Botulinum toxin-induced paralysis of frontotemporal muscles improves seizure focus localization.

BACKGROUND: Scalp EEG localization of epileptic foci may be obscured by electromyographic (EMG) artifact produced by ictal contraction of cranial muscles. Injection of botulinum toxin type A (BTX-A) into frontotemporal scalp muscles reduces EMG activity. Initial scalp video-EEG monitoring in three patients suggested partial seizures, but definitive lateralization or localization was precluded by EMG artifact. METHODS: EMG-guided BTX-A injection to bilateral frontotemporal muscles was performed. When artifact persisted, BTX-A administration was selectively repeated. Patients subsequently underwent scalp video-EEG monitoring 1 week later. RESULTS: All patients had reduction of EMG artifact during subsequent scalp video-EEG monitoring. No patient had adverse effects after BTX-A administration. All three patients had localization to either frontal or temporal lobes and definitive lateralization. Two of the three patients were able to proceed to invasive placement of frontotemporal subdural grid electrodes based on the BTX-A scalp video-EEG localization, and the third patient was determined to have a multifocal seizure disorder. CONCLUSIONS: Paralysis of frontotemporal scalp muscle after BTX-A administration reduces EMG artifact and may improve localization and lateralization of a seizure focus, providing a noninvasive technique for advancement toward epilepsy surgery.

Verbal encoding deficits in a patient with a left retrosplenial lesion.

Over the past decade, memory impairments associated with retrosplenial damage have received increased attention among neuroscientists, although the exact role of the retrosplenial region in memory has not been clearly defined. Evidence from lesion studies and functional neuroimaging has implicated the retrosplenial region in verbal episodic memory, temporal ordering of information, and topographical memory. In addition, recent positron emission tomography studies have shown increased activation of the retrosplenial cortex during tasks involving both the encoding and retrieval of episodic information. The objective of this study was to define more clearly the nature of memory impairments observed in retrosplenial amnesia. A 47-year-old amnesic male with a left retrosplenial arteriovenous malformation was examined on neurocognitive tasks of automatic and directed encoding, temporal ordering of information, and remote memory. Despite normal performance on frontal cognitive tasks, intact memory for remote information, and a superior IQ, this individual exhibited a profound deficit in the encoding of information, evidenced by poor release from proactive interference, poor category clustering on word list recall, poor semantic encoding on a levels of processing task, and mild impairments in temporal ordering. These results imply that the retrosplenial region plays a role in the verbal encoding of information, which contributes to the profound verbal memory impairment reported in previous case studies of patients with retrosplenial damage.

Neglect and related disorders.

Neglect is a failure to report, respond, or orient to contralateral stimuli that is not caused by an elemental sensorimotor deficit. Subtypes of neglect are distinguished by input (attentional) or output (intentional) demands, the distribution (personal, spatial, and representational), and the means of eliciting the signs (unilateral or bilateral stimuli). In this article we discuss how to assess patients for neglect, the pathophysiology of neglect, and the treatment of neglect.

Chemotherapy for pancreatic cancer: a neuroimaging clinicopathologic correlation.

This 52-year-old male without a significant medical history was receiving chemotherapy with diethylnorspermine (DENSPM), a polyamine analogue, for a partially resected pancreatic adenocarcinoma. Ten months after his initial diagnosis, he was admitted to an outside hospital for evaluation of altered mental status. Over the course of the next few days the patient developed progressive neurologic signs and symptoms including lethargy, tonic deviation of his eyes to the left, asymmetic pupils, and right-sided decerebrate posturing elicited by painful stimuli. Neuroimaging studies revealed multiple lesions scattered in the periventricular white matter, thalamus, midbrain pons, and cerebellar peduncles. The clinical and neuroimaging differential diagnoses are discussed, and postmortem neuropathologic correlation is presented.

Tapping, talking and the thalamus: possible influence of the intralaminar nuclei on basal ganglia function.

A patient with a discrete lesion of the left, intralaminar thalamic, nuclei exhibited a paradoxical finding with regard to finger-tapping. Normal subjects typically reduce their tapping rate when performing simultaneous verbal activity. Tapping was impaired in our patient's contralesional hand on baseline trials; however, performing the controlled oral word association (COWA) task, while finger-tapping, normalized her deficit. Subsequent experiments showed that motoric tasks rather than cognitive aspects of the COWA task were critical in potentiating finger-tapping performance. A SPECT study performed at rest revealed focal perfusion asymmetries in motor and premotor cortices. Because the caudal intralaminar nuclei project heavily to the striatum, striatal deafferentiation may account for these asymmetries. These observations provide some insight into the influences of the caudal intralaminar thalamic nuclei on basal ganglia function and the basal ganglia's influence on motor gating.

Frontal lobe neglect in monkeys.

Using a crossed-response task, monkeys with neglect induced by frontal lesions appear to have motor rather than sensory neglect. However, the crossed-response task may not reveal sensory neglect (inattention) if no perceptual discrimination is required. We therefore trained two monkeys in a perceptually complex crossed-response task. Following unilateral frontal (arcuate gyrus) ablation, we found no contralateral perceptual disorders or sensory neglect in either monkey but did find a failure to respond with the contralateral arm (motor neglect) in both monkeys. We also found that the monkeys made more incorrect responses with the arm ipsilateral to the lesion than they did with the contralateral arm. The errors made by the ipsilateral arm could be a compensatory strategy or a disinhibition phenomenon. Because these incorrect responses were not rewarded and became more frequent as motor neglect improved, the incorrect responses of the ipsilateral arm are not a compensatory strategy, but rather a defect we term "disinhibition hyperkinesia" or "allokinesia."

Posterior neocortical systems subserving awareness and neglect. Neglect associated with superior temporal sulcus but not area 7 lesions.

OBJECTIVE: In humans and monkeys, the intraparietal sulcus separates the superior parietal lobule from the inferior parietal lobule (IPL). Whereas in humans Brodmann's area 7 is above this sulcus, in monkeys it is below and therefore part of the IPL. In humans, the IPL consists of Brodmann's areas 39 and 40. Some investigators contend that the monkey homologue of the human IPL (areas 39 and 40) is the monkey's IPL (area 7). Others contend that it is, at least in part, in the monkey's superior temporal sulcus (STS). In humans, IPL lesions induce neglect. Although IPL lesions in monkeys also have been reported to induce neglect, the STS was involved in these lesions. We sought to learn which of these two areas, when ablated, produces neglect. DESIGN: Study of five adult stump-tailed macaque monkeys by making five isolated STS and six IPL lesions. RESULTS: Inferior parietal lobule lesions were associated with misreaching but not with unilateral neglect. Neglect was observed in association with five of the six STS lesions. CONCLUSIONS: With regard to neglect, STS may be the monkey homologue of the human IPL. Animals with STS lesions and humans with IPL lesions may manifest unilateral neglect because these areas are necessary for normal awareness of external stimuli. This awareness may result from the integration of the areas important in stimulus localization (the "where is it?" system) and stimulus identification (the "what is it?" system), as well as the areas important in defining the biologic importance of stimuli, such as the frontal lobes and limbic areas.

Contributions of the left intralaminar and medial thalamic nuclei to memory. Comparisons and report of a case.

A patient complained of memory disturbance after a small left thalamic infarction. Neuropsychological testing revealed her memory to be normal provided that she was allowed to rehearse or use semantic encoding strategies. When these strategies were prevented, her performance was impaired. Mapping of the lesion demonstrated involvement of the caudal intralaminar nuclei (centre médian and parafascicular nuclei), and portions of the medial nuclei (medioventral [reuniens], centromedial, and the most inferior aspect of the mediodorsal nucleus). The majority of mediodorsal nucleus, the mammillary bodies, the mammillothalamic tract, and the anterior thalamic nuclei, were spared. A comparison among our patient's performances and those of alcoholic Korsakoff patients, patient NA, and amnestic patients with circumscribed diencephalic lesions suggests that there are two distinct behavioral and anatomic types of memory impairment associated with diencephalic lesions. The severe amnesia associated with damage to the mammillary bodies, midline nuclei, mammillothalamic tract, and/or dorsomedial nucleus of the thalamus (eg, Korsakoff and NA) is characterized by encoding deficits that never approximate normal performance. The memory disturbance associated with damage to the intralaminar and medial nuclei of the thalamus is milder and is characterized by severe distractibility.

What psychological process mediates feeding evoked by electrical stimulation of the lateral hypothalamus?

Because electrical stimulation of the lateral hypothalamus (ESLH) can elicit both feeding and reward, most investigators have concluded that stimulation does not evoke the aversive cues associated with hunger. It has been hypothesized, instead, that ESLH primes ingestion by evoking pleasurable taste sensations. A direct taste of this hedonic hypothesis was undertaken in rats that showed stimulus-bound feeding. Contrary to the prediction, it was found that the taste reactions (gapes, tongue protrusions, etc.) during ESLH were more aversive than hedonic. It is suggested that the stimulation influences behavior by potentiating the salience, but not the hedonic value, of external stimuli. The advantages of this incentive salience hypothesis are that it circumvents the need to postulate a hedonic sensory experience during stimulation and that it can explain how evoked feeding may switch to other behaviors when conditions are altered.

Frontal hypermetabolism and thalamic hypometabolism in a patient with abnormal orienting and retrosplenial amnesia.

A patient with verbal amnesia and a propensity to direct his attention to the right following a retrosplenial area lesion was studied with positron emission tomography using [F-18] fluorodeoxyglucose. These studies showed that the left thalamus was hypometabolic, and the anterior 2/3 of the left hemisphere was hypermetabolic when compared with the right. There were no significant differences seen in the medial temporal lobes. Based on this study, it is posited that interruption of hippocampal input into the anterior thalamus was responsible for the amnesia, and the left frontal hyperactivity was associated with the propensity to attend contralaterally.

Effect of vitamin E deficiency on neurologic function in patients with cystic fibrosis.

We evaluated neurologic function in 18 patients, ages 5 to 26 years, with cystic fibrosis. Eight were deficient in vitamin E. Sural nerve conduction latency was increased and nerve action potential amplitude decreased in the vitamin E-deficient group in comparison with the vitamin E-sufficient group. Two vitamin E-deficient patients had absent deep tendon reflexes; findings of clinical neurologic examinations were otherwise normal. We recommend early supplementation with vitamin E for patients with cystic fibrosis who have pancreatic insufficiency, to prevent neurologic dysfunction.

Impaired acquisition of temporal information in retrosplenial amnesia.

In this paper we describe the performance of an amnesic with a left retrosplenial lesion on three memory tasks assessing his ability to judge when a previously learned event had occurred. This patient was dramatically impaired in acquiring temporal information about new stimuli, and this defect could not be attributed to recognition failures or to frontal lobe dysfunction. In contrast to his impaired acquisition of temporal information, he had no difficulty judging the temporal order of remote historical events. The pattern of performance displayed by this patient suggests a specific defect in "time-tagging" of new incoming information.

Retrosplenial amnesia.

A 39-year-old man developed retrograde and anterograde amnesia following haemorrhage from an arteriovenous malformation situated near the splenium of the corpus callosum. MRI studies demonstrated damage to the splenium, and to a region containing the retrosplenial cortex and the cingulate bundle. The fornix was anterior and inferior to the site of maximal damage, but may have been involved; the stria terminalis was probably spared. Structures known to be important in memory but spared by the lesion included the hippocampus, thalamus, and basal forebrain. The retrosplenial cortex receives input from the subiculum and projects to the anterior thalamus, thus providing an alternative route between hippocampus and thalamus. Perhaps more importantly, medial temporal structures involved in memory receive anterior thalamic input directly via the cingulate bundle and indirectly through a relay in the retrosplenial cortex. We suggest that this thalamocortical portion of Papez' circuit may be important in memory, and that lesions of the cingulum and retrosplenial cortex may cause amnesia by disrupting this pathway.

Dopamine agonist therapy for neglect in humans.

Lesions of ascending dopaminergic pathways induce neglect in animals. Apomorphine, a dopamine receptor agonist, decreases the magnitude of neglect in rats with cortical lesions. We treated two patients with 15 mg of bromocriptine daily for 3 to 4 weeks, one with chronic (longer than 6 months) and one with relatively more acute disabling neglect. Tests for neglect that significantly improved on therapy and worsened after its withdrawal included line, letter, and geometric figure cancellation tasks. Neither patient noted any untoward effects. Based on this open trial of dopamine agonist therapy in humans with neglect, larger controlled studies may be warranted.

Response time in monkeys with unilateral neglect.

Four monkeys were trained to open a door with either the right or left hand in response to a tactile stimulus to either leg. After unilateral frontal arcuate ablation inducing unilateral neglect, the response time on this task increased most when the monkey responded with the hand contralateral to the lesion, but also increased when the monkey used the hand ipsilateral to the lesion. The side of stimulation had no effect on response time. Control (anterior superior temporal) lesions did not cause neglect and only affected response time slightly in one monkey (using the limb contralateral to the lesion). We conclude that response time is increased in animals with unilateral neglect and that the increase results from a defect in intention to act (motor neglect) rather than from sensory neglect.