Assessment of language lateralization in epilepsy patients using the super-selective Wada test.

BACKGROUND: The classical Wada test (cWada), performed by injecting a short-acting anesthetic through the intracarotid route, helps determine language dominance. In the cWada, adverse effects are observed in 10-30% of trials, hindering accurate assessments. In this study, we assessed the effectiveness of the super-selective Wada test (ssWada), a more selective approach for anesthetic infusion into the middle cerebral artery (MCA). METHODS: We retrospectively examined the data of 17 patients with epilepsy who underwent ssWada via anesthetic injection into one M1 segment of the MCA and at least one contralateral trial. RESULTS: The ssWada identified 12 patients with left language dominance, 3 with right language dominance, and 2 with bilateral language distribution. Nine trials on the language dominant side resulted in global aphasia for patients with left- or right language dominance. Of the 13 trials conducted on the non-dominant language side, 12 revealed intact language function and one resulted in confusion. Among these, the outcomes of global aphasia or no language impairment were confirmed in the contralateral trials. Among the 22 trials of unilateral M1 injections in patients with unilateral language dominance, 21 (95.5%) showed either global aphasia or no language impairment, indicating language dominance. CONCLUSIONS: The ssWada yields clear results, with a high rate of over 90% in determining the language dominant hemisphere with few side effects.

Referral odyssey plot to visualize causes of surgical delay in mesial temporal lobe epilepsy with hippocampal sclerosis.

The "odyssey plot" was used to visualize referral delays in epilepsy surgery. Participants were 36 patients (19 males; 13-67 years, median 27 years) with mesial temporal lobe epilepsy with hippocampal sclerosis (HS) who underwent resection surgery. The "referral odyssey plot" included five clinical episodes: seizure onset (T1), first visits to a non-epileptologist (T2) and to an epileptologist (T3), first admission to our epilepsy monitoring unit (EMU) (T4), and resection surgery (T5). For each patient, we identified the first seizure type: the physician who first diagnosed focal aware seizure (FAS), focal impaired awareness seizure (FIAS), focal to bilateral tonic-clonic seizure (FBTCS), and radiologically suspected HS. Within the overall delay (T1-T5, median 18 years; interquartile range [IQR] 14), non-epileptologist's delay (T2-T3, 11.5 years; IQR 12.25) was far (p < 0.0001) longer than patient's (T1-T2, 0 year; IQR 2.25), epileptologist's (T3-T4, 1 year; IQR 4), or after-EMU delay (T4-T5, 1 year; IQR 1). FAS onset cases had significantly longer T1-T2 (N = 5, median 7 years; IQR 6) than FIAS (N = 22, 0 year; IQR 1, p < 0.005) or FBTCS onset cases (N = 9, 0 year; IQR 0, p < 0.001). FAS was correctly diagnosed first by non-epileptologists in 17.9%, by out-patient epileptologists in 35.7%, and at the EMU in 46.4%. FIAS was correctly diagnosed first by non-epileptologists in 94.4% and by out-patient epileptologists in 5.6%. Non-epileptologists diagnosed FBTCS in all cases. HS was diagnosed by non-epileptologists in 13.9%, by out-patient epileptologists in 47.2%, and at the EMU in 38.9%. Early referral to epileptologists is most critical for early surgery. Early utilization of the EMU is highly recommended because FAS is often overlooked by outpatient epileptologists. The odyssey plot will be useful to improve the healthcare system for other types of epilepsy.

Remission of startle epilepsy provoked by acoustic stimuli following complete callosotomy: A case study.

Herein, we present the case of a 21-year-old man with a history of generalized tonic seizures since the age of 4 years. These seizures occurred either spontaneously or could be provoked by auditory stimuli such as the sounds of a vacuum cleaner or an electric shaver. Despite trials with 10 different anti-seizure medications, his seizures remained refractory. Interictal electroencephalography (EEG) revealed generalized epileptiform activity, whereas ictal EEG showed a generalized attenuation pattern. Magnetic resonance imaging revealed extensive chronic infarctions, predominantly in the bilateral cerebral watershed areas. At the age of 17, the patient underwent a one-stage complete callosotomy, which only achieved remission of auditory-provoked seizures. Based on this experience and published reports, we propose that the posterior corpus callosum, particularly the isthmus and anterior splenium, may be involved in seizures caused by unexpected sound stimuli.

"Caterpillar sign" in corpus callosum associated with curvilinear pericallosal lipoma in MRI: A case report.

Lipoma of the corpus callosum, also known as pericallosal lipoma, is a rare congenital brain abnormality associated with corpus callosum dysgenesis or agenesis. Two morphological types are described: tubulonodular and curvilinear, with the latter being mostly asymptomatic. We present the case of a 30-year-old woman with epilepsy, whose magnetic resonance imaging revealed a "caterpillar sign" in the corpus callosum associated with a curvilinear pericallosal lipoma. The "caterpillar sign" in the corpus callosum showed low signal intensity on magnetization prepared rapid acquisition with gradient echo, high signal on fluid-attenuated inversion recovery, and low on susceptibility-weighted imaging, possibly indicating abnormal blood vessels penetrating from the ventricle to the posterior callosal vein. We need to be conscious of this unusual finding, particularly when considering surgical intervention in the corpus callosum in cases of pericallosal lipoma, to avoid vascular complications.

Super-selective injection of propofol into the intracranial arteries enables Patient's self-evaluation of expected neurological deficit.

INTRODUCTION: It is hard to realize the extent of the expected postoperative neurological deficit for patients themselves. The provision of appropriate information can contribute not only to examining surgical indications but also to filling the gap between patient and expert expectations. We hypothesized that propofol infusion into the intracranial arteries (ssWada) could induce focal neurological symptoms with preserved wakefulness, enabling the patients to evaluate the postsurgical risk subjectively. METHODS: Presurgical evaluation using ssWada was performed in 28 patients with drug-resistant epilepsy. Based on anatomical knowledge, propofol was super-selectively infused into the intracranial arteries including the M1, M2, and M3 segments of the middle cerebral artery (MCA), A2 segment of the anterior cerebral artery, and P2 segment of the posterior cerebral artery to evaluate the neurological and cognitive symptoms. We retrospectively analyzed a total of 107 infusion trials, including their target vessels, and elicited symptoms of motor weakness, sensory disturbance, language, unilateral hemispatial neglect (UHN), and hemianopsia. We evaluated preserved wakefulness which enabled subjective evaluations of the symptoms and comparison of the subjective experience to the objective findings, besides adverse effects during the procedure. RESULTS: Preserved wakefulness was found in 97.2% of all trials. Changes in neurological symptoms were positively evaluated for motor weakness in 51.4%, sensory disturbance in 5.6%, language in 48.6%, UHN in 22.4%, and hemianopsia in 32.7%. Six trials elicited seizures. Multivariate analysis showed significant correlations between symptom and infusion site of language and left side, language and MCA branches, motor weakness and A2 or M2 superior division, and hemianopsia and P2. Transient adverse effect was observed in 8 cases with 12 infusion trials (11.2 %). CONCLUSION: The ssWada could elicit focal neurological symptoms with preserved wakefulness. The methodology enables specific evaluation of risk for cortical resection and subjective evaluation of the expected outcome by the patients.

Ictal chest discomfort in a patient with temporal lobe seizures and amygdala enlargement.

Chest discomfort is the representative symptom of dangerous coronary artery disease (CAD), but rarely occurs in patients with seizures. We treated a 74-year-old man with right mesial temporal lobe epilepsy and amygdala enlargement, who was initially suspected of CAD and underwent repeated cardiac angiography because of recurrent episodes of paroxysmal chest discomfort starting from 68 years old. He visited an epileptologist and underwent long-term video electroencephalography monitoring (LTVEM), which confirmed right temporal seizure onset during a habitual episodes of "chest discomfort," stereotyped movement of chest rubbing with the right hand, followed by impaired conscousness. Brain magnetic resonance imaging revealed right amygdala enlargement. The present case emphasizes the importance of the wide range of symptoms, such as chest discomfort, which may associated with epielpsy and result in a delayed diagnosis. LTVEM is useful for diagnosis of epilepsy with unusual seizure semiology by recording ictal EEG changes during chest discomfort.

Causal involvement of medial inferior frontal gyrus of non-dominant hemisphere in higher order auditory perception: A single case study.

The medial side of the operculum is invisible from the lateral surface of cerebral cortex, and its functions remain largely unexplored using direct evidence. Non-invasive and invasive studies have proved functions on peri-sylvian area including the inferior frontal gyrus (IFG) and superior temporal gyrus within the language-dominant hemisphere for semantic processing during verbal communication. However, within the non-dominant hemisphere, there was less evidence of its functions except for pitch or prosody processing. Here we add direct evidence for the functions of the non-dominant hemisphere, the causal involvement of the medial IFG for subjective auditory perception, which is affected by the context of the condition, regarded as a contribution in higher order auditory perception. The phenomenon was clearly distinguished from absolute and invariant pitch perception which is regarded as lower order auditory perception. Electrical stimulation of the medial surface of pars triangularis of IFG in non-dominant hemisphere via depth electrode in an epilepsy patient rapidly and reproducibly elicited perception of pitch changes of auditory input. Pitches were perceived as either higher or lower than those given without stimulation and there was no selectivity for sound type. The patient perceived sounds as higher when she had greater control over the situation when her eyes were open and there were self-cues, and as lower when her eyes were closed and there were investigator-cues. Time-frequency analysis of electrocorticography signals during auditory naming demonstrated medial IFG activation, characterized by low-gamma band augmentation during her own vocal response. The overall evidence provides a neural substrate for altered perception of other vocal tones according to the condition context.

Bilateral and asymmetrical localization of language function identified by the superselective infusion of propofol in an epilepsy patient with a mild malformation of cortical development: illustrative case.

BACKGROUND: Atypical localization of language function can result in unexpected postsurgical deficits after cortical resection, but it is difficult to predict the risk in the presurgical evaluation. The authors experienced a rare case of the bilateral and independent existence of different components of language function identified by segmented evaluation of anatomical anterior and posterior language areas using the superselective infusion of propofol. OBSERVATIONS: A 32-year-old right-handed female presented with drug-resistant epilepsy. Comprehensive epilepsy evaluation suggested that the epileptic foci involved the whole left frontal lobe but provided less evidence of structural abnormality. To estimate the extent of functional deterioration likely to be caused by an extended left frontal lobectomy, the authors evaluated segmented cortical function in the ipsi- and contralateral hemispheres by the superselective infusion of propofol into the branches of the intracranial artery. The results revealed bilateral and asymmetrical localization of language function because the patient presented with different components of aphasia in each hemisphere. Based on the authors' assessment of her functional tolerance, an extended left frontal lobectomy was performed and resulted in neurological deficits within the anticipated range. LESSONS: An accurate understanding of the correlations between vascular and functional anatomy and the highly specific evaluation of language function provides more advanced presurgical assessment, allowing more tailored planning of cortical resection.

Age-Related Recovery of Daily Living Activity After 1-Stage Complete Corpus Callosotomy: A Retrospective Analysis of 41 Cases.

BACKGROUND: Recovery time after corpus callosotomy (CC) is known to be longer in elderly than in younger patients. OBJECTIVE: To evaluate the relationship between patient age and recovery time of activities of daily living (ADL) after 1-stage complete CC. METHODS: This study included 41 patients (22 women; aged 13 months-34 years, median 7 years) who underwent 1-stage complete CC for medically intractable seizures with drop attacks, infantile spasms, and/or bilaterally synchronized electroencephalographic discharges between August 2009 and April 2019. The timing of restart of competence in 5 ADL categories and surgical outcomes were recorded. RESULTS: Patients (1) restarted speech at 2.2 ± 1.3 (mean ± 2 standard deviations; range 1-5) days, (2) restarted replying with their own name on request at 5.5 ± 8.6 (2-33) days, (3) restarted oral intake at 1.6 ± 1.7 (1-11) days, (5) discontinued intravenous feeding at 6.0 ± 3.0 (2-16) days, and (5) restarted ambulation or wheelchair movement at 5.8 ± 3.4 (2-10) days. Younger patients showed significantly (P < .0223) earlier recovery of ambulation or wheelchair movement, but no age difference was found in the other 4 ADL categories. Overall seizure freedom was achieved in 5 patients, excellent (>80%) seizure reduction in 11, good (50%-80%) seizure reduction in 5, and poor (<50%) seizure reduction in 20. CONCLUSION: Early ADL recovery after 1-stage complete CC is favorable in both young and adult patients. These findings, with good surgical outcomes, will encourage more positive consideration of 1-stage complete CC in both pediatric and adult patients.

Determination of language areas in patients with epilepsy using the super-selective Wada test.

The Wada test is the gold standard for determining language-dominant hemisphere. However, the precise determination of language areas in each patient requires more invasive methods, such as electrocortical stimulation. Some studies have reported the use of anesthetic injection into selective cerebral arteries to predict postoperative function. To assess the function of the anterior and posterior language areas separately, we developed an advanced test named the "super-selective Wada test" (ssWada). The ssWada procedure is as follows: an endovascular neurosurgeon identifies the arterial branches of the middle cerebral artery (MCA) perfusing the anterior language area of the inferior frontal gyrus and the posterior language area of the posterior part of the superior temporal gyrus using angiography. Behavioral neurologists assess language symptoms before and after propofol administration using a microcatheter tip in the selected arterial branch. From 30 serial patients with epilepsy who underwent ssWada test at Tohoku University Hospital, we retrospectively reviewed patients in whom multiple areas in the bilateral MCA region was examined. Eight cases were identified in this study. All eight cases had been considered for resection of the area overlapping the classical language area. Three of the eight cases were left-dominant, and the within-hemisphere distribution was also considered typical. One case was determined to be left-dominant but atypical in the intra-hemispheric functional distribution. Two cases were right-dominant, and the intra-hemispheric functional distribution was considered a mirror image of the typical pattern. The remaining two cases were considered atypical, not only in terms of bilateral language function, but also in terms of anterior-posterior functional distribution. This case series demonstrates the potential utility of ssWada in revealing separate function of the anterior and posterior language areas. The ssWada allows simulation of local surgical brain resection and detailed investigation of language function, which potentially contributes to planning the resection area. Although indications for ssWada are quite limited, it could play a complementary role to noninvasive testing because it provides information related to resection using a different approach.

Epilepsy in Five Long-term Survivors of Pineal Region Tumors.

Cognitive decline is a well-known chronic side effect of multidisciplinary treatment of pineal region tumors, whereas epilepsy is an under-reported chronic consequence caused by multiple potential factors including radiotherapy, surgery, or chemotherapy. Some long-term survivors have suffered drug-resistant epilepsy after treatment, which impaired the quality of life. We report five consecutive patients with drug-resistant epilepsy after combined treatment of pineal region tumor (5 men, aged 21-42 years) among 1201 epilepsy patients who underwent comprehensive evaluation in our tertiary epilepsy center from 2011 to 2018. The comprehensive epilepsy evaluation included medical interview, long-term video electroencephalography (EEG) monitoring (VEM), and magnetic resonance (MR) imaging. The patients started to have seizures at 2-22 years after initial treatment for the tumor. Four of the five patients had focal impaired awareness seizures, whereas one patient had only visual aura. All patients had EEG seizures during VEM, which confirmed the diagnosis of focal epilepsy, but three patients had no interictal epileptiform discharges (IEDs). Two patients had diagnoses of focal epilepsy arising from the left occipital region based on ictal EEG findings. Both patients had MR imaging lesion in the left occipital lobe, radiation-induced cavernoma, or surgical injury. The remaining three patients showed poor localization of epileptogenic foci based on VEM and MR imaging. Drug-resistant epilepsy after multidisciplinary treatment of pineal region tumor is characterized by focal impaired awareness seizures with poorly localized EEG onset or rare interictal spikes.

A Super-selective Wada Test Successfully Detected an Artery That Supplied Broca's Area in a Case of Left Frontal Lobe Glioblastoma: Technical Case Report.

In cases of malignant gliomas located at language eloquent area, it is often difficult to preoperatively detect those area with functional MRI. Awake surgery is often used to spare the language eloquent area during surgery for such tumors; it is not available for a patient whose intracranial pressure is elevated due to the malignant tumor. The Wada test involves infusing anesthetic agents into the internal carotid artery to determine language dominancy before surgery for epilepsy or brain tumor. The super-selective Wada test is a technique to detect more detailed functional localization by infusing anesthetics into far distal middle cerebral artery branches. We present a 37-year-old man suffering from a left frontal lobe glioblastoma, in whom detection of an artery supplying Broca's area was attempted by a super-selective Wada test. The super-selective Wada test successfully detected the branch of middle cerebral artery supplying Broca's area. Total resection of the contrast-enhancing area was achieved without damaging the artery supplying Broca's area without any neurological sequelae. This is the first report describing the usefulness of the super-selective Wada test in glioblastoma treatment. Our findings suggest that the super-selective Wada test is a powerful and useful means to distinguish the artery that supplies the language area from the tumor feeding artery in cases of tumors in the language eloquent area.

Your verbal questions beginning with 'what' will rapidly deactivate the left prefrontal cortex of listeners.

The left prefrontal cortex is essential for verbal communication. It remains uncertain at what timing, to what extent, and what type of phrase initiates left-hemispheric dominant prefrontal activation during comprehension of spoken sentences. We clarified this issue by measuring event-related high-gamma activity during a task to respond to three-phrase questions configured in different orders. Questions beginning with a wh-interrogative deactivated the left posterior prefrontal cortex right after the 1st phrase offset and the anterior prefrontal cortex after the 2nd phrase offset. Left prefrontal high-gamma activity augmented subsequently and maximized around the 3rd phrase offset. Conversely, questions starting with a concrete phrase deactivated the right orbitofrontal region and then activated the left posterior prefrontal cortex after the 1st phrase offset. Regardless of sentence types, high-gamma activity emerged earlier, by one phrase, in the left posterior prefrontal than anterior prefrontal region. Sentences beginning with a wh-interrogative may initially deactivate the left prefrontal cortex to prioritize the bottom-up processing of upcoming auditory information. A concrete phrase may obliterate the inhibitory function of the right orbitofrontal region and facilitate top-down lexical prediction by the left prefrontal cortex. The left anterior prefrontal regions may be recruited for semantic integration of multiple concrete phrases.