Residual Neurological Impairment Research Articles

Safety, tolerability, and efficacy of subcutaneous efgartigimod in patients with chronic inflammatory demyelinating polyradiculoneuropathy (ADHERE): a multicentre, randomised-withdrawal, double-blind, placebo-controlled, phase 2 trial

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system that can lead to severe disability from muscle weakness and sensory disturbances. Around a third of patients do not respond to currently available treatments, and many patients with a partial response have residual neurological impairment, highlighting the need for effective alternatives. Efgartigimod alfa, a human IgG1 antibody Fc fragment, has demonstrated efficacy and safety in patients with generalised myasthenia gravis. We evaluated the safety, tolerability, and efficacy of subcutaneous efgartigimod PH20 in adults with CIDP. ADHERE, a multistage, double-blind, placebo-controlled trial, enrolled participants with CIDP from 146 clinical sites from Asia-Pacific, Europe, and North America. Participants with evidence of clinically meaningful deterioration entered an open-label phase of weekly 1000 mg subcutaneous efgartigimod PH20 for no longer than 12 weeks (stage A). Those with confirmed evidence of clinical improvement (ECI; treatment responders) entered a randomised-withdrawal phase of 1000 mg subcutaneous efgartigimod PH20 weekly treatment versus placebo for a maximum of 48 weeks (stage B). Participants were randomised (1:1) through interactive response technology and stratified by their adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT) score change during stage A and their most recent CIDP medication within 6 months before screening. Investigators, the clinical research organisation, and participants were masked to the treatment. The primary endpoint in stage A, evaluated in the stage A safety population, was confirmed ECI (≥1 points aINCAT decrease, ≥4 points [centile metric] Inflammatory Rasch-built Overall Disability Scale increase, or ≥8 kPa grip strength increase after four injections and two consecutive visits). The primary endpoint in stage B, evaluated in the modified intention-to-treat population, was the risk of relapse (time to first aINCAT increase of ≥1 points). ADHERE is registered with ClinicalTrials.gov (NCT04281472) and EudraCT (2019-003076-39) and is completed. Between April 15, 2020, and May 11, 2023, 629 participants were screened; 322 (114 female, 208 male) entered stage A, of whom 214 (66%, 95% CI 61·0-71·6) had confirmed ECI. In stage B, 221 participants were randomised (79 female, 142 male; 111 to subcutaneous efgartigimod PH20, 110 to placebo). Subcutaneous efgartigimod PH20 significantly reduced the risk of relapse versus placebo (hazard ratio 0·39 [95% CI 0·25-0·61]; p<0·0001). 31 (27·9% [19·6-36·3]) participants given subcutaneous efgartigimod PH20 had a relapse versus 59 (53·6% [44·3-63·0]) given placebo. In stage A, treatment-emergent adverse events (TEAEs) occurred in 204 (63%) participants and serious TEAEs in 21 (7%). In stage B, TEAEs occurred in 71 (64%) participants on subcutaneous efgartigimod PH20 and 62 (56%) participants on placebo, and serious TEAEs in six (5%) on subcutaneous efgartigimod PH20 and six (5%) on placebo. Three deaths occurred: two in stage A (one non-related and one unlikely related to treatment) and one in stage B (placebo group). ADHERE showed the efficacy of subcutaneous efgartigimod PH20 in reducing the risk of relapse versus placebo in people with CIDP who responded to treatment. Further studies are needed to provide data on the longer-term effects of efgartigimod alfa and how it compares with currently available treatment options. argenx.

The mediating effect of anxiety on the association between residual neurological impairment and post-stroke participation among persons with and without post-stroke depression

ABSTRACT Previous research has reported that residual neurological impairment and emotional factors play a role in regaining successful participation post-stroke. The objective of this study was to investigate the mediating impact of anxiety on the association between residual neurological impairment and participation in survivors with and without post-stroke depressive symptoms. Participants (N = 79) were classified into 2 categories, those with post-stroke depressive symptoms (N = 40) and those without post-stroke depressive symptoms (N = 39). Variables measured in this study: residual neurological impairment (NIH Stroke Scale Score), participation (Reintegration to Normal Living Index), depressive symptoms (Patient Health Questionnaire-9), and trait anxiety (State-Trait Anxiety Inventory). A regression-based mediation analysis was conducted for each group of participants. The majority of participants had some level of anxiety. Residual neurological impairment predicted participation in stroke survivors both with (β = -.45, p = .003) and without (β = -.45, p = .004) post-stroke depressive symptoms. Anxiety mediated this relationship in participants with depressive symptoms (β = -.19, 95% CI = -.361 ∼ -.049), but not in participants without depressive symptoms (β = -.18, 95% CI = -.014 ∼ .378). Depressive and anxious symptoms should both be addressed to best facilitate participation by stroke survivors.

Vertical Transfer of Humoral Immunity against Nipah Virus: A Novel Evidence from Bangladesh.

A major obstacle to in-depth investigation of the immune response against Nipah virus (NiV) infection is its rapid progression and high mortality rate. This paper described novel information on the vertical transfer of immune properties. In January 2020, a female aged below five years and her mother from Faridpur district of Bangladesh were infected. Both had a history of raw date palm sap consumption and were diagnosed as confirmed NiV cases. The daughter passed away, and the mother survived with significant residual neurological impairment. She conceived one and a half year later and was under thorough antenatal follow-up by the surveillance authority. A healthy male baby was born. As part of routine survivor follow-up, specimens were collected from the newborn and tested for NiV infection at the reference laboratory to exclude vertical transmission. Although testing negative for anti-Nipah IgM and PCR for NiV, a high titre of anti-Nipah IgG was observed. The transfer of humoral immunity against NiV from mother to neonate was confirmed for the first time. The article will serve as a reference for further exploration regarding NiV-specific antibodies that are transferred through the placenta, their potential to protect newborns, and how this may influence vaccine recommendations.

Self-Perceived ADL/IADL Function is Influenced by Residual Neurological Impairment, Aphasia, and Anxiety.

Background. Self-perceptions of performance of activities of daily living (ADL) and instrumental activities of daily living (IADL) are reduced following stroke. Research investigating contributing factors is lacking. Purpose: We examined the extent to which aphasia status, neurological impairment and poststroke depression, and anxiety contribute to self-perceived ADL/IADL function. Method: Seventy-six community-dwelling individuals at least 6 months poststroke, 44 with and 32 without aphasia, participated in the cross-sectional study. The Stroke Impact Scale (SIS) ADL/IADL domain was the primary outcome measure with aphasia status, residual neurological impairment, depressive symptoms, and anxiety as predictor variables. Findings: Aphasia status, residual neurological impairment, and anxiety were independent predictors of self-perceived ADL/IADL function, together accounting for more than half the variance. Depression was not associated with ADL/IADL. Implications: Clinician awareness of the influence of anxiety on self-perceived ADL/IADL function, particularly for people with aphasia, may lead to future interventions that improve self-perceived ADL/IADL function.

The relationship between health behaviors and emergency department visits and hospitalizations after traumatic spinal cord injury.

Cross-sectional study. To identify demographic, injury, and behavioral predictors of emergency department (ED) visits and ED-related hospitalizations among individuals with chronic traumatic spinal cord injury (SCI). An academic medical center in the Southeastern United States. 4057 participants who were at least 18 years of age and 1 year post traumatic SCI with residual neurologic impairment were identified from three cohorts: a rehabilitation specialty hospital in the Southeastern USA and two SCI Surveillance System Registries, one in the Midwestern and one in the Southeastern USA. The participants completed a self-reported assessment on ED visits and ED hospitalizations (yes/no) in the past 12 months. Logistic regression models were used to examine the relationship between ED visits/hospitalizations and eight behavioral indicators, including body weight, healthy diet, drinking, smoking, non-medical substance usage, prescription medication usage, prescription medication misuse, and the planned exercise. During the study period, 41% of participants reported having at least one ED visit and 21% participants reported hospitalization after ED visit in the past 12 months. High frequency of prescription medication usage, prescription medication misuse, and lack of planned exercise were associated with greater odds of at least one ED visit and at least one ED-related hospitalization, while smoking was only associated with ED visits. Health care professionals should be aware that ED visit and related hospitalization prevalence remain high among people with chronic SCI, and there is significant need for intervention of managing risk behaviors and promoting healthy behaviors after SCI.

Abstract TP7: Phase 2a Study Of Elezanumab In Patients With Acute Ischemic Stroke

Introduction: Treatment of acute ischemic stroke focuses on reperfusion but is limited by timing and other exclusions, and despite intervention, patients may sustain residual neurologic impairment. In addition to initial excitotoxic reactions following occlusion, upregulation of factors such as repulsive guidance molecule A (RGMa) inhibits cell survival and neuronal repair in infarcted regions. In vivo neutralization of RGMa is associated with decreased lesion size, reduced glial scarring, and enhanced functional recovery in animal models of cerebral artery occlusion; thus, RGMa suppression represents a novel therapeutic target due to its potential protective and restorative mechanisms. Elezanumab is an investigational monoclonal antibody that binds specifically to RGMa and is being evaluated for its function after ischemic stroke. Methods: Elezanumab in Acute Ischemic Stroke (EAISE) is a 52-week, phase 2a, randomized, double-blind, placebo-controlled study evaluating safety, efficacy, and pharmacokinetics of elezanumab in patients with acute ischemic stroke (NCT04309474). Patients will be randomized 1:1 within 23 hours since “last known normal” to receive elezanumab or placebo and every 4 weeks thereafter through week 48. Patients must be aged 30-90 years with a clinical diagnosis of acute ischemic stroke in anterior circulation and have a National Institutes of Health Stroke Scale (NIHSS) total score of 7 to 21. Patients who receive tissue plasminogen activator or endovascular therapy will be eligible if they continue to exhibit an NIHSS of 7 to 21 after treatment. Patients with evidence of seizure on stroke onset and history of repeated episodes of complex migraines will be excluded. Results: Projected enrollment is 120 patients across 45 sites in multiple countries. Primary endpoint is the NIHSS total score throughout the treatment period. Secondary endpoint is a favorable outcome based on the modified Rankin Scale, defined as a score of 0-2 at week 52. Exploratory outcomes include activities of daily living, cognition, mood, and fluid and imaging biomarkers. Conclusion: This phase 2 study will evaluate safety and efficacy of elezanumab, a novel therapeutic intervention to improve neurological recovery after acute ischemic stroke.

Management of severe inaugural diabetic ketoacidosis in paediatric intensive care: retrospective comparison of two protocols.

The two paediatric DKA-management protocols differing in terms of fluid-volume, glucose, and sodium intakes had comparable effects on clinical and laboratory-test changes within 24h. Major drops in glycaemia and osmolality were common with both protocols. No patients had residual neurological impairments. •Cerebral oedema is the most severe complication of diabteic ketoacidosis in children.The risk of cerebral oedema is dependant on both patient related and treatment-related factors. •The optimal protocol for managing severe inaugural diabetic ketoacidosis in children remains unclear, and few studies have targeted this specific population. •Two management protocols that complied with ISPAD guidelines but differed regarding the amounts of fluids, glucose, and sodium administered produced similar outcomes in children with severe inaugural diabetic ketoacidosis. •Cerebral oedema was rare with both protocols and caused no lasting impairments.

Apathy and residual neurological impairment are associated with community reintegration after mild stroke

ABSTRACT This study investigated the influence of apathy and positive social support on community reintegration after stroke. A prospective, correlational, cross-sectional design was used. 85 community dwelling participants with and without aphasia were included (≥ 18 years of age, first stroke, ≥ 6 months post-stroke). The Reintegration to Normal Living Index (RNL) measured poststroke participation. The Apathy Evaluation Scale (AES) and Positive Social Interaction domain of the Medical Outcomes Study Social Support Survey assessed apathy and social support respectively. NIH Stroke Scale measured residual neurological impairment. Apathy, social support, and stroke impairment together were strongly associated with the RNL and accounted for 51% of total variance in the RNL. The AES and NIHSS were independent predictors of the RNL, though positive social interaction failed to reach significance. Persons with and without apathy differed significantly on the RNL. Therefore, stroke rehabilitation should address apathy as a potential target for intervention. Future research should determine factors that mediate the relationship between poststroke apathy and community reintegration.

Effects of Fluoxetine on Functional Recovery after Acute Stroke (AFFINITY): A Randomised, Double-Blind, Placebo-Controlled Trial

Background: Trials of fluoxetine for recovery after stroke have reported conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to determine if daily fluoxetine for 6 months after acute stroke improves functional outcomes in an Australasian and Vietnamese population. Methods: AFFINITY was an international, multicentre, randomised, parallel-group, double-blind, placebo-controlled trial. Eligible adult patients with residual neurological impairment 2-15 days after stroke were randomised centrally using a minimisation algorithm to once daily, oral fluoxetine 20mg or matching placebo for 6 months. The primary outcome was functional recovery (modified Rankin scale, mRS) at 6 months. The primary analysis was an intention-to-treat, ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. The planned sample size was 1600 patients. Findings: 1280 patients were recruited in Australia (n=532), New Zealand (n=42) and Vietnam (n=706) between 11 January 2013 and 30 June 2019; 642 were allocated fluoxetine and 638 placebo. Adherence to trial medication (mean 167 [SD 48] days) was similar between groups. At 6 months, mRS data were available in 97.2% (fluoxetine) and 99.1% (placebo) of patients. The distribution of mRS categories at 6 months was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0.936, 95% CI 0.762-1.150; p=0.5296), and consistent in all pre-defined subgroups. Compared to placebo, patients allocated fluoxetine had more falls (3.12% vs 1.10%), bone fractures (2∙96% vs 0.94%) and seizures (1.56% vs 0.31%) at 6 months. Interpretation: Fluoxetine 20mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. These results do not support the use of fluoxetine for stroke recovery. Trial registration: The trial was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN 12611000774921. Funding Statement: National Health and Medical Research Council of Australia (Project Grant 1059094). Declaration of Interests: Dr. Hankey reports grants from the National Health & Medical Research Council of Australia, Vetenskapsradet (The Swedish Research Council), and United Kingdom National Institute for Health Research Technology (NIHR), during the conduct of the study; and personal fees from American Heart Association, outside the submitted work. Dr. Hackett reports grants from National Health and Medical Research Council, during the conduct of the study. Dr. Etherton-Beer reports grants from National Health and Medical Research Council (NHMRC) of Australia, during the conduct of the study. Dr. Lung reports grants from Australian National Health and Medical Research Council, during the conduct of the study; other from George Health Enterprises, outside the submitted work; In addition, Dr. Lung has a patent Low-dose blood pressure lowering combination medications pending to George Health Enterprises. Dr. Anderson reports grants from National Health and Medical Research Council (NHMRC) of Australia, grants from Takeda, personal fees from Takeda, outside the submitted work. Drs Almeida, Flicker, Dennis, Ford, Billot, Jan, Murray, Lundstrom, Thang-Nguyen, and Gommans have nothing to disclose. Ethics Approval Statement: The trial protocol (supplementary appendix) was approved by the Royal Perth Hospital Ethics Committee on 24 February, 2012 (approval number EC2011/131). All participating sites subsequently received approval from their relevant ethics committee and institutional review board. Written informed consent was obtained from each patient or, if the patients were unable to provide consent, from their legally approved surrogate.

Sarcoidosis of the central nervous system: Safety and efficacy of treatment, and experience of biological therapies

ObjectivesNeurological complications of sarcoidosis are uncommon and the natural history and optimal treatments under-researched. With the advent of biological therapies, it is important to define the clinical characteristics and immunopathology of the disease. Patients and methodsPatients referred to and treated within the Centre for Neurosarcoidosis over a 15 year period who had biopsy proven “highly probable” disease of the central nervous system were studied prospectively. ResultsCorticosteroids were used effectively in all patients, immunosuppression in 79 % and TNFα antagonists in 23 %. Treatment with steroids alone inevitably led to relapse, and low dose immunosuppression was ineffective in those with severe forms of the disease. Use of biological therapies substantially improved outcome.Patients with cranial neuropathy had an excellent outcome. Those with pachymeningitis had marked radiological abnormalities but less disablement. Those with leptomeningitis had an invasive, destructive disease which responded well to treatment but with residual neurological impairments. Treatment was required for many years, but the risk of relapse following treatment withdrawal was low. Infective complications arose in six. There were two deaths, neither directly related to the neurological disease, nor its treatment. ConclusionsThis prospective study of the natural history and treatment response in neurosarcoidosis provides evidence that the use of high dose immunosuppression and early and prolonged use of biological therapies is associated with greatly improved outcomes and lower mortality. The data may be used to plan further studies and treatment trials, and provide class IV evidence for the effectiveness of biological agents in the treatment of Neurosarcoidosis.

Smoke inhalation injury in a 2-year-old domestic fire victim

Smoke inhalation injury is common in victims of domestic fires, among whom children are the most vulnerable. Cyanide poisoning may occur in addition to carbon monoxide poisoning and is challenging to diagnose. In France, the recommended antidotes are hydroxocobalamin for cyanide and hyperbaric oxygen for carbon monoxide. We managed a 26-month-old girl who sustained smoke inhalation injury with both carbon monoxide and cyanide poisoning during a house fire. Despite hydroxocobalamin and sodium thiosulfate therapy combined with hyperbaric oxygen, she had residual neurological impairments 3 months after the injury. The treatment challenges and detailed neurological follow-up data are described.

ПОСЛЕОПЕРАЦИОННАЯ РЕАБИЛИТАЦИЯ ПРИ ДЕГЕНЕРАТИВНЫХ ЗАБОЛЕВАНИЯХ ПОЗВОНОЧНИКА

Surgical treatment for degenerative disk diseases is widespread today. Surgery is used to decompress neural structures, eliminate pain and symptoms of neurologic impairment. Nevertheless, a successful surgical intervention does not always guarantee a favorable clinical effect, which is associated with various factors: the duration of a disease, compensatory abilities of patients, and their emotional state. Thus, post-operative rehabilitation, based on a multimodal patient-oriented personalized approach, becomes very relevant. Post-operative rehabilitation considers the degree of functional limitation or loss and the impact of situational factors. According to the concept of post-operative rehabilitation as a personalized management strategy, it is advisable to divide patients into the following groups: those who do not have alert complaints or neurological impairment after surgery; those who have chronic pain; those who have residual or persistent neurological impairment. Such an approach allows physicians to suggest an individual program for rehabilitation treatment. Keywords: postoperative rehabilitation, degenerative disk diseases, multimodal patient-oriented personalized approach.

ХИРУРГИЧЕСКАЯ КОРРЕКЦИЯ НЕДОСТАТОЧНОСТИ МОЗГОВОГО КРОВООБРАЩЕНИЯ ПРИ АТЕРОСКЛЕРОЗЕ ЭКСТРАЦЕРЕБРАЛЬНЫХ АРТЕРИЙ

There is more than 1 million people who have had a stroke in Russia; the third part of these people are of working age, and only every fourth patient returned to job. This article discusses one of the most effective methods of stroke prevention - the procedure of carotid endarterectomy. We performed 468 reconstructive operations in 448 patients. 65 % (305) of surgeries were open carotid endarterectomies. In other cases, operations of prosthetics or blood flow switching between extracerebral arteries (ECA) (163) were carried out. Short-term results of reconstructive operations showed that 96 % of outcomes were positive. Perioperative mortality at operations made 1.06 %. The general complications made 4.5 %, minor complications were observed in 21 patients (4.4 %). The five years survival rate of patients operated on ECA made 86 %, the main cause of death in recent follow-up period was a cardiac pathology (58 %), brain disorders made 15 %. Among dominating risk factors are coronary heart disease, previous transient ischemic attacks and residual neurologic impairment.

Prediction of 3- to 5-Month Outcomes from Signs of Acute Bilirubin Toxicity in Newborn Infants

To evaluate the ability of the bilirubin-induced neurologic dysfunction (BIND) score to predict residual neurologic and auditory disability and to document the relationship of BIND score to total serum bilirubin (TSB) concentration. The BIND score (assessing mental status, muscle tone, and cry patterns) was obtained serially at 6- to 8-hour intervals in 220 near-term and full-term infants with severe hyperbilirubinemia. Neurologic and/or auditory outcomes at 3-5 months of age were correlated with the highest calculated BIND score. The BIND score was also correlated with TSB. Follow-up neurologic and auditory examinations were performed for 145/202 (72%) surviving infants. All infants with severe acute bilirubin encephalopathy (BIND scores 7-9) either died or suffered residual neurologic and auditory impairment. Of 24 cases with moderate encephalopathy (BIND 4-6), 15 (62.5%) resolved following aggressive intervention and were normal at follow-up. Three of 73 infants with mild encephalopathy (BIND scores 1-3) but severe jaundice (TSB ranging 33.5-38 mg/dL; 573-650 µmol/L) had residual neurologic and/or auditory impairment. A BIND score ≥4 had a specificity of 87.3% and a sensitivity of 97.4% for predicting poor neurologic outcomes (receiver operating characteristic analysis). BIND scores trended higher with severe hyperbilirubinemia (r2 = 0.54, P < .005), but 5/39 (13%) infants with TSB ≥36.5 mg/dL (624 µmol/L) had BIND scores ≤3, and normal outcomes at 3-5 months. The BIND score can be used to evaluate the severity of acute bilirubin encephalopathy and predict residual neurologic and hearing dysfunction.

Rationale, Design and Early Trial Performance of AOSpine North America Multi-Center Double Blind Randomized Controlled Trial of Safety and Efficacy of Riluzole in CSM (CSM – Protect Trial)

Introduction While surgical decompression is an effective treatment for CSM, many patients have substantial residual neurological and functional impairment. Compelling evidence from preclinical models suggest a benefit of adding a neuroprotective drug which targets sodium/glutamate excitotoxicity to the treatment of patients with CSM. The purpose of this study is to evaluate efficacy and safety of sodium-glutamate antagonist riluzole in improving neurological outcomes in patients with cervical spondylotic myelopathy (CSM) undergoing surgical treatment. Material and Methods Prospective multi-center double-blind randomized controlled trial in which a total of 300 patients undergoing surgical decompression for CSM will be randomized 1:1 to riluzole 2x50mg daily for 14 days before the surgery and 28 days after the surgery or to the placebo. Primary outcome measure is change in mJOA between baseline and 6 months. Secondary outcomes include ASIA, SF36v2, NDI, Eq. 5D, Pain VAS and complications. The sample size of 270 completed subjects will have 80% power to detect absolute difference of 0.9 in mJOA score between the investigational and the control group. The statistical analysis is organized as a sequential adaptive trial with one interim analysis at 65% of the accrued sample for early futility and efficacy. Adaptive statistical design allows for sample size adjustment at the time of interim analysis. Results To date, 212 subjects have been enrolled. Average age of the enrolled subjects is 58.1 years (SD 10.2); 56% males. The baseline mJOA is 11.9 (SD 1.5). Baseline NDI is 42.5 (SD 20.4) and the baseline SF36v2 Physical Component Score (PCS) is 32.8 (SD 9.9). Conclusion In spite of the benefits of the surgical intervention, patients with CSM experience significant residual impairment and neurological compromise. Adding neuroprotective treatment with riluzole may improve outcomes of surgery. This talk will emphasize the unique study design and the biological rationale for considering riluzole as a potential neuroprotective adjunct for patients undergoing surgery for CSM

Pharmacotherapy to Enhance Cognitive and Motor Recovery Following Stroke.

Stroke is a leading cause of disability among older adults and more than half of stroke survivors have some residual neurological impairment. Traditionally, managing the aftermath of stroke has been by the implementation of several physical and language therapy modalities. The limitations of these rehabilitation efforts have sparked an interest in finding other ways to enhance neurological recovery. Some of these novel approaches have included pharmacological interventions, cell-derived treatments, and cortical magnetic stimulation. Mounting evidence over the last 2decades suggests that pharmacological manipulations may have the potential to modulate practice-dependent neuroplasticity and potentially improve neurological recovery after stroke. Multiple pharmacological agents with different mechanisms of action have been evaluated, showing conflicting results. Some studies suggest some promise, yet the quality of the available studies is suboptimal overall, with most of the studies being underpowered. So far, the most promising agents include the antidepressants for motor recovery and acetylcholinesterase inhibitors and memantine for aphasia. However, large, well-designed clinical trials are needed to address the shortcomings of the available data and before any pharmacological agent can be recommended for routine use as part of the standard algorithm of stroke management.

New classification of acute papilledema in children with severe malaria

Raised intracranial pressure is a feature of cerebral malaria in children living in Africa. We investigated specific clinical optic disc features of papilledema to establish their prognostic significance in this encephalopathy. We developed a classification of acute papilledema and tested it against disease outcome. Kenyan children admitted with severe falciparum malaria (cerebral or impaired consciousness) underwent dilated fundal examination using direct and indirect ophthalmoscopy. Clinical features of the optic disc were systematically recorded and compared to the child's outcome. Poor outcome defined as death or neurological impairment on discharge was used to construct and test a clinical classification of papilledema. Forty-five children were examined (26 cerebral malaria, 17 severe malaria with an impaired conscious level or prostration) of whom seven had a poor outcome (three died, four had residual neurological impairment). Loss of the optic disc cup and marked optic disc elevation were significantly correlated with a poor outcome (P < 0.05). Increasing severity in the proposed classification of acute papilledema was positively correlated with a poor outcome (P < 0.05, chi-square test for trend). Loss of the optic disc cup and marked elevation of the optic disc head appear to be correlated with poor outcome in children with severe malaria whereas the presence of dilated veins suggests a good outcome. The proposed classification of acute papilledema is useful as a prognostic indicator and may be applicable to other encephalopathies with raised intracranial pressure.

Does Magnetic Resonance Imaging Improve the Predictive Performance of a Validated Clinical Prediction Rule Developed to Evaluate Surgical Outcome in Patients With Degenerative Cervical Myelopathy?

Ambispective study. To determine whether MRI parameters improve the predictive performance of a validated clinical prediction rule used to assess functional outcomes in surgical patients with DCM. Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord dysfunction in the elderly worldwide. A clinical prediction rule was developed to discriminate between patients with mild myelopathy postoperatively (mJOA ≥ 16) and those with substantial residual neurological impairment (mJOA < 16). Recently, a separate magnetic resonance imaging (MRI)-based prediction model was created. However, a model exploring the combined predictive value of imaging and clinical variables does not exist. One hundred and fourteen patients with MRIs were examined from a cohort of 278 patients enrolled in the AOSpine CSM-North America Study. Ninety-nine patients had complete preoperative imaging and postoperative outcome data. MRIs were evaluated for the presence/absence of signal change on T2- and T1-weighted images. Quantitative analysis of the T2 signal change was conducted and maximum canal compromise and cord compression were calculated. The added predictive performance of each MRI parameter to the clinical model was evaluated using receiver operator characteristic curves. The model developed on our subsample yielded an area under the receiver operator curve (AUC) of 0.811 (95% CI: 0.726-0.896). The addition of imaging variables did not significantly improve the predictive performance. Small improvements in prediction were obtained when sagittal extent of T2 hyperintensity (AUC: 0.826, 95% CI: 0.743-0.908, 1.35% increase) or Wang ratio (AUC: 0.823, 95% CI: 0.739-0.907, 1.21%) was added. Anatomic characteristics, such as maximum canal compromise and maximum cord compression, did not improve the discriminative ability of the clinical prediction model. In our sample of surgical patients, with clinical and image-evidence of DCM, MRI parameters do not significantly add to the predictive performance of a previously published clinical prediction rule. It remains plausible that combinations of the strongest clinical and MRI predictors may yield a similar or a superior prediction model. 3.

Rationale, Design, and Early Trial Performance of AOSpine North America Multicenter Double Blind Randomized Controlled Trial of Safety and Efficacy of Riluzole in CSM (CSM—Protect Trial)

Introduction Although surgical decompression is an effective treatment for cervical spondylotic myelopathy (CSM), many patients have substantial residual neurological and functional impairment. Compelling evidence from preclinical models suggest a benefit of adding a neuroprotective drug which targets sodium/glutamate excitotoxicity to the treatment of patients with CSM. The purpose of this study is to evaluate efficacy and safety of sodium-glutamate antagonist riluzole in improving neurological outcomes in patients with CSM undergoing surgical treatment. Patients and Methods Prospective multicenter double-blind randomized controlled trial in which a total of 300 patients undergoing surgical decompression for CSM will be randomized 1:1 to riluzole 2 × 50 mg daily for 14 days before the surgery and 28 days after the surgery or to the placebo. Primary outcome measure is change in mJOA between baseline and 6 months. Secondary outcomes include ASIA, SF36v2, NDI, Eq. 5D, Pain VAS, and complications. Sample size was estimated based on data from recently completed prospective cohort study. The sample size of 270 completed subjects will have 80% power to detect absolute difference of 0.9 in mJOA score between the investigational and the control group. The statistical analysis is organized as a sequential adaptive trial with one interim analysis at 65% of the accrued sample for early futility and efficacy. Adaptive statistical design allows for sample size adjustment at the time of interim analysis. Results To date, 153 subjects have been enrolled. Average age of the enrolled subjects is 58.4 years (SD, 10.13). The baseline mJOA is 11.9 (SD, 1.5). Baseline NDI is 42.4 (SD, 20.1) and the baseline SF36v2 Physical Component Score (PCS) is 33.5 (SD, 9.3). Conclusion In spite of the benefits of the surgical intervention, patients with CSM experience significant residual impairment and neurological compromise. Adding neuroprotective treatment with riluzole may improve outcomes of surgery. This discussion will emphasize the unique study design and the biological rationale for considering riluzole as a potential neuroprotective adjunct for patients undergoing surgery for CSM.

A Clinical Prediction Rule for Clinical Outcomes in Patients Undergoing Surgery for Degenerative Cervical Myelopathy: Analysis of an International AOSpine Prospective Multicenter Data Set of 743 Subjects

Introduction Knowledge of important clinical predictors of surgical outcome can provide decision support to surgeons and enable them to appropriately manage their patients' expectations. This study aims to determine the most important global clinical predictors of surgical outcome in patients undergoing surgery for CSM, based on data from two multicenter prospective studies. Patients and Methods A total of 743 surgical patients with CSM participated in either the CSM-North America or CSM-International study. The model was developed to distinguish between patients with mild myelopathy postoperatively (mJOA ≥ 16) and those with substantial residual neurological impairment (mJOA &lt; 16). Univariate analyses were performed to evaluate the relationship between outcome and various clinical predictors. Multivariate logistic regression was used to formulate the final prediction model. Results Univariate analyses demonstrated that the odds of achieving a score ≥ 16 decreased with the presence of certain symptoms, including impaired gait; the presence of certain signs such as lower limb spasticity; positive smoking status; a higher comorbidity score; more severe preoperative myelopathy; and older age. The final prediction model included age (OR = 0.97, p = 0.0017), duration of symptoms (OR = 0.88, p = 0.049), smoking status (OR = 0.51, p = 0.0018), impairment of gait (OR = 1.94, p = 0.0168), broad-based unstable gait (OR = 1.75, p = 0.0133), baseline severity (OR = 1.23, p &lt; 0.0001), and comorbidity score (OR = 0.84, p = 0.0030). Conclusion Patients are more likely to achieve a score ≥ 16 if they are younger, have a shorter duration of symptoms, are less severe preoperatively, do not smoke, and do not have comorbidities or evidence of gait dysfunction.