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Traumatic spinal cord injury (SCI) is a devastating neurological condition that involves both primary and secondary tissue loss. Various cytotoxic events including hypoxia, hemorrhage and blood lysis, bioenergetic failure, oxidative stress, endoplasmic reticulum (ER) stress, and neuroinflammation contribute to secondary injury. The HIF prolyl hydroxylase domain (PHD/EGLN) family of proteins are iron-dependent, oxygen-sensing enzymes that regulate the stability of hypoxia inducible factor-1α (HIF-1α) and also mediate oxidative stress caused by free iron liberated from the lysis of blood. PHD inhibition improves outcome after experimental intracerebral hemorrhage (ICH) by reducing activating transcription factor 4 (ATF4)-driven neuronal death. As the ATF4-CHOP (CCAAT-enhancer-binding protein homologous protein) pathway plays a role in the pathogenesis of contusive SCI, we examined the effects of PHD inhibition in a mouse model of moderate T9 contusive SCI in which white matter damage is the primary driver of locomotor dysfunction. Pharmacological inhibition of PHDs using adaptaquin (AQ) moderately lowers acute induction of Atf4 and Chop mRNAs and prevents the acute decline of oligodendrocyte (OL) lineage mRNAs, but does not improve long-term recovery of hindlimb locomotion or increase chronic white matter sparing. Conditional genetic ablation of all three PHD isoenzymes in OLs did not affect Atf4 , Chop or OL mRNAs expression levels, locomotor recovery, and white matter sparing after SCI. Hence, PHDs may not be suitable targets to improve outcomes in traumatic CNS pathologies that involve acute white matter injury.

Background Vagal nerve stimulation (VNS) can be an effective therapy for patients with epilepsy refractory to anti-epileptic drugs or intracranial surgery. While generally well tolerated, it has been associated with laryngospasm, hoarseness, coughing, dyspnea, throat and atypical chest pain, cardiac symptoms such as bradycardia and occasionally asystole. We report on a patient receiving vagal nerve stimulation who experienced severe typical anginal chest pain during VNS firing without any evidence of cardiac ischemia or dysfunction. Thus, the pain appeared to be neuropathic from the stimulation itself rather than nociceptive secondary to an effect on heart function. Case presentation A 29-year-old man, with a history of intractable frontal lobe epilepsy refractory to seven anti-epileptic medications and subsequent intracranial surgery, underwent VNS implantation without complications. On beginning stimulation, he began to have intermittent chest pain that corresponded temporally to his intermittent VNS firing. The description of his pain was pathognomonic of ischemic cardiac chest pain. On initial evaluation, he displayed Levine’s sign and reported crushing substernal chest pain radiating to the left arm, as well as shortness of breath walking upstairs that improved with rest. He underwent an extensive cardiac workup, including 12-lead ECG, cardiac stress test, echocardiogram, 12-day ambulatory cardiac monitoring, and continuous ECG monitoring each with and without stimulation of his device. The workup was consistently negative. Inability to resolve the pain necessitated the disabling and eventual removal of the device. Conclusion To our knowledge, this is the first report of pseudoanginal chest pain associated with VNS. This occurrence prompted our review of the mechanisms of cardiac chest pain and suggests that vagal afferents may convey anginal pain separately or in parallel with known spinal cord pain mechanisms. These insights into the physiology of chest pain may be of general interest and important to surgeons implanting VNS devices who may potentially encounter such symptoms.

Background Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder usually associated with specific medical conditions that cause a disturbance of the CNS homeostasis. It has seldom been reported to be a consequence of an iatrogenic intervention causing intracranial hypotension. Case presentation We report the case of an individual 69-year-old male presenting with headache and blurred vision following cerebrospinal fluid (CSF) leak from resection of a sellar mass. The patient developed the condition following removal of the lumbar drain post-operatively. Magnetic Resonance Imaging showed bilateral occipital, parieto-occipital, and cerebellar T2 FLAIR hyper-intensities, suggesting a radiological diagnosis of posterior reversible encephalopathy syndrome (PRES). The patient’s symptoms started to improve shortly afterwards and had completely resolved at 3 months follow-up. Conclusions The absence of severe hypertension and presence of an intraoperative CSF leak requiring placement of the lumbar drain suggests that decreased CSF volume and associated reactive hyperemia could have a role in the pathophysiology of the disease.

Mutant huntingtin (mHTT), the causative protein in Huntington’s disease (HD), associates with the translocase of mitochondrial inner membrane 23 (TIM23) complex, resulting in inhibition of synaptic mitochondrial protein import first detected in presymptomatic HD mice. The early timing of this event suggests that it is a relevant and direct pathophysiologic consequence of mHTT expression. We show that, of the 4 TIM23 complex proteins, mHTT specifically binds to the TIM23 subunit and that full-length wild-type huntingtin (wtHTT) and mHTT reside in the mitochondrial intermembrane space. We investigated differences in mitochondrial proteome between wtHTT and mHTT cells and found numerous proteomic disparities between mHTT and wtHTT mitochondria. We validated these data by quantitative immunoblotting in striatal cell lines and human HD brain tissue. The level of soluble matrix mitochondrial proteins imported through the TIM23 complex is lower in mHTT-expressing cell lines and brain tissues of HD patients compared with controls. In mHTT-expressing cell lines, membrane-bound TIM23-imported proteins have lower intramitochondrial levels, whereas inner membrane multispan proteins that are imported via the TIM22 pathway and proteins integrated into the outer membrane generally remain unchanged. In summary, we show that, in mitochondria, huntingtin is located in the intermembrane space, that mHTT binds with high-affinity to TIM23, and that mitochondria from mHTT-expressing cells and brain tissues of HD patients have reduced levels of nuclearly encoded proteins imported through TIM23. These data demonstrate the mechanism and biological significance of mHTT-mediated inhibition of mitochondrial protein import, a mechanism likely broadly relevant to other neurodegenerative diseases.

Abstract BACKGROUND: Annual incidence of symptomatic adjacent level disease (ALD) following lumbar fusion surgery ranges from 0.6% to 3.9% per year. Sagittal malalignment may contribute to the development of ALD. OBJECTIVE: To describe the relationship between pelvic incidence-lumbar lordosis (PI-LL) mismatch and the development of symptomatic ALD requiring revision surgery following single-level transforaminal lumbar interbody fusion for degenerative lumbar spondylosis and/or low-grade spondylolisthesis. METHODS: All patients who underwent a single-level transforaminal lumbar interbody fusion at either L4/5 or L5/S1 between July 2006 and December 2012 were analyzed for pre- and postoperative spinopelvic parameters. Using univariate and logistic regression analysis, we compared the spinopelvic parameters of those patients who required revision surgery against those patients who did not develop symptomatic ALD. We calculated the predictive value of PI-LL mismatch. RESULTS: One hundred fifty-nine patients met the inclusion criteria. The results noted that, for a 1° increase in PI-LL mismatch (preop and postop), the odds of developing ALD requiring surgery increased by 1.3 and 1.4 fold, respectively, which were statistically significant increases. Based on our analysis, a PI-LL mismatch of >11° had a positive predictive value of 75% for the development of symptomatic ALD requiring revision surgery. CONCLUSIONS: A high PI-LL mismatch is strongly associated with the development of symptomatic ALD requiring revision lumbar spine surgery. The development of ALD may represent a global disease process as opposed to a focal condition. Spine surgeons may wish to consider assessment of spinopelvic parameters in the evaluation of degenerative lumbar spine pathology.

The Single Pedicle Embolization of the Distal Middle Meningeal Artery using n-butyl cyanoacrylate (n-BCA) (SPEED-n technique) offers an innovative approach to treating chronic subdural hematomas by targeting the pathological subdural membranes with precise and efficient embolization.1 2 3 This technical video demonstrates the SPEED-n technique, which employs a single catheter and dilute n-BCA (15–20%) to achieve distal penetration of the middle meningeal artery (MMA) network while minimizing procedure time and risks (video 1). Video 1 - Key features include a stepwise embolization strategy, leveraging inherent MMA anastomoses to ensure comprehensive vascular coverage and reduced non-target embolization. The method’s success hinges on careful anatomical considerations, precise imaging to delineate safety margins, and the advantages of dilute glue for delayed polymerization, facilitating safe catheter removal and preventing tip retention.4 5 6 This video serves as a practical guide for neurointerventionalists seeking efficient solutions for distal MMA embolization.

Total hip arthroplasty is a prevalent orthopedic intervention in the United States. Massive postoperative hematomas are a rare albeit serious complication of the procedure. Sequelae of these hematomas can include lower extremity paralysis from compression of the sciatic nerve. A 66-year-old woman taking aspirin and clopidogrel for coronary stents presented with a complete foot drop, paresthesias, and lower extremity pain 10 days after a total hip arthroplasty. The patient was initially seen by a neurology service at another hospital and thought to have lateral recess stenosis. At the authors' center, magnetic resonance imaging of the lumbar spine failed to show lateral recess stenosis. Urgent pelvic computed tomography showed a large hematoma and raised suspicion of sciatic nerve compression. Hip magnetic resonance imaging showed a right gluteal hematoma compressing the sciatic nerve. The patient was then taken to the operating room for the clot to be evacuated and was later referred for rehabilitation. Massive hematomas after total hip arthroplasty are an important consideration in the differential diagnosis of nontraumatic acute foot drop. Prompt diagnosis may correlate with improved neurological outcome and help reduce overall morbidity. [ Orthopedics. 2016; 39(2):e374–e376.]

Intracranial vascular pathologies often have overlapping clinical presentations. Dissected vessel occlusions and bifurcation aneurysms can appear similar on pretherapeutic imaging. The medical management of these two entities is drastically different. The patient is a 51-year-old man who presented with severe, sudden-onset headache. Initial presentation was consistent with a ruptured middle cerebral artery (MCA) aneurysm and surgical clipping was recommended. However, further review of radiographic findings could not definitively differentiate an aneurysmal origin of the symptoms as opposed to intracranial dissection followed by occlusion of the M2 branch of the MCA. MRI sampling perfection with application optimised contrasts using different flip angle evolution (SPACE) was performed and showed thin flow signalling distal to the dissected vessel stump confirming the diagnosis. Accurate diagnosis is a crucial step in directing treatment for intracranial vascular lesions. MRI SPACE is a simple tool in the diagnostic armamentarium to adequately direct treatment and avoid the potential for unnecessary interventions.

IntroductionRefractory headache is a common and frequently disabling disorder, affecting 2–12 million patients each year in the US alone. This case series provides initial insight into the safety and effectiveness of lidocaine infusions into the middle meningeal artery (MMAL) for the treatment of refractory headache.MethodsA retrospective review of a prospectively maintained database was conducted to identify patients undergoing MMAL at two institutions. Baseline demographics, procedural metrics, and headache measures were tracked over a 3 month period. Headache severity was assessed immediately after the procedure, and at 1, 2, and 3 months. A responder was defined as a patient who had a >50% reduction in headache days per month.Results45 patients (38 women, average age 49.8 years) underwent treatment at two institutions over 19 months. The patients reported an average of 27.5 headache days per month despite medical therapy during the month before treatment. All infusions were performed under conscious sedation and most (40, 88.9%) were performed via radial access. No neurological complications were observed. The most common adverse event (4 of 45 patients) was discomfort at the radial access site. 29 of 45 (64.4%) patients reported headache relief immediately (0–24 hours) after the infusion. At 1, 2, and 3 months, 57% (24 of 42), 34% (13 of 38), and 20.6% (7 of 34) of patients were responders. All but one (23 of 24) of the patients who were responders at 1 month had experienced acute headache relief during (or immediately after) the lidocaine infusion procedure. 23 of 27 (85.1%) patients who had relief during the procedure were responders at 1 month. Headache Impact Test-6 (HIT-6) scores were 69.4 before treatment (41 patients), 55.5 (34) at 1 month, 64.5 (31) at 2 months, and 66.0 (31) at 3 months.DiscussionThe study found that MMAL can elicit relief in patients with refractory headache, which may last as long as 3 months. Most patients who had acute relief during the procedure were responders at 1 month.

Abstract BACKGROUND Patients who survive aneurysmal subarachnoid hemorrhage (aSAH) are at risk for delayed neurological deficits (DND) and cerebral infarction. In this exploratory cohort comparison analysis, we compared in-hospital outcomes of aSAH patients administered a low-dose intravenous heparin (LDIVH) infusion (12 U/kg/h) vs those administered standard subcutaneous heparin (SQH) prophylaxis for deep vein thrombosis (DVT; 5000 U, 3 × daily). OBJECTIVE To assess the safety and efficacy of LDIVH in aSAH patients. METHODS We retrospectively analyzed 556 consecutive cases of aSAH patients whose aneurysm was secured by clipping or coiling at a single institution over a 10-yr period, including 233 administered the LDIVH protocol and 323 administered the SQH protocol. Radiological and outcome data were compared between the 2 cohorts using multivariable logistic regression and propensity score-based inverse probability of treatment weighting (IPTW). RESULTS The unadjusted rate of cerebral infarction in the LDIVH cohort was half that in SQH cohort (9 vs 18%; P = .004). Multivariable logistic regression showed that patients in the LDIVH cohort were significantly less likely than those in the SQH cohort to have DND (odds ratio (OR) 0.53 [95% CI: 0.33, 0.85]) or cerebral infarction (OR 0.40 [95% CI: 0.23, 0.71]). Analysis following IPTW showed similar results. Rates of hemorrhagic complications, heparin-induced thrombocytopenia and DVT were not different between cohorts. CONCLUSION This cohort comparison analysis suggests that LDIVH infusion may favorably influence the outcome of patients after aSAH. Prospective studies are required to further assess the benefit of LDIVH infusion in patients with aSAH.