LETTERS

PET Imaging of Brain Tumors Lorcan A. O’Tuama, MD’ and Peter C . Phillips, MD?

Dr Mazziotta (April 1991 issue of Annals) has provided an excellent account of the role of PET, especially f18F12- deoxy-2-fluoro-~-g~ucose (FDG) imaging, in the diagnosis of brain tumors [l}. His review prompts us to comment on another important aspect of PET imaging of brain tumors.

The study of amino acid metabolism in brain neoplasms has made an important contribution to the characterization of the functional activity of these lesions. The tracer L- {methyl-1 1C)methionine (1 1 C-MET) has shown uniformly high sensitivity for detection of low-grade gliomas E2, 3 , 47 and a wide range of other histological tumor types [ S ] . 11C- MET positivity for supratentorial lesions has been found to exceed that of FDG [4]. 11C-MET also holds promise as a valuable probe for the assessment of cerebral radiation injury in vivo. As noted by Dr Mazziotta, decreased uptake of FDG has been widely used I61 as an indicator of cerebral radiation injury. Significant ambiguity may attend this method, how- ever, since focal hypometabolism is found in a substantial number of primary brain tumors 171, especially in low-grade lesions [8]. 11C-MET, which was consistently elevated even with low-grade lesions, might be expected to offer a clearer choice between tumor and edema.

Further elucidation of radiation injury may be obtained through study of the mechanism underlying increased con- centration of 11C-MET in human brain tumors. Normal hu- man brains show a competitive mechanism of transport for neutral amino acids 197, which is retained by human brain neoplasms [lo, 111, but not at sites of radation injury 1113. We suggest consideration of the readily synthesized positron radiopharmaceutical 11C-MET to play a primary role in the functional imaging of human brain tumors.

*Departments of Radiology (Nuclear Medicine) and Neuroloa Children’s Hospital Boston, M A ?Department of Neumiogy Children’s Hospital of Phikadelphia Philadelphia, PA

RefeerenceJ 1. Mazziotta JC. The continuing challenge of primary brain tumor

management: the contribution of positron emission tomogra- phy. Ann Neurol 1991;29:345-346

2. Shishido F, Uemura K, Inugami A, Tomura N, Higano S, Fujita H, Murakami M, Kanno I, Yasui N, Mineura K. Value of 11C- methionine and PET in the diagnosis of low-grade gliomas. Kaku Igaku 1790;27:273-302

3. Schober 0, Cruetzig H, Meyer GJ, Becker H, Schwarzrock R, Dietz H, Hundeshagen H. 11C-Methionine-PET, IMP- SPECT, CT, and MRI bei Hirntumoren. ROFO 1985;143:

4. Ericson K, Lilja A, Bergstrom M, Collins VP, Ericksson L, Ehrin E, von Holst H, Lundqvist H, Langstrom B, Mosskm M. Posi- tron emission tomography with (I1 lC]methyl)-~-rnethionine, I1 lCID-glucose, and 168GalEDTA in supratentorial tumors. J Comput Assist Tomogr 1985;9:683-689

5. O’Tuama LA, Phillips PC, Strauss LC, Uno Y, Smith QR, Dan-

133-136

nals RF, Wilson AA, Ravert HT, LaFrance ND, Wagner H N Jr. Two-phase [l lC]~-methionine PET scanning in diagnosis of childhood brain tumors. Pediatr N e w 1 1990;6:163-170

6. Di Chiro G. Positron emission tomography using fl8F1fluoro- deoxyglucose in brain tumors: a powerful diagnostic and prog- nostic tool. Invest Radio1 1987;22:360-371

7. Alavi JB, Alavi A, Chawluk J, Kushner M, Powe J, Hickey W, Reivich J. Positron emission tomography in patients with &- oma: a predictor of prognosis. Cancer 1988;15:62:1074-1078

8. Francavilla TL, Miletich RS, Di Chiro G, Patronas NJ, Rizzoli HV, Wright DC. Positron emission tomography in the detection of malignant degeneration of low-grade gliomas. Neurosurgery

9. OTuama LA, Guilarte TR, Douglass KH, Wagner HN Jr, Wong DF, Dannals RF, Ravert HT, Wilson AA, LaFrance ND, Bice AN, Links JM. Assessment of 1 1-C-L-methionine transport into the human brain. J Cereb Blood Flow Metab 1988;8:

10. Bergstrom M, Ericson K, Hagenfeldt L, Mosskin M, von Holst H, Noren G, Eriksson L, Ehrin E, Johnstrom P. PET study of methionine accumulation in glioma and normal brain tissue: competition with branched chain amino acids. J Comput Assist Tomogr 1987;11:208-213

11. OTuarna LA. Methionine transport in brain tumors. J Neuro- psych Clin Neurosc 1989;1:S37-S44

1989;24:1-5

341-345

Current Diamos tic Criteria for Guillain-garre Syndrome F. G. A. van der Mech6, MD, PhD, J. Meulstee, MD, and R. P. Kleyweg, MD, PhD

Guillain-BarrC syndrome is an inflammatory, predominantly demyelinating polyneuropathy with an often severe course. At present this condition can be treated to decrease morbid- ity and to improve outcome. The first proven treatment was plasma exchange [ 11. Plasmapheresis is especially effective if applied early in the course of the disease 11). In this early phase, therefore, diagnostic criteria are becoming increas- ingly important, compared to 1978, for example, when the criteria were originally described to improve epidemiological studies. Recently, the criteria have been reconfirmed and expanded by Asbury and Cornblath {27. Detailed criteria may result, however, in delay of the diagnosis and, hence, appro- priate treatment, especially if physicians who are less familiar with the problem look for laboratory confirmation of an es- sentially clinical diagnosis.

It is our experience that sometimes a definite diagnosis is postponed until the protein content of the cerebrospinal fluid is raised above normal values or until electrodiagnostic signs suggesting demyelination are found. We wish to warn against such a practice. The diagnosis, as discussed in the criteria, should be based primarily on the development of more or less symmetrical motor weakness over a period ranging from days to 4 weeks. As a general rule, myotatic reflexes decrease or disappear but may be present up to grade 3 weakness (MRC-scale) if the sensory fibers are uninvolved 131. We fully agree, therefore, with the clinical criteria as confirmed

Copyright 0 1991 by the American Neurological Association 851

by Asbury and Cornblath [2]. In our view laboratory studies are-especially early in the disease-of primary importance to exclude other conditions, but they are not necessary to confirm the clinical diagnosis.

Furthermore, a general comment on electrodiagnostic cri- teria for demyelination may be worth considering. Demyelin- ation distributed along the whole nerve may result in both dispersion of motor unit potentials and conduction block. Both mechanisms result in a decrease of the CMAP ampli- tude if the stimulating electrode is progressively moved to more proximal stimulation sites. However, it is impossible to separate these two mechanisms on the basis of the duration of the CMAP amplitude [43. For diagnostic purposes, how- ever, it is not necessary to separate dispersion and conduction block because both result from demyelination. It is for this reason that we suggested the descriptive term length- &pendent amplitude reduction [31. The artificial separation of CMAP amplitude with or without a 15% or higher increase in duration will not be necessary, then, as criteria for demye- lination. At present the electrodiagnostic studies in the Dutch immunoglobulin trial, performed at entry, after 1, and after 4 weeks, are being analyzed to compare these different ap- proaches.

Erasmus Uniuersiteit Rotterdam The Netherlands

Refereences 1. Guillain-Barre Syndrome Study Group. Plasmapheresis and acute

Guillain-Barre syndrome. Neurology 1985;35: 1096- 1104 2. Asbury AK, Cornblath DR. Assessment of current diagnostic

criteria for Guillain-Barre syndrome. Ann Neurol 1990;27:

3. Van der Mechk FGA, Meulstee J, Vermeulen M, Kievit A. Pat- terns of conduction failure in the Guillain-Barri. syndrome. Brain

4. Rhee EK, Sumner AJ. A computer simulation of conduction block effects produced by actual block versus interphase cancel- lation. Ann Neurol 1990;28(2):146-156

S2 1-24

1988;111:405-416

Reply David R. Cornblath, MD

Dr van der Mech6 and associates raise an important point about applying diagnostic criteria in studies of Guillain-Bar6 syndrome. Early on, patients may not meet all diagnostic criteria, yet they clearly have Guillain-Barr& syndrome, which becomes better defined over time. This does not imply that patients cannot enter therapeutic trials until all diagnostic criteria have been met. Rather, based on a tentative diagnosis by experienced clinicians, patients could enter a therapeutic trial as long as there was a review of the original symptoms to be certain that patients indeed had the proper diagnosis. In the North American study of Guillain-Bard syndrome, for example, this was an effective method of ensuring proper diagnosis. In fact, no patient who was entered into the study based on clinical criteria was subsequently found to have another disorder (Dr J. Griffin, personal communication). This would allow for relatively rigd criteria to be applied in studies as long as the criteria were applied post hoc.

Johm Hopkins Hospital Baltimore, M D

An Alternative Amea Test for the Evaluatioiof Brain Death David H. Gutmann, MD, PhD,” and Paul L. Marino, MD, PhDt

Recent experience with the apnea test for brain death reveals serious complications that can pose a threat to patient safety and to the success of organ donation [l}. The problems arise from the use of prolonged apnea (10 minutes or longer) to promote CO, retention to excitatory levels, because the complete cessation of breathing movements eliminates the ability to provide oxygen by inhalarion and creates a risk for severe hypoxemia. Inhalation of 100% oxygen prior to the apnea period has not eliminated the problem; in fact, a recent report demonstrated an average arterial pOz of 26 mm Hg after 10 minutes of apnea despite pretest inhalation of 100% oxygen for 15 minutes 111. Continuous flow oxygen insuffla- tion into the trachea during the apnea period has been associ- ated with adequate oxygenation; however, insufflation may lead to tracheal disruption and barotrauma 11). Another drawback is the lack of effective blood gas monitoring during the test. The current practice is to obtain a blood sample for blood gas measurement at the end of the apnea period and resume mechanical ventilation pending these results. This “hit or miss” approach is not designed to identify the end- point pC02, and this can produce either unwanted hypercap- nia (overshoot) or inadequate C 0 2 retention (undershoot).

The undesirable features of the apnea maneuver can be circumvented by employing hypoventilation to promote CO, retention. The presence of breathing movements allows oxy- gen ro be inhaled during the test, which should reduce or eliminate the risk for hypoxemia. Breathing movements also create the ability to measure exhaled CO,, and the CO, at end-exhalation (end-tidal CO,) can be used as an indirect measure of arterial pC02. This on-line type of monitoring helps to identify the end-point of the test, thereby preventing unwanted overshoot or undershoot in the target pC0,.

The clinical performance of the hypoventilation test for an adult male with no spontaneous respirations is shown in the Figure. At zero minutes, the ventilation is abruptly decreased to 1.0 L/min. The upper panel represents the arterial 0, saturation measured noninvasively with a pulse oximeter placed on one of the digits. The patients should receive 100% oxygen during the hypoventilation period, and the 0, saturation should be maintained at 90% or higher. Pulse oximetry has proved reliable in a variety of clinical settings and over a wide range of hemoglobin levels 121, but the accuracy in any individual patient must be determined by blood gas measurement. The lower panel in the Figure repre- sents the end-expiratory pC02 (pETC02) measured with an infrared CO, probe placed along the expiratory ventilator tubing. When lung function is normal, the pETC0, is equiva- lent to the arterial pC02. However, when cardiopulmonary pathology produces ventilation-perfusion inequalities in the lung, the pETC0, decreases relative to the arterial CO, by an amount dictated by the severity of the abnormality [31. Nevertheless, the difference between the arterial and end- tidal pC0, remains constant as long as the clinical condition

852 Annals of Neurology Vol 30 N o 6 December 1991