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The Lateral Medullary (Wallenberg) Syndrome: Clinical Features and Prognosis
The Lateral Medullary (Wallenberg) Syndrome: Clinical Features and Prognosis ALBERT F. PETERMAN, M.D. ROBERT G. SIEKERT, M.D.
THE constellation of signs and symptoms resulting from an infarct in the dorsolateral portion of the medulla oblongata has variously been named the Wallenberg syndrome, the lateral medullary syndrome, or the syndrome of occlusion of the posterior inferior cerebellar artery. The clinical features of this syndrome consist of the relatively sudden onset of vertigo, nausea, vomiting, dysphagia, hoarseness, staggering, and incoordination of the limbs on one side of the body. Headache, pain or numbness of one side of the face, paresthesia of the limbs on the opposite side and hiccup may be Boted by the patient. Examination reveals decrease or loss of pain and temperature sensations on one side of the face, decreased corneal reflex, Horner's syndrome, paresis or paralysis of the muscles of one side of the palate and larynx, weakness of the entire face (peripheral type) and incoordination of the limbs, all on the same side as the lesion. On the opposite side one notes decrease or loss of pain and temperature sensations. The gait is ataxic. Fine or coarse nystagmus may be seen on gaze to either side, but it occurs more often to the side of the lesion. Muscle stretch reflexes and muscular strength in the limbR and sensations of light touch, position and vibration are normal. These findings result from a lesion affecting the various structures in the dorsolateral portion of the medulla including nucleus and spinal tract of the trigeminal nerve (facial and corneal anesthesia), the spinothalamic tract (limb and body anesthesia), inferior cerebellar peduncle (gait and limb ataxia), vestibular nuclei (nausea, vomiting, nystagmus), descending sympathetic fibers (Horner's syndrome), nucleus ambiguus of the vagus nerve (palatal and laryngeal palsy) and intramedullary fibers of the facial nerve (facial weakness). The lesion varies in area and in density, and thus the abnormalities listed above will vary also. The lesion may involve the adjacent portion of the cerebellum. In most instances, how-
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ever, the clinical picture is distinctive. It has been stated that the immediate prognosis for life is good. After a few months, most patients note only minimal neurologic deficits. Wallenberg is generally credited with establishing the syndrome which now bears his name. In a carefully reasoned discussion he postulated the infarction and the vascular lesion as due to embolization in the posterior inferior cerebellar artery. He noted that other authors had published cases but that no one had drawn attention to the characteristic picture. Interestingly enough, many of the authors that Wallenberg quoted aR describing cases of occlusion of this artery actually described thrombosiR of the vertebral artery with or without additional thrombosis of the posterior inferior cerebellar artery. Hun and Spiller were the first Americans interested in this condition. The former described a case that was studied by van Gieson at necropsy but made no comment concerning the arteries. Spiller wrote on the symptom-complex of occlusion of the posterior inferior cerebellar artery and used two cases to document his thesis. One case disclosed thrombosis of the vertebral and the posterior cerebellar arteries; the other disclosed thrombosis of the basilar and vertebral arteries; the posterior inferior cerebellar artery in this case was filled with a few erythrocytes but did not show distinct thrombosis. Since then, scattered reports have served to document the existence and characteristic clinical features of this syndrome. Because the immediate outlook for life is good, anatomic controls are lacking in most instances. Despite this lack, the term "thrombosis of the posterior inferior cerebellar artery" has come into use in all cases in which these clinical features are exhibited. Although it is true that the site of damage is that portion of the medulla supplied by the posterior inferior cerebellar artery, as shown by injections of anatomic specimens, the syndrome is the result of an infarct in an anatomic area rather than an occlusion of a specific artery. Such a distinction is important for accumulating scientific data. An analogous situation exists in the carotid arterial system, for an infarct may be observed in the territory of the middle cerebral artery but the occlusion is at the origin of the internal carotid artery. Anatomic studies have disclosed some variation in the vascular supply of the brain stem. These variations and the degree of collateral circulation as well as other factors will influence the exact location and degree of damage produced by any given arterial occlusion or stenosis. Our purpose in this paper is to describe the clinical variations in the syndrome and present follow-up data on the outcome of the cases. Since necropsy was performed by us in only one of our cases, this is a clinical study relating to a characteristic variety of strokes with infarction in the dorsolateral portion of the medulla. It is presumed that the territory of
Lateral Medullary Syndrome: Clinical Features and Prognosis
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the posterior inferior cerebellar artery is infarcted, although the occlusion or stenosis may be instead in the parent vertebral artery or one of the latter's other branches. MATERIALS AND METHODS
For the present study, all cases of all patients with lateral medullary syndrome examined at the Clinic in the 13 years 1945 through 1957 were reviewed. Follow-up questionnaires were sent to patients or relatives. These contained questions designed to obtain information about each patient's health, residual neurologic deficits, subsequent strokes, and associated disease as well as the cause of death, if known. Follow-up information is available in 35 cases, and these form the basis of this report. Eleven patients could not be traced and are not included, although it can be stated that their clinical manifestations were similar to those of the others. The criteria used in the selection of cases for this report were: (1) a definite history of a rapid onset of neurologic deficits, as seen in patients with cerebral infarction, and (2) evidence on neurologic examination to indicate that the lesion was confined to the dorsolateral area of the medulla. Patients with weakness or spasticity of the limbs or evidence of involvement of the structures near the midline or on the opposite side were not included. During their hospitalization of a week or more, all patients had evidence of neurologic dysfunction which persisted. Several representative cases will be reported. REPORT OF CASES CASE 1. When this patient, a 54-year-old man, was admitted, he complained of unsteady gait, dysphagia and diplopia. One week prior to admission he experienced a transient episode of staggering gait and double vision which lasted 10 minutes. On the day of admission he had noted the abrupt onset of whirling dizziness, nausea and a hot tingling sensation on the left side of his face. Within a few minutes he was so unsteady that he could not walk. In calling for aid, he noted hoarseness, and within 30 minutes he had diplopia and trouble in swallowing. Examination disclosed the following abnormalities: blood pressure of 230 mm. of mercury systolic and 100 mm. diastolic; a markedly ataxic gait; moderate incoordination of the left limbs; a hoarse voice; ptosis of the left eyelid and miosis on the left; a decrease in the pharyngeal reflex with pulling of the uvula to the right side; absence of the left corneal reflex and marked impairment of pain sensation over the forehead and cheek on the left side, and diminution (-2) of pain and temperature sense over the right limbs and right side of the body up to the clavicle. The cerebrospinal fluid contained 30 mg. of protein per 100 m!. and 31ymphocytes per cubic millimeter. The patient had trouble swallowing for a few days and was maintained with intravenous infusions. His condition improved
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gradually and in a week he was walking with aid and able to swallow with some difficulty. Three years later examination revealed minimal unsteadiness on rapid turns, tandem gait and a decrease in the left corneal reflex. He still had slight trouble in swallowing and tingling in the right lower extremity, but no other abnormalities were observed. CASle n. The patient, an 82-year-old man, had had hypertension for many years. Four days before admission pain developed behind the left eye and extended to the left temple and left side of the neck. The ni~ht prior to admission he was seized with sudden nausea and vertigo, fell to the floor and vomited. In attempting to walk he fell to the left. Swallowing was impossible. His wife observed ptosis of the left eyelid and hoarseness. He noted diplopia intermittently at first but none thereafter. Examination revealed the following abnormalities: The patient could barely walk with help because of a markedly staggering gait with falling to the left, decreased corneal reflex on the left, ptosis of the lid and miosis on the left, moderate incoordination of the left extremities, slight weakness of all the facial muscles on the left, absence of the pharyngeal reflex with paralysis of the left side of the palate and pharynx, hoarseness, nystagmus on lateral gaze, slight hypesthesia over the left side of the forehead and anesthesia to pinprick on all the right half of the body and right extremities to the level below the base of the neck. Blood pressure was 190/110. Two days later loss of pain sense was noted on the left side of the face. No improvement occurred in his condition, and he died abruptly two weeks later. Necropsy disclosed thrombosis of the left vertebral and posterior inferior cerebellar arteries with infarction of the dorsolateral portion of the medulla and the adjacent portion of the cerebellum.
RESULTS OF STUDY OF 35 CASES
Our group was composed of 28 men and seven women. A predilection for men was observed in this just as in all other types of cerebral infarctions. At the time of infarction, two patients were in their 30's, nine in their 40's, 11 in their 50's, nine in their 60's, three in their 70's, and one patient was 82 years of age. The infarction was on the right side in 18 cases, on the left in 17. Eight (23 per cent) patients gave a reliable history of previous transient ischemic episodes, lasting 10 to 30 minutes. The symptoms noted by all were suggestive of ischemia of the brain stem and consisted of rotational vertigo, nausea, vomiting and staggering, and were similar to the symptoms present in the final infarction. Two patients had associated diplopia. In four patients such episodes occurred in the week preceding the infarction; in three, during the two months preceding it, and one patient had a brief transitory spell, identical to this stroke, nine years before the infarction. Each patient had at least two such episodes; none had more than five. Many patients had associated diseases. Eighteen patients (51 per cent)
Lateral Medullary Syndrome: Clinical Features and Prognosis Table 1.
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Symptoms of 35 Patients with Lateral Medullary Syndrome SYMPTOM
Ataxia .... . Dysphagia .... . Vertigo .... . Paresthesia of limbs .. . Paresthesia of face .... . Nausea and vomiting ............. . Headache ... . Dysarthria ....... . Visual disturbances .... . Hoarseness .......... . Unilateral facial pain .. . Hiccup ....
PATIENTS AFFECTED
30
26 25 23
22
18 15 15 9 8 6 5
had hypertension (blood pressure in excess of 150/90), five (14 per cent) had diabetes mellitus, and seven had cardiac disease, either angina pectoris or history of previous myocardial infarction. In 23 patients the onset of symptoms was abrupt (instantaneous or fully developed in less than an hour), in five symptoms developed over a one to 12-hour period and in seven patients the onset of the clinical picture was more gradual: from 12 hours to three days elapsed before the syndrome was fully developed. The range of symptoms noted by these patients is listed in Table 1. As would be expected ataxia of gait or of the ipsilateral limbs but usually both was noted by almost all the patients. In many instances, the staggering was of sufficient severity to preclude walking or use of the involved upper limb in eating. Dysphagia, vertigo, nausea and vomiting were common also. The dysphagia was never severe enough that fluid came back through the nose. In a few patients the dysphagia prevented effective swallowing, and a period of tube feedings was necessary. The paresthesia and incoordination of the limbs were often first termed "weakness" by the patients. "Tingling," "crawling" and "peculiar" were other words used to describe the abnormal sensation. Head pain of some sort was recalled by almost half of the group. Six patients recalled severe ipsilateral pain in the neck, face or eye, while the remainder had more diffuse, dull pain in the head. Both the headache and this unilateral pain appeared early and preceded other symptoms, in some instances by several hours. Visual symptoms were noted as blurring in four patients and diplopia in five. The nausea and vomiting lasted several hours, rarely as long as a day. The hiccups persisted several days. The difficulty in swallowing lessened in several weeks, but did not completely disappear for some months in most patients.
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Table 2.
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PETERMAN, ROBERT
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Neurologic Deficits in 35 Patients with Lateral Medullary Syndrome ABNORMALITY
Anesthesia of body and limbs (contralateral) .... . Ataxia .................................... . Facial anesthesia (ip~ila teral) .. Decreased corneal reflex ..... . Horner's syndrome (ipsilateral) ... . Ptosis ...... " .... , ...... . Miosis .. Anhydrosis . Vagus nerve deficit (ipsilateral) .. . Nystagmus .................. . Facial nerve deficit (ipsilateral) ..
PATIENTS
35
30 30 32 25 23
21 5
26 20 15
The clinical abnormalities observed in these 35 patients are listed in Table 2. In 20 patients the ataxia was observed both in gait and as a cerebellar incoordination of the ipsilateral limbs, while in five patients the ataxia was noted only in walking; and in five, it was principally in the ipsilateral limbs. Decrease in pain and temperature sense on the face varied in degree, from minimal to absolute loss, and in extent. In two patients the only loss to pain sense was observed as a decrease in the corneal reflex. The areal extent of decrease of these senses was always over the distribution of the ophthalmic branch of the fifth cranial nerve with varying involvement of the lower half of the face. The lower border near the angle of the jaw did not conform to the typical configuration as seen following section of the trigeminal nerve, but rather can be portrayed as a gentle curve sloping downward and medially from just anterior to the tragus to the edge of the mandible where the facial artery lies. Onion ring distribution with gradual loss from the maximum about the mouth to the minimum at the edge did not occur in our cases. The variation in the loss of pain sense and temperature sense over the body and limbs was extreme. In some patients only small decreases were noted in the hand, foot or perianal areas. When the loss was severe and extended onto the neck, it extended only about half way up the neck, leaving a collar of normal sensation between it and the area of comparable loss on the face on the other side. Portions of Horner's syndrome were observed in 25 cases; complete Horner's syndrome, however, was observed in only five. Paresis of the muscles supplied by the vagus nerve was usually severe. On the other hand, weakness of the facial muscles was only minimal. Nystagmus varied from fine to coarse and was seen on lateral gaze. In two cases suggestive weakness of the ipsilateral half of the tongue
Lateral Medullary Syndrome: Clinical Features and Prognosis
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and in three cases contralateral equivocal Babinski's signs were observed. In these cases no evidence of weakness or spasticity was seen in the limbs. Roentgenograms were made of the skulls on 33 patients and were normal in all except for a few instances of calcification of the carotid arteries. The cerebrospinal fluid was studied in six patients. The proteins were as follows: 30, 35, 40, 45, 90 and 150 mg. per 100 ml.; the cells numbered 3, 6, 1, 1, 25 and llymphocytes, respectively, per cubic milIimeter. Ten patients underwent electroencephalographic examination: in eight the records were interpreted as normal or as showing minimal, nonspecific, generalized dysrhythmia; in two, the records revealed focal slow waves over the cerebral hemispheres for which no corresponding neurologic abnormalities were found. COURSE
One patient (Case II) died at our institution three weeks after the infarction. Follow-up data up to 10 years on the other patients revealed that 11 patients had died and 23 were still Jiving. All 35 patients had had their strokes one year or more prior to the cut-off date for follow-up. During this one year six patients had died and 29 survived; this gave an S3 per cent one-year survival rate. Twenty-five patients had had their strokes three or more years prior to the cut-off date and 20 were stilI living, a three-year survival rate of 80 per cent. Seventeen patients had had their strokes five or more years prior to the cut-off date and, of these, 10 were still living; this gave a five-year survival rate of 59 per cent. The death rate appears to be higher in the first year after infarction than in the next several years. These figures are obviously only an approximation since on the one hand the stroke may be considered so minor that hospital admission is not sought while on the other hand the stroke may be more severe or may have progressed to produce a larger infarct and thus it would not be included in the sample as we defined it. The causes of death were as follows: myocardial infarction in five patients; cerebrovascular episode in two; pneumonia in one; renal failure in one; and unknown in three. Although the sample is small, eight of the 12 patients who died suffered from hypertension and three suffered from diabetes mellitus; the incidence of both these conditions in the patients who died was higher percentagewise than in the entire group of 35 patients. The sample is too small to study the effect of age on mortality. Seventeen of the 23 living patients were still working at time of followup. Since the residual neurologic difficulties were equally severe in those work ing and in those not working, age may be the determining factor
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with regard to employment. The average age at follow-up of those still working was 54 years; of those not working, 68 years. Only two patients were without some residual symptoms. Sixteen still noted tingling of the limbs; 10 had unsteady gait or incoordination of the limbs; eight had trouble swallowing; three had dysarthria or hoarseness; three had paresthesia of the face; and one subsequently began to have intermittent focal cerebrovascular insufficiency for which anticoagulant therapy had been used for three years. COMMENT
The data described illustrate the range of abnormalities observed in patients with the clinical diagnosis of infarction in the dorsolateral portion of the medulla. This is in keeping with infarction elsewhere in the brain in that the resulting lesion varies in area and in the degree of damage it inflicts. The clinical features presented clearly define the type of patient included in the study. This study is not designed to relate the infarct to narrowing or closure of any particular branch or branches of the vertebral basilar arterial system. It should be pointed out, however, that pathologic studies in the literature relate the infarct to thrombosis of the vertebral or the posterior inferior cerebellar or both arteries. The clinical picture presented is generally so distinctive that a diagnosis of site and cause (vascular infarct) can be made often from either the history alone or the examination alone. The prognosis as to immediate mortality has been considered favorable. The current study bears this out in that only one of 35 patients died as the result of occlusion of the vertebral artery during hospitalization immediately after onset of symptoms. Three other patients who died in the first year did so in about four months after onset of symptoms. The cause of death was unknown in two (both had relatively severe hypertension), and the other sustained a myocardial infarct. Robinson and co-workers noted that 21 per cent of patients with cerebral infarction (of all types) died as a result of their initial attack and that about 50 per cent were dead within four years. In their group comprising those patients with only minimal or transitory neurologic abnormalities, 70 per cent were living three years and 53 per cent five years after the initial attack. Of the 62 patients who had clinical evidence of occlusion of the posterior inferior cerebellar (or vertebral) artery in the group studied by Currier, Giles and Westerberg only 54 per cent survived for five years. In addition these authors found that the survival rate was lower among patients with other significant diseases, such as hypertension, diabetes mellitus and atherosclerosis of the coronary arteries than among those without such complicating conditions.
Lateral Medullary Syndrome: Clinical Features and Prognosis
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Lewis, Littman and Foley obtained follow-up information on 20 patients with infarction in this area. Seven died within eight months, and three died from one to eight years after the stroke. Marshall and Shaw studied the records of 305 patients with cerebrovascular disease. Twenty-two died in the hospital. They were able to follow 251 and noted that the five-year survival rate of this group was 40 per cent. The five-year survival rate was 53 per cent in that portion of the follow-up group who had had infarctions in the brain stem. In both instances the rates would be lower if the hospital deaths were included. They made no distinction between transient episodes and infarction. Because the immediate prognosis for life seems relatively good in comparison to that for all types of cerebral infarctions, and the resultant deficits seem relatively so meager from a functional standpoint, anticoagulants have not been used by us for this type of infarction of the brain stem. That the process can extend is obvious and if it should, anticoagulant medication would then be strongly considered. At the present time the immediate treatment is comprised of appropriate general measures and physical therapy. SUMMARY
The records and follow-up data concerning 35 patients with infarction in the dorsolateral portion of the medulla were reviewed. The neurologic abnormalities included loss of pain and temperature senses on one side of the face and on the opposite side of the body and ataxia, dysphagia, Horner's syndrome and nystagmus. One hospital death occurred. The three-year survival rate in this sample was 80 per cent; the five-year survival rate was 59 per cent. Residual, though minimal, neurologic deficits were noted by the majority of patients for many years. REFERENCES 1. Currier, R. D., Giles, C. L. and Westerberg, Martha R.: The Prognosis of Some Brain Stem Vascular Syndromes. Neurology 8: 664-668 (Sept.) 1958. W 2. Hun, Henry: Analgesia, Thermic Anaesthesia, and Ataxia, Resulting From Foci of Softening in the Medulla Oblongata and Cerebellum, Due to Occlusion of the Left Inferior Posterior Cerebellar Artery: A Study of the Course of the Sensory and Co-ordinating Tracts in the Medulla Oblongata. New York M. J. 65: 513-519 (April 17); 581-584 (May 1); 613-620 (May 8) 1897. 3. Lewis. G. N., Littman, A. and Foley, E. F.: Syndrome of Thrombosis of PORterior Inferior Cerebellar Artery: Report of 28 Cases. Ann. Int. Med. 36: 592-602 (Feb.) 1952. 4. Marshall, John and Shaw, D. A.: The Natural History of Cerebrovascular Disease. Brit. M. J.1: 1614-1617 (June 27) 1959 5. Robinson, R. W., Cohen, W. D., Higano, Norio, Meyer, Richard, Lukowsky, G. H., McLaughlin, R. B. and MacGilpin, H. H., Jr.: Life-Table Analysis of Survival After Cerebral Thrombosis-Ten-Year Experience. J.A.M.A. 169: 1149-1152 (March 14) 1959.
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6. Spiller, W. G.: The Symptom-Complex of Occlusion of the Posterior Inferior Cerebellar Artery: Two Cases with Necropsy. J. Nerv. & Ment. Dis. 35: 365387 (June) 1908. 7. Wallenberg, Adolf: Acute Bulbiiraffection (Embolie der Art. cerebellar. post. inf. sinistr.?). Arch. Psychiat. 27: 504-540 (June) 1895.
THE constellation of signs and symptoms resulting from an infarct in the dorsolateral portion of the medulla oblongata has variously been named the Wallenberg syndrome, the lateral medullary syndrome, or the syndrome of occlusion of the posterior inferior cerebellar artery. The clinical features of this syndrome consist of the relatively sudden onset of vertigo, nausea, vomiting, dysphagia, hoarseness, staggering, and incoordination of the limbs on one side of the body. Headache, pain or numbness of one side of the face, paresthesia of the limbs on the opposite side and hiccup may be Boted by the patient. Examination reveals decrease or loss of pain and temperature sensations on one side of the face, decreased corneal reflex, Horner's syndrome, paresis or paralysis of the muscles of one side of the palate and larynx, weakness of the entire face (peripheral type) and incoordination of the limbs, all on the same side as the lesion. On the opposite side one notes decrease or loss of pain and temperature sensations. The gait is ataxic. Fine or coarse nystagmus may be seen on gaze to either side, but it occurs more often to the side of the lesion. Muscle stretch reflexes and muscular strength in the limbR and sensations of light touch, position and vibration are normal. These findings result from a lesion affecting the various structures in the dorsolateral portion of the medulla including nucleus and spinal tract of the trigeminal nerve (facial and corneal anesthesia), the spinothalamic tract (limb and body anesthesia), inferior cerebellar peduncle (gait and limb ataxia), vestibular nuclei (nausea, vomiting, nystagmus), descending sympathetic fibers (Horner's syndrome), nucleus ambiguus of the vagus nerve (palatal and laryngeal palsy) and intramedullary fibers of the facial nerve (facial weakness). The lesion varies in area and in density, and thus the abnormalities listed above will vary also. The lesion may involve the adjacent portion of the cerebellum. In most instances, how-
887
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F.
PETERMAN, ROBERT
G.
SIEKERT
ever, the clinical picture is distinctive. It has been stated that the immediate prognosis for life is good. After a few months, most patients note only minimal neurologic deficits. Wallenberg is generally credited with establishing the syndrome which now bears his name. In a carefully reasoned discussion he postulated the infarction and the vascular lesion as due to embolization in the posterior inferior cerebellar artery. He noted that other authors had published cases but that no one had drawn attention to the characteristic picture. Interestingly enough, many of the authors that Wallenberg quoted aR describing cases of occlusion of this artery actually described thrombosiR of the vertebral artery with or without additional thrombosis of the posterior inferior cerebellar artery. Hun and Spiller were the first Americans interested in this condition. The former described a case that was studied by van Gieson at necropsy but made no comment concerning the arteries. Spiller wrote on the symptom-complex of occlusion of the posterior inferior cerebellar artery and used two cases to document his thesis. One case disclosed thrombosis of the vertebral and the posterior cerebellar arteries; the other disclosed thrombosis of the basilar and vertebral arteries; the posterior inferior cerebellar artery in this case was filled with a few erythrocytes but did not show distinct thrombosis. Since then, scattered reports have served to document the existence and characteristic clinical features of this syndrome. Because the immediate outlook for life is good, anatomic controls are lacking in most instances. Despite this lack, the term "thrombosis of the posterior inferior cerebellar artery" has come into use in all cases in which these clinical features are exhibited. Although it is true that the site of damage is that portion of the medulla supplied by the posterior inferior cerebellar artery, as shown by injections of anatomic specimens, the syndrome is the result of an infarct in an anatomic area rather than an occlusion of a specific artery. Such a distinction is important for accumulating scientific data. An analogous situation exists in the carotid arterial system, for an infarct may be observed in the territory of the middle cerebral artery but the occlusion is at the origin of the internal carotid artery. Anatomic studies have disclosed some variation in the vascular supply of the brain stem. These variations and the degree of collateral circulation as well as other factors will influence the exact location and degree of damage produced by any given arterial occlusion or stenosis. Our purpose in this paper is to describe the clinical variations in the syndrome and present follow-up data on the outcome of the cases. Since necropsy was performed by us in only one of our cases, this is a clinical study relating to a characteristic variety of strokes with infarction in the dorsolateral portion of the medulla. It is presumed that the territory of
Lateral Medullary Syndrome: Clinical Features and Prognosis
889
the posterior inferior cerebellar artery is infarcted, although the occlusion or stenosis may be instead in the parent vertebral artery or one of the latter's other branches. MATERIALS AND METHODS
For the present study, all cases of all patients with lateral medullary syndrome examined at the Clinic in the 13 years 1945 through 1957 were reviewed. Follow-up questionnaires were sent to patients or relatives. These contained questions designed to obtain information about each patient's health, residual neurologic deficits, subsequent strokes, and associated disease as well as the cause of death, if known. Follow-up information is available in 35 cases, and these form the basis of this report. Eleven patients could not be traced and are not included, although it can be stated that their clinical manifestations were similar to those of the others. The criteria used in the selection of cases for this report were: (1) a definite history of a rapid onset of neurologic deficits, as seen in patients with cerebral infarction, and (2) evidence on neurologic examination to indicate that the lesion was confined to the dorsolateral area of the medulla. Patients with weakness or spasticity of the limbs or evidence of involvement of the structures near the midline or on the opposite side were not included. During their hospitalization of a week or more, all patients had evidence of neurologic dysfunction which persisted. Several representative cases will be reported. REPORT OF CASES CASE 1. When this patient, a 54-year-old man, was admitted, he complained of unsteady gait, dysphagia and diplopia. One week prior to admission he experienced a transient episode of staggering gait and double vision which lasted 10 minutes. On the day of admission he had noted the abrupt onset of whirling dizziness, nausea and a hot tingling sensation on the left side of his face. Within a few minutes he was so unsteady that he could not walk. In calling for aid, he noted hoarseness, and within 30 minutes he had diplopia and trouble in swallowing. Examination disclosed the following abnormalities: blood pressure of 230 mm. of mercury systolic and 100 mm. diastolic; a markedly ataxic gait; moderate incoordination of the left limbs; a hoarse voice; ptosis of the left eyelid and miosis on the left; a decrease in the pharyngeal reflex with pulling of the uvula to the right side; absence of the left corneal reflex and marked impairment of pain sensation over the forehead and cheek on the left side, and diminution (-2) of pain and temperature sense over the right limbs and right side of the body up to the clavicle. The cerebrospinal fluid contained 30 mg. of protein per 100 m!. and 31ymphocytes per cubic millimeter. The patient had trouble swallowing for a few days and was maintained with intravenous infusions. His condition improved
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SIEKERT
gradually and in a week he was walking with aid and able to swallow with some difficulty. Three years later examination revealed minimal unsteadiness on rapid turns, tandem gait and a decrease in the left corneal reflex. He still had slight trouble in swallowing and tingling in the right lower extremity, but no other abnormalities were observed. CASle n. The patient, an 82-year-old man, had had hypertension for many years. Four days before admission pain developed behind the left eye and extended to the left temple and left side of the neck. The ni~ht prior to admission he was seized with sudden nausea and vertigo, fell to the floor and vomited. In attempting to walk he fell to the left. Swallowing was impossible. His wife observed ptosis of the left eyelid and hoarseness. He noted diplopia intermittently at first but none thereafter. Examination revealed the following abnormalities: The patient could barely walk with help because of a markedly staggering gait with falling to the left, decreased corneal reflex on the left, ptosis of the lid and miosis on the left, moderate incoordination of the left extremities, slight weakness of all the facial muscles on the left, absence of the pharyngeal reflex with paralysis of the left side of the palate and pharynx, hoarseness, nystagmus on lateral gaze, slight hypesthesia over the left side of the forehead and anesthesia to pinprick on all the right half of the body and right extremities to the level below the base of the neck. Blood pressure was 190/110. Two days later loss of pain sense was noted on the left side of the face. No improvement occurred in his condition, and he died abruptly two weeks later. Necropsy disclosed thrombosis of the left vertebral and posterior inferior cerebellar arteries with infarction of the dorsolateral portion of the medulla and the adjacent portion of the cerebellum.
RESULTS OF STUDY OF 35 CASES
Our group was composed of 28 men and seven women. A predilection for men was observed in this just as in all other types of cerebral infarctions. At the time of infarction, two patients were in their 30's, nine in their 40's, 11 in their 50's, nine in their 60's, three in their 70's, and one patient was 82 years of age. The infarction was on the right side in 18 cases, on the left in 17. Eight (23 per cent) patients gave a reliable history of previous transient ischemic episodes, lasting 10 to 30 minutes. The symptoms noted by all were suggestive of ischemia of the brain stem and consisted of rotational vertigo, nausea, vomiting and staggering, and were similar to the symptoms present in the final infarction. Two patients had associated diplopia. In four patients such episodes occurred in the week preceding the infarction; in three, during the two months preceding it, and one patient had a brief transitory spell, identical to this stroke, nine years before the infarction. Each patient had at least two such episodes; none had more than five. Many patients had associated diseases. Eighteen patients (51 per cent)
Lateral Medullary Syndrome: Clinical Features and Prognosis Table 1.
891
Symptoms of 35 Patients with Lateral Medullary Syndrome SYMPTOM
Ataxia .... . Dysphagia .... . Vertigo .... . Paresthesia of limbs .. . Paresthesia of face .... . Nausea and vomiting ............. . Headache ... . Dysarthria ....... . Visual disturbances .... . Hoarseness .......... . Unilateral facial pain .. . Hiccup ....
PATIENTS AFFECTED
30
26 25 23
22
18 15 15 9 8 6 5
had hypertension (blood pressure in excess of 150/90), five (14 per cent) had diabetes mellitus, and seven had cardiac disease, either angina pectoris or history of previous myocardial infarction. In 23 patients the onset of symptoms was abrupt (instantaneous or fully developed in less than an hour), in five symptoms developed over a one to 12-hour period and in seven patients the onset of the clinical picture was more gradual: from 12 hours to three days elapsed before the syndrome was fully developed. The range of symptoms noted by these patients is listed in Table 1. As would be expected ataxia of gait or of the ipsilateral limbs but usually both was noted by almost all the patients. In many instances, the staggering was of sufficient severity to preclude walking or use of the involved upper limb in eating. Dysphagia, vertigo, nausea and vomiting were common also. The dysphagia was never severe enough that fluid came back through the nose. In a few patients the dysphagia prevented effective swallowing, and a period of tube feedings was necessary. The paresthesia and incoordination of the limbs were often first termed "weakness" by the patients. "Tingling," "crawling" and "peculiar" were other words used to describe the abnormal sensation. Head pain of some sort was recalled by almost half of the group. Six patients recalled severe ipsilateral pain in the neck, face or eye, while the remainder had more diffuse, dull pain in the head. Both the headache and this unilateral pain appeared early and preceded other symptoms, in some instances by several hours. Visual symptoms were noted as blurring in four patients and diplopia in five. The nausea and vomiting lasted several hours, rarely as long as a day. The hiccups persisted several days. The difficulty in swallowing lessened in several weeks, but did not completely disappear for some months in most patients.
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Table 2.
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Neurologic Deficits in 35 Patients with Lateral Medullary Syndrome ABNORMALITY
Anesthesia of body and limbs (contralateral) .... . Ataxia .................................... . Facial anesthesia (ip~ila teral) .. Decreased corneal reflex ..... . Horner's syndrome (ipsilateral) ... . Ptosis ...... " .... , ...... . Miosis .. Anhydrosis . Vagus nerve deficit (ipsilateral) .. . Nystagmus .................. . Facial nerve deficit (ipsilateral) ..
PATIENTS
35
30 30 32 25 23
21 5
26 20 15
The clinical abnormalities observed in these 35 patients are listed in Table 2. In 20 patients the ataxia was observed both in gait and as a cerebellar incoordination of the ipsilateral limbs, while in five patients the ataxia was noted only in walking; and in five, it was principally in the ipsilateral limbs. Decrease in pain and temperature sense on the face varied in degree, from minimal to absolute loss, and in extent. In two patients the only loss to pain sense was observed as a decrease in the corneal reflex. The areal extent of decrease of these senses was always over the distribution of the ophthalmic branch of the fifth cranial nerve with varying involvement of the lower half of the face. The lower border near the angle of the jaw did not conform to the typical configuration as seen following section of the trigeminal nerve, but rather can be portrayed as a gentle curve sloping downward and medially from just anterior to the tragus to the edge of the mandible where the facial artery lies. Onion ring distribution with gradual loss from the maximum about the mouth to the minimum at the edge did not occur in our cases. The variation in the loss of pain sense and temperature sense over the body and limbs was extreme. In some patients only small decreases were noted in the hand, foot or perianal areas. When the loss was severe and extended onto the neck, it extended only about half way up the neck, leaving a collar of normal sensation between it and the area of comparable loss on the face on the other side. Portions of Horner's syndrome were observed in 25 cases; complete Horner's syndrome, however, was observed in only five. Paresis of the muscles supplied by the vagus nerve was usually severe. On the other hand, weakness of the facial muscles was only minimal. Nystagmus varied from fine to coarse and was seen on lateral gaze. In two cases suggestive weakness of the ipsilateral half of the tongue
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and in three cases contralateral equivocal Babinski's signs were observed. In these cases no evidence of weakness or spasticity was seen in the limbs. Roentgenograms were made of the skulls on 33 patients and were normal in all except for a few instances of calcification of the carotid arteries. The cerebrospinal fluid was studied in six patients. The proteins were as follows: 30, 35, 40, 45, 90 and 150 mg. per 100 ml.; the cells numbered 3, 6, 1, 1, 25 and llymphocytes, respectively, per cubic milIimeter. Ten patients underwent electroencephalographic examination: in eight the records were interpreted as normal or as showing minimal, nonspecific, generalized dysrhythmia; in two, the records revealed focal slow waves over the cerebral hemispheres for which no corresponding neurologic abnormalities were found. COURSE
One patient (Case II) died at our institution three weeks after the infarction. Follow-up data up to 10 years on the other patients revealed that 11 patients had died and 23 were still Jiving. All 35 patients had had their strokes one year or more prior to the cut-off date for follow-up. During this one year six patients had died and 29 survived; this gave an S3 per cent one-year survival rate. Twenty-five patients had had their strokes three or more years prior to the cut-off date and 20 were stilI living, a three-year survival rate of 80 per cent. Seventeen patients had had their strokes five or more years prior to the cut-off date and, of these, 10 were still living; this gave a five-year survival rate of 59 per cent. The death rate appears to be higher in the first year after infarction than in the next several years. These figures are obviously only an approximation since on the one hand the stroke may be considered so minor that hospital admission is not sought while on the other hand the stroke may be more severe or may have progressed to produce a larger infarct and thus it would not be included in the sample as we defined it. The causes of death were as follows: myocardial infarction in five patients; cerebrovascular episode in two; pneumonia in one; renal failure in one; and unknown in three. Although the sample is small, eight of the 12 patients who died suffered from hypertension and three suffered from diabetes mellitus; the incidence of both these conditions in the patients who died was higher percentagewise than in the entire group of 35 patients. The sample is too small to study the effect of age on mortality. Seventeen of the 23 living patients were still working at time of followup. Since the residual neurologic difficulties were equally severe in those work ing and in those not working, age may be the determining factor
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with regard to employment. The average age at follow-up of those still working was 54 years; of those not working, 68 years. Only two patients were without some residual symptoms. Sixteen still noted tingling of the limbs; 10 had unsteady gait or incoordination of the limbs; eight had trouble swallowing; three had dysarthria or hoarseness; three had paresthesia of the face; and one subsequently began to have intermittent focal cerebrovascular insufficiency for which anticoagulant therapy had been used for three years. COMMENT
The data described illustrate the range of abnormalities observed in patients with the clinical diagnosis of infarction in the dorsolateral portion of the medulla. This is in keeping with infarction elsewhere in the brain in that the resulting lesion varies in area and in the degree of damage it inflicts. The clinical features presented clearly define the type of patient included in the study. This study is not designed to relate the infarct to narrowing or closure of any particular branch or branches of the vertebral basilar arterial system. It should be pointed out, however, that pathologic studies in the literature relate the infarct to thrombosis of the vertebral or the posterior inferior cerebellar or both arteries. The clinical picture presented is generally so distinctive that a diagnosis of site and cause (vascular infarct) can be made often from either the history alone or the examination alone. The prognosis as to immediate mortality has been considered favorable. The current study bears this out in that only one of 35 patients died as the result of occlusion of the vertebral artery during hospitalization immediately after onset of symptoms. Three other patients who died in the first year did so in about four months after onset of symptoms. The cause of death was unknown in two (both had relatively severe hypertension), and the other sustained a myocardial infarct. Robinson and co-workers noted that 21 per cent of patients with cerebral infarction (of all types) died as a result of their initial attack and that about 50 per cent were dead within four years. In their group comprising those patients with only minimal or transitory neurologic abnormalities, 70 per cent were living three years and 53 per cent five years after the initial attack. Of the 62 patients who had clinical evidence of occlusion of the posterior inferior cerebellar (or vertebral) artery in the group studied by Currier, Giles and Westerberg only 54 per cent survived for five years. In addition these authors found that the survival rate was lower among patients with other significant diseases, such as hypertension, diabetes mellitus and atherosclerosis of the coronary arteries than among those without such complicating conditions.
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Lewis, Littman and Foley obtained follow-up information on 20 patients with infarction in this area. Seven died within eight months, and three died from one to eight years after the stroke. Marshall and Shaw studied the records of 305 patients with cerebrovascular disease. Twenty-two died in the hospital. They were able to follow 251 and noted that the five-year survival rate of this group was 40 per cent. The five-year survival rate was 53 per cent in that portion of the follow-up group who had had infarctions in the brain stem. In both instances the rates would be lower if the hospital deaths were included. They made no distinction between transient episodes and infarction. Because the immediate prognosis for life seems relatively good in comparison to that for all types of cerebral infarctions, and the resultant deficits seem relatively so meager from a functional standpoint, anticoagulants have not been used by us for this type of infarction of the brain stem. That the process can extend is obvious and if it should, anticoagulant medication would then be strongly considered. At the present time the immediate treatment is comprised of appropriate general measures and physical therapy. SUMMARY
The records and follow-up data concerning 35 patients with infarction in the dorsolateral portion of the medulla were reviewed. The neurologic abnormalities included loss of pain and temperature senses on one side of the face and on the opposite side of the body and ataxia, dysphagia, Horner's syndrome and nystagmus. One hospital death occurred. The three-year survival rate in this sample was 80 per cent; the five-year survival rate was 59 per cent. Residual, though minimal, neurologic deficits were noted by the majority of patients for many years. REFERENCES 1. Currier, R. D., Giles, C. L. and Westerberg, Martha R.: The Prognosis of Some Brain Stem Vascular Syndromes. Neurology 8: 664-668 (Sept.) 1958. W 2. Hun, Henry: Analgesia, Thermic Anaesthesia, and Ataxia, Resulting From Foci of Softening in the Medulla Oblongata and Cerebellum, Due to Occlusion of the Left Inferior Posterior Cerebellar Artery: A Study of the Course of the Sensory and Co-ordinating Tracts in the Medulla Oblongata. New York M. J. 65: 513-519 (April 17); 581-584 (May 1); 613-620 (May 8) 1897. 3. Lewis. G. N., Littman, A. and Foley, E. F.: Syndrome of Thrombosis of PORterior Inferior Cerebellar Artery: Report of 28 Cases. Ann. Int. Med. 36: 592-602 (Feb.) 1952. 4. Marshall, John and Shaw, D. A.: The Natural History of Cerebrovascular Disease. Brit. M. J.1: 1614-1617 (June 27) 1959 5. Robinson, R. W., Cohen, W. D., Higano, Norio, Meyer, Richard, Lukowsky, G. H., McLaughlin, R. B. and MacGilpin, H. H., Jr.: Life-Table Analysis of Survival After Cerebral Thrombosis-Ten-Year Experience. J.A.M.A. 169: 1149-1152 (March 14) 1959.
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6. Spiller, W. G.: The Symptom-Complex of Occlusion of the Posterior Inferior Cerebellar Artery: Two Cases with Necropsy. J. Nerv. & Ment. Dis. 35: 365387 (June) 1908. 7. Wallenberg, Adolf: Acute Bulbiiraffection (Embolie der Art. cerebellar. post. inf. sinistr.?). Arch. Psychiat. 27: 504-540 (June) 1895.