Derek Denny-brown: The Man Behind The Ganglia

The authors present an historical review about the main contributions of Professor Derek Denny-Brown to neurology. Some of his achievements include the first description of sensory neuronopathies, and some of the essential textbooks on the function and anatomy of the basal ganglia. In 2016, on the 35th anniversary of his death, modern neurologists are still strongly influenced by his legacy.75212712

Genetic determinants of cerebral edema in severe traumatic brain injury: A pilot study of the role of CACNA1 and AQP4 gene mutations

Cerebral edema is the one of the most significant predictors of poor outcome after traumatic brain injury. It is still unclear what the pathophysiological and cellular mechanisms and predictors of post-traumatic edema are. The exponential growth in genetic information has opened an avenue for investigation in traumatic brain injury and implicated specific genes in the pathophysiology of post-traumatic injury edema. Two examples are the Aquaporin-4 and CACNA1 genes, which respectively encode water and calcium channels. The Aquaporin-4 gene on chromosome 18q11.2-12.1 encodes the Aquaporin-4 protein (AQP4) water channel. AQP4 is one of the bidirectional high capacity water channels that is primarily expressed in astrocytic foot processes in the central nervous system at the blood-brain barrier and is thought to be critical for brain water homeostasis. Experimental studies showed that AQP4 deficient mice had significantly reduced cerebral edema and better survival in a water intoxication model. The CACNA1 gene on chromosome 19p13 encodes the a1A subunit of a neuronal calcium channel. Patients with Familial Hemiplegic Migraine and delayed fatal cerebral edema and seizuresfrom minor trauma have been found to have mutations in CACNA1, which are hypothesized to enhance development of cytotoxic edema. A missense mutation is reported to enhance risk of delayed fatal cerebral edema. Hypothesis: The CACNA1 gene missense mutation S218L and AQP4 polymorphisms will be over-represented in patients with post-traumatic cerebral edema. Our Specific Aim is to perform full exon sequence analysis of these two genes in 20 well-defined cases of excessive cerebral edema. Our long term goal is to systematically investigate genetic variants as determinants of risk of excessive cerebral edema. It is hoped that this will further elucidate secondary mechanisms of injury specifically in the formation of post-traumatic edema and lead to targeted therapies in the future

Impact of medical and neurological ICU complications on moderate-severe traumatic brain injury (TBI)

Certain admission characteristics are known predictors of adverse outcomes in patients with moderate-severe TBI, but explain only 1/3 of outcome variability. Intensive care unit (ICU) complications occur frequently in this population, but their impact on patient outcomes remains poorly defined. In a prospective observational cohort study of 170 consecutive moderate-severe TBI patients admitted to Level I trauma center (UMASS) over the period 11/2009–2/2012, we examined the association of ICU complications and 3-month outcome (Glasgow Outcome Scale [GOS]). The mean age was 51 years, 72% were men, and the median GCS and injury severity scores were 4 and 29, respectively. Using multiple logistic regression analysis, hypotension requiring vasopressors (HRV) was the strongest predictor of poor outcome (GOS 1-3 [OR 2.8; 95% CI 1-7.5]) among medical complications. After combining medical with neurological ICU complications, brain herniation (OR 5.8; 95% CI 1.1-30.2) and intracranial rebleeding (OR 2.9; 95% CI 1-8.4) were the strongest predictors of poor outcome, while HRV approached significance (OR 2.4; 95% CI 0.9-6.4). We identified important potentially modifiable predictors of adverse outcomes after moderate-severe TBI. Confirmation of our findings in a larger cohort is warranted

Incidence rates of ICU complications in moderate-severe traumatic brain injury (TBI)

Retrospective studies suggest that non-neurologic organ failure may contribute to 2/3 of all deaths after TBI, but the actual incidence rates of specific intensive care unit (ICU) complications in moderate-severe TBI are not known. In a prospective observational cohort study of consecutive TBI patients from a single Level I trauma center (UMASS) over the period 11/2009 – 2/2012, we identified the ten most common medical complications after ICU admission according to strict pre-specified criteria in 170 moderate-severe TBI patients. The mean age of the study sample was 51 years, 72% were men, and the median GCS and injury severity scores were 4 and 29, respectively. Incidence rates of the ten most common medical complications in the ICU were: hyperglycemia (75%), fever (62%), systemic inflammatory response syndrome (38%), cardiac complications (36%), hypotension requiring vasopressors (35%), pneumonia (any type [34%]); sepsis (33%), anemia requiring transfusion (31%), other pulmonary complications (ARDS, pulmonary edema [26%]), and hyponatremia (sodium ≤134mEq/L; [23%]). Medical complications in moderate-severe TBI are very common, and their association with important patient outcomes should be further investigated. Specific medical complications may pose attractive modifiable treatment targets to improve the outcome of moderate-severe TBI patients

Serum sodium values and their association with adverse outcomes in moderate-severe traumatic brain injury (TBI)

Hypernatremia in neurocritically ill patients has been associated with worse neurological outcomes. There may, however, be a treatment effect from osmotherapy combating herniation and hyponatremia, which in turn may exacerbate brain edema, resulting in iatrogenic sodium repletion. In moderate-severe TBI, serum sodium (sNa) disturbances are common, but their impact on patient outcomes is unknown. In a prospective observational cohort study of 144 consecutive moderate-severe TBI patients admitted to a Level I trauma center (UMASS) over the period 11/2009–11/2011, we examined the association of mean, nadir, and peak sNa and hospital discharge neurological outcome (Glasgow Outcome Scale [GOS]). The mean age of this cohort was 51 years, 70% were men, and the median GCS and injury severity scores were 5 and 32, respectively. Using ordinal regression analysis, controlling for admission variables, length of ICU stay, severity of injury, presence of brain edema on head CT, administered hypertonic saline and mannitol, higher mean (p\u3c0.001), higher peak (p=0.01), and higher nadir (p\u3c0.001) sNa values were significantly associated with worse outcome. Our findings suggest that higher sNa values are associated with worse neurological outcome, independent of treatment effect by osmotherapy

Identificação molecular de Bartonella henselae em paciente com SIDA soronegativo para doença da arranhadura do gato no Rio de Janeiro, Brasil

Bartonella henselae is associated with a wide spectrum of clinical manifestations, including cat scratch disease, endocarditis and meningoencephalitis, in immunocompetent and immunocompromised patients. We report the first molecularly confirmed case of B. henselae infection in an AIDS patient in state of Rio de Janeiro, Brazil. Although DNA sequence of B. henselae has been detected by polymerase chain reaction in a lymph node biopsy, acute and convalescent sera were nonreactive.Bartonella henselae está associada a um amplo espectro de manifestações clínicas, incluindo a doença da arranhadura de gato, endocardite, e meningoencefalite, em pacientes imunocompetentes e imunocomprometidos. Relatamos o primeiro caso confirmado por método molecular de B. henselae em um paciente com SIDA no estado do Rio de Janeiro, Brasil. Apesar da sequência de DNA de B. henselae ser detectada pela reação em cadeia da polimerase em uma biópsia do linfonodo, soros das fases aguda e convalescente foram não reativos

Effective String Theory Revisited

We revisit the effective field theory of long relativistic strings such as confining flux tubes in QCD. We derive the Polchinski-Strominger interaction by a calculation in static gauge. This interaction implies that a non-critical string which initially oscillates in one direction gets excited in orthogonal directions as well. In static gauge no additional term in the effective action is needed to obtain this effect. It results from a one-loop calculation using the Nambu-Goto action. Non-linearly realized Lorentz symmetry is manifest at all stages in dimensional regularization. We also explain that independent of the number of dimensions non-covariant counterterms have to be added to the action in the commonly used zeta-function regularization.Comment: 21 pages, 4 figures, v2: typo corrected, references added, published versio

First-principles derivation of the AdS/CFT Y-systems

We provide a first-principles, perturbative derivation of the AdS5/CFT4 Y-system that has been proposed to solve the spectrum problem of N=4 SYM. The proof relies on the computation of quantum effects in the fusion of some loop operators, namely the transfer matrices. More precisely we show that the leading quantum corrections in the fusion of transfer matrices induce the correct shifts of the spectral parameter in the T-system. As intermediate steps we study UV divergences in line operators up to first order and compute the fusion of line operators up to second order for the pure spinor string in AdS5xS5. We also argue that the derivation can be easily extended to other integrable models, some of which describe string theory on AdS4, AdS3 and AdS2 spacetimes.Comment: 45 pages, 5 figures; v2: minor additions, JHEP versio

Solving the Simplest Theory of Quantum Gravity

We solve what is quite likely the simplest model of quantum gravity, the worldsheet theory of an infinitely long, free bosonic string in Minkowski space. Contrary to naive expectations, this theory is non-trivial. We illustrate this by constructing its exact factorizable S-matrix. Despite its simplicity, the theory exhibits many of the salient features expected from more mature quantum gravity models, including the absence of local off-shell observables, a minimal length, a maximum achievable (Hagedorn) temperature, as well as (integrable relatives of) black holes. All these properties follow from the exact S-matrix. We show that the complete finite volume spectrum can be reconstructed analytically from this S-matrix with the help of the thermodynamic Bethe Ansatz. We argue that considered as a UV complete relativistic two-dimensional quantum field theory the model exhibits a new type of renormalization group flow behavior, "asymptotic fragility". Asymptotically fragile flows do not originate from a UV fixed point.Comment: 32+4 pages, 1 figure, v2: typos fixed, published versio