Irving S. Cooper

JUDGMENT OF VISUAL AND POSTURAL VERTICAL BY PARKINSONIAN PATIENTS.

IN THE PAST, disorders of the basal ganglia in man have been thought to produce symptoms limited to the motor sphere.1-3 It is conceivable, however, that parkinsonism might also lead to changes in perception. We suspected specifically that patients with parkinsonism might display an abnormality of interaction between posture and distance receptors. Such disturbances would be similar to those found after injury to the human frontal lobes.4 This prediction is consistent with the view that traditional categorization of cerebral function as purely motor or purely sensory might not apply to the basal ganglia and to similar intercalated structures. The prediction is also derived from the finding that certain behavioral changes, such as the delayed-response deficit in subhuman primates, can be seen in equivalent form after striatal lesions, and not only after frontocortical removals.E--7 Moreover, there is increasing evidence of massive influx from many sense modalities into the basal ganglia.s.9 Lastly, there are experiments suggesting that stimulation of the basal ganglia might be capable of modulating sensory input received in sensory cortical projection fields;l0-12 although some of these effects have been imputed to stimulation of internal capsule.13 A role of the basal ganglia in certain aspects of perception was suggested earlier in a study by Teuber and Mi~hkin .~ They tested men with penetrating gunshot wounds of either anterior or posterior thirds of the brain on several variations of a task designed by Aubert14 and discussed by Bender and Jung.lj This task requires a subject to judge the orientation of a luminous line in the dark under various conditions of body tilt. Patients with frontal-lobe injury made large errors in adjusting such a luminous line when their heads and bodies were tilted. In fact, errors after frontal injury were significantly greater than those after injuries to the posterior third of the brain, or in normal controls. Teuber and Mishkin4 considered the possibility that this phenomenon did not derive exclusively from lesions of the frontal cortex; in some of their cases, the symptoms could have arisen from coincident damage to the basal ganglia. We therefore decided to investigate whether basal ganglia disease might produce abnormalities similar to those found after penetrating trauma of the convexity of man’s frontal lobes.

ANATOMIC VERIFICATION OF THE LESION WHICH ABOLISHES PARKINSONIAN TREMOR AND RIGIDITY.

THE FACT that surgically inflicted lesions within the basal ganglia are capable of abolishing parkinsonian tremor and rigidity, as well as many other involuntary movement disorders, has been established by clinical investigations following intracerebral surgery in human beings.1-7 However, the precise anatomic site or sites of the lesions which are capable of abolishing tremor and rigidity are not yet certain because of the paucity of long-term follow-up anatomic material. Experienced interpretation of roentgenograms obtained during basal ganglia operations and the application of stereotactic a t lases~l l~l : ’ provide a reasonably accurate and practical estimate of the inflicted lesion in each instance. However, because of anatomic and pathologic variations in each person subjected to this type of surgery, the precise microscopic neuroanatomic data required to provide accurate physiologic interpretation of the operative results in each case must await the detailed examination of each brain on which surgery was performed that becomes available for study.

Implications of a five-year study of 700 basal ganglia operations.

Selective anterior choroidal artery occlusion was performed in 55 patients between 1952 and 1955. Follow-up examination of these 55 cases of anterior choroidal artery occlusion periods ranging from two to five and one-half vears following surgery has demonstrated that this operation provided the most complete and lasting relief of far advanced incapacitating rigidity, tremor, and deformity that had been reported anywhere in the literature up until that time.1.2 Many of the patients who were completely relieved of tremor, rigidity, and deformity from the side of the body contralateral to surgery not only have remained relieved of these symptoms up to the present time, but they have also become ambulatory and independent in their daily life. Conclusions which can be documented without question as a result of the follow-up studies in these 55 cases of anterior choroidal artery occlusion are as follows: 1) The effectiveness of anterior choroidal artery occlusion is due to infarction of more than a single small anatomic structure and probably involves a physiologic unit of two or more intracerebral structures, principally the mesial part of the globus pallidus and the ventrolateral region of the thalamus (figure 1). 2) Total relief of tremor, rigidity, incapacitation, and deformity is possible by neurosurgical means without inflicting any neurologic deficit upon the patient (figure 2). 3) Objective evidence of five-year cure of the parkinsonian symptoms of tremor, rigidity, and deformity has been achieved by anterior choroidal artery occlusion. 4) The dystonic deformities seen in some parkinsonian patients are not actually fixed deformities but represent forced postures which are reversible, even after many years’ standing. 5) The so-called syndrome of the anterior choroidal artery is not invariable, and in many cases this vessel may be completely occluded without producing observable neurologic deficit. However, anatomic variations of the vessel, particularly the lack of collateral blood supply to the posterior limb of the internal capsule in the aged, would make routine employment of anterior choroidal artery occlusion unwise. 6) The unquestioned ability of this procedure to relieve tremor and rigidity without inflicting any neurologic deficit warranted further steps to develop neurosurgical technics which might be more universally applicable to a broader spectrum of the parkinsonian population.

Metabolic Disorders in Paraplegics

IT IS the purpose of this report to summarize briefly observations concerned with metabolic abnormalities observed in paraplegic patients. This review included clinical data on over 300 paraplegic patients studied during the past five years. The majority of these were paraplegic as a result of traumatic lesions of the spinal cord, and, except where otherwise indicated, this discussion deals specifically with traumatic paraplegics.

Relief of intention tremor by thalamic surgery.

In 1960, it was first reported by one of us (Cooper, 1960a) that intention tremor could be relieved by a surgical lesion placed in the ventrolateral nucleus of the thalamus. Since then, a number of reports have appeared in the literature (Cooper, 1960b; Broager and Fog, 1962; Cooper, 1962b; Krayenbuhl and Yasargil, 1962; Cooper, 1965; Laitinen, 1965; Fox and Kurtzke, 1966), corroborating the therapeutic value of thalamic surgery for intention tremor. It is the purpose of this report to summarize our results and sequelae of cryothalamectomy, carried out on 73 consecutive cases of intention tremor of diverse aetiology. These operations were performed during the period of 10 August 1966 until 26 July 1968.

A cerebellar mechanism in resting tremor

‘THIS REPORT will consider the relationship of the resting tremor of parkinsonism to the intention tremor resulting from cerebellar pathology. It also will demonstrate the role of cerebellar dentatofugal pathways in the mechanism of resting, as well as intention, tremor. Although the studies of the past two decades have provided new insights into possible tremogenic mechanisms within the multiple feedback circuits modulating muscle tone and posture, fundamental disagreement exists concerning the precise intracerebral structures which subserve the pathophysiologic mechanism of parkinsonian tremor.l-4 Most investigators have ascribed this tremor to degeneration of the substantia nigra.5,B Denny-Brown,“ however, believes that the frequently observed pathologic involvement of substantia nigra in cases of parkinsonism is unrelated to the clinically observed tremor. Rather, he considers resting tremor to depend upon degeneration of corticostriate and corticopallidal fibers as as well as of fiber tracts within the globus pallidus. The production of a Parkinson-like tremor in animals has been reported following experimental lesions of substantia nigra.x-’n However, in most instances, according to Gybels,ll the tegmentum and brachium conjunctivum adjacent to substantia nigra were involved by the experimental lesions. Mettler and Carreal213 have held that pathologic involvement of brachium conjunctivum or cerebellofugal fibers in tegmentum of midbrain invariably underlies experimental production of tremor. The pathophysiology of intention tremor has been more apparent than that of parkinsonian tremor. It is due to a lesion affecting the cerebellodentatofugal pathway up to, but not cephalad to, the red nucleus.14.15 This is the major pathway subserving sensory communication from the muscle spindle via cerebellum and thalamus to cerebral motor cortex. Pathologic or functional abnormality of the dentatofugal system, with resultant impaired feedback of sensory communication from the muscle spindle, results in a decreased, steady state gamma-fusimotor discharge to the spindle. This accounts for the hypotonic musculature at rest which is usually associated with the cerebellar syndrome of intention tremor. However, pure cerebellar tremor is not manifest until increased muscular tone and shortening are induced to subserve posture or initiation of movement. On the other hand, the characteristic feature of steady state muscle tone accompanying parkinsonian tremor is increased tonus or rigidity. This hypertonus consists of alternate intense tonic stretch reflexes, followed by lengthening reactions. It is considered by Rushworth and others to be due to hyperactivity of the gamma motor system with persistent, heightened sensitivity of the muscle spindle to stretch.l”l7 It is generally ascribed to overactivity of pallidothalamic connection^,^.^^ secondary to pathologic involvement of nigrostriopallidal cells and fibers.

Morphological changes associated with chronic cerebellar stimulation in the human

✓ The histopathology associated with chronic cerebellar stimulation is described for three human cerebellum and brain-stem specimens obtained at autopsy. The specimens were from three severely epileptic patients who received cerebellar stimulation at 10 Hz for 6½ to 15 months. The electrode arrays were completely encapsulated with loose connective tissue that included a proliferation of capillaries, an infiltration of lymphocytes, and an occasional macrophage. The capsule of one of the specimens was tightly adherent to the underlying cerebellar cortex, which may have been caused by some trauma during the surgical placement of the electrodes. Severe injury of the cerebellar cortex was generally confined to between 1 and 2 mm directly beneath the electrode array, and included thinning of the molecular layer, and loss of most Purkinje cells, interneurons, and associated fibers. Abnormal Purkinje cell dendritic patterns and loss of climbing fibers were evident 3 to 4 mm from the cortical surface. At a depth o...

Tension reduction and alerting in man following chronic cerebellar stimulation for the relief of spasticity or intractable seizures.

Neurologically impaired patients on therapeutic regimens of chronic cerebellar stimulation for periods ranging from 4 to 29 months (mean = 12.8 months) commonly reported amelioration of tension and/or anxiety. Cerebral palsy patients emphasized tension reduction while seizure patients primarily reported increased alertness. Increased alertness and improvement in speech and mood were also noted by many patients. These changes correlated significantly with symptom reduction and functional improvement. Although the mechanisms of these changes are not yet clear, psychological and neurological explanatory hypotheses were presented.

Psychological Effects Of Short Term Cerebellar Stimulation In Epilepsy

The effects of short term cerebellar stimulation on integrative functions as measured by standardized psychological tests were studied. The patient group consisted of 12 epilepsy patients undergoing chronic cerebellar stimulation as treatment for intractable seizures. Three comparison groups included nonstimulated epilepsy patients, stimulated cerebral palsy patients, and stimulated stroke patients. Cerebellar stimulation resulted in some alterations in test performance. Improvements occurred from first to second test administration for both stimulated and nonstimulated subjects, as a probable practice effect. Short term stimulation of the cerebellar cortex does not result in apparent deficits. However, significant improvement in verbal output and in visual-motor performance occurred for the stimulated epilepsy group along with a small decrement in sustained concentration in a numerical task. Preliminary hypotheses were offered to explain the results.

Production of basal ganglia lesions by chemopallidectomy.

DURING THE DEVELOPMENT of the technic of chemopallidectomy for the relief of tremor and rigidity of parkinsonism, it has become evident that not only must one be accurate in the placement of the intracerebral lesion either in the globus pallidus or ventrolateral nucleus of the thalamus, but also one must produce a large circumscribed well-localized lesion in either or both of these areas. Our own attempts with electrocoagulation, radio frequency coagulation, and incisional lesions failed to produce an area of destruction of sufficient size to completely relieve contralateral tremor and rigidity. On the other hand, the use of absolute alcohol by the technic which we have developed will produce in all cases in which it is properly followed a circumscribed, completely localized lesion of whatever size the surgeon wishes to make. Only in this way have we been able to develop a technic by which the lesion could be tailored to the needs of the individual patient. Very early during the development of this technic it became obvious to us that one technical difficulty to overcome was the possibility of reflux of the neurolytic agent along the needle tract. By staining alcohol with Pantopaque, we have been able to follow the lesion roentgenographically, and it was proved in some of our early cases that reffw did occur occasionally along the needle tract. For that reason a special cannula with a double lumen was developed. One of the lumina leads to a small inflatable balloon at the end of the cannula, while the other lumen is used for injection directly into the brain.