results, showing that RE cells are endowed with an excitable dendritic tree and a graded bursting behaviour, support the proposed role of RE nucleus as the generator and synchronizer of spindle rhythmicity.

Electrophysiological properties of intralaminar thalamocortical cells discharging rhythmic (approximately 40 HZ) spike-bursts at approximately 1000 HZ during waking and rapid eye movement sleep.

Thalamocortical neurons located in the large-celled district of the cat intralaminar centrolateral nucleus were found to discharge spike-bursts with unusually high frequencies (800-1000 Hz) during spindle oscillations of the electroencephalogram. In chronically implanted animals, similar spike-bursts were also fired during wakefulness and rapid eye movement sleep, two behavioral states in which other thalamocortical neurons tonically fire single spikes. Such high-frequency spike-bursts recurred with a fast rhythm of 20-40 Hz during waking and rapid eye movement sleep. Intracellular recordings under barbiturate anesthesia showed that, during spindle oscillations, the spike-bursts of intralaminar neurons are generated by brief low-threshold spikes with a much shorter refractory phase than in other thalamocortical cells. Depolarizing pulses from the resting membrane potential triggered fast oscillations (20-80 Hz) crowned by short high-frequency (800-1000 Hz) spike-bursts. During the inter-spindle epochs, the "tonic" firing of these neurons was, in fact, a fast oscillation (30-40 Hz) of the membrane potential leading to single spikes or spike-doublets. Autocorrelograms computed from inter-spindle epochs, at relatively depolarized levels, confirmed the presence of multiple peaks at this fast rhythm. The properties of these neurons make them well suited for the distribution of fast rhythms during arousal and rapid eye movement sleep over the cerebral cortex.

The slow (< 1 Hz) oscillation in reticular thalamic and thalamocortical neurons: scenario of sleep rhythm generation in interacting thalamic and neocortical networks.

As most afferent axons to the thalamus originate in the cerebral cortex, we assumed that the slow (< 1 Hz) cortical oscillation described in the two companion articles is reflected in reticular (RE) thalamic and thalamocortical cells. We hypothesized that the cortically generated slow rhythm would appear in the thalamus in conjunction with delta and spindle oscillations arising from intrinsic and network properties of thalamic neurons. Intracellular recordings have been obtained in anesthetized cats from RE (n = 51) and cortically projecting (n = 240) thalamic neurons. RE cells were physiologically identified by cortically evoked high-frequency spike bursts and depolarizing spindle oscillations. Thalamocortical cells were recognized by backfiring from appropriate neocortical areas, spindle-related cyclic IPSPs, and hyperpolarization-activated delta oscillation consisting of rhythmic low-threshold spikes (LTSs) alternating with afterhyperpolarizing potentials (AHPs). The slow rhythm (0.3-0.5 Hz) was recorded in 65% of RE neurons. In approximately 90% of oscillating cells, the rhythm consisted of prolonged depolarizations giving rise to trains of single action potentials. DC hyperpolarization increased the synaptic noise and, in a few cells, suppressed the long-lasting depolarizing phase of the slow rhythm, without blocking the fast EPSPs. In approximately 10% of oscillating neurons, the hyperpolarizing phase of the oscillation was much more pronounced, thus suggesting that the slow rhythm was produced by inhibitory sculpturing of the background firing. The slow oscillation was associated with faster rhythms (4-8 Hz) in the same RE neuron. The slow rhythm of RE neurons was closely related to EEG wave complexes recurring with the same frequency, and its strong dependency upon a synchronized state of cortical EEG was observed during shifts in EEG patterns at different levels of anesthesia. In 44% of thalamocortical cells the slow rhythm of depolarizing sequences was apparent and it could coexist with delta or spindle oscillations in the same neuron. The occurrence of the slowly recurring depolarizing envelopes was delayed by the hyperpolarizing spindle sequences or by the LTS-AHP sequences of delta oscillation. The hyperpolarization-activated delta potentials that tended to dampen after a few cycles were grouped in sequences recurring with the slow rhythm. We finally propose a unified scenario of the genesis of the three major sleep rhythms: slow, delta, and spindle oscillations.

Bursting and tonic discharges in two classes of reticular thalamic neurons.

1. Two types of cat reticular (RE) thalamic cells were disclosed by means of intracellular recordings under urethan anesthesia. The RE neurons were identified by their typical depolarizing spindle oscillations in response to synchronous stimulation of the internal capsule. 2. In type I neurons (n = 41), depolarizing current pulses induced tonic firing at the resting or slightly depolarized membrane potential (Vm) and triggered high-frequency spike bursts at a Vm more negative than -75 mV. As well, these cells discharged rebound bursts at the break of a hyperpolarizing current pulse. Internal capsule stimulation elicited spindle sequences made off by depolarizing waves giving rise to spike bursts. 3. Type II cells (n = 9) did not discharge spike bursts to large depolarizing current pulses even when the Vm reached -100 mV, nor did they fire rebound bursts after long-lasting hyperpolarizing current pulses or spike bursts riding on the rhythmic depolarizing components of spindle sequences. 4. Compared with type I cells, type II cells showed less frequency accommodation during tonic firing. The latter neuronal class discharged at high frequencies (40 Hz) with slight DC depolarization, approximately 8-10 Hz at the resting Vm, and no underlying synaptic or subthreshold oscillatory events could be detected when the firing was blocked by DC hyperpolarization. 5. The presence of two cell classes in the RE nucleus challenges the common view that this nucleus consists of a single neuronal class. We suggest that a different set of conductances is present in type II RE neurons, thus preventing the low-threshold Ca2+ current from dominating the behavior of these cells.

Intracellular evidence for incompatibility between spindle and delta oscillations in thalamocortical neurons of cat.

Recent studies have revealed that the thalamus does not only generate spindle oscillations (7-14 Hz), but that it also participates in the genesis of a slower (less than 4 Hz) rhythm within the frequency range of delta waves on the electroencephalogram. In thalamic cells, delta is an intrinsic oscillation consisting of low-threshold spikes alternating with afterhyperpolarizing potentials. It is known from electroencephalographic recordings in humans and animals that slow or delta waves prevail during late sleep stages, whereas spindle oscillations are characteristic for the early stages of sleep. We studied the dependence of spindles and delta oscillations on membrane potential, as well as the effects of spindles on delta oscillations, in thalamocortical neurons of cats under urethane anesthesia and in cerveau isolé preparations (low collicular transections). Spindles appeared at membrane potentials between -55 and -65 mV, whereas delta oscillations occurred by bringing the membrane potential between -68 and -90 mV. Spindles either evoked by cortical stimulation or occurring spontaneously in cerveau isolé preparations prevented delta oscillations. This effect was probably due to the increase in membrane conductance associated with spindles. Barbiturates also blocked delta activity in thalamocortical neurons, probably through the same mechanism. A certain degree of incompatibility between spindles and delta rhythms in thalamocortical cells may explain the prevalence of these two types of oscillations during different stages of sleep with synchronization of the electroencephalogram.

Various types of inhibitory postsynaptic potentials in anterior thalamic cells are differentially altered by stimulation of laterodorsal tegmental cholinergic nucleus.

The effects of stimulating the laterodorsal tegmental cholinergic nucleus upon inhibitory postsynaptic potentials recorded in relay cells of the anterior thalamic complex were studied in urethane-anesthetized cats. The inhibitory postsynaptic potentials induced in anterior thalamic relay cells by stimulating mammillary nuclei or retrosplenial cortex are generated by local-circuit inhibitory neurons since this nuclear complex is devoid of afferents from the other intrathalamic source of inhibition, the reticular thalamic nucleus. In a parallel study from this laboratory, it has been shown that cortical stimulation elicits a biphasic inhibitory postsynaptic potential consisting of two (A and B) components attributed to axonal firing of local interneurons, whereas mammillary stimulation elicits, in addition to the A-B sequence, an earlier component (a) presumably generated by presynaptic dendrites in thalamic glomeruli. In the present study, short pulse-trains applied to the laterodorsal tegmental nucleus diminished the amplitudes of A and B inhibitory components or completely suppressed them. The B component was more sensitive to the depressive effect. By contrast with the changes of the A and B components, the mammillary-evoked a inhibitory component was not reduced and, in many instances, was enhanced following laterodorsal tegmental stimulation. The effects of laterodorsal tegmental stimulation survived monoamine depletion by reserpine. We suggest that mesopontine cholinergic depressive actions on A and B inhibitory postsynaptic potentials may be due to an increased conductance in thalamocortical cells during the short-lasting nicotinic action combined with a somatic hyperpolarization of local-circuit cells, whereas the enhancement of the earliest (a) inhibitory postsynaptic potential reflects a concomitant potentiating action at the level of intraglomerular presynaptic dendrites.

Substantia nigra reticulata neurons during sleep-waking states: relation with ponto-geniculo-occipital waves.

We have previously hypothesized that the spike bursts of brainstem peribrachial (PB) neurons, leading to ponto-geniculo-occipital (PGO) waves in thalamocortical systems, are triggered by phasic hyperpolarizations of sufficient magnitude or by excitatory inputs reaching a steadily hyperpolarized membrane. We have proposed that the source of these hyperpolarizing actions are substantia nigra pars reticulata (SNr) cells that project to, and exert inhibitory effects upon, PB neurons. Here we tested this hypothesis by recording antidromically identified SNr-PB cells in chronically implanted, naturally sleeping cats. A subpopulation of SNr-PB cells exhibited tonically increased firing preceding by 70-200 ms the thalamic PGO wave. These data support the hypothesis that an enhancement in SNr-cells' discharges may lead to hyperpolarization of PB neurons, with the consequence of spike bursts in one class of PGO-related PB-thalamic neurons.

Short-lasting nicotinic and long-lasting muscarinic depolarizing responses of thalamocortical neurons to stimulation of mesopontine cholinergic nuclei.

1. The responses of thalamocortical neurons to stimulation of mesopontine [peribrachial (PB) and laterodorsal (LDT)] cholinergic nuclei were studied intracellularly in urethan-anesthetized cats. Neurons recorded from anterior thalamic (AT), ventroanterior-ventrolateral (VA-VL) and rostral intralaminar centrolateral (CL) nuclei were physiologically identified by their orthodromic responses to prethalamic stimulation and/or antidromic activation from the cerebral cortex. 2. Besides early excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) that were not sensitive to cholinergic antagonists, two types of cholinergic responses were elicited by PB/LDT stimulation: a short-lasting and a late, long-lasting depolarization. All these components survived monoamine depletion by reserpine. 3. The latency of the short-lasting depolarizing response was 147.4 +/- 27.3 (SE) ms. The response lasted for 1.3 +/- 0.1 s and had a peak amplitude of 4.2 +/- 0.3 mV. This component was associated with 10-30% increase in membrane conductance and was abolished by systemic administration of the nicotinic antagonist mecamylamine. 4. The long-lasting depolarizing response had a latency of 1.2 +/- 0.1 s, a duration of 20.8 +/- 2.2 s, and a peak amplitude of 5.4 +/- 0.4 mV. Similar values were found in decorticated animals. The duration and amplitude of the late depolarizing component were dependent on stimulation parameters and membrane potential. This response increased under depolarizing current, decreased and eventually disappeared under hyperpolarizing current, and was associated on average with 40% increase in apparent input resistance. After systemic administration of the muscarinic antagonist scopolamine, the long-lasting depolarization disappeared; the surviving short-lasting depolarization was subsequently abolished by mecamylamine. 5. The prolonged depolarizing response of thalamocortical neurons to mesopontine cholinergic stimulation was accompanied by a desynchronization of the electroencephalogram (EEG). These two phenomena had a similar time course. Stimulation of deep cerebellar nuclei, whose axons traverse the PB area, did not induce a long-lasting depolarization of target thalamic cells, nor an EEG desynchronization. 6. These data demonstrate that, in addition to an initial nicotinic excitation, brain stem cholinergic stimulation elicits a late, long-lasting muscarinic depolarization of thalamocortical neurons. We suggest that the prolonged depolarization plays an important role in cortical activation.

Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems.

This study was performed to examine the hypothesis that thalamic-projecting neurons of mesopontine cholinergic nuclei display activity patterns that are compatible with their role in inducing and maintaining activation processes in thalamocortical systems during the states of waking (W) and rapid-eye-movement (REM) sleep associated with desynchronization of the electroencephalogram (EEG). A sample of 780 neurons located in the peribrachial (PB) area of the pedunculopontine tegmental nucleus and in the laterodorsal tegmental (LDT) nucleus were recorded extracellularly in unanesthetized, chronically implanted cats. Of those neurons, 82 were antidromically invaded from medial, intralaminar, and lateral thalamic nuclei: 570 were orthodromically driven at short latencies from various thalamic sites: and 45 of the latter elements are also part of the 82 cell group, as they were activated both antidromically and synaptically from the thalamus. There were no statistically significant differences between firing rates in the PB and LDT neuronal samples. Rate analyses in 2 distinct groups of PB/LDT neurons, with fast (greater than 10 Hz) and slow (less than 2 Hz) discharge rates in W, indicated that (1) the fast-discharging cell group had higher firing rates in W and REM sleep compared to EEG-synchronized sleep (S), the differences between all states being significant (p less than 0.0005); (2) the slow-discharging cell group increased firing rates from W to S and further to REM sleep, with significant difference between W and S (p less than 0.01), as well as between W or S and REM sleep (p less than 0.0005). Interspike interval histograms of PB and LDT neurons showed that 75% of them have tonic firing patterns, with virtually no high-frequency spike bursts in any state of the wake-sleep cycle. We found 22 PB cells that discharged rhythmic spike trains with recurring periods of 0.8-1 sec. Autocorrelograms revealed that this oscillatory behavior disappeared when their firing rate increased during REM sleep. Dynamic analyses of sequential firing rates throughout the waking-sleep cycle showed that none of the full-blown states of vigilance is associated with a uniform level of spontaneous firing rate. Signs of decreased discharge frequencies of mesopontine neurons appeared toward the end of quiet W, preceding by about 10-20 sec the most precocious signs of EEG synchronization heralding the sleep onset. During transition from S to W, rates of spontaneous discharges increased 20 sec before the onset of EEG desynchronization.(ABSTRACT TRUNCATED AT 400 WORDS)

Different cellular types in mesopontine cholinergic nuclei related to ponto-geniculo-occipital waves.

The only mesopontine neurons previously described as involved in the transfer of ponto-geniculo-occipital (PGO) waves from the brain stem to the thalamus were termed PGO-on bursting cells. We have studied, in chronically implanted cats, neuronal activities in brain-stem peribrachial (PB) and laterodorsal tegmental (LDT) cholinergic nuclei in relation to PGO waves recorded from the lateral geniculate (LG) thalamic nucleus during rapid-eye-movement (REM) sleep. We constructed peri-PGO histograms of PB/LDT cells' discharges and analyzed the interspike interval distribution during the period of increased neuronal activity related to PGO waves. Six categories of PGO-related PB/LDT neurons with identified thalamic projections were found: 4 classes of PGO-on cells: PGO-off but REM-on cells: and post-PGO cells. The physiological characteristics of a given cell class were stable even during prolonged recordings. One of these cell classes (1) represents the previously described PGO-on bursting neurons, while the other five (2-6) are newly discovered neuronal types. (1) Some neurons (16% of PGO-related cells) discharged stereotyped low-frequency (120-180 Hz) spike bursts preceding the negative peak of the LG-PGO waves by 20-40 msec. These neurons had low firing rates (0.5-3.5 Hz) during all states. (2) A distinct cell class (22% of PGO-related neurons) fired high-frequency spike bursts (greater than 500 Hz) about 20-40 msec prior to the thalamic PGO wave. These bursts were preceded by a period (150-200 msec) of discharge acceleration on a background of tonically increased activity during REM sleep. (3) PGO-on tonic neurons (20% of PGO-related neurons) discharged trains of repetitive single spikes preceding the thalamic PGO waves by 100-150 msec, but never fired high-frequency spike bursts. (4) Other PGO-on neurons (10% of PGO-related neurons) discharged single spikes preceding thalamic PGO waves by 15-30 msec. On the basis of parallel intracellular recordings in acutely prepared, reserpine-treated animals, we concluded that the PGO-on single spikes arise from conventional excitatory postsynaptic potentials and do not reflect tiny postinhibitory rebounds. (5) A peculiar cellular class, termed PGO-off elements (8% of PGO-related neurons), consisted of neurons with tonic, high discharge rates (greater than 30 Hz) during REM sleep. These neurons stopped firing 100-200 msec before and during the thalamic PGO waves. (6) Finally, other neurons discharged spike bursts or tonic spike trains 100-300 msec after the initially negative peak of the thalamic PGO field potential (post-PGO elements, 23% of PGO-related neurons).(ABSTRACT TRUNCATED AT 400 WORDS)

Brainstem genesis of reserpine-induced ponto-geniculo-occipital waves: an electrophysiological and morphological investigation.

Several experimental results indicate that the peribrachial (PB) cholinergic area of the pedunculopontine nucleus is the final relay for the transfer of brainstem-generated pontogeniculo-occipital (PGO) waves to the thalamus. However, the mechanisms underlying the PGO-related activity of PB neurons remain unknown. In order to study these mechanisms, single unit recordings in the PB area were performed in reserpinized cats. Because PGO waves are closely related to rapid eye movements, our microelectrode explorations were also aimed to some structures of the preoculomotor network, namely, the superior colliculus (SC) and parts of the central tegmental field (FTC). We have found several classes of PGO-on cells in the PB area, most of them descharging 80 ms or less before the peak of PGO waves. These cell-classes comprised high-frequency bursting cells, slow-frequency bursting cells, and neurons discharging single spikes or doublets. Intracellular recordings showed that PGO-on single spikes arise from conventional excitatory postsynaptic potentials. Among PGO-related cells in structures outside the PB limits, it was found that most SC cells discharge during or after the PGO, whereas FTC cells increase their discharge rate several hundreds of ms before PGO waves, thus indicating that PGO waves are elaborated long before the activation of PB neurons. Massive retrograde labeling was found in FTC following horseradish peroxidase injections into the PB area. We suggest that long-lead FTC neurons provide an excitatory input to PGO-on PB neurons.

[Convulsive episodes caused by a suspension of lorazepam]. / Episodi convulsivi da sospensione di lorazepam.

Seven cases of convulsive seizure occurring after abrupt withdrawal of Lorazepam in non epileptic patients are reported. Five ot of them had an important cerebral damage occurred in perinatal period. All patients, before withdrawal, had been taking Lorazepam, 5-15 mg/day, for at least six months. It is stressed that in similar cases there is no need to start an anticonvulsive therapy because usually there is not a spontaneous recurrence of convulsive seizures. It is suggested that withdrawal of long term treatments with high doses of benzodiazepines be accomplished carefully and very slowly especially in patients with a previous cerebral damage.

On the intracortical activity during recruiting responses: an analysis of laminar profiles before and after topical application of GABA to the cortex.

Intracortical activity during recruiting responses (RRs) has been studied by recording laminar profiles of intracortical field potentials during repetitive stimulation, at 6 Hz, of nucleus centralis lateralis (CL) and nucleus centralis medialis (NCM) in lightly anesthetized cats, before and after topical application to the cortex of 1% GABA solution. The data obtained underwent current source density analysis (CSD) which disclosed that in the pre-GABA condition, there are two almost simultaneous sinks, one in the most superficial layer and the other in mid-cortical layers. After GABA application, a single large sink was present in mid-cortical layers. Extracellular single cortical unit activity was recorded in different animals, through a microelectrode tangentially inserted into the cortex, during repetitive stimulation of CL or NCM, both before and after GABA application. In 75% of these units there was, after GABA, a mean reduction of about 50% of firing probability while in the remaining 25% there was an increased activity. Topical application of 1% Manganese sulfate to the cortical surface appeared to completely inactivate the whole thickness of the cortex where it was applied, making evident the contribution to RRs of the potentials generated in the cortex buried in the adjacent sulci. Finally, a reciprocal facilitating effect of RRs and augmenting responses (ARs), which was studied by combined stimulation of nucleus ventralis posterolateralis (VPL) and NCM, appeared to be dependent upon an intracortical mechanism. All these data suggest that: RRs are the result of a simultaneous activation of superficial and mid-cortical layers; RRs are contaminated by a volume conducted potential arising from the cortex buried in the sulci; a superficial inhibition following the initial excitation seems to be an usual component of the response; ARs and RRs probably share a similar intracortical mechanism for incrementing the response.