Alexander G. Reeves

Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure.

This report provides the first detailed neuropathological study of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced parkinsonism in humans. All 3 subjects self‐administered the drug under the impression it was “synthetic heroin” and subsequently developed severe and unremitting parkinsonism, which was L‐dopa responsive, at least in the earlier stages of illness. Survival times ranged from 3 to 16 years. Neuropathological examination revealed moderate to severe depletion of pigmented nerve cells in the substantia nigra in each case. Lewy bodies were not present. In Patients 1 and 2, there was gliosis and clustering of microglia around nerve cells. Patient 3 had a similar picture and also showed large amounts of extraneuronal melanin. These findings are indicative of active, ongoing nerve cell loss, suggesting that a time‐limited insult to the nigrostriatal system can set in motion a self‐perpetuating process of neurodegeneration. Although the mechanism by which this occurs is far from clear, the precedent set by the cases could have broad implications for human neurodegenerative disease.

Cerebral commissurotomy for control of intractable seizures

Cerebral Commissurotomy or the “split-brain” procedure may be a valuable adjunct to anticonvulsants for the control of seizures in people whose epilepsy cannot be relieved by anticonvulsants alone, and who are not candidates for the standard methods of surgery. Corpus callosotomy, a revised form of the usual division of many commissures, is a safer operation and appears to be equally effective. The complex clinical aspects of cure and treatment are emphasized.

Division of the corpus callosum for uncontrollable epilepsy

Cerebral commissurotomy, the “split-brain” procedure, has been employed for the control of intractable seizures, in conjunction with moderate doses of anticonvulsant drugs. The results have been encouraging in several small series. The use of microsurgical techniques and the restriction of surgery to one commissure, the corpus callosum, has reduced morbidity without apparent change in result. The eight patients in our first series who underwent the prescribed division of several forebrain commissures are compared to the four patients in our second series who underwent division of the corpus callosum alone. The technique of callosotomy is described.

“Central” commissurotomy for intractable generalized epilepsy: Series two

A second consecutive series of 12 patients underwent microsurgical “central” commissurotomy (division of the entire corpus callosum and hippocampal commissure) for the relief of previously intractable generalized seizures. This modified operation was found to be safer than the multiple commissurotomies performed in the first series of eight patients and was equally effective. Central commissurotomy was modified further by being performed in two stages, which reduced the length and severity of the “acute disconnection syndrome,” a common cause of morbidity in the early postoperative phase. Best results were obtained in patients who were not severely retarded, had signs of unilateral cerebral damage, and included akinetic spells as a prominent form of their generalized seizures. EEG showed that bilateral symmetric discharges became either unilateral or asymmetric after surgery, which emphasized the important role played by the corpus callosum in conducting seizure discharges from one hemisphere to the other.

Seven cases of cerebromedullospinal disconnection The “locked‐in” syndrome

THE TERM “AKINETIC MUTISM” was coined by Cairns et al.1 in 1941 to describe a patient with an epidermoid cyst of the third ventricle. In the original description, the patient did not speak or move but followed the observer with her eyes. “Usually there a re no movements of a voluntary character” though the patient could be made to carry out simple commands and would withdraw from painful stimuli. In contradistinction, Plum and Posnerz use the term “locked-in” syndrome to describe a patient who, with bilateral basis pontis infarction, had no motion a t all other than vertical eye movements. This patient was alert and communicated intelligently by using his eyes, differing from the classic akinetic mute who has the ability to move his extremities but usually does not d o so. The purpose of this paper is to present seven patients who, a t some time during their illness, were alert and totally paralyzed save for mesencephalic-controlled eye and lid movements, their only means of communication. Seven patients with similar difficulties are abstracted from the literature (see table) . All cases are considered to have had bilateral lesions in the pons as determined by clinical evaluation, verified in most cases by postmortem examination.

Alexia without agraphia, hemianopia, or color-naming defect: a disconnection syndrome.

A patient with alexia without agraphia, hemianopia, or color-naming defect was found at operation to have a meningioma arising from the tentorium cerebelli that compressed the inferior aspect of the left temporal-occipital junction. It is presumed to have involved only the left ventral visual association cortex and its inferior outflow tracts to the angular gyrus. The input from the right occipital area also was disconnected from the visual language verbal association area by involvement of the ventral outflow of the splenium of the corpus callosum. Preservation of color naming and matching suggests that these functions are dependent on the integrity of more dorsal occipital association systems.

Forebrain commissurotomy for epilepsy. Review of 20 consecutive cases.

SummaryDuring the past 10 years, 20 patients with intractable generalized, generalized and partial, and partial seizures have been treated here by surgical division of one or more of the forebrain commissures. Modifications in the operative technique and extent of operation have resulted in continued good results in seizure control with decreased morbidity. The present operation, a two-stage division of the corpus callosum and underlying hippocampal commissure, is demonstrated to be effective in controlling intractable seizures. Good or excellent results account for more than 80 per cent of the series. Historical background, indications for operation, criteria for patient selection, operative technique, results, complications, and the value of forebrain commissurotomy as a research tool are presented.

The ciliospinal response in man

THE CILIOSPINAL REFLEX was first described and studied in 1852 by Budge.1 The reflex consists of a rapid (0.1to 0.3-second) bilateral pupillary dilatation (1 to 2 mm.) following a noxious or startling stimulus and is most easily elicited by a pinch to the face, neck, or upper trunk. Many investigations into the mechanism of this reflex in experimental animals have appeared since Budges original description and are summarized by Loewenfeld.2 However, only a few studies have emphasized the clinical usefulness of the reflex, and the mechanism of the reflex in man is still unclear. A brief review of the neuroanatomy of sympathetic and parasympathetic pupillary fibers indicates the potential clinical importance of the reflex in localizing neurologic lesions, providing controversies involving its mechanism can be resolved. Pupillary size is regulated by the interplay between the parasympathetic pupilloconstrictor reflex pathways (Fig. 1A) and sympathetic pupillodilator reflex pathways (Fig. 1B). The former has, as its afferent arc: light-sensitive fibers originating in the retina, traversing the optic nerves, partially decussating at the chiasm, and following the optic tracts and quadrigeminal brachium to enter the midbrain on its lateral aspect and synapse in the pretectal nuclei. From these nuclei, fibers reach both the ipsilateral and contralateral EdingerWestphal nuclei; the contralateral nucleus is reached by fibers crossing both dorsal to the aqueduct in the posterior commissure and ventral to the aqueduct, possibly in the medial longitudinal fasciculus.3 The efferent arc3 begins in the Edinger-Westphal nucleus and follows the third nerve, usually in its upper portion,* to the episcleral ganglion and thence to the pupillary sphincter. The sympathetic efferent pathway is ipsilatera1 and has three neurons. Fibers arise in the diencephalon (posterior and lateral hypothalamus)5.6 and descend through the prerubral field, dorsal and rostral to the red nucleus,7 and through the lateral tegmentum of the midbrain, pons, and medulla*~9 to synapse on the intermediolateral cell column of the upper thoracic spinal cord. Second-order neurons arising in the intermediolateral cell column

Alexia without agraphia associated with spleniogeniculate infarction

Pure alexia, following an infarction in the distribution of the left posterior cerebral artery, is attributed to damage of the left occipital lobe and the splenium of the corpus callosum. We describe a case of pure alexia in a 57-year-old woman with infarction of the left lateral geniculate body and the splenium of the corpus callosum, a variation on this classic disconnection syndrome.

Isolation of a right hemisphere cognitive system in a patient with anarchic (alien) hand sign

We report evidence of isolated conceptual knowledge in the right hemisphere of a woman with chronic anarchic hand sign after ischemic infarction of the central four-fifths of the corpus callosum. Limited visual information was available to the right hemisphere, access to medial temporal structures subserving memory was disrupted and disconnection from left hemisphere language structures was complete. Still, the right hemisphere could build mental representations of objects via tactile input and use them in cross-modal matching. These representations were not accessed consistently in auditory comprehension or naming tasks. This functional specificity and its pathoanatomical correlates demonstrate that the study of anarchic hand sign can illuminate not just motor control issues but may inform our understanding of the representation and lateralization of conceptual knowledge as well.