Anand Venkatraman

Post-cardiac arrest temperature manipulation alters early EEG bursting in rats

OBJECTIVES Hypothermia improves outcomes after cardiac arrest (CA), while hyperthermia worsens injury. EEG recovers through periodic bursting from isoelectricity after CA, the duration of which is associated with outcome in normothermia. We quantified burst frequency to study the effect of temperature on early EEG recovery after CA. METHODS Twenty-four rats were divided into three groups, based on 6h of hypothermia (T=33 degrees C), normothermia (T=37 degrees C), or hyperthermia (T=39 degrees C) immediately post-resuscitation from 7-min asphyxial CA. Temperature was maintained using surface cooling and re-warming. Neurological recovery was defined by 72-h neurological deficit score (NDS). RESULTS Burst frequency was higher during the first 90min in rats treated with hypothermia (25.6+/-12.2min(-1)) and hyperthermia (22.6+/-8.3min(-1)) compared to normothermia (16.9+/-8.5min(-1)) (p<0.001). Burst frequency correlated strongly with 72-h NDS in normothermic rats (p<0.05) but not in hypothermic or hyperthermic rats. The 72-h NDS of the hypothermia group (74, 61-74; median, 25-75th percentile) was significantly higher than the normothermia (49, 47-61) and hyperthermia (43, 0-50) groups (p<0.001). CONCLUSIONS In normothermic rats resuscitated from CA, early EEG burst frequency is strongly associated with neurological recovery. Increased bursting followed by earlier restitution of continuous EEG activity with hypothermia may represent enhanced recovery, while heightened metabolic rate and worsening secondary injury is likely in the hyperthermia group. These factors may confound use of early burst frequency for outcome prediction.

YouTube as a source of information on dialysis: A content analysis

End‐stage renal disease is a prevalent and growing health problem worldwide. With increasing Internet use, video‐sharing websites could potentially serve as a powerful platform for dissemination of information on dialysis. We conducted a cross‐sectional study to assess the accuracy, content and viewership of YouTube videos on dialysis.

The Brainstem in Emotion: A Review

Emotions depend upon the integrated activity of neural networks that modulate arousal, autonomic function, motor control, and somatosensation. Brainstem nodes play critical roles in each of these networks, but prior studies of the neuroanatomic basis of emotion, particularly in the human neuropsychological literature, have mostly focused on the contributions of cortical rather than subcortical structures. Given the size and complexity of brainstem circuits, elucidating their structural and functional properties involves technical challenges. However, recent advances in neuroimaging have begun to accelerate research into the brainstem’s role in emotion. In this review, we provide a conceptual framework for neuroscience, psychology and behavioral science researchers to study brainstem involvement in human emotions. The “emotional brainstem” is comprised of three major networks – Ascending, Descending and Modulatory. The Ascending network is composed chiefly of the spinothalamic tracts and their projections to brainstem nuclei, which transmit sensory information from the body to rostral structures. The Descending motor network is subdivided into medial projections from the reticular formation that modulate the gain of inputs impacting emotional salience, and lateral projections from the periaqueductal gray, hypothalamus and amygdala that activate characteristic emotional behaviors. Finally, the brainstem is home to a group of modulatory neurotransmitter pathways, such as those arising from the raphe nuclei (serotonergic), ventral tegmental area (dopaminergic) and locus coeruleus (noradrenergic), which form a Modulatory network that coordinates interactions between the Ascending and Descending networks. Integration of signaling within these three networks occurs at all levels of the brainstem, with progressively more complex forms of integration occurring in the hypothalamus and thalamus. These intermediary structures, in turn, provide input for the most complex integrations, which occur in the frontal, insular, cingulate and other regions of the cerebral cortex. Phylogenetically older brainstem networks inform the functioning of evolutionarily newer rostral regions, which in turn regulate and modulate the older structures. Via these bidirectional interactions, the human brainstem contributes to the evaluation of sensory information and triggers fixed-action pattern responses that together constitute the finely differentiated spectrum of possible emotions.

The histone deacetylase HDAC3 is essential for Purkinje cell function, potentially complicating the use of HDAC inhibitors in SCA1

Spinocerebellar ataxia type 1 (SCA1) is an incurable neurodegenerative disease caused by a pathogenic glutamine repeat expansion in the protein ataxin-1 (ATXN1). One likely mechanism mediating pathogenesis is excessive transcriptional repression induced by the expanded ATXN-1. Because ATXN1 binds HDAC3, a Class I histone deacetylase (HDAC) that we have found to be required for ATXN1-induced transcriptional repression, we tested whether genetically depleting HDAC3 improves the phenotype of the SCA1 knock-in mouse (SCA1(154Q/2Q)), the most physiologically relevant model of SCA1. Given that HDAC3 null mice are embryonic lethal, we used for our analyses a combination of HDAC3 haploinsufficient and Purkinje cell (PC)-specific HDAC3 null mice. Although deleting a single allele of HDAC3 in the context of SCA1 was insufficient to improve cerebellar and cognitive deficits of the disease, a complete loss of PC HDAC3 was highly deleterious both behaviorally, with mice showing early onset ataxia, and pathologically, with progressive histologic evidence of degeneration. Inhibition of HDAC3 may yet have a role in SCA1 therapy, but our study provides cautionary evidence that this approach could produce untoward effects. Indeed, the neurotoxic consequences of HDAC3 depletion could prove relevant, wherever pharmacologic inhibition of HDAC3 is being contemplated, in disorders ranging from cancer to neurodegeneration.

Greater freedom of speech on Web 2.0 correlates with dominance of views linking vaccines to autism

INTRODUCTION It is suspected that Web 2.0 web sites, with a lot of user-generated content, often support viewpoints that link autism to vaccines. METHODS We assessed the prevalence of the views supporting a link between vaccines and autism online by comparing YouTube, Google and Wikipedia with PubMed. Freedom of speech is highest on YouTube and progressively decreases for the others. RESULTS Support for a link between vaccines and autism is most prominent on YouTube, followed by Google search results. It is far lower on Wikipedia and PubMed. Anti-vaccine activists use scientific arguments, certified physicians and official-sounding titles to gain credibility, while also leaning on celebrity endorsement and personalized stories. CONCLUSIONS Online communities with greater freedom of speech lead to a dominance of anti-vaccine voices. Moderation of content by editors can offer balance between free expression and factual accuracy. Health communicators and medical institutions need to step up their activity on the Internet.

Two- and three-locus haplotypes of the paraoxonase (PON1) gene are associated with coronary artery disease in Asian Indians.

INTRODUCTION In view of the reported association of SNPs in the paraoxonase (PON1) gene with coronary artery disease (CAD), and the absence of conclusive data from India, we investigated the relationship of three SNPs at different loci (-108C/T, L55M and Q192R) of the PON1 gene and their haplotypes with CAD among people residing in the northern plains of India. MATERIALS AND METHODS One hundred and seventy-eight healthy controls and two hundred and four angiographically-proven CAD patients were genotyped using PCR-RFLP. RESULTS Of the three SNPs, only the R allele of Q192R polymorphism was associated with CAD (p<0.05). Two locus haplotypes QT (OR 0.55, p=0.0004, 95% CI 0.39-0.77, significant) and LQ (odds ratio 0.73, p=0.03, 95% CI 0.55-0.97, trend) showed protective effects, while haplotypes MR (OR=5.36, p=0.0001, 95% CI 2.045-14.049) and MC (OR=2.71, p=0.011, 95% CI 1.221-6.046) were associated with increased risk of CAD. MRT, a minor three-locus haplotype also displayed significant association (OR 4.93, 95% CI 1.7-13.5) with the disease. Significance was assessed after applying Bonferronis correction. CONCLUSIONS Our study revealed that only one SNP at a single locus but several haplotype combinations of PON1 coding and promoter-region polymorphisms were associated with the risk of or protection against CAD. Thus, haplotype analysis brought better insights into the association of PON1 gene polymorphisms with CAD in Asian Indians.

Paraneoplastic cerebellar degeneration with anti‐Yo antibodies – a review

The ataxic syndrome associated with Anti‐Yo antibody, or Purkinje cell cytoplasmic antibody type 1 (PCA1), is the most common variant of paraneoplastic cerebellar degeneration (PCD). The typical presentation involves the subacute development of pancerebellar deficits with a clinical plateau within 6 months. The vast majority of cases have been reported in women with pelvic or breast tumors. Magnetic resonance imaging of the brain is often normal in the early stages, with cerebellar atrophy seen later. The underlying mechanism is believed to be an immunological reaction to cerebellar degeneration‐related protein 2 (CDR2), a protein usually found in the cerebellum that is ectopically produced by tumor cells. Although both B‐ and T‐cell abnormalities are seen, there is debate about the relative importance of the autoantibodies and cytotoxic T lymphocytes in the neuronal loss. Cerebrospinal fluid abnormalities, primarily elevated protein, lymphocytic pleocytosis, and oligoclonal bands, are common in the early stages. The low prevalence of this condition has not allowed for large‐scale randomized controlled trials. Immunotherapies, such as steroids, intravenous immune globulins, and plasma exchange, have been extensively used in managing this condition, with limited success. Although some reports indicate benefit from antitumor therapies like surgery and chemotherapy, this has not been consistently observed. The prognosis for anti‐Yo PCD is almost uniformly poor, with most patients left bedridden. Further studies are required to clarify the pathophysiology and provide evidence‐based treatment options.

Cardiogenic shock from atypical Takotsubo cardiomyopathy attributed to acute disseminated encephalomyelitis lesion involving the medulla.

We present here a case of atypical Takotsubo cardiomyopathy arising as a result of a lesion in the medulla oblongata. The patient was diagnosed with acute disseminated encephalomyelitis, and had improvement with intravenous steroids.

Intra-arterial vasodilators for vasospasm following aneurysmal subarachnoid hemorrhage: a meta-analysis

Objective The efficacy of intra-arterial vasodilators (IADs) for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) remains debatable. The objective of this meta-analysis was to pool estimates of angiographic and neurological response, clinical outcome, and mortality following treatment of vasospasm with IADs. Methods We searched PubMed, Embase, Scopus, Clinicaltrials.gov, Cochrane database, and CINAHL in December 2015 and August 2016. Studies reporting angiographic and neurological response, clinical outcome, and mortality following IAD treatment of vasospasm in 10 or more adults with aSAH were included. All established IADs were allowed. Two authors independently selected studies and abstracted the data. Mean weighted probabilities (MWP) were calculated using random effects model. Results Inclusion criteria were met by 55 studies (n=1571). MWP for immediate angiographic response to IAD treatment was 89% (95% CI 83% to 94%), post-IAD neurological improvement 57% (95% CI 49% to 65%), good outcome 66% (95% CI 60% to 71%), and mortality was 9% (95% CI 7% to 12%). After adjusting for publication bias, MWP for mortality was 5% (95% CI 4% to 7%). When transcranial Doppler (TCD) was used along with clinical deterioration for patient selection, rates of neurological response (64%) and good outcome (72%) were better. IADs were not superior to controls (balloon angioplasty or medical management). Conclusion IAD treatment leads to a robust angiographic response and fair (but lower) rates of neurological response and good clinical outcome. Mortality was lower than the average reported in the literature. Rates of neurological response and good outcome were better when TCD was used for patient selection. Carefully designed studies are needed to compare IADs against medical management and balloon angioplasty.

Perfusion Mri Can Impact Treatment Decision in Ictal–interictal Continuum

Summary: Lateralized periodic discharges (LPDs) are commonly seen on EEG in critically ill patients. They are often associated with seizures, but some patients may have them without seizures. Therefore, they are considered to lie in the ictal–interictal continuum. When ictal, they require multiple antiepileptic drugs to treat effectively, which can expose the patient to iatrogenic complications. Therefore, optimal management is controversial. We present here two cases where perfusion-weighted MRI was useful in distinguishing ictal from interictal LPDs. In the first patient, hyperperfusion in the area showing LPDs was considered an indication that the LPDs were ictal, and aggressive treatment led to clinical improvement. The second patient had no asymmetry on perfusion-weighted MRI, and therefore, we did not escalate antiepileptic therapy, and the LPDs resolved spontaneously over the next few days. Perfusion-weighted MRI offers several advantages over other techniques, such as single-photon emission computerized tomography that have been used for this purpose before. It does not expose the patient to radiation, and newer techniques like arterial spin labeling can even obviate the need for intravenous contrast. Larger scale studies using perfusion-weighted MRI will be of great value to clinical practice.