Effects of a higher dose of alglucosidase alfa on ventilator-free survival and motor outcome in classic infantile Pompe disease: an open-label single-center study.

BACKGROUND: Though enzyme-replacement therapy (ERT) with alglucosidase alfa has significantly improved the prospects for patients with classic infantile Pompe disease, some 50 % of treated infants do not survive ventilator-free beyond the age of 3 years. We investigated whether higher and more frequent dosing of alglucosidase alfa improves outcome. METHODS: Eight cross-reactive immunological material (CRIM) positive patients were included in the study. All had fully deleterious mutations in both GAA alleles. Four received a dose of 20 mg/kg every other week (eow) and four received 40 mg/kg/week. Survival, ventilator-free survival, left-ventricular mass index (LVMI), motor outcome, infusion-associated reactions (IARs), and antibody formation were evaluated. RESULTS: All eight patients were alive at study end, seven of them remained ventilator-free. The patient who became ventilator dependent was treated with 20 mg/kg eow. Three of the four patients receiving 20 mg/kg eow learned to walk; two of them maintained this ability at study end. All four patients receiving 40 mg/kg/week acquired and maintained the ability to walk at study end (ages of 3.3-5.6 years), even though their baseline motor functioning was poorer. There were no apparent differences between the two dose groups with respect to the effect of ERT on LVMI, the number of IARs and antibody formation. CONCLUSIONS: Our data may suggest that a dose of 40 mg/kg/week improves outcome of CRIM positive patients over that brought by the currently recommended dose of 20 mg/kg eow. Larger studies are needed to draw definite conclusions.

Functional characterization of the TSC2 c.3598C>T (p.R1200W) missense mutation that co-segregates with tuberous sclerosis complex in mildly affected kindreds.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by a combination of neurological symptoms and hamartomatous growths, and caused by mutations in the TSC1 and TSC2 genes. Overall, TSC2 mutations are associated with a more severe disease phenotype. We identified the c.3598C>T (R1200W) change in the TSC2 gene in seven different families. The clinical phenotypes in the families were mild, characterized by mild skin lesions, remitting epilepsy and a lack of severe mental retardation or major organ involvement. Functional analysis of the TSC2 R1200W variant, and four other TSC2 missense variants associated with a mild TSC phenotype, confirmed that the changes disrupted the TSC1-TSC2 function. Interestingly however, in each case, the TSC1-TSC2 interaction was not affected by the amino acid substitution.

Effects of immunomodulation in classic infantile Pompe patients with high antibody titers.

PURPOSE: To evaluate whether immunomodulation can eliminate high sustained antibody levels, and thereby improve clinical outcome in classic infantile Pompe patients receiving enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA). METHODS: Three patients (two cross-reactive immunologic material (CRIM) negative) with high sustained antibodies received a three-week treatment protocol with Rituximab and Bortezomib, followed by daily Rapamycin and monthly IVIG. Patients received 40 mg/kg/week rhGAA. Antibody titers were measured using ELISA. Neutralizing effects on cellular uptake were determined. Clinical efficacy was measured in terms of (ventilator-free) survival, reduction in left ventricular mass index (LVMI) and improvement in motor function. RESULTS: Before immunomodulation anti-rhGAA antibody titers ranged from 1:156,250 to 1:781,250 and at last assessment from 1:31,250 to 1:156,250. Neutralizing effects of anti-rhGAA antibody titers (observed in two patients) disappeared. Infusion-associated reactions were no longer present. Immunomodulation resulted in substantial increases of aspartate transaminase, alanine transaminase, and creatine kinase levels. The two CRIM-negative patients who could walk at start of immunomodulation maintained their ability to walk; the patient who had lost this ability did not regain it. CONCLUSIONS: To some extent, the immunomodulation protocol used in our study reduced antibody titers, but it did not eliminate them. Overall, there have been few reports on secondary immunomodulation, and various protocols have been applied. Future research should seek to identify the most successful immunomodulation protocol in patients with high sustained titers.

The Emergent Literacy Skills of Preschool Children with Autism Spectrum Disorder.

A high percentage of school-age students with autism spectrum disorder (ASD) have reading comprehension difficulties leading to academic disadvantage. These difficulties may be related to differences in children's emergent literacy development in the preschool years. In this study, we examined the relationship between emergent literacy skills, broader cognitive and language ability, autism severity, and home literacy environment factors in 57 preschoolers with ASD. The children showed strengths in code-related emergent literacy skills such as alphabet knowledge, but significant difficulties with meaning-related emergent literacy skills. There was a significant relationship between meaning-related skills, autism severity, general oral language skills, and nonverbal cognition. Identification of these meaning-related precursors will guide the targets for early intervention to help ensure reading success for students with ASD.

The factor structure of the CVLT-C in pediatric epilepsy.

The current study used archival data to evaluate the fit of six latent variable models, originally generated by Donders (1999), for the California Verbal Learning Test-Children's Version (CVLT-C; Delis, Kramer, Kaplan, & Ober, 1994) in a large (N = 289) sample of pediatric epilepsy cases presenting at three tertiary treatment centers. Using confirmatory factor analysis, we found that a model including factors of Attention Span, Learning Efficiency, Free Delayed Recall, Cued Delayed Recall, and Inaccurate Recall demonstrated the best relative fit for our data. These findings are consistent with those reported by Donders (1999) in his reanalysis of the CVLT-C standardization sample data, supporting the validity of this factorial model in pediatric epilepsy populations.

Detection of minimal disease using rearranged immunoglobulin heavy chain genes from intermediate- and high-grade malignant B cell non-Hodgkins lymphoma.

Rearranged immunoglobulin heavy chain (IgH) genes provide unique clonal markers for B cells. Since amplification of the rearranged gene by polymerase chain reaction (PCR) and demonstrating that the amplified sequence is indeed derived from tumor cells is more problematic in non-Hodgkin's lymphoma (NHL) than in other B cell malignancies, we used a comprehensive PCR primer set and formulated stringent selection criteria to identify tumor-specific rearranged IgH genes. Rearranged IgH genes amplified from lymphoma DNA were considered to be of tumor origin if they were monoclonal, and if the same rearrangement was amplified with at least two independent VH-specific primers. From 11 of 13 (85%) intermediate- and high-grade malignant NHL, IgH rearrangements were isolated. Intraclonal IgH sequence heterogeneity was studied in four lymphomas, and detected in two of them. PCR using a lymphoma-specific primer followed by Southern hybridization of PCR product with a specific probe allowed detection of lymphoma DNA after 10,000-fold dilution. Circulating lymphoma cells were detected in patient blood and bone marrow samples which were negative by morphological and immunological criteria. Thus, also in intermediate- and high-grade malignant lymphoma, sensitive minimal disease detection using the rearranged IgH gene as a marker appears feasible.

Rearranged immunoglobulin light chain genes as minimal residual disease markers in intermediate- and high-grade malignant B cell non-Hodgkin's lymphoma.

Minimal residual disease (MRD) detection in B cell non-Hodgkin's lymphoma (NHL) patients has been shown to be possible using the rearranged heavy (IgH) chain gene as a tumor marker. To explore a second independent tumor marker, we used specific PCR primer sets to identify tumor-specific rearranged Ig light chain (IgL) genes. Rearranged IgL genes were amplified from lymphoma DNA by multiplex PCR using separate primer sets for the Igkappa and the Iglambda genes. They were considered to be of tumor origin if they were monoclonal, and if the same rearrangement was isolated from at least two independent PCR products. From 12 out of 13 intermediate- and high-grade malignant NHL, PCR products could be obtained with IgL specific primers. PCR products from five NHL were studied in detail by cloning and sequencing. The rearranged IgL genes showed 85-100% homology with their closest germ line counterparts. Intraclonal IgL sequence heterogeneity was studied in five lymphomas and detected in only one. Minimal disease was studied in three patients by PCR, followed by Southern hybridization of the PCR product with a lymphoma-specific oligonucleotide probe, which allowed for detection of lymphoma DNA following 1000-fold dilution. Blood samples from one patient, who is in long-term clinical remission, were negative for the lymphoma-specific rearranged Igkappa gene. In the second patient the rearranged Iglambda gene was detected during the first clinical remission, that was followed by a nodal relapse, but not during the second remission, that has been stable for almost 3 years now. The third patient was negative for the rearranged Iglambda gene in blood samples up to 102 months after diagnosis. Circulating lymphoma cells were detected in blood and bone marrow samples which were negative by morphological and immunological criteria. Our studies show that the rearranged IgL gene can be used as a second independent tumor marker in intermediate- and high-grade malignant NHL.

The neural substrate of memory impairment demonstrated by the intracarotid amobarbital procedure.

The intracarotid amobarbital sodium (Amytal) procedure (IAP) was performed for 46 patients with temporal lobe epilepsy (21 with left seizure foci; 25 with right seizure foci). After anteromedial temporal lobectomy, neuronal densities were established for hippocampal subfields CA1, CA2, and CA3; the hilum; and the dentate granule cell layer. Intracarotid amobarbital procedure memory results were related to CA3 neuronal loss only. Patients who did not demonstrate memory after injection contralateral to the seizure focus had significantly fewer cells in CA3 than patients who did. Additionally, a significant correlation was observed between the intracarotid amobarbital procedure memory examination raw score after injection contralateral to the seizure focus and CA3 cell density. Using chi 2 analysis, significant differences were documented in the frequency with which memory was demonstrated after injection contralateral to the seizure focus for groups of patients classified by degree of CA3 neuronal loss. This finding supports prior research showing subfield specificity in some memory processes.

General cognitive ability following unilateral and bilateral fetal ventral mesencephalic tissue transplantation for treatment of Parkinson's disease.

OBJECTIVE: To contrast the neuropsychological profiles of Parkinsonian patients, before and after fetal ventral mesencephalic tissue transplantation. DESIGN: Case series of personally examined patients. SETTING: Patients were evaluated by neurologists, neurosurgeons, and neuropsychologists as outpatients at a university hospital. PATIENTS: Fetal mesencephalic tissue was implanted in the right caudate nucleus of three patients and both nuclei of one patient. These patients were evaluated prior to surgery and at 12, 24, and 26 months postoperatively. RESULTS: Factor analysis of the test battery identified four statistically orthogonal test clusters. No statistically significant changes were identified postoperatively for clusters assessing verbal cognitive ability, nonverbal cognitive ability, and information-processing speed. An improvement of verbal memory cluster index was observed 12 months after surgery, and the improvement reached the level of statistical significance at 24 months after surgery. However, the verbal memory of all patients declined between 24 and 36 months after surgery. CONCLUSIONS: Fetal tissue transplantation to one or both caudate nuclei did not permanently arrest cognitive dysfunction. Although there is some evidence of improved cognitive ability after transplantation, it is improbable that normal cognitive function can be restored by this procedure because the impairments of cognitive ability associated with Parkinson's disease do not appear to originate solely from dopamine deficiency.

Verbal memory impairment resulting from hippocampal neuron loss among epileptic patients with structural lesions.

We recently demonstrated statistically significant correlations between presurgical memory impairment and hippocampal volumetric cell densities (in CA3 and the hilar area only) for patients with idiopathic left temporal lobe epilepsy who exhibited marked hippocampal neuron loss. In the present research we determine whether the same relationship exists for patients with structural lesions, in whom hippocampal neuron loss was minimal. Rank-order correlations of verbal memory test results (ie, Long Term Retrieval score of the verbal Selective Reminding Test, Percent Retention index of the Logical Memory subtest of the Wechsler Memory Scale) and hippocampal volumetric cell densities (subfields CA1, CA2, CA3, the hilar area, and the granule layer of area dentata) were computed for 22 patients with structural lesions and medically refractory epilepsy of temporal lobe onset (11 left, 11 right). There were statistically significant correlations between Long Term Retrieval and the volumetric cell density of CA1 (r = 0.62, p < 0.05) and between percent retention and the volumetric cell density of CA2 (r = 0.60, p < 0.05) for patients with left hemisphere lesions. No other correlations were found for patients with left or right temporal lobe lesions.

Verbal memory impairment correlates with hippocampal pyramidal cell density.

Thirty-five patients with medically refractory epilepsy localized to the temporal lobe (18 left, 17 right) completed the verbal Selective Reminding Test before surgery. Verbal memory impairments existed before surgery regardless of the lateralization of the seizure focus, but patients with left temporal seizure foci were significantly more impaired. After surgical removal of the mesial temporal lobe structures, 2 blinded observers established volumetric cell densities for hippocampal subfields CA1, CA2, CA3, the hilar area, and the granule cell layer of the area dentata. Statistically significant correlations existed between presurgical memory impairment and cell counts (in CA3 and the hilar area, only) for patients with left temporal seizure foci. These findings support the hippocampal model of memory and complement prior research documenting the memory impairments present after surgical removal of the mesial temporal structures.

Effects of anomalous language representation on neuropsychological performance in temporal lobe epilepsy.

OBJECTIVE: To examine the effects of anomalous language representation (i.e., mixed- and right-cerebral dominant) on neuropsychological performance. BACKGROUND: Right cerebral language dominance resulting from early cerebral injury is associated with relatively preserved language function with decreased visuospatial ability. However, previous reports of this phenomenon have examined patients with relatively large cerebral injuries (e.g., infantile hemiplegia) or limited sample sizes. METHODS: A total of 561 patients with complex partial seizures of left temporal lobe origin were studied. Patients were classified into left (n = 455), bilateral (n = 58), and right (n = 48) language dominant groups based on Wada testing. RESULTS: Right language dominant patients performed more poorly on multiple tests of visuospatial function, including Performance IQ (PIQ), than did left language patients. No significant group differences were detected for measures of language or general verbal function. The effects of bilateral language on PIQ differed according to handedness. Lowered PIQ was present in the bilateral nondextral group but not for bilateral dextral patients, and this pattern was observed with other visuospatial measures. CONCLUSIONS: In patients with relatively small lesions restricted to the left mesial temporal lobe, a shift in language dominance to the right hemisphere is associated with decreased visuospatial functions but preserved verbal abilities. Nondextral patients with bilateral language representation also displayed decreased visuospatial performance, although dextral patients with bilateral language did not.

Outcome of children in the indomethacin intraventricular hemorrhage prevention trial.

BACKGROUND: For preterm infants, intraventricular hemorrhage (IVH) may be associated with adverse neurodevelopmental outcome. We have demonstrated that early low-dose indomethacin treatment is associated with a decrease in both the incidence and severity of IVH in very low birth weight preterm infants. In addition, we hypothesized that the early administration of low-dose indomethacin would not be associated with an increase in the incidence of neurodevelopmental handicap at 4.5 years of age in our study children. METHODS: To test this hypothesis, we provided neurodevelopmental follow-up for the 384 very low birth weight survivors of the Multicenter Randomized Indomethacin IVH Prevention Trial. Three hundred thirty-seven children (88%) were evaluated at 54 months' corrected age, and underwent neurodevelopmental examinations, including the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), the Peabody Picture Vocabulary Test-Revised (PPVT-R), and standard neurologic examinations. RESULTS: Of the 337 study children, 170 had been randomized to early low-dose indomethacin therapy and 167 children had received placebo. Twelve (7%) of the 165 indomethacin children and 11 (7%) of the 158 placebo children who underwent neurologic examinations were found to have cerebral palsy. For the 233 English-monolingual children for whom cognitive outcome data follow, the mean gestational age was significantly younger for the children who received indomethacin than for those who received placebo. In addition, although there were no differences in the WPPSI-R or the PPVT-R scores between the 2 groups, analysis of the WPPSI-R full-scale IQ by function range demonstrated significantly less mental retardation among those children randomized to early low-dose indomethacin (for the indomethacin study children, 9% had an IQ <70, 12% had an IQ of 70-80, and 79% had an IQ >80, compared with the placebo group, for whom 17% had an IQ <70, 18% had an IQ of 70-80, and 65% had an IQ >80). Indomethacin children also experienced significantly less difficulty with vocabulary skills as assessed by the PPVT-R when compared with placebo children. CONCLUSIONS: These data suggest that, for preterm neonates, the early administration of low-dose indomethacin therapy is not associated with adverse neurodevelopmental function at 54 months' corrected age.

The etiology and outcome of cerebral ventriculomegaly at term in very low birth weight preterm infants.

BACKGROUND: Despite improvements in survival data, the incidence of neurodevelopmental handicaps in preterm infants remains high. To prevent these handicaps, one must understand the pathophysiology behind them. For preterm infants, cerebral ventriculomegaly (VM) may be associated with adverse neurodevelopmental outcome. We hypothesized that although the causes of VM are multiple, the incidence of handicap at 4.5 years of age in preterm infants with this ultrasonographic finding at term would be high. METHODS: To test this hypothesis, we provided neurodevelopmental follow-up for all 440 very low birth weight survivors of the Multicenter Randomized Indomethacin Intraventricular Hemorrhage (IVH) Prevention Trial. A total of 384 children (87%) were evaluated at 54 months' corrected age (CA), and 257 subjects were living in English-speaking, monolingual households and are included in the following data analysis. RESULTS: Moderate to severe low pressure VM at term was documented in 11 (4%) of the English-speaking, monolingual survivors. High grade IVH and bronchopulmonary dysplasia (BPD) were both risk factors for the development of VM. Of 11 (45%) children with VM, 5 suffered grades 3 to 4 IVH, compared with 2/246 (1%) children without VM who experienced grades 3 to 4 IVH. Similarly, 9/11 (82%) children with VM had BPD, compared with 120/246 (49%) children without VM who had BPD. Logistic regression analysis was performed using birth weight, gestational age, gender, Apgar score at 5 minutes, BPD, sepsis, moderate to severe VM, periventricular leukomalacia, grade of IVH, and maternal education to predict IQ <70. Although maternal education was an important and independent predictor of adverse cognitive outcome, in this series of very low birth weight prematurely born children, VM was the most important predictor of IQ <70 (OR: 19.0; 95% CI: 4.5, 80.6). Of children with VM, 6/11 (55%) had an IQ <70, compared with 31/246 (13%) of children without VM. Children with VM had significantly lower verbal and performance scores compared with children without VM. CONCLUSIONS: These data suggest that, for preterm neonates, VM at term is a consequence of the vulnerability of the developing brain. Furthermore, its presence is an important and independent predictor of adverse cognitive and motor development at 4.5 years' CA.

Neurodevelopmental outcome at 36 months' corrected age of preterm infants in the Multicenter Indomethacin Intraventricular Hemorrhage Prevention Trial.

OBJECTIVES: Low-dose indomethacin has been shown to prevent intraventricular hemorrhage (IVH) in very low birth weight neonates, and long-term neurodevelopmental follow-up data are needed to validate this intervention. We hypothesized that the early administration of low-dose indomethacin would not be associated with adverse cognitive outcome at 36 months' corrected age (CA). METHODS: We enrolled 431 neonates of 600 to 1250 g birth weight with no IVH at 6 to 12 hours in a randomized, prospective trial to determine whether low-dose indomethacin would prevent IVH. A priori, neurodevelopmental follow-up examinations, including the Stanford-Binet Intelligence Scale and Peabody Picture Vocabulary Test-Revised, and standard neurologic examinations were planned at 36 months' CA. RESULTS: Three hundred eighty-four of the 431 infants survived (192 [92%] of 209 infants receiving indomethacin versus 192 [86%] of 222 infants receiving saline), and 343 (89%) children were examined at 36 months' CA. Thirteen (8%) of the 166 infants who received indomethacin and 14 (8%) of 167 infants receiving the placebo were found to have cerebral palsy. There were no differences in the incidence of deafness or blindness between the two groups. For the 248 English-monolingual children for whom IQ data follow, the mean gestational age was significantly younger for the infants who received indomethacin than for those who received the placebo. None of the 115 infants who received indomethacin was found to have ventriculomegaly on cranial ultrasound at term, compared with 5 of 110 infants who received the placebo. The mean +/- SD Stanford-Binet IQ score for the 126 English-monolingual children who had received indomethacin was 89.6 +/- 18.92, compared with 85.0 +/- 20.79 for the 122 English-monolingual children who had received the placebo. Although maternal education was strongly correlated with Stanford-Binet IQ at 36 months' CA, there was no difference in educational levels between mothers of the infants receiving indomethacin and the placebo. CONCLUSIONS: Indomethacin administered at 6 to 12 hours as prophylaxis against IVH in very low birth weight infants does not result in adverse cognitive or motor outcomes at 36 months' CA.

Visual confrontation naming following left anterior temporal lobectomy: a comparison of surgical approaches.

Change in visual confrontation naming was examined following left (speech dominant) anterior temporal lobectomy (ATL) as a function of surgical technique and patient characteristics. Two hundred seventeen patients with intractable left temporal lobe epilepsy were selected according to standard criteria across 8 centers, and combined into 4 surgical approaches to ATL: (a) tailored resections with intraoperative mapping of eloquent cortex, (b) tailored resections with extraoperative mapping, (c) standard resections with sparing of superior temporal gyrus, and (d) standard resections including excision of superior temporal gyrus. Changes in visual confrontation naming were examined with an index of reliable change derived from an independent sample of 90 nonsurgical patients with complex partial seizures. Results showed significant decline in visual confrontation naming following left ATL, regardless of surgical technique. Across surgical approaches, the risk for decline in visual confrontation naming was associated with a later age of seizure onset and more extensive resection of lateral temporal neocortex.

Temporal lobectomy in children: cognitive outcome.

OBJECT: The authors sought to determine the impact of early temporal lobectomy (in patients younger than age 17 years) on intellectual functioning. The efficacy of temporal lobectomy for treating seizures is well established and the procedure is becoming more acceptable as a treatment for children whose seizures are intractable. However, cognitive outcomes of temporal lobectomy in children and adolescents are largely unreported. The present study takes advantage of a unique multicenter collaboration to examine retrospectively intellectual functioning in a large sample of children who underwent temporal lobectomy. METHODS: Intellectual functioning was assessed before and after temporal lobectomy for treatment of medication-resistant seizures in 82 patients at eight centers of epilepsy surgery. All children underwent standard presurgical examinations, including electroencephalography-video monitoring, magnetic resonance (MR) imaging, and neuropsychological testing, at their respective centers. Forty-three children underwent left temporal lobectomy and 39 underwent right temporal lobectomy. For the entire sample, there were no significant declines in intelligence quotient (IQ) following surgery. Children who underwent left temporal lobectomy demonstrated no significant loss in verbal intellectual functioning and improved significantly in nonverbal intellectual functioning. Children who underwent right temporal lobectomy did not demonstrate significant changes in intellectual functioning. Although group scores showed no change in overall IQ values, an analysis of individual changes revealed that approximately 10% of the sample experienced a significant decline and 9% experienced significant improvement in verbal functioning. Significant improvement in nonverbal cognitive function was observed in 16% of the sample and only 2% of the sample showed significant declines. Risk factors for significant decline included older patient age at the time of surgery and the presence of a structural lesion other than mesial temporal sclerosis on MR imaging. CONCLUSIONS: The present study provides preliminary data for establishing the risk of cognitive morbidity posed by temporal lobectomy performed during childhood. With respect to global intellectual functioning, a slight improvement was significantly more likely to occur than a decline. However, there were several patients in whom significant declines did occur. It will be necessary to study further the factors associated with such declines. In addition, further study of more specific cognitive functions, particularly memory, is needed.

MRI hippocampal volume and neuropsychology in epilepsy surgery.

A review is provided of recent findings on relationships between neurocognitive test data and magnetic resonance imaging (MRI)-determined hippocampal volumes in nonlesional temporal lobectomy patients. The difference between the right and left hippocampal volumes is correlated with postoperative verbal memory in left temporal lobectomy patients who do not have lesional pathology. MRI hippocampal volume data are not associated with measures of executive functioning or naming. Sex differences have been found for verbal memory outcome as women have better verbal memory following left temporal lobectomy. Sex differences have also been found in the relationships between verbal and visual memory, and hippocampal volume data. The systematic combination of MRI-acquired morphological data and neuropsychological test data may further our understanding of neurocognitive function, and provide clinically useful data for counseling epilepsy surgery patients. The current data are promising with regard to prediction of memory outcome following temporal lobectomy, but they do not yet allow for prediction of specific individual patient outcomes. Rather, the currently available data support counseling patients based on the memory outcome of others with similar characteristics.

[Intracarotid amytal testing in the evaluation for epilepsy surgery]. / Test del amital intracarotídeo para evaluar la cirugía de la epilepsia.

INTRODUCTION: The Wada test for language and memory still plays an important role in evaluating the surgery performed on epileptic patients. The measures of the functional deficits carried out with the Wada test, associated with known brain lesions, aid in determining the lateralization of the onset of seizures and provide some estimate of the risk to memory after a temporal lobotomy. DEVELOPMENT: A more refined procedure, based on the correlations with the titration from MRI, fMR and MR spectroscopy, will be needed. Moreover, using the Wada test it is possible to make long term forecasts about the cognitive outcome and about the control of seizures. When used together with other neurological, functional and psychometric evaluations, it becomes easier to select the patients with most chances of benefiting from surgical epilepsy treatment. Finally, the non invasive measures of brain functioning include fMR, which provides far more information than that obtained using the Wada test. However, it remains to be determined whether the procedure based on activation provides data of the same quality as those obtained by the Wada test, which can provide a more adequate reversible model of the effects of surgery on cognition. CONCLUSION: . Ideally, as MRI and other imaging techniques progress, they will be able to offer complementary images, which will improve our capacity to forecast and prevent important post operative cognitive deficiencies.

The Wada test in the evaluation for epilepsy surgery.

The Wada test is the standard part of the pre-operative evaluation for epilepsy surgery. The procedure involves the slow injection of sodium amobarbital (typically 100-500mg) into the internal carotid artery following a transfermoral approach. The amobarbital anesthetizes the anterior two-thirds of the ipsilateral cerebral hemisphere for approximately 5-10 minutes. During this period of hemispheric anesthesia, assessment of expressive and receptive language can establish cerebral language representation. In addition, the procedure provides a reversible model to assess the risk of significant memory change following surgery. This is important because patients undergoing surgery involving the temporal lobe may experience significant memory decline following surgical resection of a temporal lobe seizure focus. This paper will represent information about the use of Wada testing, and discuss issues involved in establishing cerebral language representation, lateralization of temporal lobe dysfunction, seizure and memory outcome prediction, and future directions of this technique.