Correspondence

Imaging the Brain

N Engl J Med 1998; 339:407-409August 6, 1998

Article

To the Editor:

In his excellent review article “Imaging the Brain” (March 19 and 26 issues),1 Dr. Gilman introduces us to the fascinating role of magnetic resonance imaging (MRI) in the evaluation of patients with multiple sclerosis. He states that “MRI demonstrates disease activity in the absence of clinical findings, thereby permitting more effective evaluation of patients and facilitating objective determination of the efficacy of therapy.”

MRI indeed is a sensitive, objective way to detect plaques in multiple sclerosis. Although the use of this technique has considerably increased our knowledge of multiple sclerosis, MRI is by no means a perfect technology. For example, the exact relation between changes on MRI and clinical changes (disability) is unclear, and the cost of MRI is considerable, particularly if large populations must undergo frequent imaging. In individual cases, there may be little correlation: patients with minimal disability may have extensive changes on MRI, and the reverse may also be true. Increasingly, however, large clinical series and clinical trials are able to show differences between groups and correlations of changes on MRI with the clinical course.2

MRI is a frequently used secondary outcome measure for the assessment of putative treatments for multiple sclerosis. Although early studies, which compared scores on the Expanded Disability Status Scale,3 suggested a poor correlation between MRI-measured disease and the clinical course of disease,4 more recent studies allow more optimism about the role of MRI.

Xavier Bosch, M.D., Ph.D.
Hospital Casa Maternitat, Barcelona 08028, Spain

4 References

1
Gilman S. Imaging the brain. N Engl J Med 1998;338:812-20, 889
Full Text | Web of Science | Medline

2
Khoury SJ, Guttmann CR, Orav EJ, et al. Longitudinal MRI in multiple sclerosis: correlation between disability and lesion burden. Neurology 1994;44:2120-2124
Web of Science | Medline

3
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an Expanded Disability Status Scale (EDSS). Neurology 1983;33:1444-1452
Web of Science | Medline

4
Bastianello S, Pozzilli C, D'Andrea F, et al. A controlled trial of mitoxantrone in multiple sclerosis: serial MRI evaluation at one year. Can J Neurol Sci 1994;21:266-270
Web of Science | Medline

To the Editor:

Dr. Gilman's informative review of brain imaging may create an overly optimistic view of the utility of imaging procedures in the evaluation of dementia. In Table 1 of his article, MRI, positron-emission tomography, and single-photon-emission computed tomography are referred to as “preferred imaging procedures” for dementia. Dr. Gilman describes anatomical brain imaging (with the use of computed tomography and MRI) as “essential in the evaluation of dementia,” yet he also concedes that computed tomography and MRI possess too little specificity or sensitivity to allow a definitive diagnosis of dementia. Given the importance of using resources efficiently, shouldn't we reserve anatomical imaging in the assessment of dementia to patients with evidence of structural brain disease (e.g., focal signs) and forgo its use in patients at low risk for structural lesions (e.g., an 85-year-old patient with a gradual onset of progressive dementia)?

Are physiologic imaging procedures really “preferred” tests for the assessment of dementia? Although Dr. Gilman cites studies that show evidence of abnormalities on positron-emission tomography and single-photon-emission computed tomography in various dementias, no one has demonstrated that these techniques are sufficiently sensitive or specific to be used to diagnose dementia in general or a specific cause of dementia. These are very expensive tests. Their use should be guided by accepted principles of the utility of diagnostic testing.

James L. Levenson, M.D.
Virginia Commonwealth University, Richmond, VA 23298-0268

To the Editor:

In regard to the review of techniques for imaging the brain by Gilman, we would like to highlight some additional uses of ultrasonography. Transcranial Doppler ultrasonography is an excellent noninvasive technique for the evaluation of intracranial hemodynamics. Analysis of the wave form and blood-flow velocity can provide indirect information on cerebral blood flow, vascular resistance, and intracranial pressure.1 It is a versatile and widely available technique that has actually become an essential tool in diagnosis, monitoring, and therapeutic guidance in critically ill patients with neurologic diseases.

In addition to its usefulness in detecting cerebral vasospasm after subarachnoid hemorrhage and as a monitoring agent during surgical procedures of the brain, transcranial Doppler ultrasonography has other major current applications, including determining the patency of vessels during ischemic stroke and thrombolytic therapy; assessing the capacity for collateral formation in the circle of Willis; identifying cerebral arteriovenous malformation, post-traumatic cerebral vasospasm, and markedly increased intracranial pressure; and monitoring cerebral hemodynamics in high-risk patients with neurologic diseases.1,2 Furthermore, arrest of the intracranial circulation can be reliably detected by transcranial Doppler ultrasonography, which may be a helpful ancillary test in the early identification of brain death.1,3,4 In fact, the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology has accepted transcranial Doppler ultrasonography as a reliable test for the confirmation of brain death.5

Rafael Martín-Bermúdez, M.D.
Francisco Murillo-Cabezas, M.D.
Jose María Dominguez-Roldán, M.D.
Hospital Universitario Virgen del Rocío, 41013 Seville, Spain

5 References

1
Newell DW. Transcranial Doppler measurements. New Horiz 1995;3:423-430
Medline

2
Karnik R, Stelzer P, Slany J. Transcranial Doppler sonography monitoring of local intra-arterial thrombolysis in acute occlusion of the middle cerebral artery. Stroke 1992;23:284-287
CrossRef | Web of Science | Medline

3
Dominguez-Roldan JM, Murillo-Cabezas F, Munoz-Sanchez A, Santamaria Mifsut JL, Villen-Nieto J. Changes in the Doppler waveform of intracranial arteries in patients with brain-death status. Transplant Proc 1995;27:2391-2392
Web of Science | Medline

4
Petty GW, Mohr JP, Pedley TA, et al. The role of transcranial Doppler in confirming brain death: sensitivity, specificity, and suggestions for performance and interpretation. Neurology 1990;40:300-303
Web of Science | Medline

5
American Academy of Neurology, Therapeutics and Technology Assessment Subcommittee. Assessment: transcranial Doppler. Neurology 1990;40:680-681
Web of Science | Medline

To the Editor:

The review article on imaging of the brain in neurologic disease by Dr. Gilman was comprehensive. However, a discussion of the usefulness of imaging studies in the legal determination of brain death was omitted.

Ultrasonography, angiography, and radionuclide scanning have all been used as adjuncts in the diagnosis of brain death. We have had experience with the use of radionuclide imaging in our population of patients with trauma. By using nuclear-medicine techniques for the objective determination of the absence of cerebral blood flow to declare brain death, we have shortened the length of hospitalization and minimized associated costs in a population of patients with lethal injuries while increasing the number of organs procured per donor.1 In addition, in this population, the use of nuclear-medicine scanning to determine brain death objectively and definitively has been associated with a significant increase in organ-donation rates.2

Patrick M. Reilly, M.D.
Abass Alavi, M.D.
Donald H. Jenkins, M.D.
University of Pennsylvania Medical Center, Philadelphia, PA 19104

2 References

1
Jenkins DH, Reilly PM, McMahon DJ, Grossman MD, Alavi A, Schwab CW. Minimizing charges associated with the determination of brain death. Crit Care 1997;1:65-70
CrossRef | Medline

2
Jenkins DH, Reilly PM, Shapiro MB, et al. Effect of rapid brain death determination on organ donation rates: a preliminary report. Crit Care Med 1998;26:Suppl:A31-A31 abstract.
CrossRef

Author/Editor Response

Dr. Gilman replies:

To the Editor: I agree with Dr. Bosch that although MRI provides a sensitive means of detecting plaques in multiple sclerosis, the procedure is expensive and the relation of changes on MRI to the extent of clinical disability in individual patients is unclear. I also agree that correlations between the level of disability and the lesion burden have been found in large clinical series and that MRI is useful as a secondary outcome measure for the assessment of experimental therapies. Indeed, as Dr. Bosch knows, a recent international workshop on the design of therapeutic trials in multiple sclerosis recommended the incorporation of frequent MRI studies in phase 1 and 2 clinical trials.1

Dr. Levenson disagrees with my statement that anatomical brain imaging is essential in the evaluation of dementia and states that anatomical imaging should be restricted to patients with focal signs suggesting structural brain disease. He suggests that an 85-year-old patient with a gradual onset of progressive dementia would not need to undergo anatomical imaging. I strongly disagree with this suggestion. Many structural disorders can cause dementia without focal abnormalities and will be missed unless anatomical imaging is performed. Examples are subdural and epidural hematomas, primary and metastatic brain tumors (which can occur without focal abnormalities, particularly when they involve the prefrontal cortex), normal-pressure hydrocephalus, and multiple-infarct dementia. Indeed, the 85-year-old patient with progressive dementia whom Dr. Levenson uses as an example could have a subdural hematoma, and surgical evacuation may restore the patient's intellect. Dr. Levenson also states that physiologic imaging tests are not sufficiently sensitive or specific to be used to diagnose dementia and that they are expensive. The sensitivity and specificity of physiologic imaging in dementia have not been determined, but the utility of these tests has been demonstrated repeatedly at many institutions, where subsequent autopsy examinations show that they have differentiated Alzheimer's disease from the frontal dementias, Creutzfeldt–Jakob disease, and multiple-infarct dementia. With respect to expense, the most efficient use of resources in patients with dementia is to delay or avert the need for long-term or institutional care, and this is best fostered by making a specific diagnosis. The cost of imaging is trivial as compared with the cost of long-term care.

I appreciate the detailed comments of Dr. Martín-Bermúdez and colleagues on the utility of transcranial Doppler ultrasonography and agree with the statement of Reilly et al. concerning the utility of physiologic imaging in the diagnosis of brain death.

Sid Gilman, M.D.
University of Michigan, Ann Arbor, MI 48109-0316

1 References