Stroke Due to Cerebral Vasculitis in a Patient with Relentless Placoid Chorioretinitis.

PURPOSE: To report the first case of stroke in a patient with relentless placoid chorioretinitis. METHODS: Observational case report. RESULTS: A 20-year-old female with newly diagnosed relentless placoid chorioretinitis was urgently evaluated for unilateral paresthesias. She was found to have acute bilateral pontine strokes and cerebral vasculitis on magnetic resonance imaging of the brain and cerebral angiography. CONCLUSIONS: We report the first case of stroke due to cerebral vasculitis in a patient with relentless placoid chorioretinitis. This case emphasizes the need for timely evaluation of neurological symptoms in patients with this ocular diagnosis.

The cytotoxic mechanism of karlotoxin 2 (KmTx 2) from Karlodinium veneficum (Dinophyceae).

This study demonstrates that the polyketide toxin karlotoxin 2 (KmTx 2) produced by Karlodinium veneficum, a dinoflagellate associated with fish kills in temperate estuaries world-wide, alters vertebrate cell membrane permeability. Microfluorimetric and electrophysiological measurements were used to determine that vertebrate cellular toxicity occurs through non-selective permeabilization of plasma membranes, leading to osmotic cell lysis. Previous studies showed that KmTx 2 is lethal to fish at naturally-occurring concentrations measured during fish kills, while sub-lethal doses severely damage gill epithelia. This study provides a mechanistic explanation for the association between K. veneficum blooms and fish kills that has long been observed in temperate estuaries worldwide.

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.

Reproducibility of ABC/2 method to determine infarct volume and mismatch percentage with CT perfusion.

BACKGROUND: 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. METHODS: Twenty patients with anterior circulation strokes who underwent CT perfusion and received intravenous tissue plasminogen activator (IV tPA) were analyzed retrospectively. Nine blinded viewers determined volume of infarct and ischemic penumbra using the ABC/2 method and also the mismatch percentage. RESULTS: Interrater reliability using the volumetric formula (ABC/2) was very good (intraclass correlation [ICC] = .9440 and ICC = .8510) for hemodynamic parameters infarct (CBV) and penumbra (MTT). ICC coefficient using the mismatch formula (1-MTT/CBV × 100%) was good (ICC of .635). CONCLUSIONS: The ABC/2 method of volume estimation on CT perfusion is a reliable and efficient approach to determine infarct and penumbra volumes. The 1-CBV/MTT × 100% formula produces a mismatch percentage assisting providers in communicating the proportion of salvageable brain and guides therapy in the setting of patients with unclear time of onset with potentially salvageable tissue who can undergo mechanical retrieval or intraarterial thrombolytics.

Pathophysiology of acute coma and disorders of consciousness: considerations for diagnosis and management.

Disorders of consciousness are due to failure of the arousal system. In this review, the authors introduce the spectrum of disorders of consciousness and describe the structures, projections, and neurotransmitters involved in the generation and maintenance of arousal. Next, they discuss the neurologic diseases frequently associated with arousal failure. Evaluation of patients with disorders of arousal is summarized, including the neurologic exam, electrophysiological studies, biochemical testing, and imaging modalities. Finally, they review treatment options, including therapeutic hypothermia, medications, and deep brain and spinal cord stimulation.

Effective treatment of refractory intracranial hypertension after traumatic brain injury with repeated boluses of 14.6% hypertonic saline.

OBJECT: Normal intracranial pressure (ICP) and cerebral perfusion pressure (CPP) have been identified as favorable prognostic factors in the outcome of patients with traumatic brain injuries (TBIs). Osmotic diuretics and hypertonic saline (HTS) are commonly used to treat elevated ICP in patients with TBI; however, sustained effects of repeated high-concentration HTS boluses for severely refractory ICP elevation have not been studied. The authors' goal in this study was to determine whether repeated 14.6% HTS boluses were efficacious in treating severely refractory intracranial hypertension in patients with TBI. METHODS: In a prospective cohort study in a neurocritical care unit, adult TBI patients with sustained ICP > 30 mm Hg for more than 30 minutes after exhaustive medical and/or surgical therapy received repeated 15-minute boluses of 14.6% HTS over 12 hours through central venous access. RESULTS: Response to treatment was evaluated in 11 patients. Within 5 minutes of bolus administration, mean ICP decreased from 40 to 33 mm Hg (30% reduction, p < 0.05). Intracranial pressure-lowering effects were sustained for 12 hours (41% reduction, p < 0.05) with multiple boluses (mean number of boluses 7 ± 5.5). The mean CPP increased 22% and 32% from baseline at 15 and 30 minutes, respectively (p < 0.05). The mean serum sodium level (SNa) at baseline was 155 ± 7.1 mEq/L, and after multiple boluses of 14.6% HTS, S(Na) at 12 hours was 154 ± 7.1 mEq/L. The mean heart rate, systolic blood pressure, blood urea nitrogen, and creatinine demonstrated no significant change throughout the study. CONCLUSIONS: The subset of TBI patients with intracranial hypertension that is completely refractory to all other medical therapies can be treated effectively and safely with repeated boluses of 14.6% HTS rather than a one-time dose.

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.

Boomerang sign on MRI.

INTRODUCTION: Altered mental status and more subtle cognitive and personality changes after traumatic brain injury (TBI) are pervasive problems in patients who survive initial injury. MRI is not necessarily part of the diagnostic evaluation of these patients. METHODS: Case report with relevant image and review of the literature. RESULTS: Injury to the corpus callosum is commonly described in traumatic brain injury; however, extensive lesions in the splenium are not well described. This image shows an important pattern of brain injury and demonstrates a common clinical syndrome seen in patients with corpus callosum pathology. CONCLUSION: Injury to the splenium of the corpus callosum due to trauma may be extensive and can cause significant neurologic deficits. MRI is important in the diagnostic evaluation of patients with cognitive changes after TBI.

Sleep rounds: a multidisciplinary approach to optimize sleep quality and satisfaction in hospitalized patients.

BACKGROUND: Poor sleep has adverse affects on heath, yet few studies have addressed the goal of improving sleep among hospitalized patients. We evaluated the effectiveness of a sleep-promoting intervention on the quality and quantity of sleep among inpatients. METHODS: This study was conducted on a neurological ward in a large, tertiary care hospital. Sleep quality, quantity, and disruptors were assessed using questionnaires completed by patients during their hospital stay and Press Ganey surveys completed retrospectively. Room noise was also measured using noise meters. Data from each of 4 chronological phases of the study (baseline, basic intervention, "washout," and deluxe intervention) were analyzed. In the intervention phases, nurses conducted "Sleep Rounds" at bedtime, during which sleep-promoting practices were implemented, including lights out, television off, temperature adjustment, and a final restroom usage. RESULTS: Patients reported 5 (interquartile range [IQR] 3) hours of sleep per night, awoke 3 (IQR 3) times nightly, and reported a median sleep latency of 11 to 15 minutes. Pain, staff interruptions, and roommates were the most significant barriers to good sleep. Noise levels were adequately low (35-40 dB) at night but were not positively impacted by our sleep-promoting interventions. Patients perceived noise on the unit to be worse during phases of the study in which there was no intervention. CONCLUSIONS: Patient perception of sleep experience improved during the phases in which Sleep Rounds were implemented, despite the fact that there was no measurable improvement in sleep or sleep-disrupting factors.

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.

Acute lung injury in critical neurological illness.

OBJECTIVE: Acute lung injury and acute respiratory distress syndrome have been reported in a significant proportion of patients with critical neurologic illness. Our aim was to identify risk factors for acute lung injury/acute respiratory distress syndrome in this population. DESIGN: Prospective, observational study. SETTING: A 22-bed, adult neurosciences critical care unit at a tertiary care hospital. PATIENTS: Primary neurologic disorder, mechanical ventilation >48 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 192 patients were enrolled with a range of neurologic disorders. Among these, 68 (35%) were diagnosed with acute lung injury/acute respiratory distress syndrome. In a multivariate logistic regression analysis, independent risk factors for acute lung injury/acute respiratory distress syndrome were pneumonia (odds ratio [95% confidence interval] 3.12 [1.5-6.0], p = .002), circulatory shock (2.2 [1.07-4.57], p = .03), and absence of a gag or cough reflex (3.41 [1.34-8.68], p = .01). Neither neurologic diagnosis nor neurologic severity, assessed with the Glasgow Coma Scale, was significantly associated with the development of acute lung injury/acute respiratory distress syndrome. CONCLUSION: Acute lung injury/acute respiratory distress syndrome occurred in more than one third of mechanically ventilated neurosciences critical care unit patients. Loss of the cough or gag reflex is strongly predictive of acute lung injury/acute respiratory distress syndrome, while neurologic diagnosis and Glasgow Coma Scale are not. Lower brainstem dysfunction, a clinical marker of neurologic injury not captured by the Glasgow Coma Scale, is a risk factor for acute lung injury/acute respiratory distress syndrome and could inform decisions regarding airway protection and mechanical ventilation.

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.

A case of postpartum cerebral angiopathy with subarachnoid hemorrhage.

BACKGROUND: A 33-year-old woman experienced a thunderclap headache immediately postpartum. The headache recurred over the next 10 days, and the patient also developed generalized tonic-clonic seizures. A subarachnoid hemorrhage was demonstrated on a head CT scan. INVESTIGATIONS: Physical examination, laboratory tests, brain CT scan, brain MRI scan, brain magnetic resonance angiogram, brain magnetic resonance venogram, cerebral angiography, transcranial Doppler ultrasound, EEG. DIAGNOSIS: Postpartum cerebral angiopathy. MANAGEMENT: NSAIds and opioid analgesics administered on postpartum day 3 provided partial headache relief. The next day, a blood patch was performed and intravenous caffeine, fluid and opioid analgesia were given to treat a suspected dural puncture headache. Following diagnosis of postpartum cerebral angiopathy on postpartum day 10, nimodipine was initiated to treat the vasospasm, and the headache was treated with opioid analgesics and toradol, followed by naproxen. The patient also received a 3-day course of intravenous magnesium sulfate.

Coma after global ischemic brain injury: pathophysiology and emerging therapies.

Cardiac arrest is a major cause of death and morbidity in the United States, and neurological injury contributes significantly to this. Neurological complications associated with global cerebral ischemia include disorders of responsiveness, such as coma and the vegetative state, seizures, motor deficits, and brain death. Coma, complete unresponsiveness, is the most pervasive of these. Therapies that improve neurological outcomes in general after cardiac arrest and therapies that stimulate arousal from coma could have enormous clinical impact. The authors review the physiology of arousal and describe the biochemical and pathophysiological derangements that develop after global cerebral ischemia. We then describe the potential therapeutic mechanisms of hypothermia and deep brain stimulation, which provide hope for better neurological outcomes after global cerebral ischemia.

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 degrees C-34 degrees 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.

Localized IP3-evoked Ca2+ release activates a K+ current in primary vagal sensory neurons.

Electrophysiological and microfluorimetric techniques were used to determine whether intracellular photorelease of caged IP(3), and the consequent release of Ca(2+), could trigger a Ca(2+)-activated K(+) current (I(IP3)). Photorelease of caged IP(3) evoked an I(IP3) that averaged 2.36 +/- 0.35 (SE) pA/pF in 24 of 28 rabbit primary vagal sensory neurons (nodose ganglion neurons, NGNs) voltage-clamped at -50 mV. I(IP3) was abolished by intracellular BAPTA (2 mM), a Ca(2+) chelator. Changing the K(+) equilibrium potential by increasing extracellular K(+) ion concentration caused a predicted Nernstian shift in the reversal potential of I(IP3). These results indicated that I(IP3) was a Ca(2+)-dependent K(+) current. I(IP3) was unaffected by three common antagonists of Ca(2+)-activated K(+) currents: bath-applied iberiotoxin (50 nM) or apamin (100 nM), and intracellular 8-Br-cAMP (100 microM) included in the patch pipette. We have previously demonstrated that both IP(3)-evoked Ca(2+) release and Ca(2+)-induced Ca(2+) release (CICR) are co-expressed in NGNs and that CICR can trigger a Ca(2+)-activated K(+) current. In the present study, using caffeine, a CICR agonist, to selectively attenuate intracellular Ca(2+) stores, we showed that IP(3)-evoked Ca(2+) release occurs independently of CICR, but interestingly, that a component of I(IP3) requires CICR. These data suggest that IP(3)-evoked Ca(2+) release activates a K(+) current that is pharmacologically distinct from other Ca(2+)-activated K(+) currents in NGNs. We describe several models that explain our results based on Ca(2+) signaling microdomains in NGNs.

Coexistence of functional IP(3) and ryanodine receptors in vagal sensory neurons and their activation by ATP.

Intracellular photorelease of caged D-myo-inositol 1,4,5-trisphosphate (IP(3)), caffeine application, and immunofluorescence confocal microscopy were used to determine that D-myo-inositol 1,4,5-trisphosphate receptors (IP(3)Rs) and ryanodine receptors (RyRs) coexist in rabbit vagal sensory nodose ganglion neurons (NGNs). ATP, an extracellular physiological signaling molecule, consistently evoked robust transient increases in cytosolic free Ca(2+) concentration (Ca(2+) transients). ATP applied in Ca(2+)-free physiological saline elicited Ca(2+) transients that averaged approximately 70% of the amplitude of transients evoked in the presence of extracellular Ca(2+). The component of the ATP-evoked Ca(2+) transient that was independent of extracellular Ca(2+) corresponds to Ca(2+) release from intracellular stores. This release component was sensitive to the pharmacological antagonists pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), U73122, neomycin, and heparin (13.5-15 kD), indicating that P2 purinoreceptors (P2Y) and the IP(3) signaling pathway are required for ATP-evoked Ca(2+) release. Additionally, a portion of ATP-evoked Ca(2+) release was inhibited by ryanodine, a selective blocker of RyRs. The ryanodine-insensitive component (approximately 70%) of ATP-evoked Ca(2+) release corresponds to IP(3)-induced Ca(2+) release via IP(3)Rs, while the ryanodine-sensitive component (approximately 30%) corresponds to consequent Ca(2+)-induced Ca(2+) release (CICR) via RyRs. These results indicate that functional IP(3)Rs and RyRs coexist in nodose neurons and that both IP(3)-induced Ca(2+) release and CICR can be activated by ATP.