topiramate and Language-Disorders

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).. 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.. 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.. 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.

Topics: Adult; Anticonvulsants; Brain Mapping; Cognition; Epilepsy; Female; Frontal Lobe; Fructose; Gyrus Cinguli; Humans; Language Disorders; Longitudinal Studies; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Topiramate; Withholding Treatment; Young Adult

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

Topics: Adult; Anticonvulsants; Brain; Brain Mapping; Cognition; Epilepsy, Temporal Lobe; Female; Fructose; Functional Laterality; Humans; Image Processing, Computer-Assisted; Language Disorders; Magnetic Resonance Imaging; Male; Middle Aged; Names; Neuropsychological Tests; Oxygen; Topiramate; Young Adult

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.. To verify the occurrence of language disturbances as a side effect of topiramate treatment in episodic and chronic migraine patients.. 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.. 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.. 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.

Topics: Adult; Analysis of Variance; Female; Fructose; Humans; Language Disorders; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Neuropsychological Tests; Psychiatric Status Rating Scales; Topiramate

Six migraine patients experienced significant topiramate-related cognitive and language dysfunction that improved with donepezil treatment and allowed uninterrupted topiramate use. These patients represent the first report of topiramate-related cognitive and language dysfunction that improved with a cholinesterase inhibitor. Although, the mechanism responsible for this effect is uncertain, cholinesterase inhibition resulting in cholinergic augmentation and enhanced cognition probably account for some if not most of the improvement.

Topics: Adult; Cholinesterase Inhibitors; Cognition Disorders; Donepezil; Female; Fructose; Humans; Indans; Language Disorders; Male; Middle Aged; Migraine Disorders; Piperidines; Topiramate; Treatment Outcome

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.

Topics: Adult; Anticonvulsants; Cognition; Epilepsy; Female; Fructose; Humans; Language Disorders; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Prefrontal Cortex; Topiramate

Profound language regression developed in three children with epilepsy 4 to 28 weeks after beginning topiramate (TPM). TPM was administered as an adjunctive antiepileptic drug at doses of 2.5 to 6.0 mg/kg/day. Language functions recovered while TPM was being reduced in dose or stopped.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy, Complex Partial; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Language Disorders; Speech Disorders; Topiramate