Role of neurorehabilitation in the recovery of bilateral thalamic stroke related to the artery of Percheron anatomical variant.

Bilateral thalamic stroke is a rare condition, mostly related to the presence of the artery of Percheron (AoP) variant. The clinical presentation of AoP-related strokes is remarkably heterogeneous and often includes cognitive and behavioural alterations. Our report describes the clinical course of an AoP-related bilateral thalamic stroke and highlights the pivotal role of a tailored rehabilitation programme plays in enhancing recovery. A man in his 40s was admitted to the neurology ward due to the abrupt onset of mental status alterations and weakness in his left limbs. The first brain CT scan and subsequent MRI exam revealed a bilateral thalamic stroke and the presence of an AoP anatomical variant. After the first critical phase, the patient's condition became stable, but he still suffered from severe attention, memory and speech deficits. The patient was then transferred to the rehabilitation unit and was subjected to a tailored neurorehabilitation programme that allowed a complete recovery of the symptoms. Neurorehabilitation plays a pivotal role in the patient's recovery and should always be pursued to minimise the residual deficits and, most importantly, to prevent permanent cognitive deficits.

Robotic rehabilitation for end-effector device and botulinum toxin in upper limb rehabilitation in chronic post-stroke patients: an integrated rehabilitative approach.

BACKGROUND: Determine the effects of an integrated rehabilitation protocol, including botulinum toxin and conventional rehabilitation exercise plus end-effector (EE) robotic training for functional recovery of the upper limb (UL) compared to training with the robot alone in post-chronic stroke patients with mild to severe spasticity, compared to training with the robot alone. METHODS: In this prospective, observational case-control study, stroke patients were allocated into 2 groups: robot group (RG, patients who underwent robotic treatment with EE) and robot-toxin group (RTG, patients who in addition have carried out the injection of botulinum toxin for UL recovery). All patients were assessed by Fugl-Meyer Assessment (FMA), Motricity Index (MI), modified Ashworth scale (MAS), numeric rating scale (NRS), Box and Block Test (BBT), Frenchay Arm Test (FAT), and Barthel Index (BI) at baseline (T0), T1 (end of treatment), and T2 (3 months of follow-up). RESULTS: Forty-four patients were included and analyzed (21RG; 23RTG). From the analysis between groups, the results suggested how there was a statistically significant difference in favor of RTG, specifically ΔT0-T1 and ΔT0-T2 for B&B p = 0.009 and p = 0.035; ΔT0-T1 and ΔT0-T2 for FAT with p = 0.016 and p = 0.031; ΔT0-T1 for MAS shoulder p = 0.016; ΔT0-T1 and ΔT0-T2 with p = 0.010 and p = 0.005 for MAS elbow; and ΔT0-T1 and ΔT0-T2 with p = 0.001 and p = 0.013 for MAS wrist. CONCLUSION: Our results suggest, in line with the literature, a good efficacy in the reduction of spasticity and in the improvement of the function of the UL, with the reduction of pain, adopting a rehabilitation protocol integrated with BoTN, robot-assisted training, and traditional physiotherapy.

Diagnosis and treatment of pain in plexopathy, radiculopathy, peripheral neuropathy and phantom limb pain. Evidence and recommendations from the Italian Consensus Conference on Pain on Neurorehabilitation.

Pain may affect all aspects of social life and reduce the quality of life. Neuropathic pain (NP) is common in patients affected by plexopathy, radiculopathy, mononeuropathy, peripheral neuropathy. Phantom limb pain (PLP) is a painful sensation that is common after amputation, and its pathophysiological mechanisms involve changes in the peripheral and central nervous system. Given the lack of conclusive evidence and specific guidelines on these topics, the aim of the Italian Consensus Conference on Pain on Neurorehabilitation (ICCPN) was to collect evidence and offer recommendations to answer currently open questions on the assessment and treatment of NP associated with the above conditions and PLP. When no evidence was available, recommendations were based on consensus between expert opinions. Current guidelines on the assessment and pharmacological treatment of NP can be applied to plexopathy, radiculopathy, mononeuropathy, peripheral neuropathy, while evidence for invasive treatments and physical therapy is generally poor because of the low quality of studies. Treatment of PLP is still unsatisfactory. Data on the functional outcome and impact of pain on neurorehabilitation outcome in these conditions are lacking. In most cases, a multidisciplinary approach is recommended to offer a better outcome and reduce side effects. High quality studies are requested to address the unmet needs in this field.

Brain-derived neurotrophic factor controls cannabinoid CB1 receptor function in the striatum.

The role of brain-derived neurotrophic factor (BDNF) in emotional processes suggests an interaction with the endocannabinoid system. Here, we addressed the functional interplay between BDNF and cannabinoid CB(1) receptors (CB(1)Rs) in the striatum, a brain area in which both BDNF and CB(1)s play a role in the emotional consequences of stress and of rewarding experiences. BDNF potently inhibited CB(1)R function in the striatum, through a mechanism mediated by altered cholesterol metabolism and membrane lipid raft function. The effect of BDNF was restricted to CB(1)Rs controlling GABA-mediated IPSCs (CB(1)R(GABA)), whereas CB(1)Rs modulating glutamate transmission and GABA(B) receptors were not affected. The action of BDNF on CB(1)R(GABA) function was tyrosine kinase dependent and was complete even after receptor sensitization with cocaine or environmental manipulations activating the dopamine (DA)-dependent reward system. In mice lacking one copy of the BDNF gene (BDNF(+/-)), CB(1)R(GABA) responses were potentiated and were preserved from the action of haloperidol, a DA D(2) receptor (D(2)R) antagonist able to fully abolish CB(1)R(GABA) function in rewarded animals. Haloperidol also enhanced BDNF levels in the striatum, suggesting that this neurotrophin may act as a downstream effector of D(2)Rs in the modulation of cannabinoid signaling. Accordingly, 5 d cocaine exposure both reduced striatal BDNF levels and increased CB(1)R(GABA) activity, through a mechanism dependent on D(2)Rs. The present study identifies a novel mechanism of CB(1)R regulation mediated by BDNF and cholesterol metabolism and provides some evidence that DA D(2)R-dependent modulation of striatal CB(1)R activity is mediated by this neurotrophin.

Preservation of striatal cannabinoid CB1 receptor function correlates with the antianxiety effects of fatty acid amide hydrolase inhibition.

The endocannabinoid anandamide (AEA) plays a crucial role in emotional control, and inhibition of its degradation by the fatty acid amide hydrolase (FAAH) has a potent antianxiety effect. The mechanism by which the magnification of AEA activity reduces anxiety is still largely undetermined. By using FAAH mutant mice and both intraperitoneal and intracerebroventricular administration of the FAAH inhibitor (3'-(aminocarbonyl)[1,1'-biphenyl]-3-yl)-cyclohexylcarbamate (URB597), we found that enhanced AEA signaling reversed, via central cannabinoid CB1 receptors (CB1Rs), the anxious phenotype of mice exposed to social defeat stress. This behavioral effect was associated with preserved activity of CB1Rs regulating GABA transmission in the striatum, whereas these receptors were dramatically down-regulated by stress in control animals. The hypothalamic-pituitary-adrenal (HPA) axis was not involved in the antistress effects of FAAH inhibition, although the HPA axis is a biological target of endogenous AEA. We also provided some physiological indications that striatal CB1Rs regulating GABA synapses are not the receptor targets of FAAH inhibition, which rather resulted in the stimulation of striatal CB1Rs regulating glutamate transmission. Collectively, our findings suggest that preservation of cannabinoid CB1 receptor function within the striatum is a possible synaptic correlate of the antianxiety effects of FAAH inhibition.

Exercise attenuates the clinical, synaptic and dendritic abnormalities of experimental autoimmune encephalomyelitis.

Voluntary exercise is beneficial in models of primarily neurodegenerative disorders. Whether exercise also affects inflammatory neurodegeneration is unknown. In the present study, we evaluated the clinical, synaptic and neuropathological effects of voluntary wheel running in mice with myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. Exercising EAE mice exhibited less severe neurological deficits compared to control EAE animals. The sensitivity of striatal GABA synapses to the stimulation of cannabinoid CB1 receptors was dramatically downregulated following EAE induction, and was rescued by exercise in EAE mice with access to a running wheel. Finally, we found that exercise was able to contrast dendritic spine loss induced by EAE in striatal neurons, although the degree of inflammatory response was similar in the two experimental groups. Our work suggests that life style and experiences can impact the clinical course of inflammatory neurodegenerative diseases by affecting their synaptic bases.

Intranasal HB-EGF administration favors adult SVZ cell mobilization to demyelinated lesions in mouse corpus callosum.

In the adult rodent brain, the subventricular zone (SVZ) represents a special niche for neural stem cells; these cells proliferate and generate neural progenitors. Most of these migrate along the rostral migratory stream to the olfactory bulb, where they differentiate into interneurons. SVZ-derived progenitors can also be recruited spontaneously to damaged brain areas to replace lost cells, including oligodendrocytes in demyelinated lesions. In this study, we searched for factors able to enhance this spontaneous recruitment of endogenous progenitors. Previous studies have suggested that epidermal growth factor (EGF) could stimulate proliferation, migration, and glial differentiation of SVZ progenitors. In the present study we examined EGF influence on endogenous SVZ cell participation to brain repair in the context of demyelinated lesions. We induced a focal demyelinated lesion in the corpus callosum by lysolecithin injection and showed that intranasal heparin-binding epidermal growth factor (HB-EGF) administration induces a significant increase in SVZ cell proliferation together with a stronger SVZ cell mobilization toward the lesions. Besides, HB-EGF causes a shift of SVZ-derived progenitor cell differentiation toward the astrocytic lineage. However, due to the threefold increase in cell recruitment by EGF treatment, the absolute number of SVZ-derived oligodendrocytes in the lesion of treated mice is higher than in controls. These results suggest that enhancing SVZ cell proliferation could be part of future strategies to promote SVZ progenitor cell mobilization toward brain lesions.

Enriched environment promotes adult neural progenitor cell mobilization in mouse demyelination models.

Since the discovery of adult neural stem cells, mobilization of endogenous stem cells from the subventricular zone (SVZ) emerges as a promising strategy to promote brain repair. Here, we examined the effect of environment enrichment on SVZ cell mobilization in demyelinating pathologies. We showed that enriched housing conditions reduced functional impairment in experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis. Furthermore, both in a focal demyelination model (lysolecithin injection) and in the inflammatory EAE model, SVZ mitotic activity and the number of SVZ-derived cells in demyelinated areas were significantly increased by environment enrichment. Enriched housing conditions also promoted the oligodendrocyte fate of SVZ-recruited cells in the EAE lesions. Altogether our results show that environment enrichment provides beneficial conditions to promote the mobilization of neural progenitors into demyelinating lesions and to favour functional recovery.