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Pain of Cerebral Origin
Pain of Cerebral Origin MOIlI~IS I~.
BENDEI1, 1VI:.D.,
ROB~ER,T
:F.A.(~.P.*
JAFFE, M.D.**
IN 'rHE practice of medicine pain as a symptom, if not psychogenic, is usually due to a localized disease process. In these cases the pain is localized to the particular region of the body. 11'or example, if there is pain in a shoulder or in a wrist the physician seeks the cause in the area of complaint. Rarely does one suspect pain in an extremity to be of cerebral origin. 'I'he usual approach is to examine the involved extremity. If there is pain and resistance on movement at the shoulder joint, a local arthritic process is considered. Other symptoms may be more characteristic of periarthritis or bursitis. More thorough searches may be made to exclude gout, neoplasia or some other systemic condition \vhich will produce pain in a shoulder. A similar situation may arise \vith pain in a \vrist, hand, or in a forearm, or, for that matter, in a lower extremity. In these cases there may be no physical signs and, if the various x-rays and special laboratory tests prove to be negative, the physician may stop investigation and entertain a psychogenic basis for pain. Even \vhen a neurogenic site is suspected, the lesion is usually localized to a spinal root or a peripheral nerve. Occasionally the pain may be suspected to originate in the spinal cord, but a cerebral basis for pain is rarely considered. As neurologists ,ve like to emphasize that \ve often see patients with pain due to direct involvement of cerebrum. A ,videI' a\vareness of this syndrome will lead physicians to recognize many more such cases. GENERAL ANATOMIC CONSIDERATIONS l~ain may be produced by lesions at any level of the nervous system. In general the pain in these cases is associated with some degree of
From the Department of Neurology of The Mount Sina?: Hospital and New York University-Bellevue Medical Center, New York, N. Y.
* Professor of Clinical Neurology, New York [Jniversity-Bellevue Medical Cenier; Dtrector, Neurologic Service, 'The Mount Sinai H osp'£tal, and of Neurologic Service (Ill Div'ision), Bellevue Hospital. ** Clinical Assistant in Neurology, New York fJniversity-Bellevue Medical Center)· Assistant Attending Neurologist, The Mount Sinai Hospital. 691
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Morris B. Bender, Robert Jaffe
impairment of sensation. The pain is usually described as having a Htingling" or "burning" quality, tends to involve a large area rather than being sharply localized, and often occurs ,vith a dysesthetic hypersensitivity to contact stimulation. These sensory characteristics may appear to be bilateral in peripheral neuropathy, polyradiculopathy and myelopathy. There are cases, however, in which the pain is well localized, such as occurs in irritation of a single spinal root, or the pain in the neuralgias such as tic douloureux. Pain due to involvement of the cerebral hemispheres may show the characteristics of a spinal root irritation but differs in many important respects. Cerebral pain is almost always unilateral, affecting the side opposite the cerebral lesion. Sometimes only one limb, part of a limb, or even the side of the head or trunk may be involved. More frequently the upper as well as the lower limbs and even the face, all on the same side, may be affected. There is spontaneous pain of a particularly unpleasant, dysesthetic, anxiety-producing type. Although marked overreactivity to all forms of tactile stimuli may be present, there are cases in which dysesthesia is absent. Defects in sensation, when present, may be quite severe, with prominent involvement of proprioception but relative preservation of appreciation of vibration. Thresholds to touch and pin prick may be distinctly elevated and tend to fluctuate. This circumstance leads to the paradoxical coexistence of decreased sensitivity and hyperreactivity, since any stimulus of above-threshold intensity causes far more discomfort than equivalent stimulus applied to the unaffected half of the body. These patients often have an associated weakness of the hemiparetic type and may show some ataxia and involuntary movements in the implicated extremities. Homonymous hemianopia may be present. The pattern of signs and symptoms just described conforms to the classical "thalamic syndrome" first reported in detail by Dejerine and Roussyl and by Head and Holmes. 2 Hovvever, quite similar syndromes of pain have been observed with lesions situated anywhere along the entire sensory pathways as high as the parietal lobe itself. 3 , 4 In general, parietal lobe lesions are more likely to cause symptoms limited to a single extremity and tend to cause a more severe and complex pattern of sensory impairment in the distal portions of the limb. Another and less common form of pain syndrome seen with lesions in the cerebral hemisphere is that analogous to painful phantom limb. 5 Just as the amputation of an extremity may lead to the perception of a painful illusory substitute, so may the functional denervation of a limb by severe plexus injury produce the same kind of pain. In rare cases of cerebral disease with severe sensory loss and concomitant disturbance in "body image," the patient may be aware of a substitute extremity which may be quite painful and may have uncomfortable and
Pain of Cerebral Origin
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disturbing involuntary movements. When pain occurs concomitantly with presence of other neurological signs and symptoms, it is not too difficult to recognize the cerebral basis. Pain may also be a prominent manifestation of irritative cerebral lesions without there being neurologic signs. 6 , 7 This symptom is often confusing because it may be similar to somatic pain, and may in some cases be diagnosed as being due to local disease in bone, joint or nerve root. 'rhis is the type of pain which is often not recognized as being of cerebral origin. It may appear as an aura preceding a convulsive seizure or may be the only indication of the presence of an irritative focus. In some cases the pain may be due to excessive muscle contraction but it has been shown to occur under circumstances and in locations where this factor could not have been operating. The pain may be intermittent or even continuous and sho"v none of the paroxysmal qualities which are, in general, characteristic of irritative cerebral lesions. In considering the subject of sensory discomfort due to cerebral lesions, one must bear in mind the quite common incidence of pain as a secondary symptom of such lesions. Any lesion causing significant impairment of motor functions may be associated with pain. Paresis of the limbs, particularly in the absence of adequate physiotherapy, may cause the appearance of "frozen" joints, contracture of muscles and tendons, or mechanical compression of nerve roots and blood vessels. All of these conditions may result in pain on active or passive movements, and even pain at rest. ILLUSTRATIVE CASE HISTORIES
The following case histories, which are part of a larger series, serve to illustrate how cerebral lesions may be accompanied by contralateral pain and in some instances by arthropathy. * CASE I (R.G.). The patient was a 67 year old woman who was admitted to The Mount Sinai Hospital in May 1957 with the chief complaint of pain in the left leg. The illness began in 1942 with jerking of the left arnl. The incidence of these focal motor seizures increased, and in 1949, following a ventriculogram, a large parasagittal meningioma was removed. The tumor was in the right parietal region but involved and occluded the sagittal sinus, and spread to the left of the midline. After craniotomy there was a complete left hemiplegia which lessened in intensity \vithin 3 months. When she was able to stand with a brace and walk, there developed "gnawing pain" in the left groin. This persistent gnawing later spread to involve the entire left lower extremity. Although the patient conlplained of pain at rest, her major disability was in walking, caused by marked increase in severity of pain. She was also unable to sit comfortably because of severe discomfort when there was pressure on the left buttock and thigh. There was no pain in the left upper extremity when at rest but any amount of pressure
* The problem of arthropathy, edema or vasomotor changes in limbs opposite to a cerebral lesion is not considered in this communication.
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over that extremity caused the disagreeable sensation. There had been no seizures during the past few years until November 1956, when she frequently ,vas awakened from sleep by sudden sharp pain in the left foot and tibial region, associated with brief jerking of the foot and leg. She complained of a constant feeling of "pain and movement under the skin" of the left foot. Neurological examination revealed weakness of both lower extremities, especially the left. The patient was barely able to walk. There was pronounced hyperextension at the left knee joint, dysdiadokokinesis in the left upper extremity, left hyperreflexia and Babinski sign. The sensory status disclosed occasional errors in perception of position sense in the left toes, increased two-point threshold in the left hand, defective sensation for pin prick and touch in a small area on the dorsum of the left foot over the first and second metatarsals and first and second toes. Vibration appreciation, graphesthesia, stereognosis and adaptation were normal. There was severe pain whenever light or firm touch stimulation was applied to the left foot, especially in the region of the great toe. The patient also had pain on firm compression of the left calf, thigh, arm and forearm. X-rays revealed the presence of a right parasagittal parietal bone flap with the defect crossing the midline to the left side. X-rays of the spine showed considerable hypertrophic changes. X-rays of the left foot disclosed generalized soft tissue swelling and some narrowing and osteoporosis of the bones of the foot. Electroencephalograms were minimally abnormal with some slowing in both parietal regions. The patient remained in the hospital for 7 weeks during which time progressively active physiotherapy was carried out. With the addition of analgesic and tranquilizing medication she left the hospital and was able to walk ,vithout a cane. At the time of discharge she no longer complained of spontaneous pain and was able to tolerate pressure on the foot \vith relatively slight discomfort.
Comment. The fact that the pain was localized to the left-sided extremities indicates that the sensory symptoms were of cerebral origin. The accentuation of the symptonls in the lo\ver extremity was consistent with the locus of the original lesion, namely the parasagittal or foot area. It is doubtful whether the extensive vertebral arthropathy could account for the pain syndrome. This is an example of pain of cerebral origin lasting over eight years. The treatment of this has been difficult, and she had previously been hospitalized many times during the eight year period. The fact that the patient improved with physiotherapy and tranquilizers, while encouraging, does not prove that the lessening of the pain will be permanent or even long-lasting. CASE 11 (M.T.). A 45 year old woman was admitted to The Mount Sinai Hospital in July 1953 with a chief complaint of "pain and spasms of the right arm." In July 1952, she first experienced a sudden onset of a "heavy sensation" followed by a feeling of "pins and needles" in the right arm. These paresthesias, which lasted 5 minutes, spread up into the right side of the face and to the right side of the trunk. During the next 2 months she had 2 similar sensory episodes. The third such attack, however, was accompanied by jerking movements of the right arm, followed by a temporary weakness of the right arm. During the next 6 months she had frequent spells involving the right upper extremity. Since April 1953, there developed considerable pain in the right shoulder and arm.
695 On neurologic examination there was moderate weakness and clumsiness in all movements of the right upper extremity and concomitant hyperreflexia. Sensation was intact. An electroencephalogram showed focal delta bursts in the left temporal lobe. A left carotid angiogram disclosed a vascular "stain" in the left Rolandic area. At operation a meningioma ,vas found on the surface, but most of its bulk ,vas removed froln the left 110landic fissure. Following operation there ,vaR a slight increase in the :unount of weakness in the right upper extrenlity. For a while the patient continued to have sensory but no motor seizures. Within 48 hours after the operation the patient noted a decrease in the pain in her right upper extremity and several days later she had almost full range of motion without pain.
Comment. The fact that the patient had motor seizures indicated that the pains and other paresthesias in the right upper limb were of cerebral or,igin. However, during the early course of the illness there were no motor seizures and the pains were considered to be arthritic in nature. l"'his despite the fact that the paresthesias extended up into the ipsilateral face and trunk. Removal of the left-sided tumor caused a disappearance of the pain. A two year follow-up revealed that there was no recurrence. CAS}] III (M.H.) A 54 year old housewife was admitted to The Mount Sinai Hospital in November 1955 with a chief complaint of pain in the arm. In ,July 1955, she had a shaking spell involving the right extremities. She had several such episodes which were follo,ved by right-sided weakness. Since then there was slow improvement. However, in April 1955 there appeared progressive and severe pain in the right arm, shoulder, elbow and, to a lesser extent, in the right hand and fingers. These symptoms were classified as being arthritic. On neurological examination there was a minimal right hemiparesis, with greater weakness and hyperreflexia in the upper extremity. Sensation was intact. There was no hyperesthesia and no pressure tenderness of the skin or muscles. The outstanding features were the patient's complaints of pain and limitation of motion at the right shoulder, elbow, wrist and fingers. An electroencephalogram showed a minimal abnormality, with diffuse left-sided low voltage delta bursts. A pneumoencephalogram disclosed depression and displacement of the left lateral and third ventricles, suggesting a space-occupying mass in the left frontopal:ietal region. At operation a left frontoparietal parasagittal meningioma \vas relnoved through a transcortical incision in the precentral gyrus. I~"ollowing the operation the patient developed a cOlnplete right hemiplegia, without iInpail'ment of sensation. The patient continued to complain of pain, particularly on passive movement of the right upper extremity. In time she improved so that she was able to walk but still had severe weakness in the right upper and lower extremities. The pain had diminished but she still required simple analgesics.
Comment. '1"'his is still another example of pain of cerebral origin. Here again this syndrome was not recognized until she was examined by a neurologist. The pain and limitation of movement at most of the joints in the right upper extremity \vere misleading but the clue was in the
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Morris B. Bender, Roberl J affe
history, namely the motor seizures and \veakness of the extremity. Sometimes the confusion lies in the fact that many patients with hemiparesis develop "arthropathy," and it is even possible that the so-called pain due to arthropathy is partly due to cerebral lesion. Not all arthropathies are necessarily painful. We have observed patients who have nonpainful arthropathy localized to an extremity on the side opposite to a cerebral lesion. A number of patients with unilateral cerebral disease and contralateral bone and joint involvement (disproportionate to the degree of hemiparesis) have been seen. The possibility of a direct pathogenetic influence is being investigated. CASE IV (E.F.). The patient was a 72 year old woman who was admitted to The Mount Sinai Hospital in February 1957. She complained of "numbness" of the left side and recent fainting spells. Her illness had begun several weeks earlier, with pain in the left side of the face, then "pins and needles" sensation in the left arm and leg and the left side of the trunk. These paresthesias had persisted but were less worrisome to her than the episodes of loss of consciousness. General physical examination revealed the presence of several large ecchymoses. The neurological examination was negative. A pneumoencephalogram and right carotid arteriogram were normal. The white blood cell counts were consistently below 2500, platelets were consistently below 25,000. Bone marrow studies were not diagnostic. During her hospital stay she was found to have a marked postural hypotension. She complained more and more strongly of the pain in the left side of her body. On one occasion she was observed while having a generalized seizure which started in the left upper limb. The patient was discharged and readmitted in June 1957 in a state of agitation and depression, complaining bitterly of pain on the left side of the body. The blood dyscrasia was unchanged and still undiagnosed. Following transfusions with platelet-rich blood, she was given three electroshock treatments and experienced transient relief of pain.
Comment. This patient was extremely anxious and depressed. The absence of positive neurologic findings and the negative laboratory studies might well have led to an exclusion diagnosis of psychogenic pain. The only specific finding which clearly pointed to an organic basis for her complaints was the carefully described convulsive seizure with focal onset involving the left extremities. 'I~his ease illustrates the possible difficulties which may be encountered in differential diagnosis, and the extreme importance of careful, detailed history and clinical observations. A single finding may, as in this case, be sufficient to establish the diagnosis of pain of cerebral origin. We have observed similar cases in which the patient was depressed and agitated, complaining of great pain on onehalf of the body. One of these was considered to be severely neurotic despite a history of a "stroke." Of significance is that these patients do not necessarily have sensory disturbances, such as dysesthesia which occurs in the thalamic syndrome.
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CASE V (S.A.). The patient was a 45 year old woman who was admitted to The Mount Sinai Hospital in September 1957. She had been well until 1955 when there developed headache, followed by left-sided motor and sensory defects. Subsequently an "encapsulated convexity meningioma" was removed from the right temporal-parietal area. Postoperatively there was improvement in almost all respects, but she continued to have minimal, sensory defects. Early in 1957, she began to have episodes of extremely unpleasant, painful, tingling, pins and needles sensation, starting in the left hand and spreading to the arm, shoulder, throat, tongue and face. At other times she complained of severe pain and showed marked emotional response to her left-sided sensory symptoms. The neurological examination showed minimal weakness of the left upper extremity and slight hypalgesia, hypesthesia and defects in position sense on the left side.
Comment. This case illustrates the problems which may arise in interpreting the history and complaints. The quality of severe Jacksonian sensory seizures is such as to make the borderline between pain and unpleasant paresthesias very difficult to establish. Different patients, or even the same patient at different times (as above), may describe the symptoms as more or less painful. Another feature was that the pain and discomfort appeared some time after the operation. Postoperative pain in affected extremities has been observed in several other cases. Thus \ve have seen patients with pain of cerebral origin relieved by operation while in others it followed the removal of diseased tissue. VI (1.0.). The patient was a 47 year old woman who was first admitted to the Bellevue Hospital in October 1953. At that time she complained of constant, severe, "pulling" pain in the left lower extremity, most marked proximally, with a less severe degree of pain of similar quality in the left upper extremity. She was unable to stand or walk, since any firm contact or pressure on the left foot caused severe pain. The symptoms began in November 1950 when she experienced a sudden severe paresthesia involving the dorsal aspect of the left foot and toes, followed by clonic movements spreading from the left foot to involve both left extremities. Following the left-sided clonic seizure she became unconscious for one or two minutes. After several similar episodes an exploratory craniotomy was performed. No tumor ,vas found but the surgeon described the presence of "one small microgyrus in the postcentral area corresponding to the representation of the arm or fingers." Her recovery from the operation was uneventful and for several months her only complaint was a constant mild tingling of the left foot. The left-sided Jacksonian sensory and motor seizures recurred, however, and as time passed she suffered increasingly severe "pulling, twisting pain" in the left foot and leg. The foot became more and more sensitive to touch and pressure, so that ultimately she ,vas able to move ahout in her house only by resting her knee on a chair. In February 1953, she was admitted to a private mental hospital. In view of her marked agitation, the absence of objective neurologic signs and the history of a "negative" exploratory craniotomy, a diagnosis of conversion hysteria was made. She received 9 electroshock treatments, became significantly less agitated and depressed but was relieved of the painful paresthesias for only a few days. CASE
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Morr/is B. Bender, Robert Jaifc
Her pain and disability gradually recurred and, follo\ving a fairly severe generalized convulsion, she was admitted to Bellevue Hospital. On examination there were no objective neurologic findings. She was extremely tense and fearful. She resisted any contact or pressure of the left foot and leg. When examined under fairly heavy barbiturate sedation, however, she was found to have normal strength and tendon reflexes in the affected limb. The electroencephalogram showed mild diffuse slowing, without unequivocal focal accentuation. A pneumoencephalogram and a right carotid arteriogram were normal. Procaine block of the lumbar sympathetic ganglia did not relieve the pain. Left popliteal and left sciatic nerve blocks \vere also ineffective. Spinal anesthesia \vith 100 mg. of procaine, however, did bring about a complete relief of symptoms. After nurnerous studies and a period of observation, it was decided to reexplore the right side of the brain in January 1954. With the patient under local anesthesia, stimulation of the exposed cortex was carried out and it was found that the patient's characteristic symptoms could be elicited by such stirnulation. A portion of the postcentral gyrus was resected with the hope it would relieve the pain. Following the operation the patient had a mild left hemiparesis, \vith disturbance in position sense, two-point discrimination and stereognosis. She complained of "electric-like" sensations in the left limbs, evoked by cutaneous stimulation but not present spontaneously. The "pulling and twisting" sensations no longer existed. She remained in the hospital and by March 1954 the hemiparesis and sensory defects had largely cleared. However, the spontaneous pain had recurred, almost in its original intensity.
Comment. This case illustrates quite .clearly how severe and disabling the pain and dysesthesia of cerebral origin may be. The lesion, presumably mainly involving the cortex, was not sufficiently large to cause objectively demonstrable neurologic defects. In this extremely agitated and depressed patient, the characteristically organic Jacksonian features were so masked that a diagnosis of conversion hysteria was made. This type of misjudgment may easily be made in dealing with patients suffering from continuous and unbearable pain of cerebral origin. The quality of the pain often evokes bizarre descriptions by the patient and the patients usually show depression and emotional instability. Some patients describe the sensation as a pulling, uncomfortable feeling and use the word pain only on occasions. When they feel less depressed, the pulling and discomfort disappear. It may, indeed, be the case that personality factors are important in determining whether certain patients will, or will not, develop pain in the presence of parietal lobe or thalamic lesions. The data so far accumulated, however, are insufficient to answer this question. This patient also illustrates the difficulty in eradicating the symptoms. Nonspecific measures, such as electroconvulsive therapy, caused only transient improvement. Only slightly better results \vere obtained by cortical excision. The only absolute relief obtained was \vith spinal anesthesia. rrhis effect is difficult to interpret. It has been reported, however, in a somewhat similar case by A. E. Walker. 3 In some patients with excised brain tumor, the pain, pulling or disagreeable sensory
699 Hyrnptoms localized to an extremity or Hide of the body may disappear only following electroshock therapy. As the depression subsides, the sensory symptoms become less disagreeable. DISCUSSION
Although fairly \vell documented cases of pain of cerebral origin have been reported sporadically in the neurological literature for many years, surprisingly little attention has been paid to this phenomenon. Most standard textbooks of neurology do not even mention it, except for the usual description of the "thalamic syndrome." Nevertheless, with a certain degree of sensitivity to the existence of central pain, such cases may readily be seen on any busy neurology service. If the examiner does not allow himself to be distracted by the presence of gross findings, such as.hemiplegia or arthropathy, and if he refrains from too rapid rationalization, reassurance and medication of the patient's complaints of pain, he will find the pain to be of cerebral origin in a surprising number of cases. 'fhe same plea for increased sensitivity to this syndrome may be made in the case of patients \vhose preesnting or chief complaint is of pain. A\vareness of the possibility that the pain may be due to direct involvement of the central nervous system \villlead to increased attention to the details of history and physical examination \vhich might reveal accessory evidence of such involvement. We have presented several of the many cases in our series illustrating the diagnostic problems and possibilities which arise when pain is a prominent complaint in patients with cerebral lesions. This is particularly true of patients \vho have a concomitant depression. }1-'or, as the depression deepens, the disagreeable sensation becomes more unbearable. Conversely, when the depression lifts, the pain is less manifest. Patients with pain due to cerebral lesions offer valuable opportunities for research in the central mechanisms of pain perception. Since the quality of pain is so highly subjective and difficult to define, even by the most intelligent human subject, one can readily see the limitations set for experimentation with animals. Much can be learned from the relatively simple process of careful clinical examination and correlation with operative or postmortem findings. 8 Little is known about the thalamocortical interrelationships involved, and histologic study of the brain in well-evaluated cases may lead to important conclusions. As an example of one of the problems which may be elucidated in this way; we may consider the "thalamic syndrome." Even before the syndrome was named by Dejerine and Rous~y, Gowers 9 described it and attributed it to "irritation" of the fibers in the "posterior extremity" of the internal capsule. Since that time the syndrome has been attributed by some to an irritative lesion of the thalamus; by others to the interruption of a corticofugal inhibiting pathway, with consequent hyperactivity of the
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"released" thalamus. 4 , 10, 11 This question is still unsettled, and other, still undiscovered factors may eventually be revealed as of primary significance. This problem, and other problems in the physiology and pathophysiology of pain may be profitably studied in the human by methods other than anatomical. Electrical stimulation of the exposed brain at operation,7 recording from the surface and with depth electrodes, and topical, systemic and intra-arterial application of various drugs in the conscious patient may all be used. Since pain is, in effect, an aspect of consciousness, it cannot be isolated from other aspects of consciousness, from mental function in general, including mood and affect. The emotional state of the individual influences the perception of all kinds of stimuli, but is particularly influential in the perception of pain. The relatively simple diagrammatic theories which may be invoked to interpret the peripheral anq spinal cord mechanisms of sensation cannot be reasonably applied in this case. Just as the entire brain is probably involved in all conscious processes, it is involved in the perception of pain. The "pain pathway," if it exists, may represent the spinothalamocortical input side of the perception of pain, but this input is undoubtedly modulated by, and feeds into, a very complex and dynamic mechanism-the mechanism which forms the total background of brain function. REFERENCES 1. Dejerine, J. and Roussy, A.: Le Syndrome Thalamique. Rev. Neurol. 14.: 521,
1906. 2. Read, H.: Studies in Neurology. London, Rodder & Stoughton, 1920, pp. 551569 and 597-609. 3. Walker, A. E.: Central Representation of Pain. A. Research Nerv. & Ment. Dis. 23: 63-85, 1943. 4. Critchley, M.: The Parietal Lobes. London, Edward Arnold & Co. 1953. 5. Lhermitte, J.: Les alga-hallucinoses, les hallucinations de la douleur. Chapter in La douleur et les douleurs, Alajouanine, T. (Ed.), Paris, Masson et cie. 1957, pp. 241-258. 6. Michelsen, J. J. : Subjective Disturbances of the Sense of Pain from Lesions of the Cerebral Cortex. A. Research Nerv. & Ment. Dis. 23: 86-99, 1943. 7. Penfield, W. and Kristiansen, K.: Epileptic Seizure Patterns. Springfield, Ill., C. C Thomas, 1951. 8. Biemond, A.: The Conduction of Pain Above the Level of the Thalamus Opticus. A.M.A. Arch. Neurol. & Psychiat. 75: 231-244, 1956. 9. Gowers, W. R.: Diseases of the Nervous System. London, J. & A. Churchill. 1893. 10. Garcin, R.: La douleur dans les affections du systeme nerveux central. Chapter in La douleur et les douleurs, Alajouanine, T. (Ed.), Paris, Masson et cie., 1957, pp. 199-213. 11. Davison, C. and Schick, W.: Spontaneous Pain and Other Subjective Sensory Disturbances. A. Res. Nerv. & Ment. Dis. 15: 457-496, 1935. Mount Sinai Hospital Fifth Avenue and 100th Street New York 29, N. Y.
BENDEI1, 1VI:.D.,
ROB~ER,T
:F.A.(~.P.*
JAFFE, M.D.**
IN 'rHE practice of medicine pain as a symptom, if not psychogenic, is usually due to a localized disease process. In these cases the pain is localized to the particular region of the body. 11'or example, if there is pain in a shoulder or in a wrist the physician seeks the cause in the area of complaint. Rarely does one suspect pain in an extremity to be of cerebral origin. 'I'he usual approach is to examine the involved extremity. If there is pain and resistance on movement at the shoulder joint, a local arthritic process is considered. Other symptoms may be more characteristic of periarthritis or bursitis. More thorough searches may be made to exclude gout, neoplasia or some other systemic condition \vhich will produce pain in a shoulder. A similar situation may arise \vith pain in a \vrist, hand, or in a forearm, or, for that matter, in a lower extremity. In these cases there may be no physical signs and, if the various x-rays and special laboratory tests prove to be negative, the physician may stop investigation and entertain a psychogenic basis for pain. Even \vhen a neurogenic site is suspected, the lesion is usually localized to a spinal root or a peripheral nerve. Occasionally the pain may be suspected to originate in the spinal cord, but a cerebral basis for pain is rarely considered. As neurologists ,ve like to emphasize that \ve often see patients with pain due to direct involvement of cerebrum. A ,videI' a\vareness of this syndrome will lead physicians to recognize many more such cases. GENERAL ANATOMIC CONSIDERATIONS l~ain may be produced by lesions at any level of the nervous system. In general the pain in these cases is associated with some degree of
From the Department of Neurology of The Mount Sina?: Hospital and New York University-Bellevue Medical Center, New York, N. Y.
* Professor of Clinical Neurology, New York [Jniversity-Bellevue Medical Cenier; Dtrector, Neurologic Service, 'The Mount Sinai H osp'£tal, and of Neurologic Service (Ill Div'ision), Bellevue Hospital. ** Clinical Assistant in Neurology, New York fJniversity-Bellevue Medical Center)· Assistant Attending Neurologist, The Mount Sinai Hospital. 691
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impairment of sensation. The pain is usually described as having a Htingling" or "burning" quality, tends to involve a large area rather than being sharply localized, and often occurs ,vith a dysesthetic hypersensitivity to contact stimulation. These sensory characteristics may appear to be bilateral in peripheral neuropathy, polyradiculopathy and myelopathy. There are cases, however, in which the pain is well localized, such as occurs in irritation of a single spinal root, or the pain in the neuralgias such as tic douloureux. Pain due to involvement of the cerebral hemispheres may show the characteristics of a spinal root irritation but differs in many important respects. Cerebral pain is almost always unilateral, affecting the side opposite the cerebral lesion. Sometimes only one limb, part of a limb, or even the side of the head or trunk may be involved. More frequently the upper as well as the lower limbs and even the face, all on the same side, may be affected. There is spontaneous pain of a particularly unpleasant, dysesthetic, anxiety-producing type. Although marked overreactivity to all forms of tactile stimuli may be present, there are cases in which dysesthesia is absent. Defects in sensation, when present, may be quite severe, with prominent involvement of proprioception but relative preservation of appreciation of vibration. Thresholds to touch and pin prick may be distinctly elevated and tend to fluctuate. This circumstance leads to the paradoxical coexistence of decreased sensitivity and hyperreactivity, since any stimulus of above-threshold intensity causes far more discomfort than equivalent stimulus applied to the unaffected half of the body. These patients often have an associated weakness of the hemiparetic type and may show some ataxia and involuntary movements in the implicated extremities. Homonymous hemianopia may be present. The pattern of signs and symptoms just described conforms to the classical "thalamic syndrome" first reported in detail by Dejerine and Roussyl and by Head and Holmes. 2 Hovvever, quite similar syndromes of pain have been observed with lesions situated anywhere along the entire sensory pathways as high as the parietal lobe itself. 3 , 4 In general, parietal lobe lesions are more likely to cause symptoms limited to a single extremity and tend to cause a more severe and complex pattern of sensory impairment in the distal portions of the limb. Another and less common form of pain syndrome seen with lesions in the cerebral hemisphere is that analogous to painful phantom limb. 5 Just as the amputation of an extremity may lead to the perception of a painful illusory substitute, so may the functional denervation of a limb by severe plexus injury produce the same kind of pain. In rare cases of cerebral disease with severe sensory loss and concomitant disturbance in "body image," the patient may be aware of a substitute extremity which may be quite painful and may have uncomfortable and
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disturbing involuntary movements. When pain occurs concomitantly with presence of other neurological signs and symptoms, it is not too difficult to recognize the cerebral basis. Pain may also be a prominent manifestation of irritative cerebral lesions without there being neurologic signs. 6 , 7 This symptom is often confusing because it may be similar to somatic pain, and may in some cases be diagnosed as being due to local disease in bone, joint or nerve root. 'rhis is the type of pain which is often not recognized as being of cerebral origin. It may appear as an aura preceding a convulsive seizure or may be the only indication of the presence of an irritative focus. In some cases the pain may be due to excessive muscle contraction but it has been shown to occur under circumstances and in locations where this factor could not have been operating. The pain may be intermittent or even continuous and sho"v none of the paroxysmal qualities which are, in general, characteristic of irritative cerebral lesions. In considering the subject of sensory discomfort due to cerebral lesions, one must bear in mind the quite common incidence of pain as a secondary symptom of such lesions. Any lesion causing significant impairment of motor functions may be associated with pain. Paresis of the limbs, particularly in the absence of adequate physiotherapy, may cause the appearance of "frozen" joints, contracture of muscles and tendons, or mechanical compression of nerve roots and blood vessels. All of these conditions may result in pain on active or passive movements, and even pain at rest. ILLUSTRATIVE CASE HISTORIES
The following case histories, which are part of a larger series, serve to illustrate how cerebral lesions may be accompanied by contralateral pain and in some instances by arthropathy. * CASE I (R.G.). The patient was a 67 year old woman who was admitted to The Mount Sinai Hospital in May 1957 with the chief complaint of pain in the left leg. The illness began in 1942 with jerking of the left arnl. The incidence of these focal motor seizures increased, and in 1949, following a ventriculogram, a large parasagittal meningioma was removed. The tumor was in the right parietal region but involved and occluded the sagittal sinus, and spread to the left of the midline. After craniotomy there was a complete left hemiplegia which lessened in intensity \vithin 3 months. When she was able to stand with a brace and walk, there developed "gnawing pain" in the left groin. This persistent gnawing later spread to involve the entire left lower extremity. Although the patient conlplained of pain at rest, her major disability was in walking, caused by marked increase in severity of pain. She was also unable to sit comfortably because of severe discomfort when there was pressure on the left buttock and thigh. There was no pain in the left upper extremity when at rest but any amount of pressure
* The problem of arthropathy, edema or vasomotor changes in limbs opposite to a cerebral lesion is not considered in this communication.
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over that extremity caused the disagreeable sensation. There had been no seizures during the past few years until November 1956, when she frequently ,vas awakened from sleep by sudden sharp pain in the left foot and tibial region, associated with brief jerking of the foot and leg. She complained of a constant feeling of "pain and movement under the skin" of the left foot. Neurological examination revealed weakness of both lower extremities, especially the left. The patient was barely able to walk. There was pronounced hyperextension at the left knee joint, dysdiadokokinesis in the left upper extremity, left hyperreflexia and Babinski sign. The sensory status disclosed occasional errors in perception of position sense in the left toes, increased two-point threshold in the left hand, defective sensation for pin prick and touch in a small area on the dorsum of the left foot over the first and second metatarsals and first and second toes. Vibration appreciation, graphesthesia, stereognosis and adaptation were normal. There was severe pain whenever light or firm touch stimulation was applied to the left foot, especially in the region of the great toe. The patient also had pain on firm compression of the left calf, thigh, arm and forearm. X-rays revealed the presence of a right parasagittal parietal bone flap with the defect crossing the midline to the left side. X-rays of the spine showed considerable hypertrophic changes. X-rays of the left foot disclosed generalized soft tissue swelling and some narrowing and osteoporosis of the bones of the foot. Electroencephalograms were minimally abnormal with some slowing in both parietal regions. The patient remained in the hospital for 7 weeks during which time progressively active physiotherapy was carried out. With the addition of analgesic and tranquilizing medication she left the hospital and was able to walk ,vithout a cane. At the time of discharge she no longer complained of spontaneous pain and was able to tolerate pressure on the foot \vith relatively slight discomfort.
Comment. The fact that the pain was localized to the left-sided extremities indicates that the sensory symptoms were of cerebral origin. The accentuation of the symptonls in the lo\ver extremity was consistent with the locus of the original lesion, namely the parasagittal or foot area. It is doubtful whether the extensive vertebral arthropathy could account for the pain syndrome. This is an example of pain of cerebral origin lasting over eight years. The treatment of this has been difficult, and she had previously been hospitalized many times during the eight year period. The fact that the patient improved with physiotherapy and tranquilizers, while encouraging, does not prove that the lessening of the pain will be permanent or even long-lasting. CASE 11 (M.T.). A 45 year old woman was admitted to The Mount Sinai Hospital in July 1953 with a chief complaint of "pain and spasms of the right arm." In July 1952, she first experienced a sudden onset of a "heavy sensation" followed by a feeling of "pins and needles" in the right arm. These paresthesias, which lasted 5 minutes, spread up into the right side of the face and to the right side of the trunk. During the next 2 months she had 2 similar sensory episodes. The third such attack, however, was accompanied by jerking movements of the right arm, followed by a temporary weakness of the right arm. During the next 6 months she had frequent spells involving the right upper extremity. Since April 1953, there developed considerable pain in the right shoulder and arm.
695 On neurologic examination there was moderate weakness and clumsiness in all movements of the right upper extremity and concomitant hyperreflexia. Sensation was intact. An electroencephalogram showed focal delta bursts in the left temporal lobe. A left carotid angiogram disclosed a vascular "stain" in the left Rolandic area. At operation a meningioma ,vas found on the surface, but most of its bulk ,vas removed froln the left 110landic fissure. Following operation there ,vaR a slight increase in the :unount of weakness in the right upper extrenlity. For a while the patient continued to have sensory but no motor seizures. Within 48 hours after the operation the patient noted a decrease in the pain in her right upper extremity and several days later she had almost full range of motion without pain.
Comment. The fact that the patient had motor seizures indicated that the pains and other paresthesias in the right upper limb were of cerebral or,igin. However, during the early course of the illness there were no motor seizures and the pains were considered to be arthritic in nature. l"'his despite the fact that the paresthesias extended up into the ipsilateral face and trunk. Removal of the left-sided tumor caused a disappearance of the pain. A two year follow-up revealed that there was no recurrence. CAS}] III (M.H.) A 54 year old housewife was admitted to The Mount Sinai Hospital in November 1955 with a chief complaint of pain in the arm. In ,July 1955, she had a shaking spell involving the right extremities. She had several such episodes which were follo,ved by right-sided weakness. Since then there was slow improvement. However, in April 1955 there appeared progressive and severe pain in the right arm, shoulder, elbow and, to a lesser extent, in the right hand and fingers. These symptoms were classified as being arthritic. On neurological examination there was a minimal right hemiparesis, with greater weakness and hyperreflexia in the upper extremity. Sensation was intact. There was no hyperesthesia and no pressure tenderness of the skin or muscles. The outstanding features were the patient's complaints of pain and limitation of motion at the right shoulder, elbow, wrist and fingers. An electroencephalogram showed a minimal abnormality, with diffuse left-sided low voltage delta bursts. A pneumoencephalogram disclosed depression and displacement of the left lateral and third ventricles, suggesting a space-occupying mass in the left frontopal:ietal region. At operation a left frontoparietal parasagittal meningioma \vas relnoved through a transcortical incision in the precentral gyrus. I~"ollowing the operation the patient developed a cOlnplete right hemiplegia, without iInpail'ment of sensation. The patient continued to complain of pain, particularly on passive movement of the right upper extremity. In time she improved so that she was able to walk but still had severe weakness in the right upper and lower extremities. The pain had diminished but she still required simple analgesics.
Comment. '1"'his is still another example of pain of cerebral origin. Here again this syndrome was not recognized until she was examined by a neurologist. The pain and limitation of movement at most of the joints in the right upper extremity \vere misleading but the clue was in the
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history, namely the motor seizures and \veakness of the extremity. Sometimes the confusion lies in the fact that many patients with hemiparesis develop "arthropathy," and it is even possible that the so-called pain due to arthropathy is partly due to cerebral lesion. Not all arthropathies are necessarily painful. We have observed patients who have nonpainful arthropathy localized to an extremity on the side opposite to a cerebral lesion. A number of patients with unilateral cerebral disease and contralateral bone and joint involvement (disproportionate to the degree of hemiparesis) have been seen. The possibility of a direct pathogenetic influence is being investigated. CASE IV (E.F.). The patient was a 72 year old woman who was admitted to The Mount Sinai Hospital in February 1957. She complained of "numbness" of the left side and recent fainting spells. Her illness had begun several weeks earlier, with pain in the left side of the face, then "pins and needles" sensation in the left arm and leg and the left side of the trunk. These paresthesias had persisted but were less worrisome to her than the episodes of loss of consciousness. General physical examination revealed the presence of several large ecchymoses. The neurological examination was negative. A pneumoencephalogram and right carotid arteriogram were normal. The white blood cell counts were consistently below 2500, platelets were consistently below 25,000. Bone marrow studies were not diagnostic. During her hospital stay she was found to have a marked postural hypotension. She complained more and more strongly of the pain in the left side of her body. On one occasion she was observed while having a generalized seizure which started in the left upper limb. The patient was discharged and readmitted in June 1957 in a state of agitation and depression, complaining bitterly of pain on the left side of the body. The blood dyscrasia was unchanged and still undiagnosed. Following transfusions with platelet-rich blood, she was given three electroshock treatments and experienced transient relief of pain.
Comment. This patient was extremely anxious and depressed. The absence of positive neurologic findings and the negative laboratory studies might well have led to an exclusion diagnosis of psychogenic pain. The only specific finding which clearly pointed to an organic basis for her complaints was the carefully described convulsive seizure with focal onset involving the left extremities. 'I~his ease illustrates the possible difficulties which may be encountered in differential diagnosis, and the extreme importance of careful, detailed history and clinical observations. A single finding may, as in this case, be sufficient to establish the diagnosis of pain of cerebral origin. We have observed similar cases in which the patient was depressed and agitated, complaining of great pain on onehalf of the body. One of these was considered to be severely neurotic despite a history of a "stroke." Of significance is that these patients do not necessarily have sensory disturbances, such as dysesthesia which occurs in the thalamic syndrome.
Pain of Cerebral Origin
697
CASE V (S.A.). The patient was a 45 year old woman who was admitted to The Mount Sinai Hospital in September 1957. She had been well until 1955 when there developed headache, followed by left-sided motor and sensory defects. Subsequently an "encapsulated convexity meningioma" was removed from the right temporal-parietal area. Postoperatively there was improvement in almost all respects, but she continued to have minimal, sensory defects. Early in 1957, she began to have episodes of extremely unpleasant, painful, tingling, pins and needles sensation, starting in the left hand and spreading to the arm, shoulder, throat, tongue and face. At other times she complained of severe pain and showed marked emotional response to her left-sided sensory symptoms. The neurological examination showed minimal weakness of the left upper extremity and slight hypalgesia, hypesthesia and defects in position sense on the left side.
Comment. This case illustrates the problems which may arise in interpreting the history and complaints. The quality of severe Jacksonian sensory seizures is such as to make the borderline between pain and unpleasant paresthesias very difficult to establish. Different patients, or even the same patient at different times (as above), may describe the symptoms as more or less painful. Another feature was that the pain and discomfort appeared some time after the operation. Postoperative pain in affected extremities has been observed in several other cases. Thus \ve have seen patients with pain of cerebral origin relieved by operation while in others it followed the removal of diseased tissue. VI (1.0.). The patient was a 47 year old woman who was first admitted to the Bellevue Hospital in October 1953. At that time she complained of constant, severe, "pulling" pain in the left lower extremity, most marked proximally, with a less severe degree of pain of similar quality in the left upper extremity. She was unable to stand or walk, since any firm contact or pressure on the left foot caused severe pain. The symptoms began in November 1950 when she experienced a sudden severe paresthesia involving the dorsal aspect of the left foot and toes, followed by clonic movements spreading from the left foot to involve both left extremities. Following the left-sided clonic seizure she became unconscious for one or two minutes. After several similar episodes an exploratory craniotomy was performed. No tumor ,vas found but the surgeon described the presence of "one small microgyrus in the postcentral area corresponding to the representation of the arm or fingers." Her recovery from the operation was uneventful and for several months her only complaint was a constant mild tingling of the left foot. The left-sided Jacksonian sensory and motor seizures recurred, however, and as time passed she suffered increasingly severe "pulling, twisting pain" in the left foot and leg. The foot became more and more sensitive to touch and pressure, so that ultimately she ,vas able to move ahout in her house only by resting her knee on a chair. In February 1953, she was admitted to a private mental hospital. In view of her marked agitation, the absence of objective neurologic signs and the history of a "negative" exploratory craniotomy, a diagnosis of conversion hysteria was made. She received 9 electroshock treatments, became significantly less agitated and depressed but was relieved of the painful paresthesias for only a few days. CASE
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Her pain and disability gradually recurred and, follo\ving a fairly severe generalized convulsion, she was admitted to Bellevue Hospital. On examination there were no objective neurologic findings. She was extremely tense and fearful. She resisted any contact or pressure of the left foot and leg. When examined under fairly heavy barbiturate sedation, however, she was found to have normal strength and tendon reflexes in the affected limb. The electroencephalogram showed mild diffuse slowing, without unequivocal focal accentuation. A pneumoencephalogram and a right carotid arteriogram were normal. Procaine block of the lumbar sympathetic ganglia did not relieve the pain. Left popliteal and left sciatic nerve blocks \vere also ineffective. Spinal anesthesia \vith 100 mg. of procaine, however, did bring about a complete relief of symptoms. After nurnerous studies and a period of observation, it was decided to reexplore the right side of the brain in January 1954. With the patient under local anesthesia, stimulation of the exposed cortex was carried out and it was found that the patient's characteristic symptoms could be elicited by such stirnulation. A portion of the postcentral gyrus was resected with the hope it would relieve the pain. Following the operation the patient had a mild left hemiparesis, \vith disturbance in position sense, two-point discrimination and stereognosis. She complained of "electric-like" sensations in the left limbs, evoked by cutaneous stimulation but not present spontaneously. The "pulling and twisting" sensations no longer existed. She remained in the hospital and by March 1954 the hemiparesis and sensory defects had largely cleared. However, the spontaneous pain had recurred, almost in its original intensity.
Comment. This case illustrates quite .clearly how severe and disabling the pain and dysesthesia of cerebral origin may be. The lesion, presumably mainly involving the cortex, was not sufficiently large to cause objectively demonstrable neurologic defects. In this extremely agitated and depressed patient, the characteristically organic Jacksonian features were so masked that a diagnosis of conversion hysteria was made. This type of misjudgment may easily be made in dealing with patients suffering from continuous and unbearable pain of cerebral origin. The quality of the pain often evokes bizarre descriptions by the patient and the patients usually show depression and emotional instability. Some patients describe the sensation as a pulling, uncomfortable feeling and use the word pain only on occasions. When they feel less depressed, the pulling and discomfort disappear. It may, indeed, be the case that personality factors are important in determining whether certain patients will, or will not, develop pain in the presence of parietal lobe or thalamic lesions. The data so far accumulated, however, are insufficient to answer this question. This patient also illustrates the difficulty in eradicating the symptoms. Nonspecific measures, such as electroconvulsive therapy, caused only transient improvement. Only slightly better results \vere obtained by cortical excision. The only absolute relief obtained was \vith spinal anesthesia. rrhis effect is difficult to interpret. It has been reported, however, in a somewhat similar case by A. E. Walker. 3 In some patients with excised brain tumor, the pain, pulling or disagreeable sensory
699 Hyrnptoms localized to an extremity or Hide of the body may disappear only following electroshock therapy. As the depression subsides, the sensory symptoms become less disagreeable. DISCUSSION
Although fairly \vell documented cases of pain of cerebral origin have been reported sporadically in the neurological literature for many years, surprisingly little attention has been paid to this phenomenon. Most standard textbooks of neurology do not even mention it, except for the usual description of the "thalamic syndrome." Nevertheless, with a certain degree of sensitivity to the existence of central pain, such cases may readily be seen on any busy neurology service. If the examiner does not allow himself to be distracted by the presence of gross findings, such as.hemiplegia or arthropathy, and if he refrains from too rapid rationalization, reassurance and medication of the patient's complaints of pain, he will find the pain to be of cerebral origin in a surprising number of cases. 'fhe same plea for increased sensitivity to this syndrome may be made in the case of patients \vhose preesnting or chief complaint is of pain. A\vareness of the possibility that the pain may be due to direct involvement of the central nervous system \villlead to increased attention to the details of history and physical examination \vhich might reveal accessory evidence of such involvement. We have presented several of the many cases in our series illustrating the diagnostic problems and possibilities which arise when pain is a prominent complaint in patients with cerebral lesions. This is particularly true of patients \vho have a concomitant depression. }1-'or, as the depression deepens, the disagreeable sensation becomes more unbearable. Conversely, when the depression lifts, the pain is less manifest. Patients with pain due to cerebral lesions offer valuable opportunities for research in the central mechanisms of pain perception. Since the quality of pain is so highly subjective and difficult to define, even by the most intelligent human subject, one can readily see the limitations set for experimentation with animals. Much can be learned from the relatively simple process of careful clinical examination and correlation with operative or postmortem findings. 8 Little is known about the thalamocortical interrelationships involved, and histologic study of the brain in well-evaluated cases may lead to important conclusions. As an example of one of the problems which may be elucidated in this way; we may consider the "thalamic syndrome." Even before the syndrome was named by Dejerine and Rous~y, Gowers 9 described it and attributed it to "irritation" of the fibers in the "posterior extremity" of the internal capsule. Since that time the syndrome has been attributed by some to an irritative lesion of the thalamus; by others to the interruption of a corticofugal inhibiting pathway, with consequent hyperactivity of the
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"released" thalamus. 4 , 10, 11 This question is still unsettled, and other, still undiscovered factors may eventually be revealed as of primary significance. This problem, and other problems in the physiology and pathophysiology of pain may be profitably studied in the human by methods other than anatomical. Electrical stimulation of the exposed brain at operation,7 recording from the surface and with depth electrodes, and topical, systemic and intra-arterial application of various drugs in the conscious patient may all be used. Since pain is, in effect, an aspect of consciousness, it cannot be isolated from other aspects of consciousness, from mental function in general, including mood and affect. The emotional state of the individual influences the perception of all kinds of stimuli, but is particularly influential in the perception of pain. The relatively simple diagrammatic theories which may be invoked to interpret the peripheral anq spinal cord mechanisms of sensation cannot be reasonably applied in this case. Just as the entire brain is probably involved in all conscious processes, it is involved in the perception of pain. The "pain pathway," if it exists, may represent the spinothalamocortical input side of the perception of pain, but this input is undoubtedly modulated by, and feeds into, a very complex and dynamic mechanism-the mechanism which forms the total background of brain function. REFERENCES 1. Dejerine, J. and Roussy, A.: Le Syndrome Thalamique. Rev. Neurol. 14.: 521,
1906. 2. Read, H.: Studies in Neurology. London, Rodder & Stoughton, 1920, pp. 551569 and 597-609. 3. Walker, A. E.: Central Representation of Pain. A. Research Nerv. & Ment. Dis. 23: 63-85, 1943. 4. Critchley, M.: The Parietal Lobes. London, Edward Arnold & Co. 1953. 5. Lhermitte, J.: Les alga-hallucinoses, les hallucinations de la douleur. Chapter in La douleur et les douleurs, Alajouanine, T. (Ed.), Paris, Masson et cie. 1957, pp. 241-258. 6. Michelsen, J. J. : Subjective Disturbances of the Sense of Pain from Lesions of the Cerebral Cortex. A. Research Nerv. & Ment. Dis. 23: 86-99, 1943. 7. Penfield, W. and Kristiansen, K.: Epileptic Seizure Patterns. Springfield, Ill., C. C Thomas, 1951. 8. Biemond, A.: The Conduction of Pain Above the Level of the Thalamus Opticus. A.M.A. Arch. Neurol. & Psychiat. 75: 231-244, 1956. 9. Gowers, W. R.: Diseases of the Nervous System. London, J. & A. Churchill. 1893. 10. Garcin, R.: La douleur dans les affections du systeme nerveux central. Chapter in La douleur et les douleurs, Alajouanine, T. (Ed.), Paris, Masson et cie., 1957, pp. 199-213. 11. Davison, C. and Schick, W.: Spontaneous Pain and Other Subjective Sensory Disturbances. A. Res. Nerv. & Ment. Dis. 15: 457-496, 1935. Mount Sinai Hospital Fifth Avenue and 100th Street New York 29, N. Y.