Joan A. Conry

Noninvasive assessment of language dominance in children and adolescents with functional MRI: a preliminary study.

Background Assessment of language organization is crucial in patients considered for epilepsy surgery. In children, the current techniques, intra-carotid amobarbital test (IAT) for language dominance, and cortical electrostimulation mapping (ESM), are invasive and risky. Functional magnetic resonance imaging (fMRI) is an alternative method for noninvasive functional mapping, through the detection of the hemodynamic changes associated with neuronal activation. We used fMRI to assess language dominance in children with partial epilepsy. Methods Eleven right handed children and adolescents performed a word generation task during fMRI acquisition focused on the frontal lobes. Areas where the signal time course correlated with the test paradigm (r = 0.7) were considered activated. Extent and magnitude of signal changes were used to calculate asymmetry indices. Seven patients had IAT, ESM, or surgery outcome available for comparison. Results fMRI language dominance always agreed with IAT (6 cases) and ESM (1 case), showing left dominance in six and bilateral language in one. fMRI demonstrated left dominance in three additional children, and right dominance in one with early onset of left temporal epilepsy. Four children whose initial studies were equivocal due to noncompliance or motion artifacts were restudied successfully. Conclusions fMRI can be used to assess language lateralization noninvasively in children. It has the potential to replace current functional mapping techniques in patients, and to provide important data on brain development.

Language dominance in partial epilepsy patients identified with an fMRI reading task

Background fMRI language tasks readily identify frontal language areas; temporal activation has been less consistent. No studies have compared clinical visual judgment to quantitative region of interest (ROI) analysis. Objective To identify temporal language areas in patients with partial epilepsy using a reading paradigm with clinical and ROI interpretation. Methods Thirty patients with temporal lobe epilepsy, aged 8 to 56 years, had 1.5-T fMRI. Patients silently named an object described by a sentence compared to a visual control. Data were analyzed with ROI analysis from t-maps. Regional asymmetry indices (AI) were calculated ([L−R]/[L+R]) and language dominance defined as >0.20. t-Maps were visually rated by three readers at three t thresholds. Twenty-one patients had intracarotid amobarbital test (IAT). Results The fMRI reading task provided evidence of language lateralization in 27 of 30 patients with ROI analysis. Twenty-five were left dominant, two right, one bilateral, and two were nondiagnostic; IAT and fMRI agreed in most patients, three had partial agreement, none overtly disagreed. Interrater agreement ranged between 0.77 to 0.82 (Cramer V;p < 0.0001); agreement between visual and ROI reading with IAT was 0.71 to 0.77 (Cramer V;p < 0.0001). Viewing data at lower thresholds added interpretation to 12 patients on visual analysis and 8 with ROI analysis. Conclusions An fMRI reading paradigm can identify language dominance in frontal and temporal areas. Clinical visual interpretation is comparable to quantitative ROI analysis.

A Comparison of Rectal Diazepam Gel and Placebo for Acute Repetitive Seizures

BACKGROUND Acute repetitive seizures are readily recognizable episodes involving increased seizure frequency. Urgent treatment is often required. Rectal diazepam gel is a promising therapy. METHODS We conducted a randomized, double-blind, parallel-group, placebo-controlled study of home-based treatment for acute repetitive seizures. Patients were randomly assigned to receive either rectal diazepam gel, at a dosage varying from 0.2 to 0.5 mg per kilogram of body weight on the basis of age, or placebo. Children received one dose at the onset of acute repetitive seizures and a second dose four hours later. Adults received three doses -- one dose at onset, and two more doses 4 and 12 hours after onset. Treatment was administered by a care giver, such as a parent, who had received special training. The number of seizures after the first dose was counted for 12 hours in children and for 24 hours in adults. RESULTS Of 125 study patients (64 assigned to diazepam and 61 to placebo) with a history of acute repetitive seizures, 91 (47 children and 44 adults) were treated for an exacerbation of seizures during the study period. Diazepam treatment was superior to placebo with regard to the outcome variables related to efficacy: reduced seizure frequency (P<0.001) and improved global assessment of treatment outcome by the care giver (frequency and severity of seizures and drug toxicity) (P<0.001). Post hoc analysis showed diazepam to be superior to placebo in reducing seizure frequency in both children (P<0.001) and adults (P=0.02), but only in children was it superior with regard to improvement in global outcome (P<0.001). The time to the first recurrence of seizures after initial treatment was longer for the patients receiving diazepam (P<0.001). Thirty-five patients reported at least one adverse effect of treatment; somnolence was the most frequent. Respiratory depression was not reported. CONCLUSIONS Rectal diazepam gel, administered at home by trained care givers, is an effective and well-tolerated treatment for acute repetitive seizures.

fMRI language task panel improves determination of language dominance.

Background: fMRI language tasks reliably identify language areas in presurgical epilepsy patients, but activation using single paradigms may disagree with the intracarotid amobarbital test (IAT). Objective: To determine whether a panel of fMRI tasks targeting different aspects of language processing increases accuracy in determining hemisphere language dominance. Methods: Twenty-six patients age 12 to 56 years, predominantly with temporal lobe epilepsy, were studied using whole-brain 1.5 T fMRI (echo planar imaging, blood oxygenation level–dependent) with three task categories using a block design: verbal fluency, reading comprehension, and auditory comprehension. fMRI t maps were visually rated at three thresholds. All patients had assessment of language lateralization by IAT. Results: fMRI showed left dominance in 21 patients, right dominance in 2, and bilateral activation in 2; raters disagreed over a left vs right bilateral rating in 1 patient. There was full agreement between IAT and fMRI in 21 of 25 patients (IAT failed in 1). In three instances of partial disparity with IAT, the fMRI panel showed consistent findings across raters. Agreement between raters was excellent (partial disagreement in only one patient); the panel of tasks was superior to any single task for interrater agreement (Cramer V 0.93 [range 0.91 to 1.0] vs 0.72 [range 0.60 to 0.86]). Conclusions: A panel of fMRI language paradigms may be more accurate for evaluating partial epilepsy patients than a single task. A panel of tasks reduces the likelihood of nondiagnostic findings, improves interrater reliability, and helps confirm language laterality.

Vagus Nerve Stimulation in Children with Refractory Seizures Associated with Lennox–Gastaut Syndrome

Summary:  Purpose: Vagus nerve stimulation (VNS) is approved for use for refractory partial seizures. Nevertheless, information regarding VNS therapy for special populations, including Lennox–Gastaut syndrome (LGS) is limited. We discuss the effectiveness, tolerability, and safety of VNS therapy in patients with LGS.

Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: retrospective study.

This six-center, retrospective study evaluated the effectiveness, tolerability, and safety of vagus nerve stimulation in children. Data were available for 125 patients at baseline, 95 patients at 3 months, 56 patients at 6 months, and 12 patients at 12 months. The typical patient, aged 12 years, had onset of seizures at age 2 years and had tried nine anticonvulsants before implantation. Collected data included preimplant history, seizures, implant, device settings, quality of life, and adverse events. Average seizure reduction was 36.1% at 3 months and 44.7% at 6 months. Common adverse events included voice alteration and coughing during stimulation. Rare adverse events, unique to this age group, included increased drooling and increased hyperactivity. Quality of life improved in alertness, verbal communication, school performance, clustering of seizures, and postictal periods. We concluded that vagus nerve stimulation is an effective treatment for medically refractory epilepsy in children. (J Child Neurol 2001;16:843—848).

Clinical spectrum of succinic semialdehyde dehydrogenase deficiency.

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder affecting CNS γ-aminobutyric acid (GABA) degradation. SSADH, in conjunction with GABA transaminase, converts GABA to succinate. In the absence of SSADH, GABA is converted to 4-OH-butyrate. The presence of 4-OH-butyrate, a highly volatile compound, may be undetected on routine organic acid analysis. Urine organic acid testing was modified at the authors’ institution in 1999 to screen for the excretion of 4-OH-butyrate by selective ion monitoring gas chromatography-mass spectrometry in addition to total ion chromatography. Since then, five patients with 4-hydroxybutyric aciduria have been identified. The authors add the clinical, neuroimaging, and EEG findings from a new cohort of patients to 51 patients reported in the literature with clinical details. Ages ranged from 1 to 21 years at diagnosis. Clinical findings include mild-moderate mental retardation, disproportionate language dysfunction, hypotonia, hyporeflexia, autistic behaviors, seizures, and hallucinations. Brain MRI performed in five patients at the authors’ institution revealed symmetric increased T2 signal in the globus pallidi. SSADH deficiency is an under-recognized, potentially manageable neurometabolic disorder. Urine organic acid analysis should include a sensitive method for the detection of 4-hydroxybutyrate and should be obtained from patients with mental retardation or neuropsychiatric disturbance of unknown etiology.

Atypical language in lesional and nonlesional complex partial epilepsy

Objective: We investigated the relationship between partial epilepsy, MRI findings, and atypical language representation. Methods: A total of 102 patients (4 to 55 years) with left hemisphere epileptogenic zones were evaluated using three fMRI language tasks obtained at 1.5 or 3T with EPI BOLD techniques: verbal fluency, reading comprehension, and auditory comprehension. fMRI maps were visually interpreted at a standard threshold and rated as left or atypical language. Results: Atypical language dominance occurred in 30 patients (29%) and varied with MRI type (p < 0.01). Atypical language representation occurred in 36% (13/36) with normal MRI, 21% (6/29) with mesial temporal sclerosis, 14% (4/28) with focal cortical lesions (dysplasia, tumor, vascular malformation), and all (6/6) with a history of stroke. Multivariate logistic regression analysis found handedness, seizure onset, and MRI type accounted for much of the variance in language activation patterns (χ2 = 24.09, p < 0.01). Atypical language was more prevalent in patients with early seizure onset (43.2%, p < 0.05) and atypical handedness (60%, p < 0.01). None of the three clinical factors were correlated with each other (p > 0.40). Patients with atypical language had lower verbal abilities (F = 6.96, p = 0.01) and a trend toward lower nonverbal abilities (F = 3.58, p = 0.06). There were no differences in rates of atypical language across time, age groups, or MRI scanner. Conclusion: Early seizure onset and atypical handedness, as well as the location and nature of pathologic substrate, are important factors in language reorganization. GLOSSARY: FOV = field of view; MTS = mesial temporal sclerosis; RRN = read response naming; TE = echo time; TR = repetition time; WAIS = Wechsler Adult Intelligence Scale; WISC = Wechsler Intelligence Scale for Children.

Cerebral MRI abnormalities associated with vigabatrin therapy.

Purpose:  Investigate whether patients on vigabatrin demonstrated new‐onset and reversible T2‐weighted magnetic resonance imaging (MRI) abnormalities.

Seizure focus affects regional language networks assessed by fMRI.

Objective: To investigate the degree of language dominance in patients with left and right hemisphere seizure foci compared to normal volunteers using a fMRI reading comprehension task. Methods: Fifty patients with complex partial epilepsy, aged 8 to 56 years and 33 normal volunteers, aged 7 to 34 had fMRI (1.5 T) and neuropsychological testing. Participants silently named an object described by a sentence compared to a visual control. Data were analyzed with region of interest (ROI) analysis based on t maps for inferior frontal gyrus (IFG), midfrontal gyrus (MFG), and Wernicke area (WA). Regional asymmetry indices (AIs) were calculated [(L − R)/(L + R)]; AI >0.20 was deemed left dominant and AI <0.20 as atypical language. Results: Left hemisphere focus patients had a higher likelihood of atypical language than right hemisphere focus patients (21% vs 0%, χ2 < 0.002). Left hemisphere focus patients, excluding those with atypical language, had lower regional AI in IFG, MFG, and WA than controls. Right hemisphere focus patients were all left language dominant and had a lower AI than controls in WA and MFG, but not for IFG. AI in MFG and WA were similar between left hemisphere focus/left language patients and right hemisphere focus patients. Patients activated more voxels than healthy volunteers. Lower AIs were attributable to greater activation in right homologous regions. Less activation in the right-side WA correlated with better verbal memory performance in right focus/left hemisphere-dominant patients, whereas less strongly lateralized activation in IFG correlated better with Verbal IQ in left focus/left hemisphere-dominant patients. Conclusions: Patients had lower asymmetry indices than healthy controls, reflecting increased recruitment of homologous right hemisphere areas for language processing. Greater right hemisphere activation may reflect greater cognitive effort in patient populations, the effect of epilepsy, or its treatment. Regional activation patterns reflect adaptive efforts at recruiting more widespread language processing networks that are differentially affected based on hemisphere of seizure focus.