The Intracerebral Hemorrhage Score: A Self-Fulfilling Prophecy?

BACKGROUND: The ICH Score has become the standard for risk-stratification of 30-d mortality in patients with intracerebral hemorrhage (ICH), but treatment has evolved over the last 17 yr since its inception. We sought to determine if the ICH Score remains an accurate predictor of 30-d mortality in these high acuity patients. OBJECTIVE: To determine the role the ICH Score has on mortality in current treatment of patients. METHODS: A retrospective review of 554 patients treated for acute, spontaneous ICH at 2 large academic institutions between 2010 and 2014 was carried out. Surgical intervention in the form of external ventricular drain or craniotomy was performed when indicated. All patients were managed medically until discharge or death. RESULTS: Over half (53.6%) of the patients presented with ICH of the basal ganglia/thalamus and the majority (71%) presented with ICH Scores of 0 to 2. Overall mortality was 25.1%. Observed mortality in moderate grade ICH Score patients (3 and 4) was lower than expected (49% vs 72%, P < .001) and (71% vs 97%, P < .001) when compared to the original ICH Score results. Despite differences in ICH and intraventricular hemorrhage volume, and Glasgow Coma Scale there was no difference in surgical intervention (12.2% vs 11.8%, P = .94) between the two groups. Withdrawal of care was instituted in 56.6% of all patients who died and increased with ICH Score. CONCLUSION: In our cohort, the original ICH score did not accurately predict the mortality rate. Patient survival exceeded ICH Score-predicted mortality regardless of surgical intervention. Reevaluation of predictive scores could be useful to aid in more accurate prognoses.

C3 transferase gene therapy for continuous conditional RhoA inhibition.

Regrowth inhibitory molecules prevent axon regeneration in the adult mammalian central nervous system (CNS). RhoA, a small GTPase in the Rho family, is a key intracellular switch that mediates the effects of these extracellular regrowth inhibitors. The bacterial enzyme C3-ADP ribosyltransferase (C3) selectively and irreversibly inhibits the activation of RhoA and stimulates axon outgrowth and regeneration. However, effective intracellular delivery of the C3 protein in vivo is limited by poor cell permeability and a short duration of action. To address this, we have developed a gene therapy approach using viral vectors to introduce the C3 gene into neurons or neuronal progenitors. Our vectors deliver C3 in a cell-autonomous (endogenous) or a cell-nonautonomous (secretable/permeable) fashion and promote in vitro process outgrowth on inhibitory chondroitin sulfate proteoglycan substrate. Further conditional control of our vectors was achieved via the addition of a Tet-On system, which allows for transcriptional control with doxycycline administration. These vectors will be crucial tools for promoting continued axonal regeneration after CNS injuries or neurodegenerative diseases.

The Effect of External Ventricular Drain Use in Intracerebral Hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) commonly presents with intraventricular hemorrhage (IVH) and remains a highly disabling form of stroke. External ventricular drains (EVDs) are associated with decreased short-term mortality, but indications for use and outcomes benefit are controversial. METHODS: A multi-institutional, retrospective analysis of 563 patients with spontaneous ICH from 2010 to 2014 was performed with multivariate regression modeling. Primary outcomes were patient mortality and functional status with modified Rankin Scale score. To control for differences in patient and clinical characteristics influencing EVD utilization, a propensity score analysis was performed with patient-specific predicted probability of EVD use. RESULTS: The multivariable logistic regression model showed odds of EVD use increased with younger age, lower ICH volume, ICH located outside the brainstem, increasing IVH volume, and concurrent IVH; the model showed high discriminability for EVD use (area under the receiver operating curve 0.84, R2McFadden = 0.27). The use of EVD was associated with lower 30-day mortality in patients with ICH score of 4 (odds ratio = 0.09, P = 0.002), greater ICH volume (>11 cc, odds ratio = 0.47, P = 0.019), and lower initial GCS (<13, 0.38, P = 0.003) in propensity score-adjusted analyses, as well as a trend toward lower mortality in patients with IVH and greater modified Graeb score. There was no benefit to morbidity in patients receiving an EVD. CONCLUSIONS: Among a large, multi-institutional cohort, this statistical propensity analysis model accurately predicted EVD use in ICH. EVD use was associated with a trend towards decreased mortality but greater modified Rankin Scale score for functional outcomes.

Technological advances in the surgical treatment of movement disorders.

Technological innovations have driven the advancement of the surgical treatment of movement disorders, from the invention of the stereotactic frame to the adaptation of deep brain stimulation (DBS). Along these lines, this review will describe recent advances in inserting neuromodulation modalities, including DBS, to the target, and in the delivery of therapy at the target. Recent radiological advances are altering the way that DBS leads are targeted and inserted, by refining the ability to visualize the subcortical targets using high-field strength magnetic resonance imaging and other innovations, such as diffusion tensor imaging, and the development of novel targeting devices enabling purely anatomical implantations without the need for neurophysiological monitoring. New portable computed tomography scanners also are facilitating lead implantation without monitoring, as well as improving radiological verification of DBS lead location. Advances in neurophysiological mapping include efforts to develop automatic target verification algorithms, and probabilistic maps to guide target selection. The delivery of therapy at the target is being improved by the development of the next generation of internal pulse generators (IPGs). These include constant current devices that mitigate the variability introduced by impedance changes of the stimulated tissue and, in the near future, devices that deliver novel stimulation patterns with improved efficiency. Closed-loop adaptive IPGs are being tested, which may tailor stimulation to ongoing changes in the nervous system, reflected in biomarkers continuously recorded by the devices. Finer-grained DBS leads, in conjunction with new IPGs and advanced programming tools, may offer improved outcomes via current steering algorithms. Finally, even thermocoagulation-essentially replaced by DBS-is being advanced by new minimally-invasive approaches that may improve this therapy for selected patients in whom it may be preferred. Functional neurosurgery has a history of being driven by technological innovation, a tradition that continues into its future.