**3. Diagnosis and clinical presentation**

#### **3.1 Phase I**

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

contributes to decreased spinal reflexes [33, 34].

contributor to **Phase II** developments [40–45].

during the initial period of 1–3 days post-SCI [3].

clinical picture in **Phase I**.

**2.2 Phase II**

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

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

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

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

**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].

**112**

**2.3 Phases III and IV**

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.

#### **3.2 Phase II**

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].

#### **3.3 Phase III**

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 during this period [3, 68]. The return of these reflexes is as follows: Babinski sign recovery will follow AJ recovery closely, with the AJ preceding the return of the KJ [3, 68, 74]. The clinician should expect to see most DTRs resolve during this phase with only 10% persisting beyond **Phase III** [3]. Ditunno discussed the variability of reflex return regarding the timing trend. There have been studies showing reduced tendon reflex excitability in certain trained populations, such as ballet dancers and power-trained athletes, relative to untrained or even endurance athletes [75–77]. There has also been evidence that pre-SCI experiences could influence the reflex excitability below an SCI [78, 79]. During this time the clinician will have to be aware of the developing autonomic functions. There is expected improvement in the bradyarrhythmia and hypotension described before; however, around this time autonomic dysreflexia can arise and is most commonly due to a distended bladder or bowel causing a massive sympathetic outflow below the neurologic level of injury [3]. Autonomic dysreflexia can lead to difficult-to-control hypertension and bradycardia and is most commonly seen in patients with SCI at or above T6 but has been seen as low as T10 [80].
