Medical management of aneurysmal subarachnoid hemorrhage.
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Combined Modality Therapy↗
Biomedical subjects
D F Hanley
Publications and source records attributed to D F Hanley.
Sedation for the critically ill neurologic patient.
OBJECTIVE: To review the scientific basis for sedation of critically ill neurologic patients by summarizing the distinct neurophysiologic disturbances present in this population and presenting the central nervous system effects of sedative agents to permit optimal drug therapy. DATA SOURCES: Review of the English language clinical and scientific literature using MEDline data search. STUDY SELECTION: Literature references were selected through a key word search of sedative therapy, drugs used for sedation, and specific neurologic disorders and processes to provide an in-depth overview of sedative drug mechanisms of action, effects on neurophysiology and intracranial dynamics, pharmacokinetics, and toxicity profile. Special emphasis was placed on neurologic side effects. DATA EXTRACTION: Clinical and scientific literature was reviewed and data relevant to neurophysiologic effects of sedative drug therapy were summarized. Recommendations for institution of sedative therapy and of particular agents were made as a result of analysis of all pooled data. DATA SYNTHESIS: Critically ill patients with neurologic pathology present as a unique subset of individuals cared for in an acute care setting. Because monitoring of neurologic patients requires frequent assessment of the neurologic examination, the goal of sedative therapy should be to enhance, or to minimally perturb elicitation of the examination. Neurophysiologic disturbances introduce distinct risks for sedation and require their identification and understanding before the initiation of any sedative therapy. Sedative drugs, in particular, act to disturb central nervous system function and their effects may result in diagnostic confusion and further neurologic deterioration. The pharmacokinetic and neurophysiologic actions of the common classes of sedative agents, such as benzodiazepines, opioids, barbiturates, and neuroleptics, as well as ketamine, propofol, and clonidine are discussed. Recommendations are presented based on the specific type of sedation required and the underlying neurologic disturbance. Several specific examples, including head trauma, neuromuscular disease, and alcohol withdrawal, are provided. CONCLUSIONS: Preservation of the neurologic examination is paramount in documenting clinical improvement or deterioration in the critically ill neurologic patient. Pharmacologic sedation in this unique population of acute care patients requires careful consideration of the underlying neurophysiologic disturbances and potential adverse effects introduced by sedative drugs.
Critical Illness↗
Localization of nitric oxide synthase in spinal nuclei innervating pelvic ganglia.
We employed retrograde axonal tracing techniques and nitric oxide synthase (NOS) and choline acetyltransferase (ChAT) immunohistochemistry to identify NOS-containing neuronal populations within the lumbosacral spinal cord and determine whether these project to the major pelvic ganglion in the adult male Sprague-Dawley rat. Immunohistochemical localizations of NOS included neurons situated at the L5 to S2 segments of the spinal cord, which corresponded to the sacral parasympathetic nucleus. Another prominent locus for NOS was a group of neurons identified in the L1 segment corresponding to the dorsal commissural nucleus. These regions correlated directly with preganglionic parasympathetic and sympathetic neuronal origins, respectively, which were established with ChAT colocalizations. Retrograde tracing verified the projection of these neurons to the pelvis. Additional neuronal localizations of NOS were observed throughout the intermediolateral cell column, involving the superficial laminae of the dorsal horn, in the region surrounding the central canal and occasionally in the medial area of the ventral horn. These results indicate that the regulation of pelvic visceral activity may involve NO-based neuronal mechanisms operating at the level of the lumbosarcal spinal cord.
Amino Acid Oxidoreductases↗
Nonlinear changes in brain's response in the event of injury as detected by adaptive coherence estimation of evoked potentials.
Injury-related changes in evoked potentials are studied with the aid of the coherence function, which effectively measures the degree of linear association between a pair of signals recorded during normal and abnormal states of the brain. The performance of an adaptive algorithm for estimating coherence function is studied, and the effects of additive noise on the estimated coherence function is discussed. Further, a linearity index is formulated and, through analysis and simulations, the index is shown to respond in a predictable manner to increasing nonlinearity while maintaining the robustness to the observation noise. Somatosensory evoked potentials are shown to be sensitive to injury resulting from acute cerebral hypoxia. We analyze the somatosensory evoked potentials recorded from anesthetized cats during inhalation of 8-9% oxygen gas mixtures and during recovery with 100% oxygen. Analyses of the experimental data show a very sharp drop in the magnitude coherence estimates during hypoxic injury and a corresponding rapid decline in the linearity index at the very early stages of the hypoxic injury. Thus, injury may lead to nonlinearities in the electrical response of the brain, and such measurements analyzed by the adaptive coherence estimation method may be used for diagnostic purposes.
Algorithms↗
Cat brain cytochrome-c oxidase redox changes induced by hypoxia after blood-fluorocarbon exchange transfusion.
We used rapid-scanning near-infrared (NIR) spectroscopy (730-960 nm) to study the effects of graded or acute hypoxia on cerebral cytochrome-c oxidase (cyt aa3) redox state in blood-perfluoro-carbon-exchanged cats with somatosensory evoked potential (SEP) monitoring. In graded hypoxia [10 min each at fractional inspiratory O2 concentration (FIO2) 0.9, 0.8, 0.7, 0.6, and 0.5], cyt aa3 reduction occurred at FIO2 0.6 when cerebral O2 delivery was < 3.5 ml.100 g-1.min-1. In acute hypoxia (FIO2 0.6 for 10 min), significant cyt aa3 reduction occurred from 5 to 10 min (cerebral O2 delivery 3.1 +/- 0.3 ml.100 g-1.min-1) and recovered with reoxygenation (FIO2 1.0). Cyt aa3 redox changes preceded or coincided with SEP alterations in both hypoxia protocols. These results demonstrate that cerebral cyt aa3 reduction occurs with severe reduction of cerebral O2 delivery, but no significant change in cerebral cyt aa3 redox state occurs with small reductions of cerebral O2 delivery. We conclude that substantial changes in cerebral cyt aa3 do not occur at physiological levels of O2 delivery and that current NIR clinical instruments would detect oxygen-dependent cerebral cyt aa3 redox changes only when O2 delivery is extremely compromised.
Animals↗
Adenosine modulates N-methyl-D-aspartate-stimulated hippocampal nitric oxide production in vivo.
BACKGROUND AND PURPOSE: Adenosine acts presynaptically to inhibit release of excitatory amino acids (EAAs) and is thus considered to be neuroprotective. Because EAA-stimulated synthesis of nitric oxide (NO) may play an important role in long-term potentiation and excitotoxic-mediated injury, we tested the hypotheses that adenosine agonists attenuate basal and EAA-induced NO production in the hippocampus in vivo and that adenosine A1 receptors mediate this response. METHODS: Microdialysis probes were placed bilaterally into the CA3 region of the hippocampus of adult Sprague-Dawley rats under pentobarbital anesthesia. Probes were perfused for 5 hours with artificial cerebrospinal fluid containing 3 mumol/L [14C]L-arginine. Recovery of [14C]L-citrulline in the effluent was used as a marker of NO production. In 10 groups of rats, time-dependent increases in [14C]L-citrulline recovery were compared between right- and left-sided probes perfused with various combinations of N-methyl-D-aspartate (NMDA), adenosine agonists, adenosine antagonists, and the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). RESULTS: Recovery of [14C]L-citrulline during perfusion with artificial cerebrospinal fluid progressively increased to 141 +/- 27 fmol/min (+/- SEM) over 5 hours. Contralateral perfusion with 1 mmol/L NMDA augmented [14C]L-citrulline recovery to 317 +/- 62 fmol/min. Perfusion of 1 mmol/L L-NAME with NMDA inhibited [14C]L-citrulline recovery compared with NMDA alone. Perfusion with 0.1 mmol/L 2-chloroadenosine attenuated basal as well as NMDA-enhanced [14C]L-citrulline recovery. This action of 2-chloroadenosine was reversed by infusion of 0.1 mmol/L 8-cyclopentyl-1,3-dipropylxanthine, a specific A1 receptor antagonist. Infusion of 0.1 mmol/L (2S)-N6-[2-endo-norboryl]adenosine, a specific A1 receptor agonist, also attenuated the 0.1 mmol/L and 1 mmol/L NMDA-enhanced [14C]L-citrulline recovery. CONCLUSIONS: Using an indirect method of assessing NO production in vivo, these data are consistent with in vitro results showing that NMDA receptor stimulation enhances NO production. Furthermore, we conclude that stimulation of A1 receptors can attenuate the basal as well as NMDA-induced production of NO. Because NMDA receptor stimulation amplifies glutamate release, our data are consistent with presynaptic A1 receptor-mediated inhibition of EAA release and consequent downregulation of NO production.
2-Chloroadenosine↗
Brain death: an update on the North American viewpoint.
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Attitude to Death↗
Validation of transcranial Doppler ultrasound with a stereotactic neurosurgical technique.
Vessel identification during a transcranial Doppler (TCD) ultrasound examination is usually based on well-established inferential criteria without confirmation by imaging. Part of a routine study involves taking measurements from the M1 segment of the middle cerebral artery (MCA) and the A1 segment of the anterior cerebral artery (ACA) at the points of maximum mean linear blood flow velocity (LBFV). The authors tested the hypothesis that insonation is from the midpoints of the M1 and A1 segments during clinical TCD examinations. Conventional hand-held TCD examinations were performed on five volunteers. The points of maximum mean LBFV of the M1 and A1 segments of the MCA and ACA were located. Measurements were also taken from the midpoints of the M1 and A1 segments using a magnetic resonance (MR) imaging-guided stereotactic TCD technique. Values for depths of insonation and maximum mean LBFV obtained with the two techniques were compared. There was no significant difference between the two techniques for the measured values of depth of insonation of either the individual vessels (p > 0.11) or the aggregate (p = 0.46). There was a significant difference between the aggregate maximum mean LBFV measurements (p = 0.0022). The hand-held technique systematically produced higher maximum mean LBFV than the MR-guided stereotactic technique. The authors conclude that when using traditional criteria for TCD examination of the ACA and MCA, the points of insonation approximate the middle of the A1 and M1 segments.
Adult↗
Nitric oxide synthase does not contribute to cerebral autoregulatory phenomenon in anesthetized dogs.
Nitric oxide (NO) is a potent vasodilator produced by nitric oxide synthase (NOS). We tested the following hypotheses: (1) cerebral blood flow (CBF) is NO dependent, (2) NO contributes to CBF autoregulation, and (3) NO participates in the neurohypophysial vasodilator response to hypotension. Three groups of sodium pentobarbital anesthetized dogs were studied using microspheres. In 7 dogs, N omega-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg, i.v.) increased mean arterial pressure (MAP) by 12%. Cerebrovascular resistance (CVR) increased more than MAP, resulting in a 20 +/- 4% reduction (range 12-67%) in baseline CBF. In unblocked conditions, actively autoregulated regions (e.g. cortex, white matter, median eminence) demonstrated a correlation between CVR and MAP whereas passive regions (neural lobe) did not. NOS block did not effect the relationship between MAP and CVR in most brain regions. However, a significant relationship between CVR and MAP developed in neural lobe after NOS block. Abrupt hypotension increased neural lobe blood flow to 239 +/- 37% control at 3 min, despite NOS block. These results show that baseline cerebral vessel tone depends upon NOS activity. Enhanced NO release cannot explain either cerebral autoregulation or the transient hyperperfusion seen in neural lobe immediately following rapid hemorrhage.
Amino Acid Oxidoreductases↗
Rat spinal cord neurons contain nitric oxide synthase.
We describe the distribution and characteristics of nitric oxide synthase-containing neurons in rat spinal cord using a polyclonal affinity-purified antibody against rat cerebellar nitric oxide synthase. Numerous neurons were stained throughout the entire rostrocaudal extent of the spinal cord. Cell bodies, dendrites and axons stained in a uniform manner. Nitric oxide synthase immunoreactivity was intense in neurons of laminae I-IV and X throughout the entire spinal cord. Neurons in the intermediolateral cell column of the thoracic and lumbar spinal cord were also intensely stained for nitric oxide synthase. The sacral cord demonstrated substantial nitric oxide synthase immunostaining within lamina VII. For the entire cord, scattered neurons in laminae V, VI, VII, and VIII were weakly positive. In addition, punctate nitric oxide synthase staining throughout laminae I, III and surrounding some large motor neurons in the ventral horn suggested the presence of nitric oxide synthase at synapses. Axons and dendritic terminals located in the gray and white matter were also stained. The majority of nitric oxide synthase positive neurons in the intermediolateral cell column were double-labelled by subcutaneously injected FluoroGold confirming that these cells were preganglionic autonomic neurons. Most NADPH-diaphorase-stained neurons were also nitric oxide synthase-positive. The distribution of nitric oxide synthase-containing neurons in spinal cord suggests that nitric oxide plays a role in spinal cord neurotransmission including: preganglionic sympathetic and parasympathetic, somatosensory, visceral sensory and possibly motor pathways. In particular, the autonomic nervous system appears enriched with nitric oxide synthase immunoreactivity. The precise role of each neuron type remains to be demonstrated in physiologic and pathophysiologic paradigms.
Amino Acid Oxidoreductases↗
Acute stroke: evaluation with serial proton MR spectroscopic imaging.
PURPOSE: To investigate the evolution of metabolic changes detectable with proton magnetic resonance (MR) spectroscopic imaging in acute stroke and to compare these findings with those of conventional MR imaging. MATERIALS AND METHODS: A patient with middle cerebral artery stroke underwent conventional proton-density (PD)- and T2-weighted MR imaging, MR angiography, and multisection proton two-dimensional MR spectroscopic imaging over a period of 3 hours to 5 months after symptom onset. RESULTS: On 3-hour MR images, no abnormal signal intensity change was detectable. Spectroscopic images obtained at 24 hours showed localized elevation of cerebral lactate levels. In most regions with high lactate levels, infarction subsequently occurred. In the chronic stage (5 months), the infarct was associated with reduced N-acetylaspartate levels, increased choline levels, and absence of lactate. CONCLUSION: Spectroscopic imaging enables mapping of ischemic and infarcted brain regions with greater sensitivity than does conventional MR imaging.
Acute Disease↗
Validation of transcranial Doppler ultrasound with an in vivo stereotactic technique.
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Adult↗
Peri-arterial innervation within the neurohypophysis.
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Animals↗
Intensive management and treatment of severe Guillain-Barré syndrome.
OBJECTIVE: To review the management and therapeutic approaches to severe acute Guillain-Barré syndrome, with emphasis on the ventilatory dysfunction, and cardiovascular instability seen in patients with this syndrome. DATA SOURCES/STUDY SELECTION: Clinical studies on Guillain-Barré syndrome patients, physiologic studies on animals and humans. DATA EXTRACTION/SYNTHESIS: Guillain-Barré syndrome is an acutely evolving, immune-mediated, inflammatory disorder of the peripheral nervous system, leading to demyelination and axonal loss. Clinical hallmarks are symmetric flaccid muscle paresis and areflexia in the presence of an increased cerebrospinal fluid protein content, and electrophysiologic studies demonstrating evolving demyelination. The only well-investigated, efficacious immunomodulatory therapy is plasmapheresis. Plasmapheresis has been shown to decrease ventilator dependence in severe Guillain-Barré syndrome. Ventilatory failure and cardiovascular instability are the main reasons for intensive care support. Ventilatory failure is caused by involvement of airway and respiratory muscles, particularly the diaphragm. Cardiovascular instability is due to involvement of the autonomic nervous system and results in labile blood pressure, cardiac arrhythmias, and hypovolemia. After admission to the intensive care unit, the most serious complications result from mechanical ventilation, circulatory disturbances, thrombosis, starvation, and sepsis. Special emphasis should be given to psychologic support and management of pain. CONCLUSIONS: With modern intensive care support, the outcome is excellent (> 80% recovery). In severe cases, a higher frequency of persistent residual paresis occurs; however, the majority of this group ultimately have a good functional recovery.
Acute Disease↗
Ventilatory drive and carbon dioxide response in ventilatory failure due to myasthenia gravis and Guillain-Barré syndrome.
OBJECTIVE: To test the hypothesis that either decreased ventilatory drive or decreased CO2 responsiveness accounts for the hypoventilation observed in patients during acute ventilatory failure from myasthenia gravis or Guillain-Barré syndrome. DESIGN: Prospective, consecutive case series evaluating trials of ventilatory muscle performance, ventilatory drive, and CO2 response in patients during recovery from ventilatory failure until they were weaned from mechanical ventilation. SETTING: Neurosciences critical care unit in a university hospital. PATIENTS: Seven intubated, mechanically ventilated patients with myasthenia gravis or Guillain-Barré syndrome. INTERVENTIONS: Patients repeatedly performed mechanically unsupported, spontaneous breathing trials to the limits of endurance. After spontaneous breathing trials, patients underwent CO2 rebreathing studies. MEASUREMENTS AND MAIN RESULTS: Seventy-three breathing trials were performed in three patients with Guillain-Barré syndrome and four patients with myasthenia gravis. Patients were unable to sustain spontaneous ventilation in 55 trials averaging 27 +/- 5 mins. In these trials, significant increases occurred in mean end-tidal CO2 (41 +/- 1 to 44 +/- 1 torr [5.6 +/- 0.1 to 6.0 +/- 0.1 kPa]) and respiratory rate (31 +/- 1 to 35 +/- 1 breaths/min, p < .01). Ventilatory drive (as measured by airway occlusion pressure for 100 msecs) increased significantly p < .01 from 3.7 +/- 0.3 to 4.9 +/- 0.3 cm H2O. The response of airway occlusion pressure to CO2 rebreathing after these trials was 0.33 +/- 0.07 cm H2O/sec/mm Hg, while the minute ventilation response to CO2 rebreathing was only 0.30 +/- 0.06 L/min/mm Hg. CONCLUSIONS: These results suggest that ventilatory drive increases during acute hypoventilation, and the ventilatory drive response to CO2 remains intact, even when the minute ventilation response to CO2 is poor. Therefore, a decrease in ventilatory drive or CO2 response is unlikely to account for hypoventilation during ventilatory failure in patients with myasthenia gravis or Guillain-Barré syndrome.
Acute Disease↗
Neurocritical care for coma, intracranial pressure, head injury, and neoplasia.
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Brain Damage, Chronic↗
Orthonormal (Fourier and Walsh) models of time-varying evoked potentials in neurological injury.
Estimation of time-varying changes in evoked potentials (EP's) has important applications, such as monitoring high-risk neurosurgical procedures. We test the hypothesis that injury related changes in EP signals may be modeled by orthonormal basis functions. We evaluate two models of time-varying EP signals: the Fourier series model (FSM) and the Walsh function model (WFM). We estimate the Fourier and Walsh coefficients with the aid of an adaptive least-mean-squares technique. Results from computer simulations illustrate how selection of model order and of the adaptation rate of the estimator affect the signal-to-noise ratio (SNR). The FSM results in a somewhat higher steady-state SNR than does the WFM; however, the WFM is less computationally complex than is the FSM. We apply these two orthonormal functions to evaluate transient response to hypoxic hypoxia in anesthetized cats. Trends of the first five frequencies (Fourier) and sequencies (Walsh) show that the lower frequencies and sequencies may be sensitive indicators of hypoxic neurological injury.
Adaptation, Physiological↗
Multiresolution wavelet analysis of evoked potentials.
Neurological injury, such as from cerebral hypoxia, appears to cause complex changes in the shape of evoked potential (EP) signals. To characterize such changes we analyze EP signals with the aid of scaling functions called wavelets. In particular, we consider multiresolution wavelets that are a family of orthonormal functions. In the time domain, the multiresolution wavelets analyze EP signals at coarse or successively greater levels of temporal detail. In the frequency domain, the multiresolution wavelets resolve the EP signal into independent spectral bands. In an experimental demonstration of the method, somatosensory EP signals recorded during cerebral hypoxia in anesthetized cats are analyzed. Results obtained by multiresolution wavelet analysis are compared with conventional time-domain analysis and Fourier series expansions of the same signals. Multiresolution wavelet analysis appears to be a different, sensitive way to analyze EP signal features and to follow the EP signal trends in neurologic injury. Two characteristics appear to be of diagnostic value: the detail component of the MRW displays an early and a more rapid decline in response to hypoxic injury while the coarse component displays an earlier recovery upon reoxygenation.
Algorithms↗