4.3 NUCLEAR MEDICINE IN NEUROLOGICAL EMERGENCIES

INTRODUCTION

The observation, clinical evaluation and prognosis of coma patients is always a de- manding matter and one that requires reliable diagnostic instruments capable of providing answers in real time. This evaluation is further complicated by the varying aetiology of comas of acute onset. Some of the most frequent causes of coma include: head injuries, brain tu- mours, cerebrovascular lesions, meningitis, en- cephalitis and cerebral abscesses, epilepsy (postcritical coma), exogenous intoxication, endogenous intoxication (metabolic coma, se- vere hydroelectrolytic imbalances), respiratory insufficiency, and cardiocirculatory insufficien- cy. However, irrespective of the cause of the coma, the pathophysiology of functional brain damage rests on dynamic factors whose evo- lution must be recognized and monitored with care.

We believe that in neuroresuscitation, alongside the essential, accurate objective neurological examination and monitoring of cardiorespiratory and metabolic functions, diagnostic examinations with medical instru- ments are finding an increasingly important place. It is now possible to study the many aspects of cerebral pathophysiology using

neurophysiological (e.g.: EEG, evoked poten- tials), morphological (e.g.: CT, MRI) and functional (e.g.: PET, SPECT) methods aimed at swiftly understanding events that al- ter the balance between the various compo- nents of the cranioencephalic system and cerebral perfusion.

Alterations in cerebral perfusion can be studied using two possible categories of analy- sis: invasive (e.g.: measuring ICP; measuring the jugular venous saturation of oxygen, SvjO ₂ ; conventional selective angiography) and non- invasive (transcranial Doppler [TCD] and ra- dionuclide scintigraphy of brain perfusion [SPECT]).

The introduction of SPECT into clinical neuroresuscitation practice has made it pos- sible to obtain more rapid and accurate di- agnoses and make more certain prognostic judgements. The most satisfactory results have been obtained in the examination of postanoxic coma, where perfusion parame- ters have proved reliable for guiding thera- py, and in cases of suspected brain death, where SPECT is useful in dispelling doubts in either direction. In cases of posttraumat- ic coma or coma caused by stroke, brain per- fusion as determined by SPECT has enabled a more certain prognostic prediction.

4.3

NUCLEAR MEDICINE IN NEUROLOGICAL EMERGENCIES

M.G. Bonetti, P. Ciritella, G. Valle, T. Scarabino

MEASURING CBF

The brain is the organ that more than any other requires a constant supply of oxygen and glucose transported by the blood (7). Measur- ing CBF makes it possible to visualize the haemodynamic and pathophysiological conse- quences of intracerebral pathology.

At the current time, there are no valid alter- natives to the use of radionuclides to obtain quantitative flow measurements, especially in the posterior cerebral fossa and brainstem. The principal methods of the various techniques for studying CBF with gamma-emitting radioactive tracers are shown in Table 4.1. In our experi- ence, we have used the repartition method utilizing hexamethyl propylene-amine-oxime (HMPAO) marked with 99mTc as a tracer.

The main steps of the technique we use are as follows (1, 3):

1. intravenous injection of a 99mTC HM- PAO;

2. when the fat-soluble HM-PAO molecules are taken by the blood to the brain, they pass through the blood-brain barrier, with a high ex- traction from the blood bed, and bond to the brain tissue;

3. as a consequence the distribution within the brain is proportionate to the regional cere- bral blood flow (rCBF);

4. a bond between the HM-PAO mole- cule and the cerebral tissue forms and re-

mains constant for at least one hour (suffi- cient time in which to perform the SPECT examination);

5. subsequent redistribution of the molecule in the white and grey matter.

The interpretation of the images obtained using brain SPECT with hexametazyme is based on visual criteria (through a comparison with chromatic scales correlated with the lev- els of radioactivity recorded in the various ar- eas of the brain) and on the possibility of a semiquantitative study performed by compar- ing homologous areas with gamma-emission differences higher than 12-16%. In particular, in all those cases in which a cerebral hemi- sphere, or part of it, is significantly different- ly perfused than the contralateral, it is possi- ble to calculate a perfusion ratio using the fol- lowing expression (2):

Perfusion ratio = Counts/pixel affected side x 100 Counts/pixel healthy side

The resulting value constitutes a measure- ment of the asymmetry between the two hemi- spheres.

SPECT also makes it possible to make a more accurate prognostic evaluation of the un- derlying problem, which is usually simply clas- sified into a favourable or unfavourable prog- nosis (Table 4.1).

Tab. 4.1 - Prognostic evaluation of cerebral lesions by SPECT.

Method Radiotracer Advantages/Disadvantages

Vascular Clearance 133Xe A: quantitative

(if intracarotid injection) D: invasive

Dilution 99mTcO ₄ A: simple, easily

available radiotracer 99mTc-albumin D: not quantitative 99mTc-DTPA

Repartition 99mTc-HM-PAO A: steady state

123I-IMP D: unknown uptake process

Good prognosis Bad prognosis Meningeal lesions Focal lesions Not focal lesions Many lesions Small lesions Large lesions

Few lesions Parietal lesions

Occipital lesions Brainstem lesions Frontal lesions Cerebellar lesions Temporal lesions Tab. 4.2 - Prognostic evaluation of brain lesion using SPECT.

In our practice we use a rotating gammacam- era with a single dedicated head (GE 400 AC, Milwaukee, Wisconsin, USA) a few minutes af- ter an intravenous injection of freshly prepared 950 MBq of 99mTc -HM-PAO (Ceretec, Amer- sham-Sorin, Saluggia, Italy).The following ac- quisition parameters are used: 64 planar images with a 1.6x zoom, 64 x 64 pixel matrix, radius of rotation = 15 cm (on average), 20% symmetric window on photopeak of 140 keV of the 99mTc, acquisition time 25-30 minutes and a general purpose parallel hole collimator.

During the examination the patient is venti- lated using a portable automatic respirator (Pu- ritan Bennet Companion 2801, USA), monitor- ing blood pressure with a portable electronic modulus (Propaq 102, Protocol System Inc.

Oregon, USA); ECG and the arterial saturation of O ₂ of the haemoglobin is determined with a peripheral digital detector.

CLINICAL USAGE OF HM-PAO SPECT The study of brain perfusion in coma patients has come to be part of routine clinical practice in our Resuscitation Centre in all those cases in which conventional neurophysiological and radi- ological techniques are inadequate in providing a reliable prognostic estimate. The findings from a number of coma patients are summarized in the text below. For comparative purposes, Fig. 4.23 shows a SPECT image for a normal brain.

Posttraumatic coma

SPECT’s superiority over CT in studying head injuries that do not demonstrate focal le-

sions consists mainly in its ability to detect patho- physiological cerebral perfusion alterations be- fore the appearance of gross injuries that CT can detect (8).

Cerebral ischaemia can be a consequence of vasospasm occurring immediately after a trau- ma or following episodes of cardiocirculatory instability. This situation calls for serial studies of cerebral flow in order to detect either in- creases or decreases in perfusion. CBF also cor- related with the final clinical outcome: persist- ently low CBF values have an unfavourable prognosis, whereas patients whose CBF rapidly returns to normal levels will typically have a better recovery.

Another important aspect of CBF measure- ments is that SPECT highlights a reduction in flow that may be directly proportionate to the degree of cerebral oedema. For example, an in- crease in cerebral oedema can reduce or even completely interrupt CBF.

Clinical Case

PATIENT T.R.

AGE 25 years

DIAGNOSIS head injury

GCS on admission 5

SAPS (Simplified

acute Physiology Score) 8

Fig. 4.23 - Normal SPECT examination. SPECT examination

of the brain utilising 99mTC HM-PAO in a healthy subject for

comparison.

The CT examination (Fig. 4.24) was nega- tive for focal lesions; the BAEP’s determination (Brainstem Auditory Evoked Potentials) was normal. The scintigraphic study of cerebral perfusion in this patient showed (Fig. 4.25) multiple small perfusion defects in both cere- bral hemispheres, with good perfusion of the cerebral cortex. The patient came out of coma approximately one month from the injury. He was subsequently referred to a functional reha- bilitation centre in order to complete the re- covery of neuromuscular activity.

Acute cerebrovascular pathology

To reiterate, in studies of rCBF in cere- brovascular disease, SPECT is able to docu- ment flow alterations at an early stage, within a few hours after the trauma. This is observed be- fore CT becomes positive, which in this stage occurs in less than 1 case every 5. Serial rCBF studies have considerable prognostic impor- tance: patients with limited perfusion defects subsequently generally show complete or near complete recovery, whereas almost 50% of pa-

Fig. 4.24 - Post-traumatic coma. Unenhanced CT shows no abnormality.

tients with diffuse areas of hypoperfusion, or es- pecially a complete absence of perfusion (4,5), have an unfavourable outcome as is shown in the following case.

Clinical Case

PATIENT A. G.

AGE 75 years

DIAGNOSIS right temporoparietal haemorrhage

GCS on admission 6

SAPS 14

CT documented the presence of an extensive right temporoparietal haemorrhagic focus with lateral ventricular compression and midline shift (Fig. 4.26). SPECT demonstrated a large area of perfusion absence involving the upper portion of the right parietal lobe that extended more caudally, frontally, medially and posterior- ly, thereby including the right subcortical grey matter structures. Overall, the remaining cere- bral cortical and subcortical structures ap- peared to be well perfused. Crossed cerebellar diaschisis was also present (Fig. 4.27).

A subsequent SPECT examination per- formed approximately one month from the first

study documented (Fig. 4.28): discreet im- provement of the perfusion in a right posterior- frontal region, immediately in front of the haemorrhagic area; marked recovery of perfu- sion at the right temporal level, substantial nor- malization of the crossed cerebellum diaschisis.

Overall, the picture showed a more or less com- plete recovery of perfusion within the areas of ischaemic penumbra surrounding the haemor- rhage. Nevertheless, the patient, who died ap- proximately 6 months after the stroke due to the extent of the original focus, was unable to recover beyond the level of coma.

Postanoxic coma

The cerebral consequences of cardiocircula- tory arrest often determine the vital prognosis regardless of the success of the initial car- diopulmonary resuscitation. In fact, only 15- 30% of patients with cardiopulmonary arrest survive either with or without neurological se- quelae (6).

Two separate clinical conditions precipitated by cardiopulmonary arrest can be identified:

global cerebral hypoxia and incomplete cere- bral ischaemia. The former is due to dimin- ished arterial oxygen content together with an increase in cerebral blood flow requirement that occur in acute respiratory insufficiency; the second is due to a reduction in the blood sup- ply to the brain with normal arterial oxygen content that occurs in cases of shock and in in- tracranial hypertension (6).

The relationship between cerebral blood flow, O ₂ transport (DO ₂ ) and cerebral oxygen consumption (VO ₂ ) are shown in Table 4.3.

Fortunately, there is a margin of safety that the brain has in hypoxia or anoxia, because the quantity of O ₂ transported by the blood is equal to 2 or 3 times cerebral VO ₂ . Cerebral perfusion SPECT in postanoxic coma therefore shows impoverished cerebral blood flow, or if this is normal, depressed neuronal function, thus enabling the neuroresuscitator to con- struct a prognostic judgement while guiding him in the implementation of a specific thera- peutic protocol.

Fig. 4.25 - Same case as in Fig. 4.24. Left hand images:

SPECT images reveal multiple small perfusion defects. Right

hand images: Another normal case is shown on the right for

comparison.

CBF x CaO ₂ = DO ₂

CBF=5Oml/min/ 100 g CaO ₂ = 20 ml / 100 ml DO ₂ = 10 ml / min / 100 g VO ₂ = 3-5 ml / min / 100 g CaO ₂ = arterial oxygen concentration

Tab. 4.3 - Relationship between CBF, O

transport (DO

) and cerebral oxygen consumption (VO

).

Clinical case

PATIENT T.A

AGE 49 years

DIAGNOSIS postanoxic coma GCS on admission 7

SAPS 14

The first scintigraphic study in this patient documented a marked reduction in blood sup-

Fig. 4.26 - Acute cerebrovascular pathology. Unenhanced CT demonstrates a large intraparenchymal haemorrhagic focus associated

with rupture into the ventricular system and ventricular dilatation.

ply throughout the cerebral cortex and in the subcortical grey matter structures, without demonstrating focal deficits. Cerebellum and

brainstem perfusion were generally well con- served (Fig. 4.29). A subsequent study (Fig.

4.30) highlights the asymmetry of the peripher- al blood flow distribution between the two cerebral hemispheres with global hypoperfu- sion of the left hemisphere.

Finally, the third examination (Fig. 4.31) per- formed 15 days from the first, documented good overall cortical perfusion within both cerebral hemispheres and the disappearance of lateralized flow asymmetries. The improvement in brain perfusion documented by SPECT correctly pre- dicted the patient’s gradual recovery from coma.

Fig. 4.26 - (Contd.).

Fig. 4.27 - Same case as in Fig. 4.26. Note that the SPECT im-

ages reveal extensive perfusion defects and evidence of cere-

bellar diaschisis.

REFERENCES

1. Avogaro F, Zamperetti N, Pellizzari A: Studio del flusso ematico cerebrale. In: Trattato Enciclopedico di Anestesio- logia, Rianimazione e Terapia Intensiva, pp. 51-76. Piccin ed., Padova. 1991.

2. Choksey MS, Costa DC, Iannotti F et al: 99mTc-HM-PAO SPECT stuclies in traumatic intracerebral haematoma. J.

Neurol. Neurosurg. Psych. 54: 6-11, 1991.

3. Costa DC, Ell PJ, Cullum ID et al: The in vivo distribution of` 99mTcHM-PAO in normal man. Nucl. Med. Com. 7:

647-652, 1986.

Fig. 4.28 - Same case as in Figs. 4.26 and 4.27. The follow up SPECT examination shows an improvement in brain perfusion.

Fig. 4.29 - Post-anoxic coma. The SPECT study demonstrates diffuse, bilateral marked reduction in perfusion of the cerebral cortex.

Fig. 4.30 - Same case as in Fig. 4.29. A SPECT follow up ex- amination conducted seven days later shows that the global hy- poperfusion of the left cerebral hemisphere persists. The CT study in this patient was negative (not shown).

Fig. 4.31 - Same case as in Figs. 4.29 and 4.30. Two weeks after

the first examination, the SPECT images show good cerebral

perfusion recovery.

4. Fayad PB, Brass LM: Single Photon Emission Computed Tomography in cerebrovascular disease. Stroke 26: 950- 954, 1991.

5. Giubilei F, Lenzi GL, Di Piero V et al: Predictive value of brain perfusion single-photon emission computed tomo- graphy in acute ischemic stroke. Stroke 21: 895-900,1990.

6. Haberer JR, Hottier E: Encéphalopathies postanoxiques.

Ann. Fr. Anesth. Réan. 9: 212-219, 1990.

7. Manni C, Della Corte F, Rossi R et al: La perfusione ce- rebrale in Anestesia e Rianimazione. Atti XLV Congr.

Naz.le SIAARTI, pp. 1117-1127, Milano 8-12 ottobre 1991.

8. Obrist WD, Gennarelli TA, Segawa H et al: Relation of

CBF to neurological status and outcome in head injured pa-

tients. J. Neurosurg. 51: 292-297, 1979.