Mariagrazia D'Ippolito

Increased levels of serum MAP-2 at 6-months correlate with improved outcome in survivors of severe traumatic brain injury

Objective: To evaluate microtubule-associated proteins (MAP-2), a dendritic marker of both acute damage and chronic neuronal regeneration after injury, in serum of survivors after severe TBI and examine the association with long-term outcome. Methods: Serum concentrations of MAP-2 were evaluated in 16 patients with severe TBI (Glasgow Coma Scale score [GCS] ≤ 8) 6 months post-injury and in 16 controls. Physical and cognitive outcomes were assessed, using the Glasgow Outcome Scale Extended (GOSE) and Levels of Cognitive Functioning Scale (LCFS), respectively. Results: Severe TBI patients had significantly higher serum MAP-2 concentrations than normal controls with no history of TBI (p = 0.008) at 6 months post-injury. MAP-2 levels correlated with the GOSE (r = 0.58, p = 0.02) and LCFS (r = 0.65, p = 0.007) at month 6. Significantly lower serum levels of MAP-2 were observed in patients in a vegetative state (VS) compared to non-VS patients (p < 0.05). A trend tracking the level of consciousness was observed. Conclusions: Severe TBI results in a chronic release of MAP-2 into the peripheral circulation in patients with higher levels of consciousness, suggesting that remodelling of synaptic junctions and neuroplasticity processes occur several months after injury. The data indicate MAP-2 as a potential marker for emergence to higher levels of cognitive function.

Functional locked-in syndrome as recovery phase of vegetative state

Recently, functional neuroimaging and advanced electrophysiology studies showed residual cortical processing in the absence of behavioural signs of consciousness in some non-communicative, severely brain-damaged patients. The term ‘functional locked-in syndrome’ has been proposed to describe patients with a dissociation between extreme motor dysfunction and preserved higher cortical functions identified only by functional imaging techniques [1]. Nevertheless, patients clinically diagnosed in the vegetative state who are able to perform mental imagery tasks [2] are still considered in the vegetative state with preserved islands of consciousness, not as having functional locked-in syndrome. Although patients with functional locked-in syndrome who are misdiagnosed as unaware persons are considered rare [3], the syndrome is not uncommon during recovery from a vegetative state. Indeed, locked-in syndrome may present with initial attempts to engage in eye-coded communication after a vegetative or minimally conscious state [4]. In the latter case, the low sensitivity of functional neuroimaging with mental imagery tasks may be due to concomitant cognitive deficits, which are also generally present after prolonged disorders of consciousness (DOC) in patients who have already emerged from a minimally conscious state. More recently, Cruse at al. [5] demonstrated that it is also possible to detect the hidden awareness of patients in the vegetative state using an electroencephalography (EEG) technique. The scientific community should clearly indicate that patients who are behaviourally in a vegetative state in whom residual cortical processing has been demonstrated by means of fMRI or neurophysiology are not vegetative/unresponsive/ unaware. In fact, these persons with wilful communication ability have functional locked-in syndrome, clinically misdiagnosed as a vegetative state. Although the presence of islands of residual consciousness in individuals with VS should challenge the clinical diagnosis of vegetative state, the lack of residual cortical processing should not exclude the presence of islands of consciousness. Vigilance fluctuations and severe cognitive deficits may, in fact, cover any evidence of residual cortical activation [5]. Thus, functional neuroimaging and electrophysiology can be used in doubtful cases of DOC to rule out tests for the diagnosis of vegetative state. Indeed, patients with residual cognitive functions who are able to perform complex mental imagery tasks or show intentional communication ability should be diagnosed with functional locked-in syndrome and not vegetative state with hidden consciousness.

Urologic Dysfunction and Neurologic Outcome in Coma Survivors After Severe Traumatic Brain Injury in the Postacute and Chronic Phase

OBJECTIVES To investigate voiding dysfunction and upper urinary tract status in survivors of coma resulting from traumatic brain injury (TBI), and to compare clinical and urodynamic results with neurologic and psychological features as well as functional outcomes. DESIGN Observational study focused on urologic dysfunction and neurologic outcome in coma survivors after traumatic brain injury in the postacute and chronic phase. SETTING A postcoma unit in a rehabilitation hospital. PARTICIPANTS Consecutive patients (N=57) who recovered from coma of traumatic etiology and who were admitted during a 1-year period to a postcoma unit of a rehabilitation hospital. INTERVENTIONS Patients underwent clinical urologic assessment, urodynamics with the assessment of the Schafer nomogram and the projected isovolumetric detrusor pressure to evaluate detrusor contractility, ultrasound assessment of the lower and upper urinary tract and voiding cystourethrography, routinely performed, according to the International Continence Society Standards. Neurologic variables assessed were brain injury and disability severity, and neuropsychological status. Neuroimaging identified the site of cerebral lesions. MAIN OUTCOME MEASURES Urinary symptoms, disability by means of the Glasgow Outcome Scale (GOS), and neuropsychological status by means of the Neurobehavioral Rating Scale (NBRS), and the relationships among them. RESULTS Of the 57 patients studied, 30 had overactive bladder (urge incontinence) symptoms, 28 had detrusor overactivity, and 18 had detrusor underactivity with associated pseudodyssynergia in 15 of these patients. Eleven patients had hypertrophic bladder; 3, bilateral pyelectasia; and 2, vesicoureteral reflux. Disability measured by GOS was severe in 8 patients and moderate in 27, while recovery was good in 22 patients. The mean NBRS total score indicated a mild cognitive impairment. Neuroimaging showed diffuse brain injury in all patients. Statistically significant relationships were found between urge incontinence, detrusor overactivity, and poor neurologic functional outcome, between detrusor overactivity and right hemisphere damage (P=.0001), and between impaired detrusor contractility and left hemisphere injuries (P=.0001). CONCLUSIONS Most patients who recovered from coma resulting from TBI have symptoms of overactive bladder syndrome and voiding difficulties. These urinary problems correlate with cerebral involvement and neurologic functional outcome.

O001. The Italian Consensus Conference “Chronic Pain in Neurorehabilitation” - Group 29: headache and facial pain

Headaches and other cranio-oro-facial pains are widely distributed in the general population. Unfortunately, there is very little evidence regarding the impact of these conditions in patients admitted to rehabilitation units, regardless of the disease or syndrome requiring rehabilitation. The availability of diagnostic and therapeutic guidelines, as well as the increasing number of data coming from controlled clinical trials, should be implemented in these patients to reduce the burden of pain and improve their global outcome. The Italian Society for Neurorehabiltation, in collaboration with the Italian Society of Physical Medicine and Rehabilitation, has promoted the Consensus Conference on Pain with the aim to foster attention on pain also in the rehabilitative field (http://www.doloreinneuroriabilitazione.it/). The working group has proposed the following recommendations: - Standard methods or criteria exist to evaluate head and cranio-facial pain in terms of intensity (B); - Standard methods exist to evaluate migraine in terms of disability (A); - It is important to evaluate the impact of cephalic and cranio-facial pain in neurorehabilitation (D); - Standard methods or criteria exist to diagnose head and cranio-facial pain (GL); - It is important to identify predictive factors associated with the development of cephalic and cranio-facial pain in association with a condition requiring neurorehabilitation (D); - Effective pharmacological treatment exists for primary headaches and for trigeminal neuralgia (GL); - Manual therapy is indicated in the management of migraine and tension-type headache (GL); - Manual therapy may be effective in TMD-associated pain (D); - Botulinum toxin A is effective in the treatment of idiopathic trigeminal neuralgia (B); - Botulinum toxin A is effective in the treatment of hemifacial spasm (B); - Topical capsaicin is effective in chronic neuropathic pain (B); - Evidence is needed to evaluate the impact of treating cephalic and cranio-facial pain on the outcome of patients undergoing neurorehabilitation (D). The recommendations are presently under evaluation by the Consensus Conference panel.

Effects of Osteopathic Manipulative Therapy on Pain and Mood Disorders in Patients With High-Frequency Migraine

Context The substantial functional impairment associated with migraine has both physical and emotional ramifications. Mood disorders are often comorbid in patients with migraine and are known to adversely affect migraine activity. Objectives To explore the effects of osteopathic manipulative therapy (OMTh; manipulative care provided by foreign-trained osteopaths) on pain and mood disorders in patients with high-frequency migraine. Methods Retrospective review of the medical records of patients with high-frequency migraine who were treated with OMTh at the Headache Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia from 2011 to 2015. Clinical assessments were made using the Headache Disability Inventory (HDI), the Headache Impact Test (HIT-6), the Hamilton Depression Rating Scale (HDRS), and the State-Trait Anxiety Inventory (STAI) forms X-1 and X-2. Results Medical records of 11 patients (6 women; mean age, 47.5 [7.8] years) with a diagnosis of high-frequency migraine who participated in an OMTh program met the inclusion criteria and were included in the study. When the questionnaire scores obtained at the first visit (T0) and after 4 OMTh sessions (T1) were compared, significant improvement in scores were observed on STAI X-2 (T0: 43.18 [2.47]; T1: 39.45 [2.52]; P<.05), HIT-6 (T0: 63 [2.20]; T1: 56.27 [2.24]; P<.05), and HDI (T0: 58.72 [6.75]; T1: 45.09 [7.01]; P<.05). Conclusion This preliminary study revealed that patients with high-frequency migraine and comorbid mood disorders showed significant improvement after four 45-minute OMTh sessions. Further investigation into the effects of OMTh on pain and mood disorders in patients with high-frequency migraine is needed.

Care pathways models and clinical outcomes in Disorders of consciousness

Patients with Disorders of consciousness, are persons with extremely low functioning levels and represent a challenge for health care systems due to their high needs of facilitating environmental factors. Despite a common Italian health care pathway for these patients, no studies have analyzed information on how each region have implemented it in its welfare system correlating data with patients’ clinical outcomes.