TROPONIN LEVELS IN TRANSIENT ISCHEMIC ATTACK AND ISCHEMIC STROKE: DOES "TRANSIENT" IN YOUR BRAIN MEAN "BETTER" FOR YOUR HEART?

PURPOSE: transient ischemic attack (TIA) is defined as a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, with clinical symptoms typically lasting less than one hour, and without evidence of acute infarction. In this type of ischemic event, there are no data about a possible cardiac injury tested with troponin. After a stroke, it is well established the cardiac involvement due to a neuro-inflammatory response (recently defined as Stroke Heart Syndrome). The aim of this study is to compare the troponin elevation after a stroke with TIA. MATERIALS AND METHODS: this is a retrospective, single center study on 565 patients (73 TIAs, 492 stroke). We collected demographic characteristics, cardiovascular risk factors, cardiac data such as troponin, NT-proBNP, left atrial dilatation, etiology of the ischemic event (TOAST classification). RESULTS: we compare IS and TIA for each TOAST subtype. In all groups no substantial differences were found in demographic and past medical history (p>0.05). However, the maximum troponin level reached were significantly lower in TIAs than IS (p<0.05), except in lacunar etiology were troponin elevation was low also in IS group. We found a trend in favor to IS in the rise and fall troponin elevation over 30% in all the TOAST subgroups, but only in the cryptogenic etiology the difference was significant. About the others cardiac markers of injury, a significant higher rate of elevated NT-proBNP was found in the IS cohort. CONCLUSIONS: troponin level after TIAs is significantly lower than after IS. Troponin elevation after an ischemic event may be more relevant in patients with higher NT-proBNP levels and older age. More studies are needed to better understand the patho-physiology of this phenomenon after an ischemic event.

Serum proteomic profiling reveals potential inflammatory biomarkers in long-COVID patients: a comparative analysis with healthy controls.

OBJECTIVE: The highly transmissible severe acute respiratory syndrome-Coronavirus-2 was responsible for the 2020 COVID-19 pandemic. COVID-19 mostly affects the respiratory system; however, this infection also affects several other organs. In addition, the sequelae of this disease affect patients for several months after recovery, resulting in long-COVID syndrome. PATIENTS AND METHODS: In order to characterize the differences between healthy control individuals and long-COVID patients, proteomic profiling of the serum of both groups was performed by mass spectrometry. The obtained data were analyzed with multivariate and univariate statistical analyses. RESULTS: Initially, performing a partial latent square discriminant analysis (PLS-DA) made it possible to identify thirty-three proteins of interest, which were then subjected to a receiver operating characteristic (ROC) analysis. Four proteins were identified as potential stand-alone biomarkers: Sirtuin 1, Natriuretic Peptide B, Hemopexin, and Arachidonate 5-Lipoxygenase. Moreover, a multivariate ROC analysis identified a panel of biomarkers composed of Natriuretic Peptide B, Anterior Gradient 2 Protein, Adiponectin, Endothelin Converting Enzyme 1, Interferon Induced Transmembrane Protein 1, Mannose Binding Lectin 2, Prostaglandin-Endoperoxide Synthase 2, Pirin, Prostaglandin Reductase 1 and Cystatin C. CONCLUSIONS: The identified biomarkers are associated with inflammatory processes, corroborating literature evidence that long-COVID patients develop an inflammatory state that damages many tissues. Nevertheless, these data should be validated in a larger cohort.

Linking pathogenic and likely pathogenic gene variants to long-COVID symptoms.

OBJECTIVE: Long-COVID is a clinical syndrome characterized by the presence of symptoms related to SARS-CoV-2 infection that persist for at least four weeks after recovery from COVID-19. Genetics have been proposed to play an important role in long-COVID syndrome onset. This study aimed to identify genetic pathogenetic and likely pathogenetic causative variants of Mendelian genetic diseases in patients with Long-COVID syndrome. Additionally, we aimed to establish an association between these genetic variants and the clinical symptoms manifested during long-COVID syndrome. PATIENTS AND METHODS: 95 patients affected by long-COVID syndrome were analyzed with a Next-Generation Sequencing (NGS) panel comprising 494 genes. The analyzed genes and the symptoms of the patients collected with an ad-hoc questionnaire were divided into four groups (cardiological, respiratory, immunological, and neurological). Finally, a statistical analysis comprising descriptive statistics, classification based on reported symptoms, and comparative analysis against a control group of healthy individuals was conducted. RESULTS: 12 patients resulted positive for genetic testing with an autosomal dominance (8) or autosomal recessive (4) inheritance, showing a higher prevalence of cardiovascular genetic diseases (9) in the analyzed cohort compared to the normal population. Moreover, the onset of the long-COVID syndrome and its cardiovascular manifestations was compliant with the onset reported in the literature for the identified genetic diseases, suggesting that COVID-19 could manifest late-onset genetic diseases associated with their appearance. Apart from the 12 positive patients, 57 were healthy carriers of genetic diseases. Analyzing the whole cohort, a statistical correlation between prevalent symptomatology and the gene class was established, suggesting an association between the genetic susceptibility of an individual and the possibility of developing specific long-COVID syndrome symptoms, especially cardiovascular symptoms. Furthermore, 17 genetic variants were identified in CFTR. Finally, we identified genetic variants in IFNAR2 and POLG, supporting their respective involvement in inflammation and mitochondria mechanisms, correlated with long-COVID syndrome according to literature data. CONCLUSIONS: This study proposed COVID-19 to act as a manifest of underlying late-onset genetic diseases Mendelian associated with carrier status. Moreover, according to our results, mutations in cardiological genes are more present in patients who show cardiological symptoms during the syndrome. This underscores the necessity for cardiological investigation and genetic screening in long-COVID patients to address existing or potential clinical implications.

Omics sciences and precision medicine in glioblastoma.

Abstract: Glioblastoma is a highly aggressive and malignant type of brain cancer with a poor prognosis, despite current treatment options of surgery, radiation therapy, and chemotherapy. These treatments have limitations due to the aggressive nature of the cancer and the difficulty in completely removing the tumor without damaging healthy brain tissue. Personalized medicine, using genomic profiling to tailor treatment to the patient's specific tumor, and immunotherapy have shown promise in clinical trials. The blood-brain barrier also poses a challenge in delivering treatments to the brain, and researchers are exploring various approaches to bypass it. More effective, personalized treatment approaches are needed to improve outcomes for glioblastoma patients. This tumor is studied using genomics, transcriptomics, and proteomics techniques, to better understand its underlying molecular mechanisms. Recent studies have used these techniques to identify potential therapeutic targets, molecular subtypes, and heterogeneity of tumor cells. Advancements in omics sciences have improved our understanding of glioblastoma biology, and precision medicine approaches have impli-cations for more accurate diagnoses, improved treatment outcomes, and personalized preventive care. Precision medicine can match patients with drugs that target specific genetic mutations, improve clinical trials, and identify individuals at higher risk for certain diseases. Precision medicine, which involves customizing medical treatment based on an individual's genetic makeup, lifestyle, and environmental factors, has shown promise in improving treatment outcomes for glioblastoma patients. Identifying biomarkers is essential for patient stratification and treatment selection in precision medicine approaches for glioblastoma, and several biomarkers have shown promise in predicting patient response to treatment. Targeted therapies are a key component of precision medicine approaches in glioblastoma, but there is still a need to improve their effectiveness. Technical challenges, such as sample quality and availability, and challenges in analyzing and interpreting large amounts of data remain significant obstacles in omics sciences and precision medicine for glioblastoma. The clinical implementation of precision medicine in glioblastoma treatment faces challenges related to patient selection, drug development, and clinical trial design, as well as ethical and legal considerations related to patient privacy, informed consent, and access to expensive treatments.

Telemedicine during the SARS-Cov-2 pandemic lockdown: Monitoring stress and quality of sleep in patients with epilepsy.

SARS-CoV-2 pandemic heavily hit the western healthcare system saturating the hospital beds in wards and clogging the emergency departments. To avoid the collapse of Italian hospitals, office visits to outpatients were limited to emergencies and the general population went in a lockdown state. Physicians had to approach new problems in the management of chronic patients who could not leave their homes. In our experience as epilepsy clinic, the use of telemedicine was of crucial importance for monitoring our patients: phone call during lockdown let us monitor the stability of our 38 patients and psychometric parameters and habits that could influence seizures frequency. In particular, we found that in our patients, sleep quality was low resulting in high daily sleepiness and associated high stress levels. Secondly, we found an increase in daily screen hours and an association with daily sleepiness. In conclusion, we report our experience in managing people with epilepsy during the lockdown, underlining the utility of telemedicine as a valid monitoring tool and the necessity of a psychometric and behavioral screening.

Deep brain stimulation of the subthalamic nucleus and the temporal discounting of primary and secondary rewards.

Although deep brain stimulation of the subthalamic nucleus is an effective surgical treatment for Parkinson's disease, it may expose patients to non-motor side effects such as increased impulsivity and changes in decision-making behavior. Even if several studies have shown that stimulation of the subthalamic nucleus increases the incentive salience of food rewards in both humans and animals, temporal discounting for food rewards has never been investigated in patients who underwent STN-DBS. In this study, we measured inter-temporal choice after STN-DBS, using both primary and secondary rewards. In particular, PD patients who underwent STN-DBS (in ON medication/ON stimulation), PD patients without STN-DBS (in ON medication) and healthy matched controls (C) performed three temporal discounting tasks with food (primary reward), money and discount vouchers (secondary rewards). Participants performed also neuropsychological tests assessing memory and executive functions. Our results show that STN-DBS patients and PD without DBS behave as healthy controls. Even PD patients who after DBS experienced weight gain and/or eating alterations did not show an increased temporal discounting for food rewards. Interestingly, patients taking a higher dosage of dopaminergic medications, fewer years from DBS surgery and, unexpectedly, with better episodic memory were also those who discounted rewards more. In conclusion, this study shows that STN-DBS does not affect temporal discounting of primary and secondary rewards. Furthermore, by revealing interesting correlations between clinical measures and temporal discounting, it also shed light on the clinical outcomes that follow STN-DBS in patients with PD.

The use ultrasound guided for refilling intrathecal baclofene pump in complicated clinical cases: A practical approach.

Muscular spasticity due to neurological disorders is a heavy cause of severe pain and disability for many patients, compromising the independence and quality life. Baclofene is a good tool to guarantee patients independence and pain control. Anyway in chronic therapy oral treatment become unsatisfactory. In all these cases, intrathecal baclofen therapy (ITB), after sub fascial implantation of intrathecal pumps is used as an important long term treatment to reduce spasticity. After pump implantation the drug reservoir must be refilled periodically in order to maintain the reduction of spasticity and avoid the symptoms and signs of withdrawal. ITB refilling, which involves the insertion of a needle through the skin until the access port of the pump, is often hard, mainly due to the layer of abdominal fat, spasticity, suboptimal pump positioning, pump rotation or inversion, and scar formation over the implantation site. To avoid the difficulties of ITB refilling radiography or other invasive supportive examinations are sometimes needed. We reported here our experience and we suggest a simple method to use the ultrasound in refilling with particular attention to some cases with complications after implantation with a difficult approach in refilling. We used the ultrasound examination to identify the access port of her pump so as to avoid multiple needle punctures and infections and radiation exposition. Ultrasound-guided technique may facilitate ITB refill in technically challenging cases. With ultrasound ITB was easily detectable and was quite simple to identify the exact point of needle injection. In the last years different new applications for ultrasounds are emerging. In our opinion the use of Doppler ultrasounds in the study of muscles and nerves represent an emerging tool for the physician's neurological rehabilitation.

Epilepsy in multiple sclerosis: The role of temporal lobe damage.

BACKGROUND: Although temporal lobe pathology may explain some of the symptoms of multiple sclerosis (MS), its role in the pathogenesis of seizures has not been clarified yet. OBJECTIVES: To investigate the role of temporal lobe damage in MS patients suffering from epilepsy, by the application of advanced multimodal 3T magnetic resonance imaging (MRI) analysis. METHODS: A total of 23 relapsing remitting MS patients who had epileptic seizures (RRMS/E) and 23 disease duration matched RRMS patients without any history of seizures were enrolled. Each patient underwent advanced 3T MRI protocol specifically conceived to evaluate grey matter (GM) damage. This includes grey matter lesions (GMLs) identification, evaluation of regional cortical thickness and indices derived from the Neurite Orientation Dispersion and Density Imaging model. RESULTS: Regional analysis revealed that in RRMS/E, the regions most affected by GMLs were the hippocampus (14.2%), the lateral temporal lobe (13.5%), the cingulate (10.0%) and the insula (8.4%). Cortical thinning and alteration of diffusion metrics were observed in several regions of temporal lobe, in insular cortex and in cingulate gyrus of RRMS/E compared to RRMS ( p< 0.05 for all comparisons). CONCLUSIONS: Compared to RRMS, RRMS/E showed more severe damage of temporal lobe, which exceeds what would be expected on the basis of the global GM damage observed.

Acute myelitis as presenting symptom of HIV-HTLV-1 co-infection.

A 21-year-old woman presented with acute-onset spastic paraparesis. The MRI spinal scan revealed a contrast-enhanced T2 hyperintensity between C5-T2. The most common neurotropic pathogens were excluded by first level tests. Under suspicion of an acute immune-mediated myelitis, a corticosteroid therapy was administered. However, a seropositivity for both human immunodeficiency virus (HIV) type 1 and human T-lymphotropic virus (HTLV) subsequently emerged. An antiretroviral therapy was started while steroids discontinued. Patient's clinical conditions remained unchanged. HIV-HTLV-1 co-infection should be included in the differential diagnosis of any acute myelitis, even in patients with a preserved immune status and no risk factors.

Modelling hemodynamic response function in epilepsy.

OBJECTIVE: Electroencephalography and functional magnetic resonance imaging (fMRI) can be combined to noninvasively map abnormal brain activation elicited by epileptic processes. A major aim was to investigate the impact of a subject-specific hemodynamic response function (HRF) to describe the differences across patients versus the use of a standard model. METHODS: We developed and applied on simulated and real data a method designed to choose optimum HRF model for identifying fMRI activation maps. In simulation, the ability of five models to reproduce data was assessed: four standard and an individual-based HRF model (ibHRF). In clinical data, drug-resistant epileptic patients underwent fMRI to investigate hemodynamic responses evoked by interictal activity. RESULTS: When data are simulated with models different from the standard ones, the results obtained with ibHRF are superior to those obtained with the standard HRFs. Results on real data indicate an increase in extent and degree of activation with the ibHRF in comparison of the results obtainable using standard HRFs. CONCLUSIONS: The use of the same HRF in all patients is inappropriate and resolves in biased extension of the activation maps. SIGNIFICANCE: The new method could represent an useful diagnostic tool for other clinical studies that may be biased because of misspecification of HRF.

Role, indications and controversies of levodopa administration in chronic stroke patients.

Stroke leaves many patients disabled even after rehabilitative training, representing a major cause of disability. Several approaches to improve outcomes have been attempted in recent years, with only relative benefit. Emerging evidences show a potential role of pharmacological intervention to enhance motor recovery after stroke. Contrasting evidence are coming from experimental and clinical studies, so far, and pharmacological intervention during rehabilitation represents a major controversial in neurorehabilitation. Dopaminergic stimulation appears as one of the most promising way to improve motor recovery. Subject of this paper will be the ratio underlying the clinical use of levodopa in chronic stroke patients, trying to outline the most convincing evidences about a potential role of this drug in rehabilitative strategies.

Fixation-off sensitivity.

Fixation-off sensitivity (FOS) is a phenomenon induced by elimination of central vision/fixation, and may either manifest clinically with seizures or only represent an EEG abnormality. FOS is characterized by posterior or generalized epileptiform discharges that consistently occur after closing of the eyes and last as long as the eyes are closed. It is most commonly encountered in patients with idiopathic childhood occipital epilepsies, but may also be observed in cases of symptomatic or cryptogenic focal and generalized epilepsies, as well as in asymptomatic non-epileptic individuals. FOS should be differentiated from pure forms of scotosensitivity, in which EEG discharges or epileptic seizures are elicited by darkness, and from epileptiform discharges triggered by eye closure, which refer to eye closure sensitivity. Although FOS is probably associated with occipital hyperexcitability its intrinsic epileptogenic potential is presumed to be low.

Effect of median-nerve electrical stimulation on BOLD activity in acute ischemic stroke patients.

OBJECTIVE: To investigate blood oxygenation level-dependent (BOLD) activation during somatosensory electrical stimulation of the median nerve in acute stroke patients and to determine its correlation with ischemic damage and clinical recovery over time. METHODS: Fourteen acute stroke patients underwent functional magnetic resonance imaging (fMRI) during contralesional median-nerve electrical stimulation 12-48 h after stroke. Findings were then validated by diffusion tensor imaging (DTI) and motor evoked potential by transcranial magnetic stimulation (TMS). RESULTS: Poor clinical recovery at three months was noted in four patients with no activation in the early days after stroke, whereas good clinical recovery was observed in eight patients with a normal activation pattern in the primary sensory motor area in the acute phase. In two patients BOLD activation correlated weakly with clinical recovery. Findings from TMS and DTI partially correlated with clinical recovery and functional scores. CONCLUSIONS: Clinically relevant insights into the "functional reserve" of stroke patients gained with peripheral nerve stimulation during fMRI may carry prognostic value already in the acute period of a cerebrovascular accident. SIGNIFICANCE: BOLD activation maps could provide insights into the functional organization of the residual systems and could contribute to medical decision making in neurological and rehabilitative treatment.

A double blind placebo RCT to investigate the effects of serotonergic modulation on brain excitability and motor recovery in stroke patients.

Motor excitability is increased in both hemispheres in stroke patients during motor recovery. Pharmacologically controlled changes of cortical excitability might be beneficial for synaptic plasticity and therefore facilitate functional recovery after a brain lesion. In particular, it has been suggested that antidepressant drugs can modulate motor excitability. Several recent reports suggest the possibility of monitoring pharmacological effects on brain excitability through transcranial magnetic stimulation (TMS). The aim of this study was to investigate motor area excitability in patients with stroke after oral administration of citalopram. We conducted a prospective randomised placebo controlled study. Twenty patients with unilateral stroke were included in the study: ten patients treated by antidepressive drug and ten patients with placebo. A selective serotonergic drug (citalopram) or a placebo was administered using a mean dosage of 10 mg/day in combination with physiotherapy. Motor cortex excitability was studied by single and paired transcranial magnetic stimulation. TMS recording was tested before (T1) and 1 month after (T2) beginning drug treatment. Patients treated by the serotonergic drug, compared to patients that received a placebo, showed a significant improvement in neurological status as measured by NIHSS and a decrease of motor excitability over the unaffected hemisphere, while no differences were observed over the affected hemisphere. Our findings suggest that treatment with serotonergic drugs can bring about a significant decrease of the motor cortex excitability in stroke patients with effects on both the affected and unaffected hemispheres associated with a better motor recovery.

Motor cortical disinhibition during early and late recovery after stroke.

BACKGROUND: Functional neuroimaging studies show adaptive changes in areas adjacent and distant from the stroke. This longitudinal study assessed whether changes in cortical excitability in affected and unaffected motor areas after acute stroke correlates with functional and motor recovery. METHODS: We studied 13 patients with moderate to severe hemiparesis 5 to 7 days (T1), 30 days (T2), and 90 days (T3) after acute unilateral stroke, as well as 10 healthy controls. We used paired-pulse transcranial magnetic stimulation to study intracortical inhibition and facilitation, recording from the bilateral thenar eminences. F waves were also recorded. RESULTS: At T1, all patients showed significantly reduced intracortical inhibition in the unaffected hemisphere. At T2, in patients whose motor function recovered, intracortical inhibition in the unaffected hemisphere returned to normal. In patients with poor clinical motor recovery, abnormal disinhibition persisted in both hemispheres. At T3, in patients whose motor function progressively recovered, the abnormal disinhibition in the unaffected hemisphere decreased further, whereas in patients whose motor function remained poor, abnormal inhibition in the unaffected hemisphere persisted. No modification of F-wave latency and amplitude were found in patients and controls. CONCLUSIONS: During early days after stroke, motor cortical disinhibition involves both cerebral hemispheres. Longitudinal changes in motor disinhibition of the unaffected hemisphere may reflect the degree of clinical motor recovery.

f-MRI in Epilepsy with Spike and Wave Activity Evoked by Eye Closure: Different Bold Activation in a Patient with Idiopathic Partial Epilepsy with Occipital Spikes and a Control Group.

We performed functional magnetic resonance imaging (fMRI) in a 30-year-old man with idiopathic partial epilepsy with occipital spikes whose scalp EEG activity was characterized by persistent epileptiform discharges on eye closure, ceasing upon eye opening. We compared BOLD activation in the patient and in a control group of three normal volunteers. f-MRI showed that occipital cortex and frontal areas were activated in relation to eye movement in normal subjects during eye opening but not during eye closing. While persistent interictal spike and wave activity was present over the posterior and anterior scalp in the patient upon eye closing, f-MRI showed bilateral activation of the parietal and temporal regions. This fMRI study documents the activation of posterior and temporal areas related to continuous intercritical spikes evoked by eye closure, which are diffuse over the scalp. This activation was absent in the control group during eye closure.

Continuous EEG-fMRI in Pre-Surgical Evaluation of a Patient with Symptomatic Seizures: Bold Activation Linked to Interictal Epileptic Discharges Caused by Cavernoma.

We used continuous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) to identify the linkage between the "epileptogenic" and the "irritative" area in a patient with symptomatic epilepsy (cavernoma, previously diagnosed and surgically treated), i.e. a patient with a well known "epileptogenic area", and to increase the possibility of a non invasive pre-surgical evaluation of drug-resistant epilepsies. A compatible MRI system was used (EEG with 29 scalp electrodes and two electrodes for ECG and EMG) and signals were recorded with a 1.5 Tesla MRI scanner. After the recording session and MRI artifact removal, EEG data were analyzed offline and used as paradigms in fMRI study. Activation (EEG sequences with interictal slow-spiked-wave activity) and rest (sequences of normal EEG) conditions were compared to identify the potential resulting focal increase in BOLD signal and to consider if this is spatially linked to the interictal focus used as a paradigm and to the lesion. We noted an increase in the BOLD signal in the left neocortical temporal region, laterally and posteriorly to the poro-encephalic cavity (residual of cavernoma previously removed), that is around the "epileptogenic area". In our study "epileptogenic" and "irritative" areas were connected with each other. Combined EEG-fMRI may become routine in clinical practice for a better identification of an irritative and lesional focus in patients with symptomatic drug-resistant epilepsy.

Effect of a Static Magnetic Field (1.5T) on Brain Oscillatory Activities in Resting State Condition.

The aim of the present study was to compare the EEG signal recorded outside and inside a 1.5T magnetic resonance (MR) scanner. The EEG was recorded in eyes open and eyes closed conditions using a digital recording MR-compatible system. To characterize how a static magnetic field induces changes in EEG signal, EEG data were analyzed using FFT frequency analysis. No significant difference between the alpha powers recorded outside and inside the magnetic field was observed in eyes closed conditions. However, in eyes open condition there was a significant increase in alpha power inside the magnet in comparison to the outside position. The changes in alpha power according to the eyes open/closed conditions could be inversely correlated to a subject's state of wakefulness and due to some physiological changes, rather than an effect of the magnetic field. This experiment suggests that subjects' state of wakefulness is of prime concern when performing functional MRI.

Monitoring of motor pathways during brain stem surgery: what we have achieved and what we still miss?

Intraoperative neurophysiological monitoring (IOM) has established itself as one of the paths by which modern neurosurgery can improve surgical results while minimizing morbidity. IOM consists of both monitoring (continuous "on-line" assessment of the functional integrity of neural pathways) and mapping (functional identification and preservation of anatomically ambiguous nervous tissue) techniques. In posterior-fossa and brainstem surgery, mapping techniques can be used to identify - and therefore preserve - cranial nerves, their motor nuclei and corticospinal or corticobulbar pathways. Similarly, free-running electromyography (EMG) and muscle motor-evoked potential (mMEP) monitoring can continuously assess the functional integrity of these pathways during surgery. Mapping of the corticospinal tract, at the level of the cerebral peduncle as well as mapping of the VII, IX-X and XII cranial nerve motor nuclei on the floor of the fourth ventricle, is of great value to identify "safe entry-zones" into the brainstem. Mapping techniques allow recognizing anatomical landmarks such as the facial colliculus, the hypoglosseal and glossopharyngeal triangles on the floor of the fourth ventricle, even when normal anatomy is distorted by a tumor. On the basis of neurophysiological mapping, specific patterns of motor cranial nuclei displacement can be recognized. However, brainstem mapping cannot detect injury to the supranuclear tracts originating in the motor cortex and ending on the cranial nerve motor nuclei. Therefore, monitoring techniques should be used. Standard techniques for continuously assessing the functional integrity of motor cranial nerves traditionally rely on the evaluation of spontaneous free-running EMG in muscles innervated by motor cranial nerves. Although several criteria have been proposed to identify those EMG activity patterns that are suspicious for nerve injury, the terminology remains somewhat confusing and convincing data regarding a clinical correlation between EMG activity and clinical outcome are still lacking. Transcranial mMEPs are also currently used during posterior-fossa surgery and principles of MEP monitoring to assess the functional integrity of motor pathways are similar to those used in brain and spinal-cord surgery. Recently, current concepts in muscle MEP monitoring have been extended to the monitoring of motor cranial nerves. So-called "corticobulbar mMEPs" can be used to monitor the functional integrity of corticobulbar tracts from the cortex through the cranial motor nuclei and to the muscle innervated by cranial nerves. Methodology for this purpose has appeared in the literature only recently and mostly with regards to the VII cranial nerve monitoring. Nevertheless, this technique has not yet been standardized and some limitations still exist. In particular, with regards to the preservation of the swallowing and coughing reflexes, available intraoperative techniques are insufficient to provide reliable prognostic data since only the efferent arc of the reflex can be tested.