Motor behavior unmasks residual cognition in disorders of consciousness.

Disorders of consciousness (DOC) are a common consequence of severe brain injuries, and clinical evaluation is critical to provide a correct diagnosis and prognosis. The revised Motor Behavior Tool (MBT-r) is a clinical complementary tool aiming to identify subtle motor behaviors that might reflect residual cognition in DOC. In this prospective study including 30 DOC patients in the early stage after brain injury, we show that the revised MBT-r has an excellent inter-rater agreement and has the ability to identify a subgroup of patients, underestimated by the Coma Recovery Scale-Revised, showing residual cognition and a subsequent recovery of consciousness. ANN NEUROL 2019;85:443-447.

Cerebellar syndrome after occipital nerve block: A case report.

BACKGROUND: Occipital nerve blocks are commonly used in the treatment of different types of refractory headaches. The procedure is considered safe, and serious complications have rarely been described. CASE PRESENTATION: We report a serious complication of occipital nerve blockade secondary to the penetration of local anesthetic and non-steroidal anti-inflammatory drugs into the posterior fossa in a patient affected by type I Arnold Chiari malformation. CONCLUSIONS: This case reminds that a proper injection technique is mandatory to avoid potentially severe complications when performing occipital nerve blocks.

A Focus on Subtle Signs and Motor Behavior to Unveil Awareness in Unresponsive Brain-Impaired Patients: The Importance of Being Clinical.

Brain-injured patients in a state of cognitive motor dissociation (CMD) exhibit a lack of command following using conventional neurobehavioral examination tools but a high level of awareness and language processing when assessed using advanced imaging and electrophysiology techniques. Because of their behavioral unresponsiveness, patients with CMD may seem clinically indistinguishable from those with a true disorder of consciousness that affects awareness on a substantial level (coma, vegetative state/unresponsive wakefulness state, or minimally conscious state minus). Yet, by expanding the range of motor testing across limb, facial, and ocular motricity, we may detect subtle, purposeful movements even in the subset of patients classified as vegetative state/unresponsive wakefulness state. We propose the term of clinical CMD to describe patients showing these slight but determined motor responses and exhibiting a characteristic akinetic motor behavior as opposed to a pyramidal motor system behavior. These patients may harbor hidden cognitive capabilities and significant potential for a good long-term outcome. Indeed, we envision CMD as ranging from complete (no motor response) to partial (subtle clinical motor response) forms, falling within a spectrum of progressively better motor output in patients with considerable cognitive capabilities. In addition to providing a decisional flowchart, we present this novel approach to classification as a graphical model that illustrates the range of clinical manifestations and recovery trajectories fundamentally differentiating true disorders of consciousness from the spectrum of CMD.

Structural connectivity in recovery after coma: Connectome atlas approach.

AIM: Pathological states of recovery after coma as a result of a severe brain injury are marked with changes in structural connectivity of the brain. This study aimed to identify a topological correlation between white matter integrity and the level of functional and cognitive impairment in patients recovering after coma. METHODS: Structural connectomes were computed based on fractional anisotropy maps from 40 patients using a probabilistic human connectome atlas. We used a network based statistics approach to identify potential brain networks associated with a more favorable outcome, assessed with clinical neurobehavioral scores at the patient's discharge from the acute neurorehabilitation unit. RESULTS: We identified a subnetwork whose strength of connectivity correlated with a more favorable outcome as measured with the Disability Rating Scale (network based statistics: t >3.5, P =.010). The subnetwork predominated in the left hemisphere and included the thalamic nuclei, putamen, precentral and postcentral gyri, and medial parietal regions. Spearman correlation between the mean fractional anisotropy value of the subnetwork and the score was ρ = -0.60 (P <.0001). A less extensive overlapping subnetwork correlated with the Coma Recovery Scale Revised score, consisting mostly of the left hemisphere connectivity between the thalamic nuclei and pre- and post-central gyri (network based statistics: t >3.5, P =.033; Spearman's ρ = 0.58, P <.0001). CONCLUSION: The present findings suggest an important role of structural connectivity between the thalamus, putamen and somatomotor cortex in the recovery from coma as evaluated with neurobehavioral scores. These structures are part of the motor circuit involved in the generation and modulation of voluntary movement, as well as the forebrain mesocircuit supposedly underlying the maintenance of consciousness. As behavioural assessment of consciousness depends heavily on the signs of voluntary motor behaviour, further work will elucidate whether the identified subnetwork reflects the structural architecture underlying the recovery of consciousness or rather the ability to communicate its content.

Case Report: Behavioral Unresponsiveness in Acute COVID-19 Patients: The Utility of the Motor Behavior Tool-Revised and 18F-FDG PET/CT.

Along with the propagation of COVID-19, emerging evidence reveals significant neurological manifestations in severely infected COVID-19 patients. Among these patients admitted to the intensive care unit (ICU), behavioral unresponsiveness may occur frequently, yet, there are still only a few cases reported and with rare descriptions of their motor behavior after pathological awakening. Several hypotheses regarding central lesions in these patients are conceivable. Here, we describe two acute SARS-CoV-2- infected patients who developed neurological symptoms evoking the condition of clinical cognitive motor dissociation (CMD). This diagnosis could be confirmed first by clinical observation of a dissociation between preserved cognitive abilities and lack of initial motor interaction and second, by performing 18F- FDG PET imaging. Accurate diagnosis led to an appropriate neuro-rehabilitation regimen with long-term neuro-rehabilitation leading to an improved outcome for both patients.

Discriminating cognitive motor dissociation from disorders of consciousness using structural MRI.

An accurate evaluation and detection of awareness after a severe brain injury is crucial to a patient's diagnosis, therapy, and end-of-life decisions. Misdiagnosis is frequent as behavior-based assessments often overlook subtle signs of consciousness. This study aimed to identify brain MRI characteristics of patients with residual consciousness after a severe brain injury and to develop a simple MRI-based scoring system according to the findings. We retrieved data from 128 patients and split them into a development or validation set. Structural brain MRIs were qualitatively assessed for lesions in 18 brain regions. We used logistic regression and support vector machine algorithms to first identify the most relevant brain regions predicting a patient's outcome in the development set. We next built a diagnostic MRI-based score and estimated its optimal diagnostic cut-off point. The classifiers were then tested on the validation set and their performance compared using the receiver operating characteristic curve. Relevant brain regions predicting negative outcome highly overlapped between both classifiers and included the left mesencephalon, right basal ganglia, right thalamus, right parietal cortex, and left frontal cortex. The support vector machine classifier showed higher accuracy (0.93, 95% CI: 0.81-0.96) and specificity (0.97, 95% CI: 0.85-1) than logistic regression (accuracy: 0.87, 95% CI: 0.73 - 0.95; specificity: 0.90, 95% CI: 0.75-0.97), but equal sensitivity (0.67, 95% CI: 0.24-0.94 and 0.22-0.96, respectively) for distinguishing patients with and without residual consciousness. The novel MRI-based score assessing brain lesions in patients with disorders of consciousness accurately detects patients with residual consciousness. It could complement valuably behavioral evaluation as it is time-efficient and requires only conventional MRI.

Early discrimination of cognitive motor dissociation from disorders of consciousness: pitfalls and clues.

Bedside assessment of consciousness and awareness after a severe brain injury might be hampered by confounding clinical factors (i.e., pitfalls) interfering with the production of behavioral or motor responses to external stimuli. Despite the use of validated clinical scales, a high misdiagnosis rate is indeed observed. We retrospectively analyzed a cohort of 49 patients with severe brain injury admitted to an acute neuro-rehabilitation program. Patients' behavior was assessed using the Motor Behavior Tool and Coma Recovery Scale Revised. All patients underwent systematic assessment for pitfalls including polyneuropathy and/or myopathy and/or myelopathy, major cranial nerve palsies, non-convulsive status epilepticus, aphasia (expressive or comprehensive), cortical blindness, thalamic involvement and frontal akinetic syndrome. A high prevalence (75%) of pitfalls potentially interfering with sensory afference (polyneuropathy, myopathy, myelopathy, and sensory aphasia), motor efference (polyneuropathy, myopathy, motor aphasia, and frontal akinetic syndrome), and intrinsic brain activity (thalamic involvement and epilepsy) was found. Nonetheless, the motor behavior tool identified residual cognition (i.e. a cognitive motor dissociation condition) regardless of the presence of these pitfalls in 70% of the patients diagnosed as unresponsive using the Coma Recovery Scale Revised. On one hand, pitfalls might contribute to misdiagnosis. On the other, it could be argued that they are clues for diagnosing cognitive motor dissociation rather than true disorders of consciousness given their prominent effect on the sensory-motor input-output balance.

Recovery in cognitive motor dissociation after severe brain injury: A cohort study.

OBJECTIVE: To investigate the functional and cognitive outcomes during early intensive neurorehabilitation and to compare the recovery patterns of patients presenting with cognitive motor dissociation (CMD), disorders of consciousness (DOC) and non-DOC. METHODS: We conducted a single center observational cohort study of 141 patients with severe acquired brain injury, consecutively admitted to an acute neurorehabilitation unit. We divided patients into three groups according to initial neurobehavioral diagnosis at admission using the Coma Recovery Scale-Revised (CRS-R) and the Motor Behavior Tool (MBT): potential clinical CMD, [N = 105]; DOC [N = 19]; non-DOC [N = 17]). Functional and cognitive outcomes were assessed at admission and discharge using the Glasgow Outcome Scale, the Early Rehabilitation Barthel Index, the Disability Rating Scale, the Rancho Los Amigos Levels of Cognitive Functioning, the Functional Ambulation Classification Scale and the modified Rankin Scale. Confirmed recovery of conscious awareness was based on CRS-R criteria. RESULTS: CMD patients were significantly associated with better functional outcomes and potential for improvement than DOC. Furthermore, outcomes of CMD patients did not differ significantly from those of non-DOC. Using the CRS-R scale only; approximatively 30% of CMD patients did not recover consciousness at discharge. INTERPRETATION: Our findings support the fact that patients presenting with CMD condition constitute a separate category, with different potential for improvement and functional outcomes than patients suffering from DOC. This reinforces the need for CMD to be urgently recognized, as it may directly affect patient care, influencing life-or-death decisions.

Intensive Care Admission and Early Neuro-Rehabilitation. Lessons for COVID-19?

Coronavirus disease 2019 (COVID-19) requires admission to intensive care (ICU) for the management of acute respiratory distress syndrome in about 5% of cases. Although our understanding of COVID-19 is still incomplete, a growing body of evidence is indicating potential direct deleterious effects on the central and peripheral nervous systems. Indeed, complex and long-lasting physical, cognitive, and functional impairments have often been observed after COVID-19. Early (defined as during and immediately after ICU discharge) rehabilitative interventions are fundamental for reducing the neurological burden of a disease that already heavily affects lung function with pulmonary fibrosis as a possible long-term consequence. In addition, ameliorating neuromuscular weakness with early rehabilitation would improve the efficiency of respiratory function as respiratory muscle atrophy worsens lung capacity. This review briefly summarizes the polymorphic burden of COVID-19 and addresses possible early interventions that could minimize the neurological and systemic impact. In fact, the benefits of early multidisciplinary rehabilitation after an ICU stay have been shown to be advantageous in several clinical conditions making an early rehabilitative approach generalizable and desirable to physicians from a wide range of different specialties.

Neurosensory stimulation outdoors enhances cognition recovery in cognitive motor dissociation: A prospective crossover study.

BACKGROUND: Neurosensory stimulation is effective in enhancing the recovery process of severely brain-injured patients with disorders of consciousness. Multisensory environments are found in nature, recognized as beneficial to many medical conditions. Recent advances detected covert cognition in patients behaviorally categorized as un- or minimally responsive; a state described as cognitive motor dissociation (CMD). OBJECTIVE: To determine effectiveness of a neurosensory stimulation approach enhanced by outdoor therapy, in the early phases of recovery in patients presenting with CMD. METHODS: A prospective non-randomized crossover study was performed. A two-phase neurosensory procedure combined identical individually goal assessed indoor and outdoor protocols. All sessions were video-recorded and observations rated offline. The frequency of volitional behavior was measured using a behavioral grid. RESULTS: Fifteen patients participated in this study. The outdoor group patients had statistically significant higher number of intentional behaviors than the indoor group on seven features of the grid. Additionally, for all items assessed, total amount of behaviors in the outdoor condition where higher than those in the indoor condition. CONCLUSIONS: Although preliminary, this study provides robust evidence supporting the effectiveness and appropriateness of an outdoor neurosensory intervention in patients with covert cognition, to improve adaptive goal-oriented behavior. This may be a step towards helping to restore functional interactive communication.

A neurophysiological study of myoclonus in patients with DYT11 myoclonus-dystonia syndrome.

Mutations in the epsilon-sarcoglycan (SGCE) gene have been associated with DYT11 myoclonus-dystonia syndrome (MDS). The aim of this study was to characterize myoclonus in 9 patients with DYT11-MDS presenting with predominant myoclonus and mild dystonia by means of neurophysiological techniques. Variously severe multifocal myoclonus occurred in all of the patients, and included short (mean 89.1 +/- 13.3 milliseconds) electromyographic bursts without any electroencephalographic correlate, sometimes presenting a pseudo-rhythmic course. Massive jerks could be evoked by sudden stimuli in 5 patients, showing a "startle-like" muscle spreading and latencies consistent with a brainstem origin. Somatosensory evoked potentials and long-loop reflexes were normal, as was silent period and long-term intracortical inhibition evaluated by means of transcranial magnetic stimulation; however, short-term intracortical inhibition revealed subtle impairment, and event-related synchronization (ERS) in the beta band was delayed. Blink reflex recovery was strongly enhanced. Myoclonus in DYT11-MDS seems to be generated at subcortical level, and possibly involves basal ganglia and brainstem circuitries. Cortical impairment may depend from subcortical dysfunction, but it can also have a role in influencing the myoclonic presentation. The wide distribution of the defective SCGE in DYT11-MDS may justify the involvement of different brain areas.

Cardiac autonomic control during sleep in patients with myotonic dystrophy type 1: the effects of comorbid obstructive sleep apnea.

OBJECTIVE: Myotonic dystrophy type 1 (DM1) is a hereditary myopathy characterized by an autosomal dominant inheritance with important cardiovascular and autonomic deregulation. DM1 patients have a high prevalence of obstructive sleep apnea (OSA), but the effects of this comorbidity on cardiovascular autonomic control (CAC) are unknown. The present study aimed to investigate CAC during sleep-wake cycle in DM1 patients, taking into account the effects of OSA comorbidity. METHOD: Twenty-three patients with a diagnosis of DM1, and a control group, underwent a complete polysomnographic study (PSG). Electrocardiogram and respiration were extracted from PSG, divided according to the sleep stages, and analyzed using spectral analysis (SpA) of heart rate variability (HRV). SpA identified three components: very low frequency (VLF), low frequency (LF), a marker of sympathetic modulation, and high frequency (HF), a marker of vagal modulation. RESULTS: The results showed that in DM1 patients, the sympathovagal balance shifted towards a vagal predominance during non-rapid eye movement (NREM) sleep and a sympathetic predominance during rapid eye movement (REM) sleep. Second, this preserved cardiac autonomic modulation was not affected by the comorbidity with obstructive sleep apnea syndrome (OSAS). Third, in DM1 patients, OSAS comorbidity was associated with a reduction in HRV during the whole sleep-wake cycle. Lastly, in DM1 patients with OSA, cardiorespiratory coupling was reduced compared to controls. CONCLUSIONS: DM1 patients had preserved cardiac autonomic dynamics during NREM and REM sleep, and this phenomenon was not affected by the presence of OSA. However, the comorbidity with OSA was characterized by a reduction in total HRV, which is a marker of the ability of autonomic control to respond to stressors stimuli.

Panencephalopathic Creutzfeldt-Jakob disease with distinct pattern of prion protein deposition in a patient with D178N mutation and homozygosity for valine at codon 129 of the prion protein Gene.

Prion diseases include sporadic, acquired and genetic forms linked to mutations of the prion protein (PrP) gene (PRNP). In subjects carrying the D178N PRNP mutation, distinct phenotypes can be observed, depending on the methionine/valine codon 129 polymorphism. We present here a 53-year-old woman with D178N mutation in the PRNP gene and homozygosity for valine at codon 129. The disease started at age 47 with memory deficits, progressive cognitive impairment and ataxia. The clinical picture slowly worsened to a state of akinetic mutism in about 2 years and the disease course was 6 years. The neuropathologic examination demonstrated severe diffuse cerebral atrophy with neuronal loss, spongiosis and marked myelin loss and tissue rarefaction in the hemispheric white matter, configuring panencephalopathic Creutzfeldt-Jakob disease. PrP deposition was present in the cerebral cortex, basal ganglia and cerebellum with diffuse synaptic-type pattern of immunoreactivity and clusters of countless, small PrP deposits, particularly evident in the lower cortical layers, in the striatum and in the molecular layer of the cerebellum. Western blot analysis showed the presence of type 1 PrP(Sc) (Parchi classification). These findings underline the clear-cut distinction between the neuropathological features of Creutzfeldt-Jakob disease associated with D178N PRNP mutation and those of fatal familial insomnia.

Sleep breathing disorders in 40 Italian patients with Myotonic dystrophy type 1.

The aim of this study was to estimate the prevalence and nature of sleep breathing disorders in Myotonic dystrophy type 1 (DM1). We wanted to determine whether there is a relationship between sleep breathing disorders and clinical parameters such as pulmonary function, degree of neuromuscular impairment, daytime sleepiness, and fatigue. This will help assess the prevalence of DM1 patients requiring nocturnal ventilatory treatments. We studied a random sample of 40 unrelated patients and found that 22/40 patients had obstructive sleep apnoea. Of these 22 patients, five showed also periodic breathing and four showed sleep hypoventilation. Nine patients were put on nocturnal ventilation following clinical and instrumental evaluations. Our study reveals that obstructive sleep apnoea is very common in these patients, but cannot be predicted on the basis of clinical-neurological features and diurnal functional respiratory tests. Our data emphasize that a periodical evaluation by polysomnography should be mandatory to ascertain, and treat if necessary, the presence of obstructive sleep apnoea, periodic breathing or nocturnal hypoventilation.

Mutant prion protein expression causes motor and memory deficits and abnormal sleep patterns in a transgenic mouse model.

A familial form of Creutzfeldt-Jakob disease (CJD) is linked to the D178N/V129 prion protein (PrP) mutation. Tg(CJD) mice expressing the mouse homolog of this mutant PrP synthesize a misfolded form of the mutant protein, which is aggregated and protease resistant. These mice develop clinical and pathological features reminiscent of CJD, including motor dysfunction, memory impairment, cerebral PrP deposition, and gliosis. Tg(CJD) mice also display electroencephalographic abnormalities and severe alterations of sleep-wake patterns strikingly similar to those seen in a human patient carrying the D178N/V129 mutation. Neurons in these mice show swelling of the endoplasmic reticulum (ER) with intracellular retention of mutant PrP, suggesting that ER dysfunction could contribute to the pathology. These results establish a transgenic animal model of a genetic prion disease recapitulating cognitive, motor, and neurophysiological abnormalities of the human disorder. Tg(CJD) mice have the potential for giving greater insight into the spectrum of neuronal dysfunction in prion diseases.