Diffusion-Weighted Magnetic Resonance Imaging in Brain Death
To the Editor:
The case report on diffusion-weighted imaging (DWI) in brain death by Lövblad and Bassetti1 in the February issue of Stroke may be appealing but deserves elaboration. The DWI studies in the case report shows widespread ischemia, and the MR angiography shows absence of flow in the intracranial portion of the carotid arteries. However, it is not stated in the report whether there was flow void in the extracranial carotid arteries. Its presence may have suggested a diagnosis of bilateral carotid artery occlusion (eg, due to dissection) resulting in bilateral hemispheric infarction as the cause for the patient’s coma. Additionally, the authors did not comment on whether there was flow in the basilar artery. This information may have been available to the authors but was not commented on in the text.
However, much more disturbing is that this communication wrongly suggests that an imaging modality can diagnose brain death even when the clinical examination shows some remnant of brain stem reflexes. We are not certain what the authors meant by “The neurological examination after the MRI showed an intubated comatose patient who had deteriorated neurologically.”1 It is possible that the patient had met the criteria for brain death, but the authors did not provide details on clinical testing.
Brain death is the irreversible loss of function of the brain and brain stem.2 3 The diagnosis of brain death in adults in the United States is not, as the authors stated, “usually supported by confirmatory tests.” The article quoted here did not propose that view.2 The guidelines proposed by the American Academy of Neurology stated that “… confirmatory test is not mandatory but desirable when specific components of the clinical testing cannot be reliably performed. …”3 Differences in recommendations for confirmatory tests after a clinical diagnosis of brain death exist in European countries and are even mandatory in Italy, Luxembourg, and Holland. In addition, the Swiss brain death code requires mandatory repeat testing by two physicians, and confirmatory tests are considered optional (“facultative”).4
Before a clinical examination is performed, the proximate cause should be known, and obviously a compatible neuroimaging study does not obviate a search for confounders. It is incorrect to state that “on the basis of the imaging findings it was concluded that the patient had entered a state of brain death,” and we truly hope this was merely an oversight.
It is a seeming contradiction of our time, as much as we embrace high technology and innovational equipment, that we have to continue to use a clinical approach in the determination of brain death. No matter what, brain death remains a clinical diagnosis. Unless the authors can provide a comprehensive neurological examination with a detailed apnea test, the claim that this is the first example of a DWI image of brain death should be withdrawn.
- Copyright © 2000 by American Heart Association
Lovblad K, Bassetti C. Diffusion-weighted magnetic resonance imaging in brain death. Stroke.. 2000;31:539–542.
Wijdicks EFM. Determining brain death in adults. Neurology.. 1995;45:1003–1011.
Quality Standards Subcommittee of the American Academy of Neurology. Practice parameters for determining brain death in adults. Neurology.. 1995;45:1012–1014.
Haupt WF, Rudolf J. European brain death codes: a comparison of national guidelines. J. Neurol.. 1999;246:432–437.
To the Editor:
Lövblad and BassettiR1 in the February 2000 issue of Stroke described the DWI findings of an elderly woman with ischemic heart disease who suddenly became comatose and developed generalized convulsions. The neurological examination revealed a deeply comatose subject with bilateral pyramidal signs and partially preserved brain stem reflexes. MRI imaging of the brain performed 1 day later revealed diffusely increased signal on the DWI sequence, a herniated temporal lobe, and areas of hemorrhage in the right basal ganglia. On the basis of such findings, the authors diagnosed brain death.
The diagnosis of brain death, also termed death by neurological criteria, relies on the presence of coma of irreversible origin, brain stem arreflexia, and apnea. The diagnosis is entirely clinical, and confirmatory testing is required only in patients in whom specific components of clinical testing cannot be reliably evaluated.R2 The diagnosis is particularly complex in patients with coma of undetermined origin. In such cases, prolonged observation is warranted, and testing to determine absent cerebral blood flow should be performed.R2 Imaging studies are often used to confirm that a neurological catastrophe that could lead to death by neurological criteria has occurred. The Guidelines for Determination of Death published in the United States by the President’s Commission indicate that imaging studies are useful only to help determine the cause of coma and to limit the period of observation.R2 When confirmatory tests such as cerebral angiography or transcranial Doppler examination are used, the anterior and posterior circulation should be examined.R2
Abnormal signal on DWI sequences and associated decreases in apparent diffusion coefficient likely represent non-Brownian diffusion of water as a result of energy failure and cytotoxic edema.R3 R4 DWI abnormalities may be nonspecific and may occur with nonischemic insults. DWI maybe normal in patients with evolving strokes.R4 R5 DWI abnormalities may occur at cerebral blood flow levels as high as 41 mL/100 g/min, while brain death implies absent blood flow to the brain.R4 Standard axial and coronal MRI imaging may readily identify signs of transtentorial or diencephalic herniation.R6 Nevertheless, such findings do not necessarily indicate irreversible brain injury or brain death, because they may occur in patients who do not meet clinical criteria for brain death.R6
In our opinion, the imaging findings described in this unfortunate woman suggest a diffuse ischemic insult to the brain, with resultant compartment shifts. The absent flow-void signal in the carotid arteries can not be interpreted as a sign of brain death unless the extracranial carotid arteries are patent and absent flow is also documented in the posterior circulation. Diagnosing brain death in this patient was particularly difficult, as the cause of coma was not certain.
MRI imaging may have a role in the diagnosis of brain death, as observational studies performed in recent years have already suggested. Ishii and colleaguesR7 considered absence of the intracranial carotid arteries above the supraclinoid portions, diffuse cerebral swelling, as well as tonsillar and central herniation findings suggestive of brain death. Such findings were noted in a small case series study but have not been validated in larger studies and have not been compared with cerebral angiography. It is possible that 3D time-of-flight MR angiography may give a false diagnosis of brain death in patients with increased intracranial pressure, reduced cerebral perfusion pressure, and very slow blood flow. Given the enormous ethical implications that the diagnosis of death by neurological criteria carries, caution should be exerted before embracing these new techniques as confirmatory diagnostic tools. These DWI findings can not be considered specifically diagnostic of brain death.
Lövblad K-O, Bassetti C. Diffusion-weighted magnetic resonance imaging in brain death. Stroke.. 2000;31:539–542.
Wijdicks EFM. Determining brain death in adults. Neurology.. 1995;45:1003–1009.
Prichard JW, Grossman RI. New reasons for early use of MRI in acute stroke. Neurology.. 1999;52:1733–1736.
Baird AE, Warach S. Magnetic resonance imaging of acute stroke. J Cereb Blood Flow Metab.. 1998;18:583–609.
Ay H, Buonanno FS, Rordorf G, Schaefer PW, Schawn LH, Wu O, Gonzalez RG, Yamamda K, Sorensen GA, Koroshetz WJ. Normal diffusion-weighted MRI during stroke like deficits. Neurology.. 1999;52:1784–1792.
Reich JB, Sierra J, Camp W, Zanzonico P, Deck MDF, Plum F. Magnetic resonance imaging measurements and clinical changes accompanying transtentorial and foramen magnum brain herniation. Ann Neurol.. 1993;33:159–170.
Ishii K, Onuma T, Kinoshita T, Shiina G, Kameyama M, Shimosegawa Y. Brain death: MR and MR angiography. AJNR Am J Neuroradiol.. 1996;17:731–735.
We thank Drs Phan, Wijdicks, Chalela, and Kasner for giving us the opportunity to be more precise on certain points that might be misunderstood in our recent article in Stroke.1 We agree that brain death is, as Drs Phan and Wijdicks state, a clinical diagnosis,2 and we did not intend to imply that DWI could replace or even challenge the well-accepted methods of establishing this diagnosis. The aim of our paper was to report new MRI findings with DWI that may in the future be used to support the clinical diagnosis of brain death. In our patient, it was MRI that first suggested brain death. This diagnosis was, however, clinically confirmed immediately after the radiological testing. The clinical examination, which we did not report in detail in our short communication, revealed loss of signs of brain and brain stem function, and the patient died later the same day. Because the patient was not considered a potential organ donor, an apnea test was not performed. Despite this limitation, we believe that the reported clinical examination and evolution allow us to consider our DWI findings as new MRI correlates of clinical brain death.
As to the technical points raised, there was no flow in the intracranial arteries on spin-echo imaging and there were no visible intracranial vessels on MR angiography (MRA); these findings, in addition to herniation, are previously reported MRI correlates of clinical brain death.3 We were also not able to demonstrate a proximal cause: there was no evidence of carotid dissection, either clinically or on spin-echo MRI. There was also no flow in the basilar artery, either on spin-echo imaging or in the MRA. We do not consider the conventional time-of-flight (TOF) MRA method we performed (using a slab covering the intracranial arteries) to be suitable for examination of the extracranial carotid arteries since they are located peripherally, even if flow could be detected at the edge of the slab in small vessels in the areas corresponding to the extracranial arteries. Also, TOF sequences are prone to signal degradation due to blood flow disturbances.
In addition to what was mentioned in our report, we performed a first-pass 3D gadolinium-enhanced MRA of the head and neck vessels, which covered the arteries of the brain and neck from the aortic arch to the circle of Willis; this sequence is much less prone to flow-related artifacts4 than conventional TOF sequences and is closer to conventional angiography than TOF sequences in its capacity to demonstrate vascular occlusions. Using this method, we could see patent extracranial carotid arteries on both sides but no intracranial vessels: neither the internal carotid arteries nor the basilar artery were present (Figure⇑), even in the later time series. There was also no visible string sign compatible with dissection.
While it is a method which has proved to be of interest for the investigation of cerebral ischemia, we are also well aware that DWI is very sensitive to tissular damage, and may also be nonspecific and even provide false-negative or false-positive results for ischemia under certain circumstances5 ; DWI, indeed, demonstrates changes in tissular motion which have to be completely elucidated; it can, however, explore interesting underlying pathophysiological changes in ischemic states; DWI and ADC changes have been observed to be reversible in experimental models of ischemia,6 but this is still debated.7 However, there seem to exist thresholds of ADC changes under which reversibility is less likely.8 Also, the extent anatomically and ADC-wise makes such recovery in our patient rather unlikely, in our opinion.
In summary, we believe that DWI could become a further ancillary diagnostic tool supporting but not required for the diagnosis of brain death, in addition to cerebral angiography, Doppler ultrasound, and conventional MRI. This was the intended message of our report.
Lövblad KO, Bassetti C. Diffusion-weighted magnetic resonance imaging in brain death. Stroke.. 2000;31:539–542.
Wijdicks EFM. Determining brain death in adults. Neurology.. 1995;45:1003–1011.
Aichner F, Felber S, Birbamer G, Luz G, Judmaier, Schmutzhard E. Magnetic resonance: a noninvasive approach to metabolism, circulation, and morphology in human brain death. Ann Neurol.. 1992;32:507–511.
Remonda L, Heid O, Schroth G. Carotid artery stenosis, occlusion and pseudo-occlusion: first-pass gadolinium-enhanced, three dimensional MR angiography: preliminary study. Radiology.. 1998;209:95–102.
Lövblad KO, Laubach HJ, Baird AE, Curtin F, Schlaug G, Edelman RR, Warach S: Clinical experience with diffusion-weighted MR in patients with acute stroke. AJNR Am J Neuroradiol.. 1998;19:1061–1066.
Hasegawa Y, Fisher M, Latour LL, Dardzinski BJ, Sotak CH. MRI diffusion mapping of reversible and irreversible ischemia. Neurology. 1994;44;1484–1490.
Li F, Han SS, Tatlisumak T, Liu KF, Garcia JH, Sotak CH, Fisher M. Reversal of acute apparent diffusion coefficient abnormalities and delayed neuronal death following transient focal cerebral ischemia in rats. Ann Neurol.. 1999;46:333–342.
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