Oral and fecal microbiota perturbance in cocaine users: Can rTMS-induced cocaine abstinence support eubiosis restoration?

The effects of cocaine on microbiota have been scarcely explored. Here, we investigated the gut (GM) and oral (OM) microbiota composition of cocaine use disorder (CUD) patients and the effects of repetitive transcranial magnetic stimulation (rTMS). 16S rRNA sequencing was used to characterize GM and OM, whereas PICRUST2 assessed functional changes in microbial communities, and gas-chromatography was used to evaluate fecal short and medium chain fatty acids. CUD patients reported a significant decrease in alpha diversity and modification of the abundances of several taxa in both GM and OM. Furthermore, many predicted metabolic pathways were differentially expressed in CUD patients' stool and saliva samples, as well as reduced levels of butyric acid that appear restored to normal amounts after rTMS treatment. In conclusion, CUD patients showed a profound dysbiotic fecal and oral microbiota composition and function and rTMS-induced cocaine abstinence determined the restoration of eubiotic microbiota.

Do changes in SSEP amplitude over time predict the outcome of comatose survivors of cardiac arrest?

AIM: To assess if the amplitude of the N20 wave (N20Amp) of somatosensory evoked potentials (SSEPs) changes between 12-24 h and 72 h from the return of spontaneous circulation (ROSC) after cardiac arrest and if an N20Amp decrease predicts poor neurological outcome (CPC 3-5) at six months. SETTING: Retrospective analysis of the ProNeCA multicentre prognostication study dataset. (NCT03849911). METHODS: In adult comatose cardiac arrest survivors whose SSEPs were recorded at both 12-24 h and 72 h after ROSC, we measured the median N20Amp at each timepoint and the individual change in N20Amp across the two timepoints. We identified their cutoffs for predicting poor outcome with 0% false positive rate (FPR) and compared their sensitivities. RESULTS: We included 236 patients. The median [IQR] N20Amp increased from 1.90 [0.78-4.22] µV to 2.86 [1.52-5.10] µV between 12-24 h and 72 h (p = 0.0019). The N20Amp cutoff for 0% FPR increased from 0.6 µV at 12-24 h to 1.23 µV at 72 h, and its sensitivity increased from 56[48-64]% to 71[63-77]%. Between 12-24 h and 72 h, an N20Amp decrease > 53% predicted poor outcome with 0[0-5]% FPR and 26[19-35]% sensitivity. Its combination with an N20Amp < 1.23 µV at 72 h increased sensitivity by 1% to 72[64-79]%. CONCLUSION: In comatose cardiac arrest survivors, the median N20Amp and its cutoff for predicting poor neurological outcome increase between 12-24 and 72 h after ROSC. An N20Amp decrease greater than 53% between these two timepoints predicts poor outcome with 0% FPR, confirming the unfavourable prognostic signal of a low N20Amp at 72 h.

Eye-opening in brain death: A case report and review of the literature.

Background: According to Italian law, brain death is diagnosed when the patient is in a coma, showing the absence of respiratory drive under specific clinical conditions, and without any brain stem reflexes. On the other hand, presence of spinal reflexes, when correctly identified, does not hamper the diagnosis. Case report: We present a case of eyelid elevation two seconds after thoracic pain stimulation in a patient who otherwise fulfilled all clinical and instrumental brain-death criteria due to a residual preserved function of the superior cervical ganglion. Conclusion: Although the observed reflex is to be considered extracerebral, and therefore it should not hamper the diagnosis of BD, the authors propose implementing cerebral flow evaluation, considered "prudential", as a preliminary assessment before determining BD.

Multiple Electroencephalogram Recordings for Monitoring the Evolution of Neurological Complications during Baclofen Withdrawal Syndrome.

Baclofen withdrawal syndrome represents a clinical emergency that can lead to life-threatening complications. It is often a diagnostic challenge because of its nonspecific nature of presentation and degree of symptom overlap with other clinical diseases. Electroencephalography (EEG) might provide important supporting evidence when neurological complications are involved. We present the case of a 55-year-old woman with sudden onset of motor manifestations at the limbs and an altered mental status 24 hours after cessation of intrathecal baclofen administration, following the removal of the pump due to infection, in whom a computed tomography did not show any acute-onset brain injuries, and multiple EEG recordings were performed. The first EEG showed the presence of bilateral sharply contoured waves, in the absence of epileptic discharges and seizures. No correlation between motor manifestations and EEG changes were detected. This EEG pattern was considered to be the expression of an overexcitation of the central nervous system (CNS) due to the loss of baclofen inhibitory effects, excluding an epileptic origin of motor manifestations. Another EEG, performed 24 hours later, showed the presence of triphasic waves with severe generalised slowing, suggesting the presence of encephalopathy. The last EEG, performed 48 hours after the previous recording, when a recovered state of consciousness was already present, showed regression of the triphasic waves and a reorganisation of the background activity. In our case, repeated EEG evaluation allowed monitoring the evolution of acute encephalopathy developed during baclofen withdrawal syndrome, from the initial phase of CNS hyperexcitability, through the phase of metabolic encephalopathy, and to its resolution. This modality allowed for optimising the diagnostic-therapeutic management of the patient during her stay in the intensive care unit.

A randomised, double-blind, sham-controlled study of left prefrontal cortex 15 Hz repetitive transcranial magnetic stimulation in cocaine consumption and craving.

BACKGROUND: Cocaine use disorder (CUD) is a global health issue with no effective treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) is a recently proposed therapy for CUD. METHODS: We conducted a single-center, randomised, sham-controlled, blinded, parallel-group research with patients randomly allocated to rTMS (15 Hz) or Sham group (1:1) using a computerised block randomisation process. We enrolled 62 of 81 CUD patients in two years. Patients were followed for eight weeks after receiving 15 15 Hz rTMS/sham sessions over the left dorsolateral prefrontal cortex (DLPFC) during the first three weeks of the study. We targeted the DLFPC following the 5 cm method. Cocaine lapses in twice a week urine tests were the primary outcome. The secondary outcomes were craving severity, cocaine use pattern, and psychometric assessments. FINDINGS: We randomly allocated patients to either an active rTMS group (32 subjects) or a sham treatment group (30 subjects). Thirteen (42%) and twelve (43.3%) of the subjects in rTMS and sham groups, respectively, completed the full trial regimen, displaying a high dropout rate. Ten/30 (33%) of rTMS-treated patients tested negative for cocaine in urine, in contrast to 4/27 of placebo controls (p = 0.18, odd ratio 2.88, CI 0.9-10). The Kaplan-Meier survival curve did not state a significant change between the treated and sham groups in the time of cocaine urine negativisation (p = 0.20). However, the severity of cocaine-related cues mediated craving (VAS peak) was substantially decreased in the rTMS treated group (p<0.03) after treatment at T1, corresponding to the end of rTMS treatment. Furthermore, in the rTMS and sham groups, self-reported days of cocaine use decreased significantly (p<0.03). Finally, psychometric impulsivity parameters improved in rTMS-treated patients, while depression scales improved in both groups. CONCLUSIONS: In CUD, rTMS could be a useful tool for lowering cocaine craving and consumption. TRIAL REGISTRATION: The study number on clinicalTrials.gov is NCT03607591.

SSEP amplitude accurately predicts both good and poor neurological outcome early after cardiac arrest; a post-hoc analysis of the ProNeCA multicentre study.

AIM: To assess if, in comatose resuscitated patients, the amplitude of the N20 wave (N20amp) of somatosensory evoked potentials (SSEP) can predict 6-months neurological outcome. SETTING: Multicentre study in 13 Italian intensive care units. METHODS: The N20amp in microvolts (µV) was measured at 12 h, 24 h, and 72 h from cardiac arrest, along with pupillary reflex (PLR) and a 30-min EEG classified according to the ACNS terminology. Sensitivity and false positive rate (FPR) of N20amp alone or in combination were calculated. RESULTS: 403 patients (age 69[58-68] years) were included. At 12 h, an N20amp >3 µV predicted good neurological outcome (Cerebral Performance Categories [CPC] 1-2) with 61[50-72]% sensitivity and 11[6-18]% FPR. Combining it with a benign (continuous or nearly continuous) EEG increased sensitivity to 91[82-96]%. For poor outcome (CPC 3-5), an N20Amp ≤0.38 µV, ≤0.73 µV and ≤1.01 µV at 12 h, 24 h, and 72 h, respectively, had 0% FPR with sensitivity ranging from 61[51-69]% and 82[76-88]%. Sensitivity was higher than that of a bilaterally absent N20 at all time points. At 12 h and 24 h, a highly malignant (suppression or burst-suppression) EEG and bilaterally absent PLR achieved 0% FPR only when combined with SSEP. A combination of all three predictors yielded a 0[0-4]% FPR, with maximum sensitivity of 44[36-53]%. CONCLUSION: At 12 h from arrest, a high N20Amp predicts good outcome with high sensitivity, especially when combined with benign EEG. At 12 h and 24 h from arrest a low-voltage N20amp has a high sensitivity and is more specific than EEG or PLR for predicting poor outcome.

Electrodiagnostic findings in patients with non-COVID-19- and COVID-19-related acute respiratory distress syndrome.

BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) is a frequent neurological manifestation in patients with acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19) infection. CIPNM diagnosis is usually limited to clinical evaluation. We compared patients with ARDS from COVID-19 and other aetiologies, in whom a neurophysiological evaluation for the detection of CIPNM was performed. The aim was to determine if there were any differences between these two groups in frequency of CINPM and outcome at discharge from the intensive care unit (ICU). MATERIALS AND METHODS: This was a single-centre retrospective study performed on mechanically ventilated patients consecutively admitted (January 2016-June 2020) to the ICU of Careggi Hospital, Florence, Italy, with ARDS of different aetiologies. Neurophysiological evaluation was performed on patients with stable ventilation parameters, but marked widespread hyposthenia (Medical Research Council score <48). Creatine phosphokinase (CPK), lactic dehydrogenase (LDH) and mean morning glycaemic values were collected. RESULTS: From a total of 148 patients, 23 with COVID-19 infection and 21 with ARDS due to other aetiologies, underwent electroneurography/electromyography (ENG/EMG) recording. Incidence of CIPNM was similar in the two groups, 65% (15 of 23) in COVID-19 patients and 71% (15 of 21) in patients affected by ARDS of other aetiologies. At ICU discharge, subjects with CIPNM more frequently required ventilatory support, regardless the aetiology of ARDS. CONCLUSION: ENG/EMG represents a useful tool in the identification of the neuromuscular causes underlying ventilator wean failure and patient stratification. A high incidence of CIPNM, with a similar percentage, has been observed in ARDS patients of all aetiologies.

Are neurophysiologic tests reliable, ultra-early prognostic indices after cardiac arrest?

OBJECTIVES: Determining early and reliable prognosis in comatose subjects after cardiac arrest is a central component of post-cardiac arrest care both for developing realistic prognostic expectations for families, and for better determining which resources are mobilized or withheld for individual patients. The aim of the study was to evaluate the prognostic accuracy of EEG and SEP patterns during the very early period (within the first 6 h) after cardiac arrest. METHODS: We retrospectively analysed comatose patients after CA, either inside or outside the hospital, in which prognostic evaluation was made during the first 6 h from CA. Prognostic evaluation comprised clinical evaluation (GCS and pupillary light reflex) and neurophysiological (electroencephalography (EEG) and somatosensory evoked potentials (SEP)) studies. Prognosis was evaluated with regards to likelihood of recovery of consciousness and also likelihood of failure to regain consciousness. RESULTS: Forty-one comatose patients after cardiac arrest were included. All patients with continuous and nearly continuous EEG recovered consciousness. Isoelectric EEG was always associated with poor outcome. Burst-suppression, suppression and discontinuous patterns were usually associated with poor outcome although some consciousness recovery was observed. Bilaterally absent SEP responses were always associated with poor outcome. Continuous and nearly continuous EEG patterns were never associated with bilaterally absent SEP. CONCLUSIONS: During the very early period following cardiac arrest (first 6 h), EEG and SEP maintain their high predictive value to predict respectively recovery and failure of recovery of consciousness. A very early EEG exam allows identification of patients with very high probability of a good outcome, allowing rapid use of the most appropriate therapeutic procedures.

Severe neurological nicotine intoxication by e-cigarette liquids: Systematic literature review.

Electronic cigarettes are a popular, easily purchased, alternative source of nicotine that is considered safer than conventional tobacco. However, Intentional or accidental exposure to e-liquid substances, mainly nicotine, can lead to serious, potentially fatal toxicity. Emergency and critical care physicians should keep in mind acute intoxication of this poison with a biphasic toxic syndrome. We highlight its potentially fatal outcome and suggest monitoring the adverse effects of nicotine according to a multimodal protocol integrating somatosensory evoked potentials, electroencephalography and neuroimaging data with anamnestic report and toxicological and laboratory data.

Does a combination of ≥2 abnormal tests vs. the ERC-ESICM stepwise algorithm improve prediction of poor neurological outcome after cardiac arrest? A post-hoc analysis of the ProNeCA multicentre study.

BACKGROUND: Bilaterally absent pupillary light reflexes (PLR) or N20 waves of short-latency evoked potentials (SSEPs) are recommended by the 2015 ERC-ESICM guidelines as robust, first-line predictors of poor neurological outcome after cardiac arrest. However, recent evidence shows that the false positive rates (FPRs) of these tests may be higher than previously reported. We investigated if testing accuracy is improved when combining PLR/SSEPs with malignant electroencephalogram (EEG), oedema on brain computed tomography (CT), or early status myoclonus (SM). METHODS: Post-hoc analysis of ProNeCA multicentre prognostication study. We compared the prognostic accuracy of the ERC-ESICM prognostication strategy vs. that of a new strategy combining ≥2 abnormal results from any of PLR, SSEPs, EEG, CT and SM. We also investigated if using alternative classifications for abnormal SSEPs (absent-pathological vs. bilaterally-absent N20) or malignant EEG (ACNS-defined suppression or burst-suppression vs. unreactive burst-suppression or status epilepticus) improved test sensitivity. RESULTS: We assessed 210 adult comatose resuscitated patients of whom 164 (78%) had poor neurological outcome (CPC 3-5) at six months. FPRs and sensitivities of the ≥2 abnormal test strategy vs. the ERC-ESICM algorithm were 0[0-8]% vs. 7 [1-18]% and 49[41-57]% vs. 63[56-71]%, respectively (p < .0001). Using alternative SSEP/EEG definitions increased the number of patients with ≥2 concordant test results and the sensitivity of both strategies (67[59-74]% and 54[46-61]% respectively), with no loss of specificity. CONCLUSIONS: In comatose resuscitated patients, a prognostication strategy combining ≥2 among PLR, SSEPs, EEG, CT and SM was more specific than the 2015 ERC-ESICM prognostication algorithm for predicting 6-month poor neurological outcome.

Is there inter-observer variation in the interpretation of SSEPs in comatose cardiac arrest survivors? Further considerations following the Italian multicenter ProNeCa study.

BACKGROUND: Bilateral absence of N20 peak in median nerve Somatosensory Evoked Potentials (SSEPs) is considered the most valid predictor of poor outcome in comatose survivors after cardiopulmonary resuscitation. We investigated the consistency in interpreting SSEP recordings in a multicentre study. METHODS: 44 SSEP recordings randomly extracted from 600 recordings of 392 patients included in the "Prognostication of Neurological outcome after Cardiac Arrest (ProNeCa) study" were blindly read by three expert neurophysiologists. Agreement between raters, and individual agreement of each rater vs. reference standard (RS), were calculated using Kappa Coefficients. Inter-rater reliability was calculated with Intra-class Correlation Coefficient (ICC). RESULTS: When raters had to evaluate the presence of N20 with normal amplitude, the inter-rater agreement was very high (Kappa = 0.84). In the case of N20 absence the agreement was good (Kappa = 0.66), but when N20 amplitude was low, the agreement decreased to moderate (Kappa = 0.579) becoming even weaker when it was "Non Assessable" (Kappa = 0.107). The agreement of each rater with the RS had a range from moderate to very good; rater1 Kappa = 0.589 (95%CI 0.397-0.781; p < 0.001), rater2 Kappa = 0.644 (95%CI 0.460-0.828; p < 0.001), rater3 Kappa = 0.859 (95%CI 0.698-1.000; p < 0.001). The ICC was barely good, 0.682 (95%CI 0.539-0.798; p = 0.0075). CONCLUSION: Different health professionals, using different equipment in a multicentre study, had very good inter-rater agreement in interpreting SSEP records. The interpretation of "Non Assessable" SEPPs, mainly in relation to noise level, is still a crucial issue because it increases rater uncertainty. For this reason, it is important to focus on improving recording quality and interpretation of records.

Electroencephalography during SARS-CoV-2 outbreak: practical recommendations from the task force of the Italian Society of Neurophysiology (SINC), the Italian League Against Epilepsy (LICE), and the Italian Association of Neurophysiology Technologists (AITN).

BACKGROUND: During COVID-19 lockdown, non-urgent medical procedures were suspended. Grade of urgency of electroencephalography (EEG) may vary according to the clinical indication, setting, and status of infection of SARS-CoV-2 virus. "Italian Society of Clinical Neurophysiology" (SINC), "Italian League Against Epilepsy" (LICE), and the "Italian Association of Neurophysiology Technologists" (AITN) aimed to provide clinical and technical recommendation for EEG indications and recording standards in this pandemic era. METHODS: Presidents of SINC, LICE, and AITN endorsed three members per each society to formulate recommendations: classification of the degree of urgency of EEG clinical indications, management and behavior of physicians and neurophysiology technologists, hygiene and personal protection standards, and use of technical equipment. RESULTS: Scientific societies endorsed a paper conveying the recommendation for EEG execution in accordance with clinical urgency, setting (inpatients/outpatients), status of SARS-CoV-2 virus infection (positive, negative and uncertain), and phase of governmental restrictions (phase 1 and 2). Briefly, in phase 1, EEG was recommended only for those acute/subacute neurological symptoms where EEG is necessary for diagnosis, prognosis, or therapy. Outpatient examinations should be avoided in phase 1, while they should be recommended in urgent cases in phase 2 when they could prevent an emergency room access. Reduction of staff contacts must be encouraged through rescheduling job shifts. The use of disposable electrodes and dedicated EEG devices for COVID-19-positive patients are recommended. CONCLUSIONS: During the different phases of COVID-19 pandemic, the EEG should be reserved for patients really benefiting from its execution in terms of diagnosis, treatment, prognosis, and avoidance of emergency room access.

Brain death following ingestion of E-cigarette liquid nicotine refill solution.

BACKGROUND: The use of electronic cigarettes (e-cigarettes) is very common worldwide. To date, an increase of nicotine intoxication following an accidental or intentional ingestion/injection of refill solution (e-liquid) has been detected. CASE: A 23-year-old man presented with sudden loss of consciousness, bradycardia, and respiratory muscle paralysis after intentional ingestion of e-liquid. Early clinical data, brain computed tomography, and neurophysiological tests (electroencephalogram [EEG] and somatosensory evoked potentials [SEPs]) did not show features with a poor neurological prognostic meaning of an hypoxic encephalopathy. After 4 days, the patient showed bilateral loss of the pupillary reflex, and severe and cytotoxic edema was detected on brain magnetic resonance imaging. SEPs showed a bilateral loss of cortical responses and EEG a suppressed pattern. Nine days after the onset of coma, the patient evolved toward brain death (BD). DISCUSSION: Because nicotine intoxication might cause respiratory muscle paralysis, without cardiac arrest (CA), it would be important to understand the mechanisms underlying brain damage and to take into account that the current neurological prognostic evidence for hypoxic-ischemic encephalopathy, based on data from patients who all experienced CA may not be reliable. Reporting cases of nicotine intoxication through e-liquid is relevant in order to improve regulatory parameters for e-liquid sale.

EEG and Coma Recovery Scale-Revised prediction of neurological outcome in Disorder of Consciousness patients.

OBJECTIVE: According to electroencephalogram (EEG) descriptors included in the American Clinical Neurophysiology Society (ACNS) terminology, we generated a score, and we compared it to the EEG scores previously proposed in order to identify the one with the best prognostic power for neurological outcome at post-acute stages in patients with severe disorders of consciousness (DoC). MATERIALS AND METHODS: Patients included in the analysis were clinically evaluated with the Coma Recovery Scale-Revised (CRS-R). An EEG was performed within the first week after admission to Intensive Rehabilitation Unit (IRU). EEGs were classified according to the ACNS terminology and to the scores of Bagnato and Estraneo. RESULTS: A total of 260 patients admitted to the IRU were analysed. A total of 160 patients (61%) improved their consciousness level during IRU stay. EEG score based on the ANCS terminology showed higher overall performance (receiver-operating area under the curve = 0.79) and greater sensitivity (65%), at comparable specificities (80%), for clinical improvement as compared to both CRS-R admission score and other EEG scores. Combining our EEG score with CRS-R score at admission, the cumulative sensitivity increased to 76% when at least one good prognostic index test was present in the same patient, whereas specificity increased up to 93% if both the good prognostic patterns of clinical and instrumental parameters were simultaneously present. CONCLUSION: The EEG scored according to the ACNS terminology is the best among those looked at for the prediction of short-term clinical improvement in patients with DoC and represents a useful instrumental test, complementary to clinical evaluation at admission, to be added in post-acute neurological prognostication methods.

Neurophysiology for predicting good and poor neurological outcome at 12 and 72 h after cardiac arrest: The ProNeCA multicentre prospective study.

AIMS: To assess the accuracy of electroencephalogram (EEG) and somatosensory evoked potentials (SEPs) recorded at 12 and 72 h from resuscitation for predicting six-months neurological outcome in patients who are comatose after cardiac arrest. METHODS: Prospective multicentre prognostication study. EEG was classified according to the American Clinical Neurophysiology Society terminology. SEPs were graded according to the presence and amplitude of their cortical responses. Neurological outcome was defined as good (cerebral performance categories [CPC] 1-3) vs. poor (CPC 4-5). None of the patients underwent withdrawal of life-sustaining treatment. RESULTS: A total of 351 patients were included, of whom 134 (38%) had good neurological outcome. At 12 h, a continuous, nearly continuous and low-voltage EEG pattern predicted good neurological outcome with 71[61-80]% sensitivity, while an isoelectric EEG and a bilaterally absent/absent-pathological amplitude (AA/AP) cortical SEP pattern predicted poor neurological outcome with 14[8-21]% and 59[50-68]% sensitivity, respectively. Specificity was 100[97-100]% for all predictors. At 72 h, both an isoelectric, suppression or burst-suppression pattern on EEG and an AA/AP SEP pattern predicted poor outcome with 100[97-100]% specificity. Their sensitivities were 63[55-70]% and 66[58-74]%, respectively. When EEG and SEPs were combined, sensitivity for poor outcome prediction increased to 79%. CONCLUSIONS: In comatose resuscitated patients, EEG and SEPs predicted good and poor neurological outcome respectively, with 100% specificity as early as 12 h after cardiac arrest. At 72 h after arrest, unfavourable EEG and SEP patterns predicted poor neurological outcome with 100% specificity and high sensitivity, which further increased after their combination.

Neurophysiological and neuroradiological test for early poor outcome (Cerebral Performance Categories 3-5) prediction after cardiac arrest: Prospective multicentre prognostication data.

The data presented here are related to our research article entitled "Neurophysiology and neuroimaging accurately predict poor neurological outcome within 24 hours after cardiac arrest: a prospective multicentre prognostication study (ProNeCA)" [1]. We report a secondary analysis on the ability of somatosensory evoked potentials (SEPs), brain computed tomography (CT) and electroencephalography (EEG) to predict poor neurological outcome at 6 months in 346 patients who were comatose after cardiac arrest. Differently from the related research article, here we included cerebral performance category (CPC) 3 among poor outcomes, so that the outcomes are dichotomised as CPC 1-2 (absent to mild neurological disability: good outcome) vs. CPC 3-5 (severe neurological disability, persistent vegetative state, or death: poor outcome). The accuracy of the index tests was recalculated accordingly. A bilaterally absent/absent-pathological amplitude (AA/AP) N20 SEPs wave, a Grey Matter/White Matter (GM/WM) ratio <1.21 on brain CT and an isoelectric or burst suppression EEG predicted poor outcome with 49.6%, 42.2% and 29.8% sensitivity, respectively, and 100% specificity. The distribution of positive results of the three predictors did not overlap completely in the population of patients with poor outcome, so that when combining them the overall sensitivity raised to 61.2%.

Neurophysiology and neuroimaging accurately predict poor neurological outcome within 24 hours after cardiac arrest: The ProNeCA prospective multicentre prognostication study.

AIMS: To investigate the ability of 30-min electroencephalogram (EEG), short-latency somatosensory evoked potentials (SEPs) and brain computed tomography (CT) to predict poor neurological outcome (persistent vegetative state or death) at 6 months in comatose survivors of cardiac arrest within 24 h from the event. METHODS: Prospective multicentre prognostication study in seven hospitals. SEPs were graded according to the presence and amplitude of their cortical responses, EEG patterns were classified according to the American Clinical Neurophysiology Society terminology and brain oedema on brain CT was measured as grey/white matter (GM/WM) density ratio. Sensitivity for poor outcome prediction at 100% specificity was calculated for the three tests individually and in combination. None of the patients underwent withdrawal of life-sustaining treatments before the index event occurred. RESULTS: A total of 346/396 patients were included in the analysis. At 6 months, 223(64%) had poor neurological outcome; of these, 68 were alive in PVS. Bilaterally absent/absent-pathological amplitude cortical SEP patterns, a GM/WM ratio<1.21 on brain CT and isoelectric/burst-suppression EEG patterns predicted poor outcome with 100% specificity and sensitivities of 57.4%, 48.8% and 34.5%, respectively. At least one of these unfavourable patterns was present in 166/223 patients (74.4% sensitivity). Two unfavourable patterns were simultaneously present in 111/223 patients (49.7% sensitivity), and three patterns in 38/223 patients (17% sensitivity). CONCLUSIONS: In comatose resuscitated patients, a multimodal approach based on results of SEPs, EEG and brain CT accurately predicts poor neurological outcome at 6 months within the first 24 h after cardiac arrest.

Prognostic value of post-acute EEG in severe disorders of consciousness, using American Clinical Neurophysiology Society terminology.

OBJECTIVE: To evaluate whether electroencephalographic (EEG) features recorded during the post-acute stage in patients with severe disorders of consciousness (DoC) after acute brain injury (ABI), contribute to neurological outcome prediction of these patients at discharge from the intensive rehabilitation unit (IRU). METHODS: We retrospectively evaluated all patients consecutively admitted to the IRU from August 2012 to December 2016. Inclusion criteria were: 1) age >18years, 2) patients with unresponsive wakefulness syndrome (UWS) or in a minimally conscious state (MCS), and 3) EEG and a coma recovery scale-revised (CRS-R) score available within the first week after admission. Clinical evaluation was performed using the Italian version of the CRS-R score. EEGs were classified according to American Clinical Neurophysiology Society (ACNS) terminology. Clinical state at final discharge was evaluated using the CRS-R score. RESULTS: In total, 102 patients were included in the analysis. After a mean of five months of IRU stay, among the 61 UWS subjects, 19 transitioned to MCS and 11 recovered to exit-MCS (E-MCS); twenty-three of the 41 subjects in MCS progressed to E-MCS. Using logistic regression, consciousness level (UWS/MCS-OR=13.4), CRS-R score at admission (OR=1.33) and use of activating drugs (OR=4.7) were significant predictors of clinical improvement. Multivariable analysis showed that specific EEG patterns were independent predictors of improved consciousness at discharge in UWS patients. DISCUSSION: EEG performed within the first week after IRU admission, classified according to ACNS-terminology in patients with UWS at admission, can provide useful prognostic contribution.

Efficacy of high-frequency (15Hz) repetitive transcranial magnetic stimulation (rTMS) of the left premotor cortex/dorsolateral prefrontal cortex in decreasing cocaine intake (the MagneTox study): A study protocol for a randomized placebo-controlled pilot trial.

BACKGROUND: Cocaine use disorder (CUD) is very common and has psychological and physical consequences. Patients with CUD present hypoactivity of the prefrontal cortical area. Thus, excitatory repetitive transcranial magnetic stimulation (rTMS) targeting the premotor cortex/dorsolateral prefrontal cortex (PMC/DLPFC), given its ability to increase prefrontal area excitability and to modulate cortico-limbic activity, could result in a decrease in cocaine intake. METHODS: We designed a protocol for a monocentric, randomized, double-blind, placebo-controlled, parallel-group pilot trial, with the principal aim of assessing the efficacy of rTMS on the reduction of cocaine intake. Patients with CUD will be recruited according to inclusion and exclusion criteria, and then randomized to undergo active or sham rTMS. Our rTMS protocol will consist of 15 days of 15Hz rTMS targeting the left PMC/DLPFC. Toxicological and psychiatric assessments, urine drug tests, the Cocaine Craving Questionnaire (CCQ) and the Visual Analogic Scale (VAS) will be used to assess changes from baseline in cocaine intake and craving, mood and quality of life. DISCUSSION: Only a few studies have evaluated the efficacy of rTMS for CUD treatment in humans, with limitations concerning small sample size, short treatment duration, different rTMS protocols and the absence of a placebo-controlled group. Our study will attempt to overcome these shortcomings and will provide data that can be used for future larger studies of non-invasive left PMC/DLPFC stimulation as a treatment for CUD.