Treatment of Chronic Inflammatory Demyelinating Polyneuropathy with Intravenous Immunoglobulin David R. Cornblath, MD," Vinay Chaudhry, MD," and John W. Griffin, MD"?
Chronic inflammatory demyelinating polyneuropathy is an immune-mediated demyelinating peripheral neuropathy usually treated with immunosuppressants. We reviewed our experience treating 15 patients (9 men, 6 women) with intravenous immunoglobulin. Six patients were on other therapies at the time of intravenous immunoglobulin infusions (4, prednisone; 2, prednisone and azathioprine). T h e dose of intravenous immunoglobulin was either 0.3 or 0.4 gmlkgiday for 4 to 5 days. Transient fever occurred in 1 patient. Subjective improvement in sensory symptoms was reported by almost all patients. Objective improvements in strength or functional tasks occurred in only 3 patients, a man with human immunodeficiency virus infection, a 14-yea-old girl, and a woman with an immunoglobulin G kappa paraprotein. O u r results suggest that individual patients may respond to intravenous immunoglobulin therapy. A multicenter controlled trial is needed to assess properly the role of intravenous immunoglobulin therapy in patients with chronic inflammatory demyelinating polyneuropathy . Cornblath DR, Chaudhry V, Griffin JW. Treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulin. Ann Neurol 1991;30:104-106
Chronic inflammatory demyelinating polyneuropathy (CIDP) is postulated to be an immune-mediated peripheral nervous system demyelinating disorder [ l]. Both prednisone 121 and plasmapheresis [37 have been shown in short-term trials t o improve neurological function when compared with placebo. Both therapies are associated with side effects, however, and not all patients respond to treatment. Recently, intravenous administration of human immunoglobulin (IVIg) has
From the Departments of *Neurology and ?Neuroscience, The Johns Hopluns University School of Medicine, Baltimore, MD. Received Dec 12, 1990. Accepted for publication Jan 11, 1991. Address correspondence to Dr Cornblath, Meyer 2-147, 600 N Wolfe Street, Baltimore, MD 21205.
been reported to have beneficial effects in several small series [4-131. We present o u r experience of 15 patients with CIDP treated with IVIg.
Patients and Methods From 1988 to 1990, we treated 15 patients with CIDP with IVIg. There were 9 men and 5 women, ranging in age from 35 to 68 years, and one 14-year-old girl. The diagnosis of CIDP was based on clinical history, examination, standardized testing including spinal fluid examination, electrodiagnostic studies, and nerve biopsy in all patients except Patient 10. In our center, prednisone is the treatment that is most often given for CIDP, and this is reflected in the Table. Other modalities are used, but less frequently. The indications for using IVIg were as follows: failed one or more other therapies (4 patients), desire to avoid another therapy because of possible side effects (4patients), and unsatisfactory response to current therapy (7 patients). In all patients, IVIg was given during the hospital stay. The dose of IVIg ranged from 0.3 gmlkgiday for 4 days ( 5 patients) to 0.4 gmikgiday for 4 to 5 days (10 patients). The first infusion was usually given over 6 hours with subsequent infusions occurring over 2 to 4 hours. Only 1patient (Patient 13) had a side effect of therapy. H e developed fever and "flu-like" symptoms lasting 48 hours. The response to therapy was highly variable. Almost all patients noted an immediate subjective improvement in sensation. Most reported that their numbness lessened; however, this was short-lived. Three patients responded significantly to IVIg therapy (Patients 7, 10, and 15). All 3 patients were on prednisone at the time of IVIg infusion, but the response to prednisone was incomplete. Patient 10 had a quantitative improvement in gait and balance and has been able to decrease steroids by 50p while receiving IVIg every 2 weeks. Patient 7 had a marked quantitative improvement in distal strength and was able to stop prednisone without relapse, something this patient had been unable to do previously. Patient 15, a 14year-old girl who had previously improved with prednisone but had significant side effects, improved rapidly and dramatically and was able to stop her prednisone. She is now maintained on IVIg infusions every 6 to 8 weeks. Three additional patients (Patients 4, 6, and 8) noted increased strength, but this was transient. In 1 patient (Patient S), repeated courses did not provide additional benefit. The other two patients (Patients 4 and 6) subsequently improved with prednisone. The other 9 patients had no clear response to IVIg. Two of these 9 responded to treatment with prednisone or azathioprine. Long-term follow-up and response to further therapies are shown in the Table.
Discussion In o u r review of IVIg therapy in patients with CIDP, only 3 of 15 (20%) had positive responses. In 2 of the 3 patients, the effect was transient, and maintenance IVIg therapy was required to continue the therapeutic response. In 3 other patients, a positive response to therapy occurred, but was transient. In the other 9 patients, no clear effect was seen. Our results contrast with those currently in the literature [4-131. In 1985, Vermeulen and colleagues {4}
104 Copyright 0 1771 by the American Neurological Association
Clinicdl Features of IVIg-treated Patients
Age (yr)/ Sex
Prior Treatment
Treatment During IVIg
1
66lM
PE
...
2
41lM
PE, P
3
38lF
4
Time from Diagnosis to Treatment (mo)
Associated Medical Disorders
Result of IVIg
Median MNCV
Long-term Follow-up
4
...
Unchanged
27
...
18
DM
Unchanged
19
PE
...
4
...
Unchanged
15
68lF
P, AZA
P, AZA
20
Breast cancef
Temporarily improved
35
5
56lM
PE, P
...
84
...
Unchanged
25
6
53lF
P
...
38
IgG lambda
35
7
45lM 45lM
PE, P PE
P P, AZA
27 24
HIV
8
9
49lM
P
...
48
HIV
Temporarily improved Improved Temporarily improved Unchanged
Died of unrelated medical illness No further treatment Treated with P and improves Improves on P, AZA; died from cancer No response to cyclosporine Improves on P
37
10 11
48lF 35iM
P PE, P
P ...
24 30
IgG kappa HIV'
Improved Unchanged
36 12
12
61lF
PE, P
...
106
IgM kappa
Unchanged
21
56iM
P, CTX ... P
P ... P
59 15
... ...
55
...
Unchanged Unchanged Improved
50 48 13
Patient
13 14 15
48lM 14iF
+
...
16 24
Off Y Cyclosporine added No further treatment Taper P No further treatment No further treatment Taper P Improves on AZA Off P, maintained on IVIg
IVIg = intravenous immunoglobulin; PE = piasmapheresis; P = prednisone; AZA = azarhioprine; IgG = immunoglobulin G; HIV' human immunodeficiency virus positive; CTX = cyclophosphamide; MNCV = motor nerve conduction velocity.
reported on the positive effect of fresh-frozen plasma (FFP) in the therapy of 17 patients with CIDP. In that report, they treated with IVIg 9 of those who responded favorably to FFP. Eight of those 9 patients also responded to IVIg. Other small series have also reported positive responses { 5- 131. Recently, van Doom and co-workers {G} performed a doublemasked, placebo, crossover study of IVIg in 7 patients known to respond to IVIg therapy. All responded to IVIg and not to placebo. Reviewing the Dutch experience, van Doorn and associates {13] reported that 38 of 52 patients responded favorably to IVIg, with 9 attaining complete remission after a single course of therapy and 2 1 requiring intermittent infusions to maintain improvement. The mechanism of action of IVIg in patients with CIDP and other autoimmune disorders is unknown. Postulated mechanisms include binding of Ig to Fc receptors on macrophages (which inhibits them), anti-idiotypical antibodies in the infused Ig, feedback inhibition of antibody production, direct effects on an-
=
tibody binding sites on nerve, nonspecific effects on natural killer cells, increased activity of nonspecific Tsuppressor cells, and solubilitation of immune complexes 1141. In their review, van Doorn and associates [ 131 used statistical techniques to determine factors associated with improvement. They found that (1) disease duration of less than 1 year, (2) similar degrees of weakness in arms and legs, (3) arm areflexia, and (4)slow median motor forearm conduction velocity were highly correlated with improvement. In their series, if all four factors were present, then the probability of significant improvement was 93%. Conversely, if none of the factors was present, then the probability of improvement was only 2%. Comparing our 3 patients who improved with the 12 who did not, there was no difference in either disease duration (38 months vs. 35 months) or median motor nerve conduction velocity (29 m/sec vs. 22 m/sec). It may require larger numbers of patients, however, to determine factors associated with improvement.
Brief Communication: Cornblath et d: Treatment of CIDP with IV lg
105
Use of Computed
Combining our patients with others in the literature, a total of 102 patients have been treated with IVIg. Clinically significant responses have occurred in 69 (68%). Undoubtedly, many more patients have been treated with this therapy but have not been reported. Because of the variability of response to IVIg, a multicenter controlled trial is needed to properly assess the value of IVIg therapy in patients with CIDP. Larger studies may be able to determine subgroups of patients who respond to this novel therapy and thus enable neurologists to use this expensive therapy more selectively.
Tomography, Magnetic Resonance Imaging, and Localized 1H Magnetic Resonance Spectroscopy in Canavan’s Disease: A Case Report
Presented in part at the 115th Annual Meeting of the American Neurological Association, Atlanta, GA, October 14-17, 1990.
Harold G. Marks, MD,’ Pilar A. Caro, MD,* Zhiyue Wang, PhD,t John A. Detre, MD,t Andrew R. Hogdan, PhDJ Debra A. Gusnard, MD,? and Robert A. Zimmerman, MDT
-
-
Rod Graham prepared the manuscript.
The neuroradiological evaluation of Canavan’s disease in References 1. Hartung H-P, Heininger K, Schafer €3, et al. Immune mecha-
nisms in inflammatory polyneuropathy. Ann NY Acad Sci 1988;540:122-161 2. Dyck PJ, O’Brien PC, Oviatt KF, et al. Prednisone improves chronic inflammatory demyelinating polyradiculoneuropathy more than no treatment. Ann Neurol 1982;11:136-141 3. Dyck PJ, Daube J, OBrien P, et al. Plasma exchange in chronic inflammatory demyelinating polyradiculoneuropathy. N Engl J Med 1986;314:461-465 4. Vermeulen M, van der Meche FGA, Speelman JD, er al. Plasma and gamma-globulin infusion in chronic inflammatory polyneuroparhy. J Neurol Sci 1985;70:317-326 5. Faed JM, Day B, Pollock M, et al. High-dose intravenous human immunoglobulin in chronic inflammatory demyelinating polyneuropathy. Neurology 1989;39:422-425 6. Van Doorn PA, Brand A, Strengers PFW, et al. High-dose intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy. Neurology 1990;40:209-2 12 7. Cook I>, Dalakas M, Galdi A, et al. High-dose intravenous immunoglobulin in the treatment of demyelinating neuropathy associated with monoclonal gammopathy. Neurology 1990; 40:212-2 14 8. Curro Dossi B, Tezzon F. High-dose intravenous gammaglobulin for chronic inflammatory demyelinating polyneuropathy. Ital J Neurol Sci 1987;8:321-326 9. Albala M, McNamara ME, Sokol M, Wyshock E. Improvement of neurologic function in chronic inflammatory demyelinating polyradiculoneuropathy following intravenous gammaglobulin infusion. Arch Neurol 1987;44:248-249 10. Teasley JE, Parry GJG, Sumner AJ, et al. Electrophysiologic studies in patients with chronic inflammatory demyelinating polyneuropathy treated with intravenous immune globulin. Muscle Nerve 1990;13:853-854 (Abstract) 11. Ropper AH, Zuniga G, Wijdicks E. Comparison of treatment for chronic inflammatory demyelinating polyneuropathy. Ann Neurol 1990;28:238-239 (Abstract) 12. Chimowitz MI, Audet A-MJ, Hallet A, Kelly JJ Jr. HIVassociated CIDP. Muscle Nerve 1989;12:695-696 13. Van Doom PA, Verrneulen M, Brand A, et al. Intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating polyneuropathy. Arch Neurol 1991;48: 217-220 14. Garner RJ, Sacher RA. Intravenous gammaglobulin therapy. Arlington, VA: American Association of Blood Banks, 1988
a 38-month-old girl is discussed. Computed tomography
showed diffuse symmetrical low attenuation values of the subcortical and deep cerebral white matter. Magnetic resonance imaging demonstrated symmetrical diffuse low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. With the use of 1H magnetic resonance spectroscopy, we were able to show elevated levels of N-acetylaspartic acid in the occipital lobe of our patient. The in vivo measurement of N-acetylaspartic acid in the brain by 1H magnetic resonance spectroscopy offers an additional noninvasive diagnostic test for establishing the diagnosis of Canavan’s disease. With the increasing availability of magnetic resonance spectroscopy, clinicians may be able to confirm the diagnosis of Canavan’s disease immediately after magnetic resonance imaging reveals the typical abnormalities of the white matter. Marks HG, Car0 PA, Wang Z, Detre JA, Bogdan AR, Gusnard DA, Zimmerman RA. Use of computed tomography, magnetic resonance imaging, and localized 1H magnetic resonance spectroscopy in Canavan’s disease: a case report. Ann Neurol 1991;30:106-110
Canavan’s disease, o r spongy degeneration of the brain in infancy, is a rare autosomal recessive leukodystrophy that is most prevalent among Ashkenazi Jews [l}and Saudi Arabians [2]. In the first few months of life, patients develop psychomotor retardation, spasticity, megaloencephaly, and blindness with optic atrophy.
From the +Alfred I. duPont Institute, Wilmington, DE; ?Children’s Hospital of Philadelphia, Philadelphia, PA; and Siemens Medical Systems, Iselin, NJ. Received Nov 26, 1990, and in revised form Jan 23, 1991. Accepted for publication Jan 23, 1991. Address correspondence to Dr Marks, do Editorial Services, Alfred I. duPont Institute, PO Box 269, Wilmington, DE 19899.
106 Copyright 0 1991 by the American Neurological Association
Chronic inflammatory demyelinating polyneuropathy is an immune-mediated demyelinating peripheral neuropathy usually treated with immunosuppressants. We reviewed our experience treating 15 patients (9 men, 6 women) with intravenous immunoglobulin. Six patients were on other therapies at the time of intravenous immunoglobulin infusions (4, prednisone; 2, prednisone and azathioprine). T h e dose of intravenous immunoglobulin was either 0.3 or 0.4 gmlkgiday for 4 to 5 days. Transient fever occurred in 1 patient. Subjective improvement in sensory symptoms was reported by almost all patients. Objective improvements in strength or functional tasks occurred in only 3 patients, a man with human immunodeficiency virus infection, a 14-yea-old girl, and a woman with an immunoglobulin G kappa paraprotein. O u r results suggest that individual patients may respond to intravenous immunoglobulin therapy. A multicenter controlled trial is needed to assess properly the role of intravenous immunoglobulin therapy in patients with chronic inflammatory demyelinating polyneuropathy . Cornblath DR, Chaudhry V, Griffin JW. Treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulin. Ann Neurol 1991;30:104-106
Chronic inflammatory demyelinating polyneuropathy (CIDP) is postulated to be an immune-mediated peripheral nervous system demyelinating disorder [ l]. Both prednisone 121 and plasmapheresis [37 have been shown in short-term trials t o improve neurological function when compared with placebo. Both therapies are associated with side effects, however, and not all patients respond to treatment. Recently, intravenous administration of human immunoglobulin (IVIg) has
From the Departments of *Neurology and ?Neuroscience, The Johns Hopluns University School of Medicine, Baltimore, MD. Received Dec 12, 1990. Accepted for publication Jan 11, 1991. Address correspondence to Dr Cornblath, Meyer 2-147, 600 N Wolfe Street, Baltimore, MD 21205.
been reported to have beneficial effects in several small series [4-131. We present o u r experience of 15 patients with CIDP treated with IVIg.
Patients and Methods From 1988 to 1990, we treated 15 patients with CIDP with IVIg. There were 9 men and 5 women, ranging in age from 35 to 68 years, and one 14-year-old girl. The diagnosis of CIDP was based on clinical history, examination, standardized testing including spinal fluid examination, electrodiagnostic studies, and nerve biopsy in all patients except Patient 10. In our center, prednisone is the treatment that is most often given for CIDP, and this is reflected in the Table. Other modalities are used, but less frequently. The indications for using IVIg were as follows: failed one or more other therapies (4 patients), desire to avoid another therapy because of possible side effects (4patients), and unsatisfactory response to current therapy (7 patients). In all patients, IVIg was given during the hospital stay. The dose of IVIg ranged from 0.3 gmlkgiday for 4 days ( 5 patients) to 0.4 gmikgiday for 4 to 5 days (10 patients). The first infusion was usually given over 6 hours with subsequent infusions occurring over 2 to 4 hours. Only 1patient (Patient 13) had a side effect of therapy. H e developed fever and "flu-like" symptoms lasting 48 hours. The response to therapy was highly variable. Almost all patients noted an immediate subjective improvement in sensation. Most reported that their numbness lessened; however, this was short-lived. Three patients responded significantly to IVIg therapy (Patients 7, 10, and 15). All 3 patients were on prednisone at the time of IVIg infusion, but the response to prednisone was incomplete. Patient 10 had a quantitative improvement in gait and balance and has been able to decrease steroids by 50p while receiving IVIg every 2 weeks. Patient 7 had a marked quantitative improvement in distal strength and was able to stop prednisone without relapse, something this patient had been unable to do previously. Patient 15, a 14year-old girl who had previously improved with prednisone but had significant side effects, improved rapidly and dramatically and was able to stop her prednisone. She is now maintained on IVIg infusions every 6 to 8 weeks. Three additional patients (Patients 4, 6, and 8) noted increased strength, but this was transient. In 1 patient (Patient S), repeated courses did not provide additional benefit. The other two patients (Patients 4 and 6) subsequently improved with prednisone. The other 9 patients had no clear response to IVIg. Two of these 9 responded to treatment with prednisone or azathioprine. Long-term follow-up and response to further therapies are shown in the Table.
Discussion In o u r review of IVIg therapy in patients with CIDP, only 3 of 15 (20%) had positive responses. In 2 of the 3 patients, the effect was transient, and maintenance IVIg therapy was required to continue the therapeutic response. In 3 other patients, a positive response to therapy occurred, but was transient. In the other 9 patients, no clear effect was seen. Our results contrast with those currently in the literature [4-131. In 1985, Vermeulen and colleagues {4}
104 Copyright 0 1771 by the American Neurological Association
Clinicdl Features of IVIg-treated Patients
Age (yr)/ Sex
Prior Treatment
Treatment During IVIg
1
66lM
PE
...
2
41lM
PE, P
3
38lF
4
Time from Diagnosis to Treatment (mo)
Associated Medical Disorders
Result of IVIg
Median MNCV
Long-term Follow-up
4
...
Unchanged
27
...
18
DM
Unchanged
19
PE
...
4
...
Unchanged
15
68lF
P, AZA
P, AZA
20
Breast cancef
Temporarily improved
35
5
56lM
PE, P
...
84
...
Unchanged
25
6
53lF
P
...
38
IgG lambda
35
7
45lM 45lM
PE, P PE
P P, AZA
27 24
HIV
8
9
49lM
P
...
48
HIV
Temporarily improved Improved Temporarily improved Unchanged
Died of unrelated medical illness No further treatment Treated with P and improves Improves on P, AZA; died from cancer No response to cyclosporine Improves on P
37
10 11
48lF 35iM
P PE, P
P ...
24 30
IgG kappa HIV'
Improved Unchanged
36 12
12
61lF
PE, P
...
106
IgM kappa
Unchanged
21
56iM
P, CTX ... P
P ... P
59 15
... ...
55
...
Unchanged Unchanged Improved
50 48 13
Patient
13 14 15
48lM 14iF
+
...
16 24
Off Y Cyclosporine added No further treatment Taper P No further treatment No further treatment Taper P Improves on AZA Off P, maintained on IVIg
IVIg = intravenous immunoglobulin; PE = piasmapheresis; P = prednisone; AZA = azarhioprine; IgG = immunoglobulin G; HIV' human immunodeficiency virus positive; CTX = cyclophosphamide; MNCV = motor nerve conduction velocity.
reported on the positive effect of fresh-frozen plasma (FFP) in the therapy of 17 patients with CIDP. In that report, they treated with IVIg 9 of those who responded favorably to FFP. Eight of those 9 patients also responded to IVIg. Other small series have also reported positive responses { 5- 131. Recently, van Doom and co-workers {G} performed a doublemasked, placebo, crossover study of IVIg in 7 patients known to respond to IVIg therapy. All responded to IVIg and not to placebo. Reviewing the Dutch experience, van Doorn and associates {13] reported that 38 of 52 patients responded favorably to IVIg, with 9 attaining complete remission after a single course of therapy and 2 1 requiring intermittent infusions to maintain improvement. The mechanism of action of IVIg in patients with CIDP and other autoimmune disorders is unknown. Postulated mechanisms include binding of Ig to Fc receptors on macrophages (which inhibits them), anti-idiotypical antibodies in the infused Ig, feedback inhibition of antibody production, direct effects on an-
=
tibody binding sites on nerve, nonspecific effects on natural killer cells, increased activity of nonspecific Tsuppressor cells, and solubilitation of immune complexes 1141. In their review, van Doorn and associates [ 131 used statistical techniques to determine factors associated with improvement. They found that (1) disease duration of less than 1 year, (2) similar degrees of weakness in arms and legs, (3) arm areflexia, and (4)slow median motor forearm conduction velocity were highly correlated with improvement. In their series, if all four factors were present, then the probability of significant improvement was 93%. Conversely, if none of the factors was present, then the probability of improvement was only 2%. Comparing our 3 patients who improved with the 12 who did not, there was no difference in either disease duration (38 months vs. 35 months) or median motor nerve conduction velocity (29 m/sec vs. 22 m/sec). It may require larger numbers of patients, however, to determine factors associated with improvement.
Brief Communication: Cornblath et d: Treatment of CIDP with IV lg
105
Use of Computed
Combining our patients with others in the literature, a total of 102 patients have been treated with IVIg. Clinically significant responses have occurred in 69 (68%). Undoubtedly, many more patients have been treated with this therapy but have not been reported. Because of the variability of response to IVIg, a multicenter controlled trial is needed to properly assess the value of IVIg therapy in patients with CIDP. Larger studies may be able to determine subgroups of patients who respond to this novel therapy and thus enable neurologists to use this expensive therapy more selectively.
Tomography, Magnetic Resonance Imaging, and Localized 1H Magnetic Resonance Spectroscopy in Canavan’s Disease: A Case Report
Presented in part at the 115th Annual Meeting of the American Neurological Association, Atlanta, GA, October 14-17, 1990.
Harold G. Marks, MD,’ Pilar A. Caro, MD,* Zhiyue Wang, PhD,t John A. Detre, MD,t Andrew R. Hogdan, PhDJ Debra A. Gusnard, MD,? and Robert A. Zimmerman, MDT
-
-
Rod Graham prepared the manuscript.
The neuroradiological evaluation of Canavan’s disease in References 1. Hartung H-P, Heininger K, Schafer €3, et al. Immune mecha-
nisms in inflammatory polyneuropathy. Ann NY Acad Sci 1988;540:122-161 2. Dyck PJ, O’Brien PC, Oviatt KF, et al. Prednisone improves chronic inflammatory demyelinating polyradiculoneuropathy more than no treatment. Ann Neurol 1982;11:136-141 3. Dyck PJ, Daube J, OBrien P, et al. Plasma exchange in chronic inflammatory demyelinating polyradiculoneuropathy. N Engl J Med 1986;314:461-465 4. Vermeulen M, van der Meche FGA, Speelman JD, er al. Plasma and gamma-globulin infusion in chronic inflammatory polyneuroparhy. J Neurol Sci 1985;70:317-326 5. Faed JM, Day B, Pollock M, et al. High-dose intravenous human immunoglobulin in chronic inflammatory demyelinating polyneuropathy. Neurology 1989;39:422-425 6. Van Doorn PA, Brand A, Strengers PFW, et al. High-dose intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy. Neurology 1990;40:209-2 12 7. Cook I>, Dalakas M, Galdi A, et al. High-dose intravenous immunoglobulin in the treatment of demyelinating neuropathy associated with monoclonal gammopathy. Neurology 1990; 40:212-2 14 8. Curro Dossi B, Tezzon F. High-dose intravenous gammaglobulin for chronic inflammatory demyelinating polyneuropathy. Ital J Neurol Sci 1987;8:321-326 9. Albala M, McNamara ME, Sokol M, Wyshock E. Improvement of neurologic function in chronic inflammatory demyelinating polyradiculoneuropathy following intravenous gammaglobulin infusion. Arch Neurol 1987;44:248-249 10. Teasley JE, Parry GJG, Sumner AJ, et al. Electrophysiologic studies in patients with chronic inflammatory demyelinating polyneuropathy treated with intravenous immune globulin. Muscle Nerve 1990;13:853-854 (Abstract) 11. Ropper AH, Zuniga G, Wijdicks E. Comparison of treatment for chronic inflammatory demyelinating polyneuropathy. Ann Neurol 1990;28:238-239 (Abstract) 12. Chimowitz MI, Audet A-MJ, Hallet A, Kelly JJ Jr. HIVassociated CIDP. Muscle Nerve 1989;12:695-696 13. Van Doom PA, Verrneulen M, Brand A, et al. Intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating polyneuropathy. Arch Neurol 1991;48: 217-220 14. Garner RJ, Sacher RA. Intravenous gammaglobulin therapy. Arlington, VA: American Association of Blood Banks, 1988
a 38-month-old girl is discussed. Computed tomography
showed diffuse symmetrical low attenuation values of the subcortical and deep cerebral white matter. Magnetic resonance imaging demonstrated symmetrical diffuse low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. With the use of 1H magnetic resonance spectroscopy, we were able to show elevated levels of N-acetylaspartic acid in the occipital lobe of our patient. The in vivo measurement of N-acetylaspartic acid in the brain by 1H magnetic resonance spectroscopy offers an additional noninvasive diagnostic test for establishing the diagnosis of Canavan’s disease. With the increasing availability of magnetic resonance spectroscopy, clinicians may be able to confirm the diagnosis of Canavan’s disease immediately after magnetic resonance imaging reveals the typical abnormalities of the white matter. Marks HG, Car0 PA, Wang Z, Detre JA, Bogdan AR, Gusnard DA, Zimmerman RA. Use of computed tomography, magnetic resonance imaging, and localized 1H magnetic resonance spectroscopy in Canavan’s disease: a case report. Ann Neurol 1991;30:106-110
Canavan’s disease, o r spongy degeneration of the brain in infancy, is a rare autosomal recessive leukodystrophy that is most prevalent among Ashkenazi Jews [l}and Saudi Arabians [2]. In the first few months of life, patients develop psychomotor retardation, spasticity, megaloencephaly, and blindness with optic atrophy.
From the +Alfred I. duPont Institute, Wilmington, DE; ?Children’s Hospital of Philadelphia, Philadelphia, PA; and Siemens Medical Systems, Iselin, NJ. Received Nov 26, 1990, and in revised form Jan 23, 1991. Accepted for publication Jan 23, 1991. Address correspondence to Dr Marks, do Editorial Services, Alfred I. duPont Institute, PO Box 269, Wilmington, DE 19899.
106 Copyright 0 1991 by the American Neurological Association
