Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are both characterized pathologically by the presence of neuronal inclusions termed Lewy bodies (LBs). A common feature found in LBs are aggregates of alpha-synuclein (alpha-Syn), and although it is now recognized that alpha-Syn is the major building block for these toxic filaments, the mechanism of how this occurs remains unknown. In the present study, we demonstrate that proteolytic processing of alpha-Syn by the protease calpain I leads to the formation of aggregated high-molecular weight species and adoption of a beta-sheet structure. To determine whether calpain-cleavage of alpha-Syn occurs in PD and DLB, we designed site-directed calpain-cleavage antibodies to alpha-Syn and tested their utility in several animal model systems. Detection of calpain-cleaved alpha-Syn was evident in mouse models of cerebral ischemia and PD and in a Drosophila model of PD. In the human PD and DLB brain, calpain-cleaved alpha-Syn antibodies immunolabeled LBs and neurites in the substantia nigra. Moreover, calpain-cleaved alpha-Syn fragments identified within LBs colocalized with activated calpain in neurons of the PD and DLB brains. These findings suggest that calpain I may participate in the disease-linked aggregation of alpha-Syn in various alpha-synucleinopathies.

Our purpose is to describe a case of atlanto-occipital dislocation and discuss treatment approaches to minimize subsequent neurological deficits. Traumatic atlanto-occipital dislocation, has traditionally been considered rare and lethal, due to resulting high levels of spinal cord injury. Outcomes are generally expected to be poor. However, recent case reports indicate that survival is increasing. Of patients who survive cranio-cervical dislocation, many endure resulting neurological deficits. We present a rare case of a 23-year-old male, who sustained an atlanto-occipital dislocation in a motor vehicle accident. The patient presented with a Glasgow Coma Scale (GCS) of 11T. Lateral C-spine x-ray and thin-section slices CT delineated a C1 ring fracture on the left side with approximately 1 cm anterior and superior subluxation of the occipital condyles of the cranium in reference to C1. The patient was completely awake, alert, and was following commands. The patient underwent a cranio-cervical stabilization from occiput to C3, using lateral mas screws (C1-C3) and transarticular screws (C2-C3). The Vertex (Medtronics) system used included longitudinal bars connected to the lateral mas plating system, which was subsequently used to place screws within the keel of the occipital bone. Motor strength and sensation remained intact following surgery. One-week post-operation, the patient was ambulating 140 feet, conversationally appropriate, and had a GCS of 15. This case illustrates the possibility for neurosurgical intervention of cranio-cervical dislocations to achieve optimal outcome and demonstrates that survival from this injury is not only conceivable, but recovery of function is also possible.

No abstract