**2. Spinal shock: etiology and pathophysiology**

Spinal cord injuries (SCI) are typically divided into two subtypes, complete and incomplete. An SCI is considered incomplete if there is some degree of residual motor and/or sensory function below the neurologic level of injury that includes the lowest sacral segments, where the neurologic level of injury is defined as the most caudal level at which both motor and sensory modalities remain preserved [10]. It follows that patients affected by a complete SCI will not retain sensory or motor function in the lowest sacral segments.

**111**

*Spinal Shock: Differentiation from Neurogenic Shock and Key Management Approaches*

describe the previously outlined "four phases" of spinal shock.

These two pathways will now be discussed in more detail.

the modulation of voluntary movement and reflexes.

to be mediated through sustained activation of Ca*2*<sup>+</sup>

the background basal excitatory stimulation [28–30]*.*

Before directing our discussion to the management in incomplete SCI, additional information will be provided regarding complete SCIs, specifically in the context of SS. The understanding of key processes surrounding complete SCI is conceptually easier, especially when compared to the understanding of incomplete SCI. It is important to note that although severed neurons are separated from descending input—both excitatory and inhibitory—there remains synaptic contact with associated interneurons and reflex afferents, and even new synaptic connections can be established with sprouting neurons [11, 12]. Our subsequent discussion will

As outlined in **Table 1**, **Phase I** of SS is marked by areflexia/hyporeflexia, a consequence of the loss of descending mediation. This phase occurs from 0 to 24 hours from time of injury. Under normal circumstances, both spinal motor neurons and interneurons receive certain baseline levels of background excitatory input from supraspinal axons. When an individual wishes to initiate voluntary movement, additional stimulus is superimposed above this "background activity." Supraspinal inputs mediating the background excitation of spinal motor neurons and interneurons are numerous and include vestibulospinal and reticulospinal pathways [13].

The vestibulospinal pathway arises from first-order neurons located in Scarpa's ganglion which is situated in the distal part of the internal auditory meatus [14]. Afferents are sent from the ganglion through the vestibular part of the eighth cranial nerve before entering the brainstem at the pontomedullary junction. Upon entry, there are four second-order vestibular nuclei; however, we shall focus on the medial and lateral vestibulospinal tracts for the purposes of our current discussion. The medial and lateral vestibulospinal tracts arise from the medial and lateral vestibular nuclei, respectively [15, 16]. The latter descends the entire length of the spinal cord ipsilaterally and plays a crucial role in walking upright, while the former descends bilaterally in the medial longitudinal fasciculus and terminates at the midthoracic level, facilitating the integration of head and eye movements [17, 18]. The reticulospinal pathway arises from the brainstem, the pontine reticular formation, and the medullary reticular formation [19, 20]. Pontine reticular fibers traveling in the pontine reticulospinal tract remain uncrossed as they descend in the medial longitudinal fasciculus, terminating in axial and limb muscles involved in posture and gait stability [21]. At the level of the muscle, their effects are at least threefold: (a) facilitation of movement, (b) regulation of reflexes, and (c) contribution to muscle tone. The medullary reticular fibers traveling in the medullary reticulospinal tract serve a slightly different role [22–24]. First, the fibers originating from the medullary reticulospinal formation are located bilaterally in the reticulospinal tracts as they descend; however, most of the fibers remain uncrossed. As they terminate on axial and limb muscles, they serve an inhibitory role during

In addition to supraspinal inputs, serotonergic (5-HT) neurons and noradrenergic (NE) neurons originating from the raphe nucleus and locus coeruleus, respectively, may also play a role in the background excitatory input as they influence spinal cord motor systems [25]*.* Mechanistically, this may involve the production of plateau potentials [26, 27]. The plateau potentials originate on dendrites, believed

fication of excitatory inputs, with approximately sixfold "gain," thus allowing for prolonged neuronal firing with minimal excitatory input, as well as contributing to

channels, and provide ampli-

*DOI: http://dx.doi.org/10.5772/intechopen.92026*

**2.1 Phase I**

*Spinal Shock: Differentiation from Neurogenic Shock and Key Management Approaches DOI: http://dx.doi.org/10.5772/intechopen.92026*

Before directing our discussion to the management in incomplete SCI, additional information will be provided regarding complete SCIs, specifically in the context of SS. The understanding of key processes surrounding complete SCI is conceptually easier, especially when compared to the understanding of incomplete SCI. It is important to note that although severed neurons are separated from descending input—both excitatory and inhibitory—there remains synaptic contact with associated interneurons and reflex afferents, and even new synaptic connections can be established with sprouting neurons [11, 12]. Our subsequent discussion will describe the previously outlined "four phases" of spinal shock.

#### **2.1 Phase I**

*Clinical Management of Shock - The Science and Art of Physiological Restoration*

1 0–1 day 1.Decreased spinal and supraspinal excitation

2 1–3 days 1.Increased postsynaptic sensitivity

4 1–12 months 1.Synapse growth in long axons

**Phase Timing Neurological changes**

working model for our subsequent discussions of diagnosis, patient presentation,

Ditunno made a subtle point that the controversy surrounding the definition of SS could be attributed to observations made clinically. More specifically, he noted that not all reflexes are eradicated in a strictly binary on/off fashion. Some reflexes may only be depressed and yet still can be technically elicited. Finally, he noted that the resolution of SS does not occur in a binary fashion and often follows a prolonged course of weeks to months [3]. Similar observations by Illis suggested that the definition of SS cannot be comprehensive without including subcomponent definitions of clinical phases [4]. For the purposes of this chapter, we will utilize Ditunno's four-phase model of spinal shock, building upon the groundwork described by various pioneers such as Whytt and Hall [1, 3]. This model allows for clarification of the ambiguity surrounding the disease process while still retaining flexibility to appreciate the variability among clinical presentations. The details of Ditunno's

2.Loss of 5-HT production leading to loss of plateau potentials

2.Receptor upregulation due to decreased neurotransmitter activity

3.Reduction of available synapses and dendrites

3.Plateau potentials recovered in spinal neurons

3 1–4 weeks 1.Increased neurotrophin activity allows for increased synaptic growth 2.Increased interneuron growth

The phases are organized according to post-injury time and the nervous system's response to insult. Of note, we will hold off on the discussion of each phase until the *Etiology and Pathophysiology* section as the separation of phases requires delving into how the neurons are responding to their environment as time progresses.

In 2007, there was an estimated global spinal cord injury (SCI) incidence of 2.3 cases/100,000 inhabitants [5]. It has been estimated 45% of SS cases are associated with motor vehicle collisions (MVC), 34% with domestic accidents, 15% with sporting accidents, and 6% with self-harm [6]. The incidence of SCI can vary across geographic, socioeconomic, and cultural factors, including the prevalence of contact sports and differences in primary transportation modality. All of the above factors are important determinants of the incidence of SCI. Finally, no discussion of the topic of SCI is complete without mentioning the tremendous human and

Spinal cord injuries (SCI) are typically divided into two subtypes, complete and incomplete. An SCI is considered incomplete if there is some degree of residual motor and/or sensory function below the neurologic level of injury that includes the lowest sacral segments, where the neurologic level of injury is defined as the most caudal level at which both motor and sensory modalities remain preserved [10]. It follows that patients affected by a complete SCI will not retain sensory or motor

and treatment approaches.

*Four phases of spinal shock by Ditunno et al.*

**Table 1.**

four-phase model can be seen in **Table 1** [3].

economic cost associated with these injuries worldwide [7–9].

**2. Spinal shock: etiology and pathophysiology**

function in the lowest sacral segments.

**110**

As outlined in **Table 1**, **Phase I** of SS is marked by areflexia/hyporeflexia, a consequence of the loss of descending mediation. This phase occurs from 0 to 24 hours from time of injury. Under normal circumstances, both spinal motor neurons and interneurons receive certain baseline levels of background excitatory input from supraspinal axons. When an individual wishes to initiate voluntary movement, additional stimulus is superimposed above this "background activity." Supraspinal inputs mediating the background excitation of spinal motor neurons and interneurons are numerous and include vestibulospinal and reticulospinal pathways [13]. These two pathways will now be discussed in more detail.

The vestibulospinal pathway arises from first-order neurons located in Scarpa's ganglion which is situated in the distal part of the internal auditory meatus [14]. Afferents are sent from the ganglion through the vestibular part of the eighth cranial nerve before entering the brainstem at the pontomedullary junction. Upon entry, there are four second-order vestibular nuclei; however, we shall focus on the medial and lateral vestibulospinal tracts for the purposes of our current discussion. The medial and lateral vestibulospinal tracts arise from the medial and lateral vestibular nuclei, respectively [15, 16]. The latter descends the entire length of the spinal cord ipsilaterally and plays a crucial role in walking upright, while the former descends bilaterally in the medial longitudinal fasciculus and terminates at the midthoracic level, facilitating the integration of head and eye movements [17, 18].

The reticulospinal pathway arises from the brainstem, the pontine reticular formation, and the medullary reticular formation [19, 20]. Pontine reticular fibers traveling in the pontine reticulospinal tract remain uncrossed as they descend in the medial longitudinal fasciculus, terminating in axial and limb muscles involved in posture and gait stability [21]. At the level of the muscle, their effects are at least threefold: (a) facilitation of movement, (b) regulation of reflexes, and (c) contribution to muscle tone. The medullary reticular fibers traveling in the medullary reticulospinal tract serve a slightly different role [22–24]. First, the fibers originating from the medullary reticulospinal formation are located bilaterally in the reticulospinal tracts as they descend; however, most of the fibers remain uncrossed. As they terminate on axial and limb muscles, they serve an inhibitory role during the modulation of voluntary movement and reflexes.

In addition to supraspinal inputs, serotonergic (5-HT) neurons and noradrenergic (NE) neurons originating from the raphe nucleus and locus coeruleus, respectively, may also play a role in the background excitatory input as they influence spinal cord motor systems [25]*.* Mechanistically, this may involve the production of plateau potentials [26, 27]. The plateau potentials originate on dendrites, believed to be mediated through sustained activation of Ca*2*<sup>+</sup> channels, and provide amplification of excitatory inputs, with approximately sixfold "gain," thus allowing for prolonged neuronal firing with minimal excitatory input, as well as contributing to the background basal excitatory stimulation [28–30]*.*

Baseline excitability in muscle spindles may also be handled in part by gammamotor neurons [31, 32]. Upon SCI, gamma-motor neurons caudal to the injury may lose their ability to influence motor neurons via stretch reflex afferents as they lose their tonic descending facilitation. The loss of descending inhibition of inhibitory pathways within the spinal cord must also be considered, primarily because it likely contributes to decreased spinal reflexes [33, 34].

Finally, some of the more delayed developments involving the injured cord, both metabolic and structural, could contribute to the observed areflexia/hyporeflexia characteristics of SS. At the same time, the observed areflexia/hyporeflexia usually occurs immediately post-SCI, making any other pathophysiologic considerations secondary—rather than primary—factors [35, 36]. This "secondary factor" list includes (a) dendritic retraction and synaptic degeneration seen within 1–3 days post-SCI; (b) impaired delivery of metabolites and secretion of neurotrophins; and (c) the impact of growth factors caudal to the neurologic level of injury [36–38].

Upon traumatic injury resulting in complete SCI, the baseline excitation from supraspinal inputs will be lost, leading to hyperpolarization of the neurons [39]. This hyperpolarization leads to the neurons becoming less excitable and yields the clinical picture in **Phase I**.

## **2.2 Phase II**

Appearing 1–3 days following the SCI, the return of cutaneous reflexes is observed [3]. It is still unknown whether this is due to replacement of synapses or to denervation supersensitivity. Morphological changes in the synapses have been documented within hours to days of SCI; however, these synapses may not become functional until weeks—or even months—have passed, making this an unlikely contributor to **Phase II** developments [40–45].

Denervation supersensitivity is defined as increased neuronal firing in response to a neurotransmitter [46]. This phenomenon has been shown to occur in both the peripheral (PNS) and central (CNS) nervous systems, including the brain and the spinal cord [47–51]. The proposed mechanisms involves upregulation of mRNA transcription and protein translation that begins within hours and peaks within days post-SCI, which is within the time scale of empirically observed changes [52]. More specifically, the overall process leads to increased synthesis and insertion of receptors into the postsynaptic membrane, altered synthesis and assembly of receptor subunits, decreased removal and/or degradation of receptor(s), and reduced excitatory neurotransmitter reuptake [52–55]. Mechanistically, NMDA glutamate receptors, serotonin 2A, and vanilloid VR1 receptors have been shown to increase either in association with mRNA synthesis or the observed density at the synapse [54, 56–58]. Hypoactivity of neurons has been shown to constitute a sufficient stimulus to increase production of the NMDA glutamate receptors [55]. Although the exact details are yet to be elucidated, neurotrophins, growth factors, and their respective receptors have been shown to stimulate an increase in transcription and translation [59–64]. Postulated downstream effects involve the modulation of NMDA receptors, resulting in increased excitability and/or decreasing GABA synaptic inhibition [65]. These effects seem to play a role in the development of SS during the initial period of 1–3 days post-SCI [3].

#### **2.3 Phases III and IV**

**Stages III (1–4 weeks)** and **IV (1–12 months)** of SS are often linked together and are best described through the lens of the human tibial H-reflex. The H-reflex has been used to model the recovery of reflexes caudal to SCI over time [66, 67].

**113**

**3.3 Phase III**

*Spinal Shock: Differentiation from Neurogenic Shock and Key Management Approaches*

reflex excitability at approximately 3–4 months post-SCI [3].

relative to the monosynaptic Ia afferents to motoneurons [3].

**3. Diagnosis and clinical presentation**

**3.1 Phase I**

**3.2 Phase II**

In this context, an interesting phenomenon is observed beyond post-injury "day 3" temporal marker. More specifically, there is an increased reflex excitability observed at 2–4 weeks post-SCI with an increase in latency and another increase in

Overall, it has been shown that the 2–4-week mark increase in excitability can be attributed to axon-supplied synapse growth and/or disynaptic interneurons, while the increase in excitability at 3–4 months is mediated by primary afferents and/or soma-supplied synapse growth [3]. The timing of the observed changes in excitability suggests that there is an axon-length-dependent rate of synapse growth. Two mechanisms have been proposed to explain this phenomenon: (a) two periods of synaptic growth—early findings dependent on axonal synthesis and the later growth period dependent on somal synthesis and (b) disynaptic stretch reflex pathways, such as the Golgi tendon organ reflex, are preferentially hyperexcitable

Caudal to complete SCI within the first 24 hours, Phase I will present with flaccid, paralyzed muscles and deep tendon reflexes (DTRs) being initially absent. While the DTRs such as the ankle jerk (AJ) and knee jerk (KJ) are absent, a pathologic reflex, delayed plantar response (DPR), is often the first to return and should be observed within hours post-SCI [68]. Other cutaneous and polysynaptic reflexes such as the bulbocavernosus (BC), cremasteric (CM), and anal wink (AW) can also be seen to return during Phase I. Location of the lesion can be determined based on presenting symptoms. Lesions above the mid-pons will cause decerebrate rigidity, while those located below the mid-pons cause hyporeflexia [69]. In addition to skeletal motor and reflex findings during this time, there are autonomic findings that may be relevant if the lesion is in the cervical area. Findings include hypotension, atrioventricular conduction block, and bradyarrhythmia, and these can be continued through Phases II and III [3]. These findings are consistent with neurogenic shock, detailed in a separate chapter.

One to 3 days post-SCI, the clinician should expect to see continued reflex return. Building upon Phase I, the cutaneous reflexes, BC, AW, and CM, become stronger [3]. Except for two patient populations, namely, the elderly and children, DTRs are still absent; however, the tibial H-reflex returns around the 24-hour marker [70, 71]. In the elderly, DTRs and the Babinski sign can occur during this phase [68]. Although not known for certain, the presence of pre-existing subclinical myelopathy might contribute to this early recovery as some animal studies have exhibited quicker recovery of DTRs in the setting of prior upper motor neuron lesions [68, 72, 73]. Children exhibit similar recovery, showing DTRs sometimes 3 days post-SCI, which might be attributable to their still developing descending supraspinal tracts, predisposing them to spinal hyperreflexia. The recovery of cutaneous reflexes during phase II is likely due to receptor plasticity [3].

The third phase (days 4–30) is marked by early hyperreflexia. Excluding the two patient populations discussed in Phase II, almost all patients will regain DTRs

*DOI: http://dx.doi.org/10.5772/intechopen.92026*

*Spinal Shock: Differentiation from Neurogenic Shock and Key Management Approaches DOI: http://dx.doi.org/10.5772/intechopen.92026*

In this context, an interesting phenomenon is observed beyond post-injury "day 3" temporal marker. More specifically, there is an increased reflex excitability observed at 2–4 weeks post-SCI with an increase in latency and another increase in reflex excitability at approximately 3–4 months post-SCI [3].

Overall, it has been shown that the 2–4-week mark increase in excitability can be attributed to axon-supplied synapse growth and/or disynaptic interneurons, while the increase in excitability at 3–4 months is mediated by primary afferents and/or soma-supplied synapse growth [3]. The timing of the observed changes in excitability suggests that there is an axon-length-dependent rate of synapse growth. Two mechanisms have been proposed to explain this phenomenon: (a) two periods of synaptic growth—early findings dependent on axonal synthesis and the later growth period dependent on somal synthesis and (b) disynaptic stretch reflex pathways, such as the Golgi tendon organ reflex, are preferentially hyperexcitable relative to the monosynaptic Ia afferents to motoneurons [3].
