Evolution of the use of intraosseous vascular access in prehospital advanced cardiopulmonary resuscitation: The IOVA-CPR study.

INTRODUCTION: Obtaining vascular access is crucial in critically ill patients. The EZ-IO® device is easy to use and has a high insertion success rate. Therefore, the use of intraosseous vascular access (IOVA) has gradually increased. AIM: We aim to determine how IOVA was integrated into management of vascular access during out-of-hospital cardiac arrest (OHCA) resuscitation. METHODS: Analysing the data from the OHCA French registry for events occurring between 1 January 2013 and 15 March 2021, we studied: demography, circumstances of occurrence and management including vascular access, delays and evolution. The primary outcome was the rate of IOVA implantation. RESULTS: Among the 7156 OHCA included in the registry, we analysed the 3964 (55%) who received cardiopulmonary resuscitation. The vascular access was peripheral in 3122 (79%) cases, intraosseous in 775 (20%) cases and central in 12 (<1%) cases. The use of IOVA has increased linearly (R2 = 0.61) during the 33 successive trimesters studied representing 7% of all vascular access in 2013 and 33% in 2021 (p = 0.001). It was significantly more frequent in traumatic cardiac arrest: 12% versus 5%; p < 0.0001. The first epinephrine bolus occurred significantly later in the IOVA group, at 6 (4-10) versus 5 (3-8) min; p < 0.0001. Survival rate in the IOVA group was significantly lower, at 1% versus 7%; p < 0.0001. CONCLUSION: The insertion rate of IOVA significantly increased over the studied period, to reach 30% of all vascular access in the management OHCA patients. The place of the intraosseous route in the strategy of venous access during the management of prehospital cardiac arrest has yet to be determined.

Digit preference and biased conclusions in cardiac arrest studies.

BACKGROUND: In cardiac arrest (CA), time is directly predictive of patients' prognosis. The increase in mortality resulting from delayed cardiopulmonary resuscitation has been quantified minute by minute. Times reported in CA management studies could reflect a timestamping bias referred to as "digit preference". This phenomenon leads to a preference for certain numerical values (such as 2, 5, or 10) over others (such as 13). Our objective was to investigate whether or not digit preference phenomenon could be observed in reported times of the day related to CA management, as noted in a national registry. METHODS: We analyzed data from the French National Electronic Registry of Cardiac Arrests. We analyzed twelve times-of-the-day corresponding to each of the main steps of CA management reported by the emergency physicians who managed the patients in prehospital settings. We postulated that if CA occurred at random times throughout the day, then we could expect to see events related to CA management occurring at a similar rate each minute of each hour of the day, at a fraction of 1/60. We compared the fraction of times reported as multiples of 15 (0, 15, 30, and 45 - on the hour, quarters, half hour) with the expected fraction of 4/60 (i.e. 4 × 1/60). MAIN RESULTS: A total of 47,211 times-of-the-day in relation to 6131 CA were analyzed. The most overrepresented numbers were: 0, with 3737 occurrences (8% vs 2% expected, p < 0.0001) and 30, with 2807 occurrences (6% vs 2% expected, p < 0.0001). Times-of-the-day as multiples of 15 were overrepresented (22% vs 7% expected, p < 0.0001). CONCLUSION: Prospectively collected times were considerably influenced by digit preference phenomenon. Studies that are not based on automatic time recordings and that have not evaluated and considered this bias should be interpretated with caution.

Posterior Cingulate Epilepsy: A Systematic Review.

SUMMARY: In this review, authors discuss epilepsy originating from posterior cingulate regions, a challenging entity to diagnose and most likely underrecognized. A systematic review of posterior middle and posterior cingulate epilepsy cases was conducted to present a summary of current knowledge about this localization-based type of epilepsy. The literature search identified 32 articles, for a total of 69 patients (34 with posterior middle cingulate epilepsy [pMCE] and 35 with posterior cingulate epilepsy [PCE]). Most patients were children and young adults with drug-resistant lesional epilepsy with high seizure burden. In both groups, most patients reported auras, mainly sensory, but various types were reported, including autonomic, behavioral, and cognitive manifestations. Most pMCE and PCE showed motor manifestations (mainly respectively asymmetric tonic posturing and automotor features). Impaired awareness during seizures was more frequently reported in PCE than in pMCE. As for ictal scalp EEG, epileptogenic abnormalities were poorly lateralized and did not localize the seizure onset zone. An ictal temporal involvement was only observed in PCE. Interictal EEG findings were nonspecific. As for other presurgical noninvasive investigations, data are limited, and no studies have adequately assessed their value. Partly explained by our inclusion criteria, most patients underwent a surgical procedure (either lesionectomy or resection of epileptogenic zone as defined by intracranial EEG study results), which overall yielded good outcomes.

Déjà-vu evoked by electrical stimulation of the insula.

OBJECTIVE: Déjà-vu is a mental phenomenon commonly experienced during temporal lobe seizures and can be evoked by electrical stimulation of the temporal lobe. We analyzed reproducible déjà-vu experiences evoked by stimulating the insula in two patients with pharmacoresistant temporal lobe epilepsy. METHODS: We reviewed video-electroencephalography (EEG) recordings from extraoperative electrical cortical stimulation sessions. In addition, we performed the directed transfer function (DTF) effective connectivity measure of monopolar signals in Patient 1. To highlight elective changes due to each stimulation, we subtracted pre-stimulation DTF matrices from early poststimulation matrices. This analysis was performed for both non-inducing-déjàvu stimulation (control matrix) and déjà-vu-inducing stimulation (active matrix). Finally, the control matrix was subtracted from the active matrix. RESULTS: Comparison of effective connectivity during control stimulation versus déjà-vu-inducing stimulation revealed a reversal of connectivity levels in three main regions: the contralateral inferior insula (the ipsilateral insula could not be analyzed), bilateral mesiotemporal regions and the ipsilateral superior frontal gyrus. The drivers of evoked déjà-vu were the mesiotemporal regions (mainly ipsilateral) and the ipsilateral superior frontal gyrus. SIGNIFICANCE: Although our findings are possibly anecdotal, the insula may (in rare instances) remotely generate unexpected déjà-vu. If confirmed by further studies, this might change the assessment strategy for possible causes of anterior temporal lobectomy failure.

Déjà-vu evoked by electrical stimulation of the insula: Stimulation-induced insular déjà-vu.

OBJECTIVE: Déjà-vu is a mental phenomenon commonly experienced during temporal lobe seizures and can be evoked by electrical stimulation of the temporal lobe. We analyzed reproducible déjà-vu experiences evoked by stimulating the insula in two patients with pharmacoresistant temporal lobe epilepsy. METHODS: We reviewed video-electroencephalography (EEG) recordings from extraoperative electrical cortical stimulation sessions. In addition, we performed the directed transfer function (DTF) effective connectivity measure of monopolar signals in Patient 1. To highlight elective changes due to each stimulation, we subtracted pre-stimulation DTF matrices from early poststimulation matrices. This analysis was performed for both non-inducing-déjàvu stimulation (control matrix) and déjà-vu-inducing stimulation (active matrix). Finally, the control matrix was subtracted from the active matrix. RESULTS: Comparison of effective connectivity during control stimulation versus déjà-vu-inducing stimulation revealed a reversal of connectivity levels in three main regions: the contralateral inferior insula (the ipsilateral insula could not be analyzed), bilateral mesiotemporal regions and the ipsilateral superior frontal gyrus. The drivers of evoked déjà-vu were the mesiotemporal regions (mainly ipsilateral) and the ipsilateral superior frontal gyrus. SIGNIFICANCE: Although our findings are possibly anecdotal, the insula may (in rare instances) remotely generate unexpected déjà-vu. If confirmed by further studies, this might change the assessment strategy for possible causes of anterior temporal lobectomy failure.

Correcting for physiological ripples improves epileptic focus identification and outcome prediction.

OBJECTIVE: The integration of high-frequency oscillations (HFOs; ripples [80-250 Hz], fast ripples [250-500 Hz]) in epilepsy evaluation is hampered by physiological HFOs, which cannot be reliably differentiated from pathological HFOs. We evaluated whether defining abnormal HFO rates by statistical comparison to region-specific physiological HFO rates observed in the healthy brain improves identification of the epileptic focus and surgical outcome prediction. METHODS: We detected HFOs in 151 consecutive patients who underwent stereo-electroencephalography and subsequent resective epilepsy surgery at two tertiary epilepsy centers. We compared how HFOs identified the resection cavity and predicted seizure-free outcome using two thresholds from the literature (HFO rate > 1/min; 50% of the total number of a patient's HFOs) and three thresholds based on normative rates from the Montreal Neurological Institute Open iEEG Atlas (https://mni-open-ieegatlas. RESEARCH: mcgill.ca/): global Atlas threshold, regional Atlas threshold, and regional + 10% threshold after regional Atlas correction. RESULTS: Using ripples, the regional + 10% threshold performed best for focus identification (77.3% accuracy, 27% sensitivity, 97.1% specificity, 80.6% positive predictive value [PPV], 78.2% negative predictive value [NPV]) and outcome prediction (69.5% accuracy, 58.6% sensitivity, 76.3% specificity, 60.7% PPV, 74.7% NPV). This was an improvement for focus identification (+1.1% accuracy, +17.0% PPV; p < .001) and outcome prediction (+12.0% sensitivity, +1.0% PPV; p = .05) compared to the 50% threshold. The improvement was particularly marked for foci in cortex, where physiological ripples are frequent (outcome: +35.3% sensitivity, +5.3% PPV; p = .014). In these cases, the regional + 10% threshold outperformed fast ripple rate > 1/min (+3.6% accuracy, +26.5% sensitivity, +21.6% PPV; p < .001) and seizure onset zone (+13.5% accuracy, +29.4% sensitivity, +17.0% PPV; p < .05-.01) for outcome prediction. Normalization did not improve the performance of fast ripples. SIGNIFICANCE: Defining abnormal HFO rates by statistical comparison to rates in healthy tissue overcomes an important weakness in the clinical use of ripples. It improves focus identification and outcome prediction compared to standard HFO measures, increasing their clinical applicability.

Safety of an operculoinsulectomy in the language-dominant hemisphere for refractory epilepsy.

BACKGROUND: Operculoinsular cortectomy is increasingly recognized as a therapeutic avenue for perisylvian refractory epilepsy. However, most neurosurgeons are reluctant to perform this type of procedure because of feared neurological complications, especially in the language-dominant hemisphere, as the insula is involved in speech and language processes. The goal of this retrospective study is to quantify the incidence and types of speech and language deficits associated with operculoinsulectomies in the dominant hemisphere for language, and to identify factors associated with these complications. METHODS: Clinical, imaging, and surgical data of all patients who had an operculoinsulectomy for refractory epilepsy at our center between 1998 and 2018 were reviewed. Language lateralization was determined by functional magnetic resonance imaging (fMRI) and/or Wada test. Speech and language assessments were carried out by neurosurgeons, neurologists, neuropsychologists and/or speech language pathologists, before surgery, during the first week after surgery, and at least 6 months after surgery. RESULTS: Amongst 44 operculoinsulectomies, 13 were performed in the language-dominant hemisphere. 46% of these patients presented with transient aphasia post-surgery. However, a few months later, the patients' performances on language assessments were not statistically different from before surgery, thus suggesting a complete recovery of speech and language functions. CONCLUSION: Temporary aphasias after operculoinsulectomy for refractory epilepsy in the language-dominant hemisphere are frequent, but eventually subside. Potential mechanisms underlying this recovery are discussed.

Relationship between direct cortical stimulation and induced high-frequency activity for language mapping during SEEG recording.

OBJECTIVE: The authors assessed the clinical relevance of preoperative task-induced high-frequency activity (HFA) for language mapping in patients with refractory epilepsy during stereoelectroencephalography recording. Although HFA evaluation was described as a putative biomarker of cognition, its clinical relevance for mapping language networks was assessed predominantly by studies using electrocorticography (ECOG). METHODS: Forty-two patients with epilepsy who underwent intracranial electrode implantation during both task-induced HFA and direct cortical stimulation (DCS) language mapping were evaluated. The spatial and functional relevance of each method in terms of specificity and sensitivity were evaluated. RESULTS: The results showed that the two methods were able to map classic language regions, and a large and bilateral language network was obtained with induced HFA. At a regional level, differences were observed between methods for parietal and temporal lobes: HFA recruited a larger number of cortical parietal sites, while DCS involved more cortical temporal sites. Importantly, the results showed that HFA predicts language interference induced by DCS with high specificity (92.4%; negative predictive value 95.9%) and very low sensitivity (8.9%; positive predictive value 4.8%). CONCLUSIONS: DCS language mapping appears to be more appropriate for an extensive temporal mapping than induced HFA mapping. Furthermore, induced HFA should be used as a complement to DCS to preselect the number of stimulated sites during DCS, by omitting those reported as HFA-. This may be a considerable advantage because it allows a reduction in the duration of the stimulation procedure. Several parameters to be used for each method are discussed and the results are interpreted in relation to previous results reported in ECOG studies.

Characterization of the phenotype with cognitive impairment and protein mislocalization in SCA34.

OBJECTIVE: To better characterize the neurologic and cognitive profile of patients with spinocerebellar ataxia 34 (SCA34) caused by ELOVL4 mutations and to demonstrate the presence of ELOVL4 cellular localization and distribution abnormalities in skin-derived fibroblasts. METHODS: We investigated a 5-generation French-Canadian kindred presenting with a late-onset cerebellar ataxia and recruited age- and education-matched controls to evaluate the presence of neurocognitive impairment. Immunohistochemistry of dermal fibroblasts derived from a patient's skin biopsy was performed. RESULTS: Patients had a late-onset slowly progressive cerebellar syndrome (mean age at onset 47 years; range 32-60 years) characterized by truncal and limb ataxia, dysarthria, hypometric saccades, and saccadic pursuits. No patient had past or current signs of erythrokeratodermia variabilis, which had previously been reported. MRI revealed cerebellar atrophy, with pontine atrophy (4 of 6 patients), and cruciform hypersignal in the pons (2 of 6 patients). Fluorodeoxyglucose-PET showed diffuse cerebellar hypometabolism in all 5 tested patients with subtle parietal hypometabolism in 3. Significant cognitive deficits were found in executive functioning, along with apparent visuospatial, attention, and psychiatric involvement. Immunohistochemistry of dermal fibroblasts showed mislocalization of the ELOVL4 protein, which appeared punctate and aggregated, supporting a dominant negative effect of the mutation on protein localization. CONCLUSIONS: Our findings support the pathogenicity of ELOVL4 mutations in cerebellar dysfunction and provide a detailed characterization of the SCA34 phenotype, with neurocognitive changes typical of the cerebellar cognitive-affective syndrome.

Operculoinsular cortectomy for refractory epilepsy. Part 2: Is it safe?

OBJECTIVE: Operculoinsular cortectomy (also termed operculoinsulectomy) is increasingly recognized as a therapeutic option for perisylvian refractory epilepsy. However, most neurosurgeons are reluctant to perform the technique because of previously experienced or feared neurological complications. The goal of this study was to quantify the incidence of basic neurological complications (loss of primary nonneuropsychological functions) associated with operculoinsular cortectomies for refractory epilepsy, and to identify factors predicting these complications. METHODS: Clinical, imaging, and surgical data of all patients investigated and surgically treated by our team for refractory epilepsy requiring an operculoinsular cortectomy were retrospectively reviewed. Patients with tumors and encephalitis were excluded. Logistic regression analysis was used for uni- and multivariate statistical analyses. RESULTS: Forty-four operculoinsular cortectomies were performed in 43 patients. Although postoperative neurological deficits were frequent (54.5% of procedures), only 3 procedures were associated with a permanent significant neurological deficit. Out of the 3 permanent deficits, only 1 (2.3%; a sensorimotor hemisyndrome) was related to the technique of operculoinsular cortectomy (injury to a middle cerebral artery branch), while the other 2 (arm hypoesthesia and hemianopia) were attributed to cortical resection beyond the operculoinsular area. With multivariate analysis, a postoperative neurological deficit was associated with preoperative insular hypometabolism on PET scan. Postoperative motor deficit (29.6% of procedures) was correlated with fewer years of neurosurgical experience and frontal operculectomies, but not with corona radiata ischemic lesions. Ischemic lesions in the posterior two-thirds of the corona radiata (40.9% of procedures) were associated with parietal operculectomies, but not with posterior insulectomies. CONCLUSIONS: Operculoinsular cortectomy for refractory epilepsy is a relatively safe therapeutic option but temporary neurological deficits after surgery are frequent. This study highlights the role of frontal/parietal opercula resections in postoperative complications. Corona radiata ischemic lesions are not clearly related to motor deficits. There were no obvious permanent neurological consequences of losing a part of an epileptic insula, including on the dominant side for language. A low complication rate can be achieved if the following conditions are met: 1) microsurgical technique is applied to spare cortical branches of the middle cerebral artery; 2) the resection of an opercula is done only if the opercula is part of the epileptic focus; and 3) the neurosurgeon involved has proper training and experience.

Operculoinsular cortectomy for refractory epilepsy. Part 1: Is it effective?

OBJECTIVE: Patients with refractory epilepsy of operculoinsular origin are often denied potentially effective surgical treatment with operculoinsular cortectomy (also termed operculoinsulectomy) because of feared complications and the paucity of surgical series with a significant number of cases documenting seizure control outcome. The goal of this study was to document seizure control outcome after operculoinsular cortectomy in a group of patients investigated and treated by an epilepsy team with 20 years of experience with this specific technique. METHODS: Clinical, imaging, surgical, and seizure control outcome data of all patients who underwent surgery for refractory epilepsy requiring an operculoinsular cortectomy were retrospectively reviewed. Tumors and progressive encephalitis cases were excluded. Descriptive and uni- and multivariate analyses were done to determine seizure control outcome and predictors. RESULTS: Forty-three patients with 44 operculoinsular cortectomies were studied. Kaplan-Meier estimates of complete seizure freedom (first seizure recurrence excluding auras) for years 0.5, 1, 2, and 5 were 70.2%, 70.2%, 65.0%, and 65.0%, respectively. With patients with more than 1 year of follow-up, seizure control outcome Engel class I was achieved in 76.9% (mean follow-up duration 5.8 years; range 1.25-20 years). With multivariate analysis, unfavorable seizure outcome predictors were frontal lobe-like seizure semiology, shorter duration of epilepsy, and the use of intracranial electrodes for invasive monitoring. Suspected causes of recurrent seizures were sparing of the language cortex part of the focus, subtotal resection of cortical dysplasia/polymicrogyria, bilateral epilepsy, and residual epileptic cortex with normal preoperative MRI studies (insula, frontal lobe, posterior parieto-temporal, orbitofrontal). CONCLUSIONS: The surgical treatment of operculoinsular refractory epilepsy is as effective as epilepsy surgeries in other brain areas. These patients should be referred to centers with appropriate experience. A frontal lobe-like seizure semiology should command more sampling with invasive monitoring. Recordings with intracranial electrodes are not always required if the noninvasive investigation is conclusive. The complete resection of the epileptic zone is crucial to achieve good seizure control outcome.

Associated Factors and Prognostic Implications of Stimulus-Induced Rhythmic, Periodic, or Ictal Discharges.

IMPORTANCE: The implications of stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) sometimes found on prolonged electroencephalographic (EEG) recordings are uncertain. OBJECTIVE: To evaluate the incidence of SIRPIDs and their clinical implications in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, international retrospective study was performed from October 1, 2012, through September 30, 2014, of consecutive adult patients hospitalized in intensive care units with alteration of consciousness who underwent EEG recordings at 3 separate centers. Demographic data, including admission diagnosis, age, sex, history of epilepsy, and EEG findings, were noted. Characteristics of SIRPIDs were documented. Data were evaluated for predictors of SIRPIDs and in-hospital mortality. Data analysis was performed from January 16, 2015, to June 15, 2015. MAIN OUTCOMES AND MEASURES: Incidence of SIRPIDs, association of SIRPIDs with mortality and other EEG characteristics, and EEG and clinical predictors of mortality. RESULTS: A total of 416 patients were studied. The median age of patients was 60 years (interquartile range, 46-71 years), and 252 (60.6%) were male. A total of 104 patients (25.0%) did not survive to hospital discharge. SIRPIDs were identified in 43 patients (10.3%). The proportion of patients with SIRPIDs was not significantly different across the 3 sites (P = .34). Anoxic brain injury (odds ratio [OR], 3.80; 95% CI, 1.73-8.33; P < .001), the use of antiepileptic medications (OR, 3.24; 95% CI, 1.31-8.00; P = .01), electrographic seizures (OR, 2.85; 95% CI, 1.13-7.19; P = .03), generalized periodic discharges with triphasic morphologic features (OR, 3.66; 95% CI, 1.67-8.02; P = .001), and sporadic sharp waves and periodic discharges (OR, 2.59; 95% CI, 1.13-5.92; P = .02) were independently associated with the presence of SIRPIDs. Older age (OR, 1.02; 95% CI, 1.01-1.04; P = .005), anoxic brain injury (OR, 3.49; 95% CI, 1.96-6.21; P ≤ .001), and absence of EEG reactivity (OR, 8.14; 95% CI, 4.20-15.79; P < .001) but not SIRPIDs (OR, 1.73; 95% CI, 0.79-3.78; P = .17) were independently associated with in-hospital mortality. CONCLUSIONS AND RELEVANCE: In critically ill patients undergoing EEG recordings, SIRPIDs occurred in 43 (10.3%) and were associated with other electrographic abnormalities previously reported to indicate poor prognosis. However, SIRPIDs were not independently associated with in-hospital mortality.

Therapies for ataxias.

OPINION STATEMENT: Ataxia can originate from many genetic defects, but also from nongenetic causes. To be able to provide treatment, the first step is to establish the right diagnosis. Once the cause of the ataxia is defined, some specific treatments may be available. For example, the nongenetic ataxias that arise from vitamin deficiencies can improve following treatment. In most cases, however, therapies do not cure the disease and are purely symptomatic. Physiotherapy and occupational therapy are effective in all type of ataxias and often remain the most efficient treatment option for these patients to maximize their quality of life.