Hypothesis Spinal Shock and `Brain Death': Somatic Pathophysiological

Hypothesis

Spinal shock and `brain death': Somatic pathophysiological equivalence and implications for the integrative-unity rationale

DA Shewmon*,1 1Pediatric Neurology, UCLA Medical School, Los Angeles, California, USA

The somatic pathophysiology of high spinal cord injury (SCI) not only is of interest in itself but also sheds light on one of the several rationales proposed for equating `brain death' (BD) with death, namely that the brain confers integrative unity upon the body, which would otherwise constitute a mere conglomeration of cells and tissues. Insofar as the neuropathology of BD includes infarction down to the foramen magnum, the somatic pathophysiology of BD should resemble that of cervico-medullary junction transection plus vagotomy. The endocrinologic aspects can be made comparable either by focusing on BD patients without diabetes insipidus or by supposing the victim of high SCI to have pre-existing therapeutically compensated diabetes insipidus. The respective literatures on intensive care for BD organ donors and high SCI corroborate that the two conditions are somatically virtually identical. If SCI victims are alive at the level of the `organism as a whole', then so must be BD patients (the only signi®cant dierence being consciousness). Comparison with SCI leads to the conclusion that if BD is to be equated with death, a more coherent reason must be adduced than that the body as a biological organism is dead.

Keywords: brain death; spinal cord injury; spinal shock; integrative functions; somatic integrative unity; organism as a whole

Introduction Spinal shock is a transient functional depression of the society; its legal de®nition is culturally relative, and structurally intact cord below a lesion, following acute most modern societies happen to have chosen to spinal cord injury (SCI). It does not occur with slowly recognize brain-based diagnoses); (2) psychological progressive lesions but requires a suddenness of (death is loss of personhood due to loss of potential cessation of rostral in¯uences. Its pathophysiology for all mental functions, and the brain is the organ of remains poorly understood. The hypo- or nonfunction the mind); or (3) biological (death is loss of typically lasts 2 ± 6 weeks, followed by recovery of physiological, anti-entropic unity of an organism, autonomous, disinhibited functions. and the brain is the hierarchically highest integrating The phenomenon is of interest not only in itself and organ of the body). for its eects on SCI victims and their clinical It is to this last category of rationale (and to it only) management. It also carries surprising theoretical that the phenomenon of spinal shock is conceptually implications for a clinically quite unrelated entity, relevant. It is also historically and politically the most namely `brain death' (BD): speci®cally, implications important of the three, being what could be called the for the rationale for equating BD with death. standard, quasi-ocial, or òrthodox' rationale. The (Together with Veatch,1 I prefer to place `brain idea that BD is death because the brain is the body's death' in quotation marks on account of its semantic central integrator or `critical organ', destruction of ambiguity.2) The various proposed rationales can be which entails loss of somatic integrative unity subdivided into three main categories, corresponding (cessation of the òrganism as a whole'), has been to three fundamentally dierent concepts of death: (1) endorsed by a variety of in¯uential individuals and sociological (death is loss of conferred membership in virtually every standard-setting group that has ventured to explicitly articulate a rationale.5±12 (For all practical purposes relevant to somatic pathophysiology, `destruction'3,4 is taken as equivalent to `total *Correspondence: D Alan Shewmon, Department of Pediatrics, 5 6 Division of Neurology, UCLA Medical Center, MDCC 22-474, brain infarction' and ìrreversible nonfunction. )(This Box 951752, Los Angeles, California, CA 90095-1752, USA is not to say that they do not consider consciousness Spinal shock and `brain death' DA Shewmon 314

important in itself and also a sign of life. It is simply BD, ie, to the distinction between a sick, disabled that for them consciousness is not the decisive factor organism and a non-organism. Bernat, in his defense in determining human death. Rather, what is of BD against recent critiques, alludes to the above- conceptually pivotal is the vital status of the body as mentioned similarities with spinal cord dysfunction but a biological organism: if the body is alive, then the dismisses their relevance in the following way: person is alive even if permanently unconscious; if the body (including the brain) is dead, then so is the `Scholars have pointed out correctly that the spinal person). (Thought experiments of isolated living brains cord performs a number of integrative functions for are best conceived as involving severely mutilated the organism, and that it seems arbitrary and living bodies, of which all that remains is the brain.) contrived for the whole brain proponents to Insofar as the `physiological kernel' of BD is the brain emphasize the brain's role in integration to the stem,13 the same rationale has been advanced also by exclusion of that of the spinal cord. While it is true advocates of brain-stem formulations of death14,15 (for that as part of the central nervous system, the spinal a fuller discussion and critique of which, see2,16). cord has an integrating role, it is not a critical role. A traditionally cited manifestation of the somatic For example, many patients have lived long lives `dis-integration' of BD is hemodynamic deterioration with minimal support following complete destruc- and loss of homeostasis, intractably spiraling to tion of the spinal cord by injury or disease. imminent and irreversible asystole,6,7,11,13,15,17 ± 19 Therefore, the integrating functions served by the although such outcome is not universal or intrinsi- spinal cord clearly are not necessary for life and cally necessary.20 Still, whether BD is conceived as therefore, their absence is not necessary (and `total brain infarction',5 ìrreversible cessation of all certainly not sucient) for death. Permanent functions of the entire brain' 6 or `permanent cessation of the clinical functions of the entire functional death of the brainstem' 21 it clearly brain, therefore, remains the best criterion of eliminates multiple neural centers involved in somatic death.'9 integration. A rarely entertained alternative explanation, how- The logic behind the word `therefore' in that last ever, for the somatic pathophysiology of BD is spinal sentence is unclear. The point of the critics' shock from sudden cessation of rostral in¯uences, as comparison is not that cord function is necessary for ®rst suggested by Ibe back in 1971: biological life (understood at the level of the òrganism as a whole'), but rather that, precisely because it isn't, `The clinical picture was in all cases marked by yet BD and high cord transection have similar somatic continuous loss of consciousness and persisting eects, then it logically follows that neither is brain respiratory paralysis. The brain function was function necessary for biological life (equally at the constantly extinguished. The primary spinal areflex- level of the òrganism as a whole'). The key issue is the ia, on the other hand, as well as the disorders of extent to which the two conditions are really pulse and blood pressure after overcoming the somatically physiologically similar. spinal shock (about 24 ± 36 h after the accident), The best way to assess this comparison objectively is showed a clear tendency to recovery, possibly to to consult relevant clinical literature that has neither complete restitution.'22 the comparison in mind nor any philosophical point to make about the nature of BD, ie, texts on the intensive The idea was hardly noticed, appearing in an EEG care of BD and high SCI by specialists with extensive abstract, with the phrase `spinal shock' mentioned only experience in the respective conditions. in passing. To forestall potential misunderstanding, let it be re- Later Youngner and Bartlett, critiquing the emphasized that the purpose of this comparison is not physiological rationale for `whole-brain death', al- to advance a claim that BD is clinically indistinguish- luded to certain other somatic similarities between BD able from SCI, which would be absurd. Nor is the and high cervical cord transection: issue to which the comparison is relevant the clinical criteria for diagnosing a dead brain (the validity of à spinal cord transection at the level of the second which is taken for granted for purposes of this paper), cervical vertebrae [sic] . . . leads to the immediate but rather one particular conceptual rationale (among and irreversible loss of spontaneous respiration, several) for equating a dead brain with a dead cardiovascular stability, and temperature control ± individual: namely the one that claims that a dead all of which are integrating functions.'23 brain equates with a dead body. A quite dierent rationale, promoted by advocates of `higher brain' Again the potential signi®cance of the comparison was formulations, maintains that the reason why BD is largely overlooked. death is that irreversible unconsciousness constitutes a Could it be that high cord transection and BD are loss of personhood, regardless of the vital status of the somatically similar with respect not only to these body as a biological organism.1,23 ± 28 Plainly, for this functions but to others as well? The answer is highly rationale the role of consciousness is critical and any relevant to the question of somatic integrative unity in physiological comparison with SCI is irrelevant. Spinal shock and `brain death' DA Shewmon 315

Table 1 Somatic pathophysiological parallels between high Table 1 Continued cervical cord transection and BD B. Intercurrent infections precipitate return of spinal shock and hemodyanmic decompensation I. Induction phase of neurologic lesion C. Autonomic hyperre¯exia (dysre¯exia) A. Direct multisystem damage increases early morality rate B. Indirect systemic complications from transient sympathetic storm 1. Hypertension The interest of the comparison, therefore, has to do 2. Subendocardial ischemia and infarcts with its implications for the conceptual validity of the 3. Neurogenic pulmonary edema biological rationale only ± and that interest is heigh- II. Acute phase tened by the fact that that rationale happens to be the A. Irreversible apnea mainstream or quasi-ocial one almost everywhere. B. Quadriplegia Thus, the ignoring of consciousness in what follows is C. Spinal shock in no way intended to belittle the obviously exceeding 1. `Somatic' system deactivation (a) Flaccidity value of intact consciousness and communicative (b) Depressed tendon re¯exes and plantar abilities, which SCI patients enjoy and BD patients responses lack. Subjective consciousness is simply not the main 2. Autonomic system deactivation focus of the `orthodox' rationale, so it is equally beside (a) Sympathetic (thoracolumbar) the point for the present critique of that rationale. (1) Hypotension (2) Impaired cardiac contractility (3) Increased venous capacitance Method (4) Bradycardia The contemporary neuroanesthesia and neuro-intensive (5) Cardiac arrhythmias, especially care literatures relating to high SCI and BD were bradyarrhythmias (6) Cardiovascular instability can be dicult to compared, focusing on somatic pathophysiology, treat and lead to early arrest symptomatology, treatment, and survival. To compare (7) Paralytic ileus long-term outcomes with continued aggressive treat- (b) Parasympathetic (sacral) ± ¯accid bladder ment, reliance was made on a compilation of some 175 3. Hypothermia and poikilothermia BD cases with prolonged survival,20 extensively D. Relatively preserved hypothalamic-anterior pituitary documented in two tables available for a small fee functions through the National Auxiliary Publications Service 1. Thyroid function ± euthyroid sick syndrome (NAPS) (document No. 05467), c/o Micro®che 2. Other anterior pituitary functions ± variably Publications, 248 Hempstead Turnpike, West Hemp- aected in BD and of little relevance to stead, New York 11552. (Remit in advance in U.S. somatic unity E. Predisposition to infection funds only $17.50 for photocopies or $5.00 for 1. Pneumonia, due to immobility and lack of micro®che. There is a $25.00 invoicing charge on all respiratory protective re¯exes orders ®lled before payment. Outside U.S. and Canada 2. Urinary tract infections due to bladder dysfunction add postage of $4.50 for the ®rst 20 pages and $1.00 and urinary retention for each ten pages of material thereafter, or $5.00 for 3. Sepsis from decubitus ulcers the ®rst micro®che and $1.00 for each ®che thereafter.) F. Actuarial survival curves 1. Biphasic: rapid drop-o, followed by relative stabilization Results 2. Age eect: younger patients have greater survival potential III. Chronic phase Similarities A. Resolution of spinal shock 2 ± 6 weeks after injury ± The extensive somatic parallels between high SCI and return of autonomous cord function BD, according to the literature, are as follows (outline 1. Development of spasticity, pathological increase of structure summarized in Table 1). tendon and cutaneous re¯exes 2. Recovery of sympathetic tone I. Induction phase of neurologic lesion In both (a) Hemodynamic stabilization conditions, associated multisystem damage is (b) Bradycardia and bradyarrhythmias resolve common and could account for somatic dete- (c) Gastrointestinal motility returns and enteral rioration independently of the neurologic non- feedings can resume function. (d) Piloerection and sweating return 3. Recovery of sacral parasympathetic tone ± I.A. Direct multisystem damage The primary automatic bladder function returns etiologies of SCI and BD sometimes directly 4. Thermoregulation tends to improve, although most damage non-neural organs as well: for 29 patients remain poikilothermic example, massive trauma. The early mortality rate in SCI is increased with associated injuries compared to pure cord injury.30,31 Spinal shock and `brain death' DA Shewmon 316

Similarly, the rate of early asystole in BD is at least raise the question of decorticate increased with associated injuries compared or decerebrate rigidity, which would to pure brain injury.20 exclude the diagnosis. Likewise, are¯exia I.B. Indirect systemic complications During induc- is so common in BD that the original tion of experimental cervical cord transec- Harvard Committee considered it a tion, transient hypertension occurs, probably diagnostic feature (though not absolutely from massive depolarization of sympathetic required) along with absent plantar preganglionic neurons.32 In clinical experi- responses. (Subsequent BD criteria em- ence this is not usually observed, presumably phasized the diagnostic compatibility of because it has already resolved by the time preserved tendon re¯exes without denying medical assistance arrives.32 Analogously, that are¯exia is nevertheless more char- during the process of brain herniation, prior acteristic.6,47,48) to BD, transient hypertension is common, II.C.2. Autonomic system deactivation In spinal also due to massive sympathetic hyperactivity shock, autonomic function is as depressed and release of circulating catechola- as segmental re¯exes. With cervical mines.18,33,34 lesions the entire sympathetic and sacral This sympathetic storm can produce parasympathetic systems are aected, the subendocardial ischemia or neurogenic pulmon- sympathetic dysfunction being more ary edema in acute SCI31,32,35 as well as in deleterious. severe brain injury.18,33,34,36 ± 41 The cardiac II.C.2.a. Symptoms of sympathetic paralysis pathology associated with experimental BD in both conditions include the can be prevented by prior sympathectomy following. and verapamil, con®rming the causal role of (1) Hypotension occurs in 68% of sympathetic hyperactivity.42 patients with high SCI49 and can be of life-threatening severity.31,32,35,50 II. Acute phase The non-endocrinologic manifesta- Hypotension is also very common tions of the acute phase are nearly identical in in BD.18,20(Table 1),33,34,51 high SCI and BD. (2) Impaired cardiac contractility char- II.A. Irreversible apnea is a hallmark of both cord acterizes both SCI31,32 and BD,33 as transection above C432,35,43 and BD. does II.B. Quadriplegia characterizes both high cord (3) Increased venous capacitance.32,33,35 transection,32,43 and BD. (4) In both conditions bradycardia is II.C. Spinal shock Immediately upon severe SCI, common and can help in the the intact cord below the lesion function- dierential diagnosis of hypoten- ally shuts down through poorly under- sion, suggesting sympathetic paraly- stood mechanisms. This spinal shock sis rather than hypovolemic shock typically lasts 2 ± 6 weeks, after which (characterized by compensatory ta- autonomous cord functions gradually re- chycardia if the sympathetic system turn.32,35,44 Its intensity increases with the is intact). Hypothermia or subclini- height of the lesion.32,35,45 InsofarasBD cal myocardial ischemia can exacer- is, from the cord's perspective, a transec- bate bradycardia in either con- tion at the cervico-medullary junction, one dition.34,52 should expect maximal spinal shock in (5) Cardiac arrhythmias occur in 19% of BD. Indeed, in both high cervical transec- high SCI, with peak incidence of tion and BD both `somatic' and auto- bradyarrhythmias around day nomic spinal functions are suppressed as 4.31,32,35,49,53 Arrhythmias, especially follows. (The semantic tradition distin- bradyarrhythmias, are also common guishing `somatic' from `autonomic' ner- in early BD.33,51,54 vous systems is unfortunate, especially for (6) The cardiovascular instability result- the present purpose, implying that the ing from combined hypotension, autonomic system has nothing to do with impaired myocardial contractility the body; ironically, the autonomic system and bradycardia can be dicult to is perhaps more important for somatic treat and causes signi®cant early unity than the `somatic' system.) mortality in high SCI.53,55 An II.C.1. `Somatic' system deactivation Flaccidity autopsy study of 44 cervical cord and absence of tendon re¯exes and of injury victims revealed that 30 (68%) plantar responses characterize acute died within the ®rst 11 days, mainly SCI.45 Although ¯accidity is not a of cardiovascular complica- diagnostic requirement for BD, it is so tions.45,56 Similarly, intractable car- common that positive muscle tone should diovascular instability leads to asys- Spinal shock and `brain death' DA Shewmon 317

tole in about 10% of BD prospective relatively preserved also in BD, presumably organ donors during the mainte- by virtue of the inferior hypophysial artery, nance phase,18,33 and `[h]ypotension which arises extradurally from the internal and/or cardiac arrest occur in carotid.18,59 ± 62 approximately two thirds of II.D.1. Thyroid function is frequently altered in referred donors'.33 Hemodynamic BD, but not as hypothalamic hypothyr- instability renders pharmacologic oidism: rather as euthyroid sick syn- and¯uidmanagementtrickyin drome, with relatively normal TSH and both conditions, and recommen- T4 but decreased T3,59 ± 63 due to dations are essentially the same. decreased peripheral deiodination of T4 (Some standard vasopressors can to T3, perhaps from interleukin-664,65 or have paradoxically deleterious ef- free-radical-induced selenium de®ciency. fects in the context of sympathetic (Thus the utility of thyroid replacement paralysis. If a pressor is necessary, therapy for maximizing organ viability dopamine is the drug of choice, but remains controversial.18,67 Some investi- judicious volume expansion without gators have reported improved metabolic pressors is preferable and often status and myocardial contractility fol- suces to restore blood pressure to lowing triiodothyronine administration in an acceptable range in both SCI45 BD39,68,69 or during cardiopulmonary and BD.33,34,51 The high rate of early bypass surgery,70,71 but this probably cardiac arrest in both conditions is represents a direct pharmacologic ef- partly iatrogenic, due to inability of fect.51,72±74 Others have reported no the compromised heart to accommo- bene®t from exogenous T3 in controlled date overly aggressive ¯uid resuscita- placebo comparisons,75 and in one study tion, leading to pulmonary edema metabolic acidosis actually worsened.76) and congestive heart failure in less It is a common epiphenomenon of than expert hands.17,31,33,45,51,53,57 critical illness in general,77,78 including (7) Paralytic ileus often results from SCI.79 acute autonomic dysfunction and II.D.2. Other anterior pituitary functions are general systemic disturbances in variably aected in BD59±62 and less both SCI32,35,58 and BD,20 (Table 1) relevant for somatic unity. The only as in serious illnesses in general, indication for even cortisol administra- requiring parenteral ¯uids and nutri- tion in organ donors is pre-existing adrenal tion until motility returns.53 suppression from recent steroids.18 II.C.2.b. Sacral parasympathetic tone is abol- II.E. Predisposition to infection In both conditions ished in both conditions, resulting in immobility and lack of coughing and sighing bladder ¯accidity with urinary reten- promote pneumonia and diminish antibiotic tion, requiring catheterization.33,53 ecacy.20 (Table 1),35,57 Bladder dysfunction II.C.3. Hypothermia and poikilothermia are promotes urinary tract infection,20 (Table 1),32 common in SCI, due to cutaneous and immobility predisposes to decubitus vasodilation (from sympathetic paralysis) ulcers with local infection and risk of sepsis. causing increased heat loss, plus physical Preventive nursing care is identical for both inactivity and inability to shiver (from conditions. skeletal muscle paralysis) causing de- II.F. Actuarial survival curves creased heat generation.31,32,35,50,57 For II.F.1. High cervical quadriplegia has a biphasic identical reasons, hypothermia and poi- survival curve, with rapid drop-o in the kilothermia also occur in up to 86% of ®rst three months (especially the ®rst). In BD patients.18,33,34,51 Hypothermia ex- one study 3-month survival was only acerbates cardiovascular instability in 43%.80 The subsequent chronic phase both conditions, requiring heating lamps has a relatively low death rate.80±82 and multiple blankets. Survival curves for BD treated equally Hyperthermia can result from high aggressively also feature a rapid drop-o ambient temperature or high humidity, over the ®rst several months (especially compounded by absent sympathetic con- the ®rst), followed by a chronic phase of trol of sweating, in both SCI31,32,35,50,57 relative stabilization.20 and BD.20 (Table 1) Although in both II.F.2. Age is a signi®cant determinant of conditions infection sometimes induces survival rate. Following SCI the propor- fever, usually it does not.20 (Table 1),35 tion alive at a given time after injury II.D. Hypothalamic-anterior pituitary functions, decreases signi®cantly with advancing intact in SCI, tend surprisingly to be age.30,57,80 (Table 3),81,82 A similar age ef- Spinal shock and `brain death' DA Shewmon 318

fect characterizes survival potential in (`TK') these functions did re- BD.20 turn.20 (Table 1) III. Chronic phase III.A.3 Recovery of sacral parasympathetic tone In III.A. Resolution of spinal shock Beginning 2 ± 6 SCI automatic bladder function gradually weeks after SCI, autonomous cord function returns.32 Urinary retention and asso- gradually returns. In the few BD patients ciated urinary tract infections become maintained through the acute phase, spinal- less problematic as bladder spasticity shock symptomatology also gradually re- causes smaller capacity and frequent solves around the same time frame, produ- spontaneous voidings. Again, parallel cing relative somatic stabilization. data are lacking for prolonged BD, III.A.1. Development of spasticity Following although patient `TK' did develop such SCI the ®rst clinical manifestation of bladder function, with spontaneous mic- recovery from spinal shock is return of turition about every 2 h.20 (Table 1) tendon and cutaneous re¯exes, which III.A.4 In both SCI and BD thermoregulation soon become hyperactive as ¯accid tone improves, although most patients remain becomes spastic.32,35,44 Triple ¯exion poikilothermic to some degree; hyperther- (hips, knees, ankles) and other with- mia can occur in the absence of infection, drawal re¯exes appear in response to possibly from spastic hypertonia or noxious stimuli.32,44,45 In prolonged BD, autonomic dysre¯exia (see be- tone and re¯exes likewise become patho- low).20 (Table 1),57 logically increased (barring intrinsic damage to the cord).20 (Unfortunately, III.B. In both conditions intercurrent infections can the available information regarding the precipitate recurrence of spinal shock with time course of these changes is too scanty dramatic hemodynamic decompensation. The for comparison with SCI.) symptoms dissipate upon resolution of the III.A.2. Sympathetic tone returns in parallel with infection.20 (Table 1),44 skeletal muscle tone and is perhaps the most important systemic aspect of recov- III.C. Autonomic hyperre¯exia (dysre¯exia) develops ery from spinal shock. in 65 ± 85% of SCI cases, with sudden episodes III.A.2.a During the weeks following SCI, of severe hypertension triggered by noxious or hemodynamic status stabilizes:vaso- visceral stimuli (eg, defecation, full bladder, pressors can be weaned, the heart tracheal suctioning).31,32,35,45,50 Manifestations better accommodates ¯uctuations in include profuse ¯ushing and diaphoresis of head intravascular volume, and ¯uid and neck, nasal congestion, headache and chest management simpli®es.31,35,43 Ex- pain. Pathogenesis probably involves denerva- actly the same occurs in chronic tion hypersensitivity of peripheral adrenergic BD; prior to 4 weeks the most receptors.45 frequent terminal event is sponta- Re¯ex hypertensive responses to surgical inci- neous asystole, whereas after 4 sion in unanesthetized BD organ donors are weeks it is treatment withdrawal.20 similar (apart from heart rate ± see below) yet III.A.2.b In SCI bradycardia and bradyar- occur much earlier than the several weeks typically rhythmias completely resolve by 2 ± 6 required for development of autonimic dysre¯exia weeks.49,55 Similarly, in prolonged following SCI.18,83 ± 89 The timing may not BD cardiac rhythm also stabi- represent a real point of dierence, however. lizes.20 (Table 1) Little is known about the hemodyanmic response III.A.2.c In SCI gastrointestinal motility re- to unanesthetized surgery in acute SCI, since turns and enteral feedings can anesthesia is typically employed. Perhaps split- resume.35,57 Thesameistruein ting the entire thorax and abdomen is a stimulus some prolonged BD cases (through powerful enough to overcome any spinal shock. the intrinsic neurenteric plexus and Less is known about autonomic dysre¯exia in intraspinal autonomic integra- chronic BD, but some case reports do mention tion),20 (Table 1) although lack of episodes of hypertension after a latency of several swallowing requires providing ent- weeks.20 (Table 1) Patient `TK' during the author's eral feedings by tube, in contrast to examination developed transient blotchy erythe- SCI. ma of the face, neck and shoulders in response to III.A.2.d In SCI piloerection and sweating noxious stimuli such as pinching or ice-water gradually return.32 Parallel data for trickling down the neck. Nurses have documented chronic BD are lacking in the litera- that such reaction is characteristically associated ture, although in one patient whom with a transient rise in blood pressure and heart the author personally examined rate. Spinal shock and `brain death' DA Shewmon 319

Dierences The bradycardia associated with auto- The extensiveness of somatic parallels between SCI and nomic hyperre¯exia in chronic SCI is BD contrasts markedly with the relative paucity and vagally mediated.32,35,45,50 By contrast, unimportance of the dierences, as follows (outline the hypertension upon unanesthetized structure summarized in Table 2). organ retrieval in BD (or upon somatic irritation in chronic BD) is associated I. Hypothalamic-posterior pituitary function is intact with tachycardia, presumably mediated in SCI and variable in BD. Diabetes insipidus by unopposed spinal sympathetic re- occurs in 38 ± 87% of BD patients.18,33,59 ± 62,90 ¯exes, including adrenally released circu- The inconsistency presumably stems from lating catecholamines.18,83 ± 89 vicissitudes of vascular supply from the same II.A.2. Recovery of gastrointestinal motility fol- extradural collaterals responsible for preserving lowing spinal shock may occur less often anterior pituitary functions (see above). If in BD than in SCI, perhaps because of the inadequately treated, the ensuing hypovolemia permanent vagal suppression in BD. and electrolyte imbalance will exacerbate the II.B. Aerent function The vagus nerve transmits already tenuous cardiovascular status. Diabetes signals from the baroreceptors of the cardiac insipidus can appear after a brief latency atria and aortic arch to the nucleus of the following BD, and in some chronic cases (eg, tractus solitarius, which participates in `TK') it can also gradually resolve.20 (Table 1) regulation of blood pressure and volume through vagal eerent adjustment of heart II. Vagus nerve functions are intact in SCI and rate, various bulbospinal pathways and hypo- absent in BD. thalamic modulation of sympathetic tone and II.A. Eerent functions release of antidiuretic hormone.93±95 Since II.A.1. Bradycardia In BD loss of both sympa- rostral control of sympathetic function is thetic and parasympathetic functions abolished in both SCI and BD, and since leaves the heart's rate determined solely posterior pituitary function is variably by its intrinsic pacemaker, which is aected in BD, the only meaningful compar- slower than normal and lacks ison of vagal aerent function between the spontaneous variability.91,92 The brady- two conditions involves the subset of BD cardia of high SCI is even more profound without diabetes insipidus. In SCI the atrial due to unopposed parasympathetic and aortic baroreceptors participate through tone,31,32,35,55 and severe re¯ex bradycar- vagal aerents in modulation of vagal dia can be precipitated by vagal stimula- eerent tone and antidiuretic hormone tion such as intubation, oropharyngeal secretion,32,45 whereas in BD without dia- suctioning, ocular pressure, or a sigh.35 betes insipidus they do not. Such disadvantageous reactions do not occur in BD. Atropine can treat and III. Glossopharyngeal nerve function is intact in SCI prevent severe bradycardia in SCI 45 but and absent in BD. Together with vagal aerents, has no chronotropic eect in BD because a branch of the ninth cranial nerve to the carotid vagal function is already absent.33 body conveys additional baroreceptor information, all processed together and ultimately in¯uencing homeostasis as just described.93 The Table 2 Somatic pathophysiological dierences between somatic dierences between SCI and BD high cervical cord transection and BD attributable to glossopharyngeal function are therefore the same as those attributable to vagal I. Hypothalamic-posterior pituitary function (diabetes aerents, are relatively minor, and are nonexis- insipidus in 38 ± 87% of BD, absent in SCI) tent in the context of diabetes insipidus. II. Vagus nerve functions (intact in SCI, absent in BD) A. Eerent functions 1. Bradycardia (more severe in SCI due to unopposed IV. Associated systemic complications Disseminated vagal tone; a hemodynamic disadvantage compared intravascular coagulation complicates 25 ± 65% with BD) of BD organ donors.18,51 It is not described in 2. Recovery of gastrointestinal motility following spinal the spinal cord literature, presumably because shock seems less common in BD than in SCI much less tissue thromboplastin is released by B. Aerent function (intact in SCI, absent in BD) ± SCI than by massive brain injury. irrelevant if BD involves diabetes insipidus III. Glossopharyngeal nerve function (intact in SCI, absent These, then, are the somatic dierences. Note in BD) ± irrelevant if BD involves diabetes insipidus that other cranial nerve functions and especially IV. Associated systemic complications ± disseminated intravascular coagulation in 25 ± 65% of BD, much less consciousness, though preserved in SCI and in SCI absent in BD, are not listed, because important as they are for the patient, they are unrelated Spinal shock and `brain death' DA Shewmon 320

to the focus of the comparison, namely somatic Also note that the second and third aerent pathophysiology insofar as it is relevant to the pathways are relevant only in contexts where the question whether the body in either condition corresponding eerent limbs are intact. Blood ¯ow to is a sick organism or a mere collection of and from the brain in general is conceivably an organs. additional pathway, though not for all practical purposes. Certainly extra-hypothalamic brain has Discussion receptors for various hormones and circulating chemicals, but those even remotely relevant to The similarity of eects of SCI and BD on the body is somatic integrative unity involve the hypothalamic- surprising at ®rst sight and fascinating in itself, but its pituitary axis. The brain is not known to be a relevance to one of the several rationales advanced to secretory organ (apart from the portal system of the explain why BD should be equated with death elevates adenohypophysis). Similarly, the production, circula- the comparison from a mere physiological curiosity to tion, and venous absorption of cerebrospinal ¯uid a conceptually important observation. could be another theoretically conceivable route for According to the mainstream, òrthodox' rationale, brain-body chemical interaction, but there is no the purported loss of somatic integrative unity in BD evidence that such exchange serves any somatically is attributable to destruction of the many brain-stem integrating role. and hypothalamic integrative centers.5 ± 8,11,12,15 But is Plainly disruption of any one of the signi®cant it their destruction per se or rather the body's pathways of encephalo-somatic communication does nonreception of their in¯uence that most immediately not destroy the unity of the òrganism as a whole'. aects somatic integration? Surely the latter, because Every endocrinology clinic has patients with diabetes it is more proximate to the phenomenon of interest, it insipidus or even panhypopituitarism who live is the means through which the former exerts its perfectly normal lives on replacement therapy. Every eect, and it can also be brought about by other major rehabilitation center cares for ventilator- possible causes such as mere disconnection from dependent patients with high cervical quadriplegia. cephalic structures. That the impact on somatic Sometimes for therapeutic reasons the vagus nerve is physiology of nonreception of rostral in¯uence ablated surgically or pharmacologically. should be indierent to the reason for the nonrecep- What about elimination of two of these three tion implies that body A with a destroyed brain and routes? For example, suppose that a high cervical body B with a disconnected brain (eg, due to high quadriplegic were given atropine to treat bradycardia. SCI) should have the same vital status. Logical The somatic physiology of such a patient would be consistency demands that if we assert that A is dead virtually identical to that of a BD patient without as a biological organism, we must be prepared to say diabetes insipidus (the only dierence being preserved the same of B; but if we insist that B is clearly alive carotid-body modulation of antidiuretic hormone in as a biological organism (and not merely because it is the SCI patient). conscious), then we must be willing to admit the same To complete the analogy, suppose that the of A. atropinized SCI victim was an endocrinology patient with chronic panhypopituitarism, stable on replacement therapy. The somatic physiology relevant to Somatic equivalence in theory integrative unity is now absolutely identical to that The anatomical pathways through which somatically of total brain infarction. The only dierence lies in integrative information is transferred between body consciousness and those cranial nerves restricted to and brain are relatively few. head and neck. Is such a body an implacably In the aerent direction the routes are threefold: disintegrating `collection of organs', or a live òrganism as a whole' that happens to be severely . spinal cord disabled and dependent on medical technology? If . glossopharyngeal and vagus nerves (from the the former, then we would have the bizarre anomaly atrial, aortic and carotid baroreceptors), and of a `conscious corpse'; if the latter, then the BD . arterial blood ¯ow to the hypothalamus (espe- body must equally be an òrganism as a whole' cially to supraoptic and paraventricular nuclei). despite its severe disability and technological dependence (its unconsciousness being an additional In the eerent direction the routes are likewise disability, but not one that per se settles the threefold: question: is this an unconscious organism or a non-organism?). . spinal cord, From the body's perspective, BD and atropinized . vagus nerve, and high cord transection are virtually indistinguishable . pituitary. (comparing SCI with the subset of BD without diabetes insipidus, or `total' BD with the subset of The other ten cranial nerves terminate in the head SCI with pharmacologically controlled diabetes in- or neck and are irrelevant to somatic integration. sipidus), because the caudal margin of total brain Spinal shock and `brain death' DA Shewmon 321 infarction is in fact a cervico-medullary junction equating the somatic pathophysiology of BD with infarction. Thus, regardless how one might choose to that of cervico-medullary junction transection, a de®ne operationally terms such as ìntegrative unity' or marked explanatory asymmetry has prevailed. òrganism as a whole', if they are de®ned carefully The SCI literature attributes a particular set of enough to apply properly to any ventilator-dependent signs and symptoms to functional suppression of the quadriplegic with diabetes insipidus, then ipso facto they structurally intact spinal cord below the lesion, below will apply as well to any BD patient.96 the foramen magnum, and calls it `spinal shock'. By Not only is this conclusion inescapable on contrast, the BD literature attributes the same set of theoretical grounds; it is fully rati®ed in clinical signs and symptoms directly to destruction of brain- experience. stem vegetative control centers above the foramen magnum and calls it `loss of somatic integrative unity'. Somatic equivalence in practice For example, depressed sympathetic tone in SCI is The literatures on intensive care of acute SCI and BD usually attributed to deactivation of second-order are so similar that they can almost be mutually sympathetic neurons in the intermediolateral cell transformed one into the other merely by interchan- column, but in BD it is typically attributed to ging the terms `SCI' and `BD'. Yet this curious fact destruction of ®rst-order sympathetic neurons in the seems to have passed largely unnoticed, even by hypothalamus and their axons in passage through the authors of respective chapters in the same book (eg, medulla (eg,97). But since BD includes cervico- Kofke et al.35 and MacKenzie and Geisler45 on the one medullary junction infarction, in the context of hand, and Lew and Grenvik18 on the other). which the rostral integrity of the sympathetic system is physiologically irrelevant, the most parsimonious Induction phase During the process of brain hernia- explanation of impaired sympathetic tone in BD is tion or spinal cord infarction, but prior to BD or spinal shock, just as in SCI. As another example, it is complete cord transection, secondary cardiopulmonary illogical to attribute hypothermia in BD to destruc- pathology (subendocardial microinfarcts, neurogenic tion of hypothalamic thermoregulatory centers (as pulmonary edema) due to massive sympathetic does Gert10), when the same hypothermia would discharge is common and contributes substantially to result from the caudal end of the brain pathology the acute hemodynamic instability and early mortality alone (ie, cervico-medullary junction infarction) even in both BD and SCI. In some cases multiple non- if the hypothalamus and medulla were intact, as in neural organs are also damaged directly by whatever SCI. primary etiology damaged the brain or cord. The same could be said about every other non- The time course of subsequent relative stabilization, endocrinologic somatic dysfunction in BD. This although attributable largely to recovery from spinal explanatory asymmetry is probably motivated by shock, also corresponds to resolution and healing of an aprioriconviction that BD ought to be equated such multisystem complications. That young patients with organismal death and SCI not; regardless, it is have much greater potential for survival in both a logical double standard without physiological conditions also reinforces the idea that the tendency basis. to early demise is attributable more to somatic than to Moreover, because unopposed parasympathetic tone neurologic factors. is more disadvantageous hemodynamically than It is therefore fallacious to attribute the increased absence of both sympathetic and parasympathetic incidence of early arrhythmias and cardiovascular tone, one could argue that, precisely because vagal collapse in BD to the absence of brain function per function is intact in SCI and often needs to be se. (It is also inconsistent, if a parallel attribution is pharmacologically suppressed, SCI bodies are ironi- not made for SCI). Rather, the early systemic cally even less integrated than BD bodies (at least those instabilities are more likely attributable to systemic without diabetes insipidus). Therefore, if despite this pathology, antedating the BD as suggested also by disadvantage SCI patients still possess enough Novitzky.39 If the brain or cord become infarcted in a integrative unity to quality as living òrganisms as a way that does not overactivate the sympathetic system, whole', all the more do BD patients. cardiopulmonary complications should be much less of The similarity of survival curves of the two a problem (cf42). conditions also argues that high SCI is every bit as somatically `dis-integrating' as BD during the acute Spinal shock The comparison of SCI and BD phase, yet no one concludes therefore that the bodies literatures reveals that every described manifestation of SCI patients are ipso facto `dead' or are mere of spinal shock also occurs in BD, and conversely, collections of organs without unity at the level of the every non-endocrinologic systemic dysfunction char- òrganism as a whole'. Conversely, the somatic acteristic of BD (excluding associated multisystem instability in BD is potentially every bit as transient injury) is explainable in terms of spinal shock. as in SCI. If it looks like spinal shock, acts like spinal Nevertheless, despite the similarities of somatic shock, resolves like spinal shock ± why not call it spinal symptomatology and the theoretical grounds for shock? Spinal shock and `brain death' DA Shewmon 322

Whether the somatic symptomatology of BD is best but integration, a holistic property deriving from the understood as manifesting `loss of integrative unity' or mutual interaction among all the parts.96 `spinal shock' is answerable through considering the If BD is to be coherently equated with death, constellation and temporal evolution of clinical signs. `death' must therefore be understood in a non- The comparison is greatly obscured by the fact that biological sense, as proponents of `higher-brain' or BD patients are typically not supported for the 2 ± 6 consciousness formulations have advocated.1,23±28 weeks necessary to manifest the resolution character- Whether society will want to adopt such a concept istic of spinal shock. But the case reports of BD of death ± which amounts to a notion of the human patients who have been so maintained20 indicate that person as not only conceptually distinct, but actually the respective somatic symptomatologies of BD and dissociable, from a living human body ± remains to be SCI do in fact closely parallel one another. The seen. That debate exceeds the present scope. What is parallel is not only qualitative (signs, symptoms) and clear from a somatic pathophysiological comparison quantitative (severity, high rate of early asystole) but with SCI is that the mainstream assertion that BD also temporal (gradual return of autonomous cord represents biological death of the human `organism as function and somatic stabilization) ± unless, of course, a whole' is physiologically untenable. the BD patient also sustained diuse spinal cord infarction or injury, a common yet under-appreciated association, especially if the etiology is anoxic- ischemic. References

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