Modulation of epileptic networks by transient interictal epileptic activity: A dynamic approach to simultaneous EEG-fMRI.

Epileptic networks, defined as brain regions involved in epileptic brain activity, have been mapped by functional connectivity in simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) recordings. This technique allows to define brain hemodynamic changes, measured by the Blood Oxygen Level Dependent (BOLD) signal, associated to the interictal epileptic discharges (IED), which together with ictal events constitute a signature of epileptic disease. Given the highly time-varying nature of epileptic activity, a dynamic functional connectivity (dFC) analysis of EEG-fMRI data appears particularly suitable, having the potential to identify transitory features of specific connections in epileptic networks. In the present study, we propose a novel method, defined dFC-EEG, that integrates dFC assessed by fMRI with the information recorded by simultaneous scalp EEG, in order to identify the connections characterised by a dynamic profile correlated with the occurrence of IED, forming the dynamic epileptic subnetwork. Ten patients with drug-resistant focal epilepsy were included, with different aetiology and showing a widespread (or multilobar) BOLD activation, defined as involving at least two distinct clusters, located in two different lobes and/or extended to the hemisphere contralateral to the epileptic focus. The epileptic focus was defined from the IED-related BOLD map. Regions involved in the occurrence of interictal epileptic activity; i.e., forming the epileptic network, were identified by a general linear model considering the timecourse of the fMRI-defined focus as main regressor. dFC between these regions was assessed with a sliding-window approach. dFC timecourses were then correlated with the sliding-window variance of the IED signal (VarIED), to identify connections whose dynamics related to the epileptic activity; i.e., the dynamic epileptic subnetwork. As expected, given the very different clinical picture of each individual, the extent of this subnetwork was highly variable across patients, but was but was reduced of at least 30% with respect to the initially identified epileptic network in 9/10 patients. The connections of the dynamic subnetwork were most commonly close to the epileptic focus, as reflected by the laterality index of the subnetwork connections, reported higher than the one within the original epileptic network. Moreover, the correlation between dFC timecourses and VarIED was predominantly positive, suggesting a strengthening of the dynamic subnetwork associated to the occurrence of IED. The integration of dFC and scalp IED offers a more specific description of the epileptic network, identifying connections strongly influenced by IED. These findings could be relevant in the pre-surgical evaluation for the resection or disconnection of the epileptogenic zone and help in reaching a better post-surgical outcome. This would be particularly important for patients characterised by a widespread pathological brain activity which challenges the surgical intervention.

The network integration of epileptic activity in relation to surgical outcome.

OBJECTIVE: Epilepsy is a network disease with epileptic activity and cognitive impairment involving large-scale brain networks. A complex network is involved in the seizure and in the interictal epileptiform discharges (IEDs). Directed connectivity analysis, describing the information transfer between brain regions, and graph analysis are applied to high-density EEG to characterise networks. METHODS: We analysed 19 patients with focal epilepsy who had high-density EEG containing IED and underwent surgery. We estimated cortical activity during IED using electric source analysis in 72 atlas-based cortical regions of the individual brain MRI. We applied directed connectivity analysis (information Partial Directed Coherence) and graph analysis on these sources and compared patients with good vs poor post-operative outcome at global, hemispheric and lobar level. RESULTS: We found lower network integration reflected by global, hemispheric, lobar efficiency during the IED (p < 0.05) in patients with good post-surgical outcome, compared to patients with poor outcome. Prediction was better than using the IED field or the localisation obtained by electric source imaging. CONCLUSIONS: Abnormal network patterns in epilepsy are related to seizure outcome after surgery. SIGNIFICANCE: Our finding may help understand networks related to a more "isolated" epileptic activity, limiting the extent of the epileptic network in patients with subsequent good post-operative outcome.

Spontaneous appearance of de novo intracranial arteriovenous malformation in hepatic cirrhosis.

BACKGROUND: Intracranial arteriovenous malformations (AVMs) are rare lesions that can be congenital or acquired in early childhood, with fatal outcome in approximately 30% of cases. De novo formation during adulthood without established predisposing vascular pathology or previous brain insult is even less frequent. CASE DESCRIPTION: We present a case of de novo brain AVM in an alcoholic Child-B cirrhosis setting. Thirty previously reported cases presented de novo AVM in patients of all ages that had another previous brain pathology or insult, such as AVM resection. Seventeen of those cases occurred in adult patients, with only 2 showing no significant predisposing factor. The present pathophysiological review covers and completes Mullan's hemodynamic "two-hit" model, associating probable thrombotic predisposition to AVM with brain insult triggering a later stage based on angiogenic stimuli. CONCLUSIONS: This case report and literature review renews previously discussed hemodynamic theories and contributes to a fuller understanding of the pathogenesis and progression of AVM. We postulate a causal link between hepatopathy and de novo AVM, which should be strengthened and interpreted based on recent genetic data and future prospective studies.

What to do in failed hemispherotomy? Our clinical series and review of the literature.

Hemispherotomy is an established surgical technique to cure or palliate selected, mostly young patients suffering from refractory epilepsy. However, a few patients continue to have seizures despite the surgical hemispherical disconnection. We present a case series of patients who underwent redo hemispherotomy after a first unsuccessful hemispherical disconnection and provide a roadmap for subsequent workup and treatment. The institutional database of epilepsy surgery was reviewed. Twenty-four patients who underwent hemispherotomies for refractory epilepsy were identified between 2007 and 2016. Patients' notes were checked for demographics, history, clinical presentation, preoperative workup, medical treatment, age at first hemispherotomy, and surgical technique. Complications, histopathology, postoperative antiepileptic drug, and postoperative neurological follow-up were documented. Engel class was used to determine the outcome after surgery. Three patients (one hemimegalencephaly, one perinatal stroke, and one Rasmussen's disease) underwent redo hemispherotomy after electroencephalography and MRI studies with particular importance given to diffusion tensor imaging (DTI) to demonstrate residual connection between hemispheres. In one case, redo disconnection followed by a frontal lobectomy rendered the patient seizure-free (Engel class I). In one case, the seizure frequency remained the same but generalized seizures disappeared (Engel class III), and in one case, seizure frequency was considerably reduced after the redo disconnection (Engel class II), with a minimum follow-up of 2 years. Surgical aspects, possible reasons of failure of first hemispherotomy, and rationale that led to second-look surgery are presented. Reasons for failure can be related to patient's selection and/or surgical aspects. Hemispherotomy is a technically demanding procedure and requires accurate preoperative workup. Redo hemispherotomy is a valid option on the basis of further epileptological and radiological workup to demonstrate residual interhemispheric connections and/or rule out bi-hemispheric epileptic activity.

Subdural hematoma after endoscopic third ventriculostomy: Struggling against the Laplace law.

BACKGROUND: Endoscopic third ventriculostomy (ETV) is an ideal treatment for obstructive hydrocephalus. Although ETV is a safe procedure, several complications related to this procedure have been reported in the literature. We present a rare case of late onset symptomatic bilateral subdural hematoma after an uneventful ETV that proved particularly difficult to solve. CASE DESCRIPTION: A 61-year-old male patient presented in our neurosurgery department three months after ETV (aqueductal stenosis) with progressive headaches and anomic aphasia. The MRI revealed bilateral chronic subdural hematomas (chSDH). They were treated via a burr hole evacuation, subduroperitoneal and external subdural drains proving to be refractory to the first two strategies. Postoperatively, his headaches improved. At the last follow-up the patient's status remains improved and there is no radiological evidence of significant residual collections. CONCLUSION: This case confirms that chSDH formation is a rare possible complication following ETV even in the presence of a normal early postoperative image. Patients should be followed-up more closely for possible subdural collection formation. In the cases of very long-term hydrocephalus with a thin cerebral mantle, brain elastic properties are likely to be altered. As there is no possibility to close the internal shunt, the stoma, we advocate external subdural drainage to reinflate the brain, in the first intention or at least after an initial failed burr hole evacuation.

Improvement in executive subfunctions following cerebrospinal fluid tap test identifies idiopathic normal pressure hydrocephalus from its mimics.

BACKGROUND AND PURPOSE: Patients with idiopathic normal pressure hydrocephalus (iNPH) present cognitive deficits that overlap with other neurological conditions such as Parkinson's disease or vascular dementia, therefore mimicking iNPH. This prospective study aimed to compare cognitive performances between iNPH and iNPH mimics before and after cerebrospinal fluid (CSF) tapping. METHODS: A total of 57 patients with suspicion of iNPH (75.84 ± 6.42 years; 39% female) were included in this study (37 iNPH and 20 iNPH mimics). Neuropsychological assessments were performed before and 24 h after CSF tapping of 40 ml. Multivariate logistic regressions were used to examine the association between iNPH and cognitive functions, adjusted for age, education, baseline cognitive assessment and disease duration. RESULTS: Both groups presented the same baseline cognitive performances. After CSF tapping, iNPH patients improved their semantic (P = 0.001) and phonemic verbal fluencies (P = 0.001), whereas iNPH mimics presented similar performances to before CSF tapping. The phonemic verbal fluency (odds ratio 1.43, 95% confidence interval 1.05; 1.96) and the Color Trails Test (odds ratio 0.10, 95% confidence interval 0.01; 0.76) improvements were the two discriminative cognitive tests that identified iNPH from iNPH mimics. CONCLUSION: Improvement in executive subfunctions after CSF tapping identified iNPH patients from other neurological conditions that mimic iNPH. These findings respond to clinical issues encountered on a daily basis and would improve the diagnostic process of iNPH.

Evaluation of electrode position in deep brain stimulation by image fusion (MRI and CT).

INTRODUCTION: Imaging has an essential role in the evaluation of correct positioning of electrodes implanted for deep brain stimulation (DBS). Although MRI offers superior anatomic visualization of target sites, there are safety concerns in patients with implanted material; imaging guidelines are inconsistent and vary. The fusion of postoperative CT with preoperative MRI images can be an alternative for the assessment of electrode positioning. The purpose of this study was to assess the accuracy of measurements realized on fused images (acquired without a stereotactic frame) using a manufacturer-provided software. METHODS: Data from 23 Parkinson's disease patients who underwent bilateral electrode placement for subthalamic nucleus (STN) DBS were acquired. Preoperative high-resolution T2-weighted sequences at 3 T, and postoperative CT series were fused using a commercially available software. Electrode tip position was measured on the obtained images in three directions (in relation to the midline, the AC-PC line and an AC-PC line orthogonal, respectively) and assessed in relation to measures realized on postoperative 3D T1 images acquired at 1.5 T. RESULTS: Mean differences between measures carried out on fused images and on postoperative MRI lay between 0.17 and 0.97 mm. CONCLUSION: Fusion of CT and MRI images provides a safe and fast technique for postoperative assessment of electrode position in DBS.

[Olfactory function after transsphenoidal pituitary surgery]. / Fonction olfactive après chirurgie hypophysaire transsphénoidale.

Pituitary surgery remains mainly performed trough a transnasal, transseptal and transsphenoidal way. This surgical approach can damage intranasal structures and, in particular, may impede olfactory function. Our study investigates olfactory function in 67 patients undergoing this type of surgery before and 3 months after surgery. Mean olfactory scores were identical pre- and postoperatively. However, on an individual bases seven percent of the patients showed a clear decrease in olfactory function. In conclusion, transnasal, transseptal and transsphenoidal surgery is relativelv safe with regards to olfactory function

Deformation of the corona radiata and internal capsule in normal pressure hydrocephalus.

BACKGROUND AND PURPOSE: The pathophysiology of the clinical manifestations in normal pressure hydrocephalus (NPH) remains obscure. Ventricular dilatation could generate forces on the paracentral fibers of the corona radiata (CR), hence interfering with their function and producing the classical clinical triad. The analysis of the regional displacement and deformation of the white matter bundles, forming the corona radiata and internal capsule, may clarify the relationship between ventricular dilatation and clinical manifestations in NPH. METHOD: An experimental finite element (FE) analysis was used to simulate ventricular dilatation in 3 dimensions (3D) and to calculate the strain and deformation on the surrounding parenchyma. Magnetic resonance diffusion tensor imaging-based white matter tractography was then applied to retrieve the displacement and deformation exerted along various fiber bundles of the corona radiata and internal capsule. Anterior and posterior limb displacements and elongations were compared using a paired samples t-test. RESULTS: The internal capsule, hence the corona radiata, of each cerebral hemisphere was segmented into anterior and posterior limbs. Mean displacements and elongations were calculated for each limb. Mean displacement was significantly larger in the anterior limb whereas mean deformation was larger in the posterior limb (P<0.01). CONCLUSION: The present simulation demonstrates that ventricular dilatation does not have a homogeneous effect on the periventricular fibre tracts, with a particular load on the corticospinal tract. The affection of this tract remains thereby a potential factor in the generation of the NPH gait disorders.

Ventricle equilibrium position in healthy and normal pressure hydrocephalus brains using an analytical model.

The driving force that causes enlargement of the ventricles remains unclear in case of normal pressure hydrocephalus (NPH). Both healthy and NPH brain conditions are characterized by a low transparenchymal pressure drop, typically 1 mm Hg. The present paper proposes an analytical model for normal and NPH brains using Darcy's and Biot's equations and simplifying the brain geometry to a hollow sphere with an internal and external radius. Self-consistent solutions for the large deformation problem that is associated with large ventricle dilation are presented and the notion of equilibrium or stable ventricle position is highlighted for both healthy and NPH conditions. The influence of different biomechanical parameters on the stable ventricle geometry is assessed and it is shown that both CSF seepage through the ependyma and parenchymal permeability play a key role. Although very simple, the present model is able to predict the onset and development of NPH conditions as a deviation from healthy conditions.

Pulse amplitude of intracranial pressure waveform in hydrocephalus.

BACKGROUND: There is increasing interest in evaluation of the pulse amplitude of intracranial pressure (AMP) in explaining dynamic aspects of hydrocephalus. We reviewed a large number of ICP recordings in a group of hydrocephalic patients to assess utility of AMP. MATERIALS AND METHODS: From a database including approximately 2,100 cases of infusion studies (either lumbar or intraventricular) and overnight ICP monitoring in patients suffering from hydrocephalus of various types (both communicating and non-communicating), etiology and stage of management (non-shunted or shunted) pressure recordings were evaluated. For subgroup analysis we selected 60 patients with idiopathic NPH with full follow-up after shunting. In 29 patients we compared pulse amplitude during an infusion study performed before and after shunting with a properly functioning shunt. Amplitude was calculated from ICP waveforms using spectral analysis methodology. FINDINGS: A large amplitude was associated with good outcome after shunting (positive predictive value of clinical improvement for AMP above 2.5 mmHg was 95%). However, low amplitude did not predict poor outcome (for AMP below 2.5 mmHg 52% of patients improved). Correlations of AMP with ICP and Rcsf were positive and statistically significant (N = 131 with idiopathic NPH; R = 0.21 for correlation with mean ICP and 0.22 with Rcsf; p< 0.01). Correlation with the brain elastance coefficient (or PVI) was not significant. There was also no significant correlation between pulse amplitude and width of the ventricles. The pulse amplitude decreased (p < 0.005) after shunting. CONCLUSIONS: Interpretation of the ICP pulse waveform may be clinically useful in patients suffering from hydrocephalus. Elevated amplitude seems to be a positive predictor for clinical improvement after shunting. A properly functioning shunt reduces the pulse amplitude.

Stratified gray-scale median analysis and color mapping of the carotid plaque: correlation with endarterectomy specimen histology of 28 patients.

BACKGROUND AND PURPOSE: To determine whether a stratified gray-scale median (GSM) analysis of the carotid plaque combined with color mapping could predict plaque histology better than an overall GSM measurement. METHODS: Thirty-one carotid plaques derived from 28 patients undergoing carotid endarterectomy were investigated by ultrasound. GSMs of the whole plaque were used as measurement of echogenicity. A profile of the regional GSM as a function of distance from the plaque surface could be generated. Plaque pixels were further mapped into 3 different colors depending on their GSM value. RESULTS: Plaques with large calcifications presented the highest GSM values, and those with large hemorrhagic areas or with a predominant necrotic core exhibited the lowest. Fibrous plaques had intermediate GSM values. A necrotic core located in a juxtalumenal position was associated with significantly lower GSM values (P=0.009) and with a predominant red color (GSM <50) at the surface (P=0.0019). With respect to the thickness of the fibrous cap and the position of the necrotic core, the sensitivity and specificity of the predominant red color of the whole plaque was respectively 45% and 67% and 53% and 75%; considering the predominant red color of the surface, the sensitivity and specificity increased to 73% and 67% and 84% and 75%, respectively. CONCLUSIONS: The stratified GSM measurement combined with color mapping showed a good correlation with the different histopathological components and further allowed identification with good accuracy of determinants of plaque instability. This approach should be investigated in a prospective, natural history study.

The relationship between CSF circulation and cerebrovascular pressure-reactivity in normal pressure hydrocephalus.

OBJECTIVE: Previously, we documented association between CSF circulation and transcranial-Doppler derived autoregulation in non-shunted patients suffering from hydrocephalus. In the present study we sought to investigate the relationship between the resistance to CSF outflow and pressure-reactivity both in shunted and non-shunted NPH patients. MATERIAL AND METHODS: Sixty-eight patients (47 non-shunted and 21 shunted) with NPH have been examined as a part of routine diagnostic procedure. Resistance to CSF outflow (Rcsf) was measured using a ventricular constant rate infusion test. Cerebrovascular pressure-reactivity was assessed as a moving correlation coefficient (PRx) between coherent 'slow waves' of ICP and arterial blood pressure (ABP). This variable has previously been demonstrated to correlate with the autoregulation of CBF in patients following head injury. Results. In non-shunted patients cerebrovascular pressure-reactivity (PRx) was negatively correlated with Rcsf (R = -0.5; p < 0.0005). This relationship was inverted in shunted patients: a positive correlation between PRx and Rcsf was found (R = 0.51; p < 0.03). CONCLUSION: Cerebrovascular pressure-reactivity is disturbed in patients with normal resistance to CSF outflow, suggesting underlying cerebrovascular disease. This result confirms our previous finding where transcranial Doppler autoregulation was investigated. After shunting the pressure-reactivity strongly depends on shunt functioning and deteriorates when the shunt is blocked.

Clinical testing of CSF circulation in hydrocephalus.

INTRODUCTION: Recent 'NPH Dutch trial' has re-emphasised the importance of the resistance to cerebrospinal fluid (CSF) outflow (Rcsf) in the diagnosis of hydrocephalus. We re-evaluated the clinical utility of the physiological measurements revealing CSF dynamics. The results were summarized from our previous publications. The Computerised Infusion Test was designed to perform quick and low-invasive assessment of CSF dynamics described by parameters as Rcsf, brain compliance, elasticity coefficient, estimated sagittal sinus pressure, CSF formation rate and other variables. Overnight ICP monitoring with quantitative analysis of CSF dynamics was used in those cases where infusion study was unreliable or producing results close to the borderline. We found that the threshold of normal and increased Rcsf should be age-matched because in patients older than 55 Rcsf increases 0.2 mm Hg/(ml/min) per year (p < 0.04: N = 56). Rcsf was positively correlated with cerebral autoregulation (R = 0.41; p < 0.03; N = 36) indicating that in patients with symptoms of NPH but normal Rcsf underlying cerebrovascular disease is more frequent. Computerized infusion tests and overnight ICP monitoring are useful diagnostic technique alone or in conjunction with other forms of physiological measurement.

Intracranial baroreflex yielding an early cushing response in human.

The Cushing response is a pre-terminal sympatho-adrenal systemic response to very high ICP. Animal studies have demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response. Infusion studies are routine procedures to investigate, by infusing CSF space with saline, the cerebrospinal fluid (CSF) biophysics in patients suspected of hydrocephalus. Our study aims at assessing systemic and cerebral haemodynamic changes during moderate rise of ICP in human. Infusion studies were performed in 34 patients. This is a routine test perform in patients presenting with symptoms of NPH during their pre-shunting assessment. Arterial blood pressure (ABP) and cerebral blood flow velocity (FV) were non-invasively monitored with photoplethysmography and transcranial Doppler. The rise in ICP (8.2 +/- 5.1 mmHg to 25 +/- 8.3 mmHg) was followed by a significant rise in ABP (106.6 +/- 29.7 mmHg to 115.2 +/- 30.1 mmHg), drop in CPP (98.3 +/- 29 mmHg to 90.2 +/- 30.7 mmHg) and decrease in FV (55.6 +/- 17 cm/s to 51.1 +/- 16.3 cm/s). Increasing ICP did not alter heart rate (70.4 +/- 10.4/min to 70.3 +/- 9.1/min) but augmented the heart rate variance (0.046 +/- 0.058 to 0.067 +/- 0.075/min). In a population suspected of hydrocephalus, our study demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response, demonstrating an early Cushing response in human and a putative intracranial baroreflex.

Link between vasogenic waves of intracranial pressure and cerebrospinal fluid outflow resistance in normal pressure hydrocephalus.

Recent studies on normal pressure hydrocephalus (NPH) have pointed to a possible link between the disturbance in CSF circulation and cerebrovascular factors. We investigated the quantitative relationship between the resistance to CSF outflow (Rcsf) and vasogenic waves of ICP in patients with normal pressure hydrocephalus. Forty-five patients with NPH were investigated by an infusion study. The magnitudes of vasogenic ICP components: pulse, respiratory and slow vasogenic waves were assessed, and compared with Rcsf. Both baseline respiratory and slow waves of ICP were positively correlated with Rcsf. The respiratory wave at baseline was a single independent predictor of Rcsf (r = 0.66, p < 0.0002). All vasogenic components increased significantly during the infusion test. The magnitude of the increase was positively correlated with Rcsf. The vasogenic ICP waves, notably the respiratory wave of ICP, correlate with the resistance to CSF outflow.

Occipital condyle fractures in children. Case report and review of the literature.

Occipital condyle fractures (OCF) are seldom described in children, with only 14 cases reported in the literature. We report the observation of a 13-year-old child in whom such a fracture was diagnosed. A review of the paediatric cases allowed us to identify the clinical features of OCF in children. The average age was found to be 10 years, and the causative traumatism was most often related to road traffic or sporting accidents with associated head injury. The level of consciousness was depressed in 67% of the cases, and in 53%, an injury to the cranial nerves, brain stem or high spinal cord was present. Neck pain with reduction of head mobility was reported in 27% of the cases. Treatment was generally conservative, i.e. a hard collar or halo vest for an average of 8 weeks. The course was favourable with respect to osseous consolidation, mobility and pain. On the other hand, the neurological deficits improved, but sequelae remained. Early diagnosis and treatment is mandatory since the secondary displacement of fractured fragments can injure the cranial nerves in a delayed fashion or even be fatal due to compression of the brain stem.