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

Until recently, cerebral biopsy was necessary to verify diagnosis {3}. I n 1988 and 1989, however, Matalon and co-workers [4,5 } demonstrated an excessive amount of N-acetylaspartic acid (NAA) in urine, blood, cerebrospinal fluid, and brain tissue, and a deficiency of aspartoacylase in cultured skin fibroblasts and brain tissue in children with Canavan’s disease. If further studies continue t o verify the specificity of these tests, they will likely be used to confirm the diagnosis of Canavan’s disease. In this patient report, w e illustrate the use of computed tomography (CT) or magnetic resonance imaging (MRI) followed by localized 1H magnetic resonance spectroscopy (MRS) in establishing the diagnosis of Canavan’s disease.

Patient A 38-month-old female child of Ashkenazic Jewish heritage presented at age 5 months with psychomotor retardation and macrocephaly. At age 7 months, cerebral brain biopsy confirmed a suspected diagnosis of Canavan’s disease. Over the last 30 months, she has developed severe spastic quadriparesis, optic atrophy, and dysphagia, which was treated by gastrostomy at age 27 months.

Laboratory Tests Visually evoked responses at age 27 months demonstrated a relative prolongation of the P l 0 0 latency on the left side, indicating a conduction defect of the left optic pathway. Brainstem auditory evoked responses demonstrated wellformed waves I and I1 with normal absolute latencies and absent waves 111, IV, and V. Urine organic acids demonstrated an increase in levels of NAA at 111 mgigm of creatinine (normal, :266-m 3 . MacGregor DL, Humphrey RP, Armstrong DL, Becker LE. Brain biopsies for neurodegenerative disease in chddren.J Pediatr 1978;92:703-905 4. Matalon R, Mirhals K, Sebesta D, et al. Aspartoacylase deficiency and N-acetylaspartic aciduria in patients with Canavan disease. Am J Med Genet 1988;29:463-47 1 5. Matalon K,Kaul R, CasanovaJ, et al. Aspartoacylase deficiency: the enzyme defect in Canavan disease. J Inherited Metab Dis 1989;12:329-331 6. Frahm J, Bruhn H, Gyngell ML, et al. Localized high-resolution proton NMR spectroscopy using stimulated echoes: initial applications to human brain in vivo. Magn Reson Med 1989;9:79-93 7. Klose U. In vivo proton spectroscopy in presence of eddy current. Magn Reson Med 1990;14:26-30 8. Frahm J, Bruhn H, Gyngell ML, et al. Localized proton NMR specrroscopy in different regions of the human brain in vivo. Relaxation times and concentrations of cerebral metabolites. Magn Reson Med 1989;11:47-63 9. Adachi M, Schneck L, Cara J, Volk B. Spongy degeneration of the central nervous system (Van Bogaert and Bertran type Canavan’s disease). Hum Pathol 1973;4:331-347 10. Rushton AR, Shaywia BA, Duncan CC, et al. Computed tomography in the diagnosis of Canavan’s disease. Ann Neurol 1981;I 0:57-60 11. Lane B, Carroll HA, Pedley TA. Computerized cranial tomography in cerebral diseases of white matter. Neurology 1978;28:

534-544 12. Boltshauser E, Spiess H, Isler W. Computed tomography in

neurodegenerative disorders of childhood. Neuroradiology 1978;16:4 1-43 13. McAdams HP, Geyer CA, Done SL, et al. CT and MR imaging of Canavan disease. AJNR 1990;11:397-399 14. Hagenfeldt L, Bollgren I, Venizelos N . N-Acetylaspartic aciduria due to aspartoacylase deficiency-a new aetiology of childhood leukodystrophy. J Inherited Metab Dis 1987;10:135-141 15. Grodd W, Krageloh-Mann I, Petersen D, et al. In vivo assessment of N-acetylaspartate in brain in spongy degeneration (Canavan’s disease) by proton spectroscopy. Lancet 199O;33 6 437-438 16. Tohnson AB: Deficiency of ATPase-positive astrocytic processes in spongy degeneration of the nervous system (Canavan’s type). J Neuropathol Exp Neurol 1970;29:136 (Abstract) 17. Padus W, Peiffer J. Intracerebral distribution of mitochondrial abnormalities in 2 1 cases of infantile spongy dystrophy. J Neurol Sci 1990;95:49-62 18, Kmoshita S, Rapin I, Suzuki Kinuko, Suzuki K u d i k o , Spongy degeneration of the brain. A chemical study of two cases inrluding isolation and characterization of myelin. Neurology 1968; 18:975-78>

Calcium Channel Antagonists and Human Immunodeficiency Virus Coat Protein-mediated Neuronal Injury Stuart A. Lipton, MD, PhD Recent evidence in vitro has suggested that neuronal injury observed in the acquired immunodeficiency syndrome dementia complex may depend, at least in part, on toxic effects of the human immunodeficiency virus type 1 envelope protein, gp120. This laboratory previously reported that members of the dihydropyridine class of calcium channel antagonists, nimodipine and nifedipine, greatly attenuate the rise in intracellular calcium engendered by gp120 and prevent subsequent neuronal injury. The relatively low (nanomolar) concentrations of dihydropyridines that were effective suggested that their action might be exerted at the level of the L-type of voltage-dependent calcium channels. I n the present study, I tested members of the three other major classes of Ca2+channel antagonist drugs to determine if they too could prevent neurotoxicity induced by gp120. At the maximal dose that did not cause neuronal damage in and of itself, a diphenylalkylamine piperazine derivative (flunarizine, 10 pM) was the most effective, a phenylalkylamine (verapamil, 100 pM) was possibly effective, whereas a benzothiazepine (diltiazem, 1 pM) was ineffectual in protecting rat retinal ganglion cells from gpl20-induced toxicity in vitro. To explain these results, previous work has shown that the various classes of Ca” channel antagonists may exhibit differential potency in blocking voltage-dependent Ca2 current in neurons, with dihydropyridines and flunarizine being the most potent at neuronal calcium channels. Moreover, these channels on mammalian central neurons are relatively insensitive to agents such as verapamil and diltiazem compared with other cell types like muscle. The low micromolar concentrations necessarv for Dotencv of flunarizine is in keeping with that predicted by binding and electrophysiologicd studies for block of voltagedependent calcium channels. Other mechanisms of neuroprotectionby fluniUizine from @120, however, cannot be +

Lipton SA. Calcium channel antagonists and human immunodeficiency virus coat protein-mediated neuronal injury. Ann Neurol 1991;30:110-1 14

From the Laboratory of Cellular and Molecular Neuroscience, Departments of Neurology, Children’s Hospital, Beth Israel Hospital, Brigham and Women’s Hospital, Massachusetts General Hospital, and the Program in Neuroscience, Harvard Medical School, Boston, MA. Received Sep 4, 1990, and in revised form Dec 20. Accepted for publication Jan 26, 1991. Address correspondence to Dr Lipton, Department of Neurology, Enders Bldg, Suite 361, 300 Longwood Avenue, Boston, MA 02115.

110 Copyright 0 1991 by the American Neurological Association

Use of computed tomography, magnetic resonance imaging, and localized 1H magnetic resonance spectroscopy in Canavan's disease: a case report.

The neuroradiological evaluation of Canavan's disease in a 38-month-old girl is discussed. Computed tomography showed diffuse symmetrical low attenuat...
527KB Sizes 0 Downloads 0 Views