Edward Valenstein

Two forms of ideomotor apraxia

Destruction of parietal areas containing visuokinesthetic motor engrams, where motor acts may be programmed, should be distinguishable from apraxia induced by disconnection of these parietal areas from frontal motor areas. Destruction should result in inability to distinguish well-performed from poorly performed movements, whereas disconnection should not. We gave movement and act-discrimination tasks to apraxic and nonapraxic patients with anterior lesions or nonfluent aphasia, and to patients with posterior lesions or fluent aphasia. On both tasks, the performance of posterior/fluent patients was worse than that of all other patients. Our results suggest that there are two types of patients with ideomotor apraxia.

Frontal lobe neglect in man

“My hypothesis is that the frontal lobes are the seat of coordination and fusion of the incoming and outgoing products of the several sensory and motor areas of the cortex.” Bianchi (1895)’ made this hypothesis after excising the frontal lobes in animals and observing rotary movements t o the side of the lesion and a visual disturbance that appeared as a contralateral hemianopia. Kennard’ showed that there was also a loss of cutaneous sensitivity in these animals, and Kennard and Ectors3 proposed that the visual defect was more a hemianopia in which an object is disregarded than a true hemianopia. Welch and Stuteville4 found that with lesions of the posterior part of the superior limb of the arcuate sulcus, their monkeys had unilateral neglect t o all sensory modalities tested. Although many investigators have produced and described frontal neglect in monkeys, unilateral frontal neglect has not been described in man other than in the two cases of pseudohemianopia described by Halstead’ and ThiebauL6 The purpose of this study was t o assess patients with frontal lobe lesions to establish the p r e s e n c e of unilateral neglect hemispatial agnosia, inattention, and extinction t o simultaneous stimuli -and to relate these findings t o other known phenomena attributed t o frontal lobe disease. Patients admitted t o the University of Florida Teaching Hospital o r Boston City Hospital during 1969 and 1970 who demonstrated lesions confined to the frontal lobes, as demonstrated by brain scan or postmortem examination, were included in this series. Six cases of unilateral neglect were uncovered (see table). The anatomic loci of the lesions were determined by pathological exami-

Recognition and discrimination of emotional faces and pictures

Abstract In order to learn whether patients with right-hemisphere disease (RHD) had a deficit in their ability to discriminate and comprehend emotional faces and pictures, we studied nine patients with RHD, nine patients with left-hemisphere disease (LHD), and nine controls. The subjects were presented with six picture tests that comprised either emotional faces or emotional scenes. Their task was either to denote (name or choose) an emotion or to discriminate (same, different) between two faces or emotions. Patients with RHD performed significantly worse than subjects with LHD when asked to discriminate between faces, to discriminate between emotional faces, and to name emotional scenes. There was also a trend for the RHD group to be more impaired than the LHD group when asked to name the emotional face or choose the emotional face. Except for the facial and emotional discrimination tests, the LHD patients also performed worse than controls.

Controlled Clinical Trial of Dichloroacetate for Treatment of Congenital Lactic Acidosis in Children

OBJECTIVE. Open-label studies indicate that oral dichloroacetate (DCA) may be effective in treating patients with congenital lactic acidosis. We tested this hypothesis by conducting the first double-blind, randomized, control trial of DCA in this disease. METHODS. Forty-three patients who ranged in age from 0.9 to 19 years were enrolled. All patients had persistent or intermittent hyperlactatemia, and most had severe psychomotor delay. Eleven patients had pyruvate dehydrogenase deficiency, 25 patients had 1 or more defects in enzymes of the respiratory chain, and 7 patients had a mutation in mitochondrial DNA. Patients were preconditioned on placebo for 6 months and then were randomly assigned to receive an additional 6 months of placebo or DCA, at a dose of 12.5 mg/kg every 12 hours. The primary outcome results were (1) a Global Assessment of Treatment Efficacy, which incorporated tests of neuromuscular and behavioral function and quality of life; (2) linear growth; (3) blood lactate concentration in the fasted state and after a carbohydrate meal; (4) frequency and severity of intercurrent illnesses and hospitalizations; and (5) safety, including tests of liver and peripheral nerve function. OUTCOME. There were no significant differences in Global Assessment of Treatment Efficacy scores, linear growth, or the frequency or severity of intercurrent illnesses. DCA significantly decreased the rise in blood lactate caused by carbohydrate feeding. Chronic DCA administration was associated with a fall in plasma clearance of the drug and with a rise in the urinary excretion of the tyrosine catabolite maleylacetone and the heme precursor δ-aminolevulinate. CONCLUSIONS. In this highly heterogeneous population of children with congenital lactic acidosis, oral DCA for 6 months was well tolerated and blunted the postprandial increase in circulating lactate. However, it did not improve neurologic or other measures of clinical outcome.

Hemispace and Hemispatial Neglect

A patient with hemispatial neglect may fail to report, respond, or orient toward novel or meaningful stimuli presented in the hemispace contralateral to a brain lesion. Hemispatial neglect may be induced by a sensory-attentional, motor-intentional, memory, or an exploratory disorder. This chapter defines hemispatial neglect and describes how it may be tested in patients. There is a review of hemispace studies in normal subjects. The pathophysiology of the attentional, intentional memory, and exploratory defects is discussed. Finally, recovery of function and treatments are also discussed.

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.

Apomorphine has a therapeutic effect on neglect produced by unilateral dorsomedial prefrontal cortex lesions in rats

Neglect is a disorder in which the response to stimulation is diminished or absent on the side of the body contralateral to the lesion in the absence of an elemental sensory or motor defect. Most cases of neglect in humans are induced by cortical damage, but there have been no investigations of the pharmacologic basis of neglect induced by cortical damage. We examined the role of the dopamine system in polymodal neglect caused by a unilateral lesion of the medial precentral prefrontal cortex of the rat. A dose-response examination of the effect of apomorphine on neglect revealed that apomorphine, at 0.5 mg/kg, the highest dose examined, significantly improved the orientation scores of subjects in all modalities tested and significantly decreased the total number of allesthetic responses. The therapeutic effect of apomorphine was mediated by dopamine receptors as the therapeutic effect of apomorphine was blocked by prior administration of spiroperidol. These results demonstrate the important role of disruption of dopamine mechanisms in neglect induced by a lesion of medial precentral cortex.

Evaluation of long-term treatment of children with congenital lactic acidosis with dichloroacetate.

OBJECTIVE. The purpose of this research was to report results on long-term administration of dichloroacetate in 36 children with congenital lactic acidosis who participated previously in a controlled trial of this drug. PATIENTS AND METHODS. We conducted a randomized control trial, followed by an open-label study. Data were analyzed for each patient from the time they began treatment through May 2005. RESULTS.Subject exposure to dichloroacetate totaled 110.42 years. Median height and weight increased over time, but the standardized values declined slightly and remained below the first percentile. There were no significant changes in biochemical metabolic indices, except for a 2% rise in total protein and a 22% increase in 24-hour urinary oxalate. Both the basal and carbohydrate meal-induced rises in lactate were blunted by dichloroacetate. The median cerebrospinal fluid lactate also decreased over time. Conduction velocity decreased and distal latency increased in peroneal nerves. Mean 3-year survival for all of the subjects was 79%. CONCLUSIONS. Oral dichloroacetate is generally well tolerated in young children with congenital lactic acidosis. Although continued dichloroacetate exposure is associated with evidence of peripheral neuropathy, it cannot be determined whether this is attributable mainly to the drug or to progression of underlying disease.

Unilateral hypokinesia and motor extinction

A patient with a right caudate hemorrhage demonstrated left limb hypokinesia but did not have sensory inattention or sensory extinction. The left-sided hypokinesia was increased by bilateral simultaneous movements (motor extinction).

Myokymia, muscle hypertrophy and percussion “myotonia” in chronic recurrent polyneuropathy

Three unusual features were observed in a patient with chronic relapsing polyneuropathy: myokymia, muscle hypertrophy, and prolonged contraction in response to muscle percussion. Low nerve conduction velocity and conduction block were demonstrated in all motor nerves tested, indicating a demyelinating peripheral neuropathy. Myokymia was caused by spontaneous motor unit activity which was shown to originate in peripheral nerves, since it persisted after nerve block and was abolished by regional curarization. Muscle hypertrophy was attributed to increased peripheral nerve activity, and the prolonged contraction of muscle in response to direct percussion was attributed to irritability of intramuscular nerve terminals.