1977;2:7-19. 12. Wartenberg R. Sensory polyneuritis. In: Wartenberg R, ed. Neuritis, sensory neuritis neuralgia. New York: Oxford University Press, 1958160-162. 13. Martin CA. Polyradiculite postkrieure ascendante a virus. Lava1 Med 1946;11:387-392. 14. BarrL. MJA. Syndrome sacre sensitivo-sensoriel, a Bvolution cyclique (d’apres cinq cas). Rev Neurol (Paris) 1948;80:294-297. 15. Denny-Brown D. Hereditary sensory radicular neuropathy. J Neurol Neurosurg Psychiatry 1951;14237-252. 16. Dyck PJ, Gutrecht JA, Bastron JA, Karnes WE, Dale AJ. Histologic and teased-fiber measurements of sural nerve in disorders of lower motor and primary sensory neurons. Mayo Clin Proc 1968;43:81-123. 17. Kaufman MD, Hopkins LC, Hunvitz BJ. Progressive sensory neuropathy in patients without carcinoma: a disorder with distinctive clinical and electrophysiological findings. Ann Neurol 1981;9:237-242. 18. Sterman AB, Schaumburg HH, Asbury AK. The acute sensory neuronopathy syndrome: a distinct clinical entity. Ann Neurol 1980;7:354-358. 19. Malinow K, Yannakakis GD, Glusman SM, et al. Subacute sensory neuronopathy secondary to dorsal root ganglionitis in primary Sjogren’s syndrome. Ann Neurol 1986;20:535-537. 20.Dyck PJ, Sherman WR, Hallcher LM, et al. Human diabetic endoneurial sorbitol, fructose, and myo-inositol related to sural nerve morphometry. Ann Neurol198Q8590-596. 21. Daube JR. Nerve conduction studies. In: Aminoff MJ. ed. Elec-

trodiagnosis in clinical neurology. New York: Churchill Livingstone, 1980229-264. 22. Dyck PJ, Karnes J , Lais A, Lofgren EP, Stevens JC. Pathologic alterations of the peripheral nervous system of humans. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R, eds. Peripheral neuropathy, 2nd ed, vol 1. Philadelphia: W.B. Saunders, 1984:760-870. 23. Mellgren SI, Conn DL, Stevens JC, Dyck PJ. Peripheral neuropathy in primary Sjogren’s syndrome. Neurology 1989;39:390-394. 24. Graus F, Cordon-Cardo C, Posner JB. Neuronal antinuclear antibody in sensory neuronopathy from lung cancer. Neurology 1985;35:538-543. 25. Kimmel DW, O’Neill BP, Lennon VA. Subacute sensory neuronopathy associated with small cell lung carcinoma: diagnosis aided by autoimmune serology. Mayo Clin Proc 1988;63:29-32. 26. Dyck PJ, Lais AC, Ohta M, Bastron JA, Okazaki H, Groover RV. Chronic inflammatory polyradiculoneuropathy. Mayo Clin Proc 1975;50621-637. 27. Prineas JW, McLeod JG. Chronic relapsingpolyneuritis. J Neurol Sci 1976;27:427-458. 28. Sladky J T , Brown MJ, Berman PH. Chronic inflammatory demyelinating polyneuropathy of infancy: a corticosteroid-responsive disorder. Ann Neurol 1986;20:76-81. 29. Krendel,DA, Parks HP, Anthony DC, Genter MB, Graham DG. Sural nerve biopsy in chronic inflammatory demyelinating polyradiculoneuropathy [Abstract]. Neurology 198737 (Suppl 1):365. 30. Griffin JW, Cornblath DR, Dropcho E. Differential diagnosis of t h e pure sensory neuronopathies [Abstract]. Neurology 1989;39(Suppl 1):391.

Serial study of gadolinium-DTPA MRI enhancement in multiple sclerosis S. Bastianello, MD, PhD; C. Pozzilli, MD, PhD; S. Bernardi, MD; L. Bozzao, MD; L.M. Fantozzi, MD; C. Buttinelli, MD; and C. Fieschi, MD

Article abstract-We performed serial baseline and gadolinium (Gd)-DTPA-enhanced MRI in 4 patients with definite multiple sclerosis. Studieswere performed every month for a total of 4 scans.We obtainedshort TR/short TE sequencesat 10and 60 minutes after Gd-DTPA injection. All patients had multiple hyperintense lesions seen on baseline MRI with long TR/short and long TE. There was Gd-DTPA enhancement in new, enlarging, and preexisting lesions that were unchanged in size. The enhancing lesions were always seen on T,-weighted images. There was no difference in enhancement between the 10- and 60minute studies. Six of 85 preexisting lesions enhanced whereas all new or enlarging lesions enhanced.Enhancementpersisted in only I/? of the new or enlarging lesions, suggestingthat MR enhancement is a transient phenomenondue to local temporary bloodbrain barrier breakdown. Our data indicate that Gd-DTPAenhancementmonitoringis more sensitive than unenhanced MRI for detecting disease activity in MS.

NEUROLOGY 199Q40591-595

Recent studies suggest that MRI in multiple sclerosis may be more sensitive than clinical evaluation in detecting disease To date, serial MRI has demonstrated new or enlarging asymptomatic lesion^.^ Experimental, pathologic, and imaging data have suggested that a common feature of active MS lesions is a

local breakdown of the blood-brain barrier (BBB).4-10 MRI using enhancement with gadolinium (Gd)-DTPA appears to be additionally sensitive in detecting active MS plaques.” The purpose of this longitudinal study was to determine the relationships between new or enlarging MS

From the Department of Neurological Sciences, Neuroradiological Section (Drs. Bastianello, Bozzao, and Fantozzi), and 3rd Neurological Clinic (Drs. Pozzilli. Bernardi, Buttinelli, and Fieschi), University of Rome “La Sapienza”, Italy. Received May 30, 1989. Accepted for publication in final form September 27, 1989. Address correspondenceand reprint requests to Dr. Stefan0 Bastianello, Servizio Speciale di Neuroradiologia I, Dipartimento di Scienze Neurologiche,Universitadi Roma “La Sapienza,” Viale dell’Universita 30,00185 Rome, Italy.

April 1990 NEUROLOGY 40 691

Table 1. Clinical data of the 4 patients

I Pt no. 1 2 3 4

Sex

Age (vs)

Disease duration brs)

MS type

F M M M

24 29 39 34

2 2 5 4

Remitting Remitting Remitting Remitting

EDSS

No. of clinical exacerbations

Therapy

O/l* 112.5' 1.5/2.5* 2

2 1 1 0

Steroids Steroids Steroids No

EDSS Expanded Disability Status Scale by Kurtzke.13 * EDSS during clinical exacerbations.

Table 2. Serial MRI data in t h e 4 patients Monthly MRI examinations

Pt no.

Initial total lesions (no.)

Final total lesions

New unenhancing lesions

1 2 3 4

20 13 31 21

22 15 33 25

-

2

2

-

-

1

2 3

1 1 1

85

95

3*

7

3

Total

New enhancing lesions

Enlarging preexisting enhancing lesions

Unchanged preexisting enhancing lesions

Total enhancing lesions

5

8

-

1

1 -

3 4

6

16

* Seen an average of 73 days from the baseline study.

lesions appearing on serial MRI, with and without GdDTPA enhancement. We also considered whether stable lesions on serial MRI are related to the typical chronic plaques and therefore would not show any GdDTPA enhancement. Methods. From 27 MS patients who had MRI examination, we recruited 4 patients with clinically definite MS12who could undergo the needed serial MRI study. Each patient had a neurologic examination at the beginning of the study, for 3 months on the same day as the MRI, and during clinical exacerbations. In each case, disability was rated according to the Kurtzke method.'3 MRI was performed using the 1.5 tesla superconducting unit (Philips Gyroscan). Four MRI examinations were performed in each tee; the 1st was the routine (unenhanced) study. Starting an average of 73 days later (SD 5.5; range, 61to 82), we performed the follow-up MRI examinations every month using long TR/short and long T E (2,310/50 and 100) and short TR/short TE (350/30) spin-echo sequences, respectively, prior to Gd-DTPA administration. The enhanced study performed after Gd-DTPA administration was done using T,-weighted sequences (short TR/short TE) on sagittal and axial planes performed at 10 and 60 minutes after the end of Gd-DTPA injection (0.1 mmol/kg). Slices 7.0-mm thick with a gap of 10%with respect to the slice thickness between sections were obtained for all the sequences to reduce the examination time. Side effects due to contrast medium were never observed. To obtain comparable examinations during the follow-up scans, a midline sagittal scout slice was performed at the beginning of each study. In this way we oriented axial sections 592 NEUROLOGY 40 April 1990

on the same horizontal plane along a line passing through the basis of the frontal lobe and the caudal portion of the quadrigeminal plate. Comparable images in repeated studies in the same patients could thus be obtained. The number of new and old hyperintense lesions seen on T, images (long TR/short and long TE sequences) were then evaluated. The sequential changes in number and size of MS lesions and the appearances of Gd-DTPA enhancement were monitored. The contrast enhancement was classified as being total or partial and uniform or ringlike.

Results. The clinical findings are summarized in table 1. We studied 4 relapsing-remitting MS patients, 1 woman and 3 men (aged 24 to 39,average 31.2 years) with 2- to 5-year histories of disease. The mean Expanded Disability Status Scale rating (EDSS)13was 1.1 & 0.7 at entry and 1.8 +- 0.5 at completion of the study. Three of 4 patients (nos. 1through 3) had clinical relapses during the study, with 1 patient (no. 1)having 2 relapses. All the clinical relapses came in the interval between the initial routine MRI and the beginning of the monthly serial MRI examinations,and the patients were treated with methylprednisolone 1 g intravenously, single daily dose for 5 days. Patient 4 remained clinically stable during the study (table 1). All 4 patients had abnormal unenhanced MRI examination at both the initial and follow-up studies. The distribution of the lesions is summarized in table 2. In the 4 patients, the initial unenhanced MRI examinations showed 85 hyperintense lesions, mainly localized

Figure 1. Serial M R I from patient 3. New lesion with uniform contrast enhancement after Gd-DTPA injection. (A)Baseline M R I (2,310/100) shows multiple hyperintense areas localized in the periventricular white matter. (B) One-month follow-up M R I (2,310/100) reveals a new hyperintense area o n T,-weighted images localized i n the white matter of the right frontal lobe (arrow); this area (arrow) shows a uniform enhancement on TI-weighted images (350/30) at 10 minutes (C), persisting without changes i n shape or size at 1-hour control study.

Figure 2. Serial M R I f r o m patient 2. Enlarging preexisting lesion with partial contrast enhancement after Gd-DTPA injection. (A)Baseline M R I (2,310/100) reveals a small hyperintense lesion localized in the left white matter of the centrum semiovale (arrow). (B) One month later, M R I (2,310/100) shows a marked enlargement of the plaque (arrow). (C) A partial contrast enhancement on TI-weighted images (350/30) involving the older part of the lesion is present after Gd-DTPA injection (arrow).

in the white matter of the corona radiata. During the monthly MRI studies, 10 new and 3 enlarging lesions were identified on the unenhanced scan. A total of 16 lesions-7 of 10 new, 3 enlarging, and 6 preexisting lesions (without change in size)-showed contrast enhancement. All these were always evident on the T,-weighted sequences. In 3 patients (nos. 1through

3) with clinical relapses, a total of 12 enhancing lesions were seen, but they were not related to the clinical symptoms. Furthermore, 4 enhancing lesions appeared in patient 4, who remained clinically stable during the follow-upstudy. The 7 new enhancing lesions showed a uniform contrast enhancement (figure l),whereas the 3 enlarging lesions displayed a partial Gd-DTPA enApril lBe0 NEUROLOGY 40 6BS

BBB is the main underlying pathologic feature in newly

Figure 3. Serial MRI from patient 1. Preexisting unchanged lesion with Gd-DTPA enhancement. (A) Baseline MRI examination (2,310/100) shows multiple bilateral lesions. No changes were seen on follow-up MRI (2,310/100)performed 70 days later, but (B) uniform contrast enhancement on T,-weighted images (350/30) was seen in 3 preexisting lesions that were not increased in size (arrows).

hancement involving the older part of the lesion (figure 2). Uniform enhancement was also seen in the 6 preexisting enhancing lesions, which had no evidence of increase in size (figure 3). Lesion enhancement was fully developed at 10-minuteTI-weighted images and did not change by 1hour after Gd-DTPA injection. One-third of the enhancing lesions showed persisting enhancement a t the monthly MRI control studies; only 1lesion with uniform enhancement converted to ringlike after 1 month. Three new lesions did not show contrast enhancement; however, all were seen a t the 1st monthly serial MRI examination, which was done more than 2 months from the initial study (see Methods). New unenhancing lesions were never detected during the monthly MRI series.

Discussion. In our data, every new or enlarging lesion appearing on the monthly unenhanced MRI control studies also showed Gd-DTPA enhancement. We never observed changes in size of MS lesions unaccompanied by Gd-DTPA enhancement. These results are concordant with data showing that a local breakdown of the 594 NEUROLOGY 40 April 1990

appearing or enlarging 1esi0ns.l~ Also, 6 of the 16 enhancing lesions seen in this study were older plaques that did not increase in size (figure 3). This suggests that monitoring of MS patients with unenhanced MRI would underestimate the activity of the disease.15 All the enhancing lesions in our study were also present on the unenhanced T,-weighted MRIs. These findings contrast with recent observations by Kermode et al,15 who found some enhancing lesions not visualized on baseline T,-weighted MR sequences. Gd-DTPA MRI enhancement appears to be a transient phenomenon, since only 30% of the lesions in this study and 22% of those reported by Miller et all4showed persisting contrast enhancement at the 1-month control MRI study. This might explain the lack of enhancement observed in 3 new lesions appearing in a period of 2 to 3 months between the initial and the 1st monthly MRI in our study. A different picture of Gd-DTPA enhancement occurred between the new plaques and those that were enlarging. A uniform contrast enhancement (involving the whole plaque) occurred in all the newly enhancing MS lesions. Enlarging plaques showed a partial Gd-DTPA enhancement, seemingly limited to the part of the preexisting lesion. Enlargement of a previously stable lesion with partial contrast enhancement could indicate reactivation of old plaque, possibly surrounded by a halo of edematous tissue. Ring enhancement (seen in only 1of our patients) probably arises from recent inflammation a t the periphery of a lesion in which the BBB defect is partly or completely repaired in the inner old part.16 There was no additional information from the delayed MRI a t 60 minutes. By contrast, Grossman et a12 found that occasionally the delayed Gd-DTPA images were additionally revealing, analogous to delayed enhanced CT images.17 Our data indicate that Gd-DTPA enhancement is a common feature of new and enlarging MS lesions, although it can appear in lesions that do not reveal changes in size during follow-up MRI studies. These data suggest that Gd-DTPA-enhanced MRI monitoring provides a sensitive method to detect disease activity in MS.

Acknowledgments We would like to thank Michael J. Kushner, MD, for his editorial criticisms and suggestions and Barbara Pannuti for technical assistance.

References 1. Isaac C, Li DKB, Genton M, et al. Multiple sclerosis: a serial study using MRI in relapsing patients. Neurology 1988381511-1515. 2. Grossman RI, Braffman BH, Brorson JR, Goldberg HI, Silberberg DH, Gonzales-Scarano F. Multiple sclerosis: serial study of gadolinium-enhanced MR imaging. Radiology 1988;169:117-122. 3. Willoughby EW, Grochowski E, Li DKB, Oger J, Kastrukoff LF, Paty DW. Serial magnetic resonance scanning in multiple sclerosis: a second prospective study in relapsing patients. Ann Neurol

1989;25:43-49. 4.James PB. Multiple sclerosis or blood-brain barrier disease [letter]. Lancet 1989;1:46. 5.Kukarik MA, Edwards MK, Farlow MR, et al. Gd-enhanced MR imaging of acute and chronic experimental demyelinating lesions. AJNR 1988;9643-648. 6.Broman T. Blood-brain barrier damage in multiple sclerosie: supravital test-observations. Acta Neurol Scand 1964;40(suppl 10):21-24. 7. Weinstein MA, M e r m a n RJ, Rothner AD, et al. Internal comp u t e d tomography i n multiple sclerosis. Radiology 1978;129:689-694. 8. Aita JF, Bennet DR, Anderson RE, Ziter F.Cranial CT appearance of acute multiple sclerosis. Neurology 1978;28:251-255. 9.Pozzilli C,Bernardi S, Mansi L, et al. Quantitative assessment of blood-brain barrier permeability in multiple sclerosis wing 68Ga-EDTA and positron emission tomography. J Neurol Neuros ~ r Psychiatry g 1988;51:1058-1062. 10.Koopmans RA,Li DKB, Oger JJF, Mayo J, Paty DW. The lesion of multiple sclerosis: imaging of acute and chronic stages. Neurology 198339959-963. 11. Gonzales-Scarano F, Grossman RI, Galetta S, Atlas SW, Silber-

berg DH. Multiple sclerosis disease activity correlates with gadolinium-enhanced magnetic resonance &ging. Ann Neurol 1987;21:300-306. 12. Schumacher GA, Beebe G, Kibler RF, et al. The problem of experimental trials of therapy in multiple sclerosis: report by the panel on the evaluation of experimental trials of therapy in multiple sclerosis. Ann NY Acad Sci 1965;122:552-568. 13. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33:1442-1452. 14.Miller DH, Rudge P, Johnson G, et al. Serialgadolinium enhanced magnetic resonance imaging in multiple sclerosis. Brain 1988;111:927-939. 15. Kermode AG, Tofta PS, Thompson AJ, et al. Heterogeneity of blood-brain barrier changes in multiple sclerosis: an MRI study w i t h g a d o l i n i u m - D T P A e n h a n c e m e n t . Neurology 1990;40229-235. 16. Kermode AG, Tofta PS, Macmanue DG, et al. Early lesion of multiple sclerosis. Lancet 1988;2:1203-1204. 17. Spiegel SM,Vinuela F, Fox AJ, Pelz DM. CT of multiple sclerosis: reaseessment of delayed scanning with high doses of contrast material. AJNR 1985;6533-536.

Motor neuron disease and amyotrophic lateral sclerosis: Relation of high CSF protein content to paraproteinemia and clinical syndromes D.S. Younger, MD; L.P. Fbwland, MD; N. Latov, MD, PhD; W. Sherman, MD; M. Pesce, PhD; D.J. h g e , MD; W. Trojaborg, MD; J.R. Miller, MD; R.E.Lovelace, MD; A.P. Hays, MD; and T.S. Kim, MS

Article abstract-From 1984 to 1988,ll of 120patients (9%)with motor neuron disease (MND) had paraproteinsdetected by serum immunofixation electrophoresis(IFE),compared with 4 (3%)by cellulose acetate gels: 1 patient had progressive spinal muscular atrophy,5 patients had amyotrophic lateral sclerosis (ALS),and 5 patientshad ALS with probable upper motor neuron signs.Four of 5 patients (80%)with cerebrospinal fluid (CSF)proteincontent above 75 mg/dl had paraproteins, as did 6 of 30with values above 50 mg/dl. Four of 14 patients with cerebrospinal oligoclonal bands (OCB)also had paraproteins. Two patients with ALS, CSF protein content above 75 mg/dl, and paraproteinemia had lymphoma. We conclude the following about patients with MND:high CSF protein content (especially above 75 mg/dl) or CSF OCB makes paraproteinemia more likely; some of these patients may have lymphoma; there is an inordinatelyhigh occurrence of paraproteinemia in M N D and IFE on agarose is more sensitive than electrophoresis on cellulose acetate in detecting paraproteins. Syndromes of paraproteinemia and high CSF protein are not restricted to the lower motor neuron but qualify as “ALS” with coexisting upper motor neuron signs. NEUROLOGY 1990;40595-599

The literature on motor neuron disease (MND) grows apace. Nevertheless, several simple facts are not yet known, including 2 questions about the cerebrospinal fluid (CSF): How often is the total CSF protein content abnormally increased? Does an increased CSF protein

value have any diagnostic significance? There is little information about total CSF protein content in several important general reviews of CSF or MND.1-6In 1autopsy series of MND? 15 of 38 autopsyproven cases (30%)had CSF protein content exceeding

From the Departmentsof Neurology (Drs. Younger, Rowland,Latov, Lange,Trojaborg, Miller, Lovelace,and Kim);Medicine (Division of Oncology) (Dr. Sherman); Pathology, Divisions of Clinical Pathology (Dr. Pesce), and Neuropathology (Dr. Hays), Presbyterian Hospital, Columbia University, College of Physicians and Surgeons,New York, NY. Supportedby the Center Grants from the Muscular Dystrophy Association and NIH (NINCDS-NS11766)and GCRC (RR-00645). Received June 23,1989. Accepted for publication in final form September 15,1989. Address correspondence and reprint requeststo Dr. David S.Younger, NeurologicalInstitute of the Columbia-PresbyterianMedical Center,Box 53,710 West 168th Street, New York, NY 10032-3784. April l9BO NEUROLOGY 40 SBS

Serial study of gadolinium−DTPA MRI enhancement in multiple sclerosis S. Bastianello, C. Pozzilli, S. Bernardi, et al. Neurology 1990;40;591 DOI 10.1212/WNL.40.4.591 This information is current as of April 1, 1990 Updated Information & Services

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Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 1990 by the American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.