Cause Of Neurological Deterioration Research Articles

85 - Diabetic Ketoacidosis Manifesting as Cerebral Venous Sinus Thrombosis in a Patient With Undiagnosed Diabetes Mellitus

Diabetic ketoacidosis (DKA) and uncontrolled diabetes have been recognized as prothrombotic states. Central venous sinus thrombosis (CVST) is an extremely rare complication of DKA with a highly variable clinical presentation. CVST can mimic cerebral edema as a cause of neurological deterioration in hyperglycemic emergencies.

Propentdyopents as Heme Degradation Intermediates Constrict Mouse Cerebral Arterioles and Are Present in the Cerebrospinal Fluid of Patients With Subarachnoid Hemorrhage.

Delayed ischemic neurological deficit is the most common cause of neurological impairment and unfavorable prognosis in patients with subarachnoid hemorrhage (SAH). Despite the existence of neuroimaging modalities that depict the onset of the accompanying cerebral vasospasm, preventive and therapeutic options are limited and fail to improve outcome owing to an insufficient pathomechanistic understanding of the delayed perfusion deficit. Previous studies have suggested that BOXes (bilirubin oxidation end products), originating from released heme surrounding ruptured blood vessels, are involved in arterial vasoconstriction. Recently, isolated intermediates of oxidative bilirubin degradation, known as PDPs (propentdyopents), have been considered as potential additional effectors in the development of arterial vasoconstriction. To investigate whether PDPs and BOXes are present in hemorrhagic cerebrospinal fluid and involved in the vasoconstriction of cerebral arterioles. Via liquid chromatography/mass spectrometry, we measured increased PDP and BOX concentrations in cerebrospinal fluid of SAH patients compared with control subjects. Using differential interference contrast microscopy, we analyzed the vasoactivity of PDP isomers in vitro by monitoring the arteriolar diameter in mouse acute brain slices. We found an arteriolar constriction on application of PDPs in the concentration range that occurs in the cerebrospinal fluid of patients with SAH. By imaging arteriolar diameter changes using 2-photon microscopy in vivo, we demonstrated a short-onset vasoconstriction after intrathecal injection of either PDPs or BOXes. Using magnetic resonance imaging, we observed a long-term PDP-induced delay in cerebral perfusion. For all conditions, the arteriolar narrowing was dependent on functional big conductance potassium channels and was absent in big conductance potassium channels knockout mice. For the first time, we have quantified significantly higher concentrations of PDP and BOX isomers in the cerebrospinal fluid of patients with SAH compared to controls. The vasoconstrictive effect caused by PDPs in vitro and in vivo suggests a hitherto unrecognized pathway contributing to the pathogenesis of delayed ischemic deficit in patients with SAH.

A Dual Approach for the Management of Complex Craniovertebral Junction Abnormalities: Endoscopic Endonasal Odontoidectomy and Posterior Decompression with Fusion

BackgroundVentral brainstem compression secondary to complex craniovertebral junction abnormality is an infrequent cause of neurologic deterioration in pediatric patients. However, in cases of symptomatic, irreducible ventral compression, 360° decompression of the brainstem supported by posterior stabilization may provide the best opportunity for improvement in symptoms. More recently, the endoscopic endonasal corridor has been proposed as an alternative method of odontoidectomy associated with less morbidity. We report the largest single case series of pediatric patients using this dual-intervention surgical technique. The purpose of this study was to evaluate the surgical outcomes of pediatric patients who underwent posterior occipitocervical decompression and instrumentation followed by endoscopic endonasal odontoidectomy performed to relieve neurologic impingement involving the ventral brainstem and craniocervical junction.MethodsBetween January 2011 and February 2017, 7 patients underwent posterior instrumented fusion followed by endonasal endoscopic odontoidectomy at our unit. Standardized clinical and radiological parameters were assessed before and after surgery. A univariate analysis was performed to assess clinical and radiologic improvement after surgery.ResultsA total of 14 operations were performed on 7 pediatric patients. One patient had Ehlers-Danlos syndrome, 1 patient had a Chiari 1 malformation, and the remaining 5 patients had Chiari 1.5 malformations. Average extubation day was postoperative day 0.9. Average day of initiation of postoperative feeds was postoperative day 1.0.ConclusionsThe combined endoscopic endonasal odontoidectomy and posterior decompression and fusion for complex craniovertebral compression is a safe and effective procedure that appears to be well tolerated in the pediatric population.

Reperfusion therapy in patients with minor or mild ischemic stroke

A significant number of patients with minor or mild stroke symptoms on initial presentation subsequently develop neurological deterioration and poor clinical outcomes at hospital discharge. The presence of an underlying large vessel occlusion is a strong predictor of both clinical worsening and poor outcome. Although patients with a low baseline National Institutes of Health Stroke Scale (NIHSS) could have been included in some randomized controlled trials, the benefits of the mechanical thrombectomy for patients with a low NIHSS score are unknown. The causes of neurological deterioration in patients with underlying large vessel occlusion are heterogeneous, but include collateral failure, and no straightforward mechanisms are found in the majority of cases. Patients with internal carotid artery occlusion, but with a patent middle cerebral artery (MCA), can occasionally have good collateral circulation and develop only minor or mild stroke. These patients exhibit collateral MCA flow via the circle of Willis despite ipsilateral internal carotid artery occlusion. However, thrombus migration may cause occlusion of collateral MCA flow, leading to dramatic neurological deterioration. Careful observation and detailed assessment are required for the management of these patients. Recent studies have examined the efficacy and optimal timing of thrombolysis or mechanical thrombectomy for patients with minor or mild stroke. Herein, we review the mechanisms of neurological deterioration, and the efficacy of reperfusion therapy, for patients with minor or mild stroke.

Ocular and Intracranial MR Imaging Findings in Abusive Head Trauma.

Abusive head trauma (AHT) is a form of inflicted head injury. AHT is more frequent in 2-year-old or younger children. It is an important cause of neurological impairment and the major cause of death from head trauma in this age group. Brain magnetic resonance imaging allows the depiction of retinal hemorrhages, injured bridging veins, and identifying and localizing extra- and intra-axial bleeds, contusions, lacerations, and strokes. The diagnosis of AHT is a multidisciplinary team effort which includes a careful evaluation of social, clinical, laboratory, and radiological findings. Notwithstanding, the introduction in the current clinical practice of high-resolution techniques is adding forensic evidence to the recognition of AHT.

Memory deficits and hippocampal inflammation in cerebral hypoperfusion and reperfusion in male rats: Neuroprotective role of vanillic acid

Ischemic stroke is one of the leading causes of neurological deterioration and mortality worldwide. Neuroprotective strategies are being investigated to minimize cognitive deficits after ischemic events. Here we investigated the neuroprotective potential of vanillic acid (VA) in an animal model of transient bilateral common carotid artery occlusion and reperfusion (BCCAO/R). Adult male Wistar rats (250–300 g) were randomly divided in 4 groups and submitted to either cerebral hypoperfusion-reperfusion or a sham surgery after two-weeks of pretreatment with VA and/or normal saline. To induce the animal model of hypoperfusion, bilateral common carotid arteries were occluded (2VO model) for 30 min, followed by 72 h of reperfusion. Subsequently, their cognitive performance was evaluated in a Morris water maze (MWM) test, and also hippocampi were removed for ELISA assays and TUNEL staining test. The results showed that 2VO significantly reduced the spatial memory performance in MWM. As well as, BCCAO/R increased the level of IL-6, TNF-α and TUNEL positive cells, and also decreased the contents of IL-10 in the hippocampus of vehicle- pretreated groups as compared to the sham-operated groups. Furthermore, 14 consecutive days pretreatment with VA significantly restored the spatial memory, decreased the levels of IL-6, TNF-α and TUNEL positive cells and also increased the IL-10 levels in the hippocampi of the BCCAO/R rats. VA alone did not show any change neither in the status of various cytokines nor behavioral and TUNEL staining tests over sham values. Our data confirm that VA could potentially serve as a novel, promising, and accessible neuroprotective agent against cerebrovascular insufficiency states and vascular dementia.

Abstract TP316: Epidemiology of Neurologic Deterioration in Acute Stage of Ischemic Stroke or Transient Ischemic Attack

Objective: Neurologic Deterioration (ND) is known to be related to disability and poor outcomes. However, no large epidemiologic study on ND has been reported. Methods: Patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) admitted within 7 days of symptom onset were identified. Under a component of a quality assurance program of stroke care, we have captured ND during hospitalization prospectively with regular monitoring and systemic audits. ND was defined as any new neurological symptoms/signs or neurological worsening within 3 weeks of onset, satisfying one or more of the followings: increase of total NIHSS score ≥ 2, subscore 1a, 1b, or 1c (level of consciousness) ≥ 1, or subscore 5a, 5b, 6a, or 6b (motor)≥1, or any new neurological deficit (even unmeasurable by NIHSS scores). We investigated the incidence, timing, causes and outcomes of ND. Results: From December 2010 to September 2015, 29446 patients with AIS or TIA were admitted to 15 participating centers. Seventy-one percent of the patients were hospitalized within 24hours of onset. Deterioration occurred in 18.2% during median 10.1 days of hospitalization, its cumulative incidence was 5.6% at 1 day, 9.1% at 2 days, 10.9% at 3 days, 14.2% at one week. As causes of ND, progression was most common (73%), followed by recurrence (8.5%). Compared to those without ND, patients with ND were more likely to be older, be females, be hospitalized earlier, have stroke subtypes of large arterial disease or cardioembolism, have relevant steno-occlusion of major cerebral arteries, and have severer neurologic deficits. ND was independently associated with poorer functional outcome (modified Rankin scale 3 or more) at 3 months (adjusted odds ratio, 5.58; 95% confidence intervals (CI), 5.10-6.11) and one year (4.85; 4.43-5.32), and incidence of major vascular events (stroke, myocardial infarction, all-cause death) up to one year (adjusted hazards ratio, 1.64; 95% CI, 1.50-1.79). Conclusions: Our study reveals that about one fifths of AIS or TIA patients deteriorate neurologically during hospitalization and this deterioration is associated with poor functional outcome and subsequent major vascular events. Further researches for its prediction, detection and treatment are warranted.

18F-FDG PET-CT pattern in idiopathic normal pressure hydrocephalus.

BackgroundIdiopathic normal pressure hydrocephalus (iNPH) is an important and treatable cause of neurologic impairment. Diagnosis is complicated due to symptoms overlapping with other age related disorders. The pathophysiology underlying iNPH is not well understood. We explored FDG-PET abnormalities in iNPH patients in order to determine if FDG-PET may serve as a biomarker to differentiate iNPH from common neurodegenerative disorders.MethodsWe retrospectively compared 18F-FDG PET-CT imaging patterns from seven iNPH patients (mean age 74 ± 6 years) to age and sex matched controls, as well as patients diagnosed with clinical Alzheimer's disease dementia (AD), Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD), and behavioral variant frontotemporal dementia (bvFTD). Partial volume corrected and uncorrected images were reviewed separately.ResultsPatients with iNPH, when compared to controls, AD, DLB/PDD, and bvFTD, had significant regional hypometabolism in the dorsal striatum, involving the caudate and putamen bilaterally. These results remained highly significant after partial volume correction.ConclusionsIn this study, we report a FDG-PET pattern of hypometabolism in iNPH involving the caudate and putamen with preserved cortical metabolism. This pattern may differentiate iNPH from degenerative diseases and has the potential to serve as a biomarker for iNPH in future studies. These findings also further our understanding of the pathophysiology underlying the iNPH clinical presentation.

Association between short- and medium-term air pollution exposure and risk of mortality after intravenous thrombolysis for stroke.

The exposure to air pollutants may increase both incidence and mortality of stroke. We aimed to investigate the association of short- and medium-term exposure to particulate matter (PM) and nitrogen dioxide (NO2) with the outcome of intravenous thrombolysis (IVT) for stroke. We conducted a retrospective analysis based on data prospectively collected from 944 consecutive IVT-treated stroke patients. The main outcome measure was 3-month mortality. The secondary outcome measures were causes of neurological deterioration (≥ 1 NIHSS point from baseline or death < 7 days), including intracerebral hemorrhage, cerebral edema (CED), and persistence or new appearance of hyperdense cerebral artery sign. In the adjusted model, higher PM2.5 and PM10 values in the last 3 days and 4 weeks before stroke were independently associated with higher mortality rate [hazard ratio (HR) 1.014, 95% confidence intervals (CI) 1.005-1.024, p = 0.003; HR 1.079, 95% CI 1.055-1.103, p = 0.001; HR 1.019, 95% CI 1.005-1.032, p = 0.008; and HR 1.015, 95% CI 1.004-1.027, p = 0.007; respectively]. Higher PM2.5 and PM10 values in the last 4 weeks were associated with higher CED rate [odd ratio (OR) 1.023, 95% CI 1.007-1.040, p = 0.006; and OR 1.017, 95% CI 1.003-1.032, p = 0.021; respectively]. No significant association between PM or NO2 and other causes of neurological deterioration was observed. Higher exposure to PM in the last 3 days and 4 weeks before stroke may be independently associated with 3-month mortality after IVT. Higher exposure to PM in the last 4 weeks before stroke may also be independently associated with CED after IVT.

Tuberculosis of the spine with severe angular kyphosis: mean 34-year post-operative follow-up shows that prevention is better than salvage.

To address the natural history of severe post-tuberculous (TB) kyphosis, with focus upon the long-term neurological outcome, occurrence of restrictive lung disease, and the effect on life expectancy. This is a retrospective clinical review of prospectively collected imaging data based at a single institute. A total of 24 patients of Southern Chinese origin who presented with spinal TB with a mean of 113° of kyphosis (65° to 159°) who fulfilled inclusion criteria were reviewed. Plain radiographs were used to assess the degree of spinal deformity. Myelography, CT and MRI were used when available to assess the integrity of the spinal cord and canal. Patient demographics, age of onset of spinal TB and interventions, types of surgical procedure, intra- and post-operative complications, and neurological status were assessed. All except one of the 24 patients were treated with anti-TB chemotherapy when they were first diagnosed with spinal TB. They subsequently received surgery either for neurological deterioration, or deformity correction in later life. The mean follow-up was 34 years (11 to 59) since these surgical interventions. Some 16 patients (66.7%) suffered from late neurological deterioration at a mean of 26 years (8 to 49) after the initial drug treatment. The causes of neurological deterioration were healed disease in nine patients (56.2%), re-activation in six patients (37.5%) and adjacent level spinal stenosis in one patient (6.3%). The result of surgery was worse in healed disease. Eight patients without neurological deterioration received surgery to correct the kyphosis. The mean correction ranged from 97°to 72°. Three patients who were clinically quiescent with no neurological deterioration were found to have active TB of the spine. Solid fusion was achieved in all cases and no patient suffered from neurological deterioration after 42 years of follow-up. On final follow-up, six patients were noted to have deceased (age range: 47 years to 75 years). Our study presents one of the longest assessments of spinal TB with severe kyphosis. Severe post-TB kyphosis may lead to significant health problems many years following the initial drug treatment. Early surgical correction of the kyphosis, solid fusion and regular surveillance may avoid late complications. Paraplegia, restrictive lung disease and early onset kyphosis might relate to early death. Clinically quiescent disease does not mean cure. Cite this article: Bone Joint J 2017;99-B:1381-8.

Functional abilities of children with cerebral palsy

Introduction. Cerebral palsy is one of the leading causes of neurological impairment in childhood. The dominant clinical sign is the impairment of gross motor functions; however, associated conditions may limit the child with cerebral palsy in daily activities as well. The aim of this study was to determine the functional status of children with cerebral palsy, its relationship with the types of cerebral palsy, and concomitant conditions. Material and Methods. The sample included 206 children with cerebral palsy. The data were obtained from medical records with clinical characteristics of cerebral palsy, and associated conditions. The clinical types of cerebral palsy were determined using the Surveillance of Cerebral Palsy in Europe registry and topographical categories. Gross motor function abilities were evaluated using the Gross Motor Function Classification System and manual abilities by the Manual Ability System Classification. Results. According to the Gross Motor Function Classification System, about two thirds of children with cerebral palsy (64.0%) had levels I, II or III of gross motor function impairment. A statistically significant difference was noted with respect to the distribution of various clinical types of cerebral palsy in relation to functional classification based on Gross Motor Function Classification System (p &lt; 0.001), as well as in the functional classification in terms of intellectual impairment (p &lt;0.001); children with severe forms of intellectual impairment were classified at a higher level of functional limitation. Epilepsy was more prevalent in children with higher level of functional limitation (p = 0.009). Conclusion. Two thirds of children with cerebral palsy could walk independently or with walking aids. Children with quadriplegia and dyskinetic type of cerebral palsy had the most limited functional abilities. Associated conditions were more prevalent in children with higher functional limitations.

Functional Genetic Variants of FOXP3 and Risk of Multiple Sclerosis

Background: Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS). MS is one of the most common cause of neurological impairment at a young age with a complex etiology. The forkhead/winged helix (FOXP3) gene encodes a transcription factor that plays an important role in the working and progress of regulatory T cells. Loss of the FOXP3 function impairs the suppressor activity of regulatory T (T-reg) cells, which have been reported in MS patients. Objectives: To determine whether rs2232365 and rs3761548 polymorphisms of FOXP3 are associated with the risk of MS in an Iranian population. Patients and Methods: In this case-control study, a total of 384 samples consisting of 190 MS patients and 194 unrelated healthy subjects from the Iranian population were recruited between December 2014 and September 2015. The patients were diagnosed by a neurologist based on McDonald’s criteria. The control group had no history or presence of autoimmune diseases. The polymorphisms were genotyped using tetra-ARMS PCR and PCR-restriction fragment length polymorphism (RFLP) techniques. Results: The Rs2232365 G allele was significantly associated with an increased risk of MS (P = 0.0068). In contrast, the allele and genotype frequencies of rs3761548 was not significantly different between the case and control groups (P > 0.05). Conclusions: The functional variant of the FOXP3, rs2232365 A/G, may be considered a substantial risk factor for MS.

Advances in clinical determinants and neurological manifestations of B vitamin deficiency in adults.

B vitamin deficiency is a leading cause of neurological impairment and disability throughout the world. Multiple B vitamin deficiencies often coexist, and thus an understanding of the complex relationships between the different biochemical pathways regulated in the brain by these vitamins may facilitate prompter diagnosis and improved treatment. Particular populations at risk for multiple B vitamin deficiencies include the elderly, people with alcoholism, patients with heart failure, patients with recent obesity surgery, and vegetarians/vegans. Recently, new clinical settings that predispose individuals to B vitamin deficiency have been highlighted. Moreover, other data indicate a possible pathogenetic role of subclinical chronic B vitamin deficiency in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In light of these findings, this review examines the clinical manifestations of B vitamin deficiency and the effect of B vitamin deficiency on the adult nervous system. The interrelationships of multiple B vitamin deficiencies are emphasized, along with the clinical phenotypes related to B vitamin deficiencies. Recent advances in the clinical determinants and diagnostic clues of B vitamin deficiency, as well as the suggested therapies for B vitamin disorders, are described.

Time to Neurological Deterioration in Ischemic Stroke.

Neurological deterioration (ND) is common, with nearly one-half of ND patients deteriorating within the first 24 to 48 hours of stroke. The timing of ND with respect to ND etiology and reversibility has not been investigated. At our center, we define ND as an increase of 2 or more points in the National Institutes of Health Stroke Scale (NIHSS) score within 24 hours and categorize etiologies of ND according to clinical reversibility. ND etiologies were considered non-reversible if such causes may have produced or extended any areas of ischemic neurologic injury due to temporary or permanent impairment in cerebral perfusion. Seventy-one of 350 ischemic stroke patients experienced ND. Over half (54.9%) of the patients who experienced ND did so within the 48 hours of last seen normal. The median time to ND for non-reversible causes was 1.5 days (IQR 0.9, 2.4 days) versus 2.6 days for reversible causes (IQR 1.4, 5.5 days, p=0.011). After adjusting for NIHSS and hematocrit on admission, the log-normal survival model demonstrated that for each 1-year increase in a patient's age, we expect a 3.9% shorter time to ND (p=0.0257). In addition, adjusting for age and hematocrit on admission, we found that that for each 1-point increase in the admission NIHSS, we expect a 3.1% shorter time to ND (p=0.0034). We found that despite having similar stroke severity and age, patients with nonreversible causes of ND had significantly shorter median time to ND when compared to patients with reversible causes of ND.

Secretoneurin Serum Levels in Healthy Term Neonates and Neonates with Hypoxic-Ischaemic Encephalopathy

Background: Hypoxic-ischaemic encephalopathy is a major cause of neurologic impairment and mortality in neonates. Early knowledge of brain injury is important to guide therapeutic decisions and reliably inform the parents. Increased secretoneurin levels have been detected in adult patients suffering from brain injury and it has also been shown to be a promising early serum biomarker of unfavourable neurological outcome. However, no data are available in neonates. Objective: The aim of this study was to obtain reference values for secretoneurin in healthy term neonates and then to assess the potential of this neuropeptide as a biomarker in the context of hypoxic-ischaemic encephalopathy in asphyxiated term neonates. Methods: A total number of 139 term neonates, of which 7 were asphyxiated and 132 were healthy, were prospectively enrolled. Secretoneurin serum concentrations were assessed by radioimmunoassay. Results: In healthy controls, secretoneurin serum concentrations were influenced by the mode of delivery (highest in infants born per vacuum extraction and lowest in infants born per caesarean section) and abnormal cardiotocography. In asphyxiated term neonates, secretoneurin concentrations were higher in umbilical cord blood and significantly lower 48 h after birth in comparison to healthy controls. Conclusion: Secretoneurin levels are elevated in cord blood in infants suffering from hypoxic-ischaemic encephalopathy following perinatal asphyxia. The potential of secretoneurin as a marker of neonatal hypoxic-ischaemic brain injury should be further evaluated in larger trials.

Whole-brain CT perfusion combined with CT angiography for ischemic complications following microsurgical clipping and endovascular coiling of ruptured intracranial aneurysms

Ischemic complications associated with microsurgical clipping and endovascular coiling affects the outcome of patients with intracranial aneurysms. We prospectively evaluated 58 intracranial aneurysm patients who had neurological deterioration or presented with poor grade (Hunt-Hess grades III and IV), aneurysm size >13mm and multiple aneurysms after clipping or coiling. Thirty patients had ischemic complications (52%) as demonstrated by whole-brain CT perfusion (WB-CTP) combined with CT angiography (CTA). Half of these 30 patients had treatment-associated reduction in the diameter of the parent vessels (n=6), ligation of the parent vessels or perforating arteries (n=2), and unexplained or indistinguishable vascular injury (n=7); seven of these 15 (73%) patients suffered infarction. The remaining 15 patients had disease-associated cerebral ischemia caused by generalized vasospasm (n=6) and focal vessel vasospasm (n=9); six of these 15 (40%) patients developed infarction. Three hemodynamic patterns of ischemic complications were found on WB-CTP, of which increased time to peak, time to delay and mean transit time associated with decreased cerebral blood flow and cerebral blood volume were the main predictors of irreversible ischemic lesions. In conclusion, WB-CTP combined with CTA can accurately determine the cause of neurological deterioration and classify ischemic complications. This combined approach may be helpful in assessing hemodynamic patterns and monitoring operative outcomes.

English

Background: Health care professionals from industrialized nations often travel to work in developing countries as volunteers during natural disasters, as part of short-term medical missions, or to work as members of armed forces and non-governmental organizations. When providing direct patient care, these clinicians are more likely to encounter vaccine-preventable diseases that they may rarely observe in a developed country. In addition, many children who do not have adequate vaccine coverage enter developed nations through international adoption processes or as political refugees. Additionally, despite much debunking of immunization myths, there is a sizable community of parents who choose to withhold immunizations from their children because of fear of unproven side effects. Methods and Results: This case study highlights a case of a globally-common, vaccine-preventable disease (tetanus), which rarely occurs in developed nations but is more common in Africa and Asia. Diagnosis and management of a 7-year old boy is presented with differential diagnoses and adaptation of optimal disease management within the context of an undeveloped nation. All cases of tetanus are diagnosed clinically, with laboratory testing used to rule out other causes of neurological impairment. The management of acute tetanus infection includes vaccination, antibiotics, immunoglobulin or antitoxin, and nutritional support. Even with optimal treatment, tetanus infection has a high fatality rate and requires prompt recognition for best possible outcomes. Conclusion: Educating caregivers about the importance and safety of immunizations and maintaining the appropriate vaccination schedule is vital to control these preventable diseases.

Aneurysmal Subarachnoid Hemorrhage—Status Quo and Perspective

Aneurysmal subarachnoid hemorrhage (SAH) accounts for about 5 % of all strokes and continues to be a major cause of morbidity and mortality, especially in younger patients (mean age of 52). The global incidence of SAH is 9 per 100, 000 per year with some regional variations [1]. Data from population-based studies suggests a distinct decrease in case fatality (0.9 % per year) over the past four decades to about 30 %, which is likely originated in earlier and more advanced aneurysm repair as well as improved neurocritical care of SAH patients following aneurysm repair [2]. Nevertheless, the incidence of poor functional outcome in SAH patients remains high (about one third of patients). The main determinants for poor outcome after SAH are the degree of early brain injury (EBI) and the incidence of delayed cerebral ischemia (DCI) (see below) [3, 4]. The clinical course of SAH is complex and can be divided into an acute stage (the initial 72 h after SAH ictus) and a subacute stage, which lasts up until 20 days after SAH ictus. The potential main complications in the acute phase are EBI, rebleeding from the ruptured aneurysms, with a frequency of up to 23 % within the first 72 h, and acute hydrocephalus, occurring in about 20 % of the patients, whereas the main complications occurring in the subacute phase are DCI (formerly referred to as Bvasospasm,^ see below), cardiopulmonary or other medical complications, as well as permanent hydrocephalus [5–7]. The term EBI refers not only to direct mechanical damage to the brain tissue due to the hemorrhage but also to a cascade of different pathomechanisms, incl. a temporary increase of intracranial pressure, consecutive reduction of cerebral blood flow and/or microcirculatory spasm, transient global ischemia, neuronal injury or apoptosis, and edema formation [8]. The degree of EBI is a strong and independent predictor for clinical outcome after SAH [9, 3, 4]. The term DCI describes a complex phenomenon as a consequence of several pathomechanisms, incl. (1) macrovascular or angiographic vasospasm, i.e., narrowing of proximal cerebral arteries, (2) microvascular spasm, (3) microthromboembolism, (4) cortical spreading depolarization/ischemia, (5) autoregulatory dysfunction, and (6) inflammation [10–13, 7, 14–17]. The radiological term vasospasm has been widely replaced with the clinical term DCI, which describes a secondary neurological deterioration in the course SAH, excluding other causes of neurological deterioration; an explicit definition for DCI has been proposed by a multidisciplinary research group [16]. This Bparadigm shift^ came along with the insight that angiographic vasospasm occurs in up to 70 % of SAH patients, whereas only 30 % of SAH patients develop clinical features of DCI and, moreover, because pharmaceutical treatments exclusively targeting of angiographic vasospasm failed to improve neurological outcome after SAH [18–20]. However, in those clinical studies where cerebral infarction due to DCI was effectively reduced by experimental pharmaceutical treatments, a significant improvement of clinical outcome was also seen. These data further underlined the concept that DCI comprises several, pro-ischemic pathomechanisms, which ultimately result in cerebral infarction, but the individual importance of each of these pro-ischemic pathomechanisms remains to elucidated [21, 22]. The general shift in scientific focus, i.e., away from ‘vasospasm’ towards DCI and EBI, can also be * Nima Etminan etminan@uni-duesseldorf.de

Tuberculosis of the spine – Prospective neurological and patient reported outcome study

ObjectiveTo prospectively investigate the rate of neurological recovery and patient reported outcome of tuberculosis (TB) spine patients following surgery at a tertiary referral hospital.TB spine remains a major cause of neurological impairment in the developing world fuelled by poor socio-economic conditions and HIV co-infection. Although numerous retrospective studies are available, there is a paucity of prospective data regarding rate of neurological improvement and patient reported outcome. MethodsTwenty adult patients were prospectively recruited. The average age was 44.5 years. Half had co-existent HIV infection.All patients underwent decompressive surgery utilising a variety of anterior and posterior procedures. All received a minimum of 9 months TB medication.They were followed up at 4, 8, 12, 26 and 52 weeks post operatively. Neurological status was monitored by Nurick, mJOA and ASIA systems. Patient reported outcome was monitored by SF36 questionnaires at all-time points. ResultsAll patients improved neurologically including 4 ASIA A's. By last follow up, 17 could walk as opposed to 5 pre-op. The Nurick average score improved from 5.5 to 1.9 and the mJOA lower limb score 1.8–5.5.The SF36 improved from 31 to 62 over the year with the biggest gains occurring after 3 months. This was confirmed in all domains except pain and social, which improved earlier. ConclusionsThere is a positive prognosis for neurological outcome in TB spine following a variety of surgical decompressive procedures and medical therapy. The majority of the recovery occurs after the 3 months post-operative mark.

In-hospital stroke recurrence and stroke after transient ischemic attack: frequency and risk factors.

We aimed to assess the risk of recurrent ischemic events during hospitalization for stroke or transient ischemic attack (TIA) with optimal current management and to identify associated risk factors. We performed a retrospective analysis of all patients treated for acute ischemic stroke or TIA in 3 stroke units between 2010 and 2013. Recurrent stroke was defined as new persisting (≥24 hours) neurological deficit occurring >24 hours after the index event and not attributable to other causes of neurological deterioration. Cox proportional hazard regression identified risk factors associated with recurrent stroke. The study included 5106 patients. During a median length of stay of 5 days (interquartile range, 4-8), stroke recurrence (or stroke after TIA) occurred in 40 patients (0.8%) and was independently associated with history of TIA, symptomatic carotid stenosis (≥70%), or other determined etiology. Patients with recurrent stroke and other determined etiology had cervical arterial dissection (n=2), primary angiitis of the central nervous system (n=1), giant cell arteritis (n=1), and lung cancer with nonbacterial thrombotic endocarditis (n=1). In patients with initial TIA or minor stroke (National Institutes of Health Stroke Scale ≤5) recurrence was associated additionally with pneumonia after the inciting ischemic event but before stroke recurrence. Patients with initial stroke and aphasia had a lower stroke recurrence rate and there were no recurrences in patients with lacunar stroke. Recurrence was associated with significantly higher in-hospital mortality (17.5% versus 3.1%; P<0.001). In-hospital stroke recurrence was low with optimal current management. Patients with a history of TIA, severe symptomatic carotid stenosis, or uncommon causes of stroke were at higher risk. Pneumonia was associated with a higher risk of stroke recurrence in patients with initial TIA or minor stroke but not in the overall population studied. Aphasia may bias the detection rate by concealing new neurological symptoms.