Galen V. Henderson

Neurotransplantation of fetal porcine cells in patients with basal ganglia infarcts: a preliminary safety and feasibility study.

Background: Cell transplantation is safe in animal models and enhances recovery from stroke in rats. Methods: We studied the safety and feasibility of fetal porcine transplantation in 5 patients with basal ganglia infarcts and stable neurological deficits. To prevent rejection, cells were pretreated with an anti-MHC1 antibody and no immunosuppressive drugs were given to the patients. Results: The first 3 patients had no adverse cell, procedure, or imaging-defined effects. The fourth patient had temporary worsening of motor deficits 3 weeks after transplantation, and the fifth patient developed seizures 1 week after transplantation. MRI in both patients demonstrated areas of enhancement remote from the transplant site, which resolved on subsequent imaging. Two patients showed improvement in speech, language, and/or motor impairments over several months and persisted at 4 years. The study was terminated by the FDA after the inclusion of 5 patients. Conclusion: This is the first report on the transplantation of nontumor cells in ischemic stroke patients.

Reversible Posterior Leukoencephalopathy, Cerebral Vasoconstriction, and Strokes After Intravenous Immune Globulin Therapy in Guillain-Barré Syndrome

The authors report a patient with Guillain‐Barré syndrome who developed acute hypertension, reversible posterior leukoencephalopathy syndrome, ischemic and hemorrhagic strokes, and reversible cerebral arterial vasoconstriction shortly after initiating intravenous immune globulin therapy. Possible interrelationships and mechanisms of these complications are discussed.

Increased leukocyte ROCK activity in patients after acute ischemic stroke

BACKGROUND Rho-kinase (ROCK) is a downstream effector of Rho GTPase that is known to regulate various pathological processes important to the development of ischemic stroke, such as thrombus formation, inflammation, and vasospasm. Inhibition of ROCK leads to decreased infarct size in animal models of ischemic stroke. This study tests the hypothesis that ROCK activity increases during the acute phase of ischemic stroke. METHODS Serial blood samples were drawn from 10 patients with acute ischemic stroke presenting within 24 h of symptom onset and with NIHSS scores >or=4. Samples were taken at 24, 48, and 72 h. Leukocyte ROCK activity was determined by immunoblotting leukocyte lysates with antibodies to the phosphorylated form of myosin-binding subunit (P-MBS) of myosin light chain phosphatase (MLCP). MBS and P-MBS contents were normalized to alpha-tubulin, and ROCK activity was expressed as the ratio of P-MBS to MBS. ROCK activities in these 10 patients were compared to baseline ROCK activities in 10 control subjects without acute illness and matched for sex, age, and number of vascular risk factors using a two-tailed Students t-test. RESULTS The mean NIHSS score in patients with stroke was 15.4. ROCK activity was significantly increased at 24 and 48 h in patients after acute ischemic stroke when compared to control values, with peak elevations at 48 h after stroke onset. There was no apparent correlation between ROCK activity and stroke severity based on NIHSS. CONCLUSIONS Leukocyte ROCK activity is increased in patients after acute ischemic stroke with maximal activity occurring about 48 h after stroke onset. These findings suggest that activation of ROCK may play a role in the pathogenesis of ischemic stroke in humans.

Variability of Brain Death Policies in the United States.

IMPORTANCE Brain death is the irreversible cessation of function of the entire brain, and it is a medically and legally accepted mechanism of death in the United States and worldwide. Significant variability may exist in individual institutional policies regarding the determination of brain death. It is imperative that brain death be diagnosed accurately in every patient. The American Academy of Neurology (AAN) issued new guidelines in 2010 on the determination of brain death. OBJECTIVE To evaluate if institutions have adopted the new AAN guidelines on the determination of brain death, leading to policy changes. DESIGN, SETTING, AND PARTICIPANTS Fifty-two organ procurement organizations provided US hospital policies pertaining to the criteria for determining brain death. Organizations were instructed to procure protocols specific to brain death (ie, not cardiac death or organ donation procedures). Data analysis was conducted from June 26, 2012, to July 1, 2015. MAIN OUTCOMES AND MEASURES Policies were evaluated for summary statistics across the following 5 categories of data: who is qualified to perform the determination of brain death, what are the necessary prerequisites for testing, details of the clinical examination, details of apnea testing, and details of ancillary testing. We compared these data with the standards in the 2010 AAN update on practice parameters for brain death. RESULTS A total of 508 unique hospital policies were obtained, representing the majority of hospitals in the United States that would be eligible and equipped to evaluate brain death in a patient. Of these, 492 provided adequate data for analysis. Although improvement with AAN practice parameters was readily apparent, there remained significant variability across all 5 categories of data, such as excluding the absence of hypotension (276 of 491 policies [56.2%]) and hypothermia (181 of 228 policies [79.4%]), specifying all aspects of the clinical examination and apnea testing, and specifying appropriate ancillary tests and how they were to be performed. Of the 492 policies, 163 (33.1%) required specific expertise in neurology or neurosurgery for the health care professional who determines brain death, and 212 (43.1%) stipulated that an attending physician determine brain death; 150 policies did not mention who could perform such determination. CONCLUSIONS AND RELEVANCE Hospital policies in the United States for the determination of brain death are still widely variable and not fully congruent with contemporary practice parameters. Hospitals should be encouraged to implement the 2010 AAN guidelines to ensure 100% accurate and appropriate determination of brain death.

Tremor as a Cause of Pseudo–Ventricular Tachycardia

Figure 1. An 84-year-old woman with a history of falling was found on the ground unable to get up. On admission to the hospital for evaluation of syncope, she had a normal pulse and blood pressure. Examination revealed a masklike face, bradykinesia, gait instability, and a pill-rolling tremor. An electrocardiogram showed the 4-to-6-Hz tremor associated with Parkinsons disease. The QRS complexes are indicated by the arrows. Postural instability associated with Parkinsons disease was the most likely cause of the patients falls.

Implementation of a Hospital-wide Protocol for Induced Hypothermia Following Successfully Resuscitated Cardiac Arrest.

Permanent neurologic impairment following cardiac arrest is often severely debilitating, even after successful resuscitation. Therapeutic hypothermia decreases anoxic brain injury and subsequent cognitive deficits. Current practice guidelines recommend therapeutic hypothermia in comatose survivors of cardiac arrest. To address the multifacets of therapeutic hypothermia, we assembled a multidisciplinary task force including members from various specialties to create an evidence-based guideline with transparency across disciplines and consistency of care. We describe our institutional guidelines for the initiation and management of induced hypothermia in patients successfully resuscitated from a cardiac arrest.

Posterior reversible encephalopathy syndrome in Guillain-Barré syndrome

Autonomic dysfunction is a well-known complication of Guillain-Barré syndrome (GBS) and may manifest as hemodynamic fluctuations. Posterior reversible encephalopathy syndrome (PRES) is commonly associated with acute hypertension, but is rarely reported to occur in association with GBS. We describe a patient with GBS who developed PRES in the setting of autonomic dysfunction and review the clinical features of all 12 previously reported patients with co-occurrence of GBS and PRES. Almost all cases have occurred in women over the age of 55, raising the possibility of increased sensitivity to dysautonomia in this patient group.

Effect of stimulus type and temperature on EEG reactivity in cardiac arrest

OBJECTIVE Electroencephalogram (EEG) background reactivity is a reliable outcome predictor in cardiac arrest patients post therapeutic hypothermia. However, there is no consensus on modality testing and prior studies reveal only fair to moderate agreement rates. The aim of this study was to explore different stimulus modalities and report interrater agreements. METHODS We studied a multicenter, prospectively collected cohort of cardiac arrest patients who underwent therapeutic hypothermia between September 2014 and December 2015. We identified patients with reactivity data and evaluated interrater agreements of different stimulus modalities tested in hypothermia and normothermia. RESULTS Of the 60 patients studied, agreement rates were moderate to substantial during hypothermia and fair to moderate during normothermia. Bilateral nipple pressure is more sensitive (80%) when compared to other modalities in eliciting a reactive background in hypothermia. Auditory, nasal tickle, nailbed pressure and nipple pressure reactivity were associated with good outcomes in both hypothermia and normothermia. CONCLUSIONS EEG reactivity varies depending on the stimulus testing modality as well as the temperature during which stimulation is performed, with nipple pressure emerging as the most sensitive during hypothermia for reactivity and outcome determination. SIGNIFICANCE This highlights the importance of multiple stimulus testing modalities in EEG reactivity determination to reduce false negatives and optimize prognostication.

Continuous electrodermal activity as a potential novel neurophysiological biomarker of prognosis after cardiac arrest – A pilot study☆

AIMS Neurological outcome prognosis remains challenging in patients undergoing therapeutic hypothermia (TH) after cardiac resuscitation. Technological advances allow for a novel wrist-worn device to continuously record electrodermal activity (EDA), a measure of pure sympathetic activity. METHODS A prospective cohort study was performed to determine the yield of continuous EDA in patients treated with TH for coma after cardiac arrest during hypothermia and normothermia. Association between EDA parameters (event-related and nonspecific electrodermal responses (ER-EDR, NS-EDR)) and outcome measures (cerebral performance category [CPC]) (Full Outline in UnResponsivenss (FOUR) score) were assessed. RESULTS Eighteen patients were enrolled. Total number of EDR (66.4 vs 12.0/24h, p = 0.02), ER-EDR (39.5 vs 11.2/24h, p = 0.009), median amplitude change of all EDR (0.08 vs 0.03 μSI, p = 0.03) and ER-EDR (0.14 vs 0.05 μSI, p = 0.025) were higher in patients with favorable (CPC 1-2) versus poor outcome (CPC 3-5) during hypothermia. Greater differences in EDA parameters were observed during hypothermia than normothermia. The FOUR score was correlated to the number of all EDR and median amplitudes. CONCLUSIONS Continuous EDA potentially opens a new avenue for autonomic function monitoring in neurocritically ill patients. It is feasible in the ICU setting, even during hypothermic states. As a measure of a complete neurophysiological circuit, it may be a novel neurophysiologic biomarker of outcome after cardiac resuscitation.

Hemichorea as a presentation of recurrent non-Hodgkin's lymphoma.

Sirs: The CNS manifestations of non-Hodgkin’s systemic lymphoma (NHL) can develop from either direct invasion of malignancy or secondary lymphoma-associated processes. It is fairly common for systemic lymphoma to spread directly to the CNS, but neurological presentations are not well described in the literature. Alternatively, secondary symptoms may arise from hemorrhage following thrombocytopenia, opportunistic infections within the CNS, metabolic derangements from multi-organ involvement of lymphoma, complications of radiation and chemotherapy, and paraneoplastic syndromes, including thrombotic events owing to hypercoagulability and various immune-related syndromes. Thus far, only one prior report has described a patient with choreiform movements thought to be secondary to NHL [8]. This case study adds to this prior observation, as we describe a woman with similar findings of NHL and hemichorea, who also had complications of stroke and angioedema. An 85-year-old white female was well until three years prior to admission when she presented for routine physical examination and was noted to have an elevated white cell count. Bone marrow and lymph node biopsies were diagnostic of NHL (B-cell chronic lymphocytic leukemia). The patient received daily oral chemotherapy (chlorambucil) for one month with normalization of blood counts and lymph nodes at six months. She had since been in remission. Three months before admission, she was hospitalized with headache and left arm pain to rule out myocardial infarction. Her course was complicated by a left arm superficial phlebitis with angioedema. Shortly after this, she developed left hemichorea and consequent loss of balance with no weakness. Head CT, MRI and MRA of the head and neck, and MRI of the cervical spine were all unremarkable. Chlorpromazine and lorazepam were not well tolerated. The issue of recent phlebitis raised the question of Sydenham’s chorea, and treatment with a tenday course of penicillin was initiated; however ASLO titers were negative. The patient’s chorea worsened, and she was hospitalized for further evaluation. The patient again developed angioedema and phlebitis at her IV site. Examination was remarkable for hemichorea involving the left arm more than the leg. There were occasional ballistic movements of the left arm and truncal movements exacerbated by standing and walking. The right side was not involved. Metabolic profile was within normal limits (including CBC, ESR, ANA, lupus anticoagulant assay, thyroid functions, ceruloplasmin, serum calcium, serum protein electrophoresis, 14-3-3 protein for Creutzfeldt-Jakob disease, and antiRi, Yo and Hu antibodies). D-dimer was elevated to 810 units. CT of the chest was unremarkable; abdomen/ pelvis CT revealed bilateral renal cysts and multiple 1–2 cm enlarged lymph nodes. Repeat MRI with diffusion weighted imaging of the brain revealed a subacute infarct in the left cerebellum (Fig. 1A). EEG was normal. Single-photon emission computed tomography (SPECT) perfusion scan showed decreased uptake of technetium (99mTc-HMPAO) within the posterior aspect of the right basal ganglia (Fig. 1B). Flow cytometry from both peripheral blood and a traumatic lumbar puncture (CSF: RBC 74K cells/mm3 and WBC 18 cells/mm3, protein 65 mg/dL, glucose 69 mg/dL) revealed a clonal cell population, consistent with small lymphocytic lymphoma. She received a single dose of prednisone (60 mg) while in the hospital with some reduction of her left arm hemichorea and significant improvement of her gait. LETTER TO THE EDITORS