Alpha-synuclein targets GluN2A NMDA receptor subunit causing striatal synaptic dysfunction and visuospatial memory alteration

Parkinson's disease is a progressive neurodegenerative disorder characterized by altered striatal dopaminergic signalling that leads to motor and cognitive deficits. Parkinson's disease is also characterized by abnormal presence of soluble toxic forms of \u3b1-synuclein that, when clustered into Lewy bodies, represents one of the pathological hallmarks of the disease. However, \u3b1-synuclein oligomers might also directly affect synaptic transmission and plasticity in Parkinson's disease models. Accordingly, by combining electrophysiological, optogenetic, immunofluorescence, molecular and behavioural analyses, here we report that \u3b1-synuclein reduces N-methyl-d-aspartate (NMDA) receptor-mediated synaptic currents and impairs corticostriatal long-term potentiation of striatal spiny projection neurons, of both direct (D1-positive) and indirect (putative D2-positive) pathways. Intrastriatal injections of \u3b1-synuclein produce deficits in visuospatial learning associated with reduced function of GluN2A NMDA receptor subunit indicating that this protein selectively targets this subunit both in vitro and ex vivo. Interestingly, this effect is observed in spiny projection neurons activated by optical stimulation of either cortical or thalamic glutamatergic afferents. We also found that treatment of striatal slices with antibodies targeting \u3b1-synuclein prevents the \u3b1-synuclein-induced loss of long-term potentiation and the reduced synaptic localization of GluN2A NMDA receptor subunit suggesting that this strategy might counteract synaptic dysfunction occurring in Parkinson's disease

Mechanisms underlying the impairment of hippocampal long-term potentiation and memory in experimental Parkinson's disease

Although patients with Parkinson's disease show impairments in cognitive performance even at the early stage of the disease, the synaptic mechanisms underlying cognitive impairment in this pathology are unknown. Hippocampal long-term potentiation represents the major experimental model for the synaptic changes underlying learning and memory and is controlled by endogenous dopamine. We found that hippocampal long-term potentiation is altered in both a neurotoxic and transgenic model of Parkinson's disease and this plastic alteration is associated with an impaired dopaminergic transmission and a decrease of NR2A/NR2B subunit ratio in synaptic N-methyl-d-aspartic acid receptors. Deficits in hippocampal-dependent learning were also found in hemiparkinsonian and mutant animals. Interestingly, the dopamine precursor l-DOPA was able to restore hippocampal synaptic potentiation via D1/D5 receptors and to ameliorate the cognitive deficit in parkinsonian animals suggesting that dopamine-dependent impairment of hippocampal long-term potentiation may contribute to cognitive deficits in patients with Parkinson's disease

Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS)

Background: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. Methods: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. Results: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). Conclusions: This consensus provides practical recommendations to support a clinician’s decision making in the management of tSCI polytrauma patients

Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS).

BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. RESULTS: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). CONCLUSIONS: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients

Peripheral aneurysms in the differential diagnosis of soft tissue sarcomas

The authors present four cases of peripheral aneurysm: 1 true aneurysm towards the superficial femoral artery, and 3 aneurysms of the popliteal artery, 1 of which true and 2 false. The criteria used for differential diagnosis with soft tissue sarcomas is analyzed and the importance of a complete diagnosis before planning incisional biopsy is emphasized

Chordoma of the spine above the sacrum. Treatment and outcome in 21 cases

STUDY DESIGN: Twenty-one cases of chordoma arising in the mobile spine were retrospectively reviewed. OBJECTIVES: All the cases were submitted to oncologic and surgical staging to correlate treatment and outcome. SUMMARY OF BACKGROUND DATA: Excluding plasmacytomas, chordoma is the most frequent primary malignant tumor of the spine, occurring mainly in elderly men. The course of the disease is slow, metastases occur late, and death can result from complications related to local extension of the disease. Complete excision of the tumor according to oncologic criteria can be hampered by extension of the tumor and by anatomic constraints in the mobile spine. METHODS: All charts, radiographs, and images were reviewed. The composite information provided by this review allowed for oncologic and surgical staging of these cases. Treatment was defined according to Ennekings criteria. All the patients were followed for determination of their status clinically and radiographically. RESULTS: Ten patients died (1 to 137 months after treatment, mean 65 months); four patients are alive with the disease; only seven patients (33%) are symptom free at the final follow-up (39 to 112 months after treatment, mean 65 months). Conventional radiation therapy was not effective in eradicating the tumor, even if associated with palliative or debulking surgery: of 15 cases, 12 were associated with recurrence or progression. Intralesional surgery also was not effective (two recurrences in two cases, 18 to 41 months later). En bloc excision of the lesion, sometimes combined with radiation therapy as an adjuvant, obtained the best results (four patients disease free at 39 to 112 months, mean 77 months). CONCLUSIONS: En bloc excision--even if marginal--is the treatment of choice of chordomas of the spine. Early diagnosis and careful surgical staging and planning are necessary. Megavoltage radiation can be administered as an adjuvant

Pharyngo-Esophageal Perforations After Anterior Cervical Spine Surgery: Management and Outcomes

Objective: To report about the diagnosis, surgical treatment, and postoperative management of pharyngo-esophageal perforations (PEPs) after anterior cervical spine (ACS) surgery in 17 patients. Methods: A retrospective multicenter case series of patients surgically treated for PEP after ACS surgery was performed. Data regarding cervical spine pathology and surgery, comorbidities, diagnosis and surgical management of PEP, airway management, antibiotic therapy, postoperative course, and feeding route after repair surgery at discharge and last follow-up were collected. Results: Seventeen patients were included in the study, for a total of 22 surgical procedures for PEP repair. Seven PEPs (41%) had early onset, whereas 10 (59%) were delayed. All patients underwent PEP surgical repair through an anterior prevascular retrovisceral cervicotomic approach, consisting of multiple layer sutures of the perforation, with flap interposition. Despite the challenging management of these patients, 16 of 17 patients from our series restored oral feeding. Conclusions: PEPs are among the most appalling complications of cervical spine surgery. Because of their rarity and heterogeneous presentation, a standardized management is difficult to define. From our experience with the largest case series in the literature, a multidisciplinary approach is advisable to deal with these patients