Intrathecal baclofen: effects on spasticity, pain, and consciousness in disorders of consciousness and locked-in syndrome.

Disorders of consciousness (DOCs) include coma, vegetative state (VS), and minimally conscious state (MCS). Coma is characterized by impaired wakefulness and consciousness, while VS and MCS are defined by lacking or discontinuous consciousness despite recovered wakefulness. Conversely, locked-in syndrome (LIS) is characterized by quadriplegia and lower cranial nerve paralysis with preserved consciousness. Intrathecal baclofen (ITB) is a useful treatment to improve spasticity both in patients with DOCs and LIS. Moreover, it supports the recovery of consciousness in some patients with VS or MCS. The precise mechanism underlying this recovery has not yet been elucidated. It has been hypothesized that ITB may act by reducing the overload of dysfunctional sensory stimuli reaching the injured brain or by stabilizing the imbalanced circadian rhythms. Although the current indication of ITB is the management of severe spasticity, its potential use in speeding the recovery of consciousness merits further investigation.

EEG-detected olfactory imagery to reveal covert consciousness in minimally conscious state.

PRIMARY OBJECTIVE: To reveal covert abilities in a minimally conscious state (MCS) through an innovative activation paradigm based on olfactory imagery. RESEARCH DESIGN: Case study. METHODS AND PROCEDURES: A patient in MCS was asked to 'imagine an unpleasant odour' or to 'relax' in response to the appearance on a screen of a downward pointing arrow or a cross, respectively. Electrophysiological responses to stimuli were investigated by means of an 8-channel EEG equipment and analysed using a specific threshold algorithm. The protocol was repeated for 10 sessions separated from each other by 2 weeks. Accuracy, defined as the number of successes with respect to the total number of trials, was used to evaluate the number of times in which the classification strategy was successful. MAIN OUTCOMES AND RESULTS: Analyses of accuracy showed that the patient was able to activate and to relax himself purposefully and that he optimized his performances with the number of sessions, probably as a result of training-related improvements. CONCLUSIONS: Subtle signs of consciousness may be under-estimated and need to be revealed through specific activation tasks. This paradigm may be useful to detect covert signs of consciousness, especially when patients are precluded from carrying out more complex cognitive tasks.

Bilateral remote cerebellar haemorrhage after spinal surgery: a case study and review of the literature.

BACKGROUND: Remote cerebellar haemorrhage is a rare and unpredictable complication after intracranial and spinal surgery, although less frequently found in the latter. The physiopathology of this phenomenon has not been definitely explained. OBJECTIVES: To describe and discuss the potential implications and pathomechanism of a bilateral remote cerebellar haemorrhage case after spinal surgery and review the literature related to this rare phenomenon. CASE REPORT: A 75 year-old man developed bilateral remote cerebellar haemorrhage after a lumbar laminectomy. Brain CT and MRI examinations showed chronic bilateral remote cerebellar haemorrhage, right haemoventricle and bilateral supratentorial subarachnoid haemorrhage. Subsequently, the patient underwent rehabilitation therapy with improvement of symptoms. CONCLUSION: When large cerebrospinal fluid loss is observed during spinal surgery, brain imaging study should be carried out. The pathogenetic hypothesis of microcirculation vessels tearing, the role of previous spinal surgery and of cerebellar atrophy should be considered and validated with further investigation.

Corticomotor facilitation in vegetative state: results of a pilot study.

OBJECTIVE: To investigate whether corticomotor facilitation induced by transcranial magnetic stimulation (TMS-CF) could evoke a simple purposeful motor behavior in patients with a diagnosis of vegetative state. DESIGN: Cross-sectional survey. SETTING: Post-coma and rehabilitation care unit. PARTICIPANTS: Patients (N=6) with a diagnosis of vegetative state. INTERVENTIONS: A cascade of consecutive motor-evoked potentials (MEPs) was elicited under 3 different conditions: in the first condition, patients were at rest (Rest); in the second, they were asked to open and close the right hand (Execution); in the third, the examiner modeled a movement of abduction of the thumb in front of the patient who was encouraged in advance to imitate the action (Observation to Imitate). MAIN OUTCOME MEASURES: Changes in MEP values from the abductor pollicis brevis muscle and improvement in scores on the Coma Recovery Scale-Revised. RESULTS: TMS-CF alone or combined with verbal instructions did not yield any change; only the combination with imitation caused changes in MEPs (shorter latency and increased amplitude) associated with behavioral improvement in 4 patients. CONCLUSIONS: Encouraging observation to imitate may favor the transformation of some perceived actions into motor images and performances, probably depending on the activation of mirror motor neurons. In our opinion, combining visual input with TMS-CF might have reinforced the coupling between movement planning and execution, promoting the recovery of elementary motor activities in some patients. The proposed protocol may contribute to unmasking signs of preserved consciousness in patients with latent capacities for recovery.

The perception of pain and its management in disorders of consciousness.

One of the most controversial issues in the management of patients in a vegetative state or a minimally conscious state concerns their hypothetical capacity to continue to experience pain despite an apparent absence of self- and environmental awareness. Recent functional neuroimaging studies have shown a greater perception of pain in patients in minimally conscious state compared with patients in vegetative state, suggesting the possible involvement of preserved cognitive mechanisms in the process of pain modulation in the former. In addition, a subgroup of patients might continue to experience some elementary emotional and affective feelings, as suggested by the reported activation of specific cerebral areas in response to situations, which commonly generate empathy. However, the available evidence is not sufficient to draw conclusions about the presence or absence of pain experience in patients with disorders of consciousness. Future studies should contribute to a better understanding of which central neural pathways are involved in the perception and modulation of pain in healthy subjects and in patients with severe brain injuries. Such studies should thus also improve our know-how about pain management in this particularly challenging group of patients.

Whole-brain voxel-based morphometry study of children and adolescents with Down syndrome.

In order to investigate alterations in brain morphology and a possible temporal pattern of neuroanatomical abnormalities in the gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) of young patients with Down syndrome (DS), high-resolution magnetic resonance imaging (MRI) voxel-based morphometry (VBM) was performed on 21 children and adolescents with this chromosomal aberration and 27 age-matched participants as controls. In comparison with control subjects, children and adolescents with DS showed not only an overall smaller whole-brain volume, but also volume reductions of the GM in the cerebellum, frontal lobes, frontal region of the limbic lobe, parahippocampal gyri and hippocampi and of the WM in the cerebellum, frontal and parietal lobes, sub-lobar regions and brainstem. By contrast, volume preservation was observed in the GM of the parietal lobes, temporal lobe and sub-lobar regions and in the WM of the temporal lobe and temporal regions of the limbic lobe. A lower volume of CSF was also detected in the frontal lobes. This study is the first to use the high-resolution MRI VBM method to describe a whole-brain pattern of abnormalities in young DS patients falling within such a narrow age range and it provides new information on the neuroanatomically specific regional changes that occur during development in these patients.

Impaired conscious recognition of negative facial expressions in patients with locked-in syndrome.

The involvement of facial mimicry in different aspects of human emotional processing is widely debated. However, little is known about relationships between voluntary activation of facial musculature and conscious recognition of facial expressions. To address this issue, we assessed severely motor-disabled patients with complete paralysis of voluntary facial movements due to lesions of the ventral pons [locked-in syndrome (LIS)]. Patients were required to recognize others' facial expressions and to rate their own emotional responses to presentation of affective scenes. LIS patients were selectively impaired in recognition of negative facial expressions, thus demonstrating that the voluntary activation of mimicry represents a high-level simulation mechanism crucially involved in explicit attribution of emotions.

Recognition and mental manipulation of body parts dissociate in locked-in syndrome.

Several lines of evidence demonstrate that the motor system is involved in motor simulation of actions, but some uncertainty exists about the consequences of lesions of descending motor pathways on mental imagery tasks. Moreover, recent findings suggest that the motor system could also have a role in recognition of body parts. To address these issues in the present study we assessed patients with a complete damage of descending motor pathways (locked-in syndrome, LIS) on the hand laterality task, requiring subjects to decide whether a hand stimulus in a given spatial orientation represents a left or a right hand. LIS patients were less accurate than healthy controls in judging hand laterality; more importantly, LIS patients' performance was modulated by spatial orientation of hand stimuli whereas it was not affected by biomechanical constraints. These findings demonstrate a dissociation between spared hand recognition and impaired access to action simulation processes in LIS patients.

In uno omnia: anti-thrombotic agents in challenging comorbidities.

BACKGROUND: Recurrent bleedings of cavernous malformations are quite frequent and frightful: survival is especially at risk in patients with brainstem cavernous malformations who cannot benefit from neurosurgical treatments. Nevertheless, pragmatic recommendations to prevent recurrent bleedings are still lacking, raising some questions on the daily clinical management of the above patients. METHODS: This study reports the case of a 59 year-old woman presenting with past recurrent bleedings from a brainstem cavernous malformation and with indication to start an anti-thrombotic treatment as a consequence of a developing coronary heart disease. Surprisingly, any suggestion about the usage of otherwise indicated anti-platelet treatment and anti-coagulation in patients with cavernous malformations was found in the literature. RESULTS: The authors faced a therapeutical dilemma with this patient, whose survival would be really at risk because of a 'time bomb in her brainstem'. CONCLUSIONS: This experience confirms the lack of clear pragmatic recommendations in the clinical management of these patients, whose treatment still represents a medical challenge.

Complexity loss in physiological time series of patients in a vegetative state.

Consciousness has not yet been satisfactorily defined because of its puzzling nature which involve the perception of the environment (perceptual awareness) and of the self (self-awareness). Current available methods fail in establishing prognosis in patients with vegetative state (VS): to our mind, this failure stems from the heterogeneous localization of brain damages causing VS and from available approaches tending to investigate self-awareness separately from perceptual awareness, whereas consciousness should be explored as a single and indivisible whole. Moving from the assumption that consciousness depends on the normal activity of wide neural networks, that may be regarded as complex systems whose outputs show a nonlinear behaviour, we propose a nonlinear approach applied to electroencephalographic (EEG) signal, aimed at exploring residual neural networks complexity in patients with VS. For this objective the EEG recording of 10 patients previously admitted to our department were retrospectively analyzed and compared with those of ten matched healthy control subjects. Approximate Entropy (ApEn) was calculated from the average values of time series with fixed input variables. Mean ApEn values were lower in patients than in controls (t18 18 = 12.3, p < 0.001). ApEn is able to discriminate patients from controls thus supporting the hypothesis about a decreased neural networks complexity in VS.

Action observation improves motor imagery: specific interactions between simulative processes.

In the present study, we demonstrated that observation of hand rotation had specific facilitation effects on a classical motor imagery task, the hand-laterality judgement. In Experiment 1, we found that action observation improved subjects' performance on the hand laterality but not on the letter rotation task (stimulus specificity). In Experiment 2, we demonstrated that this facilitation was not due to mere observation of a moving hand, because it was triggered by observation of manual rotation but not of manual prehension movements (motion specificity). In Experiment 3, this stimulus- and motion-specific effect was found to be right hand-specific, compatible with left-hemispheric specialization in motor imagery but not in action observation. These data provided direct support to the idea that different simulation states, such as action observation and motor imagery, share some common mechanisms but also show specific functional differences.

Intrathecal baclofen in patients with persistent vegetative state: 2 hypotheses.

Sporadic cases of recovery from persistent vegetative state (PVS) after administration of intrathecal baclofen (ITB) have been reported without giving any possible explanation for its paradoxical effect. We summarize our recent findings on 5 patients with PVS treated with ITB and make some speculations on the mechanisms responsible for the observed clinical improvement. The patients developed spasticity and were judged eligible for ITB therapy. Two weeks after pump implantation, patients began to show a clinical improvement that, at the end of the 6 months' follow-up, was stable in all but 1 patient, ranging from a mere increased alertness to a full recovery of consciousness, as revealed by changes of the Coma Recovery Scale-Revised (CRS-R) score. Our findings suggest that ITB might favor a variable degree of clinical improvement. A proposal for a pharmacodynamic explanation of this effect has not been formally put forward. We hypothesize 2 possible mechanisms: first, a modulation confined to spinal cord segmental activities and to neuronal centripetal outputs reaching the cortex; and second, a modulation of sleep-wake cycles that, although present, may be dysregulated and interfere with alertness and awareness. Although our research is confined to a few subjects, it provides follow-up information by means of the CRS-R that is a validated standardized neurobehavioral instrument expressly designed for use in patients with PVS. Our observations indicate that further systematic investigation of the mechanisms and the putative clinical applications of ITB should be undertaken.

Cognitive and Emotional Empathy in Individuals with Spinal Cord Injury.

BACKGROUND: Empathy has been conceptualized as comprising a cognitive and an emotional component, the latter being further divided into direct and indirect aspects, which refer, respectively, to the explicit evaluation of the observer's feelings while attending someone in an emotional situation and to the physiological response of the observer. Empathy has been previously investigated in several neurological disorders. OBJECTIVE: This study is aimed at investigating empathy in patients with spinal cord injury (SCI). We hypothesize that, due to deafferentation following their injury, SCI patients will display difficulty in the processing of emotional stimuli and blunted empathic responses as compared to healthy controls. MATERIALS AND METHODS: 20 patients with spinal cord injury (SCI) (12 males and 8 females, mean age = 50.9, standard deviation (SD) = 16.1 years; mean education = 10.9, SD = 4.1 years) were included in the study and compared to 20 matched healthy subjects. Participants were investigated using the State-Trait Anxiety Inventory (Form Y) (STAI-Y), the Beck Depression Scale, and the Toronto Alexithymia Scale. Moreover, participants were further evaluated by means of the Interpersonal Reactivity Index (IRI), which explores both cognitive and emotional aspects of empathy, and through an experimental protocol based on the use of a modified version of the computerized Multifaceted Empathy Test (MET) to evaluate emotional (direct and indirect) empathy and the ability to judge the valence of complex emotional scenes. RESULTS: As compared to healthy controls, SCI patients reported higher scores on the Perspective-Taking subscale of the IRI, while, on the modified MET, they were less accurate in identifying the valence of neutral scenes, notwithstanding their spared direct and indirect emotional empathy ability. Furthermore, we found a significant negative correlation between the time interval since injury and the direct emotional empathy scores on the positive images, as well as a negative correlation with the indirect emotional empathy scores on both positive and neutral images, indicating a blunting of the empathic responses as time elapses. CONCLUSION: Results suggest that SCI patients, when analyzing the meaning of emotional stimuli, tend to rely on a cognitive empathy strategy rather than on emotion simulation.

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.

Selective motor imagery defect in patients with locked-in syndrome.

Recent studies indicate that motor imagery is subserved by activation of motor information. However, at present it is not clear whether the sparing of motor efferent pathways is necessary to perform a motor imagery task. To clarify this issue, we required patients with a selective, severe de-efferentation (locked-in syndrome, LIS) to mentally manipulate hands and three-dimensional objects. Compared with normal controls, LIS patients showed a profound impairment on a modified version of the hand-laterality task and a normal performance on mental rotation of abstract items. Moreover, LIS patients did not present visuomotor compatibility effects between anatomical side of hands and spatial location of stimuli on the computer screen. Such findings confirmed that the motor system is involved in mental simulation of action but not in mental manipulation of visual images. To explain LIS patients' inability in manipulating hand representations, we suggested that the pontine lesion, both determined a complete de-efferentation, and affected a component of the motor system, which is crucial for mental representation of body parts, probably the neural connections between parietal lobes and cerebellum.

Management of pathologic laughter and crying in patients with locked-in syndrome: a report of 4 cases.

Emotional lability and pathologic laughter and crying (PLC) have been frequently mentioned in patients with locked-in syndrome (LIS) without giving any detail about the clinical characteristics and possible consequences in terms of symptoms burden, functional impact, and recovery. In the present report, we describe our approach and management of 4 patients with LIS and PLC. PLC caused discomfort to the patients and hindered the different components of their rehabilitation program, limiting communication, the execution of swallowing testing and training, and the improvement of any residual motor function. PLC was unrelated to depression, did not ameliorate after pharmacologic treatment, and improved with cognitive-behavior treatment. Our findings suggest that, in LIS patients, laughter and crying alterations do not represent symptoms of a mood disorder but are the result of the same pontine lesion that causes LIS. In relation to the complex pathway regulating laughter and crying, we hypothesized that, in patients with LIS, PLC may be the result of a direct damage to the pontine center or of an alteration in the ponto-cerebellar pathway linking emotional behavior to contextual information. Presence of PLC in patients with LIS severely affects their intelligent adaptation to the environment. Direct explanation to the patients of the origin of PLC may be helpful as a cognitive-behavior treatment, with resulting benefits to the entire rehabilitation program.

Mismatch of neurophysiological findings in partial recovery of consciousness: a case report.

AIM: Electroencephalography (EEG) and somatosensory potentials (SEP) are regarded as useful tools for exploring residual brain activity and providing information for recovery in patients with anoxic encephalopaty. However, the diagnoses of vegetative and minimally conscious states can only be made by means of repeated specific neurological examinations. In this respect, this study describes the case of a patient with mismatch of neurophysiological findings despite partial recovery to a minimally conscious state. CASE REPORT: A 52-year-old man was admitted to the Post-Coma Intensive and Rehabilitation Care Unit with a diagnosis of anoxic encephalopathy. EEG, according to Hockaday, was severely abnormal (Grade IVa). SEP showed bilateral loss of all cortical components. Four weeks after admission the Coma Recovery Scale Revised (CRS-R) score moved from 7/23 to 13/23. CONCLUSIONS: This patient persistently showed a mismatch of neurophysiological findings which did not anticipate the slight but discriminating improvement ascertained through the neurological examination. This observation confirms that electrophysiological evaluations can only be regarded as ancillary tools since level of consciousness may be reliably evaluated only by means of repeated specific neurological assessments. As this case-report suggests, neurophysiological findings may turn out to be inconclusive and misleading in relation to the assessment of consciousness and may lead to an underestimate of minimal signs of recovery across the grey-zone from the vegetative to the minimally conscious state.