growth characteristics in culture and is sensitive to
a
number of antibiotic agents. G. Franklin, MD Dept of Neurology Southwestern Med School Univ of Texas Health Science Center at Dallas Dallas, TX 75235
1. Jones HM: Cranial pneumatocoele. Proc R Soc Med 63:257-262, 1970. 2. French LA, Chou SN: Osteomyelitis of the skull and epidural abscess, in Gurdjian ES (ed): Cranial and Intracranial Suppuration. Springfield, Ill, Charles C Thomas Publisher, 1969, pp 59-72. 3. Handel SF, Kelin WC, Kimy YW: Intracranial epidural abscess. Radiology 111:117-120, 1974. 4. Dorff GJ, Jackson LJ, Rytel MW: Infections with Eikenella corrodens: A newly recognized human pathogen. Ann Intern Med 80:305-309, 1974. 5. Marsden HB, Hyde WA: Isolation of Bacteroides corrodens from infections in children. J Clin Pathol 24:117-119, 1971.
Arachnoiditis From Intrathecally Given Corticosteroids in the Treatment of Multiple Sclerosis To the Editor.\p=m-\Ina previous report,1 arachnoiditis and sterile meningitis were listed as serious side effects from methylprednisolone acetate given intrathecally to patients with acute-phase multiple sclerosis. In addition to the four previously reported patients with arachnoiditis, we have seen three others, bringing the total reported cases to seven. The following report is
typical. Report of a Case.\p=m-\Beginning36 years ago, a 53-year-old man developed retrobulbar neuritis, spasticity of the legs, paresthesia of the hands, and papillitis of the optic disks in exacerbations and remissions. Elsewhere, he was given a series of 16 intrathecal injections of methylprednisolone acetate (40 to 80 mg each) over a seven-year period. The spinal fluid protein content gradually
racic areas. They thesia of the legs
complaint might be related to the well-known elevation of spinal fluid protein and cell content following injections. Some investigators have found the protein and cell content to be directly related to the dosage of corticosteroid given. Patients with arachnoiditis thus far reported have shown a progression upward of spinal fluid protein level and a steady downhill course in leg strength and bladder function. This combination of events may well be a sign of arachnoiditis, and the harbinger of a complete spinal fluid block. The dangers of adhesive arachnoiditis and the findings of insignificant rates of improvement in several studies indicate little rationale for this mode of therapy in patients with multiple sclero¬ sis. D. Nelson, MD Wilmington Med Center Wilmington, DE 19899 1. Nelson
DA, Vates TS Jr, Thomas RB Jr: Complications from intrathecal steroid therapy in patients with multiple sclerosis. Acta Neurol Scand 49:176-188, 1973.
Platelet Hyperaggregability in Young Patients With Stroke To theEditor.\p=m-\The
interesting article by Kalendovsky et al, on platelet hyperaggregability in young patients with stroke, in the January 1975 issue of the Archives (32:13,1975) prompts me to make this report (March 1975) of results obtained from a pilot study conducted on 15 patients with stroke (mean age, 63 years) vs 15 control patients of the same age, 15 young asymptomatic persons (mean age, 25 years) and 15 other patients given anticoagulant therapy with warfarin sodium (Coumadin) (mean prothrombin time, 20.6 sec-
onds).
Comment.—Intrathecally given
corticosteroids continue to be administered to many patients for the treatment of arachnoiditis following surgery for disk disease, and for the treatment of multiple sclerosis. The lack of complications reported in patients treated for disk complica¬ tions may be due to the difficulty of evaluating possible "new" arachnoiditis added to chronic arachnoiditis. Also, there may be a difference in the pathophysiology of arachnoiditis in patients with disk disease as compared to those with multiple sclerosis. Patients who are given methylprednisolone
intrathecally
One of the coagulation tests performed was designed here. It consisted of drawing 10 ml of fresh venous blood, placing 0.5 ml in each of ten funnel-shaped glass tubes, then leaving it to clot. Exactly 15 and 30 minutes after the blood had been drawn, each set of five clot-containing glass tubes was subjected to a continuously increasing pressure induced by pumped isotonic saline, until the clots gave away. All pressures recorded from each set were averaged (we termed this test "mechanical clot resistance"). The results from this test (Figure) showed that the 15 stroke patients had a significantly higher mean clot resistance as compared to both control groups (P .01). Two other strokes due to hyper¬ tensive hemorrhage, one embolie case secondary to auricular fibrillation, and one stroke with simultaneous disseminated intravascular coagu¬ lation all showed "normal" or low mean values. The young control group demonstrated practi¬ cally the same mean values as those of the similar-age control group. But two young women had high values equivalent to those of the stroke group. Both of them suffered chronic migraine headaches. Using the aggregometer in vitro, the hyperaggregability of platelets showed no significant statistical differences between the various groups (16%). Diabetes (37%) and hyperlipidemias (types II and IV, 42%) were also not significantly different. On the other hand, hyper¬ tension (42%) and electrocardiographic evidence of previous myocardial infarction (28%) were both significantly different factors (P .05 and =
=
=
prone to develop arachnoiditis in the upper lumbar and midthoseem
Downloaded From: http://archneur.jamanetwork.com/ by a Georgetown University Medical Center User on 05/21/2015
.025, respectively).
It is of interest to note that independent studies of cerebrovascular disease, using differ¬ ent coagulation indexes, have shown seemingly consistent abnormal results.14 This information is offered only to add further
Time sequence of mechanical clot resistance. Values
given
are mean
of each group.
450
increased from 82 to 159 mg/100 ml. He had subjective spasticity of the legs during a five\x=req-\ year period that necessitated hospitalization in 1974. A myelogram revealed multiple adhesions in the subarachnoid space at T-1 through T-4 and T-12 through L-2. Loculated iophendylate (Pantopaque) was trapped in these areas and did not move although the patient was placed in the sitting position for several hours. Surgery was not recommended1 because of the multiple levels of the lesions.
acetate
frequently complain of pares¬ following such injections. This
411
261
Hypercoagulable Stroke Group Controls of Similar Age Young Controls
208 76 Warfarin Sodium Patients
200
8
10
12
18
20
22
24
26
28
30
indirect support to their notion that "hypercoagulability" may be a critical variable in the complex physiopathogenesis of arterial occlu¬ sions. E. L. Labadie, MD Dept of Neurology Arizona Med Center Tucson, AZ 85724
Ettinger MG: Coagulation studies in cerebrovascular disease: Part I. Hypercoagulability. Neurology 14:907-911, 1964. 2. Fletcher AP, Brooks J, David D, et al: Blood hypercoagulability in acute cerebrovascular syn-
appeared were secondary to life-threatening hypoxemia, possibly enhanced by some auton¬ omie dysfunction. Therapy of these arrhythmias more properly should have been directed at providing the minimum essentials of safe respi¬ ratory
care.
Maj N. L. Pace, MD, USMC Anesthesia and Operative Service Brooke Army Medical Center Fort Sam Houston, TX 78234
1.
drome. J Lab Clin Med 76:879-880, 1970. 3. Sano T, Boxer MG, Boxer LA: Platelet sensitivity to aggregation in normal and deceased groups. Thromb Diath Haemorrh 25:524-531, 1971. 4. Bonen B, Guiraud B, Fernet P: Platelet aggregation, inhibition treatment with ASA, biological bases and application to cerebrovascular accidents. Nouv Presse Med 1:863-868, 1972.
Cardiac
Monitoring
and Demand
Pacemaker in Guillain-Barr\l=e'\
Syndrome (Arch Neurol 32:59, 1975) reported the use of a temporary transvenous demand pacemaker to prevent cardiac To theEditor.\p=m-E ons
arrest from
et al
arrhythmias that developed during tracheal suctioning in an 11-year-old child with syndrome receiving continuous mechanical ventilation. Each episode of suctioning was associated with sinus bradycardia (day 6) or idioventricular bradycardia (days 7-12), as well as profuse diaphoresis, restlessness, and an ashen-gray color. Following suctioning, the cardiac rhythm reverted to a sinus tachycardia with systemic hypertension. The authors attributed these arrhythmias to the autonomic dysfunction that may occur with the Guillain\x=req-\ Barr\l=e'\syndrome. Previous work in the management of patients receiving continuous mechanical ventilation sugsevere
Guil ain-Barr\l=e'\
1. Bendixen
HH, Egbert LD, Hedley-Whyte J, airway, in Respiratory Care. Saint Louis, CV Mosby Co, 1965. 2. Marx GF, Steen SN, Arkins RE, et al:
et al: The
Endotracheal suction and death. N York J Med
68:565-571, 1968. 3. Fell T, Cheney FW: Prevention of hypoxia during endotracheal suction. Ann Surg 174:24-28, 1971. 4. Shim
C, Fine N, Fernandez R, et al: Cardiac arrhythmias resulting from tracheal suctioning. Ann Intern Med 71:1149-1153, 1969. In Reply.\p=m-\ I am grateful for Dr Pace's interest and comments. Regrettably, we did not obtain blood gas measurements while the child was being suctioned and it was not possible directly to respond to his suggestions. However, we did notice that suctioning during other times of the illness was only infrequently associated with
arrhythmias, although these became predictable when other signs of autonomic dysfunction occurred. Furthermore, suctioning continued during convalescence after the pacemaker was removed and no more arrhythmias occurred. Therefore, it may be that a combination of hypoxia and neurological damage is necessary for these serious cardiac complications to occur. Further clinical investigation undoubtedly will provide the answers. P. R. Emmons, MD 4786 Drummond Dr Vancouver, BC V6T 1B4 Canada
gests a different cause and treatment for the observed arrhythmias. With the widespread use of mechanical ventilation to manage respiratory failure, reports of cardiac arrest during and immediately following endotracheal suctioning are not infrequent.1,2 Cardiac arrest during prolonged aspiration of the airway is most likely caused by massive reduction in lung volume with subsequent hypoxia, rather than by reflex irrita¬ tion. Indeed, Fell and Cheney3 showed that significant hypoxemia (PAo2 < 65 mm Hg) does develop during suctioning. This can be avoided by prior hyperinflation for one minute with 100% 02 and by limiting suctioning time to 15 seconds.3 Shim et al4 noted a 35% incidence of cardiac arrhythmias during trachéal suctioning; how¬ ever, these arrhythmias were not observed if patients received five minutes of 100% 02 and were suctioned for only ten seconds. The case-report states that suctioning time was limited, but no precise time is given. No mention is made of pretreatment with 100% 02 prior to suctioning. Also, it is noted that diaphor¬ esis, anxiety, and an ashen-gray color developed during suctioning. It is only reasonable to conclude that the serious arrhythmias that
Steroid Therapy in Acute Cerebral Infarction To the Editor.\p=m-\The article by Norris, "Steroid Therapy in Acute Cerebral Infarction" (Arch Neurol 33:69-71,1976), seems to have some tables mixed up. Table 1, "Data on Survivors in Steroid Group," has an average initial score of 115 and an average 29-day score of 64. Yet, these values are plotted for the placebo group in the graph on page 70 and included in the placebo group in Table 3. Table 2, "Data on Survivors in Placebo Group," has an average initial score of 135 and a 29-day score of 100. Yet, these values are graphed for the steroid group on page 70 and included in the steroid group in Table 3. Assuming that Tables 1 and 2 have been reversed and Table 3 is correct, the conclusion that patients treated with the steroid did not fare as well as those receiving placebo is still not justified by the data presented because the initial
of both groups
different
(t 1.72, N 39, < .05), indicating one group (probably the steroid-treated) was sicker than the placebo scores
Downloaded From: http://archneur.jamanetwork.com/ by a Georgetown University Medical Center User on 05/21/2015
=
were
=
group. The two groups were also unequal in regard to cause of stroke. Incidentally, Norris misquoted the study I and my colleagues did on this subject.1 We did encounter exacerbation of diabetes in one patient, and the steroid administration had to be stopped within 12 hours of the initiation of therapy. Whether the patients who had cerebral hemorrhages in our series were included or excluded, we did not demonstrate any benefit of treatment in the series taken as a whole. It was only when we looked at the patients who had the most severe strokes (initial score of 25 or greater in our scoring system) that the treated did better than controls (P < .02). Our low incidence of hematemesis may have been due to the prophy¬ lactic regimen of oral antacids, and our low incidence of infection may have been due to our bladder and bowel care, frequent turning of patients, and the use of antibiotics. Since so many of Norris's patients had emboli as the cause of their stroke, I wonder if he gave anticoagu¬ lants to any patients? Also, will he explain by what route the steroid was given and why some patients were lost to follow-up? In order to ensure patient compliance in our study, we injected the steroid and placebo intramuscularly every six hours while the patient was in the hospital under observation. Dose may be important in the therapy of infarction because in the mongolian gerbil model, higher doses are associated with mortality reduc¬ tion (P < .01) and reduction of edema (P < ,03)2 whereas lower doses have no beneficial effects.3 In our study in humans, the total dose of dexamethasone was 220 mg compared to Norris's 140 mg; our duration of treatment was 17 days instead of Norris's 12 days. Cerebral edema due to infarction develops regularly and rapidly over the first five days after insult and gradually subsides, disappearing in about two weeks. A treatment period of 12 days might represent a premature tapering of the dose. In this regard it is interesting to note that Norris's Table 3 shows a 49% worsening of average scores in the steroidtreated group between day 15 and day 22, a time when steroid suppressed edema might be expected to flare. This is the only group and the only time that average scores worsened. If this point (167) had been correctly plotted on the graph on page 70, it would have shown a striking alteration of the normal recovery curve in the steroid group. None of the scores in either Table 1 or 2, however, add up to 167, so it is not clear where this number came from. Perhaps it is a
misprint.
Patten, MD Baylor Coll of Med Houston, TX 77030 1. Patten BM, Menndell J, Bruun B, et al: Double-blind study of the effects of dexamethasone on acute stroke. Neurology 4:377-383, 1972. 2. Harrison MJG, Brownbill D, Lewis PD, et al: Cerebral edema following carotid artery ligation in the gerbil. Arch Neurol 28:389-391, 1973. 3. Khan KJ, Pranzarone GF, Newman T: Dexamethasone treatment of experimental cerebral infarction. Neurology 22:406-407, 1972. B. M.
To the Editor.\p=m-\ I read Norris's article with interest and some confusion. There are several inconsistencies. The major one concerns the conclusion (I would draw attention to the para-
a
number of antibiotic agents. G. Franklin, MD Dept of Neurology Southwestern Med School Univ of Texas Health Science Center at Dallas Dallas, TX 75235
1. Jones HM: Cranial pneumatocoele. Proc R Soc Med 63:257-262, 1970. 2. French LA, Chou SN: Osteomyelitis of the skull and epidural abscess, in Gurdjian ES (ed): Cranial and Intracranial Suppuration. Springfield, Ill, Charles C Thomas Publisher, 1969, pp 59-72. 3. Handel SF, Kelin WC, Kimy YW: Intracranial epidural abscess. Radiology 111:117-120, 1974. 4. Dorff GJ, Jackson LJ, Rytel MW: Infections with Eikenella corrodens: A newly recognized human pathogen. Ann Intern Med 80:305-309, 1974. 5. Marsden HB, Hyde WA: Isolation of Bacteroides corrodens from infections in children. J Clin Pathol 24:117-119, 1971.
Arachnoiditis From Intrathecally Given Corticosteroids in the Treatment of Multiple Sclerosis To the Editor.\p=m-\Ina previous report,1 arachnoiditis and sterile meningitis were listed as serious side effects from methylprednisolone acetate given intrathecally to patients with acute-phase multiple sclerosis. In addition to the four previously reported patients with arachnoiditis, we have seen three others, bringing the total reported cases to seven. The following report is
typical. Report of a Case.\p=m-\Beginning36 years ago, a 53-year-old man developed retrobulbar neuritis, spasticity of the legs, paresthesia of the hands, and papillitis of the optic disks in exacerbations and remissions. Elsewhere, he was given a series of 16 intrathecal injections of methylprednisolone acetate (40 to 80 mg each) over a seven-year period. The spinal fluid protein content gradually
racic areas. They thesia of the legs
complaint might be related to the well-known elevation of spinal fluid protein and cell content following injections. Some investigators have found the protein and cell content to be directly related to the dosage of corticosteroid given. Patients with arachnoiditis thus far reported have shown a progression upward of spinal fluid protein level and a steady downhill course in leg strength and bladder function. This combination of events may well be a sign of arachnoiditis, and the harbinger of a complete spinal fluid block. The dangers of adhesive arachnoiditis and the findings of insignificant rates of improvement in several studies indicate little rationale for this mode of therapy in patients with multiple sclero¬ sis. D. Nelson, MD Wilmington Med Center Wilmington, DE 19899 1. Nelson
DA, Vates TS Jr, Thomas RB Jr: Complications from intrathecal steroid therapy in patients with multiple sclerosis. Acta Neurol Scand 49:176-188, 1973.
Platelet Hyperaggregability in Young Patients With Stroke To theEditor.\p=m-\The
interesting article by Kalendovsky et al, on platelet hyperaggregability in young patients with stroke, in the January 1975 issue of the Archives (32:13,1975) prompts me to make this report (March 1975) of results obtained from a pilot study conducted on 15 patients with stroke (mean age, 63 years) vs 15 control patients of the same age, 15 young asymptomatic persons (mean age, 25 years) and 15 other patients given anticoagulant therapy with warfarin sodium (Coumadin) (mean prothrombin time, 20.6 sec-
onds).
Comment.—Intrathecally given
corticosteroids continue to be administered to many patients for the treatment of arachnoiditis following surgery for disk disease, and for the treatment of multiple sclerosis. The lack of complications reported in patients treated for disk complica¬ tions may be due to the difficulty of evaluating possible "new" arachnoiditis added to chronic arachnoiditis. Also, there may be a difference in the pathophysiology of arachnoiditis in patients with disk disease as compared to those with multiple sclerosis. Patients who are given methylprednisolone
intrathecally
One of the coagulation tests performed was designed here. It consisted of drawing 10 ml of fresh venous blood, placing 0.5 ml in each of ten funnel-shaped glass tubes, then leaving it to clot. Exactly 15 and 30 minutes after the blood had been drawn, each set of five clot-containing glass tubes was subjected to a continuously increasing pressure induced by pumped isotonic saline, until the clots gave away. All pressures recorded from each set were averaged (we termed this test "mechanical clot resistance"). The results from this test (Figure) showed that the 15 stroke patients had a significantly higher mean clot resistance as compared to both control groups (P .01). Two other strokes due to hyper¬ tensive hemorrhage, one embolie case secondary to auricular fibrillation, and one stroke with simultaneous disseminated intravascular coagu¬ lation all showed "normal" or low mean values. The young control group demonstrated practi¬ cally the same mean values as those of the similar-age control group. But two young women had high values equivalent to those of the stroke group. Both of them suffered chronic migraine headaches. Using the aggregometer in vitro, the hyperaggregability of platelets showed no significant statistical differences between the various groups (16%). Diabetes (37%) and hyperlipidemias (types II and IV, 42%) were also not significantly different. On the other hand, hyper¬ tension (42%) and electrocardiographic evidence of previous myocardial infarction (28%) were both significantly different factors (P .05 and =
=
=
prone to develop arachnoiditis in the upper lumbar and midthoseem
Downloaded From: http://archneur.jamanetwork.com/ by a Georgetown University Medical Center User on 05/21/2015
.025, respectively).
It is of interest to note that independent studies of cerebrovascular disease, using differ¬ ent coagulation indexes, have shown seemingly consistent abnormal results.14 This information is offered only to add further
Time sequence of mechanical clot resistance. Values
given
are mean
of each group.
450
increased from 82 to 159 mg/100 ml. He had subjective spasticity of the legs during a five\x=req-\ year period that necessitated hospitalization in 1974. A myelogram revealed multiple adhesions in the subarachnoid space at T-1 through T-4 and T-12 through L-2. Loculated iophendylate (Pantopaque) was trapped in these areas and did not move although the patient was placed in the sitting position for several hours. Surgery was not recommended1 because of the multiple levels of the lesions.
acetate
frequently complain of pares¬ following such injections. This
411
261
Hypercoagulable Stroke Group Controls of Similar Age Young Controls
208 76 Warfarin Sodium Patients
200
8
10
12
18
20
22
24
26
28
30
indirect support to their notion that "hypercoagulability" may be a critical variable in the complex physiopathogenesis of arterial occlu¬ sions. E. L. Labadie, MD Dept of Neurology Arizona Med Center Tucson, AZ 85724
Ettinger MG: Coagulation studies in cerebrovascular disease: Part I. Hypercoagulability. Neurology 14:907-911, 1964. 2. Fletcher AP, Brooks J, David D, et al: Blood hypercoagulability in acute cerebrovascular syn-
appeared were secondary to life-threatening hypoxemia, possibly enhanced by some auton¬ omie dysfunction. Therapy of these arrhythmias more properly should have been directed at providing the minimum essentials of safe respi¬ ratory
care.
Maj N. L. Pace, MD, USMC Anesthesia and Operative Service Brooke Army Medical Center Fort Sam Houston, TX 78234
1.
drome. J Lab Clin Med 76:879-880, 1970. 3. Sano T, Boxer MG, Boxer LA: Platelet sensitivity to aggregation in normal and deceased groups. Thromb Diath Haemorrh 25:524-531, 1971. 4. Bonen B, Guiraud B, Fernet P: Platelet aggregation, inhibition treatment with ASA, biological bases and application to cerebrovascular accidents. Nouv Presse Med 1:863-868, 1972.
Cardiac
Monitoring
and Demand
Pacemaker in Guillain-Barr\l=e'\
Syndrome (Arch Neurol 32:59, 1975) reported the use of a temporary transvenous demand pacemaker to prevent cardiac To theEditor.\p=m-E ons
arrest from
et al
arrhythmias that developed during tracheal suctioning in an 11-year-old child with syndrome receiving continuous mechanical ventilation. Each episode of suctioning was associated with sinus bradycardia (day 6) or idioventricular bradycardia (days 7-12), as well as profuse diaphoresis, restlessness, and an ashen-gray color. Following suctioning, the cardiac rhythm reverted to a sinus tachycardia with systemic hypertension. The authors attributed these arrhythmias to the autonomic dysfunction that may occur with the Guillain\x=req-\ Barr\l=e'\syndrome. Previous work in the management of patients receiving continuous mechanical ventilation sugsevere
Guil ain-Barr\l=e'\
1. Bendixen
HH, Egbert LD, Hedley-Whyte J, airway, in Respiratory Care. Saint Louis, CV Mosby Co, 1965. 2. Marx GF, Steen SN, Arkins RE, et al:
et al: The
Endotracheal suction and death. N York J Med
68:565-571, 1968. 3. Fell T, Cheney FW: Prevention of hypoxia during endotracheal suction. Ann Surg 174:24-28, 1971. 4. Shim
C, Fine N, Fernandez R, et al: Cardiac arrhythmias resulting from tracheal suctioning. Ann Intern Med 71:1149-1153, 1969. In Reply.\p=m-\ I am grateful for Dr Pace's interest and comments. Regrettably, we did not obtain blood gas measurements while the child was being suctioned and it was not possible directly to respond to his suggestions. However, we did notice that suctioning during other times of the illness was only infrequently associated with
arrhythmias, although these became predictable when other signs of autonomic dysfunction occurred. Furthermore, suctioning continued during convalescence after the pacemaker was removed and no more arrhythmias occurred. Therefore, it may be that a combination of hypoxia and neurological damage is necessary for these serious cardiac complications to occur. Further clinical investigation undoubtedly will provide the answers. P. R. Emmons, MD 4786 Drummond Dr Vancouver, BC V6T 1B4 Canada
gests a different cause and treatment for the observed arrhythmias. With the widespread use of mechanical ventilation to manage respiratory failure, reports of cardiac arrest during and immediately following endotracheal suctioning are not infrequent.1,2 Cardiac arrest during prolonged aspiration of the airway is most likely caused by massive reduction in lung volume with subsequent hypoxia, rather than by reflex irrita¬ tion. Indeed, Fell and Cheney3 showed that significant hypoxemia (PAo2 < 65 mm Hg) does develop during suctioning. This can be avoided by prior hyperinflation for one minute with 100% 02 and by limiting suctioning time to 15 seconds.3 Shim et al4 noted a 35% incidence of cardiac arrhythmias during trachéal suctioning; how¬ ever, these arrhythmias were not observed if patients received five minutes of 100% 02 and were suctioned for only ten seconds. The case-report states that suctioning time was limited, but no precise time is given. No mention is made of pretreatment with 100% 02 prior to suctioning. Also, it is noted that diaphor¬ esis, anxiety, and an ashen-gray color developed during suctioning. It is only reasonable to conclude that the serious arrhythmias that
Steroid Therapy in Acute Cerebral Infarction To the Editor.\p=m-\The article by Norris, "Steroid Therapy in Acute Cerebral Infarction" (Arch Neurol 33:69-71,1976), seems to have some tables mixed up. Table 1, "Data on Survivors in Steroid Group," has an average initial score of 115 and an average 29-day score of 64. Yet, these values are plotted for the placebo group in the graph on page 70 and included in the placebo group in Table 3. Table 2, "Data on Survivors in Placebo Group," has an average initial score of 135 and a 29-day score of 100. Yet, these values are graphed for the steroid group on page 70 and included in the steroid group in Table 3. Assuming that Tables 1 and 2 have been reversed and Table 3 is correct, the conclusion that patients treated with the steroid did not fare as well as those receiving placebo is still not justified by the data presented because the initial
of both groups
different
(t 1.72, N 39, < .05), indicating one group (probably the steroid-treated) was sicker than the placebo scores
Downloaded From: http://archneur.jamanetwork.com/ by a Georgetown University Medical Center User on 05/21/2015
=
were
=
group. The two groups were also unequal in regard to cause of stroke. Incidentally, Norris misquoted the study I and my colleagues did on this subject.1 We did encounter exacerbation of diabetes in one patient, and the steroid administration had to be stopped within 12 hours of the initiation of therapy. Whether the patients who had cerebral hemorrhages in our series were included or excluded, we did not demonstrate any benefit of treatment in the series taken as a whole. It was only when we looked at the patients who had the most severe strokes (initial score of 25 or greater in our scoring system) that the treated did better than controls (P < .02). Our low incidence of hematemesis may have been due to the prophy¬ lactic regimen of oral antacids, and our low incidence of infection may have been due to our bladder and bowel care, frequent turning of patients, and the use of antibiotics. Since so many of Norris's patients had emboli as the cause of their stroke, I wonder if he gave anticoagu¬ lants to any patients? Also, will he explain by what route the steroid was given and why some patients were lost to follow-up? In order to ensure patient compliance in our study, we injected the steroid and placebo intramuscularly every six hours while the patient was in the hospital under observation. Dose may be important in the therapy of infarction because in the mongolian gerbil model, higher doses are associated with mortality reduc¬ tion (P < .01) and reduction of edema (P < ,03)2 whereas lower doses have no beneficial effects.3 In our study in humans, the total dose of dexamethasone was 220 mg compared to Norris's 140 mg; our duration of treatment was 17 days instead of Norris's 12 days. Cerebral edema due to infarction develops regularly and rapidly over the first five days after insult and gradually subsides, disappearing in about two weeks. A treatment period of 12 days might represent a premature tapering of the dose. In this regard it is interesting to note that Norris's Table 3 shows a 49% worsening of average scores in the steroidtreated group between day 15 and day 22, a time when steroid suppressed edema might be expected to flare. This is the only group and the only time that average scores worsened. If this point (167) had been correctly plotted on the graph on page 70, it would have shown a striking alteration of the normal recovery curve in the steroid group. None of the scores in either Table 1 or 2, however, add up to 167, so it is not clear where this number came from. Perhaps it is a
misprint.
Patten, MD Baylor Coll of Med Houston, TX 77030 1. Patten BM, Menndell J, Bruun B, et al: Double-blind study of the effects of dexamethasone on acute stroke. Neurology 4:377-383, 1972. 2. Harrison MJG, Brownbill D, Lewis PD, et al: Cerebral edema following carotid artery ligation in the gerbil. Arch Neurol 28:389-391, 1973. 3. Khan KJ, Pranzarone GF, Newman T: Dexamethasone treatment of experimental cerebral infarction. Neurology 22:406-407, 1972. B. M.
To the Editor.\p=m-\ I read Norris's article with interest and some confusion. There are several inconsistencies. The major one concerns the conclusion (I would draw attention to the para-
