Posttraumatic Amnesia: A Systematic Review and Meta-Analysis. Proposal for a New Severity Classification.

BACKGROUND: Posttraumatic amnesia (PTA) duration is used to predict outcome after traumatic brain injury (TBI): however, no meta-analysis exists. METHODS: A systematic review was performed following PRISMA reporting guidelines. The databases Scopus-1966, PubMed/MEDLINE, CINAHL, PsycINFO, and Embase were searched for relevant texts. Random effects meta-analysis derived pooled estimates of the odds ratio of outcomes of interest and sensitivity and specificity of PTA at different cutoffs, and subsequently a summary receiver operating curve was derived. PTA prediction of Glasgow Outcome Scale (GOS) and Glasgow Outcome Scale-Extended (GOSE) scores was assessed both qualitatively and quantitatively by pooled odds ratio regarding both a good outcome (GO: GOS-5 or GOSE-7/GOSE-8) and a severe disability outcome (SDO: GOS-3 or a GOSE-3/GOSE-4). Summary receiver operating curve analysis was performed in the prediction of composite of a moderate disability outcome (MDO: GOS-4 or GOSE-5/GOSE-6) and SDO. RESULTS: Twenty-four studies were included in qualitative synthesis, and 9 (12,386 patients; males, 64%-84%) in meta-analysis. The odds of a GO and SDO were significantly different between PTA >56 days and PTA <7 days (P = 0.04 and P = 0.03). PTA <7 days (mild TBI) excluded MDO/SDO and SDO alone with 87% and 90% sensitivity. PTA of 43-86 days (severe TBI) predicted MDO/SDO or SDO with 90%-96% and 80%-90% specificity. However, PTA of 7-42 days (moderate TBI) predicted MDO/SDO or SDO with only 38%-89% and 30%-80% specificity. CONCLUSIONS: PTA duration was reliable in predicting outcome when <7 days, and especially when >42 days but was often unreliable between 7 and 42 days duration.

Growth and Resorption of Chronic Subdural Hematomas: Gardner, Weir, and the Osmotic Hypothesis Revisited.

BACKGROUND: To explain why some chronic subdural hematomas (CSDHs) grow and/or resorb, a physically decreasing outer membrane (OM) surface area (SA) to CSDH volume (V) ratio has been reexplored, and a critical CSDH size inferred (OM SA ≈ V). Gardner showed that since CSDH protein exceeded cerebrospinal fluid (CSF) protein, CSF→CSDH osmosis occurred across a semipermeable inner membrane (n = 1). By contrast, Zollinger and Gross demonstrated that serum→CSDH osmosis could also occur across the OM (n = 1). Notably, Weir refuted Zollinger and Gross by finding equal CSDH and serum total protein (n = 20); however, Weir did not refute Gardner. Although all extant mechanisms, especially rehemorrhages, explain CSDH growth, only OM SA ≥ V simultaneously permits resorption. We aimed to reevaluate the osmotic hypothesis. METHODS: Paired serum and CSDH samples were measured in a prospective cohort. RESULTS: Results were consecutively obtained in 116 patients (87 men; mean age, 73 ± 13 years). Serum osmolality and CSDH osmolality were similar (285.70 ± 7.99 vs. 283.85 ± 7.52 mmol/kg, respectively; P = 0.11) and significantly correlated (r = 0.75, P < 0.0001). Serum total protein significantly exceeded CSDH total protein (66.6 ± 6.8 vs. 43.68 ± 20.24 g/L, P < 0.0001) as did serum albumin (35.62 ± 4.46 vs. 30.85 ± 8.5 g/L, P < 0.0001) and serum total globulins (31.5 ± 6 vs. 18.6 ± 11.4 g/L, P < 0.0001). Serum and CSDH proteins were not correlated (total protein: r = 0.003; albumin: r = 0.08; globulins: r = 0.21). CONCLUSIONS: Only crystalloids equilibrated. CSDH colloids were significantly decreased. CSDH dilution or colloidal flocculation is implied. CSDH dilution (by CSF→CSDH inner membrane [IM] osmosis or OM transudation/exudation) could favor CSDH growth, as would repeated OM hemorrhages. Contrariwise, isolated colloidal flocculation could favor CSDH shrinkage by OM CSDH→serum osmosis. The latter may result in OM SA ≥ V favorable for ultimate resolution. Our results refute Weir and Zollinger and Gross, but not Gardner. Osmotic gradients simultaneously exist for both CSDH growth and resorption. Each equilibrium could depend on each gradient relative to each IM/OM semipermeability.

S-100ß in chronic subdural haematoma: Prospective cohort study.

Chronic subdural haematoma (CSDH) is invariably classified as 'neurotrauma'. However, whilst a history of trauma/fall is frequent, it is usually distant, mild or even absent. Serum S-100ß > 1.38 µg/L is associated with a 100% specificity for mortality/poor outcome acutely after moderate-severe neurotrauma. Serum S-100ß > 0.10 µg/L is used to screen mild neurotrauma cases for emergent neuro-imaging. Serum S-100 in controls is 0.057 µg/L. S-100ß in serum or CSDH fluid (CSDHf) has not been studied. No normal 'subdural fluid' exists to compare CSDHf. We measured serum and CSDHf S-100ß at surgical drainage in a novel prospective single-centre cohort. Of n = 86/86 (100%, M65, age 73 ±â€¯13yrs), n = 66 (76%) reported mild trauma/fall 31 ±â€¯23 days previously. N = 54 (63%) presented with good clinical Markwalder Grade (MG: 0-1). Paired serum and CSDHf S-100ß samples were obtained in n = 45. CSDHf S-100ß (n = 80) was elevated (0.9 ±â€¯0.6 µg/L), was significantly higher than serum S-100ß (n = 51) (0.33 ±â€¯0.05 µg/L, P = 0.002), and was significantly correlated with midline-shift (r = 0.43, P = 0.005) and CSDH volume (r = 0.225, P = 0.046). CSDHf S-100ß was not significantly associated with any demographic factor, co-morbidity or outcome measure. CONCLUSIONS: Despite expectations, S-100ß was elevated in serum CSDH, but was significantly higher in CSDHf. Indeed, CSDHf S-100ß approached serum levels associated with a poor prognosis after acute-neurotrauma. However, CSDHf S-100ß did not represent a biomarker for trauma nor functional outcome. Whilst the non-traumatic source for on-going S-100ß release could not be determined, prolonged compression of an atrophic brain, subsequent CSF leakage, or 'subdural-space' meningeal disruption/proliferation, represent theoretical possibilities. Elevated S-100ß may therefore not be specific for mild-moderate-severe acute neurotrauma. Alternative non-traumatic intra-cranial mechanisms evidently also exist.

Long-term health outcomes in survivors after chronic subdural haematoma.

Chronic subdural haematoma (CSDH) is the most common neurosurgical presentation among the elderly. Although initially considered a non-threatening event, recent studies have highlighted poor long-term survival post-CSDH. Currently, there is a paucity of information regarding long-term health outcome in survivors after CSDH post-intervention. The objective of this research was to assess long-term functional, cognitive, and mental health outcome after CSDH. CSDH patients were administered a telephone-based assessment including a Demographic Questionnaire, Functional Activities Questionnaire (FAQ), Cognitive Telephone Screening Instrument (COGTEL), Mental Health Continuum-Short Form (MHC-SF), and the Geriatric Depression Scale (GDS). Results were obtained in n = 51 patients. CSDH patients were assessed at 5.5 + 2.1 years after CSDH and results were compared to age/gender matched controls (n = 52). Comorbidities were significantly greater in CSDH patients at the time of assessment (χ2 = 35.47, P < .01). CSDH patients demonstrated a significant reduction in functional independence (FAQ, P < .001) and Verbal Short-Term Memory (COGTEL, P = .048). Potential negative trends were observed for Verbal Long-Term Memory (P = .06) and Inductive Reasoning (P = .07). CSDH patients also demonstrated significantly poorer emotional, psychological and social well-being (MHC-SF: Emotional, P = .003; Psychological, P = .001; and Social, P < .001), with increased depressive symptomatology (GDS, P < .001). In addition to known decreased long-term survival, CSDH survivors demonstrated poorer long-term functional, cognitive and mental health outcomes than controls. Pre-existent comorbidities were also more prevalent. CSDH is therefore a sentinel health event: survivors represent a vulnerable group who require long-term, comprehensive, person-centred care. This is the first study of long term CSDH health outcomes.

Early Postoperative Morbidity After Chronic Subdural Hematoma: Predictive Usefulness of the Physiological and Operative Severity Score for Enumeration of Mortality and Morbidity, American College of Surgeons National Surgical Quality Improvement Program, and American Society of Anesthesiologists Grade in a Prospective Cohort.

BACKGROUND: Although chronic subdural hematoma (CSDH) is generally benign, long-term survival (LTS) after CSDH is poor in a significant subgroup. This dichotomy has been compared to fractured neck of femur. However, although early postoperative mortality (within 30 days of CSDH) is well recorded with CSDH and similar to fractured neck of femur (4%-8%), scant accurate data exist regarding early postoperative morbidity (POMB). POMB, which prolongs length of stay (LOS) after major nonneurosurgery, is associated with decreased LTS. One recent CSDH study suggested a POMB standard of 10% i.e., notably less than with fractured neck of femur (45%). METHODS: POMB was recorded in a novel prospective single-center cohort after CSDH. The POSSUM (Physiological and Operative Severity Score for Enumeration of Mortality and Morbidity), American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) score, and American Society of Anesthesiologists (ASA) grade were assessed as tools for potentially predicting POMB. Receiver operating characteristic (ROC) curves were calculated. RESULTS: Early postoperative mortality (within 30 days of CSDH) occurred in 3 of 114 patients (3%). Seventy-one POMB events occurred in 54 of 114 patients (47%), with 27 of 54 (50%) having a Clavien-Dindo grade ≥2. Most POMB was neurologic (n = 47/71, 66%). Age (P = 0.01), Glasgow Coma Scale (GCS) score (P = 0.001), Markwalder grade (P = 0.01), hypertension (P = 0.047), and/or ≥1 preexistent comorbidity (P = 0.041) were predictive. LOS (P = 0.01) and discharge modified Rankin Scale score (P < 0.001) were significantly associated. Predicted and observed POMB with POSSUM were significantly disparate (χ2 = 15.23; P = 0.001): POSSUM area under ROC (AUROC = 0.611) was also nondiscriminatory. ACS-NSQIP (χ2 = 18.51; P < 0.001; AUROC = 0.629) and ASA grades (P = 0.25) were also nonpredictive. CONCLUSIONS: POMB was frequently disabling, mostly neurologic, and as frequent and diverse as with fractured neck of femur. POMB was significantly correlated with LOS and discharge modified Rankin Scale score. Surprisingly, POSSUM, ACS-NSQIP, and ASA grades were not predictive and would not aid consent. Simple parameters (age, Glasgow Coma Scale, Markwalder grade, hypertension, and/or ≥1 other comorbidity) were instead predictive. Longitudinal follow-up will determine whether POMB affects LTS. CSDH, like fractured neck of femur, is distinct.

Effect of Gabapentin vs Pregabalin on Pain Intensity in Adults With Chronic Sciatica: A Randomized Clinical Trial.

Importance: Optimal pharmacologic treatment for chronic sciatica (CS) is currently unclear. While gabapentin (GBP) and pregabalin (PGB) are both used to treat CS, equipoise exists. Nevertheless, pharmaceutical regulation authorities typically subsidize one drug over the other. This hinders interchange wherever the favored drug is either ineffective or ill-tolerated. Objective: To assess GBP vs PGB head to head for the treatment of CS. Design, Setting, and Participants: A preplanned interim analysis of a randomized, double-blind, double-dummy crossover trial of PGB vs GBP for management of CS at half the estimated final sample size was performed in a single-center, tertiary referral public hospital. A total of 20 patients underwent randomization from March 2016 to March 2018, and 2 were excluded with 1 lost to follow-up and the other requiring urgent surgery unrelated to the study. Patients attending a specialist neurosurgery clinic with unilateral CS were considered for trial recruitment. Chronic sciatica was defined as pain lasting for at least 3 months radiating into 1 leg only to, at, or below the knee level. Imaging (magnetic resonance imaging with or without computed tomography) corroborating a root-level lesion concordant with symptoms and/or signs was determined by the trial clinician. Inclusion criteria included patients who had not used GBP and PGB and were 18 years or older. Analyses were intention to treat and began February 2018. Interventions: Randomly assigned participants received GBP (400 mg to 800 mg 3 times a day) then PGB (150 mg to 300 mg twice daily) or vice versa, each taken for 8 weeks. Crossover followed a 1-week washout. Main Outcomes and Measures: The primary outcome was pain intensity (10-point visual analog scale) at baseline and 8 weeks. Secondary outcomes included disability (using the Oswestry Disability Index) and severity/frequency of adverse events. Results: The total trial population (N = 18) consisted mostly of men (11 [61%]) with a mean (SD) age of 57 (16.5) years. A third of the cohort were smokers (5 [28%]), and more than half consumed alcohol (12 [67%]). Gabapentin was superior to PGB, with fewer and less severe adverse events. Both GBP (mean [SD], 7.54 [1.39] to 5.82 [1.72]; P < .001) and PGB (mean [SD], 7.33 [1.30] to 6.38 [1.88]; P = .002) displayed significant visual analog pain intensity scale reduction and Oswestry Disability Index reduction (mean [SD], 59.22 [16.88] to 48.54 [15.52]; P < .001 for both). Head to head, GBP showed superior visual analog pain intensity scale reduction (mean [SD], GBP: 1.72 [1.17] vs PGB: 0.94 [1.09]; P = .035) irrespective of sequence order; however, Oswestry Disability Index reduction was unchanged. Adverse events for PGB were more frequent (PGB, 31 [81%] vs GBP, 7 [19%]; P = .002) especially when PGB was taken first. Conclusions and Relevance: Pregabalin and GBP were both significantly efficacious. However, GBP was superior with fewer and less severe adverse events. Gabapentin should be commenced before PGB to permit optimal crossover of medicines. Trial Registration: anzctr.org.au Identifier: ACTRN12613000559718.

Spontaneous Resolution of Lumbar Facet Joint Cyst.

BACKGROUND: Juxtafacet cysts (JFCs) are uncommon spinal lesions that can cause neural compression and are typically managed surgically. Rarely, JFCs can spontaneously resolve. CASE DESCRIPTION: We present the case of a spontaneously resolving right L4/5 JFC in an otherwise fit and well 60-year-old female. She presented with progressive chronic lower back pain and intermittent sciatica. She had no neurologic deficit. The patient was keen to avoid surgical intervention. After 19 months her symptoms had significantly improved, and repeat magnetic resonance image demonstrated complete resolution of the lesion. CONCLUSIONS: While surgery to remove a JFC ± spinal stabilization remains the mainstay and definitive treatment for symptomatic JFCs, patients without neurologic deficit may be safely managed conservatively pending possible spontaneous resolution. Spontaneous resolution may reflect the natural history of the condition.

Pregabalin versus gabapentin in the treatment of sciatica: study protocol for a randomised, double-blind, cross-over trial (PAGPROS).

BACKGROUND: There is currently an absence of high-grade evidence regarding the treatment of chronic sciatica (CS). Whilst gabapentin (GBP) and pregabalin (PGB) are both currently used to treat CS, equipoise exists regarding their individual use. In particular, no head-to-head study of GBP and PGB in CS exists. Despite equipoise, most countries' formulary regulatory authorities typically favour one drug for subsidy over the other. This hinders interchange wherever the favoured drug is either ineffective or not tolerated. The primary aim of this study is to conduct a head-to-head comparison of the efficacy of PGB versus GBP for CS based on outcomes on a visual analogue scale (VAS) and the Oswestry Disability Index (ODI). METHODS/DESIGN: We are conducting a prospective, randomised, double-blind, double-dummy cross-over study. Included patients will be over 18 years old and have unilateral CS with radiological confirmation of corresponding neural compression/irritation. Pregnant women, those with major organ disease, or those with creatinine clearance < 60 ml/minute will be excluded. Patients will continue their current pain medication at study onset, conditional upon dosage consistency during the prior 30 days. Each drug will be titrated up to a target dose (GBP 400-800 mg three times daily, PGB 150-300 mg twice daily) and taken for 8 weeks. The first drug will then be ceased; however, cross-over will be deferred pending a 1-week washout period. Drug efficacy will be assessed using the VAS and ODI. Results of the Health Locus of Control Scale and side effect frequency/severity will be used to determine psychological functioning. Assuming the hypothesis that PGB will display a superior effect, the sample size required is n = 38 with 80% power and a 5% type I error rate. Results will be analysed via intention-to-treat methodology. DISCUSSION: This study will establish the efficacy of PGB compared with GBP in reducing pain in people with sciatica and lead to greater understanding of the treatment options available. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, 12613000559718 . Registered on 17 May 2013.

Utility of Retrograde Amnesia Assessment Alone, Compared with Anterograde Amnesia Assessment in Determining Recovery After Traumatic Brain Injury: Prospective Cohort Study.

BACKGROUND: Posttraumatic amnesia (PTA) after traumatic brain injury (TBI) comprises anterograde amnesia (AA), disorientation, and retrograde amnesia (RA). However, RA is often neither assessed nor emphasized. A recent study demonstrated that although AA and disorientation were both present in non-TBI inpatients uniformly taking opioids, RA was absent. This suggests potentially significant utility with RA assessment alone since opioids are commonly prescribed post TBI. METHODS: We compared RA recovery with AA recovery in a prospective cohort post TBI. The Galveston Orientation and Amnesia Test (GOAT) represented a crude test for PTA (GOAT <75). AA was primarily assessed using the Westmead PTA Scale, and RA was assessed using the GOAT. All patients were prescribed oxycodone. RESULTS: Results were obtained (n = 31). While RA recovery coincided with a GOAT recovery in 19/31 (61%), AA recovery coincided with GOAT recovery in only 6/31 (19%), (χ2 = 11.5, P < 0.001). RA recovery preceded AA recovery in 15/31 (48%), while AA recovery preceded RA recovery in 7/31 (23%) (χ2 = 8.6, P = 0.003). Where RA recovery less frequently followed AA recovery, temporal lobe contusions were more frequent. RA recovery preceded/coincided with AA recovery in 100% of those who recovered when AA was defined as ×3 consecutive 12/12 scores (as is current widespread practice). AA recovery typically followed RA recovery with minimal delay. CONCLUSIONS: In the presence of potential in-hospital confounders including opioids, RA recovered significantly sooner after TBI than AA and was predictive of imminent AA recovery. RA assessment alone therefore had significant and novel utility in post-TBI assessment. RA assessment should be routinely recorded in all PTA assessment. Given its simplicity and resilience to common confounders, RA assessment should also be incorporated into the Glasgow Coma Scale.

Anterograde amnesia and disorientation are associated with in-patients without traumatic brain injury taking opioids. Retrograde amnesia (RA) is absent. RA assessment should be integral to post-traumatic amnesia testing.

The Glasgow Coma Scale (GCS) only assesses orientation after traumatic brain injury (TBI). 'Post-traumatic amnesia' (PTA) comprises orientation, anterograde amnesia (AA) and retrograde amnesia (RA). However, RA is often disregarded in formalized PTA assessment. Drugs can potentially confound PTA assessment: e.g. midazolam can cause AA. However, potential drug confounders are also often disregarded in formalized PTA testing. One study of medium-stay elective-surgery orthopaedic patients (without TBI) demonstrated AA in 80% taking opiates after general anesthesia. However, RA was not assessed. Opiates/opioids are frequently administered after TBI. We compared AA and RA in short-stay orthopaedic surgery in-patients (without TBI) taking post-operative opioids after opiate/opioid/benzodiazepine-free spinal anesthesia. In a prospective cohort, the Westmead PTA Scale (WPTAS) was used to assess AA (WPTAS<12), whilst RA was assessed using the Galveston Orientation and Amnesia Test RA item. Results were obtained in n=25 (60±14yrs, M:F 17:8). Surgery was uncomplicated: all were discharged by Day-4. All were taking regular oxycodone as a new post-operative prescription. Only one co-administered non-opioid was potentially confounding (temezepam, n=4). Of 25, 14 (56%) demonstrated AA: five (20%) were simultaneously disorientated. Mean WPTAS was 11.08±1.22. RA occurred in 0%. CONCLUSIONS: AA and disorientation, but not RA, were associated with in-patients (without TBI) taking opioids. Caution should therefore be applied in assessing AA/orientation in TBI in-patients taking opioids. By contrast, retrograde memory was robust and more reliable: even in older patients with iatrogenic AA and disorientation. RA assessment should therefore be integral to assessing TBI severity in all formalized PTA and GCS testing.

Mathematical formulae to estimate chronic subdural haematoma volume. Flawed assumption regarding ellipsoid morphology.

Mathematical formulae are commonly used to estimate intra-cranial haematoma volume. Such formulae tacitly assume an ellipsoid geometrical morphology. Recently, the 'XYZ/2' formula has been validated and recommended for chronic subdural haematoma (CSDH) volumetric estimation. We aimed to assess the precision and accuracy of mathematical formulae specifically in estimating CSDH volume, and to determine typical CSDH 3-D morphology. Three extant formulae ('XYZ/2', 'π/6·XYZ' and '2/3S·h') were compared against computer-assisted 3D volumetric analysis as Gold standard in CTs where CSDH sufficiently contrasted with brain. Scatter-plots (n=45) indicated that, in contrast to prior reports, all formulae most commonly over-estimated CSDH volume against 3-D Gold standard ('2/3S·h': 44.4%, 'XYZ/2': 48.84% and 'π/6·XYZ': 55.6%). With all formulae, imprecision increased with increased CSDH volume: in particular, with clinically-relevant CSDH volumes (i.e. >50ml). Deviations >10% of equivalence were observed in 60% of estimates for 2/3S·h, 77.8% for 'XYZ/2' and 84.4% for 'π/6·XYZ'. The maximum error for 'XYZ/2' was 142.3% of a clinically-relevant volume. Three-D simulations revealed that only 4/45 (9%) CSDH remotely conformed to ellipsoid geometrical morphology. Most (41/45, 91%) demonstrated highly irregular morphology neither recognisable as ellipsoid, nor as any other regular/non-regular geometric solid. CONCLUSIONS: Mathematical formulae, including 'XYZ/2', most commonly proved inaccurate and imprecise when applied to CSDH. In contrast to prior studies, all most commonly over-estimated CSDH volume. Imprecision increased with CSDH volume, and was maximal with clinically-relevant CSDH volumes. Errors most commonly related to a flawed assumption regarding ellipsoid 3-D CSDH morphology. The validity of mean comparisons, or correlation analyses, used in prior studies is questioned.

Membrane Surface Area to Volume Ratio in Chronic Subdural Hematomas: Critical Size and Potential Postoperative Target.

BACKGROUND: It is unknown why some chronic subdural hematomas (CSDHs) grow and require surgery, whereas others spontaneously resolve. Although a relatively small CSDH volume (V) reduction may induce resolution, V percent reduction is often unreliable in predicting resolution. Although CSDHs evolve distinctive inner neomembranes and outer neomembranes (OMs), the OM likely dominates the dynamic growth-resorption equilibrium. If other factors remain constant, one previous hypothesis is that resorption could fail as the surface area (SA) to V ratio decreases when CSDHs exceed a critical size. We aimed to identify a critical size and an ideal target, which implies resolution without recurrence. METHODS: Three-dimensional computed tomography CSDH SA to V ratios were obtained using computer software to compare CSDH SA to V between cases requiring surgery (surgical) and cases managed conservatively with spontaneous resolution (nonsurgical). RESULTS: Data were obtained in 45 patients (surgical: n = 28; nonsurgical: n = 17). CSDH risk factors did not significantly differ between surgical and nonsurgical cases. Surgical V was 2.5× the nonsurgical V (119.9 ± 33.1 mL vs. 48.4 ± 27.4 mL, respectively; P < 0.0001). Surgical total SA was 1.4× nonsurgical SA (256.63 ± 70.65 cm2 vs. 187.67 ± 77.72 cm2, respectively; P = 0.004). Surgical total SA to V ratio was approximately one half that of nonsurgical SA to V ratio (2.14 ± 0.90 mL-1 vs. 3.88±1.22 mL-1, respectively; P < 0.0001). Surgical OM SA (SAOM) was 120.63 ± 52 cm2, and nonsurgical SAOM was 94.10 ± 41 cm2 (P < 0.0001). Nonsurgical SAOM to V ratio was 1.94 mL-1, whereas surgical SAOM to V ratio was 1.005 mL-1 (i.e., surgical SAOM ≈ V). CONCLUSIONS: Because surgical total SA to V ratio was ≈2:1, one neomembrane may indeed dominate the dynamic growth-resorption equilibrium. CSDH critical size therefore appears to be when SAOM ≈ V, which is intuitive. Practically, subtotal CSDH evacuation which approximately doubles total SA to V ratio or SAOM to V ratio implies CSDH resolution without recurrence. This could guide subdural drain removal timing, discharge, or transfer. Prospective validation studies are required.

A small animal model for early cerebral aneurysm pathology.

Prior studies, using systemic hypertension and elastase infusion, have induced cerebral aneurysm (CA) formation in mice. However, the CAs induced were rapidly formed, relatively large, and often ruptured. These features are not completely representative of human CAs. We set out to develop a mouse model representative of the early pathological features of human CA. Twenty male C57/BL6 mice were placed in a stereotactic frame. Low dose elastase solution (2µl/min) was manually injected into the right basal cistern. Human angiotensin II (0.11µl/h) was infused subcutaneously. Mice were observed for 2-3weeks prior to euthanasia. Early CA histopathological features including endothelial change (EC) and internal elastic lamina degeneration (IELD) were systematically sought at major cerebral arterial bifurcations. Brains were harvested from 11 of 15 mice, yielding 27 bifurcations. Sub-arachnoid haemorrhage (SAH) without CA formation was observed in one brain. Macroscopic CA without SAH was observed in another brain. Early CA features were observed in 8/11 (73%) brains. All bifurcations with IELD demonstrated EC: where EC was absent, IELD was also absent. EC severity appeared to correlate with IELD severity. EC and IELD were both severe within the CA. Using lower dose elastase solution than previously employed, we developed a model of early CA pathology. Our model demonstrated that the spectrum of known early CA pathology can be created at multiple bifurcations in mice, with EC severity appearing to correlate with IELD severity. This model permits the study of factors which potentially advance or retard the progression of CA formation.

Long-term survival after chronic subdural haematoma.

Outcome after chronic subdural haematoma (CSDH) is invariably assumed favourable: however, little data regarding long term survival (LTS) exists. One study reported excess mortality restricted to year 1, but with expected actuarial rates thereafter. We aimed to determine LTS after CSDH in a retrospective analysis relative to actuarial data from age-matched controls. Data was obtained in n=155, (M:F 97:58, 69.3±2.3years). Follow-up maxima was 14.19years (mean: 4.02±3.07years, median: 5.2years). Mortality in-hospital, at 6months, 1year, 2years and 5years was n=13 (8.39%), n=22 (14.19%), n=31 (20.35%), n=42 (27.1%) and n=54 (34.84%). LTS was significantly worse than controls (5.29±0.59years vs. 17.74±1.8years, hazard ratio [HR]: 3.52, P<0.0001). Death most frequently related to pneumonia/sepsis and ischemic heart disease (IHD). Median modified Rankin score (mRS) in those discharged home (n=94, 60.65%) was 2 [IQR: 1-3]. Discharge mRS in those who died at 6months, 1year, 2years and 5years was 5 [IQR: 3-6], 5 [IQR: 4-6], 3 [IQR: 1-3], 4 [IQR: 2-5]. Discharge mRS was significantly worse with year 1 mortality (P=0.014). LTS related to discharge mRS (HR: 37.006, P<0.001), post-operative motor-score (HR: 0.581, P=0.0026), IHD (HR: 5.186, P=0.005), warfarin-use (HR: 5.93, P=0.036) and dementia (HR: 5.39, P=0.031). No long term recurrences (LTR) were recorded. Although most were discharged home with mRS=2, LTS was markedly less than previously reported: peers lived 12.4years longer. Although greater in year 1, excess mortality was not restricted to year 1, but continued throughout prolonged follow-up. LTS related to discharge disability and dependence, and co-morbid risk factors for cerebral atrophy. No LTR suggests that, once ultimately closed, the 'subdural space' remains closed. CSDH patients represent a vulnerable group who require continued long-term medical surveillance.

Gabapentin Superadded to a Pre-Existent Regime Containing Amytriptyline for Chronic Sciatica.

SETTING: There is currently a gross lack of evidence base guiding the medical management of chronic sciatica (CS). Only scant previous studies have assessed gabapentin (GBP) in CS. Extrapolating NICE-UK guidelines, prescribing authorities often insist on trialling anti-depressants (e.g., amytriptyline, AMP) as a first line for neuropathic pain states such as CS. When super-adding second-line agents, such as GBP, NICE-UK encourages overlap with first-line agents to avoid decreased pain-control. No study has reflected this practice. OBJECTIVE: Evaluate efficacy and side effects (SE) of GBP superadded to a pre-existent regime containing AMP for CS. SUBJECTS AND METHODS: Prospective cohort of patients with unilateral CS attending a specialist spine clinic. Eligible patients had experienced partial benefit to a pre-existent regime containing AMP: none had significant SE. No drugs other than GBP were added or discontinued (the latter was considered inequitable) for 3 months. Visual analog pain score (VAS), Oswestry disability index (ODI), and SE were recorded. RESULTS: Efficacy: in 56% (43/77) there were reductions in VAS (5.3 ± 3.6→2.8 ± 2.7, P < 0.0001) and ODI (42.8 ± 31.1→30.7 ± 25.2, P = 0.008). SE: Eighty-two SE (23 types) were reported in 53% (41/77). Efficacy was less in those with SE: a trend existed for a lesser reduction in VAS (2.0 ± 2.4 v 3.0 ± 2.7, P = 0.08), which proved significant for ODI (8.1 ± 11.4 v 16.7 ± 18.2, P = 0.01). Thirty-four percent (26/77) discontinued GBP all within 1 week (i.e., during titration). CONCLUSION: This is the first prospective cohort study of GBP super-added to a pre-existent regime containing AMP for CS, as per routine clinical practice and NICE-UK principles. Super-added GBP demonstrated further efficacy over the previous regime in 56%; however, SE were frequent (53%) and diverse (23 types), and 34% abruptly discarded GBP. Although SE were associated with decreased efficacy, 37% nevertheless tolerated GBP despite SE.

Pregabalin and gabapentin for the treatment of sciatica.

Whilst pregabalin (PGB) and gabapentin (GBP) are both used to treat neuropathic pain, their relative role in sciatica is unclear. Our aim was to extensively review the roles of PGB and GBP in treating sciatica. The efficacy, side effects (SE) profile and cost of PGB and GBP in neuropathic pain states were reviewed with special reference to sciatica. Eleven articles matched the criteria: seven systematic reviews, one retrospective cross-sectional study, one placebo-controlled-crossover study, one randomized placebo-controlled double-blind study and one case report. GBP and PGB appeared to demonstrate comparable efficacy and SE. However, the amount and quality of evidence was low, and only indirect comparisons were available. Importantly, no direct "head-to-head" study existed. Globally, costs varied widely (by up to 31 times) and unpredictably (PGB cheaper than GBP, or vice versa). Formulary regulator rulings were globally disparate; however, many exclusively favoured the more expensive drug (whether GBP or PGB). No studies assessed PGB-GBP interchange. Weak evidence suggests that efficacy and SE with GBP and PGB are probably similar; however, firm conclusions are precluded. Despite weak data, and having cited minor titration, but definite cost, advantages, UK National Institute for Health and Clinical Excellence favoured PGB over GBP. Given that no evidence supports unhindered PGB-GBP interchange, neither drug should probably be favoured. Prospective "head-to-head" studies are urgently required to provide robust evidence-based knowledge for choice of GBP or PGB in sciatica.

Sex life and the Oswestry Disability Index.

BACKGROUND CONTEXT: Despite the option to not answer, there is widespread anecdotal belief that the Oswestry Disability Index (ODI) Section 8 (ODI-8/sex life) is answered inaccurately (ie, in relation to psychosocial factors, not pain) or that it repels ODI participation. Oswestry Disability Index versions have therefore been created that omit ODI-8; however, no evidence base justifies this. Interestingly, one recent study reported an ODI-8 response rate (RR) of 97%. PURPOSE: The aims of this study were to measure RR to sex life questions in patients with chronic low back pain (CLBP) and to validate that ODI-8 is answered appropriately and represents a specific measure of CLBP-mediated sexual inactivity. STUDY DESIGN: Original. PATIENT SAMPLE: Eighty-eight patients. OUTCOME MEASURES: The outcome measures used in this study were the ODI, the Sexual Quality of Life Scale-version 2 (SQOL-2), the Short Form-12 version 2 (mental and physical), the Depression Anxiety and Stress Scale, the Coping Strategies Questionnaire, the Short-Form McGill Pain Questionnaire-version 2, the Opioid Risk Tool, and the Fear-Avoidance Beliefs Questionnaire (work and physical). METHOD: Chronic low back pain patients older than 18 years attending a multicultural Western spinal clinic were prospectively offered the aforementioned questionnaires. Sex life disability questions--pain dependent (ODI-8) and pain independent (SQOL-2)--appeared first and fifth in every sequence. RESULTS: Results were obtained in 65 patients (male 29, female 36). Despite expected response attrition with battery progression (RRs for the first and eighth questionnaires were 100% and 64.61%, respectively), RRs for ODI-8 (52.31%) and SQOL-2 (52.31%) were equal and significantly lower than others (p<.001). Nonresponders to ODI-8 (60.57±13.3 years) and SQOL-2 (59.68±13.34 years) were significantly older than responders (ODI-8: 47.82±12.17 years, p<.001; SQOL-2: 48.27±12.76 years, p=.001). Among ODI-8 or SQOL-2 responders, ODI-8 and SQOL-2 were not correlated (r=-0.340, p=.104). Although ODI-8 significantly correlated with prospectively identified pain-correlated questionnaires, ODI-8 did not correlate significantly with non-pain-correlated questionnaires. CONCLUSION: Contrary to previous findings, 47.69% of CLBP patients specifically ignored ODI-8; however, 100% completed the ODI remainder. Among "responders," ODI-8 was validated as having measured CLBP-mediated sexual inactivity. The ODI-8 was therefore treated consistently, as directed: It was either answered appropriately (ie, in relation to pain) or it was ignored (respecting the clause "if applicable"). No ODI modification therefore appears required for adults older than 18 years attending a multicultural Western CLBP clinic: One standard form including ODI-8 appears to yield appropriate ODI-8 response-treatment, with unaffected ODI participation. Multiple ODIs circumventing ODI-8 appear unnecessary and redundant in this population.

Risk factors for chronic subdural haematoma formation do not account for the established male bias.

OBJECTIVE: The 'subdural space' is an artefact of inner dural border layer disruption: it is not anatomical but always pathological. A male bias has long been accepted for chronic subdural haematomas (CSDH), and increased male frequencies of trauma and/or alcohol abuse are often cited as likely explanations: however, no study has validated this. We investigated to see which risk factors accounted for the male bias with CSDH. METHODS: Retrospective review of prospectively collected data. RESULTS: A male bias (M:F 97:58) for CSDH was confirmed in n=155 patients. The largest risk factor for CSDH was cerebral atrophy (M:F 94% vs. 91%): whilst a male bias prevailed in mild-moderate cases (M:F 58% vs. 41%), a female bias prevailed for severe atrophy (F:M 50% vs. 36%) (χ(2)=3.88, P=0.14). Risk factors for atrophy also demonstrated a female bias, some approached statistical significance: atrial fibrillation (P=0.05), stroke/TIA (P=0.06) and diabetes mellitus (P=0.07). There was also a trend for older age in females (F:M 72±13 years vs. 68±15 years, P=0.09). The third largest risk factor, after atrophy and trauma (i.e. anti-coagulant and anti-platelet use) was statistically significantly biased towards females (F:M 50% vs. 33%, P=0.04). No risk factor accounted for the established male bias with CSDH. In particular, a history of trauma (head injury or fall [M:F 50% vs. 57%, P=0.37]), and alcohol abuse (M:F 17% vs. 16%, P=0.89) was remarkably similar between genders. CONCLUSIONS: No recognised risk factor for CSDH formation accounted for the established male bias: risk factor trends generally favoured females. In particular, and in contrast to popular belief, a male CSDH bias did not relate to increased male frequencies of trauma and/or alcohol abuse.

Brain tumour-associated status epilepticus.

We have reviewed the scant literature on status epilepticus in patients with brain tumours. Patients with brain tumour-associated epilepsy (TAE) appear less likely to develop status epilepticus (TASE) than patients with epilepsy in the general population (EGP) are to develop status epilepticus (SEGP). TASE is associated with lesions in similar locations as TAE; in particular, the frontal lobes. However, in contrast to TAE, where seizures commence early in the course of the disease or at presentation, TASE is more likely to occur later in the disease course and herald tumour progression. In marked contrast to TAE, where epilepsy risk is inversely proportional to Word Health Organization tumour grade, TASE risk appears to be directly proportional to tumour grade (high grade gliomas appear singularly predisposed). Whilst anti-epileptic drug (AED) resistance is more common in TAE than EGP (with resistance directly proportional to tumour grade and frontal location), TASE appears paradoxically more responsive to simple AED regimes than either TAE or SEGP. Although some results suggest that mortality may be higher with TASE than with SEGP, it is likely that (as with SEGP) the major determinant of mortality is the underlying disease process. Because all such data have been derived from retrospective studies, because TASE and SEGP are less common than TAE and EGP, and because TASE and SEGP classification has often been inconsistent, findings can only be considered preliminary: multi-centre, prospective studies are required. Whilst preliminary, our review suggests that TASE has a distinct clinical profile compared to TAE and SEGP.