BRIEF COMMUNICATIONS
Methods
The Transcranial Doppler Appearance of Acute Carotid Artery Occlusion Cole A. Giller, PhD, MD," Dana Mathews, PhD, MD,t Phillip Purdy, MD,$ Thomas A. Kopitnik, MD," H. Hunt Batjer, MD," and Duke S. Samson, MD"
~~
~~~~~
Transcranial Doppler ultrasound is a noninvasive technique of cerebral blood velocity measurement that is being increasingly used to detect untoward hemodynamic changes. I n this report, we describe striking transcranial Doppler ultrasound changes occurring in 2 patients after cervical carotid artery occlusion that led to cerebral infarction. These changes consist of the sudden appearance of a Doppler signal of extremely low pulsatility and moderately high velocity i n the middle cerebral artery distribution. In 1 patient, this signal was the first sign of carotid occlusion. W e suggest that these transcranial Doppler ultrasound changes can provide an early warning of carotid artery compromise. Giller CA, Mathews D, Purdy P, Kopitnik TA, Batjer HH, Samson DS. The transcranial Doppler appearance of acute carotid artery occlusion. Ann Neurol 1992;31:101-103
Acute occlusion of the carotid artery is a common event that may, a t one extreme, be well tolerated and, at the other, lead to cerebral infarction and neurological deficit El, 2). It is therefore important that the clinician recognize early warning signals arising from various monitoring methods that might indicate occlusion and impending infarction. Transcranial Doppler ultrasound ( T C D ) is a recently developed noninvasive means of assessment of cerebral hemodynamics that can detect attenuation of blood velocity in t h e cerebral vessels and thus warn of impending stroke r3-7). I n this report, we describe dramatic changes occurring in the TCD signals of 2 patients with sudden carotid artery occlusion. Both progressed to infarction. We suggest these TCD changes were a marker of poorly tolerated carotid artery occlusion.
From the Departments of *Neurological Surgery, ?Neurology, and $Radiology, The University of Texas Southwestern Medical Center, Dallas, TX.
Received Dec 27, 1990, and in revised form Mar 18, Jul 19, and Aug 15, 1991. Accepted for publication Aug 15, 1991. Address correspondence co Dr Giller, Department of Neurological Surgery, Universiry of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235-8855.
All T C D studies were performed using a 2 mHz pulsed ultrasound device (Trans-Scan, Eden Medical Electronics, Uberlingen, Germany) according to standard criteria [3, 81. Middle cerebral artery (MCA) velocities were obtained from Doppler probes held over the temporal squama using an insonation depth of 45 to 55 mm. The other intracranial arteries were also insonated and mapped in three dimensions as described elsewhere {3]. Mean velocities were averaged over four to five heartbeats and Gosling pulsatilities (defined as systolic minus diastolic divided by mean velocities) were simultaneously recorded. Elevation of the mean blood flow velocity indicates either a local stenosis or an increase in blood flow such as might occur from hyperemia [2, 3, 8-10]. The Gosling pulsatility measures the amount of pulsatile energy in the Doppler signal and decreases with downstream vasodilation or with the addition of upstream resistance to the hemodynamic circuit 13, 1 If. For example, the pulsatility decreases in the presence of proximal stenosis and increases during the pial vasoconstriction of hypocarbia. Normal mean MCA velocities for our laboratory are 45 to 70 cm/sec, and normal MCA pulsatilities are 0.60 to 1.0.
Patient Reports Patient I A 30-year-old woman presented with multiple hemispheral infarcts. Serial angiograms suggested fibromuscular dysplasia with progressive bilateral intracranial internal carotid artery stenoses. An MCA stenosis was not seen on the angiograms, and the residual carotid diameter was 40% on the right and 30% on the left. T C D studies showed mild elevation of the right MCA velocity to 125 cm/sec with a diminished pulsatility of 0.50. The left MCA velocities were in the normal range (maximum at 84 cm/sec). When either carotid artery was manually compressed, flow reversal in the anterior cerebral arteries and flow augmentation in the posterior cerebral arteries were absent. This suggested a lack of collateral flow across the anterior and posterior communicating arteries. Bilateral carotid balloon angioplasties were performed to achieve vessel dilation. Doppler studies then showed an elevation of the right MCA velocity (159 cm/sec), which normalized 1 day later. The left MCA velocities remained mildly elevated. T C D study 2 days later showed the sudden appearance of an abnormal signal in the right MCA with a normal velocity of 89 cm/sec, but with a strikingly diminished pulsatility of 0.15 (Fig 1). The remainder of the TCD study was unchanged. At the same time, the patient became lethargic and hemiparetic on the left. Angiography showed complete occlusion of the right internal carotid artery. Despite a repeat attempt at angioplasty of the right carotid artery, the patient suffered a massive right hemispheral infarct and eventually succumbed to high intracranial pressure.
Patient 2 A 15-year-old girl was found to have a left petrous carotid artery pseudoaneurysm and a left posterior carotid wall aneurysm just distal to the origin of the posterior communicating artery after a motor vehicle accident. The pseudoaneurysm
Copyright 0 1992 by the American Neurological Association
101
Fig 2. Maximal oelocities from right (A) and ldt (Bj middle cerebral arteries of Patient 2 shewing pronounced asymmetry in pulsatility. (Tick mark on y-axis indicates 100 cmlJri-.)
B
was then performed without neurological change, and T C D studies showed only a slight decrease in the right MCA pulsatility (0.81 to 0.64) with no change in velocities. The patient has remained clinically well.
-
I C
Fig I . Maximal velocities in right middle cerebral artery of Patient l before (A) and after (Bi angioplasty, and after appearance of pathologic signal (C). (Tick mark on y-axis indicates 100 cmlser.)
was trapped by ligating the internal carotid artery in the neck and by clipping the intracranial carotid artery at the time of craniotomy. The carotid aneurysm was clipped during the same operation. Postoperatively, an angiogram demonstrated collateral flow across the anterior communicating artery, but TCD studies revealed the appearance in the left MCA of an abnormal signal of high velocity (168 cm/sec) and strikingly low pulsatility (0.22) (Fig 2). Although the right MCA also showed high velocities (164 cm/sec), its pulsatility was twoto threefold that of the abnormal left MCA signal. Over the next week, the left MCA signal became somewhat more pulsatile (0.52). Despite aggressive supportive measures, however, the patient suffered a large left MCA distribution infarct.
Patient .? A 15-year-old boy was found to have a right carotid-cavernous sinus fistula after a motor vehicle accident. He was initially successfully treated with balloon occlusion of the fistula. Eight months later, however, an angiogram showed a large pseudoaneurysm as well as filling of the right MCA from the right carotid artery. T C D studies showed evidence of left-to-right collateral across the anterior communicating artery. Permanent balloon occlusion of the right carotid artery
102 Annals of Neurology
Vol 3 1
No 1 January 1992
Discussion Transcranial Doppler is being used increasingly as a monitoring tool with the intent of obtaining early warning of hemodynamic change 12, 3 , 5-7). In this report, we describe a dramatic and unique change in the T C D signal that heralds carotid artery occlusion and may predict cerebral ischemia. The sudden appearance of extremely low pulsatility in the MCA along with a high-to-normal velocity marked the sudden occlusion of the carotid artery in Patients 1 and 2. In both patients, MCA flow was supplied from collateral sources, and in both patients the ipsilateral hemisphere suffered severe ischemia that progressed to infarction. The low pulsatility of the Doppler signal suggested distal small vessel vasodilation arising as an autoregulatory response to the ischemia, and may have been exaggera,ted by the longer hemodynamic circuit taken t o reach rhe MCA. Arterial pulsatility at a given site along the cerebral vascular tree is determined both by the pulsatile energy of the blood column delivered to that tree and the degree of pial and arteriolar vasodilation in the tissue fed by the artery under study. A proximal stenosis blunts the pulsatile pattern and causes a pulsatility decrease, as seen in both acute and chronic carotid stenoses f2, 6, 71.Furthermore, tissue ischemia induced b y carotid obstruction invokes compensatory pial vasodilation, as seen directly in animal models 112) and in positron emission tomographic studies of cerebral vasospasm f 131, and also leads to a decrease in pulsatility.
The sudden onset and prolonged duration of carotid occlusion in Patients 1 and 2 are in contrast to transient manual compression or chronic carotid atherosclerotic disease, which also lead to low TCD pulsatility, and may explain the occurrence of infarction. In this report, we describe a dramatic TCD change (loss of pulsatility in the presence of high-to-normal velocity) occurring in acute carotid occlusion in 2 patients who subsequently progressed to infarction. For comparison, an example of the more common situation of minimal TCD changes is presented in a patient who tolerated carotid occlusion without difficulty. We suggest that sudden appearance of low pulsatility accompanied by high-to-normal velocity MCA signal should be recognized as a sign of poorly tolerated proximal arterial occlusion and as a warning of impending stroke.
We are grateful to Jeannie Moore for technical support and to Janis Williams for preparing this manuscript.
References 1. Swearingen B, Heros RC. Common carotid occlusion for unclippable carotid aneurysms: an old hut still effective operation. Neurosurgery 1987;21:288-295 2. Schneider PA, Rossrnan ME, Bernstein EF, et al. Effect of internal carotid artery occlusion o n intracranial hemodynamics. Stroke 1988;19:589-593 3. Aaslid R (ed). Transcranial Doppler Sonography. New York: Springer-Verlag, 1986 4. Aaslid R, Huber P, Nornes H. Evaluation of cerebrovascular spasm with transcranial Doppler ultrasound. J Neurosurg ~~
1984;60:37-41 5. Giller CA. A bedside test for cerebral autoregulation using transcranial Doppler ultrasound. Acta Neurochir (Wien) 1991; 108:7-14 6. Giller CA, Stieg PS, Batjer HH, et al. Transcranial Doppler ultrasound as a guide to graded therapeutic occlusion of the carotid artery. Neurosurgery 1990;26:307-311 7 . Halsey JH, McDoweli HA, Gelmon S, Morawetz RB. Blood velocity in the middle cerebral artery and regional blood flow during carotid endarterectomy. Stroke 1989;20:35-38 8. Aaslid R, Markwalder T-M, Nornes H. Noninvasive transcranial Doppler ulrrasound recording of flow velocity in basal cerebral arteries. J Neurosurg 1982;57:769-774 9. Purdy PD, Devous MD, Unwin DH, e t al. Angioplasry of an atherosclerotic middle cerebral artery associated with improvement in regional cerebral blood flow. AJNR 1990;11:878-880 10. Wechsler LR,Ropper AH, Kistler JP. Transcranial Doppler in cerebrovascular disease. Stroke 1986;17:905-912 11. Woodcock JP, Gosling HG, Fitzgerald DE. A new noninvasive technique for assessment of superficial femoral artery obstruction. Br J Surg 1972;59:226-231 12. Kontos H, Wei EP, Navari RM, et al. Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am J Physiol 1978;234:H371-H383 13. Martin WRW, Baker RP, Grubb RL, Raichle ME. Cerebral blood volume, blood flow, and oxygen metabolism in cerebral ischemia and subarachnoid haernorrhage: an in vivo study using positron emission tomography. Acta Neurochir (Wien) 1984; 70:3-9
Contrasting Effects of Alpha, Beta, and Gamma Interferons on Nonspecific Sumressor Function in Mxtiple Sclerosis Avertano N o r o n h a , MBBS, MD, Angela Toscas, BA, and Mark A. Jensen, BS
Interferons are biological molecules with antiviral, antiproliferative, and immunomodulatory actions. Interferon alpha (IFN-a) and -p are potentially useful in the treatment of multiple sclerosis (MS). IFN-y, in contrast, increases the frequency of exacerbations of MS. In this study, we compared the effect of recombinant human IFN-a, -p, and -y on suppressor function in patients with MS. Nonspecific suppressor cell function, measured in a concanavalin A suppressor assay, was significantly decreased in 16 patients with progressive MS (mean percent suppression k SEM, 14.4 f 5.5 in patients with MS, 33.5 f 4.8 in 16 normal subjects; p < 0.001). Recombinant human IFN-P augmented suppressor function in MS to 45.4 f 5.1% ( p < 0.001) and in control subjects to 56.8 f 3.8% ( p < 0.001). Similarly, recombinant human IFN-a improved suppression in MS to 43.0 f 5.6% ( p < 0.001) and in control subjects to 51.1 5.9%( p < 0.001). In contrast, recombinant human IFN-y had no effect on suppressor function in patients with MS and in control subjects. This study shows that IFN-a and -p augment deficient suppressor function in MS, whereas IFN-y has no effect on suppressor function in the progressive phase of the disease.
*
N o r o n h a A, Toscas A, Jensen M A . Contrasting effects of alpha, beta, a n d g a m m a interferons on nonspecific suppressor function in multiple sclerosis. A n n N e u r o l 1992;31:103-106
An important clue to the puzzle of multiple sclerosis (MS) has been provided by the observation that interferon gamma (IFN-y) provokes attacks of MS [l]. In contrast, IFN-a and IFN-P have been reported beneficial in some studies [2, 31. How does IFN-7 provoke acute attacks? Potential mechanisms include upregulation of class I1 major histocompatibility complex
From the Department of Neurology and the Brain Research Institute, University of Chicago, Chicago, IL. Received Jul 23, 1991. Accepted for publication Aug 14, 1991. Address correspondence to D r Noronha, University of Chicago, Department of Neurology, 5841 South Maryland Avenue, Chicago, IL 60637.
Copyright 0 1992 b y t h e American Neurological Association
103
Methods
The Transcranial Doppler Appearance of Acute Carotid Artery Occlusion Cole A. Giller, PhD, MD," Dana Mathews, PhD, MD,t Phillip Purdy, MD,$ Thomas A. Kopitnik, MD," H. Hunt Batjer, MD," and Duke S. Samson, MD"
~~
~~~~~
Transcranial Doppler ultrasound is a noninvasive technique of cerebral blood velocity measurement that is being increasingly used to detect untoward hemodynamic changes. I n this report, we describe striking transcranial Doppler ultrasound changes occurring in 2 patients after cervical carotid artery occlusion that led to cerebral infarction. These changes consist of the sudden appearance of a Doppler signal of extremely low pulsatility and moderately high velocity i n the middle cerebral artery distribution. In 1 patient, this signal was the first sign of carotid occlusion. W e suggest that these transcranial Doppler ultrasound changes can provide an early warning of carotid artery compromise. Giller CA, Mathews D, Purdy P, Kopitnik TA, Batjer HH, Samson DS. The transcranial Doppler appearance of acute carotid artery occlusion. Ann Neurol 1992;31:101-103
Acute occlusion of the carotid artery is a common event that may, a t one extreme, be well tolerated and, at the other, lead to cerebral infarction and neurological deficit El, 2). It is therefore important that the clinician recognize early warning signals arising from various monitoring methods that might indicate occlusion and impending infarction. Transcranial Doppler ultrasound ( T C D ) is a recently developed noninvasive means of assessment of cerebral hemodynamics that can detect attenuation of blood velocity in t h e cerebral vessels and thus warn of impending stroke r3-7). I n this report, we describe dramatic changes occurring in the TCD signals of 2 patients with sudden carotid artery occlusion. Both progressed to infarction. We suggest these TCD changes were a marker of poorly tolerated carotid artery occlusion.
From the Departments of *Neurological Surgery, ?Neurology, and $Radiology, The University of Texas Southwestern Medical Center, Dallas, TX.
Received Dec 27, 1990, and in revised form Mar 18, Jul 19, and Aug 15, 1991. Accepted for publication Aug 15, 1991. Address correspondence co Dr Giller, Department of Neurological Surgery, Universiry of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235-8855.
All T C D studies were performed using a 2 mHz pulsed ultrasound device (Trans-Scan, Eden Medical Electronics, Uberlingen, Germany) according to standard criteria [3, 81. Middle cerebral artery (MCA) velocities were obtained from Doppler probes held over the temporal squama using an insonation depth of 45 to 55 mm. The other intracranial arteries were also insonated and mapped in three dimensions as described elsewhere {3]. Mean velocities were averaged over four to five heartbeats and Gosling pulsatilities (defined as systolic minus diastolic divided by mean velocities) were simultaneously recorded. Elevation of the mean blood flow velocity indicates either a local stenosis or an increase in blood flow such as might occur from hyperemia [2, 3, 8-10]. The Gosling pulsatility measures the amount of pulsatile energy in the Doppler signal and decreases with downstream vasodilation or with the addition of upstream resistance to the hemodynamic circuit 13, 1 If. For example, the pulsatility decreases in the presence of proximal stenosis and increases during the pial vasoconstriction of hypocarbia. Normal mean MCA velocities for our laboratory are 45 to 70 cm/sec, and normal MCA pulsatilities are 0.60 to 1.0.
Patient Reports Patient I A 30-year-old woman presented with multiple hemispheral infarcts. Serial angiograms suggested fibromuscular dysplasia with progressive bilateral intracranial internal carotid artery stenoses. An MCA stenosis was not seen on the angiograms, and the residual carotid diameter was 40% on the right and 30% on the left. T C D studies showed mild elevation of the right MCA velocity to 125 cm/sec with a diminished pulsatility of 0.50. The left MCA velocities were in the normal range (maximum at 84 cm/sec). When either carotid artery was manually compressed, flow reversal in the anterior cerebral arteries and flow augmentation in the posterior cerebral arteries were absent. This suggested a lack of collateral flow across the anterior and posterior communicating arteries. Bilateral carotid balloon angioplasties were performed to achieve vessel dilation. Doppler studies then showed an elevation of the right MCA velocity (159 cm/sec), which normalized 1 day later. The left MCA velocities remained mildly elevated. T C D study 2 days later showed the sudden appearance of an abnormal signal in the right MCA with a normal velocity of 89 cm/sec, but with a strikingly diminished pulsatility of 0.15 (Fig 1). The remainder of the TCD study was unchanged. At the same time, the patient became lethargic and hemiparetic on the left. Angiography showed complete occlusion of the right internal carotid artery. Despite a repeat attempt at angioplasty of the right carotid artery, the patient suffered a massive right hemispheral infarct and eventually succumbed to high intracranial pressure.
Patient 2 A 15-year-old girl was found to have a left petrous carotid artery pseudoaneurysm and a left posterior carotid wall aneurysm just distal to the origin of the posterior communicating artery after a motor vehicle accident. The pseudoaneurysm
Copyright 0 1992 by the American Neurological Association
101
Fig 2. Maximal oelocities from right (A) and ldt (Bj middle cerebral arteries of Patient 2 shewing pronounced asymmetry in pulsatility. (Tick mark on y-axis indicates 100 cmlJri-.)
B
was then performed without neurological change, and T C D studies showed only a slight decrease in the right MCA pulsatility (0.81 to 0.64) with no change in velocities. The patient has remained clinically well.
-
I C
Fig I . Maximal velocities in right middle cerebral artery of Patient l before (A) and after (Bi angioplasty, and after appearance of pathologic signal (C). (Tick mark on y-axis indicates 100 cmlser.)
was trapped by ligating the internal carotid artery in the neck and by clipping the intracranial carotid artery at the time of craniotomy. The carotid aneurysm was clipped during the same operation. Postoperatively, an angiogram demonstrated collateral flow across the anterior communicating artery, but TCD studies revealed the appearance in the left MCA of an abnormal signal of high velocity (168 cm/sec) and strikingly low pulsatility (0.22) (Fig 2). Although the right MCA also showed high velocities (164 cm/sec), its pulsatility was twoto threefold that of the abnormal left MCA signal. Over the next week, the left MCA signal became somewhat more pulsatile (0.52). Despite aggressive supportive measures, however, the patient suffered a large left MCA distribution infarct.
Patient .? A 15-year-old boy was found to have a right carotid-cavernous sinus fistula after a motor vehicle accident. He was initially successfully treated with balloon occlusion of the fistula. Eight months later, however, an angiogram showed a large pseudoaneurysm as well as filling of the right MCA from the right carotid artery. T C D studies showed evidence of left-to-right collateral across the anterior communicating artery. Permanent balloon occlusion of the right carotid artery
102 Annals of Neurology
Vol 3 1
No 1 January 1992
Discussion Transcranial Doppler is being used increasingly as a monitoring tool with the intent of obtaining early warning of hemodynamic change 12, 3 , 5-7). In this report, we describe a dramatic and unique change in the T C D signal that heralds carotid artery occlusion and may predict cerebral ischemia. The sudden appearance of extremely low pulsatility in the MCA along with a high-to-normal velocity marked the sudden occlusion of the carotid artery in Patients 1 and 2. In both patients, MCA flow was supplied from collateral sources, and in both patients the ipsilateral hemisphere suffered severe ischemia that progressed to infarction. The low pulsatility of the Doppler signal suggested distal small vessel vasodilation arising as an autoregulatory response to the ischemia, and may have been exaggera,ted by the longer hemodynamic circuit taken t o reach rhe MCA. Arterial pulsatility at a given site along the cerebral vascular tree is determined both by the pulsatile energy of the blood column delivered to that tree and the degree of pial and arteriolar vasodilation in the tissue fed by the artery under study. A proximal stenosis blunts the pulsatile pattern and causes a pulsatility decrease, as seen in both acute and chronic carotid stenoses f2, 6, 71.Furthermore, tissue ischemia induced b y carotid obstruction invokes compensatory pial vasodilation, as seen directly in animal models 112) and in positron emission tomographic studies of cerebral vasospasm f 131, and also leads to a decrease in pulsatility.
The sudden onset and prolonged duration of carotid occlusion in Patients 1 and 2 are in contrast to transient manual compression or chronic carotid atherosclerotic disease, which also lead to low TCD pulsatility, and may explain the occurrence of infarction. In this report, we describe a dramatic TCD change (loss of pulsatility in the presence of high-to-normal velocity) occurring in acute carotid occlusion in 2 patients who subsequently progressed to infarction. For comparison, an example of the more common situation of minimal TCD changes is presented in a patient who tolerated carotid occlusion without difficulty. We suggest that sudden appearance of low pulsatility accompanied by high-to-normal velocity MCA signal should be recognized as a sign of poorly tolerated proximal arterial occlusion and as a warning of impending stroke.
We are grateful to Jeannie Moore for technical support and to Janis Williams for preparing this manuscript.
References 1. Swearingen B, Heros RC. Common carotid occlusion for unclippable carotid aneurysms: an old hut still effective operation. Neurosurgery 1987;21:288-295 2. Schneider PA, Rossrnan ME, Bernstein EF, et al. Effect of internal carotid artery occlusion o n intracranial hemodynamics. Stroke 1988;19:589-593 3. Aaslid R (ed). Transcranial Doppler Sonography. New York: Springer-Verlag, 1986 4. Aaslid R, Huber P, Nornes H. Evaluation of cerebrovascular spasm with transcranial Doppler ultrasound. J Neurosurg ~~
1984;60:37-41 5. Giller CA. A bedside test for cerebral autoregulation using transcranial Doppler ultrasound. Acta Neurochir (Wien) 1991; 108:7-14 6. Giller CA, Stieg PS, Batjer HH, et al. Transcranial Doppler ultrasound as a guide to graded therapeutic occlusion of the carotid artery. Neurosurgery 1990;26:307-311 7 . Halsey JH, McDoweli HA, Gelmon S, Morawetz RB. Blood velocity in the middle cerebral artery and regional blood flow during carotid endarterectomy. Stroke 1989;20:35-38 8. Aaslid R, Markwalder T-M, Nornes H. Noninvasive transcranial Doppler ulrrasound recording of flow velocity in basal cerebral arteries. J Neurosurg 1982;57:769-774 9. Purdy PD, Devous MD, Unwin DH, e t al. Angioplasry of an atherosclerotic middle cerebral artery associated with improvement in regional cerebral blood flow. AJNR 1990;11:878-880 10. Wechsler LR,Ropper AH, Kistler JP. Transcranial Doppler in cerebrovascular disease. Stroke 1986;17:905-912 11. Woodcock JP, Gosling HG, Fitzgerald DE. A new noninvasive technique for assessment of superficial femoral artery obstruction. Br J Surg 1972;59:226-231 12. Kontos H, Wei EP, Navari RM, et al. Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am J Physiol 1978;234:H371-H383 13. Martin WRW, Baker RP, Grubb RL, Raichle ME. Cerebral blood volume, blood flow, and oxygen metabolism in cerebral ischemia and subarachnoid haernorrhage: an in vivo study using positron emission tomography. Acta Neurochir (Wien) 1984; 70:3-9
Contrasting Effects of Alpha, Beta, and Gamma Interferons on Nonspecific Sumressor Function in Mxtiple Sclerosis Avertano N o r o n h a , MBBS, MD, Angela Toscas, BA, and Mark A. Jensen, BS
Interferons are biological molecules with antiviral, antiproliferative, and immunomodulatory actions. Interferon alpha (IFN-a) and -p are potentially useful in the treatment of multiple sclerosis (MS). IFN-y, in contrast, increases the frequency of exacerbations of MS. In this study, we compared the effect of recombinant human IFN-a, -p, and -y on suppressor function in patients with MS. Nonspecific suppressor cell function, measured in a concanavalin A suppressor assay, was significantly decreased in 16 patients with progressive MS (mean percent suppression k SEM, 14.4 f 5.5 in patients with MS, 33.5 f 4.8 in 16 normal subjects; p < 0.001). Recombinant human IFN-P augmented suppressor function in MS to 45.4 f 5.1% ( p < 0.001) and in control subjects to 56.8 f 3.8% ( p < 0.001). Similarly, recombinant human IFN-a improved suppression in MS to 43.0 f 5.6% ( p < 0.001) and in control subjects to 51.1 5.9%( p < 0.001). In contrast, recombinant human IFN-y had no effect on suppressor function in patients with MS and in control subjects. This study shows that IFN-a and -p augment deficient suppressor function in MS, whereas IFN-y has no effect on suppressor function in the progressive phase of the disease.
*
N o r o n h a A, Toscas A, Jensen M A . Contrasting effects of alpha, beta, a n d g a m m a interferons on nonspecific suppressor function in multiple sclerosis. A n n N e u r o l 1992;31:103-106
An important clue to the puzzle of multiple sclerosis (MS) has been provided by the observation that interferon gamma (IFN-y) provokes attacks of MS [l]. In contrast, IFN-a and IFN-P have been reported beneficial in some studies [2, 31. How does IFN-7 provoke acute attacks? Potential mechanisms include upregulation of class I1 major histocompatibility complex
From the Department of Neurology and the Brain Research Institute, University of Chicago, Chicago, IL. Received Jul 23, 1991. Accepted for publication Aug 14, 1991. Address correspondence to D r Noronha, University of Chicago, Department of Neurology, 5841 South Maryland Avenue, Chicago, IL 60637.
Copyright 0 1992 b y t h e American Neurological Association
103
