Neurodevelopmental outcomes after prenatal exposure to lamotrigine monotherapy in women with epilepsy: a systematic review and meta-analysis.

BACKGROUND: Lamotrigine has become one of the most commonly prescribed antiseizure medications (ASM) in epileptic women during pregnancy and therefore requires regular updates regarding its safety. The aim of this study was to estimate the association between in utero exposure to lamotrigine monotherapy and the occurrence of neurodevelopmental outcomes. METHODS: All comparative studies assessing the occurrence of neurodevelopmental outcomes after epilepsy-indicated lamotrigine monotherapy exposure during pregnancy were searched. First, references were identified through a snowballing approach, then, through electronic databases (Medline and Embase) from 2015 to June 2022. One investigator evaluated study eligibility and extracted data and a second independent investigator reviewed the meta-analysis (MA). A systematic review and random-effects model approach were performed using a collaborative WEB-based meta-analysis platform (metaPreg.org) with a registered protocol (osf.io/u4gva). RESULTS: Overall, 18 studies were included. For outcomes reported by at least 4 studies, the pooled odds ratios and 95% confidence interval obtained with the number of exposed (N1) and unexposed children (N0) included were: neurodevelopmental disorders as a whole 0.84 [0.66;1.06] (N1 = 5,271; N0 = 22,230); language disorders or delay 1.16 [0.67;2.00] (N1 = 313; N0 = 506); diagnosis or risk of ASD 0.97 [0.61;1.53] (N1 = at least 5,262; N0 = 33,313); diagnosis or risk of ADHD 1.14 [0.75;1.72] (N1 = at least 113; N0 = 11,530) and psychomotor developmental disorders or delay 2.68 [1.29-5.56] (N1 = 163; N0 = 220). The MA of cognitive outcomes included less than 4 studies and retrieved a significant association for infants exposed to lamotrigine younger than 3 years old but not in the older age groups. CONCLUSION: Prenatal exposure to lamotrigine monotherapy is not found to be statistically associated with neurodevelopmental disorders as a whole, language disorders or delay, diagnosis or risk of ASD and diagnosis or risk of ADHD. However, the MA found an increased risk of psychomotor developmental disorders or delay and cognitive developmental delay in less than 3 years old children. Nevertheless, these findings were based exclusively on observational studies presenting biases and on a limited number of included children. More studies should assess neurodevelopmental outcomes in children prenatally exposed to lamotrigine.

Cognitive dysfunction in patients with nasopharyngeal carcinoma after induction chemotherapy.

OBJECTIVE: This prospective study aimed to assess the incidence, details of the change of cognitive dysfunction, and predictive factors of cognitive function impairment associated with induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC) patients. METHOD: We prospectively included NPC patients who treated with IC from December 2018 to January 2020. Montreal cognitive assessment (MoCA) was used to measure cognitive function, and score less than 26 was defined as cognitive dysfunction. Multivariate logistic regression analysis was applied to assess the independent predictors associated with cognitive function impairment. RESULTS: A total of 76 patients were recruited, 10 patients were excluded due to refusal or unable to finish the questionnaire, and 66 patients were analyzed in this study. The median age of the patients was 48.5 years (range, 24-69 years). There was 89.4% of patients received ≥3 circles of IC. For the entire group, 27.3% had cognitive dysfunction, of which attention, language, short-term memory, and orientation showed significant downward trends, while visuospatial/executive function, naming, and abstraction demonstrated no prominent decrease. In patients having cognitive function impairment, 77.8% of them occurred after the first circle of IC. Gender (P = 0.039) and education (P = 0.03) were significant predictors for cognitive dysfunction. Female patients (female vs. male: 50% vs. 20%) and patients with lower educational levels (lower vs. higher: 37.8% vs. 11.8%) were more likely to suffer cognitive dysfunction. In addition, age (P = 0.572) and chemotherapy circles (P = 0.68) had no association with cognitive dysfunction. CONCLUSION: Approximately 25% of NPC patients suffered cognitive dysfunction after IC, especially in female patients and patients with lower educational levels.

Early adolescent language development following intrathecal chemotherapy for acute lymphoblastic leukaemia.

PURPOSE: Central nervous system (CNS) prophylaxis in the treatment of childhood acute lymphoblastic leukaemia (ALL) is routinely achieved through intrathecal chemotherapy (ITC). The presence of high level language deficits in older children who received CNS-directed ITC for ALL in early childhood is yet to be elucidated, with previous research suggesting that high level language deficits may appear later in ALL survivors' development at an age when these skills typically emerge. METHOD: A test battery covering foundational language skills and higher-order language skills was administered to five participants (aged 10-15 years) with a history of ITC for ALL. Conversion of each child's language performance scores to z scores allowed for clinical interpretation of data across the language areas tested. RESULT: Foundational language skills were, in general, of no clinical concern. Three of the five children presented with clinically impaired language skills in areas including resolving ambiguity, making inferences and composing novel sentences. Performance variation between the participants and within the individual participants was noted. CONCLUSION: Given the importance of early adolescent language abilities to academic and social development in late primary and secondary schooling, these preliminary findings suggest further research into emerging adolescent language abilities following ITC for ALL is warranted.

Duration of general anaesthetic exposure in early childhood and long-term language and cognitive ability.

BACKGROUND: The anaesthetic dose causing neurotoxicity in animals has been evaluated, but the relationship between duration of volatile anaesthetic (VA) exposure and neurodevelopment in children remains unclear. METHODS: Data were obtained from the Western Australian Pregnancy Cohort (Raine) Study, with language (Clinical Evaluation of Language Fundamentals: Receptive [CELF-R] and Expressive [CELF-E] and Total [CELF-T]) and cognition (Coloured Progressive Matrices [CPM]) assessed at age 10 yr. Medical records were reviewed, and children divided into quartiles based on total VA exposure duration before age three yr. The association between test score and exposure duration quartile was evaluated using linear regression, adjusting for patient characteristics and comorbidity. RESULTS: Of 1622 children with available test scores, 148 had documented VA exposure and were split into the following quartiles: ≤25, >25 to ≤35, >35 to ≤60 and >60 min. Compared with unexposed children, CELF-T scores for children in the first and second quartiles did not differ, but those in the third and fourth quartiles had significantly lower scores ([3 rd quartile - Unexposed] -5.3; 95% confidence interval [CI], (-10.2 - -0.4), [4 th quartile - Unexposed] -6.2; 95% CI, (-11.6 - -0.9). CELF-E showed similar findings, but significant differences were not found in CELF-R or CPM for any quartile. CONCLUSIONS: Children with VA exposures ≤35 min did not differ from unexposed children, but those with exposures >35 min had lower total and expressive language scores. It remains unclear if this is a dose-response relationship, or if children requiring longer exposures for longer surgeries have other clinical reasons for lower scores.

Zonisamide in Brain Tumor-Related Epilepsy: An Observational Pilot Study.

OBJECTIVES: Epilepsy heavily affects the quality of life (QoL) of patients with brain tumor because in addition to taking treatments for the oncological illness, patients are required to live with the long-term taking of antiepileptic drugs (AEDs). The AEDs' adverse effects are common in these patients and can negatively influence their perceptions of their QoL.We conducted an observational pilot study in patients with brain tumor-related epilepsy to verify efficacy, tolerability, and impact on QoL and global neurocognitive performances of zonisamide (ZNS) in add-on. MATERIALS AND METHODS: We recruited 13 patients (5 females, 8 males; mean age, 49.6 years) presenting uncontrolled seizures. At first visit and at final follow-up at 6 months, patients underwent neurological examination, evaluation of adverse events, and cognitive and QoL tests. A seizure diary was given. RESULTS: Eight patients underwent chemotherapy, 3 underwent radiotherapy, and 5 had disease progression. Mean dosage of ZNS at final follow-up was 300 mg/d.Of 9 patients who reached the sixth month follow-up, the mean weekly seizure number before ZNS had been 3.2 ± 5.0, and at final follow-up, the mean weekly seizure number was 0.18 ± 0.41 (P = 0.05).Compared with baseline, we observed stability in all cognitive domains, except for verbal fluency that significantly worsened.Results on QoL tests showed that QoL remained unchanged over time, which could indicate that ZNS did not influence the patients' perceived QoL. CONCLUSIONS: Zonisamide as add-on in our patients seems to be well tolerated and efficacious in controlling seizures. Despite having limitations represented by the fact that our study is observational, with a small study population and a short follow-up period, our results confirm that when choosing an AED, in addition to efficacy, the drug's effect on patients' QoL also needs to be considered, especially for patients facing many psychosocial challenges, such as those with brain tumor-related epilepsy.

Altered cerebral activity associated with topiramate and its withdrawal in patients with epilepsy with language impairment: An fMRI study using the verb generation task.

OBJECTIVE: Topiramate (TPM) is well recognized for its negative effects on language in healthy volunteers and patients with epilepsy. The aim of this study was to investigate the brain activation and deactivation patterns in TPM-treated patients with epilepsy with language impairment and their dynamic alteration during TPM withdrawal using functional magnetic resonance imaging (fMRI) with the verb generation task (VGT). METHODS: Twelve patients with epilepsy experiencing subjective language disfluency after TPM add-on treatment (TPM-on) and thirty sex- and age-matched healthy controls (HCs) were recruited. All subjects received a battery of neuropsychological tests and an fMRI scan with the VGT. Withdrawal of TPM was attempted in all patients. Only six patients reached complete withdrawal without seizure relapses (TPM-off), and these patients underwent a reassessment of neuropsychological and neuroimaging tests. RESULT: The neuropsychological tests demonstrated objective language impairments in TPM-on patients. Compared with the HCs, the bilateral medial prefrontal cortex and the posterior midline and lateral parts of the default mode network (DMN) (including the bilateral posterior cingulate cortex (PCC), the right medial prefrontal cortex, the right angular gyrus, the right inferior temporal gyrus, and the bilateral supramarginal gyrus) in TPM-on patients failed to deactivate during the VGT. Their task-induced activation patterns were largely similar to those of the HCs. After TPM withdrawal, partial improvement of both task-induced deactivation of the DMN (the left parahippocampal gyrus and the bilateral PCC) and task-related activation of the language network (the right middle frontal gyrus and the left superior occipital gyrus) was identified along with partial improvement of neuropsychological tests. CONCLUSION: Task-induced deactivation is a more sensitive neuroimaging biomarker for the impaired language performance in patients administered TPM than task-induced activation. Disruption and reorganization of the balance between the DMN and the cortical language networks are found along with reversible TPM-related language impairment. These results may suggest an underlying brain mechanism by which TPM affects cognitive function.

[Reversible neuropsychological deterioration associated to zonisamide in a paediatric patient with tuberous sclerosis]. / Deterioro neuropsicologico reversible asociado a zonisamida en un paciente pediatrico con esclerosis tuberosa.

AIM: To document reversible cognitive deterioration associated to high doses of zonisamide, using the Reliable Change Index to control practice effects derived from repetitive neuropsychological assessments. CASE REPORT: A 11 year-old boy with tuberous sclerosis complex and left frontal refractory epilepsy, evaluated within a paediatric epilepsy surgery program. The epileptogenic zone was found to be related with a tuber situated on the left inferior frontal gyrus. The effects of high doses of zonisamide simulate a disturbance of eloquent cortex within the epileptogenic zone and the impact of uncontrolled seizures on cognitive functioning over the language-dominant hemisphere. Drug withdrawal significantly improved total intelligence index, verbal comprehension intellectual index and specific language-sustained cognitive abilities, beyond practice effects. CONCLUSIONS: The differentiation between cognitive effects of drugs and functional deficits resulting from eloquent cortex involvement within the epileptogenic zone can be of crucial importance in the decision-making process for epilepsy surgery.

TITLE: Deterioro neuropsicologico reversible asociado a zonisamida en un paciente pediatrico con esclerosis tuberosa.Objetivo. Documentar el deterioro cognitivo reversible asociado a altas dosis de zonisamida, utilizando indices de cambio fiable para controlar los efectos de practica derivados de evaluaciones neuropsicologicas repetidas. Caso clinico. Niño de 11 años con complejo esclerosis tuberosa y epilepsia refractaria del lobulo frontal izquierdo, evaluado en el contexto de un programa de cirugia de la epilepsia pediatrica. La zona epileptogena se relaciono con un tuber epileptogeno localizado en el giro frontal inferior del hemisferio izquierdo. Los efectos de altas dosis de zonisamida mimetizaron una afectacion de la corteza elocuente en la zona epileptogena y un impacto de las crisis no controladas en el funcionamiento cognitivo asociado al hemisferio dominante para el lenguaje. La retirada del farmaco mejoro significativamente, mas alla de los efectos de practica, el cociente intelectual total, el indice intelectual de comprension verbal y habilidades cognitivas especificas sustentadas en el lenguaje. Conclusiones. La diferenciacion entre los efectos cognitivos de los farmacos y la existencia de un deficit funcional por afectacion de la corteza elocuente en el area epileptogena puede ser crucial para la toma de decisiones en cirugia de la epilepsia.

[Epilepsy and cognition: the role of antiepileptic drugs]. / Epilepsia y cognición: el papel de los fármacos antiepilépticos.

INTRODUCTION: Multiple factors underlie the cognitive changes associated with epilepsy, including the effect of antiepileptic drug (AED) therapy itself. The use of AEDs in the management of epilepsy requires an ongoing risk-benefit analysis that attempts to maximize seizure control while minimizing adverse cognitive side-effects. AIM: This review focuses on the global and specific cognitive effects of the classic and the new AEDs. DEVELOPMENT: All of the established AEDs can produce cognitive side effects, which are increased with polypharmacy and with increasing dosage and anticonvulsant blood levels. The main disorders are a diminished reaction and information processing time with alterations affecting memory, attention and language. Further, there is much debate concerning the existence and clinical importance of differential AED cognitive side effects and a large portion of the literature examining the comparative cognitive effects of AEDs is limited by inadequate study designs. CONCLUSIONS: Cognitive side effects of antiepileptic drugs are common and can negatively affect tolerability, compliance, and long-term retention of the treatment. The role of cognitive side effects should be kept in proper perspective when choosing AED therapy. It is important to be able to recognize early these effects and to put them into perspective as to how they affect our patients.

TITLE: Epilepsia y cognicion: el papel de los farmacos antiepilepticos.Introduccion. Multiples y muy diversos factores se relacionan con la alteracion cognitiva en la epilepsia, incluyendo el efecto adverso directo de los farmacos antiepilepticos (FAE). El uso de los FAE requiere de un riguroso equilibrio entre riesgo y beneficio para conseguir asi el mejor control de las crisis con el menor numero de efectos adversos neurocognitivos. Objetivo. Analizar los efectos adversos cognitivos generales y especificos de los FAE de primera, segunda y tercera generacion. Desarrollo. Todos los FAE disponibles pueden producir efectos adversos cognitivos, que son mas frecuentes en politerapia, con dosis totales altas y niveles sericos elevados. Las alteraciones mas comunes son el descenso de la capacidad de reaccion y de la velocidad de procesamiento con afectacion concomitante de la memoria, la atencion y el lenguaje. Sin embargo, hay gran controversia sobre la existencia o no de perfiles cognitivos especificos para cada uno de los distintos FAE y se dispone de una informacion contradictoria al respecto por la inadecuada metodologia de los estudios comparativos. Conclusiones. Los efectos adversos cognitivos de los FAE son frecuentes y pueden afectar negativamente la tolerabilidad, el cumplimiento y el mantenimiento a largo plazo del tratamiento antiepileptico. Se debe considerar el potencial efecto adverso cognitivo de los distintos FAE a la hora de elegir un tratamiento y es importante reconocer e identificar precozmente estos efectos adversos y saber como pueden afectar a los pacientes.

Anesthesia considerations in pediatric glaucoma management.

PURPOSE OF REVIEW: This article reviews the potentially adverse neurodevelopmental effects of early exposure to general anesthesia and examines a changing paradigm in the management of pediatric glaucoma. RECENT FINDINGS: Literature across multiple subspecialties has examined the potentially neurotoxic effects of general anesthesia on the developing child's brain. Associations between general anesthesia exposure early in life and attention deficit hyperactivity disorder, language processing, and cognition have been suggested but not confirmed. Several population studies support the conclusion that early anesthetic exposure may increase the risk of neurodevelopmental deficits, although this is unsupported in sibling cohorts. Newer technology such as rebound tonometry may decrease the frequency of examination under anesthesia in the long-term management of patients with pediatric glaucoma and may decrease the risk of these potentially adverse neurodevelopmental outcomes. SUMMARY: As the potential long-term adverse neurodevelopmental effects of general anesthesia become better understood, pediatric glaucoma specialists should be cognizant of the relative lifelong risks and benefits of repeat examinations under anesthesia in young patients.

The effect of moderate gestational alcohol consumption during pregnancy on speech and language outcomes in children: a systematic review.

BACKGROUND: Consensus has not been reached on safe alcohol consumption recommendations during pregnancy. The National Institutes for Care and Health Excellence (NICE) in the UK suggest that one to two drinks not more than twice per week is safe. However, the speech and language effects of even low levels of alcohol use among offspring are unknown. The aim of this study was to review systematically the evidence on studies of the effect of low to moderate levels of alcohol consumption during pregnancy (up to 70 grams of alcohol per week) compared to abstinence on speech and language outcomes in children. METHODS: Using medical subject headings, PubMed, Web of knowledge, Scopus, Embase, Cinahl and the Cochrane Library were searched from their inception up to March 2012. Case control and cohort studies were included. Two assessors independently reviewed titles, abstracts and full articles, extracted data and assessed quality. RESULTS: A total of 1,397 titles and abstracts were reviewed of which 51 full texts were retrieved. Three cohort studies totaling 10,642 women met the inclusion criteria. All three studies, (United States (2) and Australia (1)) indicated that language was not impaired as a result of low to moderate alcohol consumption during pregnancy. Two studies were judged to be of low quality based on a six-item bias classification tool. Due to heterogeneity, results could not be meta-analyzed. CONCLUSION: Studies included in this review do not provide sufficient evidence to confirm or refute an association between low to moderate alcohol use during pregnancy and speech and language outcomes in children. High quality, population based studies are required to establish the safety of low to moderate levels of alcohol use such as those set out by the NICE guidelines in the UK.

Effects of chronic ketamine use on frontal and medial temporal cognition.

BACKGROUND: Recreational ketamine use has been on the rise worldwide. Previous studies have demonstrated that it disrupts various memory systems, but few studies have examined how it affects learning and frontal functioning. The present study investigates the effects of repeated ketamine self-administration on frontal fluency, attention, learning, and memory along the verbal/nonverbal axis. METHODS: Twenty-five ketamine users and 30 healthy controls took a battery of neuropsychological tests. Frontal fluency was measured by the Verbal Fluency Test for semantic organization ability and the Figural Fluency Test for nonverbal executive functioning. Learning and memory were measured with the Chinese Auditory-Verbal Learning Test for acquisition and retention abilities of verbal information, as well as with the Continuous Visual Memory Test for nonverbal information. Participants also took several tests tapping subdomains of attention. To test for the potential effects of other drug use, 10 polydrug controls were included for comparison with the ketamine users and healthy controls. RESULTS: Ketamine users had impaired verbal fluency, cognitive processing speed, and verbal learning. Verbal learning impairment was strongly correlated with estimated lifetime ketamine use. Ketamine users showed no impairments in figural fluency, sustained attention, selective attention, visual learning, or verbal/nonverbal memory. However, heavier lifetime ketamine use was significantly correlated with deficits in verbal memory (both immediate recall and delayed recall) and visual recognition memory. Deficits in cognitive processing speed and verbal learning persisted even after polydrug controls were included in the control group, but their inclusion did make the impairment in verbal fluency barely reach statistical significance. CONCLUSIONS: This study suggests that repeated ketamine use causes differential impairment to multiple domains of frontal and medial temporal functioning, possibly specific to verbal information processing.

Topiramate and its effect on fMRI of language in patients with right or left temporal lobe epilepsy.

Topiramate (TPM) is well recognized for its negative effects on cognition, language performance and lateralization results on the intracarotid amobarbital procedure (IAP). But, the effects of TPM on functional MRI (fMRI) of language and the fMRI signals are less clear. Functional MRI is increasingly used for presurgical evaluation of epilepsy patients in place of IAP for language lateralization. Thus, the goal of this study was to assess the effects of TPM on fMRI signals. In this study, we included 8 patients with right temporal lobe epilepsy (RTLE) and 8 with left temporal lobe epilepsy (LTLE) taking TPM (+TPM). Matched to them for age, handedness and side of seizure onset were 8 patients with RTLE and 8 with LTLE not taking TPM (-TPM). Matched for age and handedness to the patients with TLE were 32 healthy controls. The fMRI paradigm involved semantic decision/tone decision task (in-scanner behavioral data were collected). All epilepsy patients received a standard neuropsychological language battery. One sample t-tests were performed within each group to assess task-specific activations. Functional MRI data random-effects analysis was performed to determine significant group activation differences and to assess the effect of TPM dose on task activation. Direct group comparisons of fMRI, language and demographic data between patients with R/L TLE +TPM vs. -TPM and the analysis of the effects of TPM on blood oxygenation level-dependent (BOLD) signal were performed. Groups were matched for age, handedness and, within the R/L TLE groups, for the age of epilepsy onset/duration and the number of AEDs/TPM dose. The in-scanner language performance of patients was worse when compared to healthy controls - all p<0.044. While all groups showed fMRI activation typical for this task, regression analyses comparing L/R TLE +TPM vs. -TPM showed significant fMRI signal differences between groups (increases in left cingulate gyrus and decreases in left superior temporal gyrus in the patients with LTLE +TPM; increases in the right BA 10 and left visual cortex and decreases in the left BA 47 in +TPM RTLE). Further, TPM dose showed positive relationship with activation in the basal ganglia and negative associations with activation in anterior cingulate and posterior visual cortex. Thus, TPM appears to have a different effect on fMRI language distribution in patients with R/L TLE and a dose-dependent effect on fMRI signals. These findings may, in part, explain the negative effects of TPM on cognition and language performance and support the notion that TPM may affect the results of language fMRI lateralization/localization.

Testicular-cancer survivors experience compromised language following chemotherapy: findings in a Swedish population-based study 3-26 years after treatment.

BACKGROUND: Studies suggest an increased risk for compromised cognitive function among cancer survivors. It is unclear to what extent chemotherapy is the cause and how the dysfunction, when present, affects everyday life. The objective was to study self-reported behaviours that may depend on cognitive function, among testicular-cancer survivors who received various cycles of cisplatin-based chemotherapy by comparing them with those who did not. MATERIAL AND METHODS: We identified 1173 eligible men diagnosed with non-seminomatous testicular cancer treated according to the national cancer-care programs SWENOTECA I-IV between 1981 and 2004. During an 18-month qualitative phase we constructed a study-specific questionnaire including questions about specific activities and behaviour in everyday life. RESULTS: We obtained information from 960 of 1173 (82%) testicular-cancer survivors diagnosed on average 11 years previously. The prevalence of "saying similar but incorrect words" at least once a week was 5% among those having received no chemotherapy versus 16% among those having received five or more cycles, giving a prevalence ratio ("relative risk", RR) of 3.3 with a 95% confidence interval of 1.5 to 7.1. The corresponding figure for "saying words in the wrong order" was 3.1 (1.7-5.8), for "difficulties understanding what other people mean" 3.1 (1.3-7.7), for "saying words other than planned" 2.2 (1.1-4.5) and for "difficulties completing sentences" 2.0 (1.0-3.6). The relative risks for those with a low level of education ranged between 4.9 (1.6-14.9) and 15.3 (1.9-120.5). CONCLUSION: Testicular-cancer survivors in Sweden who have received five or more cycles of cisplatin-based chemotherapy experience an increased incidence of long-term compromised language; the effect is primarily seen among men with a low level of education.

Central nervous system toxicity associated with ertapenem use.

OBJECTIVE: To report stroke-like symptoms and unusual central nervous system adverse effects in 2 elderly patients receiving ertapenem. CASE SUMMARY: Two patients ≥70 years of age experienced unusual mental status changes while receiving ertapenem. Patient 1 developed garbled speech and miosis 1 week after starting appropriately dosed ertapenem (1 g/day) for sacral osteomyelitis. Symptoms resolved upon ertapenem discontinuation but recurred upon rechallenge. Patient 2, a cachectic male with acute renal insufficiency, became delirious and progressively obtunded 5 days after starting ertapenem 1 g/day. Nine days after initiation of therapy, he required intubation and mechanical ventilation; ertapenem was discontinued at that time. Within 2 days of ertapenem discontinuation, his mental state cleared and the ventilator was removed. DISCUSSION: Carbapenems, including ertapenem, have been implicated in causing central nervous system toxicity, including hallucinations and seizures. However, published reports of other, nonseizure-related central nervous system events are limited. Considerable resources were expended on extensive medical interventions before ertapenem was identified as a potential cause of the delirium in our patients. When applied to our patients, the Naranjo probability scale indicated a highly probable relationship for patient 1 and a probable relationship for patient 2 between the adverse effects and ertapenem use. CONCLUSIONS: Clinicians should be cognizant of ertapenem's potential to induce profound changes in mental status that may mimic other conditions in elderly patients.

Awareness of deficits during intracarotid anesthetic procedures in epilepsy: Comparisons of motor, naming, and comprehension awareness under amobarbital versus under etomidate.

Awareness of deficits is often impaired following disruption of the right hemisphere. Intracarotid anesthetic procedures (IAPs) represent a unique method by which we can assess functioning of each hemisphere in isolation. We used this technique to explore deficits of awareness of specific functions-motor ability, naming, and comprehension-in patients with temporal lobe epilepsy. Some patients were injected with amobarbital, whereas others were injected with etomidate. We found that injection into the right hemisphere, or epileptogenic focus in the right hemisphere following injection in the left, resulted in the lowest levels of motor awareness. We also found a higher level of awareness for expressive language deficits and less awareness for receptive language deficits. Comparison of etomidate and amobarbital suggested more awareness following injection of etomidate. We discuss how these findings contribute to our understanding of the right hemisphere's special role in awareness, and how research in other disorders and in comparative neurology has shaped our conceptualization of the neuroanatomy of insight.

Language disturbances as a side effect of prophylactic treatment of migraine.

BACKGROUND: Language disturbances have been previously described as word-finding difficulties in epileptic patients. These disturbances have been recently reported in migraineurs in treatment with topiramate but they have never been defined and assessed in these patients with the aid of neuropsychological testing. OBJECTIVE: To verify the occurrence of language disturbances as a side effect of topiramate treatment in episodic and chronic migraine patients. METHODS: Language disturbances were recorded on the basis of spontaneous reports of 30 migraine patients treated with topiramate and 2 control groups (20 patients treated with other prophylactic drugs and 20 patients without prophylactic treatment) and were explored with neuropsychological tests. Psychiatric comorbidity was assessed using Zung Anxiety and Depression Scales. RESULTS: Language disturbances were referred by 26.7% (n=8) of patients during topiramate treatment but by none of the patients in the 2 control groups. All patients in the topiramate group had a worse performance on all tests compared to patients of the 2 control groups. Moreover, in the topiramate group, patients with referred language disturbances had higher scores for all neuropsychological test variables, indicative of a worse performance. Some language functions (Trail Making Tests A and B) seemed to be influenced by the concomitant presence of psychiatric comorbidities, particularly anxiety and depression. CONCLUSION: It can be hypothesized that a disorder such as migraine, which involves numerous cortical and subcortical circuits implicated in the transmission and behavioral and emotional processing of pain, represents a facilitated substrate for the occurrence of language disturbances due to topiramate. This could be the expression of a more generalized impairment of cognitive processing. These aspects should be investigated in prospective studies involving larger migraine patient samples.

Functional MRI reveals declined prefrontal cortex activation in patients with epilepsy on topiramate therapy.

Functional magnetic resonance imaging of covert word generation was used to examine brain activation abnormalities associated with topiramate-induced cognitive language impairment in patients with epilepsy. Compared with a control epilepsy group, in the topiramate-treated group, there was significantly less activation in the language-mediating regions of the prefrontal cortex; the topiramate group also had significantly lower neuropsychological language scores. These findings suggest that topiramate has a critical effect on the cerebral neural systems that mediate expressive language.