Paf1 complex subunit Rtf1 stimulates H2B ubiquitylation by interacting with the highly conserved N-terminal helix of Rad6.

Histone modifications coupled to transcription elongation play important roles in regulating the accuracy and efficiency of gene expression. The monoubiquitylation of a conserved lysine in H2B (K123 in Saccharomyces cerevisiae; K120 in humans) occurs cotranscriptionally and is required for initiating a histone modification cascade on active genes. H2BK123 ubiquitylation (H2BK123ub) requires the RNA polymerase II (RNAPII)-associated Paf1 transcription elongation complex (Paf1C). Through its histone modification domain (HMD), the Rtf1 subunit of Paf1C directly interacts with the ubiquitin conjugase Rad6, leading to the stimulation of H2BK123ub in vivo and in vitro. To understand the molecular mechanisms that target Rad6 to its histone substrate, we identified the site of interaction for the HMD on Rad6. Using in vitro cross-linking followed by mass spectrometry, we localized the primary contact surface for the HMD to the highly conserved N-terminal helix of Rad6. Using a combination of genetic, biochemical, and in vivo protein cross-linking experiments, we characterized separation-of-function mutations in S. cerevisiae RAD6 that greatly impair the Rad6-HMD interaction and H2BK123 ubiquitylation but not other Rad6 functions. By employing RNA-sequencing as a sensitive approach for comparing mutant phenotypes, we show that mutating either side of the proposed Rad6-HMD interface yields strikingly similar transcriptome profiles that extensively overlap with those of a mutant that lacks the site of ubiquitylation in H2B. Our results fit a model in which a specific interface between a transcription elongation factor and a ubiquitin conjugase guides substrate selection toward a highly conserved chromatin target during active gene expression.

The nucleosome acidic patch directly interacts with subunits of the Paf1 and FACT complexes and controls chromatin architecture in vivo.

The nucleosome core regulates DNA-templated processes through the highly conserved nucleosome acidic patch. While structural and biochemical studies have shown that the acidic patch controls chromatin factor binding and activity, few studies have elucidated its functions in vivo. We employed site-specific crosslinking to identify proteins that directly bind the acidic patch in Saccharomyces cerevisiae and demonstrated crosslinking of histone H2A to Paf1 complex subunit Rtf1 and FACT subunit Spt16. Rtf1 bound to nucleosomes through its histone modification domain, supporting its role as a cofactor in H2B K123 ubiquitylation. An acidic patch mutant showed defects in nucleosome positioning and occupancy genome-wide. Our results provide new information on the chromatin engagement of two central players in transcription elongation and emphasize the importance of the nucleosome core as a hub for proteins that regulate chromatin during transcription.

Focused Ultrasound Thalamotomy with Dentato-Rubro-Thalamic Tractography in Patients with Spinal Cord Stimulators and Cardiac Pacemakers.

Magnetic resonance image-guided high-intensity focused ultrasound (MRgFUS)-based thermal ablation of the ventral intermediate nucleus of the thalamus (VIM) is a minimally invasive treatment modality for essential tremor (ET). Dentato-rubro-thalamic tractography (DRTT) is becoming increasingly popular for direct targeting of the presumed VIM ablation focus. It is currently unclear if patients with implanted pulse generators (IPGs) can safely undergo MRgFUS ablation and reliably acquire DRTT suitable for direct targeting. We present an 80-year-old male with a spinal cord stimulator (SCS) and an 88-year-old male with a cardiac pacemaker who both underwent MRgFUS for medically refractory ET. Clinical outcomes were measured using the Clinical Rating Scale for Tremor (CRST). DRTT was successfully created and imaging parameter adjustments did not result in any delay in procedural time in either case. In the first case, 7 therapeutic sonications were delivered. The patient improved immediately and durably with a 90% CRST-disability improvement at 6-week follow-up. In our second case, 6 therapeutic sonications were delivered with durable, 75% CRST-disability improvement at 6 weeks. These are the first cases of MRgFUS thalamotomy in patients with IPGs. DRTT targeting and MRgFUS-based thermal ablation can be safely performed in these patients using a 1.5-T MRI.

Proximal junctional kyphosis following T10-pelvis fusion presenting with neurologic compromise: case presentations and review of the literature.

Purpose: Proximal Junctional Kyphosis (PJK) is a well-documented phenomenon following spinal instrumented fusion. Myelopathy associated with proximal junctional failure (PJF) is poorly described in the literature. Adjacent segment disease, fracture above the upper instrumented vertebrae and subluxation may all cause cord compression, ambulatory dysfunction, and/or lower extremity weakness in the postoperative period.Materials and methods: We review the literature on PJK and PJF, and discusses the postoperative management of three patients who experienced myelopathy associated with PJF following T9/10 to pelvis fusion at a single institution.Results and conclusions: PJF with myelopathy must be diagnosed and surgically corrected early on so as to minimize permanent neurologic injury. Patients requiring significant sagittal deformity correction are at greater risk for PJF, and may benefit from constructs terminating in the upper thoracic spine.

Local Control and Survival Outcomes After Stereotactic Radiosurgery for Brain Metastases From Gastrointestinal Primaries: An International Multicenter Analysis.

BACKGROUND: There are limited data regarding outcomes for patients with gastrointestinal (GI) primaries and brain metastases treated with stereotactic radiosurgery (SRS). OBJECTIVE: To examine clinical outcomes after SRS for patients with brain metastases from GI primaries and evaluate potential prognostic factors. METHODS: The International Radiosurgery Research Foundation centers were queried for patients with brain metastases from GI primaries managed with SRS. Primary outcomes were local control (LC) and overall survival (OS). Kaplan-Meier analysis was used for univariate analysis (UVA) of prognostic factors. Factors significant on UVA were evaluated with a Cox multivariate analysis proportional hazards model. Logistic regressions were used to examine correlations with RN. RESULTS: We identified 263 eligible patients with 543 brain metastases. Common primary sites were rectal (31.2%), colon (31.2%), and esophagus (25.5%) with a median age of 61.6 years (range: 37-91.4 years) and a median Karnofsky performance status (KPS) of 90% (range: 40%-100%). One-year and 2-year LC rates were 83.5% (95% CI: 78.9%-87.1%) and 73.0% (95% CI: 66.4%-78.5%), respectively. On UVA, age >65 years ( P = .001), dose <20 Gy ( P = .006) for single-fraction plans, KPS <90% ( P < .001), and planning target volume ≥2cc ( P = .007) were associated with inferior LC. All factors other than dose were significant on multivariate analysis ( P ≤ .002). One-year and 2-year OS rates were 68.0% (95% CI: 61.5%-73.6%) and 31.2% (95% CI: 24.6%-37.9%), respectively. Age > 65 years ( P = .006), KPS <90% ( P = .005), and extracranial metastases ( P = .05) were associated with inferior OS. CONCLUSION: SRS resulted in comparable LC with common primaries. Age and KPS were associated with both LC and OS with planning target volume and extracranial metastases correlating with LC and OS, respectively. These factors should be considered in GI cancer patient selection for SRS.

Local control and survival after stereotactic radiosurgery for colorectal cancer brain metastases: an international multicenter analysis.

OBJECTIVE: The goal of this study was to characterize local tumor control (LC), overall survival (OS), and safety of stereotactic radiosurgery for colorectal brain metastasis (CRBM). METHODS: Ten international institutions participating in the International Radiosurgery Research Foundation provided data for this retrospective case series. This study included 187 patients with CRBM (281 tumors), with a median age of 62 years and 56.7% being male. Most patients (53.5%) had solitary tumors, although 10.7% had > 5 tumors. The median tumor volume was 2.7 cm3 (IQR 0.22-8.1 cm3), and the median margin dose was 20 Gy (IQR 18-22 Gy). RESULTS: The 3-year LC and OS rates were 72% and 20%, respectively. Symptomatic adverse radiation effects occurred in 1.6% of patients. In the multivariate analysis, age > 65 years and tumor volume > 4.0 cm3 were significant predictors of tumor progression (hazard ratio [HR] 2.6, 95% CI 1.4-4.9; p = 0.003 and HR 3.4, 95% CI 1.7-6.9; p < 0.001, respectively). Better performance status (Karnofsky Performance Scale score > 80) was associated with a reduced risk of tumor progression (HR 0.38, 95% CI 0.19-0.73; p = 0.004). Patient age > 62 years (HR 1.6, 95% CI 1.1-2.3; p = 0.03) and the presence of active extracranial disease (HR 1.7, 95% CI 1.1-2.4; p = 0.009) were significantly associated with worse OS. CONCLUSIONS: Stereotactic radiosurgery offers a high LC rate and a low rate of symptomatic adverse radiation effects for the majority of CRBMs. The OS and LC favored younger patients with high functional performance scores and inactive extracranial disease.

Ethical Issues in Intraoperative Neuroscience Research: Assessing Subjects' Recall of Informed Consent and Motivations for Participation.

BackgroundAn increasing number of studies utilize intracranial electrophysiology in human subjects to advance basic neuroscience knowledge. However, the use of neurosurgical patients as human research subjects raises important ethical considerations, particularly regarding informed consent and undue influence, as well as subjects' motivations for participation. Yet a thorough empirical examination of these issues in a participant population has been lacking. The present study therefore aimed to empirically investigate ethical concerns regarding informed consent and voluntariness in Parkinson's disease patients undergoing deep brain stimulator (DBS) placement who participated in an intraoperative neuroscience study.MethodsTwo semi-structured 30-minute interviews were conducted preoperatively and postoperatively via telephone. Interviews assessed participants' motivations for participation in the parent intraoperative study, recall of information presented during the informed consent process, and participants' postoperative reflections on the research study.ResultsTwenty-two participants (mean age = 60.9) completed preoperative interviews at a mean of 7.8 days following informed consent and a mean of 5.2 days prior to DBS surgery. Twenty participants completed postoperative interviews at a mean of 5 weeks following surgery. All participants cited altruism or advancing medical science as "very important" or "important" in their decision to participate in the study. Only 22.7% (n = 5) correctly recalled one of the two risks of the study. Correct recall of other aspects of the informed consent was poor (36.4% for study purpose; 50.0% for study protocol; 36.4% for study benefits). All correctly understood that the study would not confer a direct therapeutic benefit to them.ConclusionEven though research coordinators were properly trained and the informed consent was administered according to protocol, participants demonstrated poor retention of study information. While intraoperative studies that aim to advance neuroscience knowledge represent a unique opportunity to gain fundamental scientific knowledge, improved standards for the informed consent process can help facilitate their ethical implementation.

Adverse radiation effects in volume-staged radiosurgery for large arteriovenous malformations: a multiinstitutional study.

OBJECTIVE: The optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. One approach is volume-staged stereotactic radiosurgery (VS-SRS). The authors previously reported efficacy of VS-SRS for large AVMs in a multiinstitutional cohort; here they focus on risk of symptomatic adverse radiation effects (AREs). METHODS: This is a multicentered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM, with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. The authors evaluated permanent, transient, and total ARE events that were symptomatic. RESULTS: Patients received 2-4 total volume stages. The median age was 33 years at the time of the first SRS volume stage, and the median follow-up was 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cm3 (range 7.7-94.4 cm3), with a median margin dose per stage of 17 Gy (range 12-20 Gy). A total of 64 patients (25%) experienced an ARE, of which 19 were permanent. Rather than volume, maximal linear dimension in the Z (craniocaudal) dimension was associated with toxicity; a threshold length of 3.28 cm was associated with an ARE, with a 72.5% sensitivity and a 58.3% specificity. In addition, parietal lobe involvement for superficial lesions and temporal lobe involvement for deep lesions were associated with an ARE. CONCLUSIONS: Size remains the dominant predictor of toxicity following SRS, but overall rates of AREs were lower than anticipated based on baseline features, suggesting that dose and size were relatively dissociated through volume staging. Further techniques need to be assessed to optimize outcomes.

Complication Rates During Endoscopic Microvascular Decompression Surgery Are Low With or Without Petrosal Vein Sacrifice.

OBJECTIVE: Endoscopic-microvascular decompression (E-MVD) is a well-described treatment for trigeminal neuralgia (TGN), but there has been debate on the safety of intraoperative sacrifice of the petrosal vein (PV) due to concern for subsequent venous insufficiency. Our objective was to investigate the risk of PV sacrifice during E-MVD in TGN and subsequent postoperative complications and pain outcomes. METHODS: 5 five-year review yielded 201 patients who underwent MVD for TGN. PV sacrifice, vascular compressive anatomy, and postoperative complications attributable to venous insufficiency were analyzed. Preoperative and postoperative pain outcomes were analyzed. RESULTS: PV was sacrificed in 118 of 201 (59%) of patients, with 43 of 201 (21%) patients undergoing partial sacrifice versus 75 of 201 (37%) with complete sacrifice. No cases of venous infarction, cerebellar swelling, or fatal complications were noted in either cohort. Non-neurologic complications occurred in 1.69% (2 of 118) of patients with PV sacrifice and 0% (0 of 83) of patients with PV preservation. Neurologic deficits (facial palsy, conductive hearing loss, gait instability, memory deficit) occurred in equal proportions in PV preservation and sacrifice groups (2.41% vs. 1.69%) Overall, 87.3% (145 of 166) patients reported their pain as "very much improved" or "much improved" at 1 month, and no difference between groups was identified. CONCLUSIONS: This study did not find higher complication rates in patients undergoing petrosal vein sacrifice during E-MVD for trigeminal neuralgia. In this series where petrosal vein was sacrificed only 59% of the time, it appears to be a safe technique, but larger studies will be needed to determine true incidence of complications after PV sacrifice.

Surgical Treatment of Flat Back Syndrome With Anterior Hyperlordotic Cages.

BACKGROUND: Traditional correction for flat back syndrome is performed with a posterior-based surgery or combined approaches in revision cases. OBJECTIVE: To evaluate outcome from anterior surgery with the use of hyperlordotic cages (HLCs) in patients with flat back syndrome. METHODS: All patients operated with or without prior posterior lumbar surgery were studied. Pre- to postoperative sagittal alignment was analyzed. Radiographic parameters were analyzed including T1 pelvic angle (T1PA), sagittal vertical axis (SVA), pelvic tilt (PT), pelvic incidence (PI), lumbar lordosis (LL), sacral slope (SS), pelvic incidence and lumbar lordosis (PI-LL), and T4-12TK. RESULTS: All 50 patients (mean age of 58 yr, 72% female with mean body mass index of 28) demonstrated significant radiographic alignment difference in their spinopelvic and global parameters from pre- to postoperative standing: LL (-37.04° vs -59.55°, P < .001), SS (35.12 vs 41.13, P < .001), PI-LL (23.55 vs 6.46), T4-12 TK (30.59 vs 41.67), PT (28.22 vs 22.13), SVA in mm (80.94 vs 37.39), and T1PA (28.70° vs 18.43°, P < .001). Using linear regression analysis, predicted pre- to postoperative change in standing LL corresponded to a pre- to postoperative changes in standing PI-LL mismatch, T1PA, TK, SS, PT, and SVA (R2 = 0.59, 0.38, 0.25, 0.16, 0.12, and 0.17, respectively). Five degrees of pre- to postoperative change in T1PA translates to -4.15° change in LL. CONCLUSION: Anterior surgery with HLCs followed by posterior instrumentation is an effective technique to treat flat back syndrome. HLCs are effective to maximize LL up to 30°, which is equivalent in magnitude to a pedicle subtraction osteotomy, but associated with less blood loss, quicker recovery, lower complications, and good surgical outcome.

Growth of Lumbosacral Perineural (Tarlov) Cysts: A Natural History Analysis.

BACKGROUND: Tarlov cysts (TC) are commonly found spinal perineural cysts. Symptomatic TCs are rare, however, and there is no consensus on their pathogenesis and optimal management. OBJECTIVE: To characterize cyst growth in patients with symptomatic TCs. METHODS: This is a retrospective cohort study of 28 subjects, evaluated for symptomatic TCs (2011-2017). Each of the subjects had multiple magnetic resonance imaging (MRIs) across time and was included in a natural history analysis. RESULTS: A total of 42 TCs were identified across the 28 subjects, of which 7 cysts (17%) across 5 subjects demonstrated growth. Across a mean follow-up of 4.7 ± 1.8 years, TCs grew at a relative rate of 2.9 ± 2.6% in the anteroposterior, 4.3 ± 3.8% in the craniocaudal, and 1.4 ± 1.4% in the transverse dimensions per year. None of the cysts decreased in size between successive MRIs. Symptoms of cerebrospinal fluid (CSF) hypotension (positional headaches) were positive predictors of prior cyst growth on logistic regression (P = 0.02, odds ratio = 10). A total of 2 of the 5 subjects were initially asymptomatic from their TCs, and developed symptoms during the period of cyst growth, whereas 2 others experienced worsening of their symptoms during cyst growth. CONCLUSION: We report on the growth of TCs, which is consistent with a widely-held theory that hydrostatic and pulsatile forces of CSF along with a ball-valve phenomenon allow for continuous dilation of TCs.

Association of spinal instability due to metastatic disease with increased mortality and a proposed clinical pathway for treatment.

OBJECTIVE: Multidisciplinary treatment including medical oncology, radiation oncology, and surgical consultation is necessary to provide comprehensive therapy for patients with spinal metastases. The goal of this study was to review the use of radiation therapy and/or surgical intervention and their impact on patient outcomes. METHODS: In this retrospective series, the authors identified at their institution those patients with spinal metastases who had received radiation therapy alone or had undergone surgery with or without radiation therapy within a 6-year period. Data on patient age, chemotherapy, surgical procedure, radiation therapy, Karnofsky Performance Status (KPS), primary tumor pathology, Spinal Instability Neoplastic Score (SINS), and survival after treatment were collected from the patient electronic medical records. N - 1 chi-square testing was used for comparisons of proportions. The Student t-test was used for comparisons of means. A p value < 0.05 was considered statistically significant. A survival analysis was completed using a multivariate Cox proportional hazards model. RESULTS: Two hundred thirty patients with spinal metastases were identified, 109 of whom had undergone surgery with or without radiation therapy. Among the 104 patients for whom the surgical details were reviewed, 34 (33%) had a history of preoperative radiation to the surgical site but ultimately required surgical intervention. In this surgical group, a significantly increased frequency of death within 30 days was noted for the SINS unstable patients (23.5%) as compared to that for the SINS stable patients (2.3%; p < 0.001). The SINS was a significant predictor of time to death among surgical patients (HR 1.11, p = 0.037). Preoperative KPS was not independently associated with decreased survival (p > 0.5) on univariate analysis. One hundred twenty-six patients met the criteria for inclusion in the radiation-only analysis. Ninety-eight of these patients (78%) met the criteria for potential instability (PI) at the time of treatment, according to the SINS system. Five patients (5%) with PI in the radiation therapy group had a documented neurosurgical or orthopedic surgery consultation prior to radiation therapy. CONCLUSIONS: At the authors' institution, patients with gross mechanical instability per the SINS system had an increased rate of 30-day postoperative mortality, which remained significant when controlling for other factors. Surgical consultation for metastatic spine patients receiving radiation oncology consultation with PI is low. The authors describe an institutional pathway to encourage multidisciplinary treatment from the initial encounter in the emergency department to expedite surgical evaluation and collaboration.

Dose response and architecture in volume staged radiosurgery for large arteriovenous malformations: A multi-institutional study.

BACKGROUND: Optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. Volume-staged stereotactic radiosurgery (VS-SRS) provides an effective option for these high-risk lesions, but optimizing treatment for these recalcitrant and rare lesions has proven difficult. METHODS: This is a multi-centered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. We evaluated near complete response (nCR), obliteration, cure, and overall survival. RESULTS: With a median age of 33 years old at the time of first SRS volume stage, patients received 2-4 total volume stages and a median follow up of 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cc (range: 7.7-94.4 cc) with a median margin dose per stage of 17 Gy (range: 12-20 Gy). Total AVM volume, margin dose per stage, compact nidus, lack of prior embolization, and lack of thalamic location involvement were all associated with improved outcomes. Dose >/= 17.5 Gy was strongly associated with improved rates of nCR, obliteration, and cure. With dose >/= 17.5 Gy, 5- and 10-year cure rates were 33.7% and 76.8% in evaluable patients compared to 23.7% and 34.7% of patients with 17 Gy and 6.4% and 20.6% with <17 Gy per volume-stage (p = 0.004). Obliteration rates in diffuse nidus architecture with <17 Gy were particularly poor with none achieving obliteration compared to 32.3% with doses >/= 17 Gy at 5 years (p = 0.007). Comparatively, lesions with a compact nidus architecture exhibited obliteration rates at 5 years were 10.7% vs 9.3% vs 26.6% for dose >17 Gy vs 17 Gy vs >/=17.5 Gy. CONCLUSION: VS-SRS is an option for upfront treatment of large AVMs. Higher dose was associated with improved rates of nCR, obliteration, and cure suggesting that larger volumetric responses may facilitate salvage therapy and optimize the chance for cure.

Email as an Encumbrance to Physician-patient Communication.

Physician-patient interaction through email poses several concerns regarding the security, efficiency, and misinterpretation of critical information. Incoming emails received by a single university-based physician in 2013 were analyzed in order to determine whether a general non-patient specific email is appropriate for patient use. Emails received were divided into seven categories: Informational, Academic, Advertisement, Organization/Department/ University, Mission Critical, Personal, and Patient. A total of 9,102 emails were received and read by the physician, with an average of 25 emails per day, out of which 823 (9%) emails were directly sent by patients. The total time spent reading emails was five days, seven hours, and 24 minutes. General email is not an effective means of streamlining physician-patient communication. Non-essential emails, which represent a majority of incoming messages, decrease the productivity of physicians and prevent them from responding to urgent messages in a timely manner. Additionally, this creates the chance for critical patient information getting lost with the volume of received emails. This could be detrimental to patient care and satisfaction. Recently, an online portal was instated to provide a method of secure communication, and less than five patient emails were received in the physician's personal email since then.

Long-term outcomes following deep brain stimulation for Parkinson's disease.

OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment for several movement disorders, including Parkinson's disease (PD). While this treatment has been available for decades, studies on long-term patient outcomes have been limited. Here, the authors examined survival and long-term outcomes of PD patients treated with DBS. METHODS: The authors conducted a retrospective analysis using medical records of their patients to identify the first 400 consecutive patients who underwent DBS implantation at their institution from 1999 to 2007. The medical record was used to obtain baseline demographics and neurological status. The authors performed survival analyses using Kaplan-Meier estimation and multivariate regression using Cox proportional hazards modeling. Telephone surveys were used to determine long-term outcomes. RESULTS: Demographics for the cohort of patients with PD (n = 320) were as follows: mean age of 61 years, 70% male, 27% of patients had at least 1 medical comorbidity (coronary artery disease, congestive heart failure, diabetes mellitus, atrial fibrillation, or deep vein thrombosis). Kaplan-Meier survival analysis on a subset of patients with at least 10 years of follow-up (n = 200) revealed a survival probability of 51% (mean age at death 73 years). Using multivariate regression, the authors found that age at implantation (HR 1.02, p = 0.01) and male sex (HR 1.42, p = 0.02) were predictive of reduced survival. Number of medical comorbidities was not significantly associated with survival (p > 0.5). Telephone surveys were completed by 40 surviving patients (mean age 55.1 ± 6.4 years, 72.5% male, 95% subthalamic nucleus DBS, mean follow-up 13.0 ± 1.7 years). Tremor responded best to DBS (72.5% of patients improved), while other motor symptoms remained stable. Ability to conduct activities of daily living (ADLs) remained stable (dressing, 78% of patients; running errands, 52.5% of patients) or worsened (preparing meals, 50% of patients). Patient satisfaction, however, remained high (92.5% happy with DBS, 95% would recommend DBS, and 75% felt it provided symptom control). CONCLUSIONS: DBS for PD is associated with a 10-year survival rate of 51%. Survey data suggest that while DBS does not halt disease progression in PD, it provides durable symptomatic relief and allows many individuals to maintain ADLs over long-term follow-up greater than 10 years. Furthermore, patient satisfaction with DBS remains high at long-term follow-up.

Patterns of opioid use in patients with trigeminal neuralgia undergoing neurosurgery.

OBJECTIVE: First-line treatment for trigeminal neuralgia (TN) is pharmacological management using antiepileptic drugs (AEDs), e.g., carbamazepine (CBZ) and oxcarbazepine (OCBZ). Surgical intervention has been shown to be an effective and durable treatment for TN that is refractory to medical therapy. Despite the lack of evidence for efficacy in patients with TN, the authors hypothesized that patients with neuropathic facial pain are prescribed opioids at high rates, and that neurosurgical intervention may lead to a reduction in opioid use. METHODS: This is a retrospective study of patients with facial pain seen by a single neurosurgeon. All patients completed a survey on pain medications, medical comorbidities, prior interventions for facial pain, and a validated pain outcome tool (the Penn Facial Pain Scale). Patients subsequently undergoing neurosurgical intervention completed a survey at the 1-month follow-up in the office, in addition to telephone interviews using a standardized script between 1 and 6 years after intervention. Univariate and multivariate logistic regression were used to predict opioid use. RESULTS: The study cohort consisted of 309 patients (70% Burchiel type 1 TN [TN1], 18% Burchiel type 2 [TN2], 6% atypical facial pain [AFP], and 6% TN secondary to multiple sclerosis [TN-MS]). At initial presentation, 20% of patients were taking opioids. Of these patients, 55% were receiving concurrent opioid therapy with CBZ/OCBZ, and 84% were receiving concurrent therapy with at least one type of AED. Facial pain diagnosis (for diagnoses other than TN1, odds ratio [OR] 2.5, p = 0.01) and facial pain intensity at its worst (for each unit increase, OR 1.4, p = 0.005) were predictors of opioid use at baseline. Neurosurgical intervention led to a reduction in opioid use to 8% at long-term follow-up (p < 0.01, Fisher's exact test; n = 154). Diagnosis (for diagnoses other than TN1, OR 4.7, p = 0.002) and postintervention reduction in pain at its worst (for each unit reduction, OR 0.8, p < 10-3) were predictors of opioid use at long-term follow-up. On subgroup analysis, patients with TN1 demonstrated a decrease in opioid use to 5% at long-term follow-up (p < 0.05, Fisher's exact test), whereas patients with non-TN1 facial pain did not. In the nonsurgical group, there was no statistically significant decrease in opioid use at long-term follow-up (n = 81). CONCLUSIONS: In spite of its high potential for abuse, opioid use, mostly as an adjunct to AEDs, is prevalent in patients with facial pain. Opportunities to curb opioid use in TN1 include earlier neurosurgical intervention.

Focused Ultrasound Thalamotomy for Essential Tremor in the Setting of a Ventricular Shunt: Technical Report.

BACKGROUND: A recent randomized controlled trial of magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) for essential tremor (ET) demonstrated safety and efficacy. Patients with ventricular shunts may be good candidates for FUS to minimize hardware-associated infections. OBJECTIVE: To demonstrate feasibility of FUS in this subset of patients. METHODS: A 74-yr-old male with medically refractory ET, and a right-sided ventricular shunt for normal pressure hydrocephalus, underwent FUS to the right ventro-intermedius (VIM) nucleus. The VIM nucleus was directly targeted using deterministic tractography. Clinical outcomes were measured using the Clinical Rating Scale for Tremor. RESULTS: Shunt components required 6% of the total ultrasound transducer elements to be shut off. Eight therapeutic sonications were delivered (maximum temperature, 64°), leading to a 90% improvement in hand tremor and a 100% improvement in functional disability at the 3-mo follow-up. No complications were noted. CONCLUSION: This is the first case of FUS thalamotomy in a patient with a shunt. Direct VIM targeting and achievement of therapeutic temperatures with acoustic energy is feasible in this subset of patients.

Predictors of Neurological Outcome Following Subaxial Cervical Spine Trauma.

Background The treatment of traumatic subaxial cervical spine injuries remains controversial. The American Spinal Injury Association (ASIA) impairment scale (AIS) is a widely-used metric to score neurological function after spinal cord injury (SCI). Here, we evaluated the outcomes of patients who underwent treatment of subaxial cervical spine injuries to identify predictors of neurologic function after injury and treatment. Methods We performed a retrospective logistic regression analysis to determine predictors of neurological outcome; 76 patients met the inclusion criteria and presented for a three-month follow-up. The mean age was 50.6±18.7 years old and the majority of patients were male (n=49, 64%). Results The majority of patients had stable AIS scores at three months (n=56, 74%). A subset of patients showed improvement at three months (n=16, 21%), while a small subset of patients had neurological decline at three months (n=4, 5%). In our model, increasing patient age (odds ratio [OR] 1.39, 1.10-2.61 95% confidence interval [CI], P<0.001) and a previous or current diagnosis of cancer (OR 22.4, 1.25-820 95% CI, P=0.04) significantly increased the odds of neurological decline at three months. In patients treated surgically, we found that delay in surgical treatment (>24 hours) was associated with a decreased odds of neurological improvement (OR 0.24, 0.05-0.99 95% CI, P=0.048). Cervical spine injuries are heterogeneous and difficult to manage. Conclusion We found that increasing patient age and an oncologic history were associated with neurological deterioration while a delay in surgical treatment was associated with decreased odds of improvement. These predictors of outcome may be used to guide prognosis and treatment decisions.

Predictors of Failure of Nonoperative Management Following Subaxial Spine Trauma and Creation of Modified Subaxial Injury Classification System.

BACKGROUND: Subaxial cervical spine injuries may be treated with either nonoperative stabilization or surgical fixation. The subaxial injury classification (SLIC) provides 1 method for suggesting the degree of necessity for surgery. In the current study, we examined if the SLIC score, or other preoperative metrics, can predict failure of nonoperative management. METHODS: We performed a retrospective chart review to identify patients who presented with acute, nonpenetrating, subaxial cervical spine injury within our health system between 2007 and 2016. Patient demographics, medical comorbidities, injuries, and treatments were collected. Logistic regression analysis was used to determine potential predictors of failure of nonoperative management. RESULTS: During the study period, 40 patients met the inclusion criteria. A small subset of patients failed nonoperative management (n = 5, 12.5%). The mean SLIC score was 3.9 ± 1.9; however, 14 (35%) patients had scores >4. Neither total SLIC score (P = 0.68) nor SLIC subscores (morphology [P = 0.96], discoligamentous complex [P = 0.83], neurologic status [P = 0.60]) predicted failure of nonoperative treatment. Time to evaluation/treatment did predict failure of nonoperative management. Evaluation within 8 hours of injury was a negative predictor of failure (odds ratio = 0.03, P = 0.001) and evaluation 24 hours or more after injury was a positive predictor of failure (odds ratio = 66.00, P < 0.001). We created a modified SLIC score on the basis of these findings, which significantly predicted failure of nonoperative management (P = 0.044). CONCLUSIONS: Management of subaxial spine injuries is complex. In our cohort, SLIC scoring did not adequately predict odds of failure of nonoperative management. Time to evaluation, however, did. We created a modified SLIC score that significantly predicted failure of nonoperative management.

Factors Predicting Ventriculostomy Revision at a Large Academic Medical Center.

BACKGROUND: Freehand bedside ventriculostomy placement can result in catheter malfunction requiring a revision procedure and cause significant patient morbidity. We performed a single-center retrospective review to assess factors related to this complication. METHODS: Using an administrative database and chart review, we identified 101 first-time external ventricular drain placements performed at the bedside. We collected data regarding demographics, medical comorbidities, complications, and catheter tip location. We performed univariate and multivariate statistical analyses using MATLAB. We corrected for multiple comparisons using the false discovery rate (FDR) procedure. RESULTS: Multivariate regression analyses revealed that revision procedures were more likely to occur after drain blockage (odds ratio [OR] 17.9) and hemorrhage (OR 10.3, FDR-corrected P values < 0.01, 0.05, respectively). Drain blockage was less frequent after placement in an "optimal location" (ipsilateral ventricle or near foramen of Monroe; OR 0.09, P = 0.009, FDR-corrected P < 0.03) but was more likely to occur after placement in third ventricle (post-hoc P values < 0.015). Primary diagnoses included subarachnoid hemorrhage (n = 30, 29.7%), intraparenchymal hemorrhage with intraventricular extravasation (n = 24, 23.7%), tumor (n = 20, 19.8%), and trauma (n = 17, 16.8%). Most common complications included drain blockage (n = 12, 11.8%) and hemorrhage (n = 8, 7.9%). In total, 16 patients underwent at least 1 revision procedure (15.8%). CONCLUSIONS: Bedside external ventricular drain placement is associated with a 15% rate of revision, that typically occurred after drain blockage and postprocedure hemorrhage. Optimal placement within the ipsilateral frontal horn or foramen of Monroe was associated with a reduced rate of drain blockage.