Primary neurolymphomatosis of the trigeminal nerve.

We report a case of a primary malignant lymphoma of the trigeminal nerve that was associated with facial pain. A 65-year-old man was examined at another hospital for unilateral facial pain. Carbamazepine was prescribed, but his symptoms did not improve. Magnetic resonance imaging (MRI) revealed swelling of the trigeminal nerve and a mass lesion in Meckel's cave. The patient was referred to our hospital at this point. Gadolinium-enhanced MRI and F18-Fluorodeoxyglucose-position emission tomography suggested a likely malignant tumour and a biopsy was performed. Histopathological examination showed diffuse a large B cell lymphoma. The patient was treated with high-dose methotrexate (HD-MTX) and radiotherapy. Despite responding well to initial treatment, the patient relapsed, with lymphoma observed throughout the body. He died of pneumonia 18 months after the initial diagnosis. Facial pain is a symptom that is commonly managed in general practice. If symptoms do not improve, repeated imaging studies, including contrast MRI, is warranted. This is the first reported case of primary neurolymphomatosis (NL) of the trigeminal nerve associated with facial pain alone. Furthermore, HD-MTX and radiotherapy may be considered for the management of primary NL of a cranial nerve.

Facephenes and rainbows: Causal evidence for functional and anatomical specificity of face and color processing in the human brain.

Neuroscientists have long debated whether some regions of the human brain are exclusively engaged in a single specific mental process. Consistent with this view, fMRI has revealed cortical regions that respond selectively to certain stimulus classes such as faces. However, results from multivoxel pattern analyses (MVPA) challenge this view by demonstrating that category-selective regions often contain information about "nonpreferred" stimulus dimensions. But is this nonpreferred information causally relevant to behavior? Here we report a rare opportunity to test this question in a neurosurgical patient implanted for clinical reasons with strips of electrodes along his fusiform gyri. Broadband gamma electrocorticographic responses in multiple adjacent electrodes showed strong selectivity for faces in a region corresponding to the fusiform face area (FFA), and preferential responses to color in a nearby site, replicating earlier reports. To test the causal role of these regions in the perception of nonpreferred dimensions, we then electrically stimulated individual sites while the patient viewed various objects. When stimulated in the FFA, the patient reported seeing an illusory face (or "facephene"), independent of the object viewed. Similarly, stimulation of color-preferring sites produced illusory "rainbows." Crucially, the patient reported no change in the object viewed, apart from the facephenes and rainbows apparently superimposed on them. The functional and anatomical specificity of these effects indicate that some cortical regions are exclusively causally engaged in a single specific mental process, and prompt caution about the widespread assumption that any information scientists can decode from the brain is causally relevant to behavior.

Biopsy-proven case of Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system.

A 75-year-old woman was admitted to our hospital with rapidly deteriorating consciousness disturbance. She had a 7-year history of rheumatoid arthritis (RA), which had been treated with methotrexate (MTX) and prednisolone. Brain T2-weighted MRI showed diffuse high-intensity lesions in the cerebral subcortical and deep white matter, bilateral basal ganglia and thalamus. A cerebrospinal fluid examination revealed elevated protein levels and positive Epstein-Barr virus (EBV) DNA. Human immunodeficiency virus was negative. Brain biopsy showed perivascular lymphocytic infiltration in the parenchyma and meninx with EBV-encoded small RNA (EBER). Since this case did not fulfill the criteria for chronic active EBV infection (CAEBV), she was diagnosed with Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system. High-dose methylprednisolone, acyclovir, ganciclovir and foscarnet were not effective. Although EBV is a causative agent of infectious mononucleosis (IM), lymphomas and nasopharyngeal carcinomas, vasculitic pathology of the central nervous system with EBV reactivation in the elderly is rare. Immunosuppressive drugs such as steroids and MTX are widely used to treat autoimmune disorders, but may exacerbate the reactivation of EBV. This is the first case of biopsy-proven EBV-positive/HIV-negative vasculitis during the treatment of RA with MTX and steroids. This case indicates that EBV-associated vasculitis needs to be considered as a differential diagnosis of CNS vasculitis.

Long-term outcome and neuroradiologic changes after multiple hippocampal transection combined with multiple subpial transection or lesionectomy for temporal lobe epilepsy.

OBJECTIVE: Multiple hippocampal transection (MHT) is a surgical procedure developed to avoid postoperative memory decline. Its efficacy has been documented in only a few small series with relatively short observation periods. We prospectively evaluated the long-term seizure and cognitive outcomes of MHT combined with multiple subpial transection or lesionectomy (MHT + MST/L). Moreover, we quantitatively evaluated the structural and metabolic neuroradiologic changes after the procedure to elucidate the anatomofunctional correlates of memory preservation. METHODS: Twenty-four patients underwent MHT + MST/L for treatment of drug-resistant mesial temporal lobe epilepsy (mTLE) and were followed for more than 5 years. Indications for the procedure were the following: (1) verbally dominant-sided surgery in patients with a radiologically normal hippocampus or normal/near normal memory, and (2) surgery for patients with concomitant epileptic activity on the contralateral side, that is, when the surgery was considered a high risk for severe postoperative memory decline. Seizure outcome was evaluated using Engel's classification 1, 2, and 3 years after surgery, and at the last visit (LV). Three subgroups were evaluated as well: magnetic resonance imaging (MRI) negative (MN), hippocampal sclerosis (HS), and normal hippocampus with extrahippocampal lesion (NHEL). The long-term cognitive outcome was followed through to LV in patients who underwent verbally dominant-sided surgery. Hippocampal volume (HV), diffusion tensor parameters (DTP), and glucose utilization (GU) were determined from MRI and fluorodeoxyglucose-positron emission tomography (FDG-PET) studies performed before and >6 months after surgery. RESULTS: Whereas the rate of Engel class I as a whole was 71% at 1 year and 67% at LV, the rates in the MN, HS, and NHEL groups were 60%, 67%, and 100% at 1 year, respectively, and 70%, 56%, and 80% at LV, respectively. Memory indices after verbally dominant-sided surgery transiently declined at 1 month but recovered to and remained at the preoperative level through LV. The HV, DTP of the fornix, and GU of the temporal lobe on the treated side showed pathologic changes even when the transiently declined memory indices had recovered to the preoperative level. SIGNIFICANCE: The long-term outcome for complex partial seizures after MHT + MST/L was comparable to that seen after anterior temporal lobectomy. The long-term cognitive outcome was favorable, even for patients with a high risk of severe postoperative memory decline. MHT + MST/L may be a treatment option for mTLE in which resective surgery carries a risk of postoperative memory decline, particularly in patients without MRI lesion. A discrepancy between the preserved memory and the pathologic neuroradiologic changes indicates the necessity for further studies including functional MRI.

Proceedings of the Seventh International Workshop on Advances in Electrocorticography.

The Seventh International Workshop on Advances in Electrocorticography (ECoG) convened in Washington, DC, on November 13-14, 2014. Electrocorticography-based research continues to proliferate widely across basic science and clinical disciplines. The 2014 workshop highlighted advances in neurolinguistics, brain-computer interface, functional mapping, and seizure termination facilitated by advances in the recording and analysis of the ECoG signal. The following proceedings document summarizes the content of this successful multidisciplinary gathering.

Feasibility of diffusion tensor tractography for preoperative prediction of the location of the facial and vestibulocochlear nerves in relation to vestibular schwannoma.

BACKGROUND: According to recent findings, diffusion tensor tractography (DTT) only allows prediction of facial nerve location in relation to vestibular schwannoma (VS) with high probability. However, previous studies have not mentioned why only the facial nerve was selectively visualized. Our previous report investigated the optimal conditions of DTT for normal facial and vestibulocochlear nerves. In the present study, we applied the optimal conditions of DTT to VS patients to assess the feasibility of DTT for the facial and vestibulocochlear nerves. METHODS: We investigated 11 patients with VS who underwent tumor resection. Visualized tracts were compared with locations of the facial and cochlear nerves as identified by intraoperative electrophysiological monitoring. RESULTS: With the proposed method, visualized tracts corresponded to pathway area of the facial or cochlear nerves in nine of 11 patients (81.8%); specifically, to the pathway area of the facial nerve in three of 11 patients (27.3%), and to the pathway area of the cochlear nerve in six of 11 patients (54.5%). CONCLUSIONS: We visualized facial or vestibulocochlear nerves in nine of 11 patients (81.8%). For the first time, DTT proved able to visualize not only the facial nerve but also the vestibulocochlear nerve in VS patients. Despite our findings, good methods for distinguishing whether a visualized nerve tract represents facial nerve, vestibulocochlear nerve, or only noise remain unavailable. Close attention should therefore be paid to the interpretation of visualized fibers.

A case of pathology-proven neuromyelitis optica spectrum disorder with Sjögren syndrome manifesting aphasia and apraxia due to a localized cerebral white matter lesion.

A woman with Sjögren syndrome manifesting as aphasia with a left deep cerebral white matter lesion tested positive for anti-aquaporin 4 (AQP4) antibody. Open biopsy of the lesion revealed active demyelination with edematous changes and the preservation of most axons, indicating a non-necrotic demyelinating lesion. Immunostaining for AQP4 was diffusely lost, whereas the loss of glial fibrillary acidic protein immunostaining was limited but with highly degenerated astrocytic foot processes in perivascular areas. These results suggested neuromyelitis optica spectrum disorder (NMOSD) pathology rather than Sjögren-related vasculitis. Only cerebral cortical symptoms with a cerebral white matter lesion could be observed in NMOSDs.

The significance of parahippocampal high gamma activity for memory preservation in surgical treatment of atypical temporal lobe epilepsy.

OBJECTIVE: Resective surgery for mesial temporal lobe epilepsy (MTLE) with a correspondent lesion has been established as an effective and safe procedure. Surgery for temporal lobe epilepsies with bilateral hippocampal sclerosis or without correspondent lesions, however, carries a higher risk of devastating memory decline, underscoring the importance of establishing the memory-dominant side preoperatively and adopting the most appropriate procedure. In this study, we focused on high gamma activities (HGAs) in the parahippocampal gyri and investigated the relationship between memory-related HGAs and memory outcomes after hippocampal transection (HT), a hippocampal counterpart to neocortical multiple subpial transection. The transient nature of memory worsening after HT provided us with a rare opportunity to compare HGAs and clinical outcomes without risking permanent memory disorders. METHODS: We recorded electrocorticography from parahippocampal gyri of 18 patients with temporal lobe epilepsy while they executed picture naming and recognition tasks. Memory-related HGA was quantified by calculating differences in power amplification of electrocorticography signals in a high gamma range (60-120 Hz) between the two tasks. We compared memory-related HGAs from correctly recognized and rejected trials (hit-HGA and reject-HGA). Using hit-HGA, we determined HGA-dominant sides and compared them with memory outcomes after HT performed on seven patients. RESULTS: We observed memory-related HGA mainly between 500 and 600 msec poststimulus. Hit-HGA was significantly higher than reject-HGA. Three patients who had surgery on the HGA-dominant side experienced transient memory worsening postoperatively. The postoperative memory functions of the other four patients remained unchanged. SIGNIFICANCE: Parahippocampal HGA was indicated to reflect different memory processes and be compatible with the outcomes of HT, suggesting that HGA could provide predictive information on whether the mesial temporal lobe can be resected without causing memory worsening. This preliminary study suggests a refined surgical strategy for atypical MTLE based on reliable memory lateralization.

Proceedings of the Fifth International Workshop on Advances in Electrocorticography.

The Fifth International Workshop on Advances in Electrocorticography convened in San Diego, CA, on November 7-8, 2013. Advancements in methodology, implementation, and commercialization across both research and in the interval year since the last workshop were the focus of the gathering. Electrocorticography (ECoG) is now firmly established as a preferred signal source for advanced research in functional, cognitive, and neuroprosthetic domains. Published output in ECoG fields has increased tenfold in the past decade. These proceedings attempt to summarize the state of the art.

Upper extremity training followed by lower extremity training with a brain-computer interface rehabilitation system.

Introduction: Brain-computer interfaces (BCIs) based on functional electrical stimulation have been used for upper extremity motor rehabilitation after stroke. However, little is known about their efficacy for multiple BCI treatments. In this study, 19 stroke patients participated in 25 upper extremity followed by 25 lower extremity BCI training sessions. Methods: Patients' functional state was assessed using two sets of clinical scales for the two BCI treatments. The Upper Extremity Fugl-Meyer Assessment (FMA-UE) and the 10-Meter Walk Test (10MWT) were the primary outcome measures for the upper and lower extremity BCI treatments, respectively. Results: Patients' motor function as assessed by the FMA-UE improved by an average of 4.2 points (p < 0.001) following upper extremity BCI treatment. In addition, improvements in activities of daily living and clinically relevant improvements in hand and finger spasticity were observed. Patients showed further improvements after the lower extremity BCI treatment, with walking speed as measured by the 10MWT increasing by 0.15 m/s (p = 0.001), reflecting a substantial meaningful change. Furthermore, a clinically relevant improvement in ankle spasticity and balance and mobility were observed. Discussion: The results of the current study provide evidence that both upper and lower extremity BCI treatments, as well as their combination, are effective in facilitating functional improvements after stroke. In addition, and most importantly improvements did not stop after the first 25 upper extremity BCI sessions.

Mapping of the central sulcus using non-invasive ultra-high-density brain recordings.

Brain mapping is vital in understanding the brain's functional organization. Electroencephalography (EEG) is one of the most widely used brain mapping approaches, primarily because it is non-invasive, inexpensive, straightforward, and effective. Increasing the electrode density in EEG systems provides more neural information and can thereby enable more detailed and nuanced mapping procedures. Here, we show that the central sulcus can be clearly delineated using a novel ultra-high-density EEG system (uHD EEG) and somatosensory evoked potentials (SSEPs). This uHD EEG records from 256 channels with an inter-electrode distance of 8.6 mm and an electrode diameter of 5.9 mm. Reconstructed head models were generated from T1-weighted MRI scans, and electrode positions were co-registered to these models to create topographical plots of brain activity. EEG data were first analyzed with peak detection methods and then classified using unsupervised spectral clustering. Our topography plots of the spatial distribution from the SSEPs clearly delineate a division between channels above the somatosensory and motor cortex, thereby localizing the central sulcus. Individual EEG channels could be correctly classified as anterior or posterior to the central sulcus with 95.2% accuracy, which is comparable to accuracies from invasive intracranial recordings. Our findings demonstrate that uHD EEG can resolve the electrophysiological signatures of functional representation in the brain at a level previously only seen from surgically implanted electrodes. This novel approach could benefit numerous applications, including research, neurosurgical mapping, clinical monitoring, detection of conscious function, brain-computer interfacing (BCI), rehabilitation, and mental health.

Characteristic profiles of high gamma activity and blood oxygenation level-dependent responses in various language areas.

High gamma activity (HGA) has been shown to be positively correlated with blood oxygenation level-dependent (BOLD) responses in the primary cortices with simple tasks. It is, however, an open question whether the correlation is simply applied to the association areas related to higher cognitive functions. The aim of this study is to investigate quantitative correlation between HGA and BOLD and their spatial and temporal profiles during semantic processing. Thirteen patients with intractable epilepsy underwent fMRI and electrocorticography (ECoG) with a word interpretation task to evoke language-related responses. Percent signal change of BOLD was calculated at each site of ECoG electrode, which has power amplification of high gamma band (60-120 Hz) activity. We transformed locations of individual electrodes and brains to a universal coordination using SPM8 and made the quantitative comparisons on a template brain. HGAs were increased in several language-related areas such as the inferior frontal and middle temporal gyri and were positively correlated with BOLD responses. The most striking finding was different temporal dynamics of HGAs in the different brain regions. Whereas the frontal lobe showed longer-lasting HGA, the HGA-intensity on the temporal lobe quickly declined. The different temporal dynamics of HGA might explain why routine language-fMRI hardly detected BOLD in the temporal lobe. This study clarified different neural oscillation and BOLD response in various brain regions during semantic processing and will facilitate practical utilization of fMRI for evaluating higher-order cognitive functions not only in basic neuroscience, but also in clinical practice.

Characterization of High-Gamma Activity in Electrocorticographic Signals.

Introduction: Electrocorticographic (ECoG) high-gamma activity (HGA) is a widely recognized and robust neural correlate of cognition and behavior. However, fundamental signal properties of HGA, such as the high-gamma frequency band or temporal dynamics of HGA, have never been systematically characterized. As a result, HGA estimators are often poorly adjusted, such that they miss valuable physiological information. Methods: To address these issues, we conducted a thorough qualitative and quantitative characterization of HGA in ECoG signals. Our study is based on ECoG signals recorded from 18 epilepsy patients while performing motor control, listening, and visual perception tasks. In this study, we first categorize HGA into HGA types based on the cognitive/behavioral task. For each HGA type, we then systematically quantify three fundamental signal properties of HGA: the high-gamma frequency band, the HGA bandwidth, and the temporal dynamics of HGA. Results: The high-gamma frequency band strongly varies across subjects and across cognitive/behavioral tasks. In addition, HGA time courses have lowpass character, with transients limited to 10 Hz. The task-related rise time and duration of these HGA time courses depend on the individual subject and cognitive/behavioral task. Task-related HGA amplitudes are comparable across the investigated tasks. Discussion: This study is of high practical relevance because it provides a systematic basis for optimizing experiment design, ECoG acquisition and processing, and HGA estimation. Our results reveal previously unknown characteristics of HGA, the physiological principles of which need to be investigated in further studies.

Brain-computer interface treatment for gait rehabilitation in stroke patients.

The use of Brain-Computer Interfaces (BCI) as rehabilitation tools for chronically ill neurological patients has become more widespread. BCIs combined with other techniques allow the user to restore neurological function by inducing neuroplasticity through real-time detection of motor-imagery (MI) as patients perform therapy tasks. Twenty-five stroke patients with gait disability were recruited for this study. Participants performed 25 sessions with the MI-BCI and assessment visits to track functional changes during the therapy. The results of this study demonstrated a clinically significant increase in walking speed of 0.19 m/s, 95%CI [0.13-0.25], p < 0.001. Patients also reduced spasticity and improved their range of motion and muscle contraction. The BCI treatment was effective in promoting long-lasting functional improvements in the gait speed of chronic stroke survivors. Patients have more movements in the lower limb; therefore, they can walk better and safer. This functional improvement can be explained by improved neuroplasticity in the central nervous system.

Portable rehabilitation system with brain-computer interface for inpatients with acute and subacute stroke: A feasibility study.

The feasibility and safety of brain-computer interface (BCI) systems for patients with acute/subacute stroke have not been established. The aim of this study was to firstly demonstrate the feasibility and safety of a bedside BCI system for inpatients with acute/subacute stroke in a small cohort of inpatients. Four inpatients with early-phase hemiplegic stroke (7-24 days from stroke onset) participated in this study. The portable BCI system showed real-time feedback of sensorimotor rhythms extracted from scalp electroencephalograms (EEGs). Patients attempted to extend the wrist on their affected side, and neuromuscular electrical stimulation was applied only when the system detected significant movement intention-related changes in EEG. Between 120 and 200 training trials per patient were successfully and safely conducted at the bedside over 2-4 days. Our results clearly indicate that the proposed bedside BCI system is feasible and safe. Larger clinical studies are needed to determine the clinical efficacy of the system and its effect size in the population of patients with acute/subacute post-stroke hemiplegia.

Refined analysis of complex language representations by non-invasive neuroimaging techniques.

OBJECTIVE: The determination of language lateralisation is important for patients with medically intractable epilepsy or a brain tumour near the language areas to avoid the risk of post-surgical language deficits. The aim of this study was to evaluate the clinical usefulness of near-infrared spectroscopy (NIRS) to identify language lateralisation compared with functional MRI (fMRI) and magnetoencephalography (MEG) in multiple language tasks. METHODS: We investigated 28 patients whose language dominance was evaluated by the Wada test. fMRI, MEG and NIRS were performed to investigate language representation. All patients were asked to read three-letter words silently for fMRI and MEG (Kana reading) and to write words beginning with a visually presented letter (word generation) for NIRS. The laterality index was calculated to assess language lateralisation in each investigation. RESULTS: In 24 cases (85.7%), of which two investigations showed the same laterality, the results had perfect concordance with the Wada test. In patients with left dominance, the sensitivity and specificity of fMRI, MEG and NIRS was 95.0% and 62.5%, 100% and 87.5%, 75.0% and 87.5%, respectively. In three patients with right lateralization, only NIRS showed a significant increase of oxygenated-haemoglobin in the right inferior frontal region, indicating right dominance. CONCLUSION: We established a method to determine language lateralisation by co-utilising fMRI, MEG and NIRS with high reliability. NIRS recognised atypical language representation, in addition to fMRI and MEG. While fMRI, MEG and NIRS are not currently as accurate as the Wada test in determining language lateralisation, this non-invasive and repeatable method has great potential as an alternative to the Wada test in time following further research and refinement of these techniques.

[A case of brain herniation due to delayed bone flap sinking].

Marked depression of the skin flap after external decompressive craniotomy, affecting the brain function, is known as sinking flap syndrome. However, to our knowledge, there have been no reports of delayed sinking of the entire bone flap after the procedure, inducing neurological symptoms. We encountered a patient with neurological symptoms due to sinking of the entire bone flap 15 years after the first operation. A 59-year-old male underwent clipping by craniotomy due to subarachnoid hemorrhage resulting from the rupture of a left internal carotid aneurysm 15 years earlier. He was discharged, but developed paresis in the right upper and lower limbs 6 months before symptom onset. CT showed sinking of the free bone flap, while MRI revealed left uncal herniation. After uncal resection and free flap fixation, the symptoms improved. This case confirmed the necessity of firm bone flap fixation at the time of cranial closure.

Tailor-Made Surgery Based on Functional Networks for Intractable Epilepsy.

Normal and pathological networks related to seizure propagation have got attention to elucide complex seizure semiology and contribute to diagnosis and surgical monitoring in epilepsy treatment. Since focal and generalized epileptogenic syndromes abnormalities might involve multiple foci and large-scale networks, we applied electrophysiolpgy (cortco-cortico evoked potential; CCEP), and tractography to make detailed diagnosis for complex syndrome. All 14 epilepsy patients with no or little abnormality on images investigations underwent subdural grid implantation for epilepsy diagnosis. To perform quick network analysis, we recorded and analyzed high gamma activity (HGA) of epileptogenic activity and CCEPs to identify pathological activity distribution and network connectivity. [Results] Pathological CCEPs showed two negative deflections consisting of early (>40 ms) and late (>150 ms) components in electrically stable circumstance at bed side and early CCEPs appeared in 57% of the patients. On the basis of the CCEP findings, tractography detected anatomical connections. Early components of pathological CCEPs diminished after complete disconnection of tractoography-based fibers between the foci in seven of eight cases. One case with residual pathological CCEPs showed poorer outcome. Thirteen (92.8%) patients with or without CCEPs who underwent network surgery had favorable prognosis except for a case with wide traumatic epilepsy. Intraoperative CCEP measurements and HGA mapping enabled visualization of pathological networks and clinical impotence as a biomarker to improve functional prognosis. HGA/CCEP recording should shed light on pathological and complex propagation for epilepsy surgery.