A Simplified Double-Bundle Anterior Cruciate Ligament Reconstruction by the Three-Inside Technique With Two Suspension Buttons and One Interference Screw.

In comparison with the single-bundle technique, double-bundle anterior cruciate ligament (ACL) reconstruction has proven its superiority regarding biomechanical studies and clinical outcomes in both rotational knee stability and anterior translation function. However, the complexity and risk of complications remain a great concern for the orthopaedic surgeon performing double-bundle ACL reconstruction. We present a simplified double-bundle ACL reconstruction by the 3-inside technique with 2 suspension buttons and 1 interference screw. The semitendinosus tendon is tripled to be the anteromedial (AM) bundle, whereas the gracilis is doubled for the posterolateral (PL) bundle. We perform a 3-socket approach with an inside-out femoral tunnel for the AM bundle, an outside-in femoral tunnel for the PL bundle, and a retrograde tibial socket for the tibial bundle. Thus, this technique is, simply, a combination of 2 procedures: one single all-inside method (for the AM bundle) and one outside-in method (for the PL bundle), with which most arthroscopic surgeons are familiar. The AM and PL bundles are fixed at 30° and 45°, respectively, using 2 suspension buttons and 1 interference screw. Our simplified technique could reduce surgical costs and minimize complications while maintaining isometric position and appropriate graft size for each patient.

Role of Dual-Energy Computed Tomography in the Identification of Monosodium Urate Deposition in Gout Patients: A Comprehensive Analysis of 828 Joints According to Structural Joint Damage.

Background Dual-energy computed tomography (DECT) has become a promising, non-invasive procedure for the visualization, characterization, and quantification of monosodium urate (MSU) crystals, which aids clinicians in the diagnosis of gout. In this study, we aimed to examine the diagnostic accuracy of DECT in the evaluation of gout. Methodology This cross-sectional retrospective study included patients who were clinically diagnosed with gout and underwent a DECT scan. Results A majority (80.4%) of the MSU deposits were found in the ankle joints. The presence of MSU deposits on DECT scan was highly correlated with bone erosion in the upper limb (odds ratio [OR] = 132; 95% confidence interval [CI] = 17.3-1004.3), bone sclerosis in the lower limb (OR = 36.4; 95% CI = 15.4-86.1), bone erosion in metacarpophalangeal joints (OR = 160; 95% CI = 42.7-600.2), and bone sclerosis in metatarsophalangeal joints (OR = 35.6; 95% CI = 15.5-81.9). Using linear regression analysis on patient-level data, correlations were found between DECT MSU crystal deposition and damage on all categories of structural joint damage showing significant association with erosion (r = 0.91, p < 0.001) and space narrowing (r = 0.75, p < 0.001) but not with joints having periarticular calcification (r = 0.52, p < 0.041). Conclusions Our study established DECT as a valid method for detecting MSU deposits and their association with structural joint deterioration in a Vietnamese population.

Concordance of bone and non-bone specimens in microbiological diagnosis of osteomyelitis: A systematic review and meta-analysis.

BACKGROUND: The diagnosis of osteomyelitis is invasive and expensive as the current standard technique is the bone biopsy. Our aim was to compare the degree of agreement and concordance between standard bone biopsy and other non-bone techniques. METHODS: We performed an electronic search through 12 electronic databases to retrieve relevant studeis. Our criteria included any original article that reported the degree of agreement and/or the concordance between bone biopsy and other non-bone techniques in diagnosing osteomyelitis. We published our protocol in PROSPERO with a registration number, CRD42017080336. RESULTS: There were 29 studies included in the qualitative analysis, of which 15 studies were included in the meta-analysis. Samples from sinus tract had the highest concordance with bone biopsy samples, while swab samples were the least concordant with bone biopsy samples. Additionally, Staphylococcus aureus was the most common bacteria isolated and the most concordant from samples, compared to other types of causative agents. Sinus tract had a significantly very high degree of agreement with bone samples. S. aureus had the highest degree of agreement in bone smaples. CONCLUSION: Diagnosis of osteomyelitis using sinus tract swab is close in results' accuracy to bone biopsy. S. aureus was the most common extracted organism found in these samples and had the highest degree of agreement.

Efficacy of kinesio taping in treatment of shoulder pain and disability: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Kinesio tape is an elastic therapeutic tape used for treating sports injuries and various other disorders. A systematic review and network meta-analysis approach was used to synthesise all related evidence on the clinical effectiveness of kinesio taping for the treatment of shoulder pain. METHODS: A literature search was performed using 10 major databases. Randomised clinical trials reporting usage of kinesio taping for shoulder pain have been included. Quality and risk of bias were assessed using the Cochrane Collaboration's quality assessment tool. Meta-analysis was conducted to calculate standardised mean differences and corresponding 95% confidence intervals (CI). The corresponding 95% CI of pooled effect size were calculated using a fixed-effects or random-effects model based on the level of heterogeneity. In addition, meta-regression was used to assess the influence of underlying shoulder disease on the efficacy of kinesio taping. RESULTS: This systematic review and meta-analysis included 12 studies, with a total of 555 participants. Pairwise comparisons inferred that kinesio taping only showed significant improvement of shoulder pain and disability when combined with exercise. However, kinesio taping did not produce better results than placebo or treatment with steroids. The duration of treatment and underlying shoulder pathology did not influence the efficacy of kinesio taping. CONCLUSION: There is insufficient evidence to support the use of kinesio taping in clinical practice as a treatment for shoulder pain. However, there is limited evidence of its benefit as a complementary treatment in shoulder pain syndromes. CLINICAL TRIAL REGISTRATION NUMBER: PROSPERO CRD42017065881.

The value of daily platelet counts for predicting dengue shock syndrome: Results from a prospective observational study of 2301 Vietnamese children with dengue.

BACKGROUND: Dengue is the most important mosquito-borne viral infection to affect humans. Although it usually manifests as a self-limited febrile illness, complications may occur as the fever subsides. A systemic vascular leak syndrome that sometimes progresses to life-threatening hypovolaemic shock is the most serious complication seen in children, typically accompanied by haemoconcentration and thrombocytopenia. Robust evidence on risk factors, especially features present early in the illness course, for progression to dengue shock syndrome (DSS) is lacking. Moreover, the potential value of incorporating serial haematocrit and platelet measurements in prediction models has never been assessed. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed data from a prospective observational study of Vietnamese children aged 5-15 years admitted with clinically suspected dengue to the Hospital for Tropical Diseases in Ho Chi Minh City between 2001 and 2009. The analysis population comprised all children with laboratory-confirmed dengue enrolled between days 1-4 of illness. Logistic regression was the main statistical model for all univariate and multivariable analyses. The prognostic value of daily haematocrit levels and platelet counts were assessed using graphs and separate regression models fitted on each day of illness. Among the 2301 children included in the analysis, 143 (6%) progressed to DSS. Significant baseline risk factors for DSS included a history of vomiting, higher temperature, a palpable liver, and a lower platelet count. Prediction models that included serial daily platelet counts demonstrated better ability to discriminate patients who developed DSS from others, than models based on enrolment information only. However inclusion of daily haematocrit values did not improve prediction of DSS. CONCLUSIONS/SIGNIFICANCE: Daily monitoring of platelet counts is important to help identify patients at high risk of DSS. Development of dynamic prediction models that incorporate signs, symptoms, and daily laboratory measurements, could improve DSS prediction and thereby reduce the burden on health services in endemic areas.

A Prognostic Model for Development of Profound Shock among Children Presenting with Dengue Shock Syndrome.

PURPOSE: To identify risk factors and develop a prediction model for the development of profound and recurrent shock amongst children presenting with dengue shock syndrome (DSS). METHODS: We analyzed data from a prospective cohort of children with DSS recruited at the Paediatric Intensive Care Unit of the Hospital for Tropical Disease in Ho Chi Minh City, Vietnam. The primary endpoint was "profound DSS", defined as ≥2 recurrent shock episodes (for subjects presenting in compensated shock), or ≥1 recurrent shock episodes (for subjects presenting initially with decompensated/hypotensive shock), and/or requirement for inotropic support. Recurrent shock was evaluated as a secondary endpoint. Risk factors were pre-defined clinical and laboratory variables collected at the time of presentation with shock. Prognostic model development was based on logistic regression and compared to several alternative approaches. RESULTS: The analysis population included 1207 children of whom 222 (18%) progressed to "profound DSS" and 433 (36%) had recurrent shock. Independent risk factors for both endpoints included younger age, earlier presentation, higher pulse rate, higher temperature, higher haematocrit and, for females, worse hemodynamic status at presentation. The final prognostic model for "profound DSS" showed acceptable discrimination (AUC=0.69 for internal validation) and calibration and is presented as a simple score-chart. CONCLUSIONS: Several risk factors for development of profound or recurrent shock among children presenting with DSS were identified. The score-chart derived from the prognostic models should improve triage and management of children presenting with DSS in dengue-endemic areas.

Clinical characteristics of Dengue shock syndrome in Vietnamese children: a 10-year prospective study in a single hospital.

BACKGROUND: Dengue shock syndrome (DSS) is a severe manifestation of dengue virus infection that particularly affects children and young adults. Despite its increasing global importance, there are no prospective studies describing the clinical characteristics, management, or outcomes of DSS. METHODS: We describe the findings at onset of shock and the clinical evolution until discharge or death, from a comprehensive prospective dataset of 1719 Vietnamese children with laboratory-confirmed DSS managed on a single intensive care unit between 1999 and 2009. RESULTS: The median age of patients was 10 years. Most cases had secondary immune responses, with only 6 clear primary infections, and all 4 dengue virus serotypes were represented during the 10-year study. Shock occurred commonly between days 4 and 6 of illness. Clinical signs and symptoms were generally consistent with empirical descriptions of DSS, although at presentation 153 (9%) were still febrile and almost one-third had no bleeding. Overall, 31 (2%) patients developed severe bleeding, primarily from the gastrointestinal tract, 26 of whom required blood transfusion. Only 8 patients died, although 123 of 1719 (7%) patients had unrecordable blood pressure at presentation and 417 of the remaining 1596 (26%) were hypotensive for age. The majority recovered well with standard crystalloid resuscitation or following a single colloid infusion. All cases were classified as severe dengue, while only 70% eventually fulfilled all 4 criteria for the 1997 World Health Organization classification of dengue hemorrhagic fever. CONCLUSIONS: With prompt intervention and assiduous clinical care by experienced staff, the outcome of this potentially fatal condition can be excellent.

Clinical features of dengue in a large Vietnamese cohort: intrinsically lower platelet counts and greater risk for bleeding in adults than children.

BACKGROUND: As dengue spreads to new geographical regions and the force of infection changes in existing endemic areas, a greater breadth of clinical presentations is being recognised. Clinical experience suggests that adults manifest a pattern of complications different from those observed in children, but few reports have described the age-related spectrum of disease in contemporaneous groups of patients recruited at the same geographical location. METHODOLOGY/PRINCIPAL FINDINGS: Using detailed prospectively collected information from ongoing studies that encompass the full spectrum of hospitalised dengue cases admitted to a single hospital in southern Vietnam, we compared clinical and laboratory features, management, and outcome for 647 adults and 881 children with confirmed dengue. Signs of vascular leakage and shock were more frequent and more severe in children than adults, while bleeding manifestations and organ involvement were more common in adults. Additionally, adults experienced significantly more severe thrombocytopenia. Secondary infection but not serotype was independently associated with greater thrombocytopenia, although with a smaller effect than age-group. The effect of age-group on platelet count was also apparent in the values obtained several weeks after recovery, indicating that healthy adults have intrinsically lower counts compared to children. CONCLUSIONS/SIGNIFICANCE: There are clear distinctions between adults and children in the pattern of complications seen in association with dengue infection, and these depend partly on intrinsic age-dependent physiological differences. Knowledge of such differences is important to inform research on disease pathogenesis, as well as to encourage development of management guidelines that are appropriate to the age-groups at risk.

Patterns of gene transcript abundance in the blood of children with severe or uncomplicated dengue highlight differences in disease evolution and host response to dengue virus infection.

DNA microarrays and specific reverse-transcription polymerase chain reaction assays were used to reveal transcriptional patterns in the blood of children presenting with dengue shock syndrome (DSS) and well-matched patients with uncomplicated dengue. The transcriptome of patients with acute uncomplicated dengue was characterized by a metabolically demanding "host-defense" profile; transcripts related to oxidative metabolism, interferon signaling, protein ubiquination, apoptosis, and cytokines were prominent. In contrast, the transcriptome of patients with DSS was surprisingly benign, particularly with regard to transcripts derived from apoptotic and type I interferon pathways. These data highlight significant heterogeneity in the type or timing of host transcriptional immune responses precipitated by dengue virus infection independent of the duration of illness. In particular, they suggest that, if transcriptional events in the blood compartment contribute to capillary leakage leading to hypovolemic shock, they occur before cardiovascular decompensation, a finding that has implications for rational adjuvant therapy in this syndrome.

Diagnostic accuracy of NS1 ELISA and lateral flow rapid tests for dengue sensitivity, specificity and relationship to viraemia and antibody responses.

BACKGROUND: Dengue is a public health problem in many countries. Rapid diagnosis of dengue can assist patient triage and management. Detection of the dengue viral protein, NS1, represents a new approach to dengue diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: The sensitivity and specificity of the Platelia NS1 ELISA assay and an NS1 lateral flow rapid test (LFRT) were compared against a gold standard reference diagnostic algorithm in 138 Vietnamese children and adults. Overall, the Platelia NS1 ELISA was modestly more sensitive (82%) than the NS1 LFRT (72%) in confirmed dengue cases. Both ELISA and LFRT assays were more sensitive for primary than secondary dengue, and for specimens collected within 3 days of illness onset relative to later time points. The presence of measurable DENV-reactive IgG and to a lesser extent IgM in the test sample was associated with a significantly lower rate of NS1 detection in both assays. NS1 positivity was associated with the underlying viraemia, as NS1-positive samples had a significantly higher viraemia than NS1-negative samples matched for duration of illness. The Platelia and NS1 LFRT were 100% specific, being negative in all febrile patients without evidence of recent dengue, as well as in patients with enteric fever, malaria, Japanese encephalitis and leptospirosis. CONCLUSIONS/SIGNIFICANCE: Collectively, these data suggest NS1 assays deserve inclusion in the diagnostic evaluation of dengue patients, but with due consideration for the limitations in patients who present late in their illness or have a concomitant humoral immune response.

A cohort study to assess the new WHO Japanese encephalitis surveillance standards.

OBJECTIVE: To assess the field-test version of the new WHO Japanese encephalitis (JE) surveillance standards. METHODS: We applied the clinical case definition of acute encephalitis syndrome (AES), laboratory diagnostic criteria and case classifications to patients with suspected central nervous system (CNS) infections in southern Viet Nam. FINDINGS: Of the 380 patients (149 children) recruited with suspected CNS infections, 296 (96 children) met the AES case definition. 54 children were infected with JE virus (JEV), of whom 35 (65%) had AES, giving a sensitivity of 65% (95% CI: 56-73) and specificity of 39% (95% CI: 30-48). Nine adults with JEV presented with AES. 19 JEV-infected children missed by surveillance included 10 with acute flaccid paralysis, two with flaccid hemiparesis and six with meningism only. Altering the case definition to include limb paralysis and meningism improved sensitivity to 89% (95% CI: 83-95), while reducing specificity to 23% (95% CI: 15-30). Six children that did not have AES on admission had reduced consciousness after admission. Cerebrospinal fluid (CSF) analysis diagnosed seven patients negative on serum analysis. Five patients with neurological manifestations of dengue infection had JEV antibodies in serum and would have been misdiagnosed had we not tested for dengue antibodies in parallel. CONCLUSION: Children infected with JEV that presented with acute limb paralysis or neck stiffness only were missed by the surveillance standards, although some of them subsequently became encephalopathic. A footnote in the surveillance standards drawing attention to these presentations would be helpful. An acute CSF sample is more sensitive and specific than an acute serum sample.

Increased frequencies of CD4+ CD25(high) regulatory T cells in acute dengue infection.

Dengue virus infection is an increasingly important tropical disease, causing 100 million cases each year. Symptoms range from mild febrile illness to severe hemorrhagic fever. The pathogenesis is incompletely understood, but immunopathology is thought to play a part, with antibody-dependent enhancement and massive immune activation of T cells and monocytes/macrophages leading to a disproportionate production of proinflammatory cytokines. We sought to investigate whether a defective population of regulatory T cells (T reg cells) could be contributing to immunopathology in severe dengue disease. CD4(+)CD25(high)FoxP3(+) T reg cells of patients with acute dengue infection of different severities showed a conventional phenotype. Unexpectedly, their capacity to suppress T cell proliferation and to secrete interleukin-10 was not altered. Moreover, T reg cells suppressed the production of vasoactive cytokines after dengue-specific stimulation. Furthermore, T reg cell frequencies and also T reg cell/effector T cell ratios were increased in patients with acute infection. A strong indication that a relative rise of T reg cell/effector T cell ratios is beneficial for disease outcome comes from patients with mild disease in which this ratio is significantly increased (P < 0.0001) in contrast to severe cases (P = 0.2145). We conclude that although T reg cells expand and function normally in acute dengue infection, their relative frequencies are insufficient to control the immunopathology of severe disease.

Proinflammatory cytokines and chemokines in humans with Japanese encephalitis.

BACKGROUND: Japanese encephalitis virus (JEV), the mosquito-borne flavivirus, annually causes an estimated 35,000-50,000 encephalitis cases and 10,000-15,000 deaths in Asia, and there is no antiviral treatment. The role played by the immune response in determining the outcome of human infection with JEV is poorly understood, although, in animal models of flavivirus encephalitis, unregulated proinflammatory cytokine responses can be detrimental. METHODS: We studied the innate, cellular, and humoral immune responses in 118 patients infected with JEV, of whom 13 (11%) died. RESULTS: Levels of interferon (IFN)- alpha , the proinflammatory cytokine interleukin (IL)-6, and the chemokine IL-8 were all higher in the cerebrospinal fluid (CSF) of the nonsurvivors than of the survivors (P=.04, P=.006, and P=.04, respectively), as were both the IL-6 : IL-4 ratio in CSF (a marker of the balance of pro- and anti-inflammatory cytokines) and the level of the chemokine RANTES (regulated on activation, normally T cell expressed and secreted) in plasma (P=.03). In contrast, levels of immunoglobulin (Ig) M and IgG in CSF and of IgM in plasma were higher in the survivors (P=.035, P=.003, and P=.009, respectively). Levels of IFN- gamma and nitric oxide did not vary with outcome. CONCLUSIONS: During JEV infection, elevated levels of proinflammatory cytokines and chemokines are associated with a poor outcome, but whether they are simply a correlate of severe disease or contribute to pathogenesis remains to be determined.

Size and charge characteristics of the protein leak in dengue shock syndrome.

BACKGROUND: he mechanism underlying the transient vascular leak syndrome of dengue hemorrhagic fever (DHF) is unknown. We aimed to determine whether molecular size and charge selectivity, which help restrict plasma proteins within the intravascular space, are altered in patients with DHF and whether a disturbance of the anionic glycosaminoglycan (GAG) layer on the luminal endothelial surface contributes to disease pathogenesis. METHODS: We measured serial plasma levels and fractional clearances of proteins with different size and charge characteristics in 48 children with dengue shock syndrome (DSS) and urinary excretion profiles of heparan sulfate, chondroitin-4-sulfate, and chondroitin-6-sulfate in affected children and healthy control subjects. RESULTS: Compared with convalescent values, acute plasma concentrations of all proteins were reduced, with increased fractional clearances. Smaller proteins were more affected than larger molecules. Albumin, which is normally protected from leakage by its strong negative charge, demonstrated a clearance pattern similar to that of transferrin, a neutral molecule of similar size. Urinary heparan sulfate excretion was significantly increased in children with DSS. CONCLUSIONS: The endothelial size-dependent sieving mechanism for plasma proteins is at least partially retained, whereas selective restriction based on negative charge is impaired. The increased heparan sulfate excretion suggests a role for GAGs in the pathogenesis of the vascular leak.

Interferon alfa-2a in Japanese encephalitis: a randomised double-blind placebo-controlled trial.

BACKGROUND: Japanese encephalitis virus (JEV), although confined to Asia, causes about 35000-50000 cases and 10000 deaths every year, and is the most important cause of encephalitis worldwide. There is no known antiviral treatment for any flavivirus. Results from in-vitro studies and work in animals have shown inteferon alfa has antiviral activity on Japanese encephalitis and other flaviviruses; therefore, we aimed to assess the efficacy of inteferon alfa-2a in Japanese encephalitis. METHODS: We did a randomised double-blind placebo-controlled trial of interferon alfa-2a (10 million units/m2, daily for 7 days) in 112 Vietnamese children with suspected Japanese encephalitis, 87 of whom had serologically confirmed infections. Our primary endpoints were hospital death or severe sequelae at discharge. Analysis was by intention to treat. FINDINGS: Overall, 21 children (19%) died, and 17 (15%) had severe sequelae. Outcome at discharge and 3 months did not differ between the two treatment groups; 20 children in the interferon group had a poor outcome (death or severe sequelae), compared with 18 in the placebo group (p=0.85, difference 0.1%, 95% CI -17.5 to 17.6%), there were no long-term side effects of interferon. INTERPRETATION: The doses of interferon alfa-2a given in this regimen did not improve the outcome of patients with Japanese encephalitis.

Treatment of severe diphtheritic myocarditis by temporary insertion of a cardiac pacemaker.

Vietnamese children and adolescents with diphtheritic myocarditis and severe conduction abnormalities were treated prospectively with temporary insertion of a cardiac pacemaker. Five of 32 patients died before the procedure could be performed; the remaining 27 patients underwent successful pacemaker insertion. In children and adolescents with diphtheritic myocarditis and severe conduction defects, temporary insertion of a cardiac pacemaker may improve the outcome.

Coagulation abnormalities in dengue hemorrhagic Fever: serial investigations in 167 Vietnamese children with Dengue shock syndrome.

The pathophysiological basis of hemorrhage in dengue infections remains poorly understood, despite the increasing global importance of these infections. A large prospective study of 167 Vietnamese children with dengue shock syndrome documented only minor prolongations of prothrombin and partial thromboplastin times but moderate to severe depression of plasma fibrinogen concentrations. A detailed study of 48 children revealed low plasma concentrations of the anticoagulant proteins C, S, and antithrombin III, which decreased with increasing severity of shock, probably because of capillary leakage. Concurrent increases in the levels of thrombomodulin, tissue factor, and plasminogen activator inhibitor type 1 (PAI-1) indicated increased production of these proteins. Thrombomodulin levels suggestive of endothelial activation correlated with increasing shock severity, whereas PAI-1 levels correlated with bleeding severity. Dengue virus can directly activate plasminogen in vitro. Rather than causing true disseminated intravascular coagulation, dengue infection may activate fibrinolysis primarily, degrading fibrinogen directly and prompting secondary activation of procoagulant homeostatic mechanisms.

Seizures and raised intracranial pressure in Vietnamese patients with Japanese encephalitis.

Japanese encephalitis (JE) causes at least 10 000 deaths each year. Death is presumed to result from infection, dysfunction and destruction of neurons. There is no antiviral treatment. Seizures and raised intracranial pressure (ICP) are potentially treatable complications, but their importance in the pathophysiology of JE is unknown. Between 1994 and 1997 we prospectively studied patients with suspected CNS infections referred to an infectious disease referral hospital in Ho Chi Minh City, Vietnam. We diagnosed Japanese encephalitis virus (JEV), using antibody detection, culture of serum and CSF, and immunohistochemistry of autopsy material. We observed patients for seizures and clinical signs of brainstem herniation, measured CSF opening pressures (OP) and, on a subset of patients, performed EEGs. Of 555 patients with suspected CNS infections, 144 (26%) were infected with JEV (134 children and 10 adults). Seventeen (12%) patients died and 33 (23%) had severe sequelae. Of the 40 patients with witnessed seizures, 24 (62%) died or had severe sequelae, compared with 26 (14%) of 104 with no witnessed seizures [odds ratio (OR) 4.50, 95% confidence interval (CI) 1.94-10.52, P < 0.0001]. Patients in status epilepticus (n = 25), including 15 with subtle motor seizures, were more likely to die than those with other seizures (P = 0.003). Patients with seizures were more likely to have an elevated CSF OP (P = 0.033) and to develop brainstem signs compatible with herniation syndromes (P < 0.0001). Of 11 patients with CSF OP > or =25 cm, five (46%) died, compared with seven (9%) of 80 patients with lower pressures [OR 8.69, 95% CI 1.73-45.39, P = 0.005). Of the 50 patients with a poor outcome, 35 (70%) had signs compatible with herniation syndromes (including 19 with signs of rostro-caudal progression), compared with nine (10%) of those with better outcomes (P < 0.0001). Of 11 patients with CSF OP > or =25 cm, five (46%) died, compared with seven (9%) of 80 patients with lower pressures (OR 8.69, 95% CI 1.73-45.39, P = 0.005). The combination of coma, multiple seizures, brainstem signs and illness for 7 or more days was an accurate predictor of outcome, correctly identifying 42 (84%) of 50 patients with a poor outcome and 82 (87%) of 94 with a better outcome. These findings suggest that in JE, seizures and raised ICP may be important causes of death. The outcome may be improved by measures aimed at controlling these secondary complications.