The Prognosis of Acute and Subacute Transverse Myelopathy Based on Early Signs and Symptoms ~
Allan H. Ropper, MD, and David C. Poskanzer, MD
Fifty-two patients with acute and subacute transverse myelopathy (TM) were evaluated at the Massachusetts General Hospital between 1955 and 1975 and followed for 1 to 23 years (average, 5 ) . Nineteen had symptoms of a recent acute infectious illness, 3 had cancer, and 1 had undergone a recent operation. There were four types of initial symptom. Twenty-four patients had paresthesias at the onset of the illness, 18 had pain, usually interscapular, 7 had leg weakness, and 3 had urine retention. Prognosis depended on the nature of the onset of TM. An acute catastrophic onset was generally associated with back pain and led to a poor outcome in 7 and a good outcome in only 1 of 11 patients. A subacute progressive onset over several days to four weeks, generally with ascending paresthesias or leg weakness, was associated with a good outcome in 15 and fair outcome in 17 of 37 patients. Preceding febrile illness, treatment with corticosteroids, and the nature of CSF abnormalities had no effect on outcome. Multiple sclerosis evolved in 7 patients during the follow-up period. Because of the frequency with which mass lesions were missed, the need for myelography in the diagnosis of T M is emphasized. The distinguishing clinical characteristics of T M provide guidelines for diagnosis and prognosis. Ropper AH, Poskanzer DC: The prognosis of acute and subacute transverse myelopathy based on early signs and symptoms. Ann Neurol 4:51-59, 1978
Methods
Transverse myelopathy (TM) is an acute intramedullary dysfunction of the spinal cord, either ascending or static, involving both halves of the cord, often over a considerable length, and appearing without any history of previous neurological disease [2, 11, 151. Several neuropathological processes may affect the spinal cord at one or several adjacent segments and give rise to this syndrome; these include a periinfectious, postinfectious, or vaccinal process [ 14, 171; demyelination as part of multiple sclerosis [ 131; vascular insufficiency [9, 181; idiopathic or paracarcinomatous necrosis [4, 12, 191; direct infection by virus [ 3 , 101; irradiation [16]; and vascular malformations [6, 201. The major challenge t o the clinician is to diagnose or exclude the more readily treatable illnesses such as tumor or abscess adjacent to the cord. The present study of T M was undertaken in an effort to delineate the clinical syndrome further. The results suggest that there are three well-defined modes of presentation, that prognosis is predictable on the basis of clinical characteristics, and that multiple sclerosis is responsible for only a small proportion of cases of the syndrome.
All records of patients at the Massachusetts General Hospital with a diagnosis of TM of any sort from 1955 to 1975 were reviewed. All cases of multiple sclerosis with spinal cord symptoms were reviewed for the same period. Chosen for the study were adult and pediatric patients with no antecedent neurological illness who developed, over a four-week period and without apparent cause, signs of spinal cord dysfunction with an extensive bilateral component and well-defined upper level. In order to be included, patients must have had a myelogram to exclude a mass. Six patients with Guillain-Barr6 syndrome and an extensor plantar response were excluded. Of 164 patients initially diagnosed as having acute myelopathy or myelitis, 82 ultimately were found to have an anatomical mass lesion, usually metastatic tumor; 4 had dissecting aortic aneurysms; and 18 did not have myelograms and were excluded from the study. Eight were excluded because precise clinical information was not available. Fifty-two patients remained for analysis. These had acute or subacute onset of weakness of both legs, spinal tract sensory findings, and sphincter problems. Follow-up was obtained by questionnaires to physicians, from hospital records, and in 9 patients by examination by one of the authors. Factors affecting outcome were analyzed using the chi-square test with the Yates continuity correction where
From the Neurology Service, Massachusetts General Hospital, Boston, MA.
Address reprint requests to Dr Ropper, Neurology Service, Massachusetts General Hospital, Fruit St, Boston, MA 021 14.
Accepted for publication Feb 2 2 , 1978.
0~64-5~34/78/0004-0109$01.25 @ 1978 by Allan H. Ropper
51
appropriate. Pathological material in 3 patients was available from the C . S. Kubik Laboratory for Neuropathology at the Massachusetts General Hospital.
Preceding Illness Seventeen patients described symptoms of a recent acute illness suggestive of infection (Table 1). Two patients did not have this information recorded, and the remaining 33 denied such symptoms. Ten of the 17 patients had a history of upper respiratory tract illness, and 2 had been treated with antibiotics. Six had symptoms of a viral illness with low-grade fever, malaise, and prominent myalgias lasting less than one week. O n e patient had a febrile, nonbloody diarrhea for three days. In all but 3 cases the illness had resolved before the onset of neurological symptoms. There was no age predilection in the patients with preceding acute, self-limiting infectious illness. O n e 22-year-old man had had chickenpox one month prior to the onset of TM, and 1 patient had received oral polio vaccine 41 days before the appearance of neurological symptoms. Seven patients had preexisting medical conditions (see Table 1). Three had metastatic cancer, including 1 with a poorly differentiated lung carcinoma who had received irradiation to the hilum one year before T M occurred. O n e patient was in the second month of pregnancy at the time she presented with TM, and 1 awoke with T M from operation for a supratentorial meningioma.
lar (18 patients); bilateral leg weakness ( 7 patients); and urine retention ( 3 patients) (Table 2 ) . Seven patients reported a combination of these symptoms at the onset, most notably back pain and concomitant leg weakness or paresthesias and leg weakness. Paresthesias and back pain rarely occurred in combination. In the first group, paresthesias were described as “numbness” o r “tingling” and occasionally as “pins and needles.” “Burning” and other descriptions of sensory phenomena were uncommon. When beginning in the toes or feet, the sensation progressed proximally over a period of one to three days. This ascending pattern also occurred with sensory symptoms beginning in the fingers. The paresthesias involved all the fingers or all the toes and were usually bilateral at the onset. Patients had difficulty defining the upper boundary of sensory symptoms. T h e second group, 18 patients with pain as the presenting symptom, had a more stereotyped and sudden onset. The pain was always severe and “sharp” or “pinching” in nature. It corresponded to the segment at which the cord was found to be affected on neurological examination. The most common location was the dorsal midline at the interscapular level. Occasionally the pain was situated just lateral to the midline. O n e patient had sharp costovertebral pain radiating to the groin and then developed pins and needles in the same distribution. Three patients with interscapular pain noted radiating discomfort in a shoulder cape distribution. A third group of 7 patients presented with leg weakness. Lower extremity weakness was noticed as “stumbling,” o r as a dragging of one leg, but affecting both legs to some extent. Urine retention was the initial complaint in only 3 patients and quickly progressed to include leg weakness. Although common in cases of long standing, urinary and fecal incontinence was not reported as an
Initial Symptoms The initial symptoms of T M fell into four groups: paresthesias ( 2 4 patients); pain, generally interscapu-
F i g I . Histogram of the ages of 52 patients at the time of diagnosis of transverse myelopathy.
Findings and Results Age and Sex
The age at diagnosis ranged from 4 to 83 years with a mean of 32 years (Fig 1). Most patients were between 15 and 35, and a small group were approximately 60 years old. There was no sex preponderance (28 women, 2 4 men).
5
2
:;L 0t
111111111111
0
(0
AGE AT TIME OF DIAGNOSIS
52
Annals of Neurology
Vol 4 No 1 July 1978
Table I , Recent Symptoms of In’fkctious illness or Coexistent Medical Condition with Acute and Subacute Transfurse Myelopathy in 52 Patients No. of Patients
SvmDtom Infectious illness Respiratory infection Gastrointestinal infection Nonspecific symptoms of viral illness Chickenpox (one month) Oral polio vaccine (41 days)
10 1
6 1 1
Total
19
Other medical conditions Ovarian adenocarcinorna Prostatic adenocarcinoma Lung carcinoma, poorly differentiated
Leoel of Spinal Cord Deficit and Other Symptoms
1 1 1 1 1
Felty syndrome
Postoperative cerebral meningioma
1 1
Pregnancy
Juvenile-onset diabetes mellitus Total
7
Table 2. Initial Symptoms of‘ Acute and Subacute Tvansr,erseMyelopathy in 52 Patients
Svmotom
No. of Patients
Paresthesias Feet or toes Fingertips
20
Pain lnterscapular Calt’
Brachial Radicular Bilateral leg weakness Unilateral at onset Urine retention
maximal deficit in 1 2 to 24 hours, 28 in one to ten days, and 4 in ten to fourteen days. In 1 case this information was not available. Five patients had a subacute, gradually progressive onset over ten days to four weeks. Symptoms appeared in a stuttering fashion, and the illness stabilized before a new symptom (e.g., leg weakness, paresthesias, pain) appeared. New symptoms and signs accrued after several days of no change. Eleven patients had a hyperacute catastrophic onset, with all symptoms appearing within 12 hours and usually in less than 1 hour. Of these, 10 began with back pain and 1 with leg weakness.
24 4 18 11
4 2 1
7
2
3
initial symptom. Fever at the outset was uncommon unless a urinary tract infection was present.
Course of the Initial Illness Patients were divided into three groups based on the time their disease took to reach a maximal deficit and the nature of its onset. Thirty-six patients had a smoothly progressive syndrome beginning with ascending lower extremity paresthesias or leg weakness, or both, and all stabilized within two weeks. The illness then abruptly halted, with paraplegia or quadriplegia and a welldefined sensory level. Of 36 patients with this acute type of progressive syndrome, 3 arrived at a stable
The most reproducible physical finding was loss of pinprick sensation. The highest dermatome of analgesia was taken as the upper segment of cord dysfunction (Fig 2). This level was symmetrical o n both sides of the body except in 5 patients, in whom there was a 2 to 5 cm asymmetry. In these latter cases, the higher level of analgesia was arbitrarily taken to define the highest level of cord damage. The pinprick level most commonly lay between T6 and T12. In 6 patients this information was either unclear or unavailable. All 41 patients with a progressive illness had an ascending pinprick level as the illness evolved. In general, the level of vibratory and proprioceptive loss was below that of analgesia. In only 1 patient did dissociated spinothalamic sensory loss with posterior column sparing exist at the onset, but several patients had this constellation of signs at the end of one week. Sphincter disturbances eventually occurred in three-quarters of the patients and consisted of urinary and sometimes fecal incontinence. This usually followed bladder distention earlier in the illness. Neck stiffness was an early symptom in 12 patients and resolved within 48 hours. The syndrome of “spinal shock’ with arefexia, hypotonia, and no cord function below a discrete level occurred in 5 of the 11 patients who had a catastrophic onset and in 4 patients with a progressive onset. Treutmen t Twenty-four patients-half of those with adequate follow-up-received no specific treatment except for bedrest and analgesia if required. Eleven patients were given adrenocorticotropic hormone, and 13 received oral corticosteroids (prednisone in 9 patients, dexamethasone in 3 , and methylprednisolone in 1). The method and course of administration of the drugs varied widely, with the majority of patients receiving at least one week of treatment, and several, more than one month. Two patients underwent laminectomy with decompression within 72 hours of hospitalization.
Ropper and Poskanzer: Prognosis of Transverse Myelopathy 53
8-
7-
5 sF h
5 3
6-
54-
3-
ei-
CERVICAL
THORACIC
LUMBAR
#/WEST L E E L O f ANALGZSIA
Laboratory Results All but 3 patients had Pantopaque myelograms within the first week of illness: 2 had optic neuritis within several days of the onset of TM, and 1 entered the Massachusetts General Hospital from another hospital at a time when he was improving. In 5 patients the myelogram showed mild swelling of the cord over one to three interspaces. Complete spinal block did not occur. In the others the myelograms were normal. Opening pressures on lumbar puncture were normal or minimally elevated. Eighteen patients had 4 or more leukocytes in their cerebrospinal fluid. Six had between 200 and 300 white blood cells. These were overwhelmingly lymphocytes except in 1 patient, in whom there were 300 white blood cells with 94% polymorphonuclear leukocytes. There were no cells when rechecked two weeks later. Red blood cells were few or absent. CSF protein was greater than 50 mg/dl in 18 patients, the highest value being 203 mg/dl. An elevated protein level with no cells was present in 8 patients. A second CSF sample was obtained in 15 patients. Except for 2 patients with multiple sclerosis, only 2 patients with initially normal CSF protein had elevated protein when retested within one year. All patients with a CSF pleocytosis showed fewer than 4 cells when retested within three months. CSF gamma-globulin determination was made during the acute illness in 17 patients and was greater than 12% in 6. Twenty-three patients had colloidal gold curves checked; 16 were normal, 3 were first zone, 3 mid zone, and 1 third zone. Of the 3 patients with first-zone curves, 1 had multiple sclerosis, 1 had Felty syndrome with hypergammaglobulinemia, and 1 had otherwise typical TM. Peripheral white blood cell counts were available for 42 of the 52 patients during the first 24 hours of illness and were elevated above 11,000 in 16 patients
54
Annals of Neurology Vol 4
No 1 July 1978
Fig 2. Uppermost level of cord lesion us determined by analgesia
in 46 putientr with transverse myelopatby.
prior to the administration of steroids. The erythrocyte sedimentation rate was less than 25 mm per hour in most patients. O n e of 11 patients tested had a positive heterophil antibody titer but no symptoms of mononucleosis. In 1 patient the antinuclear antibody titer was 1:256 with a homogeneous and speckled pattern; in another it was 1:16 and homogeneous. Neither of these patients subsequently developed symptoms referable to systemic lupus erythematosus or other autoimmune d'isease. Complicating Illness Twelve patients developed venous thrombosis in the legs, and 2 others died of pulmonary emboli. More than half of the patients had a urinary tract infection within the first three weeks of illness. Development of Maltiple Sclerosis Seven patients developed multiple sclerosis by standard criteria [ 131. These included 3 patients with visual symptoms in relation to T M who are included in this series because the myelopathy, and not visual symptoms, brought them to a physician. All 3 had funduscopic changes consistent with optic neuritis at some time in their course. Three other patients had a recurrence of spinal symptoms at a different locus; 1 of them died and showed pathologically typical multiple sclerosis. O n e patient had cerebral symptoms several weeks after T M and underwent a brain biopsy that demonstrated lesions consistent with multiple sclerosis. Several of the patients with multiple sclerosis reported mild exacerbation of TM symptoms during an acute infection o r other stress.
Outcome Follow-up ranged from one to twenty-three years with an average of five years. Eleven patients had more than ten years’ follow-up. Four patients did not have complete enough follow-up data to be analyzed for outcome. Seven patients were able to walk by the end of three weeks, prior to leaving the hospital. Of 34 patients who left the hospital with paraparesis, 8 recovered completely within a year and 15 were walking with a deficit or were dependent on orthopedic appliances. Seven patients showed little or no improvement, and 4 died during the period of the study. One died of disseminated encephalomyelitis seven months after the onset of TM. She had presented with T M of a smoothly progressive type, was not able to walk, and six months later developed cerebral and then brainstem signs (Patient 3). A second patient completely recovered from T M and died eighteen years later with metastatic carcinomas of the prostate and epiglottis. Two other patients died suddenly from pulmonary emboli, 1 at one year and the other (Patient 2) at two months. Neither had improved enough to be able to walk. The patients with adequate follow-up were separated into good, fair, and poor outcome groups. Good-outcome patients had a normal gait, normal micturition or minimal urgency, and no or minimally abnormal neurological signs. The poor-outcome group were chair-bound or bedridden, were incontinent, and had marked signs of cord dysfunction. The remainder of the patients comprising the fair group were functional and ambulatory but had a spastic gait, prominent urinary urgency or incontinence, and persistent signs of spinal cord dysfunction. Of 48 patients, 16 (33%) were classified good, 20 (42%) fair, and 12 (25%) poor at last examination or just prior to death (Table 3). The average length of follow-up was similar for each group. All patients who recovered to normal did so within one year, but some patients in the fair group continued to improve for up to eighteen months. Factors Affecting Outcome The patients’ age, sex, and level of spinal cord lesion did not affect outcome, nor did a history of preceding acute infectious illness. Both types of progressive TM, i.e., gradual and stuttering, had similar outcomes and are included in one “progressive” group. They consistently had either a good (41%) or fair (46%) outcome ( p < 0.01). Back pain was a predictor of poor outcome (53%) ( p < O.Ol), especially if it signaled the onset of a rapid catastrophic syndrome of T M (64%) ( p < 0,001). CSF pleocytosis or protein elevation had no effect o n clinical outcome, and no particular treatment produced a statistically sig-
Table 3. Factors Affetttangthe Outcome of Acute and Subacute Transverse Myelopathy in 48 of 52 Patients
No. of Patients Factor
Good Fair
Poor
Total
Total group Preceding acute illness Symptoms at onset Paresthesias Back pain Leg weakness Type of onset Catastrophic Progressive Spinal shock CSF pleocytosis Treatment None ACTH Corticosteroid Laminectomy Multiple sclerosis
16 10
20
12 4
48 19
9 3 4
12
3 9 0
24 17 7 11 37
5
5 3
1
3
15 0
17 2
6
4
7 5 7 7
6 4 6
11
7
24
3 6
4
11 13 2 7
0 2
0
1 2
4
1
9 17
ACTH = adrenocorticotropic hormone.
nificant change in outcome. Patients with signs of spinal shock did poorly, but the number of patients was small, and patients with swelling of the spinal cord on myelogram had outcomes similar to those of the whole group. Patients who ultimately developed multiple sclerosis were evenly distributed with respect to outcome (see Table 3).
Pathological Material Patient 1 A 44-year-old woman experienced sharp, severe midback pain. Over 24 hours the left leg became numb and the right hip weak. I n the subsequent ten days she developed numbness ascending up to the nipples and bilateral leg weakness. There was flaccid paraplegia and a T 3 sensory level. The CSF showed 40 lymphocytes and 5 polymorphonuclear cells. Two months later her shoulders became weak and the sensory level rose. Seven months later she suffered acutely diminished vision in the left e y e and remained quadriparetic until her death. At postmortem examination no gross abnormality was seen in the cerebral hemispheres, brainstem, and cerebellum. There was an acute and subacute necrotizing process involving the midcervical to high lumbar regions of the cord to a variable extent, with the midcervical region being most severely affected. Myelin was destroyed in these regions (Fig 3A). Profuse microglial and 1ymphocytic infiltration permeated the necrotic background debris (Fig 3B). Scattered intramedullary vessels had a thin cuff of lymphocytes, but this was not a prominent feature. Few recognizable neurons were apparent at levels of intense destruction, and the gray matter area was not easily recognized. At L1
Ropper and Poskanzer: Prognosis of Transverse Myelopathy
55
and below, the destruction was limited to patches of demyelination in the posterior columns, affecting mainly the areas adjacent to the posterior root entry zones. The fasciculus gracilis and lateral corticospinal and spinothalamic tracts were also atfccted with a demyelinating process. Axon cylinders were preserved except for some disordered appearance in areas of intense and widespread necrosis. T h e anterior and posterior roots were well preserved at all levels. Sections of the optic nerve showed diffuse demyelination o n the left and no abnormality o n the right. These findings indicate a primary demyelinating process of widespread and destructive character in the cord and optic nerve. Necrotic myelopathy and optic nerve demyelination are consistent with Devic opticomyelitis [ 11, and the history is compatible with this diagnosis.
56 Annals of Neurology
Vol 4 N o 1 July 1978
F i g 3 . (Patient 1 . ) (A) Transverte section from the cewicalcovd with only a fezre irlunds of bbck-staining myelin remaining. Both gray and white mutter are afficted by a necroticprocess. (Haidenhain-Woelcke. xl0.) ( B )Area from the htwalcolumn of the cercical cord demonstrating background of necrosis with glial and inflammutovy response. (Hematoxylin and eosin, x200.1
Patient 2 A 64-year-old woman had a band of tightness around the chest beginning two weeks after an upper respiratory tract infection. Several days later the right leg became weak. This progressed, and urine retention developed. Examination revealed no movement of the right leg and 5/10 power in the left. Pinprick sensation was diminished in the left leg
and left side of the trunk to the clavicle. Vibration sense was lost bilaterally to the costal margins. CSF examination showed 3 polymorphonuclear leukocytes and 1 lymphocyte. She died 50 days later of a pulmonary embolus. At autopsy there was narrowing and softening of the cord from approximately C8 to T4. A diffuse necrotizing process involved the entire midthoracic region, sparing a small anterior rim (Fig 4A). At the highest level the lesion involved a demarcated oval portion of the ventral posterior columns and medial posterior horns. I n the high lumbar region only a small, well-demarcated area of the posterior columns was involved (Fig 4B).
F i g 4. (Patient 2.) (A) Transverse section throzlgh the midthoracic cord. An anterior and lateral rim of black-staining myelin remains. The white and gray matter is otherwise necrotic. (Haidenhain-Woelcke, x 10 before 10% redzlctivn.) (Bi Transverse section through LI . An inflammatory and necrotizing proms involves the posterior columns andposterior root entcy zones. (Haidenhain-Woelcke, ~ 1 0 . )
The nature of this lesion was necrotic and not inflammatory. Selective sparing of axons was not found. The gray and white matter were equally affected. T h e general autopsy revealed diffuse peritoneal carcinomatosis of ovarian origin. Necrotizing myelopathy accompanying carcinoma has been described previously [ 12, 291. This case appeared as CPC 26-1976 in the N e w England Journal of Medicine [ 4 ] .
Patient 3 A 25-year-old woman presented with acute myelopathy of the cervical region. It began with leg weakness that progressed over five days. After her condition had been stable for several weeks, dementia occurred and pneumoencephalography demonstrated hydrocephalus. A brain biopsy was performed because of rapidly deteriorating cerebral function. She died seven months after the onset of the illness. No autopsy was obtained. A surgical specimen from the right frontal lobe showed an active demyelinating process consistent with multiple sclerosis.
Ropper and Poskanzer: Prognosis of Transverse Myelopathy
57
Discussion Pathological studies have demonstrated that a considerable longitudinal extent of spinal cord is involved with necrosis or inflammation in T M [7, 81. I t is possible that pain is appreciated only at the highest dermatome level affected because sensation is impaired below this level. Back pain may be caused by stretching of dural structures in a similar fashion to headache pain [ 5 ] . Patient 1 and several others in our experience demonstrate that acute back pain at the onset of T M can be due to a necrotic myelopathy. Radicular pain is explained by involvement of posterior root entry zones by the pathological process. The frequently ascending sensory symptoms in T M have a different cause from similar symptoms in acute idiopathic polyneuritis. Involvement of posterior and perhaps lateral column sensory fibers in T M produces numbness o r tingling in areas supplied by fibers below the affected level. As the pathological process extends both rostrally and caudally, only the rostra1 progression is appreciated, thus causing ascending paresthesias. For this reason, sensory symptoms in the lower extremities are not accompanied by simultaneous numbness or tingling in the upper extremities as in poiyneuritis. Dissociated spinothalamic sensory loss with posterior column sparing can occur in T M without anterior spinal artery occlusion. Several of our patients with this finding had a slowly progressive course, incompatible in our experience with anterior spinal artery occlusion. The preferential involvement of the mid-
thoracic region by TM is not easily explained. Previous reports have suggested that it is due to a comparatively poor vascular supply. The lesser longitudinal extent of the lumbar as compared to the thoracic cord in part explains why it is less frequently affected in TM. Three published series of T M are available for comparison with the present cases (Table 4). Paine and Byers’ [15] cases were all in children, and 60% followed an acute infectious illness. Weakness of the legs was the most common initial presentation, and the outcome was generally good. No information was available regarding subsequent occurrence of multiple sclerosis. Altrocchi’s [ 2 ] 67 patients of all ages were similar to those in the present series. Although Altrocchi’s patients were divided approximately equally among the good, fair, and poor outcome groups, only 1 patient recovered to normal. Total follow-up was shorter than in the present series. Thirty-four patients of all ages reported by Lipton and Teasdall [ 111 were similar to those in this series. Thirty-five percent had had a preceding viral infection. Only 2 9 patients had adequate follow-up, though information about the onset of T M was available for 32. At autopsy, spinal cord infarction was seen in 2 patients, “nonspecific necrotizing lesions” in 2 , meningiomyelitis in 1, and intramedullary capillary telangiectasia in I patient. Myelography was not done in 25 of Altrocchi’s 67 patients nor in 23 of the 34 patients of Lipton and Teasdall. Because o u r initial chart review revealed that many patients initially
Table 4 . Clinical Data and Outcome in 178 Patients from Four Series of Transcevse Myelopathy
Data and Outcome
Paine and Byers [ 151
Lipton and Altrocchi [2] Teasdall [ 1I ] [this series]
Total patients Preceding febrile illness Initial symptoms Paresthesias Back pain
25 15
20
1
6 9 3
Leg weakness
Sphincter disturbance Time to maximal deficit 10 days Multiple sclerosis
Outcome Good Fair Poor ~
58
67
17 17 17 2
...
30 23
... .. .
16 4
15
22 22 16
6 ... ~
Annals of Neurology Vol 4
Total
% of Patients with Information Available 37
Ropper and Poskanzer
No 1 July 1978
34 12
52 18
178 65
9 12 11
24 18 7
51 53
44
4
3
12
32 34 28 7
15 17 2 1
13 30 7
58 70 27 12
37 45 18 7
9 9
16 20 12
62 57 30
42 38 20
2
9
diagnosed as having TM were instead found at postmortem or on myelography to have tumors impinging on the cord, there is some question about the cause of T M in a large number of patients in these series. If the Massachusetts General Hospital series is summed with the other three series, 178 patients are available for study (see Table 4). Of these, 149 have adequate follow-up to determine outcome. Major initial symptoms were paresthesias, back pain, and leg weakness, each in approximately one-third of the total group. Most of the patients (74%) had a sensory level in the thoracic region. Multiple sclerosis developed in 7% of the total group. This study suggests that three distinct types of onset occur in TM. The largest group have ascending paresthesias at the onset, usually with a course that evolves over one to fourteen days. The outcome is usually good or fair in this group. Another group has pain at onset, usually in the back, which comes on suddenly and evolves over several hours; this group tends to have a poor prognosis. In a smaller, third group the syndrome evolves over ten days to four weeks in a stuttering course. The illness seems to stabilize, and then suddenly a new symptom appears. All the major symptoms of T M are represented within this group. The prognosis tends to be the same as in the gradually progressive group, i.e., most have a good or fair outcome. The overall good or fair prognosis, low incidence of multiple sclerosis, and large number of patients with venous thromboembolic complications are emphasized.
We are indebted to Dr E. P. Richardson of the Massachusetts General Hospital and to Dr C. Masters of the National Institutes of Health for their helpful advice.
References 1. Adams RD, Kubik CS: The morbid anatomy of the de-
rnyelinating diseases. Am J Med 12:510-546, 1952 2. Altrocchi PH: Acute transverse myelopathy. Arch Neurol 9:111-119, 1963 3. Bell EJ, Russel SJM: Acute transverse myelopathy and ECHO-2 virus infection. Lancet 2:1226-1227, 1963 4. Case records of the Massachusetts General Hospital. N Engl J Med 294:1447-1454, 1976 5. Dalessio DJ (ed): Wolff's Headache and Other Head Pain. New York, Oxford University Press, 1972, pp 57-99 6. Foix C, Alajouanine T: La myelite necrotique. Rev Neurol (Paris) 2:l-42, 1926 7. Greenfield JO, Turner J W A Acute and subacute necrotic myelitis. Brain 62:227-252, 1939 8. Hoffman H L Acute necrotic myelopathy. Brain 78:377-391, 1955 9. Hogan B W Acute myelitis: syndrome of occlusion of the anterior spinal artery at the first thoracic segment with softening of the cord. US Nav Med Bull 40:175-178, 1942 10. Hogan EL, Krigman M R Herpes zoster myelitis. Evidence for viral invasion of spinal cord. Arch Neurol 29:309-313, 1973 11. Lipton LH, Teasdall RD: Acute transverse myelopathy in adults. Arch Neurol 28:252-257, 1973 12. Mancall EL, Rosales R K Necrotizing myelopathy associated with visceral carcinoma. Brain 87:639-655, 1964 13. McAlpine D, Lumsden CE, Acheson ED: Multiple Sclerosis: A Reappraisal. London, Livingstone, 1968 14. Muller H G , Stanton JB, Gibbons JL: Parainfectious encephalomyelitis and related syndromes: a critical review of the neurologic complications of certain fevers. Q J Med 25:427505, 1956 15. Paine RS, Byers RK: Transverse myelopathy in childhood. AMA Arch Dis Child 85:151-163, 1953 16. Pallis CA, Louis S, Morgan RL: Radiation myelopathy. Brain 84:460-479, 1961 17. Prussin G, Kataki G : Dorsolumbar myelitis following antirabies vaccination with duck-embryo vaccine. Ann Intern Med 60:114-116, 1963 18. Steegman A T Syndrome of the anterior spinal artery. Neurology ( h h n e a p ) 2: 15-3 5, 1952 19. Williams R, Diamond H D , Craver LF: The pathogenesis and management of neurological complications in patients with malignant lymphomas and leukemias. Cancer 11:76-82, 1958 20. Wyburn-Mason R: Venous abnormalities, in The Vascular Abnormalities and Tumors of the Spinal Cord and Its Membranes. St Louis, Mosby, 1944
Ropper and Poskanzer: Prognosis of Transverse Myelopathy 59
Allan H. Ropper, MD, and David C. Poskanzer, MD
Fifty-two patients with acute and subacute transverse myelopathy (TM) were evaluated at the Massachusetts General Hospital between 1955 and 1975 and followed for 1 to 23 years (average, 5 ) . Nineteen had symptoms of a recent acute infectious illness, 3 had cancer, and 1 had undergone a recent operation. There were four types of initial symptom. Twenty-four patients had paresthesias at the onset of the illness, 18 had pain, usually interscapular, 7 had leg weakness, and 3 had urine retention. Prognosis depended on the nature of the onset of TM. An acute catastrophic onset was generally associated with back pain and led to a poor outcome in 7 and a good outcome in only 1 of 11 patients. A subacute progressive onset over several days to four weeks, generally with ascending paresthesias or leg weakness, was associated with a good outcome in 15 and fair outcome in 17 of 37 patients. Preceding febrile illness, treatment with corticosteroids, and the nature of CSF abnormalities had no effect on outcome. Multiple sclerosis evolved in 7 patients during the follow-up period. Because of the frequency with which mass lesions were missed, the need for myelography in the diagnosis of T M is emphasized. The distinguishing clinical characteristics of T M provide guidelines for diagnosis and prognosis. Ropper AH, Poskanzer DC: The prognosis of acute and subacute transverse myelopathy based on early signs and symptoms. Ann Neurol 4:51-59, 1978
Methods
Transverse myelopathy (TM) is an acute intramedullary dysfunction of the spinal cord, either ascending or static, involving both halves of the cord, often over a considerable length, and appearing without any history of previous neurological disease [2, 11, 151. Several neuropathological processes may affect the spinal cord at one or several adjacent segments and give rise to this syndrome; these include a periinfectious, postinfectious, or vaccinal process [ 14, 171; demyelination as part of multiple sclerosis [ 131; vascular insufficiency [9, 181; idiopathic or paracarcinomatous necrosis [4, 12, 191; direct infection by virus [ 3 , 101; irradiation [16]; and vascular malformations [6, 201. The major challenge t o the clinician is to diagnose or exclude the more readily treatable illnesses such as tumor or abscess adjacent to the cord. The present study of T M was undertaken in an effort to delineate the clinical syndrome further. The results suggest that there are three well-defined modes of presentation, that prognosis is predictable on the basis of clinical characteristics, and that multiple sclerosis is responsible for only a small proportion of cases of the syndrome.
All records of patients at the Massachusetts General Hospital with a diagnosis of TM of any sort from 1955 to 1975 were reviewed. All cases of multiple sclerosis with spinal cord symptoms were reviewed for the same period. Chosen for the study were adult and pediatric patients with no antecedent neurological illness who developed, over a four-week period and without apparent cause, signs of spinal cord dysfunction with an extensive bilateral component and well-defined upper level. In order to be included, patients must have had a myelogram to exclude a mass. Six patients with Guillain-Barr6 syndrome and an extensor plantar response were excluded. Of 164 patients initially diagnosed as having acute myelopathy or myelitis, 82 ultimately were found to have an anatomical mass lesion, usually metastatic tumor; 4 had dissecting aortic aneurysms; and 18 did not have myelograms and were excluded from the study. Eight were excluded because precise clinical information was not available. Fifty-two patients remained for analysis. These had acute or subacute onset of weakness of both legs, spinal tract sensory findings, and sphincter problems. Follow-up was obtained by questionnaires to physicians, from hospital records, and in 9 patients by examination by one of the authors. Factors affecting outcome were analyzed using the chi-square test with the Yates continuity correction where
From the Neurology Service, Massachusetts General Hospital, Boston, MA.
Address reprint requests to Dr Ropper, Neurology Service, Massachusetts General Hospital, Fruit St, Boston, MA 021 14.
Accepted for publication Feb 2 2 , 1978.
0~64-5~34/78/0004-0109$01.25 @ 1978 by Allan H. Ropper
51
appropriate. Pathological material in 3 patients was available from the C . S. Kubik Laboratory for Neuropathology at the Massachusetts General Hospital.
Preceding Illness Seventeen patients described symptoms of a recent acute illness suggestive of infection (Table 1). Two patients did not have this information recorded, and the remaining 33 denied such symptoms. Ten of the 17 patients had a history of upper respiratory tract illness, and 2 had been treated with antibiotics. Six had symptoms of a viral illness with low-grade fever, malaise, and prominent myalgias lasting less than one week. O n e patient had a febrile, nonbloody diarrhea for three days. In all but 3 cases the illness had resolved before the onset of neurological symptoms. There was no age predilection in the patients with preceding acute, self-limiting infectious illness. O n e 22-year-old man had had chickenpox one month prior to the onset of TM, and 1 patient had received oral polio vaccine 41 days before the appearance of neurological symptoms. Seven patients had preexisting medical conditions (see Table 1). Three had metastatic cancer, including 1 with a poorly differentiated lung carcinoma who had received irradiation to the hilum one year before T M occurred. O n e patient was in the second month of pregnancy at the time she presented with TM, and 1 awoke with T M from operation for a supratentorial meningioma.
lar (18 patients); bilateral leg weakness ( 7 patients); and urine retention ( 3 patients) (Table 2 ) . Seven patients reported a combination of these symptoms at the onset, most notably back pain and concomitant leg weakness or paresthesias and leg weakness. Paresthesias and back pain rarely occurred in combination. In the first group, paresthesias were described as “numbness” o r “tingling” and occasionally as “pins and needles.” “Burning” and other descriptions of sensory phenomena were uncommon. When beginning in the toes or feet, the sensation progressed proximally over a period of one to three days. This ascending pattern also occurred with sensory symptoms beginning in the fingers. The paresthesias involved all the fingers or all the toes and were usually bilateral at the onset. Patients had difficulty defining the upper boundary of sensory symptoms. T h e second group, 18 patients with pain as the presenting symptom, had a more stereotyped and sudden onset. The pain was always severe and “sharp” or “pinching” in nature. It corresponded to the segment at which the cord was found to be affected on neurological examination. The most common location was the dorsal midline at the interscapular level. Occasionally the pain was situated just lateral to the midline. O n e patient had sharp costovertebral pain radiating to the groin and then developed pins and needles in the same distribution. Three patients with interscapular pain noted radiating discomfort in a shoulder cape distribution. A third group of 7 patients presented with leg weakness. Lower extremity weakness was noticed as “stumbling,” o r as a dragging of one leg, but affecting both legs to some extent. Urine retention was the initial complaint in only 3 patients and quickly progressed to include leg weakness. Although common in cases of long standing, urinary and fecal incontinence was not reported as an
Initial Symptoms The initial symptoms of T M fell into four groups: paresthesias ( 2 4 patients); pain, generally interscapu-
F i g I . Histogram of the ages of 52 patients at the time of diagnosis of transverse myelopathy.
Findings and Results Age and Sex
The age at diagnosis ranged from 4 to 83 years with a mean of 32 years (Fig 1). Most patients were between 15 and 35, and a small group were approximately 60 years old. There was no sex preponderance (28 women, 2 4 men).
5
2
:;L 0t
111111111111
0
(0
AGE AT TIME OF DIAGNOSIS
52
Annals of Neurology
Vol 4 No 1 July 1978
Table I , Recent Symptoms of In’fkctious illness or Coexistent Medical Condition with Acute and Subacute Transfurse Myelopathy in 52 Patients No. of Patients
SvmDtom Infectious illness Respiratory infection Gastrointestinal infection Nonspecific symptoms of viral illness Chickenpox (one month) Oral polio vaccine (41 days)
10 1
6 1 1
Total
19
Other medical conditions Ovarian adenocarcinorna Prostatic adenocarcinoma Lung carcinoma, poorly differentiated
Leoel of Spinal Cord Deficit and Other Symptoms
1 1 1 1 1
Felty syndrome
Postoperative cerebral meningioma
1 1
Pregnancy
Juvenile-onset diabetes mellitus Total
7
Table 2. Initial Symptoms of‘ Acute and Subacute Tvansr,erseMyelopathy in 52 Patients
Svmotom
No. of Patients
Paresthesias Feet or toes Fingertips
20
Pain lnterscapular Calt’
Brachial Radicular Bilateral leg weakness Unilateral at onset Urine retention
maximal deficit in 1 2 to 24 hours, 28 in one to ten days, and 4 in ten to fourteen days. In 1 case this information was not available. Five patients had a subacute, gradually progressive onset over ten days to four weeks. Symptoms appeared in a stuttering fashion, and the illness stabilized before a new symptom (e.g., leg weakness, paresthesias, pain) appeared. New symptoms and signs accrued after several days of no change. Eleven patients had a hyperacute catastrophic onset, with all symptoms appearing within 12 hours and usually in less than 1 hour. Of these, 10 began with back pain and 1 with leg weakness.
24 4 18 11
4 2 1
7
2
3
initial symptom. Fever at the outset was uncommon unless a urinary tract infection was present.
Course of the Initial Illness Patients were divided into three groups based on the time their disease took to reach a maximal deficit and the nature of its onset. Thirty-six patients had a smoothly progressive syndrome beginning with ascending lower extremity paresthesias or leg weakness, or both, and all stabilized within two weeks. The illness then abruptly halted, with paraplegia or quadriplegia and a welldefined sensory level. Of 36 patients with this acute type of progressive syndrome, 3 arrived at a stable
The most reproducible physical finding was loss of pinprick sensation. The highest dermatome of analgesia was taken as the upper segment of cord dysfunction (Fig 2). This level was symmetrical o n both sides of the body except in 5 patients, in whom there was a 2 to 5 cm asymmetry. In these latter cases, the higher level of analgesia was arbitrarily taken to define the highest level of cord damage. The pinprick level most commonly lay between T6 and T12. In 6 patients this information was either unclear or unavailable. All 41 patients with a progressive illness had an ascending pinprick level as the illness evolved. In general, the level of vibratory and proprioceptive loss was below that of analgesia. In only 1 patient did dissociated spinothalamic sensory loss with posterior column sparing exist at the onset, but several patients had this constellation of signs at the end of one week. Sphincter disturbances eventually occurred in three-quarters of the patients and consisted of urinary and sometimes fecal incontinence. This usually followed bladder distention earlier in the illness. Neck stiffness was an early symptom in 12 patients and resolved within 48 hours. The syndrome of “spinal shock’ with arefexia, hypotonia, and no cord function below a discrete level occurred in 5 of the 11 patients who had a catastrophic onset and in 4 patients with a progressive onset. Treutmen t Twenty-four patients-half of those with adequate follow-up-received no specific treatment except for bedrest and analgesia if required. Eleven patients were given adrenocorticotropic hormone, and 13 received oral corticosteroids (prednisone in 9 patients, dexamethasone in 3 , and methylprednisolone in 1). The method and course of administration of the drugs varied widely, with the majority of patients receiving at least one week of treatment, and several, more than one month. Two patients underwent laminectomy with decompression within 72 hours of hospitalization.
Ropper and Poskanzer: Prognosis of Transverse Myelopathy 53
8-
7-
5 sF h
5 3
6-
54-
3-
ei-
CERVICAL
THORACIC
LUMBAR
#/WEST L E E L O f ANALGZSIA
Laboratory Results All but 3 patients had Pantopaque myelograms within the first week of illness: 2 had optic neuritis within several days of the onset of TM, and 1 entered the Massachusetts General Hospital from another hospital at a time when he was improving. In 5 patients the myelogram showed mild swelling of the cord over one to three interspaces. Complete spinal block did not occur. In the others the myelograms were normal. Opening pressures on lumbar puncture were normal or minimally elevated. Eighteen patients had 4 or more leukocytes in their cerebrospinal fluid. Six had between 200 and 300 white blood cells. These were overwhelmingly lymphocytes except in 1 patient, in whom there were 300 white blood cells with 94% polymorphonuclear leukocytes. There were no cells when rechecked two weeks later. Red blood cells were few or absent. CSF protein was greater than 50 mg/dl in 18 patients, the highest value being 203 mg/dl. An elevated protein level with no cells was present in 8 patients. A second CSF sample was obtained in 15 patients. Except for 2 patients with multiple sclerosis, only 2 patients with initially normal CSF protein had elevated protein when retested within one year. All patients with a CSF pleocytosis showed fewer than 4 cells when retested within three months. CSF gamma-globulin determination was made during the acute illness in 17 patients and was greater than 12% in 6. Twenty-three patients had colloidal gold curves checked; 16 were normal, 3 were first zone, 3 mid zone, and 1 third zone. Of the 3 patients with first-zone curves, 1 had multiple sclerosis, 1 had Felty syndrome with hypergammaglobulinemia, and 1 had otherwise typical TM. Peripheral white blood cell counts were available for 42 of the 52 patients during the first 24 hours of illness and were elevated above 11,000 in 16 patients
54
Annals of Neurology Vol 4
No 1 July 1978
Fig 2. Uppermost level of cord lesion us determined by analgesia
in 46 putientr with transverse myelopatby.
prior to the administration of steroids. The erythrocyte sedimentation rate was less than 25 mm per hour in most patients. O n e of 11 patients tested had a positive heterophil antibody titer but no symptoms of mononucleosis. In 1 patient the antinuclear antibody titer was 1:256 with a homogeneous and speckled pattern; in another it was 1:16 and homogeneous. Neither of these patients subsequently developed symptoms referable to systemic lupus erythematosus or other autoimmune d'isease. Complicating Illness Twelve patients developed venous thrombosis in the legs, and 2 others died of pulmonary emboli. More than half of the patients had a urinary tract infection within the first three weeks of illness. Development of Maltiple Sclerosis Seven patients developed multiple sclerosis by standard criteria [ 131. These included 3 patients with visual symptoms in relation to T M who are included in this series because the myelopathy, and not visual symptoms, brought them to a physician. All 3 had funduscopic changes consistent with optic neuritis at some time in their course. Three other patients had a recurrence of spinal symptoms at a different locus; 1 of them died and showed pathologically typical multiple sclerosis. O n e patient had cerebral symptoms several weeks after T M and underwent a brain biopsy that demonstrated lesions consistent with multiple sclerosis. Several of the patients with multiple sclerosis reported mild exacerbation of TM symptoms during an acute infection o r other stress.
Outcome Follow-up ranged from one to twenty-three years with an average of five years. Eleven patients had more than ten years’ follow-up. Four patients did not have complete enough follow-up data to be analyzed for outcome. Seven patients were able to walk by the end of three weeks, prior to leaving the hospital. Of 34 patients who left the hospital with paraparesis, 8 recovered completely within a year and 15 were walking with a deficit or were dependent on orthopedic appliances. Seven patients showed little or no improvement, and 4 died during the period of the study. One died of disseminated encephalomyelitis seven months after the onset of TM. She had presented with T M of a smoothly progressive type, was not able to walk, and six months later developed cerebral and then brainstem signs (Patient 3). A second patient completely recovered from T M and died eighteen years later with metastatic carcinomas of the prostate and epiglottis. Two other patients died suddenly from pulmonary emboli, 1 at one year and the other (Patient 2) at two months. Neither had improved enough to be able to walk. The patients with adequate follow-up were separated into good, fair, and poor outcome groups. Good-outcome patients had a normal gait, normal micturition or minimal urgency, and no or minimally abnormal neurological signs. The poor-outcome group were chair-bound or bedridden, were incontinent, and had marked signs of cord dysfunction. The remainder of the patients comprising the fair group were functional and ambulatory but had a spastic gait, prominent urinary urgency or incontinence, and persistent signs of spinal cord dysfunction. Of 48 patients, 16 (33%) were classified good, 20 (42%) fair, and 12 (25%) poor at last examination or just prior to death (Table 3). The average length of follow-up was similar for each group. All patients who recovered to normal did so within one year, but some patients in the fair group continued to improve for up to eighteen months. Factors Affecting Outcome The patients’ age, sex, and level of spinal cord lesion did not affect outcome, nor did a history of preceding acute infectious illness. Both types of progressive TM, i.e., gradual and stuttering, had similar outcomes and are included in one “progressive” group. They consistently had either a good (41%) or fair (46%) outcome ( p < 0.01). Back pain was a predictor of poor outcome (53%) ( p < O.Ol), especially if it signaled the onset of a rapid catastrophic syndrome of T M (64%) ( p < 0,001). CSF pleocytosis or protein elevation had no effect o n clinical outcome, and no particular treatment produced a statistically sig-
Table 3. Factors Affetttangthe Outcome of Acute and Subacute Transverse Myelopathy in 48 of 52 Patients
No. of Patients Factor
Good Fair
Poor
Total
Total group Preceding acute illness Symptoms at onset Paresthesias Back pain Leg weakness Type of onset Catastrophic Progressive Spinal shock CSF pleocytosis Treatment None ACTH Corticosteroid Laminectomy Multiple sclerosis
16 10
20
12 4
48 19
9 3 4
12
3 9 0
24 17 7 11 37
5
5 3
1
3
15 0
17 2
6
4
7 5 7 7
6 4 6
11
7
24
3 6
4
11 13 2 7
0 2
0
1 2
4
1
9 17
ACTH = adrenocorticotropic hormone.
nificant change in outcome. Patients with signs of spinal shock did poorly, but the number of patients was small, and patients with swelling of the spinal cord on myelogram had outcomes similar to those of the whole group. Patients who ultimately developed multiple sclerosis were evenly distributed with respect to outcome (see Table 3).
Pathological Material Patient 1 A 44-year-old woman experienced sharp, severe midback pain. Over 24 hours the left leg became numb and the right hip weak. I n the subsequent ten days she developed numbness ascending up to the nipples and bilateral leg weakness. There was flaccid paraplegia and a T 3 sensory level. The CSF showed 40 lymphocytes and 5 polymorphonuclear cells. Two months later her shoulders became weak and the sensory level rose. Seven months later she suffered acutely diminished vision in the left e y e and remained quadriparetic until her death. At postmortem examination no gross abnormality was seen in the cerebral hemispheres, brainstem, and cerebellum. There was an acute and subacute necrotizing process involving the midcervical to high lumbar regions of the cord to a variable extent, with the midcervical region being most severely affected. Myelin was destroyed in these regions (Fig 3A). Profuse microglial and 1ymphocytic infiltration permeated the necrotic background debris (Fig 3B). Scattered intramedullary vessels had a thin cuff of lymphocytes, but this was not a prominent feature. Few recognizable neurons were apparent at levels of intense destruction, and the gray matter area was not easily recognized. At L1
Ropper and Poskanzer: Prognosis of Transverse Myelopathy
55
and below, the destruction was limited to patches of demyelination in the posterior columns, affecting mainly the areas adjacent to the posterior root entry zones. The fasciculus gracilis and lateral corticospinal and spinothalamic tracts were also atfccted with a demyelinating process. Axon cylinders were preserved except for some disordered appearance in areas of intense and widespread necrosis. T h e anterior and posterior roots were well preserved at all levels. Sections of the optic nerve showed diffuse demyelination o n the left and no abnormality o n the right. These findings indicate a primary demyelinating process of widespread and destructive character in the cord and optic nerve. Necrotic myelopathy and optic nerve demyelination are consistent with Devic opticomyelitis [ 11, and the history is compatible with this diagnosis.
56 Annals of Neurology
Vol 4 N o 1 July 1978
F i g 3 . (Patient 1 . ) (A) Transverte section from the cewicalcovd with only a fezre irlunds of bbck-staining myelin remaining. Both gray and white mutter are afficted by a necroticprocess. (Haidenhain-Woelcke. xl0.) ( B )Area from the htwalcolumn of the cercical cord demonstrating background of necrosis with glial and inflammutovy response. (Hematoxylin and eosin, x200.1
Patient 2 A 64-year-old woman had a band of tightness around the chest beginning two weeks after an upper respiratory tract infection. Several days later the right leg became weak. This progressed, and urine retention developed. Examination revealed no movement of the right leg and 5/10 power in the left. Pinprick sensation was diminished in the left leg
and left side of the trunk to the clavicle. Vibration sense was lost bilaterally to the costal margins. CSF examination showed 3 polymorphonuclear leukocytes and 1 lymphocyte. She died 50 days later of a pulmonary embolus. At autopsy there was narrowing and softening of the cord from approximately C8 to T4. A diffuse necrotizing process involved the entire midthoracic region, sparing a small anterior rim (Fig 4A). At the highest level the lesion involved a demarcated oval portion of the ventral posterior columns and medial posterior horns. I n the high lumbar region only a small, well-demarcated area of the posterior columns was involved (Fig 4B).
F i g 4. (Patient 2.) (A) Transverse section throzlgh the midthoracic cord. An anterior and lateral rim of black-staining myelin remains. The white and gray matter is otherwise necrotic. (Haidenhain-Woelcke, x 10 before 10% redzlctivn.) (Bi Transverse section through LI . An inflammatory and necrotizing proms involves the posterior columns andposterior root entcy zones. (Haidenhain-Woelcke, ~ 1 0 . )
The nature of this lesion was necrotic and not inflammatory. Selective sparing of axons was not found. The gray and white matter were equally affected. T h e general autopsy revealed diffuse peritoneal carcinomatosis of ovarian origin. Necrotizing myelopathy accompanying carcinoma has been described previously [ 12, 291. This case appeared as CPC 26-1976 in the N e w England Journal of Medicine [ 4 ] .
Patient 3 A 25-year-old woman presented with acute myelopathy of the cervical region. It began with leg weakness that progressed over five days. After her condition had been stable for several weeks, dementia occurred and pneumoencephalography demonstrated hydrocephalus. A brain biopsy was performed because of rapidly deteriorating cerebral function. She died seven months after the onset of the illness. No autopsy was obtained. A surgical specimen from the right frontal lobe showed an active demyelinating process consistent with multiple sclerosis.
Ropper and Poskanzer: Prognosis of Transverse Myelopathy
57
Discussion Pathological studies have demonstrated that a considerable longitudinal extent of spinal cord is involved with necrosis or inflammation in T M [7, 81. I t is possible that pain is appreciated only at the highest dermatome level affected because sensation is impaired below this level. Back pain may be caused by stretching of dural structures in a similar fashion to headache pain [ 5 ] . Patient 1 and several others in our experience demonstrate that acute back pain at the onset of T M can be due to a necrotic myelopathy. Radicular pain is explained by involvement of posterior root entry zones by the pathological process. The frequently ascending sensory symptoms in T M have a different cause from similar symptoms in acute idiopathic polyneuritis. Involvement of posterior and perhaps lateral column sensory fibers in T M produces numbness o r tingling in areas supplied by fibers below the affected level. As the pathological process extends both rostrally and caudally, only the rostra1 progression is appreciated, thus causing ascending paresthesias. For this reason, sensory symptoms in the lower extremities are not accompanied by simultaneous numbness or tingling in the upper extremities as in poiyneuritis. Dissociated spinothalamic sensory loss with posterior column sparing can occur in T M without anterior spinal artery occlusion. Several of our patients with this finding had a slowly progressive course, incompatible in our experience with anterior spinal artery occlusion. The preferential involvement of the mid-
thoracic region by TM is not easily explained. Previous reports have suggested that it is due to a comparatively poor vascular supply. The lesser longitudinal extent of the lumbar as compared to the thoracic cord in part explains why it is less frequently affected in TM. Three published series of T M are available for comparison with the present cases (Table 4). Paine and Byers’ [15] cases were all in children, and 60% followed an acute infectious illness. Weakness of the legs was the most common initial presentation, and the outcome was generally good. No information was available regarding subsequent occurrence of multiple sclerosis. Altrocchi’s [ 2 ] 67 patients of all ages were similar to those in the present series. Although Altrocchi’s patients were divided approximately equally among the good, fair, and poor outcome groups, only 1 patient recovered to normal. Total follow-up was shorter than in the present series. Thirty-four patients of all ages reported by Lipton and Teasdall [ 111 were similar to those in this series. Thirty-five percent had had a preceding viral infection. Only 2 9 patients had adequate follow-up, though information about the onset of T M was available for 32. At autopsy, spinal cord infarction was seen in 2 patients, “nonspecific necrotizing lesions” in 2 , meningiomyelitis in 1, and intramedullary capillary telangiectasia in I patient. Myelography was not done in 25 of Altrocchi’s 67 patients nor in 23 of the 34 patients of Lipton and Teasdall. Because o u r initial chart review revealed that many patients initially
Table 4 . Clinical Data and Outcome in 178 Patients from Four Series of Transcevse Myelopathy
Data and Outcome
Paine and Byers [ 151
Lipton and Altrocchi [2] Teasdall [ 1I ] [this series]
Total patients Preceding febrile illness Initial symptoms Paresthesias Back pain
25 15
20
1
6 9 3
Leg weakness
Sphincter disturbance Time to maximal deficit 10 days Multiple sclerosis
Outcome Good Fair Poor ~
58
67
17 17 17 2
...
30 23
... .. .
16 4
15
22 22 16
6 ... ~
Annals of Neurology Vol 4
Total
% of Patients with Information Available 37
Ropper and Poskanzer
No 1 July 1978
34 12
52 18
178 65
9 12 11
24 18 7
51 53
44
4
3
12
32 34 28 7
15 17 2 1
13 30 7
58 70 27 12
37 45 18 7
9 9
16 20 12
62 57 30
42 38 20
2
9
diagnosed as having TM were instead found at postmortem or on myelography to have tumors impinging on the cord, there is some question about the cause of T M in a large number of patients in these series. If the Massachusetts General Hospital series is summed with the other three series, 178 patients are available for study (see Table 4). Of these, 149 have adequate follow-up to determine outcome. Major initial symptoms were paresthesias, back pain, and leg weakness, each in approximately one-third of the total group. Most of the patients (74%) had a sensory level in the thoracic region. Multiple sclerosis developed in 7% of the total group. This study suggests that three distinct types of onset occur in TM. The largest group have ascending paresthesias at the onset, usually with a course that evolves over one to fourteen days. The outcome is usually good or fair in this group. Another group has pain at onset, usually in the back, which comes on suddenly and evolves over several hours; this group tends to have a poor prognosis. In a smaller, third group the syndrome evolves over ten days to four weeks in a stuttering course. The illness seems to stabilize, and then suddenly a new symptom appears. All the major symptoms of T M are represented within this group. The prognosis tends to be the same as in the gradually progressive group, i.e., most have a good or fair outcome. The overall good or fair prognosis, low incidence of multiple sclerosis, and large number of patients with venous thromboembolic complications are emphasized.
We are indebted to Dr E. P. Richardson of the Massachusetts General Hospital and to Dr C. Masters of the National Institutes of Health for their helpful advice.
References 1. Adams RD, Kubik CS: The morbid anatomy of the de-
rnyelinating diseases. Am J Med 12:510-546, 1952 2. Altrocchi PH: Acute transverse myelopathy. Arch Neurol 9:111-119, 1963 3. Bell EJ, Russel SJM: Acute transverse myelopathy and ECHO-2 virus infection. Lancet 2:1226-1227, 1963 4. Case records of the Massachusetts General Hospital. N Engl J Med 294:1447-1454, 1976 5. Dalessio DJ (ed): Wolff's Headache and Other Head Pain. New York, Oxford University Press, 1972, pp 57-99 6. Foix C, Alajouanine T: La myelite necrotique. Rev Neurol (Paris) 2:l-42, 1926 7. Greenfield JO, Turner J W A Acute and subacute necrotic myelitis. Brain 62:227-252, 1939 8. Hoffman H L Acute necrotic myelopathy. Brain 78:377-391, 1955 9. Hogan B W Acute myelitis: syndrome of occlusion of the anterior spinal artery at the first thoracic segment with softening of the cord. US Nav Med Bull 40:175-178, 1942 10. Hogan EL, Krigman M R Herpes zoster myelitis. Evidence for viral invasion of spinal cord. Arch Neurol 29:309-313, 1973 11. Lipton LH, Teasdall RD: Acute transverse myelopathy in adults. Arch Neurol 28:252-257, 1973 12. Mancall EL, Rosales R K Necrotizing myelopathy associated with visceral carcinoma. Brain 87:639-655, 1964 13. McAlpine D, Lumsden CE, Acheson ED: Multiple Sclerosis: A Reappraisal. London, Livingstone, 1968 14. Muller H G , Stanton JB, Gibbons JL: Parainfectious encephalomyelitis and related syndromes: a critical review of the neurologic complications of certain fevers. Q J Med 25:427505, 1956 15. Paine RS, Byers RK: Transverse myelopathy in childhood. AMA Arch Dis Child 85:151-163, 1953 16. Pallis CA, Louis S, Morgan RL: Radiation myelopathy. Brain 84:460-479, 1961 17. Prussin G, Kataki G : Dorsolumbar myelitis following antirabies vaccination with duck-embryo vaccine. Ann Intern Med 60:114-116, 1963 18. Steegman A T Syndrome of the anterior spinal artery. Neurology ( h h n e a p ) 2: 15-3 5, 1952 19. Williams R, Diamond H D , Craver LF: The pathogenesis and management of neurological complications in patients with malignant lymphomas and leukemias. Cancer 11:76-82, 1958 20. Wyburn-Mason R: Venous abnormalities, in The Vascular Abnormalities and Tumors of the Spinal Cord and Its Membranes. St Louis, Mosby, 1944
Ropper and Poskanzer: Prognosis of Transverse Myelopathy 59
