Linear and nonlinear interrelations show fundamentally distinct network structure in preictal intracranial EEG of epilepsy patients.

Resection of the seizure generating tissue can be highly beneficial in patients with drug-resistant epilepsy. However, only about half of all patients undergoing surgery get permanently and completely seizure free. Investigating the dependences between intracranial EEG signals adds a multivariate perspective largely unavailable to visual EEG analysis, which is the current clinical practice. We examined linear and nonlinear interrelations between intracranial EEG signals regarding their spatial distribution and network characteristics. The analyzed signals were recorded immediately before clinical seizure onset in epilepsy patients who received a standardized electrode implantation targeting the mesiotemporal structures. The linear interrelation networks were predominantly locally connected and highly reproducible between patients. In contrast, the nonlinear networks had a clearly centralized structure, which was specific for the individual pathology. The nonlinear interrelations were overrepresented in the focal hemisphere and in patients with no or only rare seizures after surgery specifically in the resected tissue. Connections to the outside were predominantly nonlinear. In all patients without worthwhile improvement after resective treatment, tissue producing strong nonlinear interrelations was left untouched by surgery. Our findings indicate that linear and nonlinear interrelations play fundamentally different roles in preictal intracranial EEG. Moreover, they suggest nonlinear signal interrelations to be a marker of epileptogenic tissue and not a characteristic of the mesiotemporal structures. Our results corroborate the network-based nature of epilepsy and suggest the application of network analysis to support the planning of resective epilepsy surgery.

Electromyographic reactivity measured with scalp-EEG contributes to prognostication after cardiac arrest.

AIM: To assess whether stimulus-induced modifications of electromyographic activity observed on scalp EEG have a prognostic value in comatose patients after cardiac arrest. METHODS: 184 adult patients from a multi-centric prospective register who underwent an early EEG after cardiac arrest were included. Auditory and somatosensory stimulation was performed during EEG-recording. EEG reactivity (EEG-R) and EMG reactivity (EMG-R) were retrospectively assessed visually by board-certified electroencephalographers, and compared with clinical outcome (cerebral performance category, CPC) at three months. A favorable functional outcome was defined as CPC 1-2, an unfavorable outcome as CPC 3-5. RESULTS: Both EEG-R and EMG-R were predictors for good outcome (EEG-R accuracy 72% (95%-CI 66-79), sensitivity 86% (78-93), specificity 60% (50-69); EMG-R accuracy 65% (58-72), sensitivity 61% (51-75), specificity 69% (60-78)). When reactivity was defined as EEG-R and/or EMG-R, the accuracy was 73% (67-70), the sensitivity 94% (90-99), and the specificity 53% (43-63). CONCLUSION: Taking EMG into account when assessing reactivity of EEG seems to reduce false negative predictions for identifying patients with favorable outcome after cardiac arrest.

Natalizumab in spinal multiple sclerosis in a daily clinical setting.

OBJECTIVE: We aimed to investigate the influence of natalizumab (NTZ) treatment on multiple sclerosis course in patients with and without spinal involvement. METHODS: Annualized relapse rate (ARR), disability progression and occurrence of new brain and spinal T2 lesions (N2TL) in 68 spinal (S-P) versus 68 non-spinal matched patients (NS-P) were retrospectively collected and compared between before (2 years) and after NTZ treatment using multivariate regression models. RESULTS: Mean duration of NTZ treatment was 31.3 ± 16.3 months in S-P and 32.1 ± 15.1 months in N-SP (p = 0.56). The mean ARR after NTZ treatment was similarly reduced in both S-P (0.07 ± 0.19) and N-SP (0.07 ± 0.16) (p < 0.001 for both). Disability progression after NTZ start was similarly low in S-P and NS-P. However, when compared to before NTZ start, disability progression was significantly reduced in S-P (p = 0.017), but not in NS-P (p = 0.68). This was largely mediated by a higher disability progression before NTZ start in S-P than N-SP. The risk of developing N2TL during NTZ was not different between S-P and NS-P (p = 0.10). CONCLUSIONS: NTZ similarly reduced the occurrence of relapses and NT2L in S-P and NS-P, whereas the effect on disability progression was particularly evident in the presence of spinal involvement. NTZ appears to be a treatment of high efficacy in both S-P and NS-P.

Life-threatening asthma attack during prolonged fingolimod treatment: case report.

BACKGROUND: Fingolimod (FTY) mediates bronchoconstriction by interacting with sphingosine-1-phosphate receptors. The majority of the reported adverse respiratory events occur during the first weeks of treatment. CASE PRESENTATION: A 49-year-old woman developed a life-threatening asthma attack after 6 months of continuous FTY treatment. The adverse event required prolonged hospitalization, and the patient recovered without sequelae after FTY interruption. A history of previous airway hyperreactivity and a concurrent viral respiratory infection possibly acted as predisposing factors. CONCLUSION: This first description of a severe, life-threatening asthma attack during prolonged FTY treatment suggests the need for long-term clinical surveillance, especially in patients with known predisposing factors.

Two decades of subcutaneous glatiramer acetate injection: current role of the standard dose, and new high-dose low-frequency glatiramer acetate in relapsing-remitting multiple sclerosis treatment.

Glatiramer acetate, a synthetic amino acid polymer analog of myelin basic protein, is one of the first approved drugs for the treatment of relapsing-remitting multiple sclerosis. Several clinical trials have shown consistent and sustained efficacy of glatiramer acetate 20 mg subcutaneously daily in reducing relapses and new demyelinating lesions on magnetic resonance imaging in patients with relapsing-remitting multiple sclerosis, as well as comparable efficacy to high-dose interferon beta. Some preclinical and clinical data suggest a neuroprotective role for glatiramer acetate in multiple sclerosis. Glatiramer acetate is associated with a relatively favorable side-effect profile, and importantly this was confirmed also during long-term use. Glatiramer acetate is the only multiple sclerosis treatment compound that has gained the US Food and Drug Administration pregnancy category B. All these data support its current use as a first-line treatment option for patients with clinical isolated syndrome or relapsing-remitting multiple sclerosis. More recent data have shown that high-dose glatiramer acetate (ie, 40 mg) given three times weekly is effective, safe, and well tolerated in the treatment of relapsing-remitting multiple sclerosis, prompting the approval of this dosage in the US in early 2014. This high-dose, lower-frequency glatiramer acetate might represent a new, more convenient regimen of administration, and this might enhance patients' adherence to the treatment, crucial for optimal disease control.

Factors associated with hopelessness in epileptic patients.

AIM: To investigate factors related to hopelessness in a sample of epileptic patients, including measures of depression and quality of life (QOL). METHODS: Sixty-nine participants were administered the following psychometric instruments: Beck Depression Inventory-II, Beck Hopelessness Scale (BHS), and QOL in Epilepsy (QOLIE)-89. Patients were dichotomized into two categories: those affected by epilepsy with generalized tonic-clonic seizures vs those having epilepsy with partial seizures. RESULTS: The groups differed on the QOLIE Role Limitation/Emotional dimension. Patients with generalized seizures reported more limitations in common social/role activities related to emotional problems than patients with other types of epilepsy (89.57 ± 25.49 vs 72.86 ± 36.38; t 63 = -2.16; P < 0.05). All of the respondents reported moderate to severe depression, and 21.7% of patients with generalized seizures and 28.6% of patients with other diagnoses had BHS total scores ≥ 9 indicating a higher suicidal risk. The study did not control for years of the illness. CONCLUSION: Patients with generalized seizures reported more limitations in common social/role activities related to emotional problems compared to patients with other types of seizures. Patients at increased suicide risk as evaluated by the BHS were older than those who had a lower suicidal risk. Future studies are required to further investigate the impact of hopelessness on the outcome of epileptic patients.

Functional MRI of sleep spindles and K-complexes.

OBJECTIVE: Sleep spindles and K-complexes are EEG hallmarks of non-REM sleep. However, the brain regions generating these discharges and the functional connections of their generators to other regions are not fully known. We investigated the neuroanatomical correlates of spindles and K-complexes using simultaneous EEG and fMRI. METHODS: EEGs recorded during EEG-fMRI studies of 7 individuals were used for fMRI analysis. Higher-level group analyses were performed, and images were thresholded at Z ≥ 2.3. RESULTS: fMRI of 106 spindles and 60 K-complexes was analyzed. Spindles corresponded to increased signal in thalami and posterior cingulate, and right precuneus, putamen, paracentral cortex, and temporal lobe. K-complexes corresponded to increased signal in thalami, superior temporal lobes, paracentral gyri, and medial regions of the occipital, parietal and frontal lobes. Neither corresponded to regions of decreased signal. CONCLUSIONS: fMRI of both spindles and K-complexes depicts signal subjacent to the vertex, which likely indicates each discharges' source. The thalamic signal is consistent with thalamic involvement in sleep homeostasis. The limbic region's signal is consistent with roles in memory consolidation. Unlike the spindle, the K-complex corresponds to extensive signal in primary sensory cortices. SIGNIFICANCE: Identification of these active regions contributes to the understanding of sleep networks and the physiology of awareness and memory during sleep.

Functional imaging of sleep vertex sharp transients.

OBJECTIVE: The vertex sharp transient (VST) is an electroencephalographic (EEG) discharge that is an early marker of non-REM sleep. It has been recognized since the beginning of sleep physiology research, but its source and function remain mostly unexplained. We investigated VST generation using functional MRI (fMRI). METHODS: Simultaneous EEG and fMRI were recorded from seven individuals in drowsiness and light sleep. VST occurrences on EEG were modeled with fMRI using an impulse function convolved with a hemodynamic response function to identify cerebral regions correlating to the VSTs. A resulting statistical image was thresholded at Z>2.3. RESULTS: Two hundred VSTs were identified. Significantly increased signal was present bilaterally in medial central, lateral precentral, posterior superior temporal, and medial occipital cortex. No regions of decreased signal were present. CONCLUSION: The regions are consistent with electrophysiologic evidence from animal models and functional imaging of human sleep, but the results are specific to VSTs. The regions principally encompass the primary sensorimotor cortical regions for vision, hearing, and touch. SIGNIFICANCE: The results depict a network comprising the presumed VST generator and its associated regions. The associated regions functional similarity for primary sensation suggests a role for VSTs in sensory experience during sleep.