Wijdicks, Eelco F. M.

AbstractMetabolic derangements, when acute and severe, affect brain function. This presents mostly with a marked decline in the level of consciousness, resulting in impaired responsiveness, abnormal receptivity, impaired content, and loss of memory retention. The term metabolic encephalopathy has been used but is conjecture that can be challenged in the age of modern neuroimaging. We now recognize that many metabolic encephalopathies may involve structural lesions and at an early stage. Common clinical conundrums are the evaluation of the degree of brain injury and its recoverability. This review discusses the appropriate terminology for these conditions, the diagnostic approach, therapy recommendations, and prediction of recovery potential. In evaluating a presumed metabolic cause for encephalopathy, we must (1) search for and rule out structural injury to the brain despite an obvious explanatory metabolic derangement, (2) recognize that several confounding conditions often co‐exist, and (3) acknowledge that resolution of brain dysfunction may be protracted despite normalization of laboratory values.

Angioinvasive fungal infections of the cerebral vasculature often lead to significant morbidity and mortality. High clinical suspicion and early antifungal therapy could improve outcomes. We describe the fatal case of a patient with a rapidly enlarging cavernous carotid aneurysm due to angioinvasive fungus. This case highlights the challenges in diagnosis and management of this condition.

Introduction: Timing of clinical grading has not been fully studied in patients with aneurysmal subarachnoid hemorrhage (aSAH). Our primary objective was to identify at which time point the clinical assessment using the World Federation of Neurological Surgeons Scale (WFNS) and the Glasgow Coma Scale (GCS) is most predictive of poor functional outcome. Methods: Retrospective cohort study on the association of clinical grading determined at presentation, nadir and post-resuscitation, and poor outcome. Poor functional outcome was defined as Glasgow Outcome Scale score of 1-3 at 6 months. The study was approved by our Institutional Review Board. Results: We identified 186 consecutive patients admitted to a teaching hospital between January 2002 and June 2008. Patients’ mean age was 56.9±13.7 years and 63% of the patients were women. Twenty-four percent had poor functional outcome (mortality was 17%). On univariable logistic regression analyses, GCS determined at presentation (OR=0.80; p<0.0001), nadir (OR=0.73; p<0.0001) and post-resuscitation (OR=0.53; p<0.0001), modified Fisher Scale (OR=2.21;p=0.0013), WFNS assessed at presentation (OR=1.92;p<0.0001), nadir (OR=3.51; <0.0001) and post-resuscitation (OR=3.91; <0.0001), intracerebral hematoma on initial CT (OR=4.55;p<0.0002), acute hydrocephalus (OR=2.29;p=0.0375), and cerebral infarction (OR=4.84; <0.0001) were associated with poor outcome. On multivariable logistic regression analysis, only cerebral infarction (OR=5.80; 0.0013) and WFNS grade post-resuscitation (OR=3.43;<0.0001) were associated with poor outcome. Receiving operating characteristics/area under the curve (AUC) analysis demonstrated that WFNS determined post-resuscitation had a stronger association with poor outcome (AUC=0.90) than WFNS assessed upon admission or at nadir. Conclusions: Timing of WFNS assessment affects its prognostic value. Outcome after aSAH is best predicted by rating WFNS after neurological resuscitation.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic state caused by autoantibodies against platelet factor 4 (PF4)-heparin complexes. Although HIT typically presents 5-10 days after the initiation of heparin, thrombosis and thrombocytopenia may occur up to several weeks following heparin withdrawal, so-called delayed-onset HIT. Although rare, there have been isolated reports of HIT-induced cerebral venous sinus thrombosis (CVST), which carry high rates of morbidity and mortality. There is a need to further characterize the etiology, clinical presentation, treatment paradigms, and outcomes of patients with HIT-induced CVST. Here, we present the case of a 57-year old female who presented to the emergency department with a headache and seizure 11 days following a right total knee arthroplasty for which she received 3 post-operative doses of enoxaparin. Work-up demonstrated acute intracerebral hemorrhage (ICH), CVST, and thrombocytopenia. Intravenous heparin resulted in rapidly deteriorating platelet count and subsequent serologic testing confirmed the diagnosis of HIT. Treatment with bivalirudin was initiated, the HIT resolved, and the patient was discharged home on hospital day 19 with long-term anticoagulation mediated by warfarin. At 3-month follow up, the patient had mild upper motor neuron pattern weakness and was living independently. This case depicts a rare case of delayed-onset HIT and CVST, highlights the importance of establishing a fluid treatment plan for managing HIT-induced CVST, and illustrates the importance of employing rapid anticoagulation despite acute ICH to achieve a desirable clinical outcome.

Diffuse subarachnoid hemorrhage is commonly attributed to the rupture of intracranial aneurysms or other vascular malformations. Non-aneurysmal hemorrhages often have a characteristic pattern or clear mechanism (e.g. trauma) with an often more benign clinical course. We report the case of a diffuse non-aneurysmal subarachnoid hemorrhage due to sudden gravitational changes encountered during complex airflight maneuvers, complicated by hydrocephalus and cerebral vasospasm. This case illustrates a rare phenomenon that may again be encountered in the future with the advent and advancement of civilian spaceflight.

Background: The influence of high body mass index (BMI) in acute stroke patients treated with intravenous thrombolysis has not been extensively studied. Previous studies have observed an “obesity paradox” among stroke patients, where better outcomes were observed among overweight and obese patients. The purpose of this study is to determine the influence of obesity and risk components of metabolic syndrome to stroke recovery in patients undergoing intravenous recombinant tissue plasminogen activator (rtPA) treatment. Methods: Patients with acute ischemic stroke who received intravenous rtPA within three-hour from symptom onset at St. Marys Hospital, Mayo Clinic, Rochester, between April 2006 and January 2011, were included in this study. Information on vascular risk factors, stroke severity, and baseline hemodynamic and laboratory indices, were collected. Study outcomes, consisting symptomatic intracerebral hemorrhage (sICH) and poor functional recovery (modified Rankin scale >2), were compared between obese (body mass index, BMI >30 kg/m 2 ), overweight (BMI 25-30 kg/m 2 ) and normal weight (BMI <25 kg/m 2 ) patients. The association between BMI, risk components of the metabolic syndrome and dose of rtPA per kg body weight to stroke outcomes were assessed in a multivariable model. Results: A total of 158 patients (mean age, 75 years; baseline NIHSS, 11), frequency-matched by age and baseline stroke severity, were included in this study. No differences in the frequency of SICH and poor functional recovery were observed among obese, overweight and normal weight patients, before and after adjusting for their baseline characteristics. A linear trend towards worse stroke recovery was observed in patients with a greater number of metabolic risk components (p-trend=0.043). By contrast, there were no significant associations between the number of risk components of metabolic syndrome with respect to sICH. Using stepwise regression analyses, age, baseline stroke severity and the number of risk components of the metabolic syndrome accounted for 52% variation in functional recovery following rtPA treatment. Conclusions: Acute stroke outcomes do not differ between obese and overweight patients. The presence of metabolic risk factors contributes significantly to functional outcomes following rtPA treatment. These results suggest that decreasing the prevalence of metabolic syndrome in the community could reduce the societal burden of stroke-related disability.