Neurology -- Correspondence for Sloan et al., 62 (9) 1468-1481

Correspondence published:

Assessment: Transcranial Doppler ultrasonography: Report of the Therapeutics and Technology Assessme: Calixto Machado (4 August 2004)

Assessment: Transcranial Doppler ultrasonography: Report of the Therapeutics and Technology Assessme: Ignacio J Previgliano (4 August 2004)

Reply to Machado and Previgliano: Michael Sloan, MD, TTA Subcommittee of the AAN (4 August 2004)

Assessment: Transcranial Doppler ultrasonography: Report of the Therapeutics and Technology Assessme 4 August 2004

Calixto Machado,
President of the Cuban Commission for the Determination and Certification of Death
Institute of Neurology and Neurosurgery, Apartado Postal 4268, Ciudad de La Habana 10400, Cuba
Send Correspondence to journal:
Re: Assessment: Transcranial Doppler ultrasonography: Report of the Therapeutics and Technology Assessme

braind{at}infomed.sld.cu Calixto Machado

The AAN Therapeutics and Technology Assessment Subcommittee presented a remarkable report on the transcranial doppler ultrasonography (TCD) applications for clinical use. [1] The use of TCD to diagnose cerebral circulatory arrest and brain death (BD) is of interest.
Bernat recently discussed that irreversibility has been a prerequisite for brain death confirmation in every set of BD diagnostic criteria arguing that �the only reliable proof of irreversibility is demonstrating the complete absence of intracranial circulation.� [2] An advantage of TCD that the Subcommittee emphasized, TCD �can be performed at the bedside and repeated as needed or applied for continuous monitoring�, make this technique applicable to the intensive care environment to comatose, intubated and unresponsive patients. A major limitation is that �it can demonstrate cerebral blood flow velocities only in certain segments of large intracranial vessels�, does not decrease its potentiality to access an intracranial circulatory arrest. [1]
Several other techniques have also shown to be useful, but contrary to TCD, it is almost always mandatory to move patients outside the ICU. [1,3]
The Subcommittee compared TCD sensitivity and specificity in different clinical settings. It is notable that the highest percentages corresponded to TCD for detecting circulatory arrest (91-100 and 97-100%). [1] Although there is no perfect ancillary test in clinical practice, [3] these values are very high.
We recently passed a law for the determination and certification of death in Cuba. [4] We proposed using confirmatory tests (still optional) to: prove absent cerebral flow; to demonstrate loss of bioelectric activity; when clinical examination is not reliable; to shorten period of observation; and in primary brainstem lesions. Among those tests to detect absent CBF, we defend the use of TCD because of the outlined advantages. [1] We concluded that by combining TCD and neurophysiologic tests (multimodality evoked potentials and electroretinography), BD diagnostic reliability could be considerably increased. [4,5]
References
1. Sloan MA, Alexandrov AV, Tegeler AH, et al. Assessment: Transcranial Doppler ultrasonography: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology, May 2004; 62: 1468 - 1481.
2. Bernat J. On irreversibility as a prerequisite for brain death determination. In: Machado C, Shewmon DA, editors. Brain Death and Disorders of Consciousness. New York: Kluwer Academic/Plenum Publishers, 2004: 161-168.
3. Cabrer C, Dom�nguez-Rold�n JM, Manyalich M, et al. Persistence of intracranial diastolic flow in transcranial Doppler sonography exploration of patients in brain death.Transplant Proc. 2003;35(5):1642-1643.
4. Machado C, Abeledo M, Alvarez C, et al. Cuba has passed a law for the determination and certification of death. In: Machado C, Shewmon DA, editors. Brain Death and Disorders of Consciousness. New York: Kluwer Academic/Plenum Publishers, 2004:139-142.
5. Machado C. Evoked potentials in brain death. Clin Neurophysiol. 2004;115(1):238-239.

Assessment: Transcranial Doppler ultrasonography: Report of the Therapeutics and Technology Assessme 4 August 2004

Ignacio J Previgliano,
Professor Critical Care Medicine, Maimonides University School of Medicine
Virrey Loreto 2676 7� ,1426 Buenos Aires, Argentina
Send Correspondence to journal:
Re: Assessment: Transcranial Doppler ultrasonography: Report of the Therapeutics and Technology Assessme

iprevi{at}intramed.net Ignacio J Previgliano

Pregnancy may have been beyond the scope of the excelent assestment by Sloan et al. [1] Nevertheless, there are four important articles [2-5] proving the hypothesis that cerebral perfusion pressure (CPP) and eclampsia-related disorders can be identified through transcranial doppler (TCD).
The first report observed laboring women with a lumbar epidural in situ with TCD insonation of the maternal middle cerebral artery (MCA) to measure systolic, diastolic, and mean velocities. The authors challenged TCD estimated CPP (mm Hg)=[V(mean)/(V(mean)- V(diastolic)]*(MAP - DBP) and directly measured CPP=MAP-ICP and found an r= 0.92 in the regression analysis.
The other two papers confirmed that there is a state of vasoconstriction in preeclamptic women that is unresponsive to stimuli that under normal circumstances result in vasodilation [3] and that uncontrolled CPP may cause barotrauma and vessel damage, leading to hypertensive encephalopathy and overperfusion injury. [4]
Perhaps the most important conclusion was that normotensive pregnant women who later have preeclampsia demonstrate lower baseline pulsatility and resistance indices but normal vasodilatory responses to challenge tests. These findings suggest that women who are destined to have preeclampsia experience cerebral hemodynamic changes that predate the development of overt preeclampsia symptoms. [5] This is a major contribution of the method to identify a group of pathologies that could be preventable or, at least, treated in advance.
References
1) Sloan MA, Alexandrov AV, Tegeler CH, et al. Assessment: Transcranial Doppler ultrasonography: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2004; 62: 1468-1481.
2) Riskin-Mashiah S, Belfort MA, Saade GR, Herd JA. Transcranial doppler measurement of cerebral velocity indices as a predictor of preeclampsia. Am J Obstet Gynecol 2002;187:1667-1672.
3) Belfort MA, Varner MW, Dizon-Townson DS, Grunewald C, Nisell H. Cerebral perfusion pressure, and not cerebral blood flow, may be the critical determinant of intracranial injury in preeclampsia: a new hypothesis. Am J Obstet Gynecol 2002;187:626-634.
4) Riskin-Mashiah S, Belfort MA, Saade GR, Herd JA. Cerebrovascular reactivity in normal pregnancy and preeclampsia. Obstet Gynecol 2001;98:827-832.
5) Belfort MA, Tooke-Miller C, Varner M et al. Evaluation of a noninvasive transcranial Doppler and blood pressure-based method for the assessment of cerebral perfusion pressure in pregnant women. Hypertens Pregnancy 2000;19:331-340.

Reply to Machado and Previgliano 4 August 2004

Michael Sloan, MD,
Rush Medical Center
1645 W. Jackson Blvd., Suite 400, Chicago, IL 60612-3227,
TTA Subcommittee of the AAN
Send Correspondence to journal:
Re: Reply to Machado and Previgliano

michael_a_sloan{at}rush.edu Michael Sloan, MD, et al.

On behalf of my colleagues, I am happy to respond to the letters of Drs. Machado and Previgliano.
We are pleased that Dr. Machado has been instrumental in passing a law for the determination of brain death in Cuba and that transcranial Doppler (TCD) may be used for that purpose. He raises the concern that the sensitivity and specificity of transcranial Doppler (TCD) for detection of cerebral circulatory arrest and brain death ��could be considered very high.�
In our article, we reviewed a number of high quality articles that also discuss some caveats that impact upon the diagnosis of brain death by TCD. We maintain that with strict criteria, TCD is highly sensitive and specific for the diagnosis of brain death. Dr. Machado infers that use of multimodal evoked potentials and electroretinography are �robust� for the detection of conditions that mimic brain death and that diagnostic reliability could be improved if both categories of techniques were used together. [1] However, in that reference [1], no specific data are provided to support this assertion. We feel that it would be of interest to design and report a study that tests this hypothesis.
Dr. Previgliano points out that use of TCD to evaluate cerebral hemodynamics in pregnancy and pre-eclampsia was not addressed in our paper and mentions the work of Belfort and colleagues. [2-4] Belfort, et al. [3] report that cerebral autoregulation, as measured by the cerebral flow index, is generally intact in preeclamptic women. The authors advanced the new hypothesis that uncontrolled cerebral perfusion pressure due to persistently elevated transmural pressure or failed autoregulation with resultant increased diastolic flow may lead to barotrauma and vascular endothelial damage, leading to hypertensive encephalopathy and hyperperfusion injury. However, in a nested case control study using responses to CO2 inhalation and isometric handgrip [2], preeclamptic women had higher middle cerebral artery flow velocities and lower pulsatility and resistivity indices than normotensive pregnant women. The reductions in pulsatility and resistivity indices were modest, but statistically significant. With CO2 inhalation, preeclamptic women had no significant change in pulsatility and resistivity indices. Instead of indicating the presence of vasoconstriction and absence of response to vasodilatatory stimuli, these findings suggest that cerebrovascular reactivity was exhausted, which would typically occur in a state of vasodilatation. The study had several limitations, including lack of clarity regarding the representativeness of case selection from a prospective cohort, uncertainty regarding blinding of clinicians and sonographers to clinical and TCD findings, and insufficient statistical power to detect a difference in response to CO2 inhalation and handgrip stimuli between the groups.
In addition, cerebrovascular responses to hyperventilation/hypocarbia may shed further light on the status of autoregulatory responses to changes in PCO2 in this setting. The other study [4] was small and only provided a univariate analysis of the relation between abnormal pulsatility/resistivity in normotensive women and the occurrence of preeclampsia.
To further add to the complexity of the pathophysiology of preeclampsia, cases of preeclampsia with vasodilatatory hyperperfusion (Vmca/Vica=2.0) and vasospastic hypoperfusion (Vmca/Vica=3.5) have been reported. [5] While it is true that cerebral hemodynamic changes may occur in women destined to develop preeclampsia, it is not yet clear that TCD can predict the occurrence of preeclampsia independent of other risk factors.
We agree that TCD may be a useful method for studying the pathophysiology of preeclampsia, but evidence is insufficient to recommend its routine use in this setting.
References
1. Machado C: Evoked potentials in brain death. Clin Neurophysiol 2004;115:238-239.
2. Riskin-Mashiah S, Belfort MA, Saade GR, Herd JA: Cerebrovascular reactivity in normal pregnancy and preeclampsia. Obstet Gynecol 2001;98:827-832.
3. Belfort MA, Varner MW, Dizon-Townson DS, Grunewald C, Nisell M: Cerebral perfusion pressure, and not cerebral blood flow, may be the critical determinant of intracranial injury in preeclampsia: A new hypothesis. Am J Obstet Gynecol 2002;187:626-634.
4. Riskin-Mashiah S, Belfort MA, Saade GR, Herd JA: Transcranial Doppler measurement of cerebral velocity as a predictor of preeclampsia. Am J Obstet Gynecol 2002;187:1667-1672.
5. Keunen RWM, Vliegen JHR, Gerretsen G, Smith SJ: Cerebral vasospasm and vasodilatation in preeclampsia.