Risk Of Permanent Neurological Deficit Research Articles

OTHR-20. MINIMALLY-INVASIVE MOLECULAR DIAGNOSIS OF INFILTRATING BRAINSTEM GLIOMAS THROUGH CEREBROSPINAL FLUID CELL-FREE DNA SEQUENCING

Abstract BACKGROUND Accurate molecular diagnosis of infiltrating brainstem tumors, including diffuse midline gliomas and IDH mutant astrocytomas, is essential for prognostication and optimal therapy. Surgical biopsy of the brainstem carries risk of permanent neurological deficits and may yield insufficient or non-diagnostic tissue. We hypothesized that minimally invasive “liquid biopsy” analyzing circulating tumor cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) could represent an alternative molecular diagnostic modality. METHODS We performed MSK-IMPACT, a New York State Department of Health authorized hybridization capture-based next-generation panel DNA sequencing clinical assay on 44 CSF samples from 37 unique patients with brainstem tumors. Ages at time of CSF collection ranged from 1–47 years (median: 29 years). For samples in which diagnostic alterations could not be detected, we performed a series of secondary analyses for known hotspot mutations such as H3F3A, IDH1/2, and BRAF, including manual review for mutant reads below the official clinical reporting threshold, as well as droplet digital PCR (ddPCR). RESULTS Among 44 samples included in this study, 10/44 (23%) samples had mutations detected by MSK-IMPACT using standard clinical calling criteria and 14 of the remaining 34 samples (41%) had supporting evidence of a diagnostically relevant mutation based on manual review. Testing by ddPCR was performed on 11 samples (based on DNA availability), uncovering 4 additional mutations. Overall positive diagnostic yield was 64% (28/44). In biopsied patients, CSF confirmed disease-defining mutations in 80% (16/20) of CSF samples, including H3F3A K28M (9/10; 90%) and IDH1/2 (5/6; 83%). Among 24 unbiopsied patients, a disease-defining mutation was identified in 60% (15/25) of CSF samples. CONCLUSIONS Analysis of CSF cfDNA in patients with brainstem tumors has a high diagnostic yield and obviates the need for tissue biopsy in a majority of patients. A tiered testing approach using next-generation sequencing and ddPCR assays helps maximize diagnostic information and sensitivity.

Comparison of the outcomes between total arch replacement and nontotal arch replacement in patients with acute type A aortic dissection

ObjectiveTo compare the outcomes between total arch replacement (TAR) and nontotal arch replacement (non-TAR) in patients with acute type A aortic dissection (ATAAD).MethodsBetween 2006 and 2018, 275 ATAAD patients were divided into 2 groups, the TAR group (n = 63) and the non-TAR group (n = 212), and multiple variables were analyzed.ResultsThe TAR patients were older than the non-TAR patients (61.5 ± 11.8 vs. 57.4 ± 14.5 years, p = 0.024). The TAR group had longer operative, cardiopulmonary bypass, aortic clamping, and circulatory arrest times than the non-TAR group (all p < 0.001). The overall hospital mortality rate was 8.7% with no statistically significant difference between the TAR and non-TAR groups (9.5% vs. 8.5%, p = 0.799). There was no significant difference in the incidence of acute kidney injury (AKI), intubation time, incidence of postoperative atrial fibrillation (AF), or reoperation for bleeding or reintervention rates between the TAR and non-TAR groups (68.3% vs. 65.7% (p = 0.912), 44.8% vs. 33.8% (p = 0.127), 30.2% vs. 22.6% (p = 0.222), 9.5% vs. 9.5% (p = 0.189), and 7.9% vs. 7.1% (p = 0.077), respectively). The TAR group had a higher rate of new permanent neurological deficit (PND) than the non-TAR group and longer median length of hospital stay (17.5% vs. 6.1% (p < 0.001) and 9 vs. 12 days (p = 0.049), respectively). TAR (relative risk (RR) 3.66, p = 0.005) and preoperative cardiopulmonary resuscitation (CPR) (RR 6.60, p = 0.019) were risk factors of PND. Survival rate was similar between the two groups.ConclusionThe mortality rates in ATAAD patients with TAR and non-TAR were similar. However, the incidence of new permanent postoperative neurological deficit was significantly higher, and the length of hospital stay was longer in patients with TAR. TAR in ATAAD should be avoided especially in patients who have experienced preoperative CPR to abate risk of PND.

CLINICAL SIGNIFICANCE OF INTRAOPERATIVE NEUROPHYSIOLOGICAL MONITORING DURING SCOLIOSIS SURGERY: A LITERATURE REVIEW

Mechanical damage to nerve fibers during scoliosis correction can result in severe neurological disorders. It has been demonstrated that intraoperative neurophysiological monitoring during spinal surgery reduces the risk of motor deficits or paraplegia. Despite significant advances in the technique and application of IONM (intraoperative neurophysiological monitoring), data reporting the impact of implementing intraoperative neurophysiological monitoring on scoliosis surgery intervention remains very limited. Therefore, this review aims to investigate the correlation between the application of IONM and the risk of neurologic deficits in scoliosis patients undergoing surgery. The database sourced from PubMed (Jan 2010 to Jan 2022) was used to identify all studies evaluating the effectiveness and impact of intraoperative neurophysiological monitoring during scoliosis surgery and reducing the risk of postoperative complications. This systematic review included five studies. Multimodal IONM, with its high sensitivity and specificity, provides an objective benchmark that surgeons can implement to review surgical strategies to reduce the risk of permanent neurologic deficits. Multimodal IONM can be considered the gold standard of IONM in scoliosis surgery to prevent neurological damage and provide a more satisfactory result of surgical intervention.

METB-05. NON-INVASIVE DIAGNOSIS OF BRAINSTEM GLIOMAS IN PEDIATRIC, ADOLESCENT, AND YOUNG ADULT PATIENTS THROUGH CEREBROSPINAL FLUID CELL-FREE DNA SEQUENCING

Abstract Intrinsic brainstem tumors arising in pediatric, adolescent, and young adult patients comprise a spectrum of entities, predominantly diffuse midline gliomas (DMG) and IDH mutant astrocytomas. Accurate molecular diagnosis is essential for prognostication and optimal therapy. Therapeutic considerations include inclusion (in IDH mutant) or exclusion (in H3K27M) of adjuvant Temozolomide post radiotherapy and use of molecular targeted therapy (IDH inhibitors). Surgical biopsy, however, is associated with increased risk of permanent neurological deficits and may yield insufficient or non-diagnostic tissue. We hypothesized that minimally-invasive “liquid biopsy” of cerebrospinal fluid (CSF) could represent a superior diagnostic modality in this patient population, employing molecular analysis of cell free DNA (cfDNA). We analyzed 44 CSF samples from 38 unique patients for recurrent driver mutations in brainstem gliomas, including H3K27M, IDH1, and IDH2. MSK-IMPACT, a NY state-authorized hybridization capture-based next-generation panel DNA sequencing assay, was used for analysis. Samples without a detectable driver mutation by MSK-IMPACT testing were further subjected to gene targeted testing by droplet digital PCR. In all, 10/44 (22.7%) samples had mutations detected by MSK-IMPACT using standard calling criteria and 13 of the remaining 34 samples (38.2%) had supporting evidence of a mutation based on manual review. Further testing by ddPCR was performed on a subset of cases (based on DNA availability) which confirmed 7 of the previous low-level mutations and uncovered 4 additional mutations. Overall, 27/44 (61.4%) of cases had detectable evidence of a mutation, and of the 23 patients without a known tissue diagnosis, a driver in the CSF was identified for 47.8% of patients (11/23). Minimally-invasive analysis of CSF cfDNA in patients with intrinsic brainstem tumors has a high diagnostic yield and may obviate the need for tissue biopsy in a majority of patients. Testing with high sensitivity assays is valuable to maximize the rate of detection.

Postoperative Spinal Hematoma and Seroma.

Fluid collections after spine surgery are rare complications, although potentially grave, and may be broadly grouped into two major categories. Symptomatic postoperative epidural hematomas have some known risk factors and can present with a widely variable profile of signs and symptoms. Treatment involves emergent surgical evacuation to reduce the risk of permanent neurologic deficit. Postoperative seroma may lead to disruption of wound healing and deep infection and has been associated with the use of recombinant human bone mineral protein. These diagnoses may present diagnostic challenges; thorough understanding of the involved pathophysiology, meticulous clinical evaluation, and radiographic interpretation are critical to appropriate management and optimal outcome.

Letter: Stereotactic Radiosurgery for Dural Arteriovenous Fistulas: A Systematic Review and Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines.

To the Editor: We read with interest the article by Singh et al1 synthesizing the modern literature around the use of stereotactic radiosurgery (SRS) in the treatment of cranial dural arteriovenous fistulas (DAVFs). Neurointervention has disrupted the established treatment paradigm for many neurosurgical conditions. From intracranial aneurysms and large vessel occlusions to hydrocephalus, neuroendovascular surgery favorably altered the natural history and reduced the treatment-related morbidity of these and other disease processes. This has changed the mindset of clinicians who treat patients with cerebrovascular disease. For instance, a patient with an unruptured wide-necked aneurysm may be better served with an endovascular treatment that leaves a small neck remnant than with clip reconstruction that affords complete occlusion but requires a considerably more invasive surgical approach. Endovascular therapy has, in a generally safe and minimally invasive fashion, lowered the clinical risk of many pathologies without affording complete cure. In light of the available literature, a similar shift in mindset may be warranted regarding SRS for the treatment of cranial DAVFs. Just as SRS met with initial skepticism regarding its efficacy for vestibular schwannomas,2 neurointerventionalists and cerebrovascular surgeons have been slow to embrace its utility for DAVFs.3 In recent years, mounting evidence has emerged to support the efficacy of SRS as more than just a salvage therapy after failed endovascular embolization of DAVFs.4,5 In light of this, a recent systematic review and meta-analysis by Singh et al1 on behalf of the International Stereotactic Radiosurgery Society has summarized the DAVF SRS outcomes and provided some practice guidelines. In their analysis of 705 SRS-treated patients with DAVF in 21 studies, the authors reported complete occlusion and symptomatic cure rates of nearly 70% and 80%, respectively.1 In comparison, a recent meta-analysis of transarterial DAVF embolization using ethylene vinyl alcohol copolymer (Onyx; Medtronic Neurovascular) reported a complete occlusion rate of 82%.6 A multicenter retrospective analysis of the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database reported a complete obliteration rate of 55% after initial Onyx embolization.7 In this CONDOR study, the final obliteration rate with Onyx was less than 70%, even after all treatments. Surgical DAVF series typically report a higher obliteration rates than endovascular series, but many of these surgical cases have failed endovascular therapy, and operative morbidity and mortality rates up to 17% have been reported.3,8,9 The rates of post-SRS hemorrhage and permanent neurological deficits reported by Singh et al1 in their meta-analysis were 1.1% and 1.3%, respectively. By comparison, the risk of permanent neurological deficit after DAVF embolization was 4% in the meta-analysis by Sadeh-Gonike et al6 and 16.1% in the CONDOR database.7 In a separate analysis of unruptured high-grade DAVFs from CONDOR, post-treatment hemorrhage rates in the observation, endovascular, surgical, and SRS groups were 6.9%. 1.6%, 2.3%, and 0%, respectively.4 Although there were relatively few patients in the SRS group (n = 19), the risk of post-treatment hemorrhage seems to be similar among the various therapeutic modalities for unruptured DAVFs. DAVFs can be rewarding lesions to address for neurointerventionalists, as they provide a satisfying combination of technical skill, anatomic knowledge, and innovative approaches (ie, transvenous, direct puncture, combined surgical and endovascular). However, these cases can require hours of radiation exposure for the patient over potentially multiple embolization sessions, and there is a modest risk of DAVF recurrence even after initial angiographic cure. Based on analyses of the CONDOR database, obliteration of a low-grade DAVF after a single embolization session was achieved in <40% of cases,10 and the rate of recurrent arteriovenous shunting after angiographic cure (which required a mean of >2 embolization sessions) was 7%.11 Based on these findings, SRS may warrant consideration as a first-line treatment for unruptured DAVFs.1 If patients understand the potential risks associated with the latency period between treatment and efficacy, SRS should be discussed with unruptured patients with DAVF as a viable and reasonable alternative to embolization and surgical ligation. Definitive evidence from randomized comparative trials among the various treatment strategies for DAVFs is unlikely to be forthcoming for such a rare condition. Therefore, we will continue to rely on large multicenter databases, such as CONDOR, for our best available evidence regarding management outcomes and complications in contemporary neurovascular practice. The practice guidelines put forth by the ISRS underscore the favorable risk to benefit profile of SRS for appropriately selected DAVFs.

In Reply: Stereotactic Radiosurgery for Dural Arteriovenous Fistulas: A Systematic Review and Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines.

To the Editor: We appreciate the insights regarding our systematic review and meta-analysis and practice guidelines from the International Stereotactic Radiosurgery Society (ISRS) on stereotactic radiosurgery (SRS) for dural arteriovenous fistulas (dAVFs) in a recent Letter to the Editor by Raper et al.1,2 As noted, our analysis found that SRS was estimated to result in complete obliteration (CO) rates of approximately 70% with very favorable symptom improvement and symptom cure rates of roughly 97% and 79%, respectively. CO rates after SRS compare quite favorably with those with Onyx embolization only per the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) of approximately 55%.3 Of note, multimodality therapy with prior embolization was also noted to be associated with improved symptom cure rates in our analysis, suggesting a potential benefit in the therapeutic ratio for patients with poor prognostic factors for achievement of CO after either SRS or embolization alone. Treatment-related morbidity was also found to be quite limited with incidences of either permanent neurological deficits or hemorrhage after SRS both estimated to be roughly 1%. In our guidelines analysis, we were unable to report on favorable outcomes (as was performed in CONDOR and defined as achievement of CO without hemorrhage) because of lack of patient-level data. As noted, the risk of permanent neurological deficits after SRS compares favorably with embolization with estimates ranging from 4% to 16.1%.3,4 Previous analyses have noted similar rates of hemorrhage after embolization of 1.6%, quite similar to those observed in our analysis after SRS.3 We also noted in our analysis that previous hemorrhage was associated with a higher risk of hemorrhage after SRS similar to findings from CONDOR noting patients with prior hemorrhage had lower rates of favorable outcomes. The favorable risk profile and outcomes of SRS highlighted by our meta-analysis suggest it is an excellent therapeutic option for management of appropriately selected patients with dAVFs. Of note, limitations regarding both our analysis and CONDOR are inclusion of data from experienced and high volume sites that may not be reflective of sites with less experience in management of dAVFs. In the absence of prospective randomized data in part secondary to the rarity of dAVFs, prospective registries are key to further characterize both efficacy and toxicity of SRS for treatment of dAVFs. The prospectively maintained NeuroPoint Alliance SRS registry allows an avenue for analysis of patient-level data and further characterization of the impact of patient, lesion, and treatment characteristics on clinical outcomes after SRS for dAVFs.5 In addition, the International Radiosurgery Research Foundation (IRRF) has a long-standing history of conducting and publishing multi-institutional outcomes on SRS for a variety of indications. On the topic of SRS for dAVFs, the IRRF has published CO rates without hemorrhage ranging from 37% to 80% for 120 patients dependent on the presence of corticovenous reflux (CVR), prior hemorrhage, and noncavernous sinus (NCS) location.6 These findings are similar to our analysis where prior hemorrhage was associated with higher risk of hemorrhage after SRS and NCS dAVF associated with poorer CO and symptom control rates. Another analysis by the IRRF of 131 patients noted inferior CO rates in patients with NCS dAVFs as compared with cavernous sinus (CS) dAVFs with an association with CO and symptom improvement among NCS dAVFs but not among CS dAVFs.7 These findings in combination with those of our analysis suggest a need for improved CO rates, potentially through multimodality approaches for NCS dAVFs. The latency period for dAVFs, similar to arteriovenous malformations treated with SRS, has been characterized through work by the IRRF with similar rates of hemorrhage noted before and after SRS before CO being achieved.8 As noted by Raper et al, counseling on the risk of hemorrhage after SRS during the latency period is key as is patient selection given the association of prior hemorrhage and risk of hemorrhage during the latency period after SRS. Through these successful multi-institutional initiatives through the IRRF, robust clinical evidence has demonstrated the efficacy and safety of SRS for dAVFs. Further studies examining the potential role of multimodality approaches for patients at risk of unfavorable outcomes (particularly those with prior hemorrhages or NCS dAVFs) are warranted.

Neuroprotective and Regenerative Effects of Growth Hormone (GH) in the Embryonic Chicken Cerebral Pallium Exposed to Hypoxic-Ischemic (HI) Injury.

Prenatal hypoxic–ischemic (HI) injury inflicts severe damage on the developing brain provoked by a pathophysiological response that leads to neural structural lesions, synaptic loss, and neuronal death, which may result in a high risk of permanent neurological deficits or even newborn decease. It is known that growth hormone (GH) can act as a neurotrophic factor inducing neuroprotection, neurite growth, and synaptogenesis after HI injury. In this study we used the chicken embryo to develop both in vitro and in vivo models of prenatal HI injury in the cerebral pallium, which is the equivalent of brain cortex in mammals, to examine whether GH exerts neuroprotective and regenerative effects in this tissue and the putative mechanisms involved in these actions. For the in vitro experiments, pallial cell cultures obtained from chick embryos were incubated under HI conditions (<5% O2, 1 g/L glucose) for 24 h and treated with 10 nM GH, and then collected for analysis. For the in vivo experiments, chicken embryos (ED14) were injected in ovo with GH (2.25 µg), exposed to hypoxia (12% O2) for 6 h, and later the pallial tissue was obtained to perform the studies. Results show that GH exerted a clear anti-apoptotic effect and promoted cell survival and proliferation in HI-injured pallial neurons, in both in vitro and in vivo models. Neuroprotective actions of GH were associated with the activation of ERK1/2 and Bcl-2 signaling pathways. Remarkably, GH protected mature neurons that were particularly harmed by HI injury, but was also capable of stimulating neural precursors. In addition, GH stimulated restorative processes such as the number and length of neurite outgrowth and branching in HI-injured pallial neurons, and these effects were blocked by a specific GH antibody, thus indicating a direct action of GH. Furthermore, it was found that the local expression of several synaptogenic markers (NRXN1, NRXN3, GAP-43, and NLG1) and neurotrophic factors (GH, BDNF, NT-3, IGF-1, and BMP4) were increased after GH treatment during HI damage. Together, these results provide novel evidence supporting that GH exerts protective and restorative effects in brain pallium during prenatal HI injury, and these actions could be the result of a joint effect between GH and endogenous neurotrophic factors. Also, they encourage further research on the potential role of GH as a therapeutic complement in HI encephalopathy treatments.

Laboratory markers and risk of secondary hemorrhagic complications after anticoagulation due to venous thromboembolism in the early postoperative phase after neurosurgical procedures

Deep venous thromboses (DVT) and venous thromboembolisms (VTE) are serious complications after neurosurgical procedures. Hemorrhagic complications of thera-peutic anticoagulation on the other hand are also highly dreaded due to the high risk of permanent neurological deficit. Clear guidelines concerning dosage and duration of anticoagulation still do not exist for neurosurgical practice. Over a 10-year episode, patients with postoperative DVT or VTE were retrospectively identified and demographic risk factors as well as routine laboratory coagulation parameters were assessed. The goal was to determine patients at risk for a severe course of thrombosis and complications due to anticoagulation. In total, 173 patients with DVT or VTE were identified. Clinical effect of thrombosis was severe in 32.4% and fatal in 5.8% of all patients. Spinal surgery was associated with a higher risk of major or fatal outcome of thrombosis as compared to cranial procedures (fatal: 12.1 vs. 4.3%, p = 0.035). Elevated partial thromboplastin time, low platelet levels and low quick on diagnosis of thrombosis were associated with a fatal clinical course (p = 0.02, 0.04 and 0.02 respectively). Severe hemorrhagic complications on the other hand occurred in 6.6%, 0.6% were fatal. D-dimer did not predict the course of DVT/VTE but higher levels of D-dimer on day 3 after diagnosis of DVT/VTE were associated with a higher risk of severe bleeding complications (cutoff 4.95 µg/mL). Partial thromboplastin time after initiation of anticoagulation was not associated with hemorrhagic complications and might thus be not helpful to determine the risk of bleeding complications during the early postoperative phase. D-dimer might be of additional use to detect early bleeding complications.

Clinical Manifestations, Pathogenesis, Diagnosis and Treatment of Peripheral Neuropathies in Connective Tissue Diseases: More Diverse and Frequent in Different Subtypes than Expected.

Purpose of review: To discuss and summarize recent findings in peripheral neuropathy (PN) related to connective tissue diseases (CTD) including its prevalence, clinical manifestations, pathogenesis, diagnosis and treatment. Recent findings: Although PN is a common complication in CTD and has been well studied, recent research has shown that PN is more diverse and frequent in different subtypes of CTD than was expected. The incidence of PN in Sjögren’s syndrome and rheumatoid arthritis (RA) varies according to different disease subtypes, and the pathogenesis of neuropathic pain in different subtypes of eosinophilic granulomatosis with polyangiitis (EGPA) may also differ. Neurogenic inflammation, autoantibody-mediated changes, ischemia of the vascular wall and metabolic mechanisms have been shown to contribute to the pathogenesis of PN in CTD. Moreover, allergic inflammation has been recently identified as a possible new mechanism producing peripheral neuropathic pain associated with MPO-ANCA negative EGPA patients. Glucocorticoids are routinely used to relieve pain caused by PN. However, these steroids may cause hyperalgesia, exacerbate neuropathic pain, and activate the early phase of pain induction and produce hyperalgesia. Recently, neuroactive steroids, such as progesterone, tetrahydroprogesterone and testosterone, have been shown to exert protective effects for several PN symptoms, and in particular neuropathic pain. Neuroactive steroids will be an interesting topic for future research into PN in CTD. Summary: It is essential for the diagnosis and treatment of PN in CTD to be updated. Timely diagnosis, appropriate treatments, and multidisciplinary care are essential to minimize morbidity and decrease the risk of permanent neurologic deficits. Further studies are needed to guide diagnosis and treatment.

Skipped multilevel lesion as an atypical tuberculous spondylitis mimicking spinal metastasis: A case report

Tuberculosis (TB) is one of major global health threats and leads to morbidity and mortality. TB is prevalent in low and middle income countries especially in Sub-Saharan Africa and South East Asia. M. tuberculosis usually affects the lungs. Spine is the most common extrapulmonary sites for TB after lymph nodes, accounts for 1% of all TB cases, and 50 to 60% of osteoarticular TB. In the case of spinal TB, two or more adjacent vertebrae are usually involved due to hematogenous spread of bacteria in which the vertebral arteries feed the two adjacent vertebrae. The incidence of multiplelevel non-contiguous spinal TB is 1.1 to 16% of all skeletal TB. Multiple-level non-contiguous, an atypical form of spinal TB is rare. It has insidious symptoms, often with diagnostic delays and a higher risk of permanent neurological deficits. We report a case of atypical TB spondylitis with non-contiguous multiple level of lesions mimicking multiple bone metastases.

Efficacy and Safety of Combined Endovascular Embolization and Stereotactic Radiosurgery for Patients with Intracranial Arteriovenous Malformations: A Systematic Review and Meta-Analysis.

Whether the use of endovascular embolization could provide additional benefits in patients treated with stereotactic radiosurgery (SRS) for intracranial arteriovenous malformations (IAVMs) remains controversial. The current meta-analysis was conducted to assess the efficacy and safety of SRS with and without prior endovascular embolization in patients with IAVMs. The electronic databases of PubMed, EmBase, and Cochrane Library were systematically searched for eligible studies published from inception to August 12, 2020. The pooled results for obliteration rate, rehemorrhage rate, and permanent neurological deficits were calculated by odds ratios (ORs) with 95% confidence intervals (CIs) using the random-effects model. The sensitivity analysis, subgroup analysis, and publication bias for investigated outcomes were also evaluated. Nineteen studies (two prospective and 17 retrospective studies) involving a total of 3,454 patients with IAVMs were selected for the final meta-analysis. We noted that prior embolization and SRS were associated with a lower obliteration rate compared with SRS alone (OR, 0.57; 95% CI, 0.44–0.74; P < 0.001). However, prior embolization and SRS were not associated with the risk of rehemorrhage (OR, 1.05; 95% CI, 0.81–1.34; P = 0.729) and permanent neurological deficits (OR, 0.80; 95% CI, 0.48–1.33; P = 0.385) compared with SRS alone. The sensitivity analysis suggested that prior embolization might reduce the risk of permanent neurological deficits in patients with IAVMs treated with SRS. The treatment effects of prior embolization in patients with IAVMs could be affected by nidus volume, margin dose, intervention, and follow-up duration. This study found that prior embolization was associated with a reduced risk of obliteration in patients with IAVMs treated with SRS. Moreover, prior embolization might reduce the risk of permanent neurological deficits in patients with IAVMs.

Posterior reversible encephalopathy syndrome as the first manifestation of mixed connective tissue disorder: a case report

BackgroundPosterior reversible encephalopathy syndrome (PRES) is a neurological syndrome characterised by a range of neurological symptoms and signs, and distinctive neuroimaging findings reflecting vasogenic oedema. Posterior reversible encephalopathy syndrome has been described in association with many autoimmune diseases, but its association with mixed connective tissue disorder (MCTD) is very rare. After an extensive review of the literature, we found only three cases of posterior reversible encephalopathy syndrome in association with mixed connective tissue disorder. But unlike other cases, in our patient, PRES is the presenting manifestation of mixed connective tissue disorder which is first of its kind.Case presentationWe present a 30-year-old female from Southern India who had initially reported with complaints of fever, multiple episodes of vomiting and cough with expectoration. She had accelerated hypertension and moderate thrombocytopenia. Two days later, she developed sudden onset of visual disturbances and had a drop in sensorium. Neuroimaging done was suggestive of atypical posterior reversible encephalopathy syndrome, and autoimmune workup was positive for mixed connective tissue disorder. With prompt blood pressure control and anti-seizure medications, she recovered completely.ConclusionEarly diagnosis and prompt control of blood pressure, along with anti-seizure measures, play a crucial role in management. Awareness about this rare association is essential for early diagnosis and treatment, and therefore reducing the risk of permanent neurologic deficits. This case is being reported because of its rarity.

Rheumatologic Disorders and the Nervous System

This article describes the neurologic manifestations of systemic autoimmune diseases. Systemic autoimmune diseases can be associated with a wide spectrum of neurologic comorbidities involving the central and peripheral nervous systems. Systemic lupus erythematosus (SLE) can be associated with a number of manifestations predominantly affecting the central nervous system (CNS), whereas peripheral neuropathy is less common. Sjögren syndrome can be associated with peripheral neuropathy in 10% of cases and CNS disease in 2% to 5% of cases. The risk of stroke is increased in SLE, rheumatoid arthritis, temporal arteritis, psoriatic arthritis, and ankylosing spondylitis. Systemic vasculitides present most commonly with mononeuritis multiplex but can also affect the CNS. Cognitive dysfunction is a common symptom among patients with systemic autoimmune diseases, most commonly seen in patients with SLE or Sjögren syndrome. Neurologic manifestations of systemic autoimmune disease are important to recognize, as they may often be the presenting manifestation leading to diagnosis of the systemic disease or may be associated with increased morbidity, other complications, or mortality. Timely diagnosis and institution of appropriate treatment, often requiring multidisciplinary care, is essential to minimize morbidity and decrease the risk of permanent neurologic deficits.

Dexmedetomidine as adjunct in awake craniotomy - improvement or not?

Over the last decade, awake craniotomy for tumor resection has become a standard to maximize tumor resection and minimize the risk of permanent neurological deficits. Different techniques and medication regimes have been tested for this procedure. Until today there is no consensus on the optimal approach. Therefore, we investigated the effect of dexmedetomidine as an adjunct in awake cerebral tumor surgery and evaluated our improved technique. Data of patients who underwent awake craniotomy for tumor resection at our institution between 09/2006 and 05/2018 were retrospectively analyzed. All patients were kept awake after cortical mapping. After changing our standard anesthetic procedure from propofol/remifentanil alone to propofol/remifentanil and dexmedetomidine, we performed an evaluation of time to arousal, drug dosages, patients' cooperation and the occurrence of periprocedural adverse events. Eighty-four patients received propofol/remifentanil alone (SG). A further 17 patients additionally received dexmedetomidine following craniotomy in order to induce rapid arousal (DG). In the dexmedetomidine group a significantly reduced infusion time for propofol (169.2 ± 47.4 vs. 212.9 ± 63.3 minutes; P = 0.008) and non-significantly shorter time to arousal (12.0 [10.0/16.5] vs. 15.0 [10.0/20.0] minutes; P = 0.271) could be identified. In general, the overall procedure was very well tolerated by all patients. The asleep-awake technique is a well-accepted and safe procedure. It allows continuous surveillance of the patient's neurological function during tumor resection and the postoperative phase, minimizing complications. In addition, our data show that the use of dexmedetomidine results in a shorter time to arousal.

Immersing Patients in a Virtual Reality Environment for Brain Mapping During Awake Surgery: Safety Study

Brain mapping by direct electrical stimulation during awake craniotomy is now a standard procedure that reduces the risk of permanent neurologic deficits. Virtual reality technology immerses the patient in a virtually controlled, interactive world, offering a unique opportunity to develop innovative tasks for perioperative mapping of complex cognitive functions. The objective of this prospective single-center study was to evaluate the tolerance and safety of a virtual reality headset (VRH) and immersive virtual experiences in patients undergoing awake craniotomy and brain mapping by direct electrical stimulation. The study included 30 patients with a brain tumor near the language area. Language mapping was performed with a naming task, DO 80, presented on a digital tablet and then in two-dimensional and three-dimensional formats through a VRH. During wound closure, different virtual reality experiences were proposed to the patient, offering different types of virtual motion or interaction with an avatar piloted by a neuropsychologist. Two patients could not use the VRH owing to technical issues. No procedure was aborted, no patient experienced virtual reality sickness and all patients reported they would repeat the procedure. Despite a high rate of intraoperative focal seizures, there was no argument to attribute the seizures to VRH use. This study shows that it is possible during awake brain surgery to immerse the patient in a virtual environment and to interact with the patient, opening the field of new brain mapping procedures for complex cognitive functions.

Surgical Dissection of a Perimedullary Fistula of Conus Medullaris With Long-Term Follow-Up: 2-Dimensional Operative Video.

Perimedullary fistulae of the spinal cord are rare vascular lesions that can present with different clinical patterns: hemorrhage, progressive myelopathy due to arterial steal and/or venous congestion, or symptoms due to compression of neural structures by engorged vessels. Treatment consists of surgical excision, endovascular embolization, or a combination of the two. If complete obliteration of the nidus exposes the patient to undue risk of permanent neurological deficits, incomplete obliteration with reduction of the vascular supply is a reasonable compromise to improve clinical symptomatology. Partial devascularization may also alter the natural history by decreasing the risk of further growth and bleeding. In this video we illustrate the case of a patient with a perimedullary fistula of the conus treated with surgical disconnection of the main fistulous component. Partial devascularization resulted in resolution of MRI signal changes and symptoms with documented good clinical and radiological outcome and progressive regression of the residual nidus over six years of follow-up.

Incidence and Risk Factors for Venous Thromboembolism After Spine Surgery in Korean Patients

Data regarding the incidence of venous thromboembolism (VTE) after spine surgery are scarce. Identifying ideal candidates for pharmacologic thromboprophylaxis and balancing the risk of thromboembolic complications against the risk of permanent neurologic deficits from a spinal epidural hematoma (SEH) are difficult. Even guidelines cannot suggest the standard of thromboprophylaxis. This study aimed to identify the incidence of and risk factors for VTE after spine surgery in the Korean population. In addition, the rate of pharmacoprophylaxis and the incidence of SEH after spine surgery were analyzed. The study cohort was generated by extracting patients with disease codes of spine surgery and VTE from the Health Insurance Review & Assessment Service National Inpatient Sample in2014. After analyzing the incidence of VTE after spine surgery, a univariate comparison was performed to examine the possible relationship between the incidence of VTE and the independent variable. Variables found to be significant were included in a multivariable analysis model for further analysis. The incidence of VTE was 2.09% among all 21,261 patients who had spine surgery, and prophylaxis was applied to 7.89% of all patients who had spine surgery. Comorbidities and surgery-related risk factors were venous disease, cancer, respiratory disease, prolonged surgery hours, and increased total blood loss. Hospital-related risk factors were the location and hospital size. On the basis of the incidence of VTE and the risk factors, more active prophylaxis is suggested for patients in the Korean population who undergo spine surgery.

First United Kingdom Experience of Navigated Transcranial Magnetic Stimulation in Preoperative Mapping of Brain Tumors

Surgery for lesions in eloquent brain areas remains challenging owing to the risk of permanent neurological deficits. To date, direct electrical stimulation (DES) and intraoperative neuromonitoring represent the reference standard. Recently, navigated transcranial magnetic stimulation (nTMS) has emerged as a mapping tool to optimize surgical planning. Our aim was to correlate nTMS with the intraoperative findings and assess its effects on surgical decision-making. We retrospectively reviewed our series of patients who had undergone craniotomy for removal of a brain tumor at our institution with preoperative nTMS, intraoperative neuromonitoring, and DES from February 2017 to February 2018. Demographic data, tumor entity and location, extent of resection, change in surgical approach, and neurological outcome were collected. Of 35 patients, 24 (68.6%) had undergone preoperative motor mapping and 11 (31.4%) had undergone mapping for language. Histopathological examination demonstrated glioma in 88.6% (high grade, n= 24; low grade, n= 6), metastasis (n= 2), epidermoid cyst (n= 1), and cavernoma (n= 1). nTMS resulted in change in the surgical strategy in 31.5% (craniotomy size, n= 7; access pathway, n= 3; surgical indication, n= 1). The specificity of nTMS for language was 66.7%, with a negative predictive value of 74.1%. nTMS motor mapping correlated with DES in all cases, with a mean abductor pollicis brevis hotspot distance of 3.50 ± 0.66 mm (n= 9). nTMS is a safe, noninvasive adjunctive tool for preoperative mapping of brain tumors in eloquent areas. Furthermore, nTMS can influence the surgical decisions in up to one third of patients in our experience.

A difficult situation \u2013 balancing critical anticoagulation versus the risk of permanent neurologic deficit: a case report

BackgroundAnticoagulation is the mainstay of treatment for pulmonary embolism. However, if bleeding unfortunately occurs, the risks and benefits of anticoagulation present a challenge. Management of one hemorrhagic complication, retroperitoneal hematoma, is rare, difficult, and controversial.Case presentationA 73-year-old white man presented with left lower extremity swelling and dyspnea. He was tachycardic, hypertensive, and demonstrated poor oxygen saturation of 81% on ambient air. A computed tomography angiogram revealed a saddle pulmonary embolus. Tissue plasminogen activator was administered and he was started on a heparin infusion. He was eventually transitioned to enoxaparin. On the day of discharge, however, he had sudden onset of right leg numbness and weakness below his hip. A computed tomography of his head was not concerning for stroke, and neurology was consulted. Neurology was concerned for spinal cord infarction versus hematoma and recommended magnetic resonance imaging of his thoracic and lumbar spine. The magnetic resonance imaging revealed a left psoas hematoma. A computed tomography scan of his pelvis also showed a right psoas and iliacus hematoma. He was transitioned to a low intensity heparin infusion. The following day his left leg exhibited similar symptoms. There was concern of progressive and irreversible nerve damage due to compression if the hematomas were not drained. Interventional radiology was consulted for drainage. The heparin infusion was paused, drainage was performed, and the heparin infusion was reinitiated 6 hours following the procedure by interventional radiology. His blood counts and neurologic examination stabilized and eventually improved. He was discharged home on a novel anticoagulant.ConclusionsManagement of a retroperitoneal hematoma can commence with recognition of the warning signs of bleeding and neurological impairment, and consulting the appropriate services in case the need for intervention arises. A conservative approach of volume resuscitation and blood transfusion can be used initially, with the need for pausing or reversing anticoagulation being assessed on an individual basis with expert consultation. If intervention becomes necessary, other interventional radiology-based modalities can be used to identify and stop the bleeding source, and interventional radiology-guided drainage can be performed to decrease the hematoma burden and relieve neurological symptoms.