Jean Ciurea

A personalized stereotactic fixture for implantation of depth electrodes in stereoelectroencephalography.

Background: The stereoelectroencephalographic (SEEG) implantation procedures still represent a challenge due to the intrinsic complexity of the method and the number of depth electrodes required. Objectives: We aim at designing and evaluating the accuracy of a custom stereotactic fixture based on the StarFix™ technology (FHC Inc., Bowdoin, ME) that significantly simplifies and optimizes the implantation of depth electrodes used in presurgical evaluation of patients with drug-resistant epilepsy. Methods: Fiducial markers that also serve as anchors for the fixture are implanted into the patients skull prior to surgery. A 3D fixture model is designed within the surgical planning software, with the planned trajectories incorporated in its design, aligned with the patients anatomy. The stereotactic fixture is built using 3D laser sintering technology based on the computer-generated model. Bilateral rectangular grids of guide holes orthogonal to the midsagittal plane and centered on the midcommissural point are incorporated in the fixture design, allowing a wide selection of orthogonal trajectories. Up to two additional grids can be accommodated for targeting structures where oblique trajectories are required. The frame has no adjustable parts, this feature reducing the risk of inaccurate coordinate settings while simultaneously reducing procedure time significantly. Results: We have used the fixture for the implantation of depth electrodes for presurgical evaluation of 4 patients with drug-resistant focal epilepsy, with nearly 2-fold reduction in the duration of the implantation procedure. We have obtained a high accuracy with a submillimetric mean positioning error of 0.68 mm for the anchor bolts placed at the trajectory entry point and 1.64 mm at target. Conclusions: The custom stereotactic fixture design greatly simplifies the planning procedure and significantly reduces the time in the operating room, while maintaining a high accuracy.

A comparative study of the effects of pulse parameters for intracranial direct electrical stimulation in epilepsy

OBJECTIVES Intracranial direct electrical stimulation (iDES) uses different parameters for mapping the epileptogenic and functional areas in patients with drug-resistant epilepsy. We aim at finding the common factor driving the electrographic responses to various iDES protocols reported in the literature. METHODS We recorded early responses to single-pulse iDES in 11 subjects undergoing stereoelectroencephalographic presurgical evaluation. We systematically explored the role of several pulse parameters in evoking responses: monophasic versus biphasic pulses, current intensity, and pulse duration. We performed a correlation and regression analysis between responses to different protocols by amplitude, duration, and charge per phase. RESULTS Regression analysis revealed that the responses were similar for the same charge per phase, regardless of their pulse duration and amplitude. Over eighty percent (82.8%) of the responses to variable pulse duration biphasic stimulation and between 58.6% and 81.9% of the responses to monophasic stimulation, depending on pulse polarity, were correlated to the responses evoked by the variable amplitude biphasic protocol, when expressing stimulus strength in terms of charge per phase. CONCLUSIONS Regardless of the combination of different stimulation currents, it is the underlying charge per phase parameter that determines the magnitude of the responses to single-pulse electrical stimulation. SIGNIFICANCE Our results provide a unifying method for comparing iDES protocols.

Intrusive Thoughts Elicited by Direct Electrical Stimulation during Stereo-Electroencephalography

Cortical direct electrical stimulation (DES) is a method of brain mapping used during invasive presurgical evaluation of patients with intractable epilepsy. Intellectual auras like intrusive thoughts, also known as forced thinking (FT), have been reported during frontal seizures. However, there are few reports on FT obtained during DES in frontal cortex. We report three cases in which we obtained intrusive thoughts while stimulating the dorsolateral prefrontal cortex and the white matter in the prefrontal region. In order to highlight the effective connectivity that might explain this clinical response, we have analyzed cortico-cortical potentials evoked by single pulse electrical stimulation.

Presurgical Evaluation and Epilepsy Surgery in MRI Negative Resistant Epilepsy of Childhood with Good Outcome.

Magnetic resonance imaging (MRI)-negative epilepsy may be successfully solved with a multidisciplinary approach using invasive recordings, image and signal analysis. The whole methodology used by the epilepsy surgery team is systematically described based on an resistant epilepsy case with all steps and rationale of choosing different investigation methods from surface electroencephalography (EEG) to invasive recordings. Due to negative MRI and non-concordant ictal surface EEG with clinical semiology, the patient was investigated with stereo- EEG (SEEG), aiming to delimitate epileptogenic and eloquent cerebral areas. Implantation strategy, seizures recordings, stimulation, resection planning using quantitative EEG analysis, and the surgery plan are presented. The patient has been seizure-free for 14 months so far, with improved behavior and daily life quality. Post-operative examination revealed focal cortical dysplasia type II B.

Modular Signatures and Neural Avalanches in Epileptic Brain Networks

Epileptic seizures are characterized by a rich dynamic spectrum consisting of excessive, abnormal and synchronized firing of neuron ensembles. Such abnormal firing has been quantitatively characterized via power laws in neural avalanches. The term “neural avalanche” has been used to illustrate the excessively amplified neural firing patterns that lead to epileptic seizures. The pattern of amplified firing in neural avalanches betrays a modular signature in the spread of activation across cortical minicolumns. According to this modular approach of epilepsy, the excessive amplification of neural firing in a cortical minicolumn results from a defect within the “inhibitory curtain” surrounding the pyramidal cells. The functional basis of this approach provides insights into potential clinical interventions.

Successful epilepsy surgery in frontal lobe epilepsy with startle seizures: a SEEG study.

Pre-surgical assessment and surgical management of frontal epilepsy with normal MRI is often challenging. We present a case of a 33-year-old, right-handed, educated male. During childhood, his seizures presented with mandibular myoclonus and no particular trigger. As a young adult, he developed seizures with a startle component, triggered by unexpected noises. During his ictal episodes, he felt fear and grimaced with sudden head flexion and tonic axial posturing. Similar seizures also occurred without startle. Neuropsychological assessment showed executive dysfunction and verbal memory deficit. The cerebral MRI was normal. Electro-clinical reasoning, investigations performed, the results obtained and follow-up are discussed in detail. [Published with video sequence].

Connectomics in Patients with Temporal Lobe Epilepsy

The human brain is an amazingly complex structure whose functionality, including high-order cognitive functions, is determined by intricate connectivity patterns between tens of billions of neurons (Azevedo et al. 2009). The signaling between neurons is deceivingly simple, using binary-like electrical impulses, such that the multitude of brain functions, that are often performed concurrently, are the result of connectivity patterns across various spatial scales (Bullock et al. 1977; Budd and Kisvarday 2012), that implement a mixed sequential, parallel or hierarchical architecture. The brain regulates breathing and heart rate, collects and processes sensory information, and controls all the voluntary and involuntary movements and actions. While some of these functions are performed by well-defined areas of the brain (i.e. visual stimuli are processed solely by the primary visual cortex), some higher level functions (i.e. speech production, problem solving, music performance) can only be accomplished by various brain areas working together in a serial or, more likely, in a parallel or distributed design (Sigman and Dehaene 2008).

EEG Assessment of Consciousness Rebooting from Coma

The bi-dimensional arousal-awareness operational framework of defining consciousness assumes a graded level of both arousal and awareness. At the lower end of both the arousal and awareness scales is coma, defined as a state of unresponsiveness, in which a patient cannot be awaken. Recovery from coma following brain injury occurs through a sequence of disorders of consciousness (DOC) ranging from unresponsive wakefulness syndrome (UWS)/vegetative state (VS) which shows no signs of awareness to minimally conscious states (MCS) from which consciousness can emerge. The graded consciousness recovery parallels scales of brain injury severity suggesting that consciousness recovers by “turning on” hierarchical services. This sequence resembles a computer “booting” process, which may “hang” at a specific “intermediate levels of consciousness” such as UWS/VS or MCS. The recovery sequence can be assessed by electroencephalography (EEG), a large-scale measure of fluctuations in electrical activity of the brain. Resting state EEG assesses the graded recovery of brain oscillations from isoelectric line to burst-suppression (BS) to EEG slowing to wakefulness alpha activity and faster rhythms. Given that some degree of “connectivity” is required for consciousness, the assessment of DOC can be improved by testing the EEG in controlled stimulation paradigms addressing either the event related potential (ERP) or the event related changes in background EEG rhythms referred to as reactivity, which can be evoked even in BS. This grading of EEG changes provides the rationale for developing EEG indexes for monitoring the “booting process” during coma recovery to improve the diagnosis and prognostication of DOC.

Neuromodulation of Consciousness Disorders

Some patients may develop an altered state of consciousness (coma, vegetative state, minimal consciousness state) following traumatic and other brain injuries. While the cause of their altered consciousness may be well documented in most cases, the precise underlying mechanisms mediating the altered consciousness and its treatment are yet to be discovered. Several hypotheses have been put forward on how the level of consciousness can be improved; all are based on the principle that an injured brain needs to reconnect its disrupted areas. To address this need, several neuromodulation therapies (using invasive and noninvasive stimulation) may serve this purpose. Invasive therapies use chronic electrodes for stimulation, while non-invasive therapies employ transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and somato-sensitive stimulation (SSS). The purpose of this chapter is to critically analyze the progress of these therapeutic methods and to review what is still needed to improve the impaired conscious states.

George Marinesco in the Constellation of Modern Neuroscience

George Marinesco is the founder of Romanian School of Neurology and one of the most remarkable neuroscientists of the last century. He was the pupil of Jean-Martin Charcot in Salpêtrière Hospital in Paris, France, but visited many other neurological centers where he met the entire constellation of neurologists of his time, including Camillo Golgi and Santiago Ramón y Cajal. The last made the preface of Nervous Cell, written in French by Marinesco. The original title was “La Cellule Nerveuse” and is considered even now a basic reference book for specialists in the field. He was a refined clinical observer with an integrative approach, as could be seen from the multitude of his discoveries. The descriptions of the succulent hand in syringomyelia, senile plaque in old subjects, palmar jaw reflex known as Marinesco-Radovici sign, or the application of cinematography in medicine are some of his important contributions. He was the first who described changes of locus niger in a patient affected by tuberculosis, as a possible cause in Parkinson disease. Before modern genetics, Marinesco and Sjögren described a rare and complex syndrome bearing their names. He was a hardworking man, focused on his scientific research, did not accepted flattering of others and was a great fighter against the injustice of the time.