Abstract
BACKGROUND
Disorder of consciousness (DOC) is a state of prolonged altered consciousness due to severe acquired brain injury (ABI). DOC can be differentiated into coma, unresponsive wakefulness syndrome (UWS), or minimally conscious state (MCS) depending on the behavioral features observed and their relationship to the level of consciousness. Spasticity is one of the most frequently reported medical comorbidities in DOC patients. Since there is a critical lack of spasticity-focused studies and, in turn, of target treatment, we designed this pilot prospective study to evaluate cervical spine muscle spasticity and its effect on rehabilitation outcome in a large cohort of patients followed from the post-acute phase to 6 months after severe ABI.
AIM
To evaluate neck muscle spasticity and investigate its impact on neurological and functional outcome in a large cohort of adult patients with DOC followed from post-acute to 6 months after severe ABI.
DESIGN
Single-center prospective pilot study.
SETTING
Highly specialized inpatient neurorehabilitation clinic.
POPULATION
Patients with severe ABI admitted within 3 months after the acute event to our Neurorehabilitation Unit between May 21st, 2019 and April 23rd, 2020 for treatment of DOC as a part of their rehabilitation program.
METHODS
In this single-center prospective pilot study demographic data, etiology of ABI (traumatic versus non-traumatic), DOC evaluated with the revised Coma Recovery Scale (CRS-R), and neurological and functional outcome assessed respectively with the Glasgow Coma Scale (GCS) and Functional Independence Measure (FIM) were considered. During cervical examination, we assessed spasticity with the Modified Ashworth Scale (MAS), deviation of head alignment with a goniometer, and pain with the Nociception Coma Scale-Revised (NCS-R).
RESULTS
Of the 48 patients, 41.7% were diagnosed with UWS and 58.3% were in a minimally conscious state (MCS). We found spasticity of neck muscles in 91.7% of patients, with no difference in severity (assessed with MAS) between UWV and MCS. The NCS-R score at cervical spine examination was lower in UWS than MCS. Spasticity was severer in patients with traumatic brain injury (TBI) compared to non-traumatic. At multiple linear regression analysis, younger age, hemisyndrome, and tetraparesis were independent predictors of severity of neck muscle spasticity in MCS. More severe spasticity was a predictor of worse neurological and functional outcome at discharge in UWS patients, independently of the other confounding variables at admission (e.g., age, severity of brain injury, functional assessment, and pain).
CONCLUSIONS
Spasticity of neck muscles frequently develops in patients with DOC and is more severe in those after TBI. UWV and MCS have different spasticity profiles as regards risk factors and neurological and functional outcome. Severity of neck muscle spasticity in UWV patients may represent an early indicator of worse neurological and functional outcome after inpatient rehabilitation.
CLINICAL REHABILITATION IMPACT
Our findings could prompt clinicians to redefine the rehabilitation aims regarding spasticity and to estimate the functional outcome in patients undergoing intensive rehabilitation after severe ABI.
Key words: Neck muscles, Muscle spasticity, Neurological rehabilitation, Consciousness disorders, Brain injuries
Disorder of consciousness (DOC) is a state of prolonged altered consciousness due to severe acquired brain injury (ABI).1 DOC can be differentiated into coma, unresponsive wakefulness syndrome (UWS), or minimally conscious state (MCS) depending on the behavioral features observed and their relationship to the level of consciousness.2 The defining clinical feature of coma is the complete loss of spontaneous or stimulus-induced arousal.2 UWS is diagnosed when reflexive behavior such as spontaneous eye opening emerges, but without any discernible evidence of awareness of self or environment.3 Finally, MCS refers to severely altered consciousness characterized by minimal but definite behavioral evidence of self or environmental awareness.4
Spasticity is one of the most frequently reported medical comorbidities in DOC patients.5 A recent review reported a prevalence of spasticity ranging from 59% to 89% after severe ABI.6 However, since recovery of consciousness is the main “medical priority” among these patients, there is a critical lack of spasticity-focused studies and, in turn, of target treatment.6
The existing literature5, 6 suggests that patients with altered state of consciousness have an atypical motor pattern due to the widespread nature of the lesions that could affect the nervous system at various levels. In this regard, despite studies describing spasticity of upper and/or lower limbs,5, 7 there are no data on neck muscle spasticity in patients with DOC. This lack of knowledge is quite unexpected given the high potential impact on the rehabilitation process and patient quality of life. Indeed, spasticity of a cervical segment can be painful and, in turn, exacerbate the spastic and dystonic symptoms. A better characterization of spasticity could help clinicians to identify individuals who would benefit most from rehabilitation care and thus provide better outcomes. Therefore, we designed this pilot prospective study to evaluate cervical spine muscle spasticity and its effect on rehabilitation outcome in a large cohort of patients followed from the post-acute phase to 6 months after severe ABI. A secondary aim was to assess the association between abnormalities of cervical spine posture and the motor and clinical pattern related to severe ABI.
Materials and methods
Study design and population
In this single-center prospective pilot study, we included patients with severe ABI admitted to the Neurorehabilitation Unit of ICS Maugeri Institute of Pavia (IRCCS) between May 21st, 2019 and April 23rd, 2020. All participants underwent inpatient intensive neurorehabilitation for a period of up to 6 months consisting of an individual 90-minute daily treatment program, 6 days a week.
The inclusion criteria were: 1) age ≥18 years; 2) admission for a rehabilitation-based DOC treatment program within 3 months after severe ABI due to traumatic, ischemic, hemorrhagic, or anoxic brain injury. We excluded patients with pre-existing neurological diseases, previous surgical approach or instability of the cervical spine.
The study design complied with the ethical guidelines of the Declaration of Helsinki and was approved by the local Ethics Committee of ICS Maugeri (#2332 CE/2019). Authorized representatives of each patient signed a written informed consent.
Variables and measurements
We included the following variables: sex, age at occurrence of injury, etiology of ABI (dichotomized into traumatic vs. non-traumatic lesions), motor pattern on admission (classified as decerebration, decortication, hemisyndrome, tetraparesis, or mixed form), and death during rehabilitation. DOC on admission was evaluated with the Italian version of the Coma Recovery Scale-Revised (CRS-R),8 which can reliably distinguish patients in the minimally conscious state from those in a vegetative state. The CRS-R consists of 29 items divided into 6 subsets addressing auditory, visual, motor, oral motor, communication, and arousal processes. We used the Glasgow Coma Scale (GCS) and Functional Independence Measure (FIM) to assess, respectively, the neurological and functional outcomes at baseline and discharge. The GCS is a standardized system for evaluating the degree of neurological impairment and level of consciousness in all types of brain injury.9 The scale investigates three aspects of responsiveness: eyes opening, verbal and motor responses. The total score ranges from 3 to 15 (complete consciousness). Rehabilitation outcomes were evaluated with the FIM scale, an 18-item measurement tool that explores an individual’s disability in terms of burden of care.10 Each of the 18 items is graded on a scale from 1 to 7 based on level of independence (1 = total assistance required, 7 = complete independence). Finally, we collected information on the prescription of antispastic drugs, including baclofen, tizanidine, dantrolene, and benzodiazepines or on treatment with botulinum toxin and intrathecal baclofen.
Cervical examination
The cervical spine examination was performed by physicians in clinically stable patients, to avoid conditions (e.g. infectious and neurological complications) that potentially increase the severity of spasticity. Spasticity of cervical muscles was evaluated by physician with the Modified Ashworth Scale (MAS). The MAS is a 0-4 grading scale assessing the resistance to passive stretch of a relaxed muscle group around a given joint.11 A muscle group was considered affected by spasticity if identified as having an MAS grade ≥1 during passive range of neck flexion, extension, and rotation, respectively.
Deviation of head alignment from the neutral position due to spasticity was assessed with the use of a universal goniometer (UG). As previously reported,12 to measure cervical flexion and extension the UG axis was positioned in the center of the subject’s external auditory meatus, with the fixed arm vertical and the movable arm aligned parallel to an imaginary line between the external auditory meatus and the base of the nostrils. During measurement of cervical lateral flexion, the examiner positioned the UG axis over the center of the subject’s sternal notch, with the fixed arm aligned parallel to a line between the subject’s acromion processes and the movable arm aligned with the center of the subject’s nose. Finally, for cervical rotation, the UG axis was positioned over the center of the subject’s head, aligning the fixed arm to a line between the subject’s acromion processes and the movable arm to the tip of the subject’s nose.
During examination, presence of pain was detected with the Nociception Coma Scale Revised (NCS-R). This scale was developed to evaluate nociceptive behavior in patients with DOC, the score ranging from 0 to 9 (maximum pain).13
Statistical analysis
Categorical variables were expressed as absolute number and percentage and compared using the Chi-square test. Continuous variables were expressed as median and interquartile range (IQR). Independent sample t-tests were utilized to assess the difference between the two patient groups (traumatic vs. non-traumatic lesions) in terms of head alignment and neck spasticity. Multivariate linear regression analysis was used to evaluate the predictive role between the considered clinical variables and pain, neck muscle spasticity, neurological function, and rehabilitation outcome.
The multivariate models included NCS-R, MAS, GCS and FIM scores at discharge (T1) as dependent variables. In turn, independent variables were age, sex (male = 0, female = 1), GCS, FIM, CRS-R and NCS-R scores at admission (T0), motor patterns and measurement of head alignment. Coefficients of determination (R2), β coefficients, and P values obtained from the models were reported. Several different models were tested to avoid collinearity. The models achieving the highest R2 were reported. Statistical significance was set at 5%. Statistical analyses were performed using SPSS Statistics 21 (IBM Corporation, Somers, NY, USA).
Data availability
The data associated with the paper are not publicly available but are available from the corresponding author on reasonable request.
Results
Demographic and clinical characteristics
The cohort included 48 adult patients with DOC due to severe ABI. A summary of the clinical and functional characteristics of the patients is reported in Table I.
Table I. —Patients’ clinical-demographic characteristics at admission according to the type of disorder of consciousness.
| Parameter | All patients (N.=48) |
Patients with UWS N.=20 (41.7%) |
Patients in minimally conscious state N.=28 (58.3%) |
P value |
|---|---|---|---|---|
| Age | 0.765 | |||
| ≤65 years | 30 (62.5) | 14 (70.0) | 16 (57.1) | |
| >65 years | 18 (37.5) | 7 (35.0) | 11 (39.3) | |
| Sex | 0.142 | |||
| Men | 22 (45.8) | 12 (57.1) | 10 (35.7) | |
| Women | 26 (54.2) | 8 (40.0) | 18 (64.3) | |
| Etiology | 0.999 | |||
| Traumatic | 12 (25.0) | 5 (25.0) | 7 (25.0) | |
| Non-traumatic | 36 (75.0) | 15 (75.0) | 21 (75.0) | |
| Clinical assessment at admission | ||||
| GCS | 8 (7-10) | 7 (6-8) | 10 (8-11) | <0.0001* |
| CRS-R | 7 (5-11) | 5 (4-5) | 10 (8.5-12) | <0.0001* |
| FIM | 18 (18-19) | 18 (18-18) | 18 (18-19) | 0.182 |
| Motor pattern at admission | ||||
| Decerebration | 7 (14.6) | 6 (30.0) | 1 (3.6) | 0.015* |
| Decortication | 4 (8.3) | 1 (14.3) | 3 (10.7) | 0.337 |
| Hemisyndrome | 14 (29.2) | 4 (20.0) | 10 (35.7) | 0.213 |
| Tetraparesis | 17 (35.4) | 7 (35.0) | 10 (35.7) | 0.700 |
| Mixed forms | 6 (12.5) | 2 (10.0) | 4 (14.3) | 0.384 |
Comparison between groups, expressed as absolute number and percentage, was by χ2 Test. Comparison between non-normally distributed data (GCS, CRS-R, and FIM scores), expressed as median and interquartile ranges, was performed using Mann-Whitney Test. CRS-R: Coma Recovery Scale-Revised; FIM: Functional Independence Measure; GCS: Glasgow Coma Scale; UWS: unresponsive wakefulness syndrome. *Statistically significant difference.
No significant differences were found between UWV and MCS in terms of sex, age at diagnosis, and etiology of brain damage. Based on the clinical evaluation at admission, 41.7% of patients were in UWS and 58.3% in MCS. Overall, 54.2% of the patients were women, and 62.5% were under 66 years of age (mean 59.2±13.6). The etiology underlying DOC was traumatic brain injury (TBI) in 25.0% of cases and non-traumatic in 75% (of which 55.6% hemorrhagic stroke, 25% ischemic stroke, and 19.4% hypoxic encephalopathy). UWS patients had significantly lower GCS (P<0.0001) and CRS-R (P<0.0001) scores than MCS. No differences were found between the two groups for FIM score.
Concerning the motor pattern, we detected a significant (P=0.015) prevalence of decerebrate posture in UWS patients whilst the remaining patterns were uniformly represented between the two groups of DOC.
Cervical spine examination
Table II shows the clinical characteristics of the cervical spine examination in patients subdivided according to the type of DOC.
Table II. —Clinical characteristics of cervical spine examination of patients according to the type of disorder of consciousness.
| Parameter | All patients (N.=48) |
Patients with UWS N.=20 (41.7%) |
Patients in Minimally conscious state N.=28 (58.3%) |
P value |
|---|---|---|---|---|
| Systemic antispastic therapy | 41 (85.4%) | 18 (90.0%) | 23 (82.1%) | 0.683 |
| Spasticity of neck muscle | 44 (91.7%) | 20 (100.0%) | 23 (82.1%) | 0.066 |
| MAS of neck muscles | 2 (1-3%) | 2 (1-3%) | 2 (1-2.5%) | 0.279 |
| NCS-R | 2 (1-3%) | 0 (0-1%) | 2 (2-3%) | <0.0001* |
| Neck malalignment | 32 (66.7%) | 15 (75.0%) | 17 (60.7%) | 0.363 |
| Neck posture | ||||
| Flexion | 13 (27.1%) | 5 (25.0%) | 8 (28.6%) | 1.0 |
| Extension | 13 (27.1%) | 8 (40.0%) | 5 (17.8%) | 0.110 |
| Right lateral inclination | 11 (22.9%) | 4 (20.0%) | 7 (25.5%) | 0.741 |
| Left lateral inclination | 15 (31.2%) | 8 (40.0%) | 7 (25.0%) | 0.341 |
| Right rotation | 9 (18.7%) | 3 (15.0%) | 6 (21.4%) | 0.716 |
| Left rotation | 18 (37.5%) | 8 (40.0%) | 10 (35.7%) | 0.772 |
| Neck alignment measurements (deg.) | ||||
| Flexion | 14.2±4.2 | 14.0±5.4 | 14.4±3.6 | 0.882 |
| Extension | 16.1±9.4 | 14.4±6.0 | 18.3±13 | 0.687 |
| Right lateral inclination | 16.5±7.7 | 15.2±7.4 | 17.3±8.3 | 0.696 |
| Left lateral inclination | 15.7±8.4 | 18.1±9.8 | 13.0±6.0 | 0.380 |
| Right rotation | 15.8±6.3 | 14.±5.6 | 12.7±9.8 | 0.494 |
| Left rotation | 19±6.1 | 20.7±5.2 | 18.7±6.8 | 0.502 |
| Death during inpatient rehabilitation | 10 (20.4%) | 4 (20.0%) | 6 (21.4%) | 1.0 |
Comparison between groups, expressed as absolute number and percentage, was by χ2 Test. Comparison between non-normally distributed data (NCS-R and MAS scores), expressed as median and interquartile ranges, was performed using Mann-Whitney Test. Independent samples t-tests were utilized to assess difference means. Deg., degrees; MAS, Modified Ashworth Scale; NCS-R, Nociception Coma Scale-Revised; UWS: unresponsive wakefulness syndrome. *Statistically significant difference.
Since the cervical spine examination was performed in clinically stable patients to avoid conditions (e.g. infectious and neurological complications) that potentially increase the severity of spasticity, the median time between admission to our Unit and cervical spine evaluation was 50.6±14.6 days. Although 85.4% of patients were in systemic antispastic therapy, spasticity was documented in 91.7% of cases, with no difference in the MAS assessment between UWV and MCS. Regarding the type of systemic antispastic therapy, baclofen per os was prescribed in 68.4% of patients, benzodiazepines in 16.3% and tizanidine in 15.3%. At the time of assessment, no patient was treated with botulinum toxin and/or intrathecal baclofen. Malalignment of the cervical spine was found in 66.7% of patients. In 37.5%, we detected neck left rotation, in 31.2% left lateral inclination, in 27.1% flexion and extension, in 22.9% right lateral inclination and in 18.7% right rotation. In several patients (87.9%), a combination of abnormal neck postures was found. The difference between right and left rotation or lateral inclination was not significant (P=0.51). Finally, cervical spine malalignment ranged from about 14 to 21 degrees independently of the plane of rotation considered. No significant differences were found between UWV and MCS in terms of cervical spine posture or malalignment. As regards etiology (Figure 1), patients with TBI presented more severe neck muscle spasticity than those with a non-traumatic origin (z=2, 13; P=0.03). After clinical examination, ten patients (20.4%) died during inpatient rehabilitation, 20.0% of whom were in UWS and 21.6% in MCS with no difference between the two groups.
Figure 1.
—Box plots of the Wilcoxon-Mann-Whitney U Test results showing significantly different medians of Modified Ashworth Scale (MAS) between traumatic and non-traumatic etiology groups.
Of note, the simultaneous administration of NCS-R during cervical spine mobilization showed significantly (P<0.0001) higher scores (i.e., more normal nociceptive behavior) in MCS than UWV patients. At multiple linear regression analysis, conducted to explore potential independent predictors of pain in the overall cohort of patients, FIM and CRS-R at admission emerged as independent predictors of pain as assessed by NCS-R (P<0.0001) during the cervical spine examination: i.e., higher scores of FIM and CRS-R predicted more normal nociceptive behavior. The models achieving the highest coefficient of determination (R2) are reported in Table III.
Table III. —Potential predictors of pain assessed with the revised Nociception Coma Scale (NCS-R).
| Predictors | NCS-R | |
|---|---|---|
| R=0.683 | ||
| beta | P value | |
| Age | 0.042 | 0.669 |
| Sex | 0.014 | 0.885 |
| Glasgow Coma Scale at admission | 0.103 | 0.350 |
| Functional Independence Measure at admission | 0.405 | <0.0001* |
| Coma Recovery Scale-revised at admission | 0.556 | <0.0001* |
| Modified Ashworth scale | 0.062 | 0.531 |
*Statistically significant difference.
To explore potential independent predictors of neck spasticity severity in the two DOC groups at admission, we conducted a multiple linear regression model analysis (Table IV).
Table IV. —Potential predictors of spasticity severity assessed with Modified Ashworth Scale (MAS) according to the type of disorder of consciousness.
| Model | Unresponsive wakefulness syndrome | Minimally conscious state | ||
|---|---|---|---|---|
| MAS of neck muscles | MAS of neck muscles | |||
| Model 1 | R=0.119 | R=0.543 | ||
| beta | P value | beta | P value | |
| Age (years) | 0.051 | 0.925 | -0.547 | 0.012* |
| Sex | -0.244 | 0.516 | -0.156 | 0.414 |
| GCS at admission | -0.101 | 0.845 | -0.163 | 0.392 |
| FIM at admission | 0.007 | 0.964 | -0.116 | 0.623 |
| CRS-R at admission | -0.071 | 0.866 | -0.133 | 0.517 |
| NCS-R | 0.366 | 0.356 | 0.074 | 0.776 |
| Antispastic medication | -0.062 | 0.829 | 0.444* | 0.039* |
| Model 2 | R=0.139 | R=0.248 | ||
|---|---|---|---|---|
| beta | P value | beta | P value | |
| Decerebration | 0.516 | 0.364 | 0.195 | 0.325 |
| Decortication | 0.245 | 0.485 | 0.217 | 0.310 |
| Hemisyndrome | 0.563 | 0.276 | 0.555 | 0.025* |
| Tetraparesis | 0.460 | 0.460 | 0.434* | 0.049* |
| Mixed forms | 0.000 | 0.999 | 0.276 | 0.211 |
| Model 3 | R=0.258 | R=0.248 | ||
|---|---|---|---|---|
| beta | P value | beta | P value | |
| Flexion (deg.) | -0.118 | 0.690 | 0.170 | 0.409 |
| Extension (deg.) | -0.196 | 0.592 | 0.480 | 0.077 |
| Right lateral inclination (deg.) | -3.236 | 0.295 | 0.334 | 0.213 |
| Left lateral inclination (deg.) | -0.350 | 0.639 | 0.403 | 0.193 |
| Right rotation (deg.) | 3.687 | 0.246 | 0.165 | 0.467 |
| Left rotation (deg.) | 0.733 | 0.337 | -0.084 | 0.805 |
Deg., degrees; GCS, Glasgow Coma Scale; FIM, Functional Independence Measure; CRS-R, Coma Recovery Scale-Revised; NCS-R, Nociception Coma Scale-Revised. *Statistically significant difference.
In the MCS group, younger age (P=0.012), hemisyndrome (P=0.025), and tetraparesis (P=0.049) were independent predictors of more severe spasticity assessed with MAS. Of note, no association was found between severity of spasticity and neurological, functional or consciousness assessment at admission, nociceptive response, and measurement of cervical spine malalignment.
Finally, on the surviving patients, a multiple linear regression was conducted to identify the independent predictors of neurological and functional outcome on discharge after 6-month inpatient rehabilitation (Table V).
Table V. —Potential predictors of neurological and functional outcome measured respectively with Glasgow Coma Scale (GCS) and Functional Independence Measure (FIM) at discharge (T1).
| Model 1 | Unresponsive wakefulness syndrome a | Minimally conscious state b | ||||||
|---|---|---|---|---|---|---|---|---|
| GCS T1 | FIM T1 | GCS T1 | FIM T1 | |||||
| R=0.715 | R=0.529 | R=0.191 | R=0.298 | |||||
| beta | P value | beta | P value | beta | P value | beta | P value | |
| Age | -0.49 | 0.326 | -0.39 | 0.53 | 0.22 | 0.50 | -0.14 | 0.65 |
| Sex | -0.23 | 0.391 | -0.29 | 0.405 | -0.08 | 0.76 | -0.11 | 0.66 |
| GCS T0 | 0.59 | 0.238 | 0.12 | 0.84 | 0.01 | 0.95 | -0.53 | 0.06 |
| FIM T0 | -0.36 | 0.228 | -0.07 | 0.84 | 0.31 | 0.37 | 0.41 | 0.22 |
| CRS T0 | 0.30 | 0.377 | -0.61 | 0.88 | 0.09 | 0.75 | 0.01 | 0.95 |
| NCS-R T0 | 0.51 | 0.096 | 0.23 | 0.53 | -0.05 | 0.89 | -0.14 | 0.66 |
| MAS-nm | -0.74 | 0.006* | -0.64 | 0.03* | -0.08 | 0.80 | 0.00 | 0.97 |
a Data available for 16 surviving patients; b data available for 22 surviving patients. CRS-R: Coma Recovery Scale-Revised; MAS-nm: Modified Ashworth Scale of neck muscles at examination; NCS-R: Nociception Coma Scale-Revised; T0: admission. *Statistically significant difference.
The linear regression analysis showed that spasticity of the neck muscles was a predictor of worse neurological and functional outcome at discharge in the UWS group, independently of the other confounding variables at admission such as age, sex, severity of brain injury, disorder of consciousness, and functional or pain assessment.
Discussion
The main aim of our study was to evaluate neck muscle spasticity and to investigate its impact on neurological and functional outcome in a large cohort of rehabilitation inpatients with DOC followed from the post-acute phase until 6 months after severe ABI. Our findings indicate that patients with UWV and MCS do not have the same neck spasticity profile as regards risk factors of developing it and the neurological and functional outcome after rehabilitation. Indeed, in our cohort, younger age, hemisyndrome, and tetraparesis were potentially important predictors of severer neck muscle spasticity in MCS patients, while severe spasticity was a predictor of worse neurological and functional outcome at discharge in UWS patients, independently of other confounding variables such as sex, age, and the severity of neurological and functional assessment at admission. These findings are in line with a recent retrospective7 study which suggested that spasticity evolves differently according to the etiology of the brain lesion and the level of consciousness.
Overall, in our cohort, patients with traumatic etiology had more severe neck spasticity than those with non-traumatic etiology. Indeed, mechanical damage after TBI is associated with biochemical, metabolic, and inflammatory alterations leading to disseminated and diffuse secondary injury, which worsens the brain damage14 and, in turn, the severity of spasticity. On the contrary, no differences were found between the traumatic and non-traumatic groups regarding the FIM assessment on admission. However, the absence of difference in FIM between traumatic and non-traumatic etiology groups might be the consequence of a possible “floor” effect of FIM in severely compromised patients as recently suggested by Lavezzi et al.15 Therefore, we cannot exclude that using other more appropriate tools, such as the Disability Rating Scale and the Glasgow Outcome Scale-Extended, would disclose differences in the outcome between the two patient groups.
In our cohort, neck muscle spasticity was detected in 91.7% of patients, with no difference in prevalence or severity between UWV and MCS. Previous studies examining spasticity in DOC reported a prevalence ranging from 59% to 89%.5-7, 16 Indeed, spasticity is one of the commonest complications following severe brain injury, due to the broad distribution and extent of brain damage at various levels of the central nervous system (cortical, infra-cortical and spinal).5, 6 As expected, we found that UWV patients presented worse CRS-R and GCS scores on admission. Contrariwise, the proportion of patients with more severe NCS-R score at baseline was higher in the MCS than UWV group. It should be emphasized that nociception relies on a wide brain network that is linked to conscious processing,17, 18 and is therefore a very important factor to consider for DOC patients. Indeed, some recent studies have shown that nociceptive response can be considered a possible marker of level of consciousness.19, 20
As regards the relationship between age and spasticity, a recent study reported that moderate-to-severe spasticity is more likely to occur in younger people after stroke.21 Older age is a potential contributing factor to deterioration of the stretch reflex.22 The possible mechanisms suggested as causes for the age-related decline of stretch reflex are changes in the contractile properties of the muscle (e.g. a progressive decrease in the number of muscle fibers)23 and age-dependent atrophy and degeneration of muscle spindle afferent.
Finally, as regards the neck malalignment due to spasticity, we detected no association between postural assessment of cervical spine and severity of DOC or spasticity. Indeed, spasticity in patients with DOC is characterized by several and atypical clinical patterns.5 These different patterns of spasticity are presumed to be due to the widespread nature of brain lesions6 and different disease processes, which vary greatly between patients. Hence, it comes as no surprise that there is no characteristic cervical alignment due to spasticity in patients with DOC.
Limitations of the study
Our study has some limitations, which should be pointed out. The study design does not allow us to draw any conclusion about the mechanisms involved in the relationship between spasticity of neck muscles and functional/neurological outcome after ABI. Finally, the study was not designed to evaluate treatment effects (pharmacological or physical therapy) in this patient population, nor regarding the evolution of spasticity or consciousness. Due to this limitation, we cannot exclude that a possible pharmacological effect could modify the clinical picture and interfere with its natural evolution. Despite these limitations, our data add important insights on this topic, describing for the first time a specific pattern of neck muscle spasticity in patients with DOC and its influence on the outcome of an intensive rehabilitation program.
Conclusions
Our results suggest that neck muscle spasticity develops frequently in patients diagnosed with a DOC, and that patients after TBI have more severe spasticity. Younger age is predictive of a higher level of spasticity in MCS. On the other hand, in UWV patients, more severe spasticity of cervical spine muscles may represent an early indicator of a worse neurological and functional outcome at the end of the 6-month inpatient rehabilitation program.
Footnotes
Conflicts of interest: The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.
Funding: This work was partially supported by the Italian Ministry of Health under the grant “Ricerca Corrente” funding schemes to the IRCCS.
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Data Availability Statement
The data associated with the paper are not publicly available but are available from the corresponding author on reasonable request.