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Patient G.S. Zachary R. Barnard UCSD Neurosurgery Sub-intern September 2012. Chief Complaint. 22 year old RHM presents with flaccid paralysis of left upper extremity after a motorcycle accident 6 months ago. History of Present Illness. - PowerPoint PPT Presentation

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Patient R.B. Prophylactic ETVin patients undergoing resection of posterior fossa tumors

Patient G.S.Zachary R. BarnardUCSD Neurosurgery Sub-internSeptember 2012Chief Complaint22 year old RHM presents with flaccid paralysis of left upper extremity after a motorcycle accident 6 months agoHistory of Present Illness6 months PTA: patient presented to UCLA medical center with a GCS of 3 after being thrown 40 feet from his motorcycle that collided with a motor vehicleMultiple surgeriesExploratory laparotomyThoracotomySplenectomyLigation of multiple bleeding intercostal vesselsReconstruction of diaphragmatic ruptureLeft nephrectomyRepair of colon lacerationNeurologicallyRight frontal hemorrhagic contusionEvidence of DAIEVD placement

History of Present Illness4 months PTA: patient was discharged from UCLA medical center2 months PTA: patient f/u with neurosurgery at UCLA for evaluation of left arm paralysisNeuro exam:Motor- Complete paralysis of his deltoids, biceps, triceps, pectoralis, wrist flexors, wrist extensors, and intrinsic hand muscles. Sensory was showed patchy sensation proximally and no sensation distallyReferred to Dr. Brown for evaluation

Left brachial plexus ImagingT2 MRI-fatsuppressed

C6-C7C7-T1T1-T2Pseudomeningoceles at C6-C7, C7-T1, T1-T2 neural foramina. Indicative of C7, C8, T1 nerve root avulsions5Left brachial plexus ImagingT2 MRI-fatsuppressed

EMG: Left armSevere C4-T1 radiculopathyEvidence of C7-T1 nerve root avulsionsC6 nerve root likely not avulsedC5 nerve root avulsion indeterminate OperationsStage 1: Brachial plexus exploration with neuroma resectionAnterior and middle scalenectomyC5-C6 nerve grafting to posterior cord and suprascapular nerveBilateral sural nerve harvestStage 2:C5 nerve root connection to suprascapular nerve through sural nerve graftStage 3:Motor intercostal of 3,4,5,7 grafted to musculocutaneous nerveSensory intercostal of 3,4 grafted to median nerveMotor intercostal 7,8 to lateral antebrachial cutaneous nerve graftLateral antebrachial cutaneous nerve graft to extensor carpi radialis longus and brevisSuprascapular- supra/infraspinatus muscules (shoulder abduction and external rotation)

Musculocutaneous nerve graft to restore biceps brachii

ECRL&B- wrist extension8Post-operative CoursePatient had an unremarkable post-operative courseDrains were removed and patient was discharged home with wound care on post-operative day eight

Peripheral nerve surgery and nuances in regenerative medicineBackgroundEarliest possible reconstructionDetailed neurological examMRI imagingEMGElbow flexion usually first priority, followed by shoulder abduction/external rotation/stability, then hand sensation

11Nerve transfer vs. nerve repair for upper brachial plexus injuryYang, et al 2012Systematic review33 studies included399 nerve transfers99 nerve repairs117 transfers + repairs InclusionsAge > 18, f/u > 6 months, injury (avulsion/rupture), function (elbow flexion or shoulder abduction)OutcomesRates ratioMRS elbow flexion & Should abductionOutcomes/Results

In elbow flexion:1. Nerve transfer better than nerve repair and nerve transfer with proximal repair to achieve MRC scale score of 3 and 42. Still advocate suprascapular proximal repair due to advantages. Only when goal is purely elbow flexion should only a transfer be an option

Short comes of study:1. no imaging confirming avulsion2. Late repair 12Ciliary neurotrophic factor promotes reinnervation of musculocutaneous nerveAim:Assess motor vs. sensory fibers in ability to sprout in end-to-side grafting with ciliary neurotrophic factor (CNTF)Model: 24 Rats MS to Uln end-to-side graftEndpts:Measure % motor neuronsFn biceps (EMG)Results:PBS motor neurons 9.9%CNTF motor neurons 17%EMGBiceps brachii larger amplitude of contract in CNTF compared to PBSFlexor carpi ulnaris no differenceMusculocutaneous nerve graft enhancement with VEGFAim:Assess phVEGF ability to reinnervate end-to-end, end-to-side nerve graftsModel: 42 Rats, cut end of nerve transfected with virusEndpts:Measure increase in motor neuron percent by diameter of neuron

BDNF and GDNF in nerve regenerationBrain-derived neurotrophic factor (BDNF)Glial cell-derived neurotrophic factor (GDNF)Electrical stimulusRolipram (PDE4 inhibitor) anti-inflammatory

BDNF and GDNF promote axon spreading but do not increase the number of neurons regenerating in animal models

Time is very important. Proximal nerve begins secreting neurotrophic factors 7 days after injury. The longer you wait to repair the less possibility of regrowth due to reduced neurotrophic factors. 15SummaryClinical rule of seven seventies for traumatic brachial plexus lesionsBased on 1068 patients (Siqueira et al, 2011)70% due to MVCsOf these, 70% motorcyclesOf these, 70% multiple injuriesOverall, 70% supraclavicular lesionsOf these, 70% at least one root avulsionOf these, 70% avulsion C7, C8, or T1Of these, 70% persistent painSummaryPeripheral nerve surgery still in infancyConclusion on best treatment difficult due to lack of randomized controlled trialsLots of basic science possibilities, but need more translational workConclusionsA certain excessiveness seems a necessary element in all greatness

-Harvey CushingReferences1.Giuffre JL, Kakar S, Bishop AT, Spinner RJ, Shin AY. Current concepts of the treatment of adult brachial plexus injuries. The Journal of hand surgery. 2010;35(4):678-88; quiz 88. Epub 2010/04/01. doi: 10.1016/j.jhsa.2010.01.021. PubMed PMID: 20353866.2.Yang LJ, Chang KW, Chung KC. A systematic review of nerve transfer and nerve repair for the treatment of adult upper brachial plexus injury. Neurosurgery. 2012;71(2):417-29; discussion 29. Epub 2012/07/20. doi: 10.1227/NEU.0b013e318257be98. PubMed PMID: 22811085.3.Bao YF, Tang WJ, Zhu DQ, Li YX, Zee CS, Chen XJ, et al. Sensory neuronopathy involves the spinal cord and brachial plexus: a quantitative study employing multiple-echo data image combination (MEDIC) and turbo inversion recovery magnitude (TIRM). Neuroradiology. 2012. Epub 2012/08/28. doi: 10.1007/s00234-012-1085-x. PubMed PMID: 22922867.4.Lee SK, Wolfe SW. Nerve transfers for the upper extremity: new horizons in nerve reconstruction. The Journal of the American Academy of Orthopaedic Surgeons. 2012;20(8):506-17. Epub 2012/08/03. doi: 10.5435/JAAOS-20-08-506. PubMed PMID: 22855853.5.Siqueira MG, Martins RS. Surgical treatment of adult traumatic brachial plexus injuries: an overview. Arquivos de neuro-psiquiatria. 2011;69(3):528-35. Epub 2011/07/15. PubMed PMID: 21755135.6.Fox IK, Mackinnon SE. Adult peripheral nerve disorders: nerve entrapment, repair, transfer, and brachial plexus disorders. Plastic and reconstructive surgery. 2011;127(5):105e-18e. Epub 2011/05/03. doi: 10.1097/PRS.0b013e31820cf556. PubMed PMID: 21532404.7.Dubovy P, Raska O, Klusakova I, Stejskal L, Celakovsky P, Haninec P. Ciliary neurotrophic factor promotes motor reinnervation of the musculocutaneous nerve in an experimental model of end-to-side neurorrhaphy. BMC neuroscience. 2011;12:58. Epub 2011/06/24. doi: 10.1186/1471-2202-12-58. PubMed PMID: 21696588; PubMed Central PMCID: PMC3224149.8.Haninec P, Kaiser R, Bobek V, Dubovy P. Enhancement of musculocutaneous nerve reinnervation after vascular endothelial growth factor (VEGF) gene therapy. BMC neuroscience. 2012;13:57. Epub 2012/06/08. doi: 10.1186/1471-2202-13-57. PubMed PMID: 22672575; PubMed Central PMCID: PMC3441459.9.Gordon T. The role of neurotrophic factors in nerve regeneration. Neurosurgical focus. 2009;26(2):E3. Epub 2009/02/21. doi: 10.3171/FOC.2009.26.2.E3. PubMed PMID: 19228105.

AcknowledgementsDr. BrownDr. CurtisNeurosurgery FacultyNeurosurgery ResidentsEric Lin