Rapid Functional Recovery After Thoracic Outlet Decompression in a Series of Adolescent Athletes With Chronic Atraumatic Shoulder-Girdle Pain, Scapular Winging/Dyskinesis, and Normal Electrodiagnostic Studies.

BACKGROUND: Spontaneous shoulder-girdle pain and scapular winging/dyskinesis can be caused by several neuromuscular disorders identifiable by electrodiagnostic studies (EDX). We describe a group of adolescent athletes with this clinical presentation but normal EDX, followed by later development of neurogenic thoracic outlet syndrome (NTOS). METHODS: We identified patients referred for evaluation of NTOS that had a history of chronic atraumatic shoulder-girdle pain, scapular winging/dyskinesis, and normal EDX. Each was refractory to conservative management and underwent supraclavicular decompression and brachial plexus neurolysis for NTOS. Functional disability was quantified by Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores. RESULTS: There were 5 female patients with a mean age at symptom onset of 14.2 ± 0.4 years, including spontaneous severe pain in the shoulder, scapula, and arm, along with prominent scapular winging/dyskinesis, and normal EDX. Symptoms had persisted for 18.9 ± 4.0 months prior to referral, with pronounced upper extremity disability (mean QuickDASH, 54.6 ± 6.9). By 3 months after surgical treatment for NTOS, all 5 patients experienced near-complete symptom resolution, including scapular winging/dyskinesis, with markedly improved function (mean QuickDASH, 2.2 ± 1.3) and a return to normal activity. CONCLUSIONS: A subset of patients with chronic atraumatic shoulder-girdle pain, scapular winging/dyskinesis, and normal EDX may develop dynamic brachial plexus compression characteristic of NTOS, exhibiting an ischemic "Sunderland-zero" nerve conduction block for which surgical decompression can result in rapid and substantial clinical improvement. The presence of surgically treatable NTOS should be considered for selected patients with long-standing scapular winging/dyskinesis who fail conservative management.

Venographic classification and long-term surgical treatment outcomes for axillary-subclavian vein thrombosis due to venous thoracic outlet syndrome (Paget-Schroetter syndrome).

OBJECTIVE: We assessed the clinical presentation, operative findings, and surgical treatment outcomes for axillary-subclavian vein (AxSCV) thrombosis due to venous thoracic outlet syndrome (VTOS). METHODS: We performed a retrospective, single-center review of 266 patients who had undergone primary surgical treatment of VTOS between 2016 and 2022. The clinical outcomes were compared between the patients in four treatment groups determined by intraoperative venography. RESULTS: Of the 266 patients, 132 were male and 134 were female. All patients had a history of spontaneous arm swelling and idiopathic AxSCV thrombosis, including 25 (9%) with proven pulmonary embolism, at a mean age of 32.1 ± 0.8 years (range, 12-66 years). The timing of clinical presentation was acute (<15 days) for 132 patients (50%), subacute (15-90 days) for 71 (27%), and chronic (>90 days) for 63 patients (24%). Venography with catheter-directed thrombolysis or thrombectomy (CDT) and/or balloon angioplasty had been performed in 188 patients (71%). The median interval between symptom onset and surgery was 78 days. After paraclavicular thoracic outlet decompression and external venolysis, intraoperative venography showed a widely patent AxSCV in 150 patients (56%). However, 26 (10%) had a long chronic AxSCV occlusion with axillary vein inflow insufficient for bypass reconstruction. Patch angioplasty was performed for focal AxSCV stenosis in 55 patients (21%) and bypass graft reconstruction for segmental AxSCV occlusion in 35 (13%). The patients who underwent external venolysis alone (patent or occluded AxSCV; n = 176) had a shorter mean operative time, shorter postoperative length of stay and fewer reoperations and late reinterventions compared with those who underwent AxSCV reconstruction (patch or bypass; n = 90), with no differences in the incidence of overall complications or 30-day readmissions. At a median clinical follow-up of 38.7 months, 246 patients (93%) had no arm swelling, and only 17 (6%) were receiving anticoagulation treatment; 95% of those with a patent AxSCV at the end of surgery were free of arm swelling vs 69% of those with a long chronic AxSCV occlusion (P < .001). The patients who had undergone CDT at the initial diagnosis were 32% less likely to need AxSCV reconstruction at surgery (30% vs 44%; P = .034) and 60% less likely to have arm swelling at follow-up (5% vs 13%; P < .05) vs those who had not undergone CDT. CONCLUSIONS: Paraclavicular decompression, external venolysis, and selective AxSCV reconstruction determined by intraoperative venography findings can provide successful and durable treatment for >90% of all patients with VTOS. Further work is needed to achieve earlier recognition of AxSCV thrombosis, prompt usage of CDT, and even more effective surgical treatment.

AAV8, 9, Rh10, Rh43 vector gene transfer in the rat brain: effects of serotype, promoter and purification method.

We compared adeno-associated virus (AAV) serotypes for expression levels of green fluorescent protein (GFP) in the adult rat hippocampus by biophotonic imaging. Preparations of AAV serotypes 8, 9, Rh10, and Rh43 incorporating cytomegalovirus (CMV) promoter-driven GFP were purified by a CsCl method. Neither AAV Rh10 nor AAV Rh43 produced greater levels of GFP than AAV8, which was used as a reference. For AAV9, there was an increase relative to AAV8. The CsCl-purified AAV8 displayed an astroglial transduction pattern in contrast to the expected neuronal expression of other AAVs. After preparing the same CMV-GFP plasmid in AAV8 with an iodixanol purification method, the expected neuronal pattern resulted. The astroglial expression with the CsCl AAV8 was probably due to relatively high levels of protein impurities. We compared the CMV promoter with the CMV/chicken beta-actin (CBA) promoter in the context of AAV8, both prepared by iodixanol, and found the CBA promoter to produce stronger GFP expression. At two doses of vectors optimized for serotype, promoter and purification, we did not observe serotype differences among AAV8, AAV9, or AAV Rh10. The purification method can therefore impact the transduction pattern as well as the results when comparing serotype strengths.

Parkin is protective for substantia nigra dopamine neurons in a tau gene transfer neurodegeneration model.

Parkin is a ubiquitin ligase involved in the ubiquitin-proteasome system. Elevating parkin expression in cells reduces markers of oxidative stress while blocking parkin expression increases oxidative stress. In parkin gene knock down mouse and fly models, mitochondria function is deficient. Parkin is neuroprotective against a variety of toxic insults, while it remains unclear which of the above properties of parkin may mediate the protective actions. One of the models for which parkin is protective is overexpression of alpha-synuclein, a protein that self-aggregates in Parkinson disease. The microtubule-associated protein tau is another protein that self-aggregates in specific neurodegenerative diseases that also involve loss of dopamine neurons such as frontotemporal dementia with parkinsonism linked to chromosome 17, progressive supranuclear palsy and corticobasal degeneration. We recently developed a tau-induced dopaminergic degeneration model in rats using adeno-associated virus vectors. In this study, we successfully targeted either a mixed tau/parkin vector or mixed tau/control vector to the rat substantia nigra. While there was significant loss of dopamine neurons in the tau/control group relative to uninjected substantia nigra, there was no cell loss in the tau/parkin group. We found no difference in total tau levels between tau/control and tau/parkin groups. Parkin therefore protects dopamine neurons against tau as it does against alpha-synuclein, which further supports parkin as a therapeutic target for diseases involving loss of dopamine neurons.