Robert E. Hoesch

Medial Premotor Cortex Shows a Reduction in Inhibitory Markers and Mediates Recovery in a Mouse Model of Focal Stroke

Background and Purpose— Motor recovery after ischemic stroke in primary motor cortex is thought to occur in part through training-enhanced reorganization in undamaged premotor areas, enabled by reductions in cortical inhibition. Here we used a mouse model of focal cortical stroke and a double-lesion approach to test the idea that a medial premotor area (medial agranular cortex [AGm]) reorganizes to mediate recovery of prehension, and that this reorganization is associated with a reduction in inhibitory interneuron markers. Methods— C57Bl/6 mice were trained to perform a skilled prehension task to an asymptotic level of performance after which they underwent photocoagulation-induced stroke in the caudal forelimb area. The mice were then retrained and inhibitory interneuron immunofluorescence was assessed in prechosen, anatomically defined neocortical areas. Mice then underwent a second photocoagulation-induced stroke in AGm. Results— Focal caudal forelimb area stroke led to a decrement in skilled prehension. Training-associated recovery of prehension was associated with a reduction in parvalbumin, calretinin, and calbindin expression in AGm. Subsequent infarction of AGm led to reinstatement of the original deficit. Conclusions— We conclude that with training, AGm can reorganize after a focal motor stroke and serve as a new control area for prehension. Reduced inhibition may represent a marker for reorganization or it is necessary for reorganization to occur. Our mouse model, with all of the attendant genetic benefits, may allow us to determine at the cellular and molecular levels how behavioral training and endogenous plasticity interact to mediate recovery.

Therapeutic hypothermia for global and focal ischemic brain injury--a cool way to improve neurologic outcomes.

Background:Therapeutic hypothermia (TH) has been employed as a neuroprotective strategy for a wide array of clinical problems since the late 1940s. Animal studies have determined that the neuroprotective effect of hypothermia is pleiotropic, impacting many steps in both the ischemic cascade and reperfusion injury. Interest in the neuroprotective effects of TH for ischemic brain injury has been resurgent, fueled by both recent positive and negative clinical trials. A review of preclinical and clinical reports on TH in adult patients is provided in this article. Review Summary:Animal data and several large clinical studies of mild to moderate TH (32°C–34°C) for global cerebral ischemia describe favorable neurologic outcomes, with few adverse effects. However, clinical implementation for global ischemia remains poor. Some animal data support a role for TH in focal cerebral ischemia, if instituted soon after the onset of ischemia, and in the setting of reperfusion. Clinical studies of TH for focal cerebral ischemia have so far been equivocal. The available data suggest that, despite sharing some common components in the ischemic cascade, focal and global cerebral ischemia are pathophysiologically disparate, and may respond to different neuroprotective strategies. Conclusion:TH is a safe, effective neuroprotective strategy for global cerebral ischemia. Because of the neuroprotective efficacy of TH in adult comatose survivors of cardiac arrest, neurologists should advocate the implementation of this strategy. TH for focal ischemia is a promising therapeutic option, but requires more basic and clinical investigation.

Repetitive use of intra-arterial verapamil in the treatment of reversible cerebral vasoconstriction syndrome

Reversible cerebral vasoconstriction syndrome (RCVS) typically presents with recurrent thunderclap headaches and neurological deficits that are usually self-limiting. The intra-arterial (IA) use of vasodilators for RCVS has been reported for severe cases. Patients with RCVS have the potential for serious and permanent neurological deficits. It is a rare disorder, with a recent surge in the number of reports, and probably continues to be under-diagnosed. We report two patients with RCVS with severe neurological sequelae, treated in a large tertiary hospital. Both patients received high-dose cortico steroids due to the possibility of angiitis of the central nervous system, but they deteriorated neurologically, which suggests that steroids may have a deleterious effect in RCVS. Treatment with IA verapamil resulted in reversal of vasoconstriction, but multiple treatments were necessary. Therefore, IA administration of verapamil is a possible treatment for severe RCVS, but there is only limited sustained improvement in vasodilation that may require repetitive treatments with a currently undetermined optimal treatment interval.

Post-cardiac arrest encephalopathy.

Brain injury continues to be a leading cause of mortality and morbidity in patients resuscitated after cardiac arrest. During periods of hypoxia and ischemia, numerous mechanisms contribute to the initial and secondary injury of the brain. Though many drugs and therapies have been evaluated for neuroprotection, only therapeutic hypothermia has been proven to be effective. Accurate prognostication after cardiac arrest is essential, and can be achieved with careful neurologic examination and several ancillary tests utilizing neurophysiology, neuroimaging, and biochemistry. Practice guidelines are now available for prognostication and postresuscitation care, with emphasis on improving survival and quality of life. Also reviewed are a wide spectrum of postarrest neurologic complications and their targeted treatments.

Therapeutic hypothermia for status epilepticus: A report, historical perspective, and review

Refractory status epilepticus is a disease associated with high morbidity and mortality, which does not always respond to standard treatments, and when they fail, alternative modalities become crucial. Therapeutic hypothermia slows nerve conduction in vitro, and has been shown to abort seizures in animal models. Therapeutic hypothermia has been experimentally used in humans since 1963 for a variety of intracranial pathologies. More recently there have been multiple reports demonstrating the effectiveness of therapeutic hypothermia in treating refractory status epilepticus. We report a case of super-refractory status epilepticus successfully treated with therapeutic hypothermia, complimented by a historical and literature review of this modality. While there is limited evidence, and some risks associated with therapeutic hypothermia, it should be considered as a reasonable and potentially effective treatment option for refractory status epilepticus.

Cerebral Air Emboli With Atrial-Esophageal Fistula Following Atrial Fibrillation Ablation A Case Report and Review

Background: Atrial-esophageal fistula (AEF) is a rare and early complication of radiofrequency ablation for medically refractory atrial fibrillation, but has devastating consequences when the diagnosis is delayed or difficult to make. Methods: Single case in a neurosciences critical care center. Results: A 69-year-old man with significant cardiac and neurologic medical history who underwent atrial fibrillation ablation 50 days prior to admission to the neurocritical care unit presented with acute left-sided weakness and gram-positive bacterial sepsis. This is an exceptional case discussing the need for early detection of AEF presenting with sepsis, neurologic deficit along with complicated decision-making in the neurocritical care setting. His hospital course was complicated by acute stroke, left ventricular (LV) aneurysm with thrombus, gastrointestinal (GI) bleed discovered to be from left atrial esophageal fistula, and subsequent cerebral air emboli leading to death. Conclusions: This is the most delayed presentation of AEF following atrial fibrillation ablation reported in the literature to date. We emphasize the need for awareness of this complication even after such an unexpected time-frame postprocedure as well as the unintended complications of cerebral air emboli following upper endoscopy.

Splenic rupture associated with primary CMV infection, AMSAN, and IVIG.

Splenic rupture is a rare complication of primary cytomegalovirus infection, but has not been reported after administration of intravenous immunoglobulin or in the setting of the Guillain-Barré syndrome and its many variants, which often lead to treatment with intravenous immunoglobulin. There is strong evidence that intravenous immunoglobulin causes sequestration of erythrocytes in the spleen and extravascular hemolytic anemia. This may result in a two-hit scenario that clinicians should be aware of, where a patient who is at risk for splenic rupture due to primary cytomegalovirus infection receives intravenous immunoglobulin as treatment for the cytomegalovirus-associated Guillain-Barré syndrome, further increasing their risk of rupture.

A pilot study of audiovisual family meetings in the intensive care unit

PURPOSE We hypothesized that virtual family meetings in the intensive care unit with conference calling or Skype videoconferencing would result in increased family member satisfaction and more efficient decision making. METHODS This is a prospective, nonblinded, nonrandomized pilot study. A 6-question survey was completed by family members after family meetings, some of which used conference calling or Skype by choice. Overall, 29 (33%) of the completed surveys came from audiovisual family meetings vs 59 (67%) from control meetings. RESULTS The survey data were analyzed using hierarchical linear modeling, which did not find any significant group differences between satisfaction with the audiovisual meetings vs controls. There was no association between the audiovisual intervention and withdrawal of care (P = .682) or overall hospital length of stay (z = 0.885, P = .376). CONCLUSIONS Although we do not report benefit from an audiovisual intervention, these results are preliminary and heavily influenced by notable limitations to the study. Given that the intervention was feasible in this pilot study, audiovisual and social media intervention strategies warrant additional investigation given their unique ability to facilitate communication among family members in the intensive care unit.

Reproducibility of ABC/2 Method to Determine Infarct Volume and Mismatch Percentage with CT Perfusion

Our aim is to implement a simple, rapid, and reliable method using computed tomography perfusion imaging and clinical judgment to target patients for reperfusion therapy in the hyper‐acute stroke setting. We introduce a novel formula (1–infarct volume [CBV]/penumbra volume [MTT] × 100%) to quantify mismatch percentage.

Antifibrinolytic Therapy in Intracranial Hemorrhage

Preclinical Research