The effect of topiramate plasma concentration on linguistic behavior, verbal recall and working memory.

This is the first study of the effect of topiramate on linguistic behavior and verbal recall using a computational linguistics system for automated language and speech analysis to detect and quantify drug-induced changes in speech recorded during discourse-level tasks. Healthy volunteers were administered a single, 100-mg oral dose of topiramate in two double-blind, randomized, placebo-controlled, crossover studies. Subjects' topiramate plasma levels ranged from 0.23 to 2.81 µg/mL. We found a significant association between topiramate levels and impairment on measures of verbal fluency elicited during a picture description task, correct number of words recalled on a paragraph recall test, and reaction time recorded during a working memory task. Using the tools of clinical pharmacology and computational linguistics, we elucidated the relationship between the determinants of a drug's disposition as reflected in plasma concentrations and their impact on cognitive functioning as reflected in spoken language discourse.

Lateralization of temporal lobe foci: depth versus subdural electrodes.

OBJECTIVES: Definitive localization of an epileptic focus correlates with a favorable outcome following epilepsy surgery. This study was undertaken to determine the incremental value of data yielded for surgical decision making when using subdural electrodes alone and in addition to depth electrodes for temporal lobe epilepsy. METHODS: Standardized placement for intracranial electrodes included: (1) longitudinal placement of bilateral temporal lobe depth electrodes; (2) bilateral subtemporal subdural strips; and (3) bilateral orbitofrontal subdural strips. Sixty-three events were randomly reviewed for: (1) subdural electrodes alone; and (2) depth electrodes in conjunction with subdural electrodes. RESULTS: Of the 63 seizures, 54 (85.7%) demonstrated congruent lateralization to ipsilateral subtemporal subdural strip electrodes (based on depth electrode localization) when subdural strip electrodes were utilized alone. In 3 of 22 patients, 7 seizures demonstrated 'false localization' on subdural electrode analysis alone when compared with depth recording and post-surgical outcome. For these 3 patients, retrospective review of neuroimaging demonstrated suboptimal ipsilateral placement of subtemporal subdural electrodes with the most mesial electrode lateral to the collateral sulcus. Four additional patients had suboptimal placement of subtemporal subdural electrodes. Two of these 4 patients had congruent localization with subdural electrodes to ipsilateral depth electrodes despite suboptimal placement. Subtemporal subdural electrodes accurately localized for all seizures from the mesial temporal lobe when the mesial electrodes of the subtemporal subdural strip recorded mesial to the collateral sulcus from the parahippocampal region. CONCLUSION: We conclude that although there are high concordance rates between subdural and depth electrodes, localization of seizure onset based on subdural strip electrodes alone may result in inaccurate focus identification with potential for possible suboptimal treatment of temporal lobe epilepsy. When subtemporal subdural electrodes provide recording from the parahippocampal region, there is accurate localization of the seizure focus. If suboptimal placement occurs lateral to the collateral sulcus, the electroencephalographer cannot make a definitive identification of the seizure focus.

Emotional conversations in Parkinson's disease.

OBJECTIVE: To learn how PD influences verbal description of emotional events. BACKGROUND: Individuals with PD exhibit emotional processing deficits. Emotional experience likely involves several dimensions (e.g., valence, arousal, motor activation) subserved by a distributed modular network involving cortical, limbic, basal ganglia, diencephalic, and mesencephalic regions. Although the neurodegeneration in PD likely affects components in this network, little is known about how PD influences emotional processing. Because PD is associated with activation deficits, one could predict that the discourse of emotional experiences involving high activation would be reduced in patients with PD compared to control subjects. Alternatively, because patients with PD exhibit paradoxical sensitivity to externally evoked motor activation (kinesia paradoxica), it is possible that emotional stimuli may facilitate verbal emotional expression more so in patients with PD than in control subjects. METHODS: The authors measured verbal descriptions of personal emotional experiences in subjects with PD and normal controls. RESULTS: Compared with control subjects, individuals with PD showed a relative increase in the number of words spoken and in discourse duration when talking about emotional experiences that are usually associated with high levels of arousal and motor activation. Although the authors did not measure arousal or activation, prior research has shown that, when asked to recall an emotional experience, people will often re-experience the emotion previously experienced during that episode. CONCLUSIONS: Recalling emotional episodes induces verbal kinesia paradoxica in patients with PD. Although recall of these emotional episodes may have been associated with increased arousal and activation, the mechanism underlying emotional verbal kinesia paradoxica is unclear.

Dissociation of anosognosia and phantom movement during the Wada test.

OBJECTIVE: Patients who misperceive that they are moving their paralysed arm (phantom movements) may not recognise its weakness. Therefore, the relation between phantom limb movements and anosognosia for hemiplegia during selective right hemispheric anaesthesia (the Wada test) was examined. METHODS: Nine patients with intractable epilepsy underwent the Wada test. During the right hemispheric injection, after the onset of hemiparesis, anosognosia was assessed by asking patients if they were weak. The patient's vision was limited such that they could not see the position of their limbs. Phantom movements were tested for by asking patients to attempt to lift their left upper limb, and to demonstrate their left limb's position by placing their right limb in the same position as their left. Proprioception was tested by lifting the patient's paretic upper limb and having patients demonstrate this position by lifting their right limb to the same position. RESULTS: Three patients experienced left phantom limb movements, and five were anosognosic for their hemiplegia. However, phantom movement occurred in only one patient with anosognosia. The other two patients with phantom movement were without anosognosia. The patient with phantom movement and anosognosia had impaired proprioception. The two patients with phantom movement but without anosognosia had intact proprioception. CONCLUSIONS: Phantom movement in the presence of a proprioceptive deficit could contribute to anosognosia. However, anosognosia and phantom movement are dissociable; therefore phantom movement cannot alone account for anosognosia. Because phantom movement occurred with and without proprioceptive deficits, proprioceptive loss is not a prerequisite for phantom movement.

Proprioception more impaired distally than proximally in subjects with hemispheric dysfunction.

Holmes noted that with hemispheric injuries proprioceptive disturbances were more marked in the distal than proximal limb segments and proposed that this difference was related to the size of cortical sensory representations. An alternative hypothesis is that sensation from distal segments projects to the contralateral hemisphere and sensation from proximal segments projects to both hemispheres. Selective hemispheric anesthesia was used to test these alternative hypotheses and revealed a decrement in distal but not proximal proprioception with hemispheric anesthesia, thereby supporting the bilateral projection hypothesis.

Vagus nerve stimulation therapy for epilepsy in older adults.

The authors assessed the efficacy, safety, and tolerability of vagus nerve stimulation (VNS) for refractory epilepsy in 45 adults 50 years of age and older. They determined seizure frequency, adverse effects, and quality of life. At 3 months, 12 patients had a >50% decrease in seizure frequency; at 1 year, 21 of 31 studied individuals had a >50% seizure decrease. Side effects were mild and transient. Quality of life scores improved significantly with time.

Conduction aphasia and the arcuate fasciculus: A reexamination of the Wernicke-Geschwind model.

Wernicke, and later Geschwind, posited that the critical lesion in conduction aphasia is in the dominant hemisphere's arcuate fasciculus. This white matter pathway was thought to connect the anterior language production areas with the posterior language areas that contain auditory memories of words (a phonological lexicon). Alternatively, conduction aphasia might be induced by cortical dysfunction, which impairs the phonological output lexicon. We observed an epileptic patient who, during cortical stimulation of her posterior superior temporal gyrus, demonstrated frequent phonemic paraphasias, decreased repetition of words, and yet had intact semantic knowledge, a pattern consistent with conduction aphasia. These findings suggest that cortical dysfunction alone may induce conduction aphasia.

Apraxia and motor-skill acquisition in Alzheimer's disease are dissociable.

Many patients with Alzheimer's disease (AD) are apraxic and the apraxia has been posited to be related to a loss of movement representations. Whereas patients with Alzheimer's disease have been reported to demonstrate normal motor learning on a rotor pursuit skill acquisition task, it is unknown whether AD subjects who are apraxic demonstrate normal skill-learning. We tested subjects with probable AD and normal controls on a rotor pursuit task. We also tested the AD subjects for ideomotor apraxia. Subjects with AD who were apraxic had normal motor learning. In addition, praxis score did not correlate with performance on the skill-acquisition task. The results suggest that ideomotor praxis and motor learning are at least partly dissociable.

Calcified cystic lesions in a patient with epilepsy and progressive dementia.

A 67-year-old woman had intractable epilepsy and developed a progressive dementia with upper motor neuron signs over the last 6 years. Magnetic resonance imaging (MRI) revealed multiple areas of large calcified cysts, which increased in number and size over the last 3 years. Discussion includes the appearance of these lesions radiologically and pathologically, as well as their differential diagnosis and clinical significance, focusing on the increasing detection of these lesions with current imaging techniques.

Anosognosia and confabulation during the Wada test.

Feinberg et al. proposed that right-hemisphere-damaged stroke patients with anosognosia for hemiplegia (AHP) confabulate seeing stimuli on the left side but those without AHP admit to having inadequate visual information. This study examines the relationship between AHP and confabulation using selective anesthesia of the cerebral hemispheres. Seventeen patients with intractable epilepsy were tested during intracarotid methohexital infusion. For half of the trials, subjects were stimulated on their paretic hand with a material (sandpaper, metal, or cloth), and for the remaining trials they were not stimulated. The subjects were trained to use a pointing response to indicate if they been stimulated and the type of material they had felt. Admission of uncertainty was defined as pointing to a question mark. Confabulation was defined as any material response to a no-touch trial. During anesthesia of either hemisphere, subjects with and without AHP confabulated responses. The AHP and non-AHP groups did not differ in admission of uncertainty. Our results support the postulate that confabulation and AHP are independent disorders, and therefore confabulation cannot fully account for AHP.

Valproate-associated carnitine deficiency and malignant cerebral edema in the absence of hepatic failure.

We describe a 27-year-old woman who developed encephalopathy and cerebral edema during treatment of refractory complex partial seizures that included acute administration of valproate (VPA) at a dosage of 35 mg/kg per day. Multiple random VPA levels were within therapeutic range, and results of liver function studies did not show evidence of hepatic failure. Cerebral computerized tomography (CT) showed evidence of massive cerebral edema with central herniation. Just prior to death, plasma levels of free and acyl carnitines were markedly decreased. Analysis of urinary organic acids showed increased excretion of lactate, but a normal distribution of VPA metabolites. Carnitine deficiency may predispose patients to the development of coma and life-threatening cerebral edema associated with acute administration of VPA, even in the absence of concomitant hepatic failure. We suggest specific guidelines for the evaluation and management of altered consciousness in patients with seizures receiving VPA.

Secondary epileptogenesis in humans.

Secondary epileptogenesis as it applies to humans remains a controversial topic despite 40 years of investigation. Part of the controversy stems from disagreement about the definition of secondary epileptogenesis, and part of the controversy stems from the imperfect fit of animal models to the human epileptic syndromes. It may be that models of secondary epileptogenesis can be useful to describe specific epileptic syndromes such as bitemporal epilepsy and secondary bilateral synchrony, but other models may be required for remitting syndromes such as the Landau-Kleffner syndrome. The concept of secondary epileptogenesis may also provide a useful construct for evaluating patients with partial epileptic syndromes, especially those under consideration for epilepsy surgery, and for the evaluation of preventive strategies in epilepsy.

Abnormalities of antioxidant metabolism in a case of Friedreich's disease.

We report a patient with Friedreich's disease (FD) who exhibited abnormalities of antioxidant metabolism, including decreased levels of glutathione peroxidase, glutathione reductase, and selenium, and an increased lipid peroxide index. These abnormalities became normal after treatment with N-acetylcysteine, selenium, and low-dose vitamin E therapy. Treatment was associated with a decreased rate of clinical decline. FD is a neurodegenerative disorder that may be related to disturbed antioxidant metabolism; the disorder may be treatable with antioxidant compounds.

Electroencephalographic findings in Hashimoto's encephalopathy.

Hashimoto's encephalopathy (HE) is a steroid-responsive relapsing disorder that frequently presents with seizures and diffuse EEG abnormalities. We report the EEG findings in seven patients with encephalopathy, seizures, or both, associated with elevated antithyroid antibodies. There were several combinations of findings within the same patient and between patients. The EEGs of five patients had generalized slowing or frontal rhythmic slowing; two also had triphasic waves and one had periodic sharp waves. Three had focal left temporal slowing. HE is heterogeneous clinically and electrographically. A high level of suspicion is necessary to establish the diagnosis.

[Surfactant interactions in model and biological membranes. IX. Theoretical model of biological activity in relation to the length of hydrocarbon chains]. / Interakcia surfaktantov s modelovými a biologickými membránami. IX. Teoretický model závislosti biologickej úcinnosti na dlzke uhl'ovodíkového ret'azca.

A theoretical model is proposed according to which the quasi-parabolic dependence of the biological activity of amphiphilic compounds on their hydrophobic substituent chain length (the "cut-off" effect) is caused by a combination of partition equilibria and geometrical parameters of these compounds interacting with the bilayer of phospholipid membranes. The most important parameter seems to be a change in the thickness of the phospholipid bilayer. The model is quantified for the case of normal alcohols.