Neck muscle spasticity in patients with disorder of consciousness: a pilot study.

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.

The Comorbidities Coma Scale (CoCoS): Psychometric Properties and Clinical Usefulness in Patients With Disorders of Consciousness.

Although comorbidities have a well-known impact on the functional recovery of patients with disorders of consciousness, including coma, vegetative state (VS), and minimally conscious state (MCS), a specific tool for their assessment in this challenging group of patients is lacking. For this aim, a multistep process was used to develop and validate the Comorbidities Coma Scale (CoCoS) in a sample of 162 patients with a diagnosis of coma, VS or MCS admitted to four Acute Inpatient Rehabilitation Units. To establish the psychometric properties of the scale, content validity, and internal consistency were investigated through Exploratory Factor Analysis in the whole sample (n = 162). Interrater reliability, assessed by the weighted Cohen's kappa (Kw), and concurrent validity of the scale as compared to the Greenfield Scale, assessed by ρ Spearman's correlation coefficient, were investigated in a subsample of patients (n = 52) within two of the above units. Our findings provided evidence of a good content validity of the scale, with the identification of a 12-factor structure representing the different comorbid dimensions of the target population. Inter-rater reliability was excellent in both the rehabilitation units where the assessment was made [Kw 0.98 (95% CI 0.96-0.99)]. CoCoS total scores correlated significantly with total scores of the Greenfield Scale (ρ = 0.932, 95% CI 0.89-0.96; P < 0.0001) indicating that CoCoS has concurrent validity while being more informative about the specific pattern of comorbidities of these challenging patients. The CoCos is a new tool which standardizes the approach to assessment of comorbid conditions and reliably identifies the category and severity of each comorbidity detected. It may be used for both clinical and research applications.

Contribution of Interoceptive Information to Emotional Processing: Evidence from Individuals with Spinal Cord Injury.

There is much evidence to suggest that recognizing and sharing emotions with others require a first-hand experience of those emotions in our own body which, in turn, depends on the adequate perception of our own internal state (interoception) through preserved sensory pathways. Here we explored the contribution of interoception to first-hand emotional experiences and to the recognition of others' emotions. For this aim, 10 individuals with sensory deafferentation as a consequence of high spinal cord injury (SCI; five males and five females; mean age, 48 ± 14.8 years) and 20 healthy subjects matched for age, sex, and education were included in the study. Recognition of facial expressions and judgment of emotionally evocative scenes were investigated in both groups using the Ekman and Friesen set of Pictures of Facial Affect and the International Affective Picture System. A two-way mixed analysis of variance and post hoc comparisons were used to test differences among emotions and groups. Compared with healthy subjects, individuals with SCI, when asked to judge emotionally evocative scenes, had difficulties in judging their own emotional response to complex scenes eliciting fear and anger, while they were able to recognize the same emotions when conveyed by facial expressions. Our findings endorse a simulative view of emotional processing according to which the proper perception of our own internal state (interoception), through preserved sensory pathways, is crucial for first-hand experiences of the more primordial emotions, such as fear and anger.

Comorbidities: a key issue in patients with disorders of consciousness.

The aim of this study was to identify the impact of comorbidities on outcomes of patients with vegetative state (VS) or minimally conscious state (MCS). All patients in VS or MCS consecutively admitted to two postacute care units within a 1-year period were evaluated at baseline and at 6 months through the Coma Recovery Scale-Revised Version and the Disability Rating Scale (DRS). Comorbidities were also recorded for each patient along the same period. Six-month outcomes included death, full recovery of consciousness, and functional improvement. One hundred and thirty-nine patients (88 male and 51 female; median age, 59 years) were included. Ninety-seven patients were in VS (70%) and 42 in MCS (30%). At 6 months, 33 patients were dead (24%), 39 had a full recovery of consciousness (28%), and 67 remained in VS or MCS (48%). According to DRS scores, 40% of patients (n=55) showed a functional improvement in the level of disability. One hundred and thirty patients (94%) showed at least one comorbidity. Severity of comorbidities (hazard ratio [HR]=2.8; 95% confidence interval [CI], 1.71-4.68; p<0.001) and the presence of ischemic or organic heart diseases (HR=2.6; 95% CI, 1.21-5.43; p=0.014) were the strongest predictors of death, together with increasing age (HR=1.0; 95% CI, 1.0-1.06; p=0.033). Respiratory diseases and arrhythmias without organic heart diseases were negative predictors of full recovery of consciousness (odds ratio [OR]=0.3; 95% CI, 0.12-0.7; p=0.006; OR=0.2; 95% CI, 0.07-0.43; p<0.001) and functional improvement (OR=0.4; 95% CI, 0.15-0.85, p=0.020; OR=0.2; 95% CI, 0.08-0.45; p<0.001). Our data show that comorbidities are common in these patients and some of them influence recovery of consciousness and outcomes.

Benefit of doxycycline treatment on articular disability caused by dialysis related amyloidosis.

Abstract Doxycycline inhibits amyloid formation in vitro and its therapeutic efficacy is under evaluation in clinical trials for different protein conformational diseases, including prion diseases, Alzheimer's disease and transthyretin amyloidosis. In patients on chronic hemodialysis, a persistently high concentration of ß2-microglobulin causes a form of amyloidosis (dialysis-related amyloidosis, DRA) localized in bones and ligaments. Since doxycycline inhibits ß2-microglobulin fibrillogenesis in vitro and accumulates in bones, DRA represents an ideal form of amyloidosis where doxycycline may reach a therapeutic concentration at the site of amyloid deposition. Three patients on long-term dialysis with severe articular impairment and uncontrollable pain due to DRA were treated with 100 mg of doxycycline daily. Pharmacokinetics and safety of treatment were conducted. Plasmatic levels of the drug reached a plateau after one week (1.1-2.3 µg/ml). Treatment was well tolerated in two patients for a year, while one was suspended after 5 months due to mild esophagitis. Treatment was associated with a significant reduction in articular pain and with a significant and measurable improvement in passive and active movements in all cases, despite the persistence of unchanged amyloid deposits measured by magnetic resonance imaging.

Validation of the Italian version of the Coma Recovery Scale-Revised (CRS-R).

PRIMARY OBJECTIVE: To validate the Italian version of the Coma Recovery Scale-Revised (CRS-R). METHODS: Two observers applied the Italian version of the CRS-R to selected patients. On day 1, observer A and B independently scored each patient; the comparison of their observations was used to evaluate inter-observer agreement. On day 2, observer A completed a second evaluation and the comparison of this observation with that obtained on day 1 by the same observer was used to evaluate test-re-test agreement. For each evaluation, also diagnostic impression (vegetative state/minimally conscious state) was reported. RESULTS: Thirty-eight patients were evaluated (mean age ± SD, 58.9 ± 13.8 years). Inter-observer (ρ = 0.81; p < 0.001) as well as test-re-test agreement (ρ = 0.97; p < 0.001) for the total score was high. Inter-observer agreement was excellent for the communication sub-scale, good for the auditory, visual and motor sub-scales and moderate for the oromotor/verbal and arousal sub-scales. Test-re-test agreement was excellent for the visual, motor, oromotor/verbal and communication sub-scales, good for the auditory sub-scale and moderate for the arousal sub-scale. When considering the diagnostic impression, inter-observer agreement was good (κ = 0.75; p < 0.001) and test-re-test agreement was excellent (κ = 0.92; p < 0.001). CONCLUSIONS: The Italian version of the CRS-R can be administered reliably and can be also employed to discriminate patients in vegetative and in minimally conscious state.