Is oral Streptococcus mutans with collagen-binding protein a risk factor for intracranial aneurysm rupture or formation?

OBJECTIVE: Streptococcus mutans (SM) with the collagen-binding protein Cnm is a unique member of the oral resident flora because it causes hemorrhagic vascular disorders. In the multicenter study, we examined the relationship between Cnm-positive SM (CP-SM) and intracranial aneurysm (IA) rupture, which remains unknown. METHODS: Between May 2013 and June 2018, we collected whole saliva samples from 431 patients with ruptured IAs (RIAs) and 470 patients with unruptured IAs (UIAs). Data were collected on age, sex, smoking and drinking habits, family history of subarachnoid hemorrhage, aneurysm size, number of teeth, and comorbidities of lifestyle disease. RESULTS: There was no difference in the positivity rate of patients with CP-SM between the patients with RIAs (17.2%) and those with UIAs (19.4%). The rate of positivity for CP-SM was significantly higher in all IAs <5 mm than in those ≥10 mm in diameter (P=0.0304). In the entire cohort, the rate of positivity for CP-SM was lower in larger aneurysms than in smaller aneurysms (P=0.0393). CONCLUSIONS: The rate of positivity for CP-SM was lower among patients with large UIAs. These findings are consistent with the hypothesis that CP-SM plays a role in the formation of vulnerable IAs that tend to rupture before becoming larger.

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.

What Part of the Brain Controls Contralateral Fine Finger Movement in a Normally Developed Patient With a Deficit of Primary Motor Cortices?

BACKGROUND: Malformations of cortical development (MCDs) often result in mental retardation, intractable epilepsy, neurodevelopmental delay, and contralateral hemiparesis. We describe herein a rare patient with MCD who had developed normally in spite of diffuse hemispheric anomaly of the brain. CASE DESCRIPTION: We report a left-handed 20-year-old healthy man. A magnetic resonance image scan revealed congenital left cerebral hemispheric dysplasia and deficit of the normal anatomical primary motor cortices although he was normally developed without hemiparesis nor aphasia. Diffusion tensor tractography showed unusual fiber radiation from the left cerebral peduncle to the much more rostral and lateral cerebral cortices compared with normal anatomy. Right finger flexion-extension task showed activation in that area on functional magnetic resonance imaging. CONCLUSIONS: Even in a congenital hemispheric dysplasia, the contralateral fine finger movement may still depend on the dysplastic hemisphere. On the other hand, speech and the other gross movements including leg, foot, and arm can be compensated with the ipsilateral normal cerebral cortices.

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.

Intracranial Multiple Pseudotumor Due to Immunoglobulin G4-Related Disease without Other Lesions: Case Report and Literature Review.

BACKGROUND: Immunoglobulin (Ig)G4-related disease (IgG4-RD) was defined only recently and can be found in many organs. As intracranial lesions, hypophysitis and pachymeningitis are well known, whereas intracranial pseudotumor is unusual. This case involved multiple intracranial pseudotumors without extracranial lesions, mimicking multiple meningioma. CASE DESCRIPTION: A 72-year-old woman was referred to our hospital with an incidental mass lesion at the craniocervical junction on magnetic resonance imaging (MRI). MRI showed diffuse enhanced extra-axial nodules around the medulla and middle cranial fossa. Surgery was performed for the gradually enlarging tumor. Intraoperative findings showed hard nodules around the vertebral artery. We performed subtotal resection. Neuropathological findings showed diffuse lymphoplasmacytic infiltration with lymphoid follicles. Immunohistochemical studies for IgG4 and IgG showed the histological criteria for IgG4-RD were met. Given the high IgG4 serum level, we diagnosed IgG4-RD. Steroid was administered initially but was then tapered, and nodules have since remained small. CONCLUSIONS: This case demonstrates IgG4-RD mimicking meningioma with multiple masses but without extracranial lesions. This case and previous descriptions suggest the possibility of pseudotumor due to IgG4-RD in the presence of multiple extra-axial lesions at the dura and supplying artery, hard nodules with thickening of the artery, and frozen section findings of lymphoplasmacytes surrounded by rich collagen fibers. In such cases, the pseudotumor due to IgG4-RD should be resected, and total resection might not be warranted.

Unexpectedly Smaller Artifacts of 3.0-T Magnetic Resonance Imaging than 1.5 T: Recommendation of 3.0-T Scanners for Patients with Magnet-Resistant Adjustable Ventriculoperitoneal Shunt Devices.

BACKGROUND: Magnetic resonance imaging (MRI) artifacts of adjustable shunt devices are thought to be similar to metal clip artifacts, in that they are larger with higher field strength scanners. We have published several reports about the artifacts of new MRI-resistant adjustable shunt devices, and we found a case in which a 3.0-T scanner showed smaller artifacts than the 1.5-T scanner. We aimed to clarify whether this claim is true or not. METHODS: Under permission of our institutional Ethical Committee, 2 volunteers underwent imaging studies using 3.0-T and 1.5-T scanners from GE, Siemens, and Philips. Four MRI-resistant adjustable shunt devices-proGAV2.0 (Miethke), Codman Certas Plus (Johnson & Johnson), Polaris (Sophysa), and Strata MR valve (Medtronic)-were fixed on the left temporal scalp. Routine MRI images, including T1-and T2-weighted imaging, fluid-attenuated inversion recovery, diffusion-weighted imaging (DWI), and magnetic resonance angiography (MRA), were obtained. We also compared artifacts between a 3.0-T scanner and a-1.5 T scanner in 4 patients. RESULTS: The 3.0 T-scanners showed smaller artifacts than the 1.5-T scanners on DWI and MRA images for all shunt devices and scanners. In the other sequences, the results depended on the MRI scanner manufacturer; however, the GE 3.0-T scanner showed smaller artifacts in every sequence. This was also true in the 4 clinical cases. CONCLUSIONS: A 3.0-T scanner is recommended over a 1.5-T scanner for patients with MRI-resistant adjustable shunt devices in the diagnosis of acute ischemic condition or when using GE scanners.

Temporal Lobe Cavernous Malformation Caused Epileptic Amnesic Episodes and Mild Cognitive Impairment.

Neuropathological features in Alzheimer's disease (AD) are amyloid ß (Aß) deposits and neurofibrillary changes. AD is characterized by memory impairment and cognitive dysfunction, with some reports associating these impairments with hyperexcitability caused by Aß in the medial temporal lobe. Epileptic seizures are known to be common in AD. We encountered a 65-year-old patient with cavernous malformation (CM) in the right temporal lobe who exhibited epileptic amnesia (EA) and AD-like symptoms. Scalp electroencephalography (EEG), including long-term video-EEG, showed no interictal discharges, but intraoperative subdural electrode (SE) recording from the right parahippocampal area showed frequent epileptiform discharges. Neuropathologically, senile plaques were found in the surrounding normal cortex of the CM. Postoperatively, the patient has remained free of EA and AD-like symptoms since total removal of the CM. This is the first surgical case report to confirm temporal lobe hyperexcitability associated with EA and AD-like symptoms.

Cerebellar Metastasis of Unknown Primary Neuroendocrine Carcinoma: Report of Case Mimicking Hemangioblastoma.

BACKGROUND: Neuroendocrine carcinoma (NEC) originates with neuroendocrine cells and is mainly found in the pancreas, lungs and gastrointestinal tract. We surgically treated a case of primary unknown NEC with only cerebral metastasis that mimicked hemangioblastoma. Recurrence was seen at the fornix, and no primary lesion had been identified as of 2 years after treatments despite careful examination. CASE DESCRIPTION: A 61-year-old man presented with dizziness. Past medical history included hypertension, dyslipidemia, hyperuricemia and colon polyp. We performed magnetic resonance imaging (MRI) to examine the cause of dizziness, revealing tumor with enhancement and peritumoral edema at the right cerebral lesion. Contrast-enhanced whole-body computed tomography (CT) showed no other lesions. We suspected hemangioblastoma from examinations and decided on surgical resection. Neuropathologically, the resected tumor was diagnosed as brain metastasis of NEC, but CT, fluorodeoxyglucose-positron emission tomography, gastrointestinal endoscopy, and somatostatin receptor scintigraphy all failed to reveal the primary lesion. As postoperative MRI showed enhancement around the resection cavity and at the right fornix, radiotherapy was performed. No other lesions were seen at 24 months postoperatively. We are continuing careful monitoring and no chemotherapy has been administered. CONCLUSIONS: We treated brain metastasis from NEC of unknown primary and mimicking hemangioblastoma using only local treatment. When an enhancing, single, solid tumor is seen in the cerebellum, brain metastasis from NEC of unknown primary is 1 differential diagnosis.

Spontaneous Regression of Germinomas After Salvage Surgery and Possible Mechanism of Induced Apoptosis.

BACKGROUND: A few cases of spontaneous regression of germ cell tumors have been reported. Possible mechanisms include steroid medication, surgical intervention, diagnostic radiation exposure, and immune response. None of these hypotheses has been supported by sufficient data. CASE DESCRIPTION: Two cases of germinoma demonstrated spontaneous regression before antitumor therapy. In the first case, a 19-year-old man presented with acute hydrocephalus due to a pineal mass and underwent emergent endoscopic third ventriculostomy. The pineal tumor started to regress on the 4th postoperative day after endoscopic third ventriculostomy. In the second case, a 22-year-old man presented with acute hydrocephalus and panhypopituitarism due to a suprasellar mass and underwent emergent external ventricular drainage, biopsy, and septostomy on the day of admission. Apparent regression of the tumor was discovered on the 5th day after initial surgery. Pathologic diagnosis was pure germinoma in both cases. Remarkable accumulations of CD4-positive lymphocytes and some apoptotic cells positive for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining were detected in both cases. Diagnostic radiation exposure is the only common condition in all reported cases. CONCLUSIONS: This unusual phenomenon of spontaneous regression of germinoma may be caused by a combination of pathognomonic characteristics of anatomic location with paraventricular development and stress induction as a trigger, such as salvage surgery or diagnostic radiation, including at extremely low dosage.

Mechanical Thrombectomy for Trousseau Syndrome in a Terminally Ill Cancer Patient.

Trousseau syndrome was first described by Armand Trousseau in 1865 and is characterized by hypercoagulation resulting from malignant tumors. This complication can markedly impact quality of life (QOL). This is the first report of a terminally ill patient who developed large-vessel occlusion stroke from Trousseau syndrome and underwent mechanical thrombectomy. A 75-year-old woman presented with Stage IV ovarian cancer. Goals of care were transitioned to palliative care. The patient was hospitalized with vertebral compression fracture and suddenly developed right hemiparesis and total aphasia during admission. Magnetic resonance imaging and angiography showed occlusion of Segment 1 of the left middle cerebral artery. We administered tissue-plasminogen activator, but symptoms remained unimproved. We performed mechanical thrombectomy based on medical indications and with the consent of her family. Thrombectomy improved symptoms dramatically. She was able to walk and talk with her family at discharge. She eventually died of respiratory failure on postoperative Day 98, but QOL remained high for those 98 days. Mechanical thrombectomy has the potential to markedly improve QOL in terminally ill patients with large-vessel occlusion associated with Trousseau syndrome.

Setting pressure can change the size and shape of MRI artifacts caused by adjustable shunt valves: a study of the 4 newest models.

OBJECTIVE: Adjustable shunt valves that have been developed for the management of hydrocephalus all rely on intrinsically magnetic components, and artifacts with these valves on MRI are thus inevitable. The authors have previously reported that the shapes of shunt artifacts differ under different valve pressures with the proGAV 2.0 valve. In the present study the authors compared the size and shape of artifacts at different pressure settings with 4 new-model shunt valves. METHODS: The authors attached 4 new models of MRI-resistant shunt valve to the temporal scalp of a healthy volunteer: the proGAV 2.0; Codman Certas Plus; Polaris; and Strata MR. They set 3 different scales of pressures for each valve, depending on magnet orientation to the body axis. Artifacts were evaluated and compared among all valves on a 3.0-T GE scanner and 2 valves were also evaluated on a Philips scanner and a Siemens scanner. In-plane artifact sizes were evaluated as the maximum distance of the artifact from the expected scalp. RESULTS: The sizes and shapes of artifacts changed depending on valve pressure for all valves on the 3 different MRI scanners. Artifacts were less prominent on spin echo sequences than on gradient echo sequences. For diffusion-weighted imaging and time-of-flight MR angiography, the authors matched image numbers within the same sequence and compared appearances of artifacts. For all valves, the number of images affected by artifacts and the image number showing the largest artifact differed among valve settings. CONCLUSIONS: Artifacts of all adjustable shunt valves showed gross changes corresponding to pressure setting. Not only the maximum distance of artifacts but also the shape changed significantly. The authors suggest that changing pressure settings offers one of the easiest ways to minimize artifacts on MRI.

An Unusual Case of Lhermitte-Duclos Disease Manifesting with Intratumoral Hemorrhage.

BACKGROUND: Lhermitte-Duclos disease (LDD) is a rare neurologic disease that causes a hamartomatous lesion in the cerebellum. LDD is usually associated with mass lesion effects, but with appropriate surgical treatment, the clinical course is usually benign. We report a rare case of a patient with LDD with contrast enhancement on magnetic resonance imaging (MRI) who died as a result of intratumoral hemorrhage. CASE DESCRIPTION: LDD was diagnosed in a 59-year-old woman after a routine MRI. She did not present with any symptoms initially or after follow-up MRI suggested minor hemorrhage in the tumor. Eleven months after her first visit to our department, she suddenly lost consciousness, and computed tomography revealed massive intratumoral hemorrhage. Surgical decompression was done, but she died 17 days after surgery. Histopathologic findings were consistent with LDD. CONCLUSIONS: Hemorrhagic events can occur with LDD, even though the growth of the lesion is slow. Long-term close follow-up of patients with LDD is needed, especially patients in whom MRI shows atypical enhancement. To avoid possible hemorrhagic events, surgical treatment should be considered even if only subtle changes are seen on neuroimaging.

A Potential New Risk Factor for Stroke: Streptococcus Mutans With Collagen-Binding Protein.

BACKGROUND: Among human oral bacteria, particular kinds of Streptococcus mutans (SM) known as dental caries pathogens contain a collagen-binding protein, Cnm, and show platelet aggregation inhibition and matrix metalloproteinase-9 activation. We have previously reported that these strains may be a risk factor for intracerebral hemorrhage. As a major sample-providing hospital, we report the clinical details, including intracranial aneurysms and ischemic stroke. METHODS: After the study received approval from the Ethical Committee, 429 samples of whole saliva were obtained from patients who were admitted to or visited our hospital between February 16, 2010, and February 28, 2011. The study cohort comprised 48 patients with cardioembolic stroke (CES), 151 with non-CES infarct, 54 with intracerebral hemorrhage (ICH), 43 with ruptured intracranial aneurysm (RIA), and 97 with unruptured intracranial aneurysm (UIA). Cultured SM was identified as Cnm-positive when the corresponding gene was positive. The results were compared with those from 79 healthy volunteers. Relationships between Cnm-positive SM and known risk factors, including hypertension, diabetes, hyperlipidemia, smoking, and alcohol consumption, were analyzed. RESULTS: A statistically significant high Cnm-positive rate was observed in patients with CES, non-CES infarct, ICH, and RIA (P = 0.002, 0.039, 0.013, and 0.009, respectively). There were no relationships between Cnm-positive SM and known risk factors. CONCLUSIONS: Specific types of oral SM can be a risk factor for cardioembolic infarct, intracerebral hemorrhage, and intracranial aneurysm rupture. Further study is needed.

[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.

Oral Cnm-positive Streptococcus Mutans Expressing Collagen Binding Activity is a Risk Factor for Cerebral Microbleeds and Cognitive Impairment.

Cerebral microbleeds (CMBs) are an important risk factor for stroke and dementia. We have shown that the collagen binding surface Cnm protein expressed on cnm-positive Streptococcus mutans is involved in the development of CMBs. However, whether the collagen binding activity of cnm-positive S. mutans is related to the nature of the CMBs or to cognitive impairment is unclear. Two-hundred seventy nine community residents (70.0 years) were examined for the presence or absence of cnm-positive S. mutans in the saliva by PCR and collagen binding activity, CMBs, and cognitive function were evaluated. Cnm-positive S. mutans was detected more often among subjects with CMBs (p < 0.01) than those without. The risk of CMBs was significantly higher (odds ratio = 14.3) in the group with S. mutans expressing collagen binding activity, as compared to the group without that finding. Deep CMBs were more frequent (67%) and cognitive function was lower among subjects with cnm-positive S. mutans expressing collagen binding activity. This work supports the role of oral health in stroke and dementia and proposes a molecular mechanism for the interaction.

Endoscopic Removal of Neonatal Acute Epidural Hematoma via Strip-Bending Osteoplastic Craniotomy. Technical Note.

We present a rare case of an acute epidural hematoma extending through a skull fracture into a cephalohematoma in a neonate. The epidural hematoma was caused by a fall after delivery. The neonate remained neurologically asymptomatic. A computed tomography scan 12 days after delivery showed the large-volume epidural hematoma with midline shift. We performed a strip-bending osteoplastic craniotomy and removed the epidural hematoma and external cephalohematoma under neuroendoscopic control. This is the first reported case of an acute epidural hematoma in a neonate treated successfully neuroendoscopically via a strip-bending craniotomy.

[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.