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The number of patients waiting for a new organ has continuously decreased in recent years. Brain death confirmation plays an important role in the clinical routine concerning a possible organ transplantation. In many countries a strictly defined protocol prescribes the required neurological examination and ancillary test criteria. Therefore, many years of experience and expertise is absolutely necessary for neurologists and neuroradiologists. Pitfalls can sometimes be very challenging for the treating physicians.

Brain ultrasonography can be used to evaluate cerebral anatomy and pathology, as well as cerebral circulation through analysis of blood flow velocities. Transcranial colour-coded duplex sonography is a generally safe, repeatable, non-invasive, bedside technique that has a strong potential in neurocritical care patients in many clinical scenarios, including traumatic brain injury, aneurysmal subarachnoid haemorrhage, hydrocephalus, and the diagnosis of cerebral circulatory arrest. Furthermore, the clinical applications of this technique may extend to different settings, including the general intensive care unit and the emergency department. Its increasing use reflects a growing interest in non-invasive cerebral and systemic assessment. The aim of this manuscript is to provide an overview of the basic and advanced principles underlying brain ultrasonography, and to review the different techniques and different clinical applications of this approach in the monitoring and treatment of critically ill patients.

Objective: Barbiturate therapy or hypothermia precludes proper diagnosis of brain death either clinically or by EEG. Specific intracranial flow patterns indicating cerebral circulatory arrest (CCA) can be visualized by transcranial Doppler ultrasonography (TCD). The aim of this study was to assess the validity of TCD in confirming brain death., Design: Meta-analysis of studies assessing the validity of TCD in confirming brain death., Methods: A systematic review of articles in English on the diagnosis brain death by TCD, published between 1980 and 2004, was performed. An oscillating or reverberating flow and systolic spikes were considered to be compatible with CCA. The quality of each study was assessed using standardized methodological criteria. The literature was searched for any article reporting a false-positive result., Results: Two high-quality and eight low-quality studies were included. Meta-analysis of the two high-quality studies showed a sensitivity of 95% (95% CI 92-97%) and a specificity of 99% (95% CI 97-100%) to detect brain death. Meta-analysis of all ten studies showed a sensitivity of 89% and a specificity of 99%. In the literature we found two false-positive results; however, in both patients brain-stem function did show brain death shortly thereafter., Conclusions: CCA by TCD in the anterior and posterior circulation predicted fatal brain damage in all patients; therefore, TCD can be used to determine the appropriate moment for angiography. Further research is needed to demonstrate that CCA by TCD on repeated examination can also predict brain death in all patients.

Objective: To review clinical outcomes in patients referred for confirmation of brain death by (99m)Tc-labelled exametazime scintigraphy and to assess any tangible benefit., Design and Setting: A retrospective casenote review in the intensive care unit and nuclear medicine department of a tertiary-level acute care hospital., Patients and Participants: 66 consecutive patients, in whom a clinical diagnosis of brain death was not possible, undergoing (99m)Tc-labelled exametazime scintigraphy from February 1993 to March 2002, and for 56 of whom casenotes were available for review., Measurements and Results: Brain death was confirmed in 77% on the basis of absent supratentorial and infratentorial uptake. Where brain death was not confirmed, a normal scan was seen in 30%, the remainder showing patchy reduced infratentorial and/or supratentorial uptake. All patients with the scintigraphic appearance of brain death subsequently died. Even when brain death could not be confirmed, 11 of 13 patients died soon afterwards. Two patients with normal brain scintigraphy regained consciousness and survived for an extended period. When brain death was not confirmed by scintigraphy, elapsed time to certification of death was longer (44.7 vs. 7 h) and organ donation was less common even when a subsequent clinical diagnosis was made., Conclusions: The results indicate that patient prognosis remains poor regardless of the findings on (99m)Tc-labelled exametazime scintigraphy, but that the scan result influences the elapsed time to withdrawal of therapy or organ donation, providing a significant cost benefit, and occasionally a long-term survivor is seen.

Unlabelled: An infant with intrauterine brain death accompanied by pulmonary hypoplasia is reported. The fetus was delivered after 36 weeks gestation, 5 weeks after fetal movements ceased. The child died 4 h after birth. Pulmonary hypoplasia and remote brainstem necrosis associated with multicystic encephalomalacia were found at autopsy., Conclusion: These findings suggest that damage to brainstem respiratory centres had led to pulmonary hypoplasia through the absence of fetal respiratory movement.

Objective: To evaluate whether a negative atropine test (i.e., increase in heart rate of less than 3% after intravenous administration of 3 mg atropine) correctly predicts circulatory arrest in the fossa posterior during craniocaudal herniation in patients with primary supratentorial lesions., Material and Methods: Prospective, observational clinical study., Setting: Two surgical intensive care units in a university hospital., Patients: In 45 consecutive patients with suspected brain death, an atropine test (AT) and a transcranial Doppler sonography were performed simultaneously and, if necessary, repeatedly., Measurements and Results: Forty-four patients fulfilled the typical criteria of a supratentorial and infratentorial circulatory arrest as the atropine test became negative. In one patient, who had undergone a decompressive craniectomy for uncontrollable intracranial pressure 4 h prior to the AT testing, we found a negative AT in the presence of an antegrade supratentorial and infratentorial flow., Conclusion: A negative atropine test indicates a circulatory arrest in the fossa posterior in patients with primary supratentorial lesions and craniocaudal herniation. In patients with brain-stem lesions, however, a negative atropine test does not unequivocally indicate a circulatory arrest.

Objective: To determine the clinical validity of transcranial Doppler ultrasonographic (TCD) signs of total cerebral circulatory arrest for confirmation of brain death and to define the test protocol., Design: Study of a diagnostic test., Setting: General and neurosurgery intensive care units., Patients: 137 patients in a coma (Glasgow Coma Score 3-5), caused by various pathological conditions, observed from January 1992 to July 1998. 84 patients met the clinical criteria of brain death; 43 patients out of 137 received sedative drug therapy and 31 of these developed brain death., Results: Total cerebral circulatory arrest was demonstrated by TCD in 81 patients. All of them proved to be brain dead according to subsequent clinical examination In 29 of 31 patients who had received sedative drug therapy TCD examination showed total cerebral circulatory arrest 12-48 h before the formal confirmation of the diagnosis. In 1 out of 84 clinically brain dead patients a false negative result was obtained. In 2 of 84 cases, no clear signals from intracranial vessels were obtainable. Fifty-three patients who did not meet the clinical criteria for brain death showed no TCD signs of total cerebral circulatory arrest. The specificity of the TCD test for confirmation of brain death was 100 % and the sensitivity 96.5 %., Conclusions: In agreement with previously published data, we conclude that TCD ultrasonography is a highly specific and sensitive confirmatory test and should be included as an additional test in the protocol for the assessment of brain death.

Objective: To evaluate the effectiveness of single proton emission tomography (SPECT) with 99mTc-HMPAO in the diagnosis of brain death (BD)., Design: Prospective study in comatose and brain-dead patients., Setting: Neurologic ICU., Patients and Methods: Fifty comatose patients (age range: 10 days-75 years) were submitted to SPECT study. In 21 of them (42%) reversible factors (e.g., influence of drugs affecting the central nervous system) were present. Thirty-eight patients were clinically brain-dead, while the remaining 12 were tested both in pre-terminal conditions and after the clinical onset of BD., Interventions: Brain SPECT following i.v. injection of 99mTc-HMPAO (300-1100 MBq), using a 4-headed gamma-camera (20 min, 360 degrees, 88 images)., Measurements and Results: All patients tested in pre-terminal conditions showed preserved brain perfusion. Two of them had flat EEGs despite the absence of any reversible cause of coma; three patients survived, but remained in persistent vegetative states. SPECT confirmed the diagnosis of BD in 45 out of 47 patients (95.7%), clearly showing the arrest of brain perfusion (picture of "empty skull"); in two clinically brain-dead children (aged 10 days and 12 months, respectively) weak perfusion of the basal ganglia, thalamus and/or brain stem was still present, precluding the diagnosis of BD; both of them died a few days later., Conclusions: Our results confirm the reliability of SPECT in the diagnosis of BD. A problem arises about its effectiveness in brain-dead children, but this seems to be a matter of definition of BD and cerebral viability, rather than a limit of SPECT.

We monitored 27 patients with HM-PAO-perfusion scintigraphy during the progress of cerebral death. The results of scintigraphy correlate well with cerebral angiography. Advantages are the possibility of bedside-examination, the non-invasiveness of the method and the possibility of in-vivo control. The non-visualized-brain in dynamic scintigraphy is a valuable additional method in the determination and documentation of cerebral death.

The case report presents evidence for the spinal origin of the marked hypertensive responses to noxious stimuli that may occur in organ donors who fulfill the commonly accepted criteria of brain death. Cardiovascular spinal reflex activity does not invalidate these criteria. For the first time, the catecholamine plasma concentrations have been determined during spinal pressor reflex activity. Circulating epinephrine increased more markedly than norepinephrine in both cases, rising to 4.7 and 44 times the baseline concentration respectively. The relation between plasma norepinephrine and epinephrine suggests involvement of the adrenal medulla in the reflex arc. The literature on spinal hemodynamic reflexes is reviewed.

Fifty consecutive patients (aged 19-77 years, median 56 years) with primary cerebral diseases and the clinical signs of absent cortical and brainstem function were subjected to electroencephalography (EEG), brainstem acoustic evoked potentials (BAEP), extracranial Doppler ultrasonography (ECD) and arterial digital subtraction angiography (DSA). In the majority of cases the results of the technical tests agreed with the clinical signs and were suggestive of brain death. However, in one patient EEG revealed clear bioelectrical activity. In 6 cases, doubts existed about whether the EEG was isoelectric; in 3 of the 6 cases biological activity might have been present. In 31 of 42 patients ECD showed a typical pattern of intracranial circulatory arrest, in 9 of 42 ECD revealed a pattern suggestive of the cessation of cerebral blood flow. In four patients BAEP recordings compatible with brain death were recorded 2-3 days before intracranial circulatory arrest. In 2 patients with isoelectric EEG and absent BAEP arterial DSA demonstrated residual perfusion. The findings are discussed in view of the conceptional differences concerning brain death. It is concluded that the strict application of the concept of death of the whole brain requires angiographic demonstration of absent intracerebral blood flow.

A total of 24 patients with clinical evidence of brain death (n = 17), severe coma (n = 2; GCS approximately 3) and apallic syndrome (n = 4) underwent a comparative investigation with 99mTc-HMPAO brain scintigraphy, EEG, auditory and somatosensory evoked potentials. Accompanied by EEG and evoked potentials, brain scintigraphy enabled confirmation of cerebral death in 15/17 patients. In one case clinical examination and evoked potentials suggest brain death, but cerebral perfusion and EEG were normal ("brain stem death"). One patient with evidence of cerebral death in clinical examination, brain scintigraphy and evoked potentials, showed questionable focal EEG activity; however, autopsy revealed intravital autolysis of the entire brain. All patients with apallic syndrome and deep coma showed a distinct cerebral perfusion, but gross EEG abnormalities; evoked potentials were delayed or absent. Planar scintigraphy with 99mTc-HMPAO appears to be superior to neurophysiological techniques discriminating patients with agonal cerebral dysfunction from those with brain death.

We report on the utility of technetium 99m hexamethylpropylene amine oxime (99mTc-HMPAO) to diagnose brain death following cardiac surgery on a 49-year-old man with triple-vessel coronary artery disease. The imaging parameters and criteria to diagnose irreversible brain damage (brain death) with 99mTc-HMPAO are outlined. Brain imaging with this tracer seems to be more reliable than classic radionuclide angiography and has a potential value to confirm the diagnosis of brain death at an early stage. In addition, it may be used to evaluate the perfusion pattern to other vital organs with potential for transplantation.

In 9 patients with the clinical diagnosis of brain death, a HM-PAO-SPECT was performed to document the arrest of cerebral circulation. Besides brain-stem areflexia, negative apnea-test and an observation time of at least 12 hours neurophysiological examinations (EEG and evoked potentials) were performed. In 4 cases, an additional arterial digital subtraction angiography proved the arrest of cerebral circulation shown in SPECT. In 5 cases, there was cortical low activity still present in EEG with negative SPECT. HM-PAO-SPECT seems to be a reliable noninvasive radiological method in the determination of brain death. It is especially helpful in cases with persisting focal cortical EEG-activity.