Shell Shock: The Response of UK Neurology.

The neurological and psychological manifestations of trauma, confinement, and terror became apparent throughout Europe as soldiers were evacuated from the trenches of the Western Front. The response in the UK evolved as a result of the experience of medical staff embedded with the troops in base hospitals and the philosophy of those treating returned soldiers in specialist establishment. There were widely disparate approaches to the management encompassing simple supportive care, a psychanalytic approach and radical electric shock therapy. The latter was partially driven by the Queen Square experience in the UK but was also concurrently widely pursued throughout Europe. With experience, care was increasingly undertaken close to the front lines using a philosophy of immediacy and expectation of recovery. Post-war analysis was startlingly unsympathetic, yet the experiences and management of shell shock have guided psychiatric and medical understanding of functional illness and post-traumatic stress over the subsequent century. In this historical review, we have sought to present features of the UK response to the neurological manifestations of trauma, the way in which these changed as the war proceeded and the political and medical response in the aftermath of war.

A Cell Line-based Immunohistochemical p53 Expression Pattern Control Panel.

TP53 gene mutations are known to manifest in distinct p53 immunohistochemical staining patterns; overexpression, wild-type, and null. These stratified staining patterns are routinely utilized in subtyping ovarian cancer subtypes. Three ovarian cancer cell lines were used in the construction of an immunohistochemical p53 expression pattern control panel that highlight respective TP53 mutation status. The cell line control panel sections demonstrated consistent clean and easily interpretable p53 immunohistochemical staining. Procured resection, biopsy, and cytologic specimens were submitted along with either standard control tissue or a p53 cell line control panel to pathologists of varying experience for interrater reliability analysis. Individual interrater reliability was near-perfect and was improved with the p53 cell line control panel when compared with the tissue control. The cell line control panel demonstrated decreased misinterpretation of null expression pattern as wild-type. Next-generation sequencing analysis was performed on the cell lines and select cases, in which there was discordance in p53 expression pattern interpretation. Next-generation sequencing analysis demonstrated low-frequency variant mutations in some cases in which there was reviewer discordance. This study suggests the addition of a p53 cell line expression pattern control panel could potentially increase p53 interpretation accuracy for ovarian cancer subtypes. We developed a cell line-based p53 control panel that has the potential to increase individual interrater reliability for p53 immunohistochemical expression pattern determination, support immunohistochemical optimization, and direct submission of difficult to interpret p53 staining cases to next-generation sequencing.

Respiratory failure because of neuromuscular disease.

PURPOSE OF REVIEW: Understanding the mechanisms and abnormalities of respiratory function in neuromuscular disease is critical to supporting the patient and maintaining ventilation in the face of acute or chronic progressive impairment. RECENT FINDINGS: Retrospective clinical studies reviewing the care of patients with Guillain-Barré syndrome and myasthenia have shown a disturbingly high mortality following step-down from intensive care. This implies high dependency and rehabilitation management is failing despite evidence that delayed improvement can occur with long-term care. A variety of mechanisms of phrenic nerve impairment have been recognized with newer investigation techniques, including EMG and ultrasound. Specific treatment for progressive neuromuscular and muscle disease has been increasingly possible particularly for the treatment of myasthenia, metabolic myopathies, and Duchenne muscular dystrophy. For those conditions without specific treatment, it has been increasingly possible to support ventilation in the domiciliary setting with newer techniques of noninvasive ventilation and better airway clearance. There remained several areas of vigorous debates, including the role for tracheostomy care and the place of respiratory muscle training and phrenic nerve/diaphragm pacing. SUMMARY: Recent studies and systematic reviews have defined criteria for anticipating, recognizing, and managing ventilatory failure because of acute neuromuscular disease. The care of patients requiring long-term noninvasive ventilatory support for chronic disorders has also evolved. This has resulted in significantly improved survival for patients requiring domiciliary ventilatory support.

A Randomized Controlled Comparison of Esophageal Clearance Times of Oral Budesonide Preparations.

BACKGROUND: Topical steroids prepared as oral viscous slurries have become common in the treatment of eosinophilic esophagitis. Esophageal mucosal contact time correlates with clinical and histologic improvement. AIM: To compare the mucosal contact time of alternative oral viscous budesonide (OVB) slurries with the conventional sucralose OVB. METHODS: A blinded randomized crossover trial investigating esophageal clearance of three OVB slurry preparations was done on healthy adults. Honey and xanthan gum OVB slurries were compared with standard sucralose OVB in 24 randomly assigned subjects. Each subject ingested the sucralose OVB and either the honey or xanthan gum OVB slurries. The esophageal clearance of each slurry was evaluated as an area under the curve (AUC) using 1 millicurie of technetium-99m-sulfur colloid (Tc99) co-administered in each OVB preparation using nuclear scintigraphy. A standardized taste survey was also administered. RESULTS: Xanthan gum had greater mucosal contact time compared to sucralose as measured by a higher AUC at 3 min (P = 0.002), while honey showed no significant difference in esophageal clearance relative to sucralose. Taste scores were significantly higher in the honey group, while scores for xanthan gum were no different from standard sucralose. CONCLUSION: OVB slurries utilizing xanthan gum may be a superior alternative to a sucralose-based slurry due to its increased mucosal contact time and similar taste tolerance. Honey may be a suitable alternative as well, due to its similar contact time and favorable taste.

Multimodal Assessment of Body Pain in Orofacial Pain Patients.

OBJECTIVE: . Patients with complaints of orofacial pain (OFP) often have other body pain, yet many do not report these to their providers. Uncontrolled pain at any location may impact the successful management of an OFP complaint. The objective of this study was to determine the number of pain regions throughout the body, and the underreporting of pain, in patients who presented to a tertiary military OFP clinic. DESIGN: A retrospective chart review was conducted on 423 consecutive new patients. Patients were given three assessment opportunities to report their pain on a whole-body pain map: 1) prior to evaluation (Pt1), 2) following an explanatory statement by their provider on the relationship between pain and prognosis (Pt2), and 3) during directed pain inquiry of specific body regions (Pro). The pain map was divided into nine anatomical regions that were assessed for the presence of pain after Pt1, Pt2, and Pro. RESULTS: Initially, 60.5% of patients did not report all pain locations (Pt1). Following the explanatory statement (Pt2), 30.5% still did not report all pain. Following the completion of all assessment methods, the most commonly reported number of pain regions was five (17.0%), and 91.5% of patients reported multiple pain regions. CONCLUSIONS: Most patients had multiple pain complaints outside the chief complaint, yet the majority did not report these until multiple forms of assessment were utilized. These data encourage the use of a pain map, a verbal pain explanation, and directed pain questioning to more accurately capture pain location and facilitate multidisciplinary care.

Lymph Node Micrometastases in Early-Stage Cervical Cancer are Not Predictive of Survival.

Although patients with early-stage cervical cancer have in general a favorable prognosis, 10% to 40% patients still recur depending on pathologic risk factors. The objective of this study was to evaluate if the presence of lymph node micrometastasis (LNmM) had an impact on patient's survival. We performed a multi-institutional retrospective review on patients with early-stage cervical cancer, with histologically negative lymph nodes, treated with radical hysterectomy and pelvic lymphadenectomy for the study period 1994 to 2004. Tissue blocks of lymph nodes from the patient's original surgery were recut and then evaluated for the presence of micrometastases. One hundred twenty-nine patients were identified who met inclusion criteria. LNmM were found in 26 patients (20%). In an average follow-up time of 70 mo, there were 11 recurrences (8.5%). Of the 11 recurrences, 2 (18%) patients had LNmM. Patients with LNmM were more likely to have received adjuvant radiation and chemotherapy. In stratified log-rank analysis, LNmM were not associated with any other high-risk clinical or pathologic variables. Survival data analysis did not demonstrate an association between the presence of LNmM and recurrence or overall survival. The presence of LNmM was not associated with an unfavorable prognosis nor was it associated with other high-risk clinical or pathologic variables predicting recurrence. Further study is warranted to understand the role of micrometastases in cervical cancer.

Risk factors for urinary retention after laparoscopic inguinal hernia repairs.

BACKGROUND: Postoperative urinary retention (POUR) is a common entity following surgery, particularly after laparoscopic inguinal hernia repair. Here the intent is to investigate the incidence of POUR in all comers at a single institution following laparoscopic inguinal hernia repair. METHODS: A retrospective chart review of all patients who underwent laparoscopic hernia repair at our institution from January 2010 through December 2013 was performed. POUR was defined as the inability to spontaneously urinate following surgery, requiring straight catheterization or placement of a Foley catheter. Perioperative data including narcotic use, operative time, type of mesh, and intraoperative fluid use were also recorded for each patient. RESULTS: A total of 346 patients underwent laparoscopic inguinal hernia repair in the specified time period, 340 patients were included in this study. The incidence of POUR after laparoscopic inguinal hernia repair at our institution was 8.2 % (n = 28) with the most common presentation of POUR being failure to void (n = 23). Postoperative narcotic use of 6.5 mg or greater of morphine or morphine equivalent was associated with higher risk of POUR via ROC analysis (OR 2.5, 95 % CI 1.2-5.6, p = 0.025). In univariate analysis, age greater than 50 years was also a risk factor for developing POUR (OR 2.8, 95 % CI 1.2-6.4, p = 0.02). Factors not found to be significant included intraoperative IV fluids, history of BPH, unilateral versus bilateral repair, and preoperative void time in relation to surgery start. CONCLUSIONS: Minimizing postoperative narcotic medications may reduce the risk of developing POUR after laparoscopic inguinal hernia repairs. If possible surgeons should consider non-steroidal anti-inflammatory drugs, acetaminophen, or regional anesthetic blocks to minimize postoperative narcotic requirements.

Fatigued on Venus, sleepy on Mars-gender and racial differences in symptoms of sleep apnea.

OBJECTIVE: Clinical guidelines for the care of obstructive sleep apnea (OSA) recommend evaluation of daytime sleepiness but do not specify evaluation of fatigue. We studied how subjects with and without OSA experience fatigue and sleepiness, examining the role of gender and race. DESIGN, SETTING, PATIENTS: Consecutive subjects entering our heart health registry completed validated questionnaires including Berlin Questionnaire for OSA, Fatigue Scale, and Epworth Sleepiness Scale. Data analysis was performed only with Whites and Blacks as there were too few subjects of other races for comparison. RESULTS: Of 384 consecutive subjects, including 218 women (57 %), there were 230 Whites (60 %) and 154 Blacks (40 %), with average age of 55.9 ± 12.8 years. Berlin Questionnaires identified 221 subjects (58 %) as having high likelihood for OSA. Fatigue was much more common in women (75 %) than in men (46 %) with OSA (p < 0.001), while frequency of fatigue was similar in women (30 %) and men (29 %) without OSA (p = 0.86). In multivariate analysis, men with OSA were sleepier than women; Black men with OSA had higher Epworth scores (mean ± SD, 12.8 ± 5.2) compared to White men (10.6 ± 5.3), White women (10.0 ± 4.5), and Black women (10.5 ± 5.2), p = 0.05. These gender differences were not related to the effects of age, body mass index, perceived stress, sleep duration, or thyroid function. CONCLUSIONS: Women report fatigue more commonly with OSA than men. Men experience sleepiness more commonly with OSA than women. The findings suggest that evaluation of sleep disorders must include an assessment of fatigue in addition to sleepiness to capture the experience of women.

Technical effects of adding 1 % lidocaine to technetium sulfur colloid for sentinel lymphatic mapping in early breast cancer: analysis of data from a double-blind randomized controlled trial.

BACKGROUND: A practice standard in sentinel lymph node (SLN) mapping in breast cancer is intradermal injection of technetium-99m sulfur colloid (Tc-99m), resulting in significant patient discomfort and pain. A previous randomized controlled trial showed that adding lidocaine to Tc-99m significantly reduced radioisotope injection-related pain. We tested whether 1 % lidocaine admixed with Tc-99m affects feasibility of SLN mapping. METHODS: Between January 2006 and April 2009, 140 patients with early breast cancer were randomly assigned (1:1:1:1) to receive standard topical 4 % lidocaine cream and intradermal Tc-99m (control) or to one of three other study groups: topical placebo cream and injection of Tc-99m containing sodium bicarbonate (NaHCO3), 1 % lidocaine, or both. All SLN data were collected prospectively. RESULTS: Study groups were comparable for clinicopathological parameters. As previously reported, the addition of 1 % lidocaine to the radioisotope solution significantly improved patient comfort. Overall SLN identification rate in the trial was 93 %. Technical aspects of SLN biopsy were similar for all groups, including time from injection to operation, first SLN (SLN 1) gamma probe counts, ex vivo counts for SLN 1 and SLN 2, and axillary bed counts. SLN identification rates were comparable statistically: control (96 %), lidocaine (90 %), sodium bicarbonate (97 %), and sodium bicarbonate-lidocaine (90 %). The control group had a significantly higher SLN 2/SLN 1 ex vivo count ratio, and the number of SLNs detected was significantly reduced in the lidocaine versus no-lidocaine groups (p < 0.05). CONCLUSIONS: Addition of 1 % lidocaine to standard radioisotope solution for SLN mapping in breast cancer is associated with fewer SLNs detected, but it does not appear to compromise SLN identification.

United States Military Cancer Institute Clinical Trials Group (USMCI GI-01) randomized controlled trial comparing targeted nodal assessment and ultrastaging with standard pathological evaluation for colon cancer.

OBJECTIVE: Our randomized controlled trial previously demonstrated improved staging accuracy with targeted nodal assessment and ultrastaging (TNA-us) in colon cancer (CC). Our objective was to test the hypothesis that TNA-us improves disease-free survival (DFS) in CC. METHODS: In this randomized trial, targeted nodal assessment and ultrastaging resulted in enhanced lymph node diagnostic yield associated with improved staging accuracy, which was further associated with improved disease-free survival in early colon cancer. RESULTS: Clinical parameters of the control (n = 94) and TNA-us (n = 98) groups were comparable. Median (interquartile range) lymph node yield was higher in the TNA-us arm: 16 (12-22) versus 13 (10-18); P = 0.002. Median follow-up was 46 (29-70) months. Overall 5-year DFS was 61% in the control arm and 71% in the TNA-us arm (P = 0.11). Clinical parameters of node-negative patients in the control (n = 51) and TNA-us (n = 55) groups were comparable. Lymph node yield was higher in the TNA-us arm: 15 (12-21) versus 13 (8-18); P = 0.03. Five-year DFS differed significantly between groups with node-negative CC (control 71% vs TNA-us 86%; P = 0.04). Survival among stage II CC alone was higher in the TNA-us group, 83% versus 65%; P = 0.03. Adjuvant chemotherapy use was nearly identical between groups. TNA-us stratified CC prognosis; DFS differed significantly between ultrastaged and conventionally staged node-negative patients [control pN0 72% vs TNA-us pN0(i-) 87%; P = 0.03]. Survival varied according to lymph node yield in patients with node-negative CC [5-year DFS: <12 lymph nodes = 57% vs 12+ lymph nodes = 85%; P = 0.011] but not in stage III CC. CONCLUSIONS: TNA-us is associated with improved nodal diagnostic yield and enhanced staging accuracy (stage migration), which is further associated with improved DFS in early CC. This study is registered at clinicaltrials.gov under the registration number: NCT01623258.

Time-dependent trends in lymph node yield and impact on adjuvant therapy decisions in colon cancer surgery: an international multi-institutional study.

BACKGROUND: Lymph node yield (LNY) and accuracy of nodal assessment are critical to staging and treatment planning in colon cancer (CC). A nationally agreed upon 12-node minimum is a quality standard in CC. The impact of this quality measure on LNY and impact on therapeutic decisions are evaluated in two international, multi-center, prospective trials comprising a well-characterized cohort assembled over 8 years (2001-2009) with long-term follow-up. HYPOTHESIS: Quality adherence through increased LNY improves staging accuracy and impacts adjuvant therapy decisions. METHODS: Retrospective analysis of prospective data to assess time-dependent LNY, the dependent variable in multivariate linear regression analysis adjusted for age, gender, body-mass-index (BMI), tumor size/stage/grade, anatomic location and surgery date. RESULTS: Two-hundred-forty-five patients with non-metastatic CC, median age 70 years, BMI 26 kg/m(2), tumor size 4.0 cm, and LNY 17 nodes were studied. Seventy-two percent had T3 (70 %)/T4 (2 %) tumors. Adherence to the 12-node minimum was 70 %(2001-2002), 81 % (2003-2004), 90 % (2005-2006), 94 % (2007-2008). LNY significantly increased over time (Median LNY: 2001-2004 = 15 vs. 2005-2008 = 17; P < 0.001) on multivariate analysis controlling for tumor size (P < 0.001), and right-sided tumor location (P < 0.001). Adjuvant therapy administration and indication for chemotherapy according to LNY (<12 vs. 12 + LNs = 33 % vs. 39 %; P = 0.48) and time period (2001-2004 vs. 2005-2008 = 39 % vs. 37 %; P = 0.89) remained unchanged. CONCLUSIONS: Despite the independent predictors of nodal yield (tumor location and size), year of study still had a significant impact on nodal yield. Despite increased quality adherence and LNY over time, there appears to be a delayed impact on adjuvant therapy decisions once quality standard adherence takes effect.

The impact of recurrent laryngeal neuromonitoring on multi-dimensional voice outcomes following thyroid surgery.

BACKGROUND: Voice changes after thyroidectomy are common but not always related to recurrent laryngeal nerve (RLN) injury. We evaluated if RLN neuromonitoring correlated with non-RLN injury-related changes in voice after thyroidectomy. METHODS: Prospective multi-dimensional voice assessment was conducted on patients undergoing thyroidectomy before, 1-4 weeks, and 6 months postoperatively. Voice outcome (VO) was determined as normal (NormVO) or negative (NegVO) based upon combinations of patient-reported symptoms, videolaryngoscopy, a composite of acoustic measurements, and clinician-perceived voice quality. Groups with and without neuromonitoring were compared for early and durable differences in VO. RESULTS: Ninety-one patients underwent thyroidectomy; 39 with RLN neuromonitoring and 52 without. The two study groups were similar with regard to baseline characteristics including voice assessment. There was no difference in NegVO between neuromonitored and non-monitored patients at 1-4 weeks (n = 89; 32% vs. 27%; P = 0.81) and 6 months (n = 71, 14% vs. 7%; P = 0.42) after thyroidectomy. Neuromonitoring was associated with a 48-min increase in median operative time, but this finding was not statistically significant in a multivariate model. CONCLUSION: In this study, recurrent laryngeal neuromonitoring did not appear to influence non-RLN injury related VO as measured by a comprehensive multidimensional voice assessment.

Topical eflornithine hydrochloride improves the effectiveness of standard laser hair removal for treating pseudofolliculitis barbae: a randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Pseudofolliculitis barbae (PFB) significantly impacts the military population, especially deployed personnel. OBJECTIVE: This study was designed to determine whether the addition of topical eflornithine to hair laser treatment would improve efficacy in treating PFB. METHODS: This was a randomized, double-blinded, placebo-controlled, paired (right and left neck) comparison study examining a combination of eflornithine and hair laser versus placebo and hair laser for the treatment of PFB. In all, 27 male patients with clinical PFB were treated with a long-pulsed neodymium:yttrium-aluminum-garnet laser with an energy fluence of 25 to 30 J/cm(2), a pulse duration of 20 to 30 milliseconds, and a 10-mm spot size to the entire bearded neck region. The laser treatment was performed every 4 weeks for a total of 16 weeks. Between laser treatments, patients applied eflornithine and placebo creams twice daily to opposite sides of the bearded neck region. The number of hairs and inflammatory papules were counted bilaterally at each visit. RESULTS: The eflornithine side had a statistically significant decrease in the number of hairs and inflammatory papules compared with the placebo side. At 16 weeks, the eflornithine side had a median hair reduction of 99.5% from baseline (range 48.5%-100.0%), whereas the placebo side had an 85.0% median hair reduction from baseline (range 50.5%-94.5%), P less than .001. LIMITATIONS: Patients were not followed up beyond 16 weeks. CONCLUSION: The addition of topical eflornithine to hair laser treatment decreased hairs and inflammatory papules faster when compared with hair laser therapy alone in the treatment of PFB.

Pain ratings by patients and their providers of radionucleotide injection for breast cancer lymphatic mapping.

BACKGROUND: Disparity between patient report and physician perception of pain from radiotracer injection for sentinel node biopsy is thought to center on the severity of the intervention, ethnic composition of population queried, and socioeconomic factors. OBJECTIVE: The objectives of this study were, first, to explore agreement between physicians' and their breast cancer patients' pain assessment during subareolar radionucleotide injection; and second, to evaluate potential ethnic differences in ratings. METHODS: A trial was conducted, from January 2006 to April 2009, where 140 breast cancer patients were randomly assigned to standard topical lidocaine-4% cream and 99mTc-sulfur colloid injection, or to one of three other groups: placebo cream and 99mTc-sulfur colloid injection containing NaHCO3, 1% lidocaine, or NaHCO3 + 1% lidocaine. Providers and patients completed numeric pain scales (0-10) immediately after injection. RESULTS: Patients and providers rated pain similarly over the entire cohort (median, 3 vs 2, P = 0.15). Patients rated pain statistically significantly higher than physicians in the standard (6 vs 5, P = 0.045) and placebo + NaHCO3 (5 vs 4, P = 0.032) groups. No significant difference in scores existed between all African Americans and their physicians (3 vs 4, P = 0.27). CONCLUSION: Patient-physician pain assessment congruence over the less painful injections and their statistically similar scores with the more painful methods suggests the importance of utilizing the least painful method possible. Providers tended to underestimate patients with the highest pain ratings-those in the greatest analgesic need. Lack of statistical difference between African American and physician scores may reflect the equal-access-to-care over the entire patient cohort, supporting the conclusion that socioeconomic factors may lie at the heart of previously reported discrepancies.

A monoclonal gammopathy precedes multiple myeloma in most patients.

Preexisting plasma cell disorders, monoclonal gammopathy of undetermined significance, or smoldering myeloma are present in at least one-third of multiple myeloma patients. However, the proportion of patients with a preexisting plasma cell disorder has never been determined by laboratory testing on prediagnostic sera. We cross-referenced our autologous stem cell transplantation database with the Department of Defense Serum Repository. Serum protein electrophoresis, immunofixation electrophoresis, and serum free light-chain analysis were performed on all sera collected 2 or more years before diagnosis to detect a monoclonal gammopathy (M-Ig). In 30 of 90 patients, 110 prediagnostic samples were available from 2.2 to 15.3 years before diagnosis. An M-Ig was detected initially in 27 of 30 patients (90%, 95% confidence interval, 74%-97%); by serum protein electrophoresis and/or immunofixation electrophoresis in 21 patients (77.8%), and only by serum free light-chain analysis in 6 patients (22.2%). Four patients had only one positive sample within 4 years before diagnosis, with all preceding sera negative. All 4 patients with light-chain/nonsecretory myeloma evolved from a light-chain M-Ig. A preexisting M-Ig is present in most multiple myeloma patients before diagnosis. Some patients progress rapidly through a premalignant phase. Light-chain detected M-Ig is a new entity that requires further study.

Corneal biomechanics following epi-LASIK.

PURPOSE: To evaluate corneal biomechanical changes following epi-LASIK. METHODS: In this prospective study of 51 patients, corneal hysteresis (CH), corneal resistance factor (CRF), and intraocular pressure (IOP) were assessed using the Ocular Response Analyzer (ORA, Reichert Technologies) preoperatively and at 1, 3, 6, and 12 months after epi-LASIK. Repeated measures analysis of variance (ANOVA) was used to compare changes over time (alpha=.05). Intraocular pressure was also measured by Goldmann applanation tonometry. RESULTS: Corneal hysteresis decreased from 10.22±1.65 mmHg preoperatively to 8.17±1.25 mmHg at 1 month, 8.46±1.44 mmHg at 3 months, 8.63±1.31 mmHg at 6 months, and 8.53±1.49 mmHg at 12 months. Corneal resistance factor decreased from 10.01±1.80 mmHg preoperatively to 7.82±1.68, 8.03±1.85, 7.77±1.50, and 7.80±1.66 mmHg at 1, 3, 6, and 12 months, respectively. Repeated measures ANOVA showed a significant change over time for both CH and CRF (P<.0005). All measures of IOP changed significantly over time (P<.0005). CONCLUSIONS: Epi-LASIK resulted in a significant change in CH and CRF postoperatively. Although some recovery occurred over time, CH, CRF, and IOP did not revert to preoperative levels.

Lesson of the month (1). Ictal asystole due to unsuspected cocaine abuse.

This lesson describes a patient who had a cardiac arrest during an episode of status epilepticus provoked by a first fit. This is an exceptional sequence of events and should lead to investigation for an underlying cause. Unsuspected cocaine abuse is common and may provoke prolonged status epilepticus, particularly if there is a low seizure threshold. A toxic screen should be undertaken in all patients presenting with unexplained status epilepticus even if abuse of illicit substances is denied.

Hypoxic-ischaemic brain injury.

Hypoxic-ischaemic brain injury is common and usually due to cardiac arrest or profound hypotension. The clinical pattern and outcome depend on the severity of the initial insult, the effectiveness of immediate resuscitation and transfer, and the post-resuscitation management on the intensive care unit. Clinical assessment is difficult and so often these days compromised by sedation, neuromuscular blockade, ventilation, hypothermia and inotropic management. Investigations can add valuable information, in particular brain MRI shows characteristic patterns depending on the severity of the injury and the timing of imaging. EEG patterns may also suggest the possibility of a good outcome. There is no entirely reliable algorithm of clinical signs or investigations which allow a definitive prognosis but the combination of careful repeated observations and appropriate ancillary investigations allows the neurologist to give an informed and accurate opinion of the likely outcome, and to advise on management. Overall, the prognosis is extremely poor and only a quarter of patients survive to hospital discharge, and often even then with severe neurological or cognitive deficits.

Prolonged Ventilatory Support for Patients Recovering From Guillain-Barré Syndrome.

BACKGROUND: Recovery from Guillain-Barré syndrome (GBS) may be protracted, and patients may need prolonged ventilatory support. We present clinical data from a tertiary referral weaning center managing patients with GBS requiring prolonged ventilatory support. METHODS: A retrospective review of patients managed in a 34-bed specialist ventilator weaning facility in London, United Kingdom, between 2006 and 2017. Data including demographics, initial presentation, and ventilatory support were collected. Functional recovery and outcome data were collected between 12 months and 3 years following disease onset. RESULTS: Twenty-nine patients with severe GBS requiring prolonged ventilation were included. In several patients, coexisting conditions or complications affected the course. Seventy-six percent (n = 22) were successfully weaned from invasive ventilation with a median time to tracheostomy decannulation of 193 days (range: 49-527 days). Use of noninvasive ventilation (NIV), as part of the weaning program, was applied in 59% (13/22), with 14% (3/22) requiring long-term nocturnal NIV. Twenty-four percent (7/29) were not decannulated, with 14% (4/29) supported on long-term invasive ventilation. Forty-five percent (10/22) weaned from invasive ventilation were able to achieve short distance-assisted ambulation. Mortality at 36 months was 17% (5/29), with 3 of these deaths occurring in patients invasively ventilated during their acute admission. CONCLUSIONS: GBS with severe respiratory muscle weakness and bulbar dysfunction may require prolonged invasive ventilation. However, there is potential for complete weaning from invasive mechanical ventilatory support with associated function recovery. These data highlight the importance of maintaining ongoing support and rehabilitation for patients with GBS requiring prolonged ventilation.