Saef Izzy

Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage and Traumatic Brain Injury

Opinion statementCerebral vasospasm (cVSP) consists of the vasoconstriction of large and small intracranial vessels which can lead to cerebral hypoperfusion, and in extreme cases, delayed ischemic deficits with stroke. While most commonly observed after aneurysmal subarachnoid hemorrhage (aSAH), cVSP can also occur after traumatic brain injury (TBI) as we have described in detail in this review. For the past decades, the research attention has focused on cVSP because of its association with delayed cerebral ischemia, which is the largest contributor of morbidity and mortality after aSAH. New discoveries in the cVSP pathophysiology involving multifactorial complex cascades and pathways pose new targets for therapeutic interventions in the prevention and treatment of cVSP. The goal of this review is to demonstrate the commonalities and differences in epidemiology and pathophysiology of both aSAH and TBI-associated cVSP, and highlight the more recently discovered pathways of cVSP. Finally, the latest cVSP surveillance methods and treatment options are illustrated.

Anterior Temporal Lobectomy for Refractory Status Epilepticus in Herpes Simplex Encephalitis.

BackgroundHerpes simplex virus (HSV) is a common cause of viral encephalitis that can lead to refractory seizures. The primary treatment of HSV encephalitis is with acyclovir; however, surgery sometimes plays a role in obtaining tissue diagnosis or decompression in cases with severe mass effect. We report a unique case in which anterior temporal lobectomy was successfully used to treat refractory status epilepticus in HSV encephalitis.MethodsCase report and review of the literature.ResultsWe report a case of a 60-year-old man with HSV encephalitis, who presented with seizures originating from the right temporal lobe refractory to maximal medical management. Right anterior temporal lobectomy was performed for the purpose of treatment of refractory status epilepticus and obtaining tissue diagnosis, with ultimate resolution of seizures and excellent functional outcome.ConclusionsWe suggest that anterior temporal lobectomy should be considered in cases of HSV encephalitis with refractory status epilepticus with clear unilateral origin.

Drug-induced thrombocytopenia secondary to natalizumab treatment

Summary A 52-year-old woman with a 10-year history of relapsing-remitting multiple sclerosis (RRMS) was started on natalizumab after she developed side effects for interferon β-1a and glatiramer acetate. The patient presented with acute severe infusion reaction after the third treatment with natalizumab, developing whole-body purpura. Laboratory testing revealed progressive worsening thrombocytopenia up to 3 weeks following natalizumab discontinuation. Platelet antibodies to platelet-specific antigen as well as antibodies against natalizumab were positive. Bone marrow biopsy was negative. The patient was diagnosed with drug-induced immune thrombocytopenia (DITP) as a rare case of natalizumab side effect which was treated with intravenous methylprednisolone followed by rituximab with successful resolution of thrombocytopenia. The patient had a stable course of RRMS with no relapses and no brain MRI changes at 2 years after initiation of rituximab.

Longitudinal Diffusion Tensor Imaging Detects Recovery of Fractional Anisotropy Within Traumatic Axonal Injury Lesions

BackgroundTraumatic axonal injury (TAI) may be reversible, yet there are currently no clinical imaging tools to detect axonal recovery in patients with traumatic brain injury (TBI). We used diffusion tensor imaging (DTI) to characterize serial changes in fractional anisotropy (FA) within TAI lesions of the corpus callosum (CC). We hypothesized that recovery of FA within a TAI lesion correlates with better functional outcome.MethodsPatients who underwent both an acute DTI scan (≤day 7) and a subacute DTI scan (day 14 to inpatient rehabilitation discharge) at a single institution were retrospectively analyzed. TAI lesions were manually traced on the acute diffusion-weighted images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were measured within the TAI lesions at each time point. FA recovery was defined by a longitudinal increase in CC FA that exceeded the coefficient of variation for FA based on values from healthy controls. Acute FA, ADC, AD, and RD were compared in lesions with and without FA recovery, and correlations were tested between lesional FA recovery and functional recovery, as determined by disability rating scale score at discharge from inpatient rehabilitation.ResultsEleven TAI lesions were identified in 7 patients. DTI detected FA recovery within 2 of 11 TAI lesions. Acute FA, ADC, AD, and RD did not differ between lesions with and without FA recovery. Lesional FA recovery did not correlate with disability rating scale scores.ConclusionsIn this retrospective longitudinal study, we provide initial evidence that FA can recover within TAI lesions. However, FA recovery did not correlate with improved functional outcomes. Prospective histopathological and clinical studies are needed to further elucidate whether lesional FA recovery indicates axonal healing and has prognostic significance.

Brachial amyotrophic diplegia in the setting of complete HIV viral load suppression

Brachial amyotrophic diplegia (BAD) is a rare segmental form of motor neuron disease which presents with asymmetric lower motor neuron weakness largely confined to the upper extremities (UE). In the case being reported, a 62-year-old gentleman on antiretroviral treatment since 1993, presented with left-arm weakness in 2007 that quickly progressed to involve the right arm. Complete HIV-viral load suppression had been achieved since 2003. Examination revealed lower motor neuron weakness in both UEs, worse proximally than distally and normal strength in the lower extremities (LEs). Nerve conduction studies showed reduced amplitudes of bilateral median and ulnar nerves’ motor responses. Needle electromyography of bilateral UE showed active and chronic denervation/reinnervation changes with normal findings in both LEs. MRI of the cervical spine showed cord atrophy. This is the first case report describing a patient who presented with BAD in the setting of complete HIV-viral load suppression for many years.

Dantrolene for cerebral vasospasm after subarachnoid haemorrhage: a randomised double blind placebo-controlled safety trial

Background Dantrolene is neuroprotective in animal models and may attenuate cerebral vasospasm (cVSP) in human aneurysmal subarachnoid haemorrhage (aSAH). We evaluated safety, feasibility and tolerability of intravenous dantrolene (IV-D) in patients with aSAH. Methods In this single-centre, randomised, double blind, placebo-controlled trial, 31 patients with aSAH were randomised to IV-D 1.25 mg every 6 h for 7 days (n=16) or equiosmolar free water/5% mannitol (placebo; n=15). Primary safety end points were incidence of hyponatraemia (sNa≤132 mmol/L) and liver toxicity (proportion of patients alanine transaminase, aspartate aminotransferase and AlkPhos >5× upper-limit-of-normal). Secondary end points included tolerability, systemic hypotension and intracranial hypertension. Efficacy was explored for clinical/radiological cVSP, delayed cerebral ischaemia (DCI), and 3-month functional outcomes. Quantitative analyses of angiograms and daily transcranial Doppler (TCD) were performed. Results Between IV-D versus placebo, no differences were observed in the primary outcomes (hyponatremia 44% vs 67% (p=0.29); liver toxicity 6% vs 0% (p=1.0)). Three patients in the IV-D versus two in the placebo group had severe adverse events possibly attributable to infusion and reached stop criteria: one IV-D patient developed liver toxicity; two patients in each group developed brain oedema requiring osmotherapy. The majority of adverse events were not related to infusion (17 vs 5 (RR 2.2; 95% CI 0.7 to 6.7; p=0.16) in IV-D vs placebo). No differences in any categorical cVSP outcomes, DCI, 3-month outcomes or quantitative angiogram and TCD analyses were seen in this small safety trial not powered to detect efficacy. Conclusions In this small trial, IV-D after aSAH was feasible, tolerable and safe. Trial registration number http://clinicaltrials.gov NCT01024972.

Predicting survival after acute civilian penetrating brain injuries: The SPIN score

Objective: To identify predictors associated with survival in civilian penetrating traumatic brain injury (pTBI) utilizing a contemporary, large, diverse 2-center cohort, and to develop a parsimonious survival prediction score for pTBI. Methods: Our cohort comprised 413 pTBI patients retrospectively identified from the local trauma registries at 2 US level 1 trauma centers, of which one was predominantly urban and the other predominantly rural. Predictors of in-hospital and 6-month survival identified in univariate and multivariable logistic regression were used to develop the simple Surviving Penetrating Injury to the Brain (SPIN) score. Results: The mean age was 33 ± 16 years and patients were predominantly male (87%). Survival at hospital discharge as well as 6 months post pTBI was 42.4%. Higher motor Glasgow Coma Scale subscore, pupillary reactivity, lack of self-inflicted injury, transfer from other hospital, female sex, lower Injury Severity Score, and lower international normalized ratio were independently associated with survival (all p < 0.001; model area under the curve 0.962). Important radiologic factors associated with survival were also identified but their addition to the full multivariable would have resulted in model overfitting without much gain in the area under the curve. Conclusions: The SPIN score, a logistic regression–based clinical risk stratification scale estimating survival after pTBI, was developed in this large, diverse 2-center cohort. While this preliminary clinical survival prediction tool does not include radiologic factors, it may support clinical decision-making after civilian pTBI if external validation confirms the probability estimates.

Significance of statins and antiplatelet molecules in hyperacute acute ischemic stroke outcome

Introduction: Ischemic stroke is a major cause of morbidity and mortality. However, the interface of various premorbid medical conditions, vascular risk factors prior, prior antithrombotic or statins medication use, and in-hospital complications in effecting outcomes is not clearly established. We attempt establishing factors associated with improved outcomes after an acute ischemic stroke (AIS). Materials and Methods: Using the prospectively collected database, University Health Consortium from 1999 to 2004, a national USA database, multivariate step-wise backward regression analysis was performed and we were able to define premorbid characteristics, and medications that affect the outcome of AIS. Results: Initial stroke severity and poststroke in-hospital complications were associated with a poor outcome, while prior antiplatelet drug use was associated with an improved outcome. Statin use demonstrated a trend toward an improved outcome.

Clinical Problem-Solving: Lethargy and Fever in an Immunocompromised Patient

We present the case of a 63-year-old woman with a glioblastoma multiforme on immunosuppressive steroid doses who developed lethargy and fever. We review the differential diagnosis and emphasize the importance of reframing the case when the clinical course differs from expectation. Once the diagnosis is evident, we discuss the incidence and clinical course in different patient populations.

Cerebrovascular Accidents During Mechanical Circulatory Support: New Predictors of Ischemic and Hemorrhagic Strokes and Outcome

Background and Purpose— Left ventricular assist devices (LVADs) have emerged as an effective treatment for patients with advanced heart failure refractory to medical therapy. Post-LVAD strokes are an important cause of morbidity and reduced quality of life. Data on risks that distinguish between ischemic and hemorrhagic post-LVAD strokes are limited. The aim of this study was to determine the incidence of post-LVAD ischemic and hemorrhagic strokes, their association with stroke risk factors, and their effect on mortality. Methods— Data are collected prospectively on all patients with LVADs implanted at Brigham and Women’s Hospital. We added retrospectively collected clinical data for these analyses. Results— From 2007 to 2016, 183 patients (median age, 57; 80% male) underwent implantation of HeartMate II LVAD as a bridge to transplant (52%), destination therapy (39%), or bridge to transplant candidacy (8%). A total of 48 strokes occurred in 39 patients (21%): 28 acute ischemic strokes in 24 patients (13%) and 20 intracerebral hemorrhages in 19 patients (10.3%). First events occurred at a median of 238 days from implantation (interquartile range, 93–515) among those who developed post-LVAD stroke. All but 9 patients (4.9%) were on warfarin (goal international normalized ratio, 2–3.5) and all received aspirin (81–325 mg). Patients with chronic obstructive pulmonary disease were more likely to have an ischemic stroke (odds ratio, 2.96; 95% confidence interval, 1.14–7.70). Dialysis-dependent patients showed a trend toward a higher risk of hemorrhagic stroke (odds ratio, 6.31; 95% confidence interval, 0.99–40.47). Hemorrhagic stroke was associated with higher mortality (odds ratio, 3.92; 95% confidence interval, 1.34–11.45) than ischemic stroke (odds ratio, 3.17; 95% confidence interval, 1.13–8.85). Conclusions— Stroke is a major cause of morbidity and mortality in patients on LVAD support. Chronic obstructive pulmonary disease increases the risk of ischemic stroke, whereas dialysis may increase the risk of hemorrhagic stroke. Although any stroke increases mortality, post-LVAD hemorrhagic stroke was associated with higher mortality compared with ischemic stroke.