Fernando D. Goldenberg

Outcome in patients with subarachnoid hemorrhage treated with antiepileptic drugs.

OBJECT Prophylactic use of antiepileptic drugs (AEDs) in patients admitted with aneurysmal subarachnoid hemorrhage (SAH) is common practice; however, the impact of this treatment strategy on in-hospital complications and outcome has not been systematically studied. The goal in this study was twofold: first, to describe the prescribing pattern for AEDs in an international study population; and second, to delineate the impact of AEDs on in-hospital complications and outcome in patients with SAH. METHODS The authors examined data collected in 3552 patients with SAH who were entered into four prospective, randomized, double-blind, placebo-controlled trials conducted in 162 neurosurgical centers and 21 countries between 1991 and 1997. The prevalence of AED use was assessed by study country and center. The impact of AEDs on in-hospital complications and outcome was evaluated using conditional logistic regressions comparing treated and untreated patients within the same study center. RESULTS Antiepileptic drugs were used in 65.1% of patients and the prescribing pattern was mainly dependent on the treating physicians: the prevalence of AED use varied dramatically across study country and center (intraclass correlation coefficients 0.22 and 0.66, respectively [p < 0.001]). Other predictors included younger age, worse neurological grade, and lower systolic blood pressure on admission. After adjustment, patients treated with AEDs had odds ratios of 1.56 (95% confidence interval [CI] 1.16-2.10; p = 0.003) for worse outcome based on the Glasgow Outcome Scale; 1.87 (95% CI 1.43-2.44; p < 0.001) for cerebral vasospasm; 1.61 (95% CI 1.25-2.06; p < 0.001) for neurological deterioration; 1.33 (95% CI 1.01-1.74; p = 0.04) for cerebral infarction; and 1.36 (95% CI 1.03-1.80; p = 0.03) for elevated temperature during hospitalization. CONCLUSIONS Prophylactic AED treatment in patients with aneurysmal SAH is common, follows an arbitrary prescribing pattern, and is associated with increased in-hospital complications and worse outcome.

Early Vasospasm on Admission Angiography in Patients with Aneurysmal Subarachnoid Hemorrhage Is a Predictor for In-Hospital Complications and Poor Outcome

Background and Purpose— Early vasospasm (EVSP), defined here as arterial narrowing seen on diagnostic angiography within the first 48 hours of aneurysmal rupture, is a rarely reported and poorly defined phenomenon in patients with subarachnoid hemorrhage (SAH). The purpose of this study was to characterize EVSP in a large database of such patients. Methods— We analyzed the relationship of EVSP to clinical characteristics, in-hospital complications, and outcome at 3 months among 3478 patients entered into 4 prospective, randomized, double-blind, placebo-controlled trials of tirilazad conducted in neurosurgical centers around the world between 1991 and 1997. Results— Three hundred thirty-nine (10%) of 3478 patients had EVSP. EVSP was significantly more likely in patients with poor neurological grade on admission, history of SAH, intracerebral hematoma, larger aneurysm, thick SAH on cranial computed tomography, and intraventricular hemorrhage. EVSP was not associated with delayed cerebral vasospasm. After adjustment for differences in admission characteristics, EVSP was associated with cerebral infarction (adjusted odds ratios [OR]=1.51; 95% CI, 1.18 to 1.94; P=0.001), neurological worsening (OR=1.41; 95% CI, 1.10 to 1.81; P=0.007), and unfavorable outcome (OR=1.51; 95% CI, 1.15 to 2.00; P=0.003). In addition, there was a trend for patients with increasingly severe EVSP to have unfavorable outcome (OR=1.84 for mild and OR=2.66 for moderate/severe EVSP). Conclusions— EVSP was seen in 10% of SAH patients and was predictive of cerebral infarction and neurological worsening as well as unfavorable outcome at 3 months. EVSP was not associated with late vasospasm. EVSP may be as important as delayed vasospasm in predicting complications and long-term morbidity in SAH patients.

Intraventricular hemorrhage from ruptured aneurysm: clinical characteristics, complications, and outcomes in a large, prospective, multicenter study population

OBJECT In this study the authors analyzed the relationship of intraventricular hemorrhage (IVH) to in-hospital complications and clinical outcome in a large population of patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS Data from 3539 patients with aneurysmal SAH were evaluated, and these data were obtained from four prospective, randomized, double-blind, placebo-controlled trials of tirilazad that had been conducted between 1991 and 1997. Clinical characteristics, in-hospital complications, and outcome at 3 months post-SAH (Glasgow Outcome Scale score) were analyzed with regard to the presence or absence of IVH. RESULTS Patients with SAH and IVH differ in demographic and admission characteristics from those with SAH but without IVH and are more likely to suffer in-hospital complications and a worse outcome at 3 months post-SAH. CONCLUSIONS The presence of IVH in patients with SAH has an important predictive value with regard to these aspects.

Practice variability in brain death determination A call to action

Objective: To characterize the present state of brain death (BD) determination in actual practice relative to contemporary American Academy of Neurology (AAN) guidelines. Methods: We reviewed the charts of all adult (16 years and older) BD organ donors during 2011 from 68 heterogeneous hospitals in the Midwest United States. Data were collected across 5 categories: guideline performance, preclinical testing, clinical examination, apnea testing, and use of ancillary tests. Practice within categories and overall adherence to AAN guidelines were assessed. Results: Two hundred twenty-six BD organ donors were included. Practice exceeded recommendations in guideline performance but varied widely and deviated from AAN guidelines in all other categories. One hundred two (45.1%) had complete documentation of brainstem areflexia and absent motor response. One hundred sixty-six (73.5%) had completed apnea testing. Of the 60 without completed apnea testing, 56 (93.3%) had ancillary tests consistent with BD. Overall, 101 (44.7%) strictly and 84 (37.2%) loosely adhered to contemporary AAN guidelines. Conclusions: There is wide variability in the documentation of BD determination, likely reflecting similar variability in practice. This is a call for improved documentation, better uniformity of policies, and comprehensive and strategically targeted educational initiatives to ensure consistently contemporary approaches to BD determination in every patient.

Decompressive hemicraniectomy for acute disseminated encephalomyelitis : Case report

OBJECTIVE AND IMPORTANCE:Acute disseminated encephalomyelitis (ADEM) varies widely in symptoms and severity. Some cases are associated with massive life-threatening cerebral edema refractory to conventional medical management. CLINICAL PRESENTATION:A 51-year-old woman with ADEM who developed severe brain swelling and herniation despite aggressive medical management is described. INTERVENTION:A decompressive hemicraniectomy and durotomy led to rapid improvement and an excellent outcome. CONCLUSION:This case report reinforces the place of this procedure in the armamentarium of treatment options for patients with medically refractory brain swelling and elevated intracranial pressure caused by ADEM. The potential for an increase in the incidence of ADEM with more frequent smallpox vaccinations emphasizes the significance of redefining the full range of management options for this treatable disease.

Prophylaxis of Venous Thrombosis in Neurocritical Care Patients: An Evidence-Based Guideline: A Statement for Healthcare Professionals from the Neurocritical Care Society

The risk of death from venous thromboembolism (VTE) is high in intensive care unit patients with neurological diagnoses. This is due to an increased risk of venous stasis secondary to paralysis as well as an increased prevalence of underlying pathologies that cause endothelial activation and create an increased risk of embolus formation. In many of these diseases, there is an associated risk from bleeding because of standard VTE prophylaxis. There is a paucity of prospective studies examining different VTE prophylaxis strategies in the neurologically ill. The lack of a solid evidentiary base has posed challenges for the establishment of consistent and evidence-based clinical practice standards. In response to this need for guidance, the Neurocritical Care Society set out to develop and evidence-based guideline using GRADE to safely reduce VTE and its associated complications.

Ammonia-induced brain swelling and neurotoxicity in an organotypic slice model

Abstract Objectives: Acute liver failure (ALF) produces cerebral dysfunction and edema, mediated in part by elevated ammonia concentrations, often leading to coma and death. The pathophysiology of cerebral edema in ALF is incompletely understood. In vitro models of the cerebral effects of ALF have predominately consisted of dissociated astrocyte cultures or acute brain slices. We describe a stable long-term culture model incorporating both neural and glial elements in a three-dimensional tissue structure offering significant advantages to the study of astrocytic-neuronal interactions in the pathophysiology of cerebral edema and dysfunction in ALF. Methods: We utilized chronic organotypic slice cultures from mouse forebrain, applying ammonium acetate in iso-osmolar fashion for 72 hours. Imaging of slice thickness to assess for tissue swelling was accomplished in living slices with optical coherence tomography, and confocal microscopy of fluorescence immunochemical and histochemical staining served to assess astrocyte and neuronal numbers, morphology, and volume in the fixed brain slices. Results: Ammonia exposure at 1-10 mM produced swelling of immunochemically identified astrocytes, and at 10 mM resulted in macroscopic tissue swelling, with slice thickness increasing by about 30%. Astrocytes were unchanged in number. In contrast, 10 mM ammonia treatment severely disrupted neuronal morphology and reduced neuronal survival at 72 hours by one-half. Discussion: Elevated ammonia produces astrocytic swelling, tissue swelling, and neuronal toxicity in cerebral tissues. Ammonia-treated organotypic brain slice cultures provide an In vitro model of cerebral effects of conditions relevant to ALF, applicable to pathophysiological investigations.

An Elderly Patient With Bickerstaff Brainstem Encephalitis and Transient Episodes of Brainstem Dysfunction

BACKGROUND Bickerstaff brainstem encephalitis (BBE) is a rare inflammatory, demyelinating disease that generally has a good prognosis. OBJECTIVE To describe the course of a patient with severe BBE and multiple medical complications. DESIGN Case report. SETTING Academic medical center. PATIENT An 81-year-old woman with BBE who fully recovered. The patient had transient and very frequent episodes of brainstem dysfunction during the recovery phase. MAIN OUTCOME MEASURES Clinical and biochemical evaluation with magnetic resonance imaging. CONCLUSIONS Bickerstaff brainstem encephalitis is a potentially reversible syndrome that needs early diagnosis (facilitated by magnetic resonance imaging) and prompt aggressive and supportive treatment. Frequent episodes of transient brainstem dysfunction occurred in our patient during recovery, possibly due to ephaptic transmission.

Identification and treatment of cervical and oromandibular dystonia in acutely brain-injured patients

AbstractIntroduction: Primary cervical and oromandibular dystonia (CD and OMD, respectively) are well-recognized movement disorders, often treated with botulinum toxin (BTx). In contrast, dystonia related to acute brain injuries is not well delineated. Our objective was to define in neurocritically ill patients the clinical characteristics of CD and OMD and to investigate the safety of BTx. Methods: All acutely brain-injured patients admitted to a neurocritical care unit over a 10-month period were prospectively screened for CD and OMD. Clinical characteristics, etiology of brain injury, and pattern of dystonia were analyzed. Patients with clinically significant CD and OMD were treated with BTx and followed for 12 weeks. Results: Of 165 patients screened, 33 had new-onset CD or OMD. Of 21 patients enrolled, 14 had CD, 5 had OMD, and 2 had both. The pattern of brain injury included 13 cerebral hemorrhages, 6 ischemic strokes, 1 status epilepticus, and 1 unclear etiology. Improvement after BTx was seen in four of seven patients with CD and two of four with OMD; no adverse effects occurred. Spontaneous improvement was recorded in 7 of 11 nontreated patients with CD or OMD. Conclusions: Acute secondary CD or OMD, associated with a variety of causes, was identified in 20% of acutely brain-injured patients. The temporal profile of dystonia onset and resolution in these patients was variable. Treatment with BTx in the neurocritical care setting seems to be safe. Future, larger scale randomized studies should evaluate the effectiveness of BTx treatment in this patient population.

Permanent cerebrospinal fluid diversion in subarachnoid hemorrhage: Influence of physician practice style.

Background: Acute hydrocephalus (HCP) after aneurysmal subarachnoid hemorrhage (SAH) often persists. Our previous study described factors that singly and combined in a formula correlate with permanent CSF diversion. We now aimed to determine whether the same parameters are applicable at an institution with different HCP management practice. Methods: We reviewed records of 181 consecutive patients who presented with SAH and received an external ventricular drain (EVD) for acute HCP. After exclusion and inclusion criteria were met, 71 patients were analyzed. Data included admission Fisher and Hunt and Hess grades, aneurysm location, treatment modality, ventricle size, CSF cell counts and protein levels, length of stay (LOS) in the hospital, and the presence of craniectomy. Outcome measures were: (1) initial EVD challenge outcome; (2) shunting within 3 months; and (3) LOS. Results: Shunting correlated with Hunt and Hess grade, CSF protein, and the presence of craniectomy. The formula derived in our previous study demonstrated a weaker correlation with initial EVD challenge failure. Several parameters that correlated with shunting in the previous study were instead associated with LOS in this study. Conclusions: The decision to shunt depends on management choices in the context of a disease process that may improve over time. Based on the treatment strategy, the shunting rate may be lowered but LOS increased. Markers of disease severity in patients with HCP after SAH correlate with both shunt placement and LOS. This is the first study to directly evaluate the effect of different practice styles on the shunting rate. Differences in HCP management practices should inform the design of prospective studies.