Effectiveness of radiation therapy on brain invasion by human papillomavirus-related multiphenotypic sinonasal carcinoma: A case report.

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is newly suggested and characterized by HPV-related tumors. HMSC has a relatively good prognosis. No cases of brain invasion have been reported to date. We encountered a case of brain invasion by HMSC, in which we assessed the effectiveness of radiotherapy in comparison with biopsy and autopsy. A 69-year-old man was referred to a hospital three months after intracerebral hemorrhage (ICH). Contrast magnetic resonance imaging revealed a tumor in the ethmoid sinus involving the brain. We performed transnasal biopsy and intensity-modulated radiotherapy for sinonasal and intracranial lesions. Despite radiotherapy, the patient died on day 41 after radiation. Biopsy specimens displayed mixed findings of epithelial and mesenchymal components. The tumor was immunoreactive for p16, and the RNA in situ hybridization for HPV was positive. Finally, we diagnosed the patient as having HMSC. Autopsy of the sinonasal tissue revealed a reduction in the number of tumor cells. There was a marked reduction in the number of tumor cells in the sinonasal tissue compared to that in the invaded brain tissue. The effectiveness of radiotherapy could depend on the histopathological components and location of the lesion, even in the same patient.

Freedom From Seizures Might Be Key to Continuing Occupation After Epilepsy Surgery.

Introduction: We hypothesized that epilepsy surgery for adult patients with temporal lobe epilepsy (TLE) who obtained freedom from seizures could provide opportunities for these patients to continue their occupation, and investigated continuity of occupation to test this postulation. Methods: Data were obtained from patients who had undergone resective surgery for medically intractable TLE between October 2009 and April 2019 in our hospital. Inclusion criteria were as follows: (1) ≥16 years old at surgery; (2) post-operative follow-up ≥12 months; (3) seizure-free period ≥12 months. As a primary outcome, we evaluated employment status before and after surgery, classified into three categories as follows: Level 0, no job; Level 1, students or homemakers (financially supported by a family member); and Level 2, working. Neuropsychological status was also evaluated as a secondary outcome. Results: Fifty-one (87.9%) of the 58 enrolled TLE patients who obtained freedom from seizures after surgery continued working as before or obtained a new job (employment status: Level 2). A significant difference in employment status was identified between before and after surgery (p = 0.007; Wilcoxon signed-rank test). Twenty-eight patients (48.3%) were evaluated for neuropsychological status both before and after surgery. Significant differences in Wechsler Adult Intelligence Scale-III scores were identified between before and after surgery (p < 0.05 each; paired t-test). Conclusion: Seizure freedom could be a factor that facilitates job continuity, although additional data are needed to confirm that possibility. Further investigation of job continuity after epilepsy surgery warrants an international, multicenter study.

Co-existence of idiopathic generalized and focal epilepsy suggested by simultaneous EEG-fMRI: a case report.

We present a rare patient clinically suspected to have mixed idiopathic generalized and focal epilepsy, which was supported by BOLD pattern based on EEG-fMRI. A 37-year-old female with three types of refractory seizures starting at age six - tonic with breathing difficulties and confusion, generalized tonic-clonic, and focal with brief impairment of awareness and versive head movement, initially thought to represent atypical absences - was evaluated by EEG-fMRI. She was also shown to have three types of interictal epileptic discharges: generalized spike or polyspikes and slow waves, and left fronto-temporal and right fronto-temporal discharges. We assessed BOLD activation and deactivation for each type. For generalized patterns, the BOLD activation and deactivation were typical of that seen in primary generalized epilepsy. Whereas maximum activation for left fronto-temporal EEG patterns was observed in the left superior frontal gyrus and posterior superior temporal gyrus, maximum activation for right fronto-temporal patterns was bilateral in the right posterior middle temporal gyrus and left posterior middle temporal gyrus. The EEG-fMRI results suggested that the patient had both refractory idiopathic generalized and focal epilepsy, and not a generalized epilepsy originating from a focus.

Neuroendoscopic Surgery with a Combination of Image Detectable Sheath, Intraoperative Computed Tomography Scan, and Navigation System Improves Accuracy and Safety in Minimally Invasive Evacuation of Intracerebral Hematoma: Technical Note.

BACKGROUND: Recent studies have confirmed the effectiveness of minimally invasive endoscopic surgery for intracerebral hematoma (ICH). However, improvements are needed because incomplete hematoma removal may offset the surgical benefits of the technique. We describe a technique of neuroendoscopic surgery using an image detectable sheath, intraoperative computed tomography (iCT) scan, and a navigation system. METHODS: This is a retrospective study of 15 consecutive patients with spontaneous ICH who received neuroendoscopic surgery. During the surgery, a transparent sheath was fastened tightly to the scalp with 3.0 nylon. The patient's head was covered with a sterilized vinyl sheet and subsequent iCT scan visualized the orientation of the endoscopic sheath and the extent of residual hematoma, allowing the surgeon to decide to continue to remove the hematoma or to finish the treatment. RESULTS: The median hematoma evacuation rate was 93% (interquartile range, 82.2%-95.9%). The Glasgow Coma Scale score of all patients significantly improved at 1 week after the operation (P < 0.05). No complications associated with the procedure were observed. CONCLUSIONS: The combination of our techniques improves accuracy and safety of minimally invasive surgical evacuation of hematoma. Performing surgery with iCT scan also improves the spatial recognition of surgeons and therefore may be of educational value.

Additional seizure reduction by replacement with Vagus Nerve Stimulation Model 106 (AspireSR).

AspireSR is a novel vagus nerve stimulation (VNS) device which detects ictal heart rate changes and automatically apply additional stimulus. We investigated the difference of the efficacy between AspireSR and preceding VNS models in patients with device replacement. We retrospectively reviewed the clinical data of 17 patients whose VNS devices were changed because of battery discharge. The rates of seizure reduction, the number of antiepileptic drugs (AEDs) used and device parameters between the two devices were evaluated. AspireSR improved significantly the rates of seizure reduction of the patients. Four patients out of 11 patients with low response to the preceding VNS models (no change or <50 % reduction) achieved>50 % seizure reduction. The AEDs used were not different in the observed periods. The device parameters were low setting in AspireSR compared to preceding VNS models. AspireSR decrease significantly seizure frequencies compared to the preceding VNS models. Change of the devices to AspireSR at the time of battery empty could be recommendable.

Widespread interictal epileptic discharge more likely than focal discharges to unveil the seizure onset zone in EEG-fMRI.

OBJECTIVE: We hypothesized that the number of interictal epileptic discharges (IEDs) during scan and their spatial extent are contributing factors in obtaining appropriate activations that reveal the seizure onset zone (SOZ) in EEG-fMRI. METHODS: 157 IED types, each corresponding to one EEG scalp distribution, in 64 consecutive EEG-fMRI studies from 64 patients with refractory localization-related epilepsy were reviewed. To determine reliable activation, we used the threshold corresponding to corrected whole-brain topological false discovery rate (FDR). The location with maximum activation was compared to the presumed SOZ as defined by a comprehensive evaluation for each patient. RESULTS: The number of IEDs was significantly higher in the types with t-value above FDR than with t-value below FDR. The presumed SOZ could be delineated in 30 of the 64 patients. Among these patients, the types of IED concordant with the SOZ had significantly larger extent on scalp EEG than the IED types discordant with the SOZ. CONCLUSIONS: The number of IEDs is important factor in obtaining reliable activations in EEG-fMRI. IEDs with larger spatial extent are more likely to reveal, on maximum BOLD, accurate location of the SOZ. SIGNIFICANCE: Widespread discharges are more likely to yield a reliable activation for SOZ in EEG-fMRI.

Seizure frequency can be reduced by changing intracranial pressure: A case report in drug-resistant epilepsy.

A relationship between seizures and intracranial pressure (ICP) has been proposed, but not clearly identified. Whether changes in ICP can evoke seizures remains controversial. We report the case of a 23-year-old man who had undergone shunt surgery in childhood and later presented with focal impaired awareness seizures and behavior arrest. Seizures were uncontrolled despite 3 years of pharmacotherapy, but suddenly stopped after shunt removal. Our case supports the hypothesis that drug-resistant epilepsy can be influenced by changes in ICP. In particular, this case indicates that elevations in ICP may help reduce some seizures.

[Experience and Solution of Complications of Vagus Nerve Stimulation Therapy in 139 Implant Patients with Medically Refractory Epilepsy].

BACKGROUND: Vagus nerve stimulation(VNS)for patients with intractable epilepsy was approved by the Japan Ministry of Health, Labour and Welfare in 2010. More than 1,500 VNS systems were implanted by the end of August 2016. The aim of the present report is to describe complications we experienced at our department and consider the way to avoid them. METHODS AND PATIENTS: We retrospectively reviewed 139 consecutive patients(122 new implantations and 17 reimplantations)between December 2010 and March 2016. RESULTS: Seven patients demonstrated eight complications. Four patients experienced recurrent nerve paralysis with hoarseness and/or cough that did not require device removal. One patient experienced subsequent aspiration pneumonia. The device was removed in one case due to lead fracture and in three owing to surgical site infection(SSI). CONCLUSION: All recurrent nerve paralysis occurred just after we started VNS implantations. It was presumed that the nerve paralysis was caused by retraction around the vagus nerve. Smaller skin incision and decreased retraction of the surgical field has eliminated this complication. The incidence of infections is reported as 2.2%. Allergic reaction to the VNS device might be one of the causes for SSI in our series. Fracture of the lead was caused by revolving of the pulse generator under the skin. Tight sutures around the pocket or subpectoral placement of a pulse generator is necessary to prevent rotation of the generator depending upon the activity of each patient. This paper provides insight into complications and successful strategies for better outcomes in VNS therapy.

Successful corpus callosotomy for Doose syndrome.

Doose syndrome (epilepsy with myoclonic-atonic seizures) is an epilepsy syndrome with an incidence of approximately 1-2% of childhood-onset epilepsies. Although this syndrome is associated with multiple types of generalized seizures, the diagnosis is based on the presence of myoclonic-atonic seizures. Eighteen percent of patients have refractory seizures and intellectual disabilities. There have, however, been a few reports on the efficacy of surgical treatment for Doose syndrome. We describe a case of Doose syndrome in a 10-year-old boy. He developed generalized tonic-clonic seizures at 3years 8months of age and subsequently developed myoclonic-atonic, myoclonic, and tonic seizures. The frequent myoclonic seizures were refractory to multiple antiepileptic medications. His cognitive development was moderately delayed. Anterior four fifths corpus callosotomy was performed at 8years 5months of age. His seizures, especially myoclonic seizures, were markedly reduced. He was given vagus nerve stimulation therapy at 9years and 1month of age, which led to complete resolution of the myoclonic seizures. Corpus callosotomy can be a good treatment strategy in patients with Doose syndrome with medically refractory generalized seizures.

Total corpus callosotomy for epileptic spasms after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) in a case with tuberous sclerosis complex.

Corpus callosotomy is a palliative therapy for refractory epilepsy, including West syndrome, without a resectable epileptic focus. The surgical outcome of corpus callosotomy is relatively favorable in cryptogenic (non-lesional) West syndrome. Tuberous sclerosis complex (TSC) is a disorder that frequently leads to the development of refractory seizures by multiple cortical tubers. The multiple cortical tubers cause multiple or wide epileptic networks in these cases. Most of West syndrome cases in TSC with multiple tubers need additional resective surgery after corpus callosotomy. We describe a case of TSC in a boy aged 4years and 8months. He had multiple cortical tubers on his brain and developed epileptic spasms. The seizures were controlled with valproate. At the age of 1year and 4months, he presented with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), and had relapsed epileptic spasms one month after the onset of the encephalopathy. The seizures were refractory to multiple antiepileptic drugs. A total corpus callosotomy was performed at the age of 3years and 8months. The patient did not show any seizures after the surgery. During 12months of the follow-up, the patient was free from any seizures. Even in cases of symptomatic WS with multiple lesions, total corpus callosotomy may be a good strategy if the patients have secondary diffuse brain insults.

Wolf-Hirschhorn (4p-) syndrome with West syndrome.

Wolf-Hirschhorn syndrome (WHS) is a chromosome disorder (4p-syndrome) which is characterized by craniofacial features and epileptic seizures. Here, we report a case of WHS with West syndrome, in whom the seizures were refractory to several antiepileptic drugs but were responsive to the addition of lamotrigine. The patient had epileptic spasms at age seven months. The interictal electroencephalogram was hypsarrhythmic. After adding lamotrigine, seizures decreased remarkably, and spasms disappeared. We have identified and described the very rare case of a girl with WHS who also developed West syndrome. In this case, adding lamotrigine to her medications effectively treated the spasms.

Potent tumor tropism of induced pluripotent stem cells and induced pluripotent stem cell-derived neural stem cells in the mouse intracerebral glioma model.

Although neural and mesenchymal stem cells have been well-known to have a strong glioma tropism, this activity in induced pluripotent stem cells (iPSCs) has not yet been fully studied. In the present study, we tested tumor tropic activity of mouse iPSCs and neural stem cells derived from the iPSC (iPS-NSCs) using in vitro Matrigel invasion chamber assay and in vivo mouse intracranial tumor model. Both iPSC and iPS-NSC had a similar potent in vitro tropism for glioma conditioned media. The migrated iPSCs to the gliomas kept expressing Nanog-GFP gene, suggesting no neuronal or glial differentiation. iPSCs or iPS-NSCs labeled with 5-bromo-2-deoxyuridine were intracranially implanted in the contralateral hemisphere to the GL261 glioma cell implantation in the allogeneic C57BL/6 mouse. Active migration of both stem cells was observed 7 days after implantation. Again, the iPSCs located in the tumor area expressed Nanog-GFP gene, suggesting that the migrated cells were still iPSCs. These findings demonstrated that both iPSCs and iPS-NSCs had potent glioma tropism and could be candidates as vehicles in stem cell-based glioma therapy.

Diffuse astrocytoma initially presenting as a massive intracerebral hemorrhage: case report.

We report the case of a 58-year-old woman with low-grade astrocytoma, who developed massive intracranial hemorrhage as the first presentation of this disease, and become comatose and subsequently underwent an emergency craniotomy. A small amount of tumor-like tissue was observed on the wall of the hematoma cavity. Histological analysis of the resected specimen indicated diffuse astrocytoma [World Health Organization (WHO) grade II]. The patient was discharged without neurological deficits 2 weeks after the operation. A non-enhanced tumor-like nodule was observed on magnetic resonance imaging 3 months after the operation, which was monitored carefully but was not treated by adjuvant therapy. The tumor grew gradually, and a second operation was performed 3 years after the first, in which the tumor was completely resected. Histological analysis of the resected specimen again indicated diffuse astrocytoma (WHO grade II). Although rare, brain tumors, including low-grade astrocytoma, should be considered a possible cause of subcortical hemorrhage in patients without risk factors for intracranial hemorrhage.

[Effectiveness and role of lamotrigine in the paradigm shift towards new antiepileptic drugs: a therapeutic strategy proposed after an investigation of a large number of cases at a single hospital].

Lamotrigine (LTG) has been recognized as one of the best newer antiepileptic drugs (AEDs) used in developed countries since 1991. A retrospective study was carried out to evaluate the efficacy, adverse reactions, and other peculiarities of LTG. Two hundred and eighty-one patients with epilepsy, aged 16 or more, were treated with LTG between December 2008 and December 2012 at the Seirei Hamamatsu General Hospital. One hundred and forty patients were found to be eligible to evaluate the effectiveness of LTG. Of them, 100 patients had localized epilepsy, and 40 patients had generalized epilepsy. Seventy-five out of these 140 (53.6%) patients obtained seizure freedom following LTG use, and 24 patients (17.1%) showed more than 50% seizure reduction, which indicates that a total of 99 patients (70.7%) were good responders. A seizure reduction of less than 50% was seen in 8 patients (5.7%), whereas 30 patients (21.4%) did not display any obvious seizure reduction. Three patients (2.1%) showed a worsening of seizure frequency. Patients with idiopathic generalized epilepsy such as juvenile myoclonic epilepsy showed satisfactory results. Many good responders were also patients with stroke or brain tumor. The number of concomitant AEDs used demonstrated a more distinctive feature. Monotherapy without any other AEDs was used in 20 patients. LTG was used as an add-on with 1 concomitant AED in 59 patients (42.1%) and as an add-on with 2 concomitant AEDs in 37 patients (26.4%). Thus, a large number of patients (68.6%) underwent early add-on treatment. LTG as an add-on in concert with concomitant AEDs contributed to the excellent results in terms of seizure reduction observed in this study. LTG administration requires established titration, particularly to prevent drug eruption. Over 60% of the patients were treated by slower titration than that used in the established titration method. However, seizure freedom was accomplished within 1-5 weeks from the beginning of LTG treatment with doses much lower than 200 mg/day, which indicated the effectiveness of low-dose LTG in the early phase of treatment. The average maintenance dose was 162.7 mg/day; however, half of the patients maintained their dose at more than 200 mg/day. The continuation rate was 77.2%. The main reasons for withdrawal were dissatisfaction with drug effectiveness and drug eruption. However, the incidence of drug eruption was only in 15 out of 281 (5.3%) patients, which is similar to previously reported rates. Therefore, LTG is an effective and safe AED. Moreover, it is a promising drug for promoting a paradigm shift towards newer AEDs. LTG administration as a first add-on AED is strongly recommended to obtain excellent results and to maintain good compliance with the epilepsy treatment course.

[Clinical efficacy of the novel antiepileptic agent levetiracetam: evaluation in patients with localization-related epilepsy].

In this retrospective study, we evaluated the safety and efficacy of levetiracetam (LEV) as an antiepileptic drug by using data in our hospital database from October 2010, when LEV became available in Japan, through August 2011. Data from patients aged 16 years or more (n=132) with localization-related epilepsy (n=112) and generalized epilepsy (n=19) were reviewed. Among patients with localization-related epilepsy, 53.6% showed a greater than 50% reduction in seizure frequency compared with the pretreatment baseline, and 28.6% of them became seizure free during the treatment period. Adverse events were reported in 27.3% of patients and caused discontinuation of LEV in 10.6%. The most frequent adverse events were somnolence (14.4%), irritability or aggressiveness (6.1%), and depression (4.5%). However, most of the adverse events were of mild to moderate severity. More than 80% of patients continued LEV treatment. The frequency of adverse events and discontinuation rate after LEV treatment were not associated with the starting dose (1,000 mg/day or less). LEV was well tolerated and efficacious as an adjunctive therapy for localization-related epilepsy.

Comparison of dense array EEG with simultaneous intracranial EEG for interictal spike detection and localization.

PURPOSE: To evaluate the clinical utility of dense array electroencephalography (dEEG) for the detection yield and localization of interictal spikes in mesial temporal lobe epilepsy. METHODS: We simultaneously recorded 256-channel dEEG and intracranial electroencephalography (icEEG) implanted over the lateral and mesial temporal lobe in patients with intractable epilepsy. We calculated the dEEG spike detection rate for mesial temporal spikes which were confirmed by icEEG and applied source estimation to dEEG to compare noninvasive localization to the invasive recordings. RESULTS: 339 of 760 interictal spikes (45%) were detected by dEEG examining the 256-channel head surface array. The average icEEG amplitude of dEEG detectable spikes was 1083 µV, and that of dEEG undetectable spikes was 780 µV (P<0.05). All spikes detected in dEEG were localized to the temporal lobe. 295 of 339 spikes (87%) were well localized in mesial temporal lobe, close to the position confirmed by subdural electrodes. SIGNIFICANCE: 256-channel dEEG may provide more precise information for the localization of interictal epileptiform discharges than conventional EEG or MEG in patients with deep spike foci. 256-channel dEEG may be clinically useful in the presurgical work-up for epilepsy, providing accurate noninvasive guidance for the placement of intracranial electrodes.

Gene expression of bone matrix proteins in a calcified tissue appeared in subcutaneously transplanted rat dental pulp.

Dental pulp self-mineralizes or induces calcified tissue formation, when it is subcutaneously transplanted. This study aims to clarify the nature and process of this tissue calcification by using histochemical techniques and in situ hybridization methods. The dental pulps of incisors from Sprague-Dawley strain rats were homogeneously transplanted into the subcutaneous tissue of the head of another rat. On the 1st day of transplantation, the mRNAs of type I collagen (COL I) and bone sialoprotein (BSP) were expressed in the transplant. On the 5th to 7th days after transplantation, von Kossa-positive, calcified tissues appeared in the transplanted tissues. The mRNAs of COL I, BSP and osteopontin (OPN) were expressed with the same distributions as those of the von Kossa-positive areas, but those of type II collagen (COL II) and bone morphogenic protein 2 (BMP-2) were not expressed in the transplant. When the cellular incorporation of BrdU was examined after its subcutaneous injection into the animals, positive cells were present in the von Kossa-positive calcified foci as well as in their surrounding areas. These results indicate that the transplanted dental pulp possesses the ability to induce cell proliferation resulting in the synthesis of several bone matrix proteins and the formation of calcified tissue. This may give us an insight into the nature and processes of pulp obliteration, which occurs in a human tooth following an episode of trauma.