Hidenori Sugano

Long-term follow-up of seizure outcomes after corpus callosotomy

PURPOSE Corpus callosotomy can be an effective surgical treatment for medically intractable generalized seizures, particularly for drop attacks. We studied long-term seizure outcomes after callosotomy, mainly focusing on drop attacks as the seizure type. METHODS This study reviews 78 patients who underwent callosotomy and were followed up for more than 3 years after surgery. Seizure outcome of callosotomy was analyzed for seizure type, including drop attacks and other types of seizures. RESULTS The followed-up time ranged from 3 to 13 years (mean; 7.0+/-2.9 years, median; 8 years). When callosotomy was total section, drop attack seizure-free rate was 90%. However, partial section yielded a drop seizure-free rate of only 54%. Thirty-five of the 46 (76%) patients who were free of drop attacks 6 years after callosotomy had no relapse thereafter. Relapse of drop attacks was also significantly different depending on the range of callosotomy. With total section, only 7% showed relapse of drop attacks. On the contrary, patients with partial section had a 31% relapse rate. In 21% patients, postural seizures newly developed after callosotomy. CONCLUSIONS These findings confirmed that callosotomy is the treatment of choice for disabling generalized seizures, especially for drop attacks. Total section is far more effective than partial section in terms of control of drop attacks and prevention of seizure relapse. However, new types of seizure could occur after callosotomy. When newly developed postural seizures were very severe, patients may fall due to sudden torsion of body, but the entire process of falling was not as sudden as that observed during previous drop attacks.

Efficacy of intraoperative electrocorticography for assessing seizure outcomes in intractable epilepsy patients with temporal-lobe-mass lesions

PURPOSE The findings of previous studies have been controversial regarding the optimal surgical procedures required for effective seizure control. In particular, there are varying views as to whether or not lesionectomy of a temporal-lobe-mass lesion is a satisfactory process or whether removal of additional seizure foci is necessary. In this study, we evaluated the efficacy of additional removal of electrically positive foci using intraoperative electrocorticography on mass lesions related to temporal lobe epilepsy. METHODS Thirty-five medically intractable epilepsy patients with temporal-lobe benign mass lesions, who had been surgically treated, were assessed. The relationship between resection of the epilepsy focus using intraoperative electrocorticography and seizure outcome was analyzed. In addition, the sites of residual spikes after lesion removal were evaluated. RESULTS In this study, the benign mass lesions consisted of 21 gangliogliomas, 8 cavernous angiomas and 6 dysembryoplastic neuroepithelial tumors. The number of 3-year postoperative seizure-free incidences for the group that underwent lesionectomy plus additional spike-positive site resection equated to 90.9%. In contrast, in the group that underwent a lesionectomy only, 76.9% were seizure-free for 3-years postoperatively. After complete removal of mass lesions, 86.4% of the residual spikes were detected over the hippocampus. CONCLUSION Even after the complete removal of temporal-lobe-mass lesions, a high frequency of residual spikes was obtained from the hippocampus. Effective surgical seizure control was achieved by carrying out additional procedures on the affected hippocampus. To detect seizure foci surrounding the lesion, especially over the hippocampus, intraoperative electrocorticogram monitoring was shown to be an effective technique.

Hippocampal transection for treatment of left temporal lobe epilepsy with preservation of verbal memory

Despite good seizure outcome with temporal lobectomy, postoperative impairment of verbal memory remains unsolved. To address this problem we developed a new method, applying the rationale of multiple subpial transection (MST) to the hippocampus. The inferior ventricle is accessed without disrupting the neuronal pathways related to verbal memory. Intraoperative electrocorticography is recorded over the hippocampus and amygdala. After the extent of the epileptic area is determined, multiple transections of the pyramidal layer under the alveus is performed using specially designed ring transectors. After this procedure, epileptic discharges from the hippocampus can be completely abolished. Of 21 cases undergoing this operation, 12 left-sided and nine right-sided, 17 were followed up for more than one year. Fourteen (82%) are seizure free, two (12%) have rare seizures, and one (6%) has significantly improved. Of eight patients who underwent a battery of neuropsychometric tests both before and after left hippocampal transection, postoperative verbal memory was completely preserved in seven cases, and one transiently worsened patient recovered within 6 months. However, these results are still preliminary as the number of patients is small and the follow-up time short. The accumulation of cases and follow-up of greater duration will be necessary to precisely confirm the efficacy of this new technique.

The somatic GNAQ mutation c.548G>A (p.R183Q) is consistently found in Sturge–Weber syndrome

Sturge–Weber syndrome (SWS) is a neurocutaneous disorder characterized by capillary malformation (port-wine stains), and choroidal and leptomeningeal vascular malformations. Previously, the recurrent somatic mutation c.548G>A (p.R183Q) in the G-α q gene (GNAQ) was identified as causative in SWS and non-syndromic port-wine stain patients using whole-genome sequencing. In this study, we investigated somatic mutations in GNAQ by next-generation sequencing. We first performed targeted amplicon sequencing of 15 blood–brain-paired samples in sporadic SWS and identified the recurrent somatic c.548G>A mutation in 80% of patients (12 of 15). The percentage of mutant alleles in brain tissues of these 12 patients ranged from 3.6 to 8.9%. We found no other somatic mutations in any of the seven GNAQ exons in the remaining three patients without c.548G>A. These findings suggest that the recurrent somatic GNAQ mutation c.548G>A is the major determinant genetic factor for SWS and imply that other mutated candidate gene(s) may exist in SWS.

Leucine-Rich α2-Glycoprotein Is a Novel Biomarker of Neurodegenerative Disease in Human Cerebrospinal Fluid and Causes Neurodegeneration in Mouse Cerebral Cortex

Leucine-rich α2-glycoprotein (LRG) is a protein induced by inflammation. It contains a leucine-rich repeat (LRR) structure and easily binds with other molecules. However, the function of LRG in the brain during aging and neurodegenerative diseases has not been investigated. Here, we measured human LRG (hLRG) concentration in the cerebrospinal fluid (CSF) and observed hLRG expression in post-mortem human cerebral cortex. We then generated transgenic (Tg) mice that over-expressed mouse LRG (mLRG) in the brain to examine the effects of mLRG accumulation. Finally, we examined protein-protein interactions using a protein microarray method to screen proteins with a high affinity for hLRG. The CSF concentration of hLRG increases with age and is significantly higher in patients with Parkinson’s disease with dementia (PDD) and progressive supranuclear palsy (PSP) than in healthy elderly people, idiopathic normal pressure hydrocephalus (iNPH) patients, and individuals with Alzheimer’s disease (AD). Tg mice exhibited neuronal degeneration and neuronal decline. Accumulation of LRG in the brains of PDD and PSP patients is not a primary etiological factor, but it is thought to be one of the causes of neurodegeneration. It is anticipated that hLRG CSF levels will be a useful biomarker for the early diagnosis of PDD and PSP.

Dural Enhancement in a Patient with Sturge-Weber Syndrome Revealed by Double Inversion Recovery Contrast Using Synthetic MRI

1Department of Radiology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan 2Department of Radiology, Graduate School of Medicine, The University of Tokyo 3Department of Radiological Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University 4Department of Neurosurgery, Juntendo University School of Medicine (Received June 10, 2015; Accepted July 20, 2015; published online November 6, 2015)

Use of External Lumbar Cerebrospinal Fluid Drainage and Lumboperitoneal Shunts with Strata NSC Valves in Idiopathic Normal Pressure Hydrocephalus: A Single-Center Experience

OBJECTIVE In Japan, idiopathic normal pressure hydrocephalus (iNPH) currently is treated mainly with lumboperitoneal (LP) shunts. Our aim was to evaluate whether LP shunting via the use of Medtronic Strata NSC programmable valves was as effective as ventriculoperitoneal shunting in the treatment of patients with iNPH from the perspectives of safety and symptomatic improvement rate. METHODS The clinical records of 51 iNPH patients (mean age, 75 years; males, 29), who underwent placement of Medtronic Strata NSC LP shunt systems were reviewed retrospectively as a cohort. LP shunting was evaluated with the modified Rankin Scale, the Japan Normal-Pressure Hydrocephalus Grading Scale, the Mini-Mental State Examination, the Frontal Assessment Battery, and the Trail-Making Test A as outcome measures. RESULTS Modified Rankin Scale scores improved from 3.2 to 2.2 (P < 0.01), indicating a 64% response rate 12 months after treatment. Total Japan Normal-Pressure Hydrocephalus Grading Scale scores decreased from 6.5 to 4.0 (P < 0.01), indicating a response rate of 81%. Mini-Mental State Examination scores improved from 22.2 to 25.4 (P < 0.01), Frontal Assessment Battery scores improved from 11.7 to 13.4 (P < 0.05), and Trail-Making Test A scores improved from 122.3 to 112.7 (P = 0.60). During the 12-month follow-up period, complications requiring surgery were observed in 6 cases (11.8%). CONCLUSION LP shunts showed effectiveness rates that were similar to those of ventriculoperitoneal shunts. Despite the relatively high complication rate, LP shunts can be recommended for the treatment of patients with iNPH because of their minimal invasiveness and lack of lethal complications.

Cerebrospinal fluid biomarkers for prognosis of long-term cognitive treatment outcomes in patients with idiopathic normal pressure hydrocephalus

The prognosis of cognitive improvement after cerebrospinal fluid (CSF) shunting in idiopathic normal pressure hydrocephalus (iNPH) remains uncertain, with no reports on CSF biomarkers related to long-term cognitive prognosis. We performed a preliminary study of CSF biomarker protein levels for cognitive outcome prognostication of two-year outcomes after shunt treated iNPH in 36 patients (13 women) with a median age of 75years (IQR 69-78). CSF biomarkers included soluble amyloid precursor proteins (sAPP, sAPPα, sAPPβ), amyloid β (Aβ)1-38, Aβ1-42 and phosphorylated tau (p-tau), lipocalin-type prostaglandin D synthase (L-PGDS)/β-trace, and cystatin C. The results clearly showed that p-tau levels (sensitivity of 71.4%, specificity of 77.8%, cut-off value of 22.0pg/mL), Aβ1-38/Aβ1-42 ratio (77.8%, 81%, 3.58), and the Aβ1-42/p-tau ratio (76%, 72.7%, 14.6) in preoperative CSF have the potential to determine postoperative prognosis. Improved cognition may be associated with the improvement in CSF circulation after LPS, which likely induces cystatin C and L-PGDS and switches synthesis from Aβ1-42 to Aβ1-38.

Efficacy of hippocampal transection for left temporal lobe epilepsy without hippocampal atrophy

We describe a case of left temporal lobe epilepsy without hippocampal atrophy. A 31-year-old woman presented with typical symptoms of complex partial seizures. Magnetic resonance imaging demonstrated slightly obscure internal structures in the left hippocampus. Scalp electroencephalography revealed interictal epileptiform discharges in the left temporal lobe. A Wada test with propofol determined the language-dominant hemisphere to be the left. Intraoperative electrocorticography revealed active epileptic discharges in the hippocampus and the anterior temporal basal area. The hippocampal epileptic area was treated with multiple transection, which led to the complete cessation of epileptic discharges. After surgery, the Rey Auditory Verbal Learning Test score decreased from 12 to 9. However, it returned to the preoperative level 6months after surgery. We describe this case as a typical example demonstrating the efficacy of hippocampal transection for seizure control and the preservation of verbal memory.

Posterior quadrant disconnection surgery for Sturge-Weber syndrome

Some patients with Sturge‐Weber syndrome (SWS) need epilepsy surgery for adequate seizure control and prevention of psychomotor deterioration. The majority of patients with SWS have leptomeningeal angioma located over the temporal, parietal, and occipital lobes. We applied posterior quadrant disconnection surgery for this type of SWS with intractable seizure. We evaluated the efficacy of this procedure in seizure control and psychomotor development.