Impact of a novel pre-hospital stroke notification programme on acute stroke care key performance indicators in Hong Kong: a multicentre prospective cohort study with historical controls.

INTRODUCTION: Early identification and initiation of reperfusion therapy is essential for suspected acute ischaemic stroke. A pre-hospital stroke notification (PSN) protocol using FASE (facial drooping, arm weakness, speech difficulties, and eye palsy) was implemented to improve key performance indicators (KPIs) in acute stroke care delivery. We assessed KPIs and clinical outcomes before and after PSN implementation in Hong Kong. METHODS: This prospective cohort study with historical controls was conducted in the Accident and Emergency Departments of four public hospitals in Hong Kong. Patients were screened using the PSN protocol between August 2021 and February 2022. Suspected stroke patients between August 2020 and February 2021 were included as historical controls. Door-to-needle (DTN) and door-to-computed tomography (DTC) times before and after PSN implementation were compared. Clinical outcomes including National Institutes of Health Stroke Scale score at 24 hours and modified Rankin Scale score at 3 months after intravenous recombinant tissue-type plasminogen activator (IV-rtPA) were also assessed. RESULTS: Among the 715 patients (266 PSN and 449 non-PSN) included, 50.8% of PSN patients and 37.7% of non-PSN patients had a DTC time within 25 minutes (P<0.001). For the 58 PSN and 134 non-PSN patients given IV-rtPA, median DTN times were 67 and 75.5 minutes, respectively (P=0.007). The percentage of patients with a DTN time within 60 minutes was higher in the PSN group than in the non-PSN group (37.9% vs 21.6%; P=0.019). No statistically significant differences in clinical outcomes were observed. CONCLUSION: Although the PSN protocol shortened DTC and DTN times, clinical outcomes did not significantly differ.

The role of intraoperative micro-Doppler ultrasound in verifying proper clip placement in intracranial aneurysm surgery.

We present the results of a retrospective study employing intraoperative micro-Doppler ultrasonography (MDU) in verifying proper clip placement during cerebral aneurysmal surgery. One hundred and thirty-four patients surgically treated for 147 intracranial aneurysms were studied. Thirteen patients harboring 17 aneurysms were surgically treated on an elective basis, while 121 patients with 130 aneurysms, presented with subarachnoid hemorrhage (SAH). Blood flow velocities of the parent and adjacent vessels as well as the aneurysmal sac were measured using a Conforma Micro-Doppler (Cook Vascular Inc., Leechburg, PA, USA). Pre- and post-operative cerebral angiography was obtained in all our patients. In 23 aneurysms (15.6%) there was decreased or absent flow in the parent vessel or in one of the adjacent vessels after clipping. In another 19 aneurysms (12.9%), MDU demonstrated flow through the aneurysmal dome even though the aneurysmal neck appeared to be totally obliterated. Presence of SAH, anatomic location and size of the aneurysm were associated with improper clip placement in a statistically significant fashion. The false positive rate for MDU was 2% while there were no false negative findings in our study. MDU appears to be a non-invasive, reliable alternative methodology to intra-operative angiography. This inexpensive method may lend itself to routine usage in aneurysm surgery.

The role of the cannabinoid CB2 receptor in pain transmission and therapeutic potential of small molecule CB2 receptor agonists.

This review gives a brief overview of the expression patterns, molecular pharmacology and physiological role of the cannabinoid 2 receptor (CB2) in pain. Particular emphasis is given to the therapeutic utility of CB2 receptor agonists. Through studies utilizing selective CB2 receptor agonists, non-selective cannabinoid agonists in conjunction with selective CB1 and CB2 receptor antagonists, or CB2 receptor knockout mice, it is now clear that this receptor plays a critical role in nociception. To this end, CB2 receptors have been shown to modulate acute pain, chronic inflammatory pain, post-surgical pain, cancer pain and pain associated with nerve injury. Here we review these studies and the compounds that were utilized. We hypothesize the mechanism of action by which the CB2 receptor could be involved in these processes. Finally we summarize the most recent novel chemical scaffolds that are being investigated towards advancing selective CB2 receptor agonists into the clinic. Many new pharmacological agents have been identified by high throughput screening and small molecule lead discovery and optimization in the past 10 years. It is anticipated that at least some of these agents may ultimately constitute effective new pain therapeutics that lack the side effects associated with traditional cannabinoid ligands.

The intracarotid amobarbital sodium procedure. False-positive errors during recognition memory assessment.

Memory performance during the intracarotid amobarbital sodium (Amytal sodium) procedure was examined in 40 patients as part of their diagnostic work-up as candidates for epilepsy surgery. Free recall was significantly better following right hemisphere injection although no left/right difference was present during recognition assessment. However, the occurrence of false-positive (FP) recognition errors was significantly more frequent following left hemisphere injection. In all conditions, no relationship to seizure focus was observed. Patients with FP errors displayed poorer delayed verbal memory during baseline neuropsychological assessment compared with patients without FP errors. Data indicate an inverse relationship between FP errors and recent verbal memory function, and they suggest that impaired memory rather than failure to suppress incorrect responses secondary to poor self-monitoring capacity is responsible for the generation of FP and intrusion errors.

Intraoperative hippocampal cooling and Wada memory testing in the evaluation of amnesia risk following anterior temporal lobectomy.

OBJECTIVE: To determine the efficacy of memory testing following localized thermal inactivation (cooling) of the hippocampus during epilepsy surgery to assess risk for postoperative memory decline. DESIGN: Memory was assessed after intraoperative thermal inactivation of the hippocampus and during the Wada procedure to help determine the clinical utility of each procedure. SETTING: A university hospital, comprehensive epilepsy surgery program. PATIENTS: Individuals undergoing unilateral temporal lobectomy for relief of intractable seizures. PROCEDURE: After temporal tip resection, iced liquid was irrigated into the temporal horn of the lateral ventricle until the hippocampus was "cooled." MAIN OUTCOME MEASURES: Multiple neuropsychological measures of learning and memory. RESULTS: Wada memory testing suggested risk for memory impairment in 15 patients while cooling indicated risk in only five patients. Predictions arising from the two procedures were concordant in 13 patients and discordant in 12 patients. Among the 12 inconsistent predictions, hippocampal cooling suggested adequate contralateral memory support in 11 (92%) of 12 patients, and none of these 11 patients had a postoperative anterograde amnesia. CONCLUSION: Intraoperative hippocampal cooling may be useful in determining the risk of postoperative memory disorder among selected patients undergoing epilepsy surgery.

Stimulus timing effects on Wada memory testing.

OBJECTIVE: To determine the effects of presenting Wada memory stimuli at different times after intracarotid amobarbital injection on Wada memory asymmetries. DESIGN: Wada memory asymmetries from three timing series were related to the laterality of eventual temporal lobectomy. SETTING: Academic institution epilepsy surgery program. PATIENTS: Forty-three patients with complex partial seizures who later underwent anterior temporal lobectomy (left temporal lobectomy, 24 patients; right temporal lobectomy, 19 patients). No patient included had abnormalities on magnetic resonance imaging scans to suggest a lesion other than gliosis. RESULTS: Memory performance for objects whose presentation began approximately 45 seconds after amobarbital administration differentiated laterality of seizure onset. Memory for items presented later and after partial return of language (on average 3 minutes 40 seconds postinjection) also differed as a function of ipsilateral vs contralateral injection, but at a lower level of statistical significance. Memory for items presented last during the procedure (on average 6 minutes postinjection) discriminated seizure groups at a still lower level of statistical significance. When used to predict lateralized temporal lobe impairment in individual patients, early object memory performance was significantly better than memory performance employing either middle (56%) or late (43%) stimulus presentation timings. CONCLUSION: The results of early object memory testing are superior to those obtained from stimulus presentation later in the procedure in documenting temporal lobe dysfunction associated with a lateralized seizure onset.

Severe behavioral complications following intracarotid sodium amobarbital injection: implications for hemispheric asymmetry of emotion.

The intracarotid sodium amobarbital (ISA) procedure is effective in determining cerebral language dominance. However, severe emotional and behavioral reactions during ISA evaluation may invalidate the results or necessitate aborting the procedure. In an effort to identify patients at risk for behavioral complications, we reviewed 92 patients undergoing ISA evaluation and found five with severe changes in affect and behavior following amobarbital injection, ranging from prolonged coma to an extended confusional state. Severe behavioral disturbances were more likely to occur in patients with left frontal structural lesions upon injecting amobarbital into the right hemisphere. Analysis of patients with structural lesions of the anterior regions of the right hemisphere showed no evidence of similar behavioral complications. These findings suggest a special role for the left frontal region in the inhibition of affective expression and provide further evidence of the importance of right hemisphere mechanisms in emotion.

Attentional mechanisms during the intracarotid amobarbital test.

We investigated the integrity of attentional mechanisms following unilateral intracarotid amobarbital injection in 23 patients undergoing preoperative evaluation for epilepsy surgery. Performance for ipsilateral hand-button response to a quasi-random strobe flash was markedly altered following unilateral amobarbital injection as evidenced by decreased correct responses and increased perseverative errors. The increase in perseverations was inversely correlated with subsequent memory performance. The results indicate that unilateral amobarbital injection commonly produces a marked reduction in attention as well as disturbances in strategic control mechanisms.

Anosognosia and asomatognosia during intracarotid amobarbital inactivation.

BACKGROUND: Anosognosia (i.e., denial of hemiparesis) and asomatognosia (i.e., inability to recognize the affected limb as one's own) occur more frequently with right cerebral lesions. However, the incidence, relative recovery, and underlying mechanisms remain unclear. METHODS: Anosognosia and asomatognosia were examined in 62 patients undergoing the intracarotid amobarbital procedure as part of their preoperative evaluation for epilepsy surgery. Additional questions were asked in the last 32 patients studied. RESULTS: During inactivation of the non-language-dominant cerebral hemisphere, 88% of the 62 patients were unaware of their paralysis, and 82% could not recognize their own hand at some point. Only 3% did not exhibit anosognosia or asomatognosia. In general, asomatognosia resolved earlier than anosognosia. When patients could not recognize their hand, they uniformly thought that it was someone else's hand. Dissociations in awareness were seen in the second series of 32 patients. Although 23 patients (72%) thought that both arms were in the air, 31% pointed to the correct position of the paralyzed arm on the table. Despite the inability of 24 of 32 patients (75%) to recognize their own hand, 21% of these patients were aware that their arm was weak, and 38% had correctly located their paralyzed arm on the angiography table. CONCLUSIONS: Anosognosia and asomatognosia are both common during acute dysfunction of the non-language-dominant cerebral hemisphere. Dissociations of perception of location, weakness, and ownership of the affected limb are frequent, as are misperceptions of location and body part identity. The dissociations suggest that multiple mechanisms are involved.

Right cerebral specialization for tactile attention as evidenced by intracarotid sodium amytal.

Although several components of neglect syndrome have been reported to occur more frequently following right cerebral lesions, a right cerebral predominance for directed tactile attention has not been demonstrated. The intracarotid sodium amytal procedure (ISA, or Wada test) offers the opportunity to investigate differential effects for symmetric acute dysfunction of each cerebral hemisphere in each subject. In the present study, 18 patients undergoing preoperative evaluation for epilepsy surgery were trained in a nonverbal task of tactile attention. Left/right mean ISA dosages and left/right tactile test times postinjection were matched. Results revealed more correct responses following left ISA, and greater tactile inattention with more extinction-type responses following right ISA. No effect of seizure focus, sex, order of injection, or dosage was present. The finding that tactile inattention occurs more frequently with right cerebral dysfunction is consistent with right cerebral dominance for scanning attentional mechanisms directed at the external milieu.

The intracarotid amobarbital procedure as a predictor of memory failure following unilateral temporal lobectomy.

We investigated the efficacy of the intracarotid amobarbital procedure to accurately predict post-temporal lobectomy anterograde amnesia. We presented items at 2 separate times during amobarbital assessment; both early and late item recall were decreased during the injection contralateral to seizure onset indicating sensitivity to bilateral temporal lobe dysfunction. Ten patients for whom follow-up neuropsychological assessment was available failed either the early or late item recognition portions of their amobarbital evaluation ipsilateral to seizure onset, but had hippocampus included in the temporal lobectomy by virtue of satisfactory performance on other tests of hippocampal function. None of these 10 patients displayed postoperative anterograde amnesia, although there was a reduction in material-specific memory in some patients. These results indicate that relying solely on amobarbital memory testing to assess the functional ability of the contralateral temporal lobe to sustain global memory prior to temporal lobectomy may needlessly exclude patients from a viable therapeutic option.

Unilateral cerebral inactivation produces differential left/right heart rate responses.

We studied heart rate following unilateral hemispheric inactivation by intracarotid amobarbital in 25 patients undergoing preoperative evaluation for epilepsy surgery. Heart rate increased after left hemisphere inactivation, but decreased following right hemisphere inactivation. The results are consistent with differential left/right cerebral hemispheric effects on autonomic function, and appear related to functional and anatomic asymmetries in both the central and peripheral nervous systems.

Wada memory performance predicts seizure outcome following anterior temporal lobectomy.

We examined the ability of Wada memory testing to predict seizure outcome 1 year following anterior temporal lobectomy. Asymmetry scores for Wada memory performance, using amobarbital doses of 125 mg or less, were calculated for 55 patients under the age of 45 years who had no radiologic evidence of structural lesions other than gliosis. Wada memory asymmetries were significantly greater (p < 0.02) in patients who were seizure free compared with those who continued to experience seizures. Furthermore, patients with Wada memory score asymmetries of at least three objects (maximum = 8) were more likely to be seizure free compared with patients with Wada memory asymmetries less than three (p < 0.01). Of the 36 patients who had Wada memory score asymmetries of at least three objects, 32 (89%) were seizure free. In contrast, of the 19 patients whose Wada memory score asymmetries were less than three, only 12 (63%) were seizure free. These data suggest that Wada memory performance is related to seizure outcome following anterior temporal lobectomy.

Behavioral state-specific changes in human hippocampal theta activity.

Although there has been extensive examination of the behavioral and physiologic correlates of hippocampal theta activity in animals, the human literature consists of a single case study. We investigated the differential effects of four behavioral states on human hippocampal theta activity in 16 epilepsy surgery patients. Behavioral conditions included resting eyes closed (RC), resting eyes open (RO), eyes open with auditory word activation (AW), and eyes open with visuospatial activation (VS). Hippocampal theta activity decreased during both RO and VS compared to both RC and AW. There were reciprocal changes in delta activity. Comparisons of RO to VS and of RC to AW were nonsignificant. The results demonstrate state-specific changes in human hippocampal theta and are consistent with the animal literature that relates hippocampal theta to sensorimotor integration and forebrain volitional mechanisms.

Effects of anomalous language representation on neuropsychological performance in temporal lobe epilepsy.

OBJECTIVE: To examine the effects of anomalous language representation (i.e., mixed- and right-cerebral dominant) on neuropsychological performance. BACKGROUND: Right cerebral language dominance resulting from early cerebral injury is associated with relatively preserved language function with decreased visuospatial ability. However, previous reports of this phenomenon have examined patients with relatively large cerebral injuries (e.g., infantile hemiplegia) or limited sample sizes. METHODS: A total of 561 patients with complex partial seizures of left temporal lobe origin were studied. Patients were classified into left (n = 455), bilateral (n = 58), and right (n = 48) language dominant groups based on Wada testing. RESULTS: Right language dominant patients performed more poorly on multiple tests of visuospatial function, including Performance IQ (PIQ), than did left language patients. No significant group differences were detected for measures of language or general verbal function. The effects of bilateral language on PIQ differed according to handedness. Lowered PIQ was present in the bilateral nondextral group but not for bilateral dextral patients, and this pattern was observed with other visuospatial measures. CONCLUSIONS: In patients with relatively small lesions restricted to the left mesial temporal lobe, a shift in language dominance to the right hemisphere is associated with decreased visuospatial functions but preserved verbal abilities. Nondextral patients with bilateral language representation also displayed decreased visuospatial performance, although dextral patients with bilateral language did not.

Wada memory asymmetries predict verbal memory decline after anterior temporal lobectomy.

We examined Wada memory and neuropsychological memory function in 34 nonlesional patients who underwent anterior temporal lobectomy (ATL) and who were seizure free at 1-year follow-up. Patients who displayed a decline on verbal memory measures that exceeded 1 SD after left ATL had significantly smaller left/right Wada memory asymmetries than left ATL patients without a significant verbal memory decline. When Wada memory asymmetries were used to predict verbal memory decline after left ATL in individual patients, similar statistically significant effects were present. No significant relationship between Wada memory and postoperative memory was present in right ATL patients, and postoperative memory function was not related to Wada memory performance after either left hemisphere or right hemisphere injection alone. We conclude that Wada memory asymmetries provide one measure of the risk to material-specific decline in verbal memory after left ATL.

Wada memory testing and hippocampal volume measurements in the evaluation for temporal lobectomy.

We examined the relationship of Wada memory performance and MRI hippocampal volume measurements to laterality of ultimate seizure localization in 20 patients with complex partial seizures who later underwent temporal lobectomy. Discriminant function analysis employing both Wada memory test asymmetries and hippocampal volume asymmetries correctly classified 100% of the patients into left and right temporal lobe groups. Wada memory asymmetries alone correctly classified 90% of the sample (80% of the sample when the discriminant function included all patients except the one being classified), and hippocampal volume asymmetries alone correctly classified 90% of the patients. A significant correlation was present between Wada memory asymmetries and hippocampal volume asymmetries (r = 0.78), indicating that structural evidence of reduced hippocampal volume has a functional correlate reflected by Wada memory performance. These data suggest that the combination of functional and structural measures is of value in the preoperative evaluation for epilepsy surgery.

Human hippocampal EEG: effects of behavioral activation.

We studied spectral components of human hippocampal EEG in relation to behavioral status in 19 patients with intractable complex partial seizures who had depth electrodes implanted into the anterior hippocampi as a part of their preoperative evaluations. Behavioral conditions included: eyes closed resting, eyes open resting, eyes open with a verbal task, and eyes open with a visuospatial task. Hippocampal EEG spectral power uniformly decreased during behavioral activation. EEG activation was quantitatively different among the 3 activated conditions, with the most prominent change occurring during the visuospatial task. The degree of EEG activation corresponded inversely with the site of epileptic focus during the verbal task. The results demonstrate the response of human hippocampal EEG to behavioral activation. The magnitude of EEG change may reflect the degree of functional activation of the given hippocampus.

Differential-handed response to verbal and visual spatial stimuli: evidence of specialized hemispheric processing following callosotomy.

Left- and right-hand responses were studied in a patient who had undergone complete corpus callosotomy to examine selective hemispheric processing employing free-field stimuli. Tests of verbal and visual spatial processing were presented, and multiple choice performances were obtained using both left and right hands. A double dissociation emerged, with superior left-handed performance on visual spatial tasks, and better right-handed performance on verbal tasks. In addition, the patient displayed hemispatial dyscalculia in which he solved written arithmetic problems disregarding free-field numerical information presented toward his left. Evidence of multimodality left-sided extinction was also present. Further, despite unilateral callosal apraxia, the left hand displayed superiority during a continuous performance task. These results demonstrate that specialized functions of the cerebral hemispheres may be observed for response output in the absence of restricted hemispheric input, and that components of the neglect syndrome may be seen following corpus callosotomy.

Electrical stimulation of the human hippocampus produces verbal intrusions during memory testing.

Verbal memory testing was conducted during electrical stimulation of the human hippocampus in 12 epilepsy surgery candidates with unilateral temporal lobe seizure onset. Performance was assessed during baseline, left hippocampal stimulation and right hippocampal stimulation. Verbal intrusion errors were greater during electrical stimulation of the hippocampus contralateral to the seizure focus. These findings suggest that verbal intrusions are related to memory deficits, and that patients with cerebral disease who intrude words from an earlier portion of a learning test are likely to have bilateral cerebral dysfunction.