Jean-Pierre Ya red, MD

• Director, Critical Care Medicine in the Heart and Vascular Institute
• Cleveland Clinic Foundation
• Cleveland, Ohio

It is believed to exert its effect by stabilizing abnormal hyperexcitability in these neurons diabetes diet brown rice discount glucotrol xl 10 mg with amex. There is evidence that participants taking gabapentin experience a variety of adverse events more frequently than those taking placebo diabetes insipidus diuretics order 10mg glucotrol xl fast delivery. They have been shown to exert direct effects on neuropathic pain as well as treat frequently encountered comorbid psychiatric conditions including depression and anxiety diabetes diet supplements generic 10mg glucotrol xl amex. There are a wide range of agents within this class of drugs and selection is often empiric diabetes insipidus coma generic 10 mg glucotrol xl fast delivery. Amitriptyline diabetes type 1 zinc buy glucotrol xl in india, a tricyclic antidepressant diabetes definition ada 2010 cheap glucotrol xl 10 mg on line, is the prototypical antidepressant agent used to treat chronic pain. Low doses of the medication (10 to 25 mg) are started orally at bedtime as it can cause sedation and may help with concurrent sleep disturbance. Side effects include sedation, orthostatic hypotension, dry mouth, blurred vision, and urinary retention. Duloxetine, a serotonin and norepinephrine reuptake inhibitor, is a newer class of antidepressant medication used to treat major depression as well as chronic pain. Duloxetine has also been effective in treating pain and fatigue associated with other pain conditions such as fibromyalgia. Opioids are occasionally added short-term if additional pain control is needed to facilitate fuller participation in functional therapies. The rationale is that they produce vasodilatory effects, improving blood flow to the affected area. Side effects may include increase in pain symptoms, arterial hypotension, myocardial depression, and cold intolerance. Clonidine, a centrally acting a2-agonist, can also be used in cases with suspected inappropriate sympathetic activity. It works by inhibiting norepinephrine release from peripheral presynaptic adrenergic terminals, leading to decreases in hyperalgesia in the areas directly below the patch. Side effects more prominently associated with systemic clonidine include sedation, arterial hypotension, and bradycardia. If the sympathetic block is helpful, meaning the patient experiences a subjective improvement in pain relief extending longer than the duration of the local anesthetic or has an objective improvement in function of the affected limb, the injections can be repeated at 1- to 2-week intervals. A successful stellate ganglion block is evidenced by an increase in temperature in the affected extremity (1 to 1. Other potential complications include respiratory distress secondary to phrenic nerve block, inadvertent vertebral artery injection with seizures, inadvertent epidural or intrathecal injection of local anesthetic resulting in high spinal, osteitis of transverse process or soft tissue infection, pneumothorax, and brachial plexus dysfunction. A lumbar sympathetic block is performed by targeting the sympathetic ganglia supplying the legs. Potential complications include pain or infection at the injection site, epidural or intrathecal injection of local anesthetic, intravascular injection, and trauma to adjacent structures including the kidney and bowel. This theory proposes that second-order neurons at the level of the dorsal horn act as a "gate" through which noxious stimuli from the periphery must pass in order to reach the higher centers of pain perception in the brain. However, if these same nerve fibers simultaneously receive a non-noxious stimulus, this can serve to "close the gate. The spinal cord stimulator lead is placed directly into the epidural space during a trial. During the trial, the stimulator is activated in order to achieve coverage over the painful body region. If it is successful, the patient can then proceed to implantation of a permanent spinal cord stimulator. Surgical sympathectomy is a procedure that has been used to treat multiple conditions with sympathetically mediated pain for many years. With medical advancements, these procedures can be done endoscopically or via percutaneous neurolysis with radiofrequency or chemical destruction (alcohol or phenol). Review of available literature revealed a high failure rate (up to 35%), which was attributed to poor patient selection. Other suggested causes of procedure failure include incorrect diagnosis, inadequate resection, reinnervation, and contralateral innervations. In addition to initial failure, there is also concern for postsympathectomy neuralgia, which can occur 6 months to 2 years after the initial ablation procedure. There should be an understanding that with any physical exercise there may be some increase in pain symptoms. The therapy should be directed at gradual increases in strength and flexibility of the affected limb. Some experts have also advocated the use of massage to facilitate lymphatic drainage and improve edema. At this 606 time, this is not a strong evidence to suggest that there is an advantage to lymphatic drainage techniques. Desensitization therapy is a graded approach to helping a patient overcome associated allodynia and hyperesthesia. In this therapy, the affected limb is incrementally exposed to a wide range of sensations including light touch with soft and coarse fabrics and temperature changes achieved by submerging the limb in cool and warm water baths. The goal of the therapy is to retrain the hyperactive nerves in the affected area to begin interpreting and transmitting sensory input in a normalized fashion. In the setting of chronic pain, comorbid conditions such as depression, anxiety, suicidal ideation, and opioid dependence are commonly present. Finally, additional psychiatric diagnoses that may be present should be identified and treated accordingly. Initially, this was based on a series of case reports from the 1970s giving the perception that children may have a milder course of the disease or that they respond more favorably to conservative therapy. They are especially helpful in identifying other psychiatric diagnoses or external stressors. Some of these therapies have already been studied and advocated by other countries around the world. The rationale for this therapy is based on the understanding that there may be episodes of ischemia followed by reperfusion and increased free radical damage to tissues and nerves. Others have also advocated the use of oral Vitamin C and Nacetyl-cysteine for the same purpose. Potential side effects include sympathetic stimulation, increased secretion production, and psychiatric manifestations including disturbing dreams and hallucinations. The rationale for this therapy is based on studies demonstrating upregulation of tetrodotoxin-resistant sodium channels on primary nociceptive afferent fibers and small dorsal root ganglia pain transmission neurons following peripheral nerve injury. The pain reduction lasted an average of 3 months and was particularly effective for thermal and mechanical allodynia. Careful monitoring for local anesthetic toxicity is necessary, as faster infusion rates and a duration of treatment longer than 5 days have resulted in dizziness, dysphoria, and hypotension. Diagnosis based on the Budapest Criteria relies upon clinical findings including sensory (allodynia, hyperalgesia), vasomotor, sudomotor, and trophic changes. The differential diagnosis may include vascular disorders, inflammatory disorders, infection, trauma, and surgery. Imaging such as X-rays and triple-phase bone scan as well as sympathetic testing, nerve testing, and thermal testing can be used to support the diagnosis. Meta-analysis of imaging techniques for the diagnosis of complex regional pain syndrome, type I. Reduction of allodynia in patients with complex regional pain syndrome: a double-blind placebo-controlled trial of topical ketamine. Complex regional pain syndrome, a prototype of a novel kind of autoimmune disease. Comparison of prednisolone with piroxicam in complex regional pain syndrome following stroke: a randomized controlled trial. Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systemic reviews (Review). Clinical and physiologic evaluation of stellate ganglion blockade for complex regional pain syndrome type I. Imaging in early posttraumatic complex regional pain syndrome: a comparison of diagnostic methods. Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo-controlled study. Efficacy of 5-day continuous lidocaine infusion for the treatment of refractory complex regional pain syndrome. Short- and long-term outcomes of children with complex regional pain syndrome type I treated with exercise therapy. Quality of life in adults with childhood-onset of complex regional pain syndrome type I. Sensitivity and specificity of 3-phase bone scintigraphy in the diagnosis of complex regional pain syndrome of the upper extremity. Brain tumors are the second most frequent cause of cancer-related death among children. Brain tumors may affect adults at any age, and often have a devastating effect on patients and their families. This review will summarize the current clinical approaches to the most common primary brain tumors. For most if not all brain tumors the therapeutic strategies are in a state of evolution, and there are more than a few uncertainties and controversies. The past several years have seen an explosion of new knowledge of the molecular genetics and basic biology of brain tumors. Although the clinical progress seems painfully slow, these new discoveries are gradually being translated into more precise disease stratification, into targets for new therapies, and into "personalized" tumor therapy. There is a predilection for infiltrating tumor to extend across the corpus callosum or to spread along other major white matter pathways. The variable topography and distance of tumor cell infiltration are serious obstacles to attempts at surgical resection or other "focal" therapies for these tumors. Several modern techniques facilitate the aggressive resection of gliomas and reduce the risk of neurologic morbidity for selected patients. For patients with symptomatic tumor mass effect, aggressive surgery usually improves neurologic function. Most (not all) retrospective studies show a survival advantage for patients who undergo an "aggressive" resection. The cutoff value of how much of the enhancing tumor needs to be resected to impact survival ranges from 75% to almost 100% in various studies. In studies where multivariate analysis showed the extent of resection to be an independent prognostic factor, the impact on survival was nearly always less than that for patient age, tumor histology, and pretreatment performance status. For selected patients with relatively young age, good performance status, and accessible lesions, a second surgical resection may improve neurologic function, and modestly prolongs survival. In addition to its antiangiogenic and antitumor effect, bevacizumab is a potent inhibitor of vascular permeability and cerebral edema. Immunotherapy trials include autologous dendritic cell vaccination, immunologic "checkpoint inhibitors," and active immunization with mutant epidermal growth factor receptor protein. Several viruses including poliovirus have been genetically modified to selectively attack tumor cells rather than normal neurons. The concepts and strategies for treating glioma-associated seizures are the same as those for treating localization-related epilepsy in general. There is no definite evidence that any particular antiepileptic drug is differentially effective for glioma-related seizures versus epilepsy caused by other structural brain lesions. For patients taking dexamethasone or receiving chemotherapy agents metabolized by the liver, the non-enzyme-inducing antiepileptic drugs. For patients who do not have seizures at initial presentation, there is no definite evidence to support long-term prophylactic antiepileptic medication. These are useful as predictors of individual patient outcome and are critically important in designing and interpreting clinical trials. Patients with anaplastic astrocytoma have a median survival of 3 to 4 years, and for those with anaplastic oligodendroglioma 4 to 6 years. Median survival is inversely proportional to age throughout all decades of adult life; older patients have a worse prognosis. Patients with a better performance status at the time of diagnosis have a better survival outlook than patients who present with severe neurologic impairment. The molecular genetic profile of grade 3 (and grade 2) gliomas has a major impact on patient outcome and is becoming an integral part of tumor classification. P53 mutation and chromosome 1p/19q codeletion are almost always mutually exclusive. Low-grade astrocytomas are poorly circumscribed and are characterized by diffuse infiltration of atypical astrocytes with hyperchromatic nuclei. Immunocytochemical staining for the intermediate filament glial fibrillary acidic protein is a marker for astroglial derivation. The classic histologic features of oligodendrogliomas are tumor cells with uniform round nuclei and clear perinuclear halos ("fried-egg appearance"), with a "chicken wire" network of branching capillaries. Mixed oligoastrocytomas contain some tumor cells with astrocytic morphology and other cells with oligodendrocytic morphology. Gadolinium enhancement is present in 10% to 30% of cases, and if present is usually faint and patchy. Infiltration of tumor cells nearly always extends beyond the margins of radiographically visible tumor.

A clinical magnetic resonance imaging study of the traumatised spinal cord more than 20 years following injury diabetes and your kidneys symptoms effective 10 mg glucotrol xl. Prognostic significance of magnetic resonance imaging in the acute phase of cervical spine injury diabetes vitamins supplements discount glucotrol xl 10 mg with visa. The radiation risk should be considered in young patients and patients likely to require numerous studies diabetic diet for weight loss buy glucotrol xl in united states online. Increased diffusion is seen in areas with fewer cells or increased extracellular water diabetes health magazine discount glucotrol xl 10 mg online, and restricted diffusion is seen in areas with tightly packed or swollen cells diabetes health prevention strategy discount 10mg glucotrol xl with amex. Mass Effect diabetic diet 500 calories buy glucotrol xl 10mg low cost, Shift, and Herniation Intracranial lesions can lead to brain herniation as a result of lesion growth, vasogenic edema, or obstructive hydrocephalus. Subfalcine herniation occurs when the medial surface of a hemisphere is pushed under the falx. Later stages show deviation of the falx, structures crossing the midline, and ischemia from compression of the anterior cerebral artery. Transalar herniation occurs when brain tissue is pushed above (ascending) or below (descending) the ridge of the greater sphenoid wing, which may lead to ischemia from compression of the middle cerebral artery. Ascending transtentorial herniation often causes symmetric effacement of the brainstem cisterns, compression of the cerebral aqueduct, and acute hydrocephalus. Tonsillar herniation through the foramen magnum can result in brainstem compression. Larger contusions may contain petechial microhemorrhages and appear as ill-defined heterogeneous lesions with little or no mass effect. As edema and mass effect increase in the first 48 hours, lesions become more evident. Except for location, the imaging characteristics of nonhemorrhagic contusions and shear injuries are similar. When subtle, a subarachnoid hemorrhage can be mistaken for generalized edema, with loss of the basal cisterns and cortical sulci. Axialcomputedtomographyimage(A)demonstratesalargeareaof acute hemorrhage (H) in right temporal lobe. AxialT1-(A)andT2-weighted (B) magnetic resonance imaging scans of an infant reveal bilateral subdural blood collections of different ages. Right collection shows bloodinthelatesubacutephase(2-4weeksold),andleftshowsblood in the chronic phase (>1 month). In the subacute stage (second to third weeks), the edema and mass effect gradually resolve. Chronic infarcts demonstrate parenchymal replacement and contraction, with sharply marginated zones of cystic encephalomalacia and gliosis. Subtle findings include stagnation of blood flow (arterial enhancement) and swelling of the involved gyri. Magnetic resonance imaging demonstrates an area of cytotoxic edema involving distal left middlecerebralarteryterritory. Axial T1-weighted image before (A) and after (B) contrast administration reveal subtle low-intensity and arterial enhancement (arrow) in right insular cortex. The brain of a term infant has its greatest myelination and metabolic activity in the brainstem, basal ganglia, cerebellum, and perirolandic cortex. From 10% to 30% of patients with aneurysmal subarachnoid hemorrhage will develop a delayed ischemic neurologic deficit from vasospasm. B, Right internal carotid artery angiogram demonstrates presence of congenital anterior communicating artery aneurysm (arrow),aswellasvasospasm(curved arrows). C, Internal carotid artery angiogram demonstrates arteriovenous malformation being fed by middle cerebralartery. A, Axial magnetic resonance imaging scan shows volume of tissue (box) selectedforspectroscopy. Meningiomas, nerve sheath tumors, and other benign tumors account for most lesions in this space. Excluding disk disease, the most common extradural pathology is metastatic disease. Most white matter diseases are slowly progressive, but acute presentations occur with toxic and vascular insults. A disk herniation with cord compression can change management from nonsurgical to surgical or change the surgical approach. Plain radiographs can show the "moth-eaten" outline of diffuse vertebral body cortical destruction. Vertebral collapse is more likely caused by neoplasia than degenerative disease when there is unilateral bone destruction, irregular or angular distortion of the vertebral endplates, involvement of the upper thoracic spine, a soft tissue mass, or pedicle destruction. Skip lesions and associated large paraspinal abscesses suggest mycobacterial infection. Nuclear medicine studies may help identify chronic spondylitis or surgical hardware infection. Epidural abscess surrounding and compressing cord is also identified(curved arrow). Sagittal T1-weighted (A) and T2-weighted (B) magnetic resonance imaging scans of spine show metastatic lesions (arrows) as low intensity on T1-weighted image, replacingnormalbrightmarrow. Hypointense lesions on T2-weighted image (in contrast to more typical hyperintensity) reflect posttreatment appearance. Edematous changes within cord secondary to compression(asterisk)arealsoidentified. SagittalT1-weighted (A) and T2-weighted (B) magnetic resonance imaging scans demonstrate compression fracture of L5. Compare signal characteristics of remaining bony elements and pedicles with signal of normal bony structures. Computed tomography alone for cervical spine clearance in the unreliable patient-are we there yet Are cervical spine radiograph examinations useful in patients with low clinical suspicion of cervical spine fracture Diffusion-perfusion mismatch: an opportunity for improvement in cortical function. Magnetic resonance spectroscopy of the brain: review of metabolites and clinical applications. Corticospinal tract injury in patients with diffuse axonal injury: a diffusion tensor imaging study. Brain single photon emission computed tomography: technological aspects and clinical applications. Neurologic complications of cerebral angiography: prospective analysis of 2,899 procedures and review of the literature. Complications of cerebral angiography: a prospective analysis of 2,924 consecutive procedures. Perfusion computed tomography in a dural arteriovenous fistula presenting with focal signs: vascular congestion as a cause of reversible neurologic dysfunction. Acute isodense intracerebral haematoma due to coagulopathy associated with prostate cancer. Hemorrhagic shearing lesions in children and adolescents with posttraumatic diffuse axonal injury: improved detection and initial results. Susceptibility-weighted imaging and proton magnetic resonance spectroscopy in assessment of outcome after pediatric traumatic brain injury. Significance of computed tomography mixed density in traumatic extra-axial hemorrhage. Magnetic resonance imaging versus computed tomography for detection of acute vascular lesions in patients presenting with stroke symptoms. Feasibility and safety of magnetic resonance imagingbased thrombolysis in patients with stroke on awakening: initial single-centre experience. Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. Cranial computed tomographic findings in a large group of children with drowning: diagnostic, prognostic, and forensic implications. The use of clinical and routine imaging data to differentiate between aneurysmal and nonaneurysmal subarachnoid hemorrhage prior to angiography. Radiographic assessment of vasospasm after aneurysmal subarachnoid hemorrhage: the physiological perspective. Radiologic assessment of brain arteriovenous malformations: what clinicians need to know. Distinguishing glioma recurrence from treatment effect after radiochemotherapy and immunotherapy. Diffusion-weighted imaging abnormalities in Wernicke encephalopathy: reversible cytotoxic edema Current and future applications of magnetic resonance imaging and spectroscopy of the brain in hepatic encephalopathy. Nuclear medicine methods for evaluation of skeletal infection among other diagnostic modalities. Jorens, and Nino Stocchetti ppropriate neurocritical care is fundamental to the success of neurosurgical interventions involving the brain and spinal cord. Great technical advances in operative procedures have made lesions previously considered inoperable now treatable, and advances in anesthesia have led to an increased number of operative procedures in both elderly and critically ill patients. Consequently, the number of patients requiring postoperative intensive care has increased. Successful care of the neurosurgical patient requires close collaboration between various specialists: neurosurgeons, anesthetists, intensivists, and neuroradiologists. The results of a technically perfect operation can be ruined by inadequate postoperative care, while a complex operative procedure requires expert intensive care to correct abnormalities in homeostatic mechanisms, ensure adequate cerebral perfusion and oxygenation, and promote recovery of brain function. Anticipation and early response prior to the full-blown development of complications are hallmarks of good neurocritical care. For example, when serum sodium levels are decreasing, correction should be implemented before hyponatremia develops, as hyponatremia may lead to increased brain edema. The best care for neurosurgical patients can be provided by dedicated specialists with knowledge of both fields and a large amount of experience in treating such patients. The benefit of concentration of care in hospitals and units with sufficient case volume has been well established in different fields of intensive care medicine, including trauma,1 neonatology, and specifically neurointensive care. In some centers, all patients who have undergone intracranial procedures are admitted for a 24-hour observation period following surgery; this is motivated by the observation that some patients, although fully alert and neurologically intact initially, may subsequently develop complications necessitating prompt intervention. The institution of high-care units, sometimes termed "step-down units", may permit more efficient use of scarce intensive care resources, while at the same time affording sufficient guarantees for adequate postoperative monitoring. Here again, however, care should be provided by personnel well experienced in the care of such patients, thus permitting early detection of possible deterioration and prevention of secondary complications. Consequently, priorities are to ensure adequate monitoring facilities, which may in the sedated and ventilated patient require further invasive monitoring of the intracranial system, and to ensure adequate oxygenation and perfusion of the brain. Systemic complications and second insults may initiate or aggravate cerebral damage. Aggressive treatment aimed at preventing and limiting second insults is of paramount importance. The main second insults, along with their causes and adverse effects on brain homeostasis and function, are summarized in Table 59-2. In such situations, treatment of hypertension is contraindicated, as this may exacerbate cerebral ischemia. In other situations, however, arterial hypertension may aggravate the occurrence of cerebral edema and/or increase the risk of intracranial bleeding. The clinical dilemma is to balance the desire of limiting edema formation and the risk of postoperative hemorrhage with the goal of maintaining adequate perfusion. Knowledge of the operative findings and close interaction with the surgeon are of paramount importance. In the absence of beta-blocking agents, hypotension in combination with bradycardia is strongly suggestive of damage to the spinal cord. The extent of left ventricular dysfunction is variable, but it may lead to cardiac failure and pulmonary edema. Neurogenic Pulmonary Edema the development of neurogenic pulmonary edema has been described early in the postoperative period after a variety of neurosurgical procedures, including brain tumors (particularly those resected in the posterior fossa), cysts, hydrocephalus, intracranial hemorrhages, and brainstem lesions. Supplemental oxygen is uniformly required, and tracheal intubation with mechanical ventilation and the application of positive endexpiratory pressure have been reported in about 75% of patients. The proposed underlying mechanisms include the release of tissue factor, hyperfibrinolysis, and, more specifically in trauma patients, hypoperfusion (with triggering of the protein C pathway) and the development of disseminated intravascular coagulation. Intuitively, mechanical therapies carry less associated risk, but pharmacologic approaches are more effective in preventing thrombotic complications. Various studies have indeed shown a higher incidence of postoperative hemorrhagic complications,41 but not all are clinically relevant. However, opinions differ, and careful estimation of the balance of benefits versus risk should be sought, informed by objective assessments of coagulation status. Any decision regarding the use of thrombosis prophylaxis must weigh efficacy against harm from the proposed intervention. In addition, early mobilization in the postoperative phase, whenever possible, is recommended. More consensus exists concerning routine administration of anticoagulant therapy in patients with spinal cord injuries. If the superficial temporal artery is damaged during the operation, ligation is preferred over coagulation. The occurrence of subgaleal hematomas can be minimized by routine use of postoperative wound drainage for 24 hours. Reoperation for subgaleal hematomas is seldom necessary unless there is a communication with the intracranial compartment with secondary compression of the brain. After every supratentorial procedure, some blood may accumulate in the epidural space.

The blood glucose level at which cerebral metabolism fails and symptoms develop varies among individuals diabetes 3 symptoms buy glucotrol xl 10 mg with visa, but in general diabetes mellitus without complication glucotrol xl 10 mg on-line, confusion occurs at levels <30 mg/dL and a coma at <10 mg/dL diabetes test limits order glucotrol xl on line. The brain stores about 2 g of glucose and glycogen diabetes symptoms metformin generic 10mg glucotrol xl with amex, so a patient in a hypoglycemic coma may survive 90 minutes without suffering irreversible brain damage diabetes type 1 job restrictions buy glucotrol xl 10mg with amex. Rather than such an internal catabolic death diabetes mellitus name origin purchase glucotrol xl with paypal, evidence suggests that neurons are killed by external factors. The toxins first disrupt the dendritic trees, sparing the intermediate axons, an indication of excitotoxic neuronal injury. The exact mechanism of excitotoxic neuronal necrosis may involve hyperexcitation and culminates in the rupture of the cell membrane. The pathophysiology of other metabolic encephalopathies is less well established and is discussed elsewhere. Altered neurotransmission may play a role in the accumulation of benzodiazepine-like substances, the imbalance of serotonergic and glutaminergic neurotransmission, and the accumulation of false neurotransmitters. The identity of the neurotoxins involved in uremic encephalopathy is uncertain and includes urea itself, guanidine and related compounds, phenols, aromatic hydroxyacids, amines, various peptide "middle molecules," myoinositol, parathormone, and amino acid imbalance. The cause of the disequilibrium syndrome may entail more than osmotic water shifts. The pathogenesis of pancreatic encephalopathy may involve demyelination of brain white matter due to liberated enzymes from a damaged pancreas, disseminated intravascular coagulation, or fat embolism. The mechanism of action of exogenous toxins or drugs depends partially on both the structure and the dose. It should also be determined that none of the sedatives taken acutely produces permanent damage to the nervous system, making prompt diagnosis and effective treatment essential. Differentiation of such states from a true coma has important diagnostic, therapeutic, and prognostic implications. Moreover, a coma is not a permanent state; patients who survive an initial coma may evolve through and into these altered behavioral states. All patients who survive beyond the stage of acute systemic complications reawaken and either proceed to recovery (with none or varying degrees of disability) or remain in a vegetative state. The vegetative state can be defined as wakefulness without awareness and is the consequence of various diffuse brain insults. Vegetative patients appear to be awake and to have cyclical sleep patterns; however, they do not exhibit evidence of cognitive function or learned behavioral responses to external stimuli. They may exhibit spontaneous eye opening, eye movements, and stereotypic facial and limb movements but are unable to demonstrate speech or comprehension and lack purposeful activity. They generate a normal body temperature and usually have functional cardiovascular, respiratory, and digestive systems but are doubly incontinent. The vegetative state should be termed persistent at 1 month after injury and permanent at 3 months after nontraumatic injury or 12 months after traumatic injury. In the locked-in syndrome, patients retain or regain arousability and self-awareness, but because of extensive bilateral paralysis. Such patients suffer bilateral ventral pontine lesions with quadriplegia, horizontal gaze palsies, and lower cranial nerve palsies. The most common etiology is pontine infarction due to basilar artery thrombosis, but others include pontine hemorrhage, central pontine myelinolysis, and mass brainstem lesions. Neuromuscular causes of the locked-in syndrome include severe acute inflammatory demyelinating polyradiculoneuropathies, myasthenia, botulism, and neuromuscular blocking agents. Akinetic mutism describes a rare subacute or chronic state of altered behavior, in which a patient who appears alert is both silent and immobile but not paralyzed. The patient usually lies with eyes opened and retains cycles of self-sustained arousal, giving the appearance of vigilance. One pattern consists of bilateral damage to the frontal lobe or limbic-cortical integration with relative sparing of the motor pathways, and vulnerable areas involve both basal and medial frontal areas. Similar behavior can also follow incomplete lesions of the deep gray matter (paramedian reticular formation of the posterior diencephalon and adjacent midbrain), but such patients usually suffer double hemiplegia and act slowly yet are not completely akinetic or noncommunicative. This behavioral disturbance is characterized by stupor or excitement and variable mutism, posturing, rigidity, grimacing, and catalepsy. It can be caused by a variety of illnesses, both psychiatric (affective more than psychotic) disorders, as well as structural or metabolic diseases. Psychiatric catatonia may be difficult to distinguish from organic disease because patients often appear lethargic or stuporous rather than totally unresponsive. Patients in a catatonic stupor do not move spontaneously and appear unresponsive to the environment despite what appears to be a normal level of arousal and consciousness. This impression is supported by a normal neurologic exam and the subsequent recall of most events that took place during the unresponsive period. Patients usually lie with their eyes opened, may not blink in response to visual threats, but one can usually elicit optokinetic responses. The pupils are semidilated and reactive to light, the oculocephalic reflexes are absent, and vestibuloocular testing evokes normal nystagmus. Passive movement of the limbs meets with waxy flexibility, and catalepsy is seen in 30% of patients. Urgent steps are required to prevent or minimize permanent brain damage from reversible causes, often before the cause of the coma is established. Serial examinations are needed with accurate documentation, to determine a change in state of the patient. The clinical approach to an unconscious patient logically entails the following steps: (1) emergency treatment; (2) history. Emergency Management the initial assessment must focus on the vital signs to determine the appropriate resuscitation measures; the diagnostic process begins later. Urgent, and sometimes empiric, therapy must be administered to avoid additional brain insult. The threshold for intubation should be low in the comatose patient, even if the respiratory function is sufficient for proper ventilation and oxygenation: the level of consciousness may deteriorate, and breathing may decompensate suddenly and unexpectedly. While preparing for intubation, maximal oxygenation can be ensured by suctioning the upper airway and manually ventilating with oxygen using a mask and bag. If cervical spine injury is a possibility or has not been excluded, intubation should be performed by the most skilled practitioner available, with cervical spine precautions. A brief neurologic examination is performed before sedation required for intubation. The key points of the rapid neurologic exam are hand drop from over the head (to assess for malingering or hysterical loss of consciousness); pupillary size and response to light; abnormal eye movements. Neuromuscular blockade required for patient management and care should be deferred if possible until the neurologic examination is completed (3-5 minutes). Signs of arousal or inadequate sedation include dilated reactive pupils, copious tears, diaphoresis, tachycardia, systemic hypertension, and increased pulmonary artery pressure. Evaluate respiratory excursions: Arterial blood gas measurement is the only certain method to determine adequate ventilation and oxygenation. Pulse oximetry is useful, however, because it provides immediate, continuous information regarding arterial oxygen saturation. The comatose patient ideally should maintain a Pao2 > 100 mm Hg and a Paco2 between 34 and 37 mm Hg. Hyperventilation (Paco2 < 35 mm Hg) should be avoided unless herniation is suspected. Unless contraindicated, place a nasogastric tube to facilitate gastric lavage and prevent regurgitation. Appropriate resuscitation fluid is normal saline and a mean arterial pressure around 100 mm Hg is adequate and safe for most patients. While obtaining venous access, collect blood samples for anticipated tests (Box 48-1). For most situations, the systolic blood pressure should not be treated unless it is >160 mm Hg. Empiric glucose treatment will prevent hypoglycemic brain damage and outweighs the theoretical risks of additional harm to the brain in hyperglycemic, hyperosmolar, or anoxic coma. Thiamine (100 mg) must be administered with the glucose infusion to prevent precipitation of Wernicke encephalopathy in malnourished, thiamine-depleted patients. Careful and mild sedation should be given to the agitated, hyperactive patient to prevent self-injury. Consider specific antidotes: Drug overdose is the largest single cause (30%) of coma in the emergency room. However, certain antagonists specifically reverse the effects of coma-producing drugs. The reversal of narcotic effect, however, may precipitate acute withdrawal in an opiate addict. In a suspected opiate coma, the minimum amount of naloxone should be given to establish the diagnosis by pupillary dilatation and to reverse respiratory depression and coma. General Physical Examination A systematic, detailed examination is helpful and necessary in the approach to the comatose patient, who is in no condition to describe prior or current medical problems. Nuchal rigidity may disappear in deeply comatose patients with meningeal infection/inflammation. The clinical neurologic functions that provide the most useful information in making a categorical diagnosis are outlined in Box 48-3. Once the cause of coma can be assigned to one of these categories, specific radiographic, electrophysiologic, or chemical laboratory studies can be used to make a disease-specific diagnosis and detect existing or potential complications. Only full awakening is characteristic of an anticholinergic drug overdose, as physostigmine has nonspecific arousal properties. Physostigmine has a short duration of action (45-60 minutes), and doses may need to be repeated. Adjust body temperature: hyperthermia is dangerous because it increases the brain metabolic demand and, at extreme levels, denatures brain proteins. Hyperthermia most often indicates an infection but may be due to intracranial hemorrhage, anticholinergic drug intoxication, or heat exposure. Hypothermia accompanies profound sepsis, sedative-hypnotic drug overdose, drowning, hypoglycemia, or Wernicke encephalopathy. Specific Management Supratentorial Mass Lesions If the cause of the coma is a presumed supratentorial mass, the severity and rate of evolution of signs should be determined. The priority in a deep coma or established/ threatening transtentorial herniation is to apply a medical treatment for intracranial hypertension successfully. This is usually achieved by adjusting the ventilation rate to 10 to 16/min and tidal volume to 12 to 14 mL/kg. The scan will reveal the nature of the supratentorial lesion and associated mass effect. Intraparenchymal masses that acutely produce deep stupor or coma initially are best managed nonsurgically. Mannitol may be repeated if necessary every 4 to 6 hours and/or hypertonic saline can be used either as bolus or infusion; serum electrolytes and fluid balance must be monitored. Infratentorial Lesions the evolution of neurologic symptoms and signs, as well as the neurologic exam, generally give sufficient information to localize the lesion to the posterior fossa; the lesions themselves may be intrinsic or extrinsic to the brainstem. Patients in a stupor or showing signs of progressive brainstem compression from a cerebellar hemorrhage or infarction require urgent evacuation. Intrinsic brainstem lesions are best treated conservatively; an incomplete stroke may benefit from thrombolysis and/or heparin anticoagulation. Placement of a ventricular catheter for acute hydrocephalus must be considered cautiously and in consultation with a neurosurgeon; the danger exists of potentially fatal upward transtentorial herniation. Metabolic and toxicologic studies must be performed on the first blood that is drawn (see Box 48-1). Treatable conditions that quickly, irreversibly damage the brain include the following. Prolonged hypoglycemic coma that has considerably damaged the brain will not be reversed by a glucose load; a glucose bolus may transiently worsen hyperglycemic hyperosmolar coma. The hyperventilating comatose patient with acute severe metabolic acidosis and threatening cardiovascular collapse requires emergency treatment. Simultaneously, a search for and specific treatment of the cause must be conducted. Carbon monoxide poisoning requires hyperoxygenation with 100% oxygen to facilitate the excretion of this toxin. Transfusion of packed red blood cells is appropriate for severe anemia (hematocrit < 25%). A lumbar puncture must be considered in any unconscious patient with fever and/or signs of meningeal irritation. Appropriate antibiotic treatment can usually await the results of spinal fluid Gram stain. If the Gram stain is negative, yet a bacterial etiology is suspected, empiric broad-spectrum antibiotic treatment with a third-generation cephalosporin and vancomycin is appropriate. Certain general principles apply to all patients suspected of having ingested sedatives. Once vital signs are stable, attempts should be made to remove, neutralize, or reverse the effects of the drug.

For example diabetes month discount 10mg glucotrol xl, children may survive protracted episodes of hypoxemia and hypotension that would be lethal in adults blood glucose log generic glucotrol xl 10 mg visa. Resistance of the immature myocardium to asphyxia does not preclude the development of cerebral damage from hypoxemia juvenile diabetes medications buy glucotrol xl online pills, because between 25% and 56% of children who suffer asphyxia without cardiac arrest have poor neurologic outcomes diabetes diet organic generic glucotrol xl 10mg without prescription. Similarly diabetes low blood sugar symptoms buy on line glucotrol xl, Myelination In humans diabetic diet juice cheap 10 mg glucotrol xl overnight delivery, considerable myelination occurs during postnatal life. At several periods in development, large numbers of excitatory amino acid receptors are produced, and these periods correlate temporally with increased synaptic plasticity. Although some of that chapter is germane to pediatric patients, the importance of asphyxia as the etiology in children mandates a separate discussion. Causes of arrest in the prehospital setting include trauma, sudden infant death syndrome, poisoning, and respiratory distress secondary to drowning, choking, severe asthma, or pneumonia. Nontraumatic arrest typically occurs as a consequence of hypoxemia and hypercarbia, leading to respiratory arrest, bradycardia, and ultimately asystole or pulseless electrical activity. Guidelines 2000 for Cardiopulmonary and Emergency Cardiovascular Care: International Consensus on Science. Patients presenting with isolated respiratory arrest have the highest rate of survival (~75%). Accurate prediction of poor outcome can enable withdrawal of support and decrease the possibility that children are rescued to survival but in a neurologically devastated state. Predictors of poor outcome should be applied with caution to children suffering cardiopulmonary arrest caused by drug overdose or hypothermic exposure (ice-cold water drowning), in which good outcomes have been reported in some cases after even prolonged durations of arrest. Treatment the optimal treatment of pediatric cardiopulmonary arrest is prevention. A recent large study in adults also showed that continuous compressions did not lead to higher survival or better outcomes than did the use of chest compressions with interruption for ventilation. Only one hand is used to deliver chest compressions to children younger than age 8 years. When only one rescuer is present, two fingers from one hand are used to provide chest compressions, and the other hand is used to maintain the head-tilt. Providing adequate ventilation is especially important for children, because most pediatric arrests are secondary to airway compromise. In contrast, adults frequently suffer from cardiac causes of arrest and require intensified efforts at providing chest compressions and early defibrillation. Thus, the recommended ratio of chest compressions to ventilations for young children is 5: 1, compared with a ratio of 15: 2 for older children and adults. Although ventricular fibrillation and ventricular tachycardia are uncommon in children, survival with this rhythm is high (about 30%), so cardiac rhythm should be ascertained as early as possible. Furthermore, the short length of the trachea combined with patient movement during transport and patient care can easily result in displacement of the tracheal tube. Although no single confirmation technique is 100% reliable in all circumstances, some effort of secondary confirmation of tube placement can be helpful. The rationale is that hypoxia often causes or contributes to the development of cardiac arrest, and an oxygen debt accumulates during cardiac arrest. However, there is increasing awareness that oxygen might contribute to reperfusion injury, and thus prolonged delivery of unnecessarily high concentrations of oxygen should be avoided. Therefore, hyperventilation should be reserved for patients with signs of cerebral herniation syndrome or suspected pulmonary hypertension. It is also prudent to guard against inadvertent hyperventilation during patient transport. Fortunately, intraosseous access can be achieved within 30 to 60 seconds and provides a route for drug and fluid administration when intravascular access cannot be readily achieved. Optimal doses for drugs given via the tracheal tube are not established, but the recommended dose of epinephrine is 0. A bedside glucose measurement should be obtained, and if hypoglycemia is present, it should be treated with 0. There is experimental evidence that hyperglycemia and hypoglycemia exacerbate ischemic injury. The most commonly used drugs in pediatric resuscitation are epinephrine, atropine, and sodium bicarbonate (Table 60-1). Magnesium and calcium are reserved for specific indications such as torsades de pointes, hypocalcemia, and calcium channel blockade. Amiodarone (5 mg/kg infused over 20 to 60 min) is also an option for ventricular tachycardia with a pulse but should be used with extreme caution because of the risk for profound hypotension. However, subsequent clinical data in adults have not consistently yielded positive results, and pediatric data are limited to small case series. It is best reserved for patients with reversible conditions or as a bridge to cardiac transplantation. Post-resuscitative Care Temperature control is a priority for patients who remain comatose after cardiac arrest. Children resuscitated from cardiac arrest often develop mild hypothermia followed by delayed fever. The practice of inducing hypothermia in normothermic children is more controversial. Clinical trials of induced hypothermia for neonatal asphyxia have been remarkably positive,102-104 and important data in newborns with asphyxia indicate that even one degree of hyperthermia after the insult is associated with neurologic morbidity. Hypotension and hypoxia should be avoided during this period to prevent development of a secondary brain injury. As previously mentioned, the optimal regimen of oxygen and pressor therapy is not known and requires further study. Miscellaneous Most pediatric victims of cardiopulmonary arrest will not be successfully resuscitated. The difficulty of accepting this reality often results in prolonged attempts at resuscitation. Surveys indicate that most family members would like to be present during resuscitation attempts of a loved one109-112; presence during resuscitation can help family members adjust to the death. Refractory status epilepticus is defined as failure of two first-line antiepileptic medications to treat this condition for greater than 60 minutes. Infants younger than 1 year of age have the highest incidence at 150 cases/100,000 per year. A child with idiopathic or cryptogenic status epilepticus has no prior history of seizures and no known risk factors. Atypical febrile status epilepticus occurs during fever in children with no prior history of seizures without fever. In these children, status epilepticus can occur without provocation, sometimes even years after the initial insult. Finally some children have status epilepticus resulting from progressive encephalopathy, including neurodegenerative diseases, malignancies, and neurocutaneous syndromes (Box 60-1). In children younger than 2 years of age, acute symptomatic status epilepticus from meningitis and encephalitis accounted for 51% of cases, whereas remote symptomatic status epilepticus in children with a prior diagnosis of epilepsy was seen in 16% of children. Older children were more likely than younger children to have a history of epilepsy. Infants are at great risk for morbidity because the etiology in this group is commonly acute symptomatic status epilepticus. Neurologic sequelae of status epilepticus include epilepsy, recurrence, mental retardation, and motor disorders. However, many of the morbidities can be attributed to the underlying disease and not status epilepticus per se. Risk of recurrence in the category of idiopathic status epilepticus is less than 5%. In contrast, recurrence of status epilepticus in children in the acute symptomatic groups can be as high as 60%. Convulsive seizures either begin as generalized seizures or progress from partial seizures. Included under the subheading of nonconvulsive seizures are complex and simple partial and absence seizures. History of present and past illness may be useful in determining the cause of status epilepticus and in choosing therapy, but obtaining the history should not delay resuscitation. Prevention of hypoxemia and hypotension, which exacerbate neuronal injury, is important. The airway should be kept open with simple maneuvers and 100% oxygen applied with a nonrebreathing mask. Ventilation efforts are assessed clinically or by arterial blood gas determinations. If the patient is unable to maintain adequate oxygenation or ventilation, tracheal intubation using a rapid sequence technique is indicated. Serum electrolyte levels, renal and liver function tests, and anticonvulsant levels should be assessed. First-line antiepileptic drugs for pediatric status epilepticus include benzodiazepines, phenytoin or fosphenytoin, and phenobarbital. The optimal first-line treatment of status epilepticus in children is controversial. Lorazepam produced less respiratory failure requiring intubation than diazepam in retrospective127 and prospective studies. Support for selection of lorazepam over diazepam was also shown in a recent Cochrane review. Fosphenytoin has the advantage of having a faster infusion rate, shorter onset of action, and fewer cardiovascular side effects than phenytoin but is more expensive. Phenobarbital is also a very effective anticonvulsant, but it is often not the first choice in the treatment of status epilepticus because of its side effects of respiratory depression and cardiovascular disorders, especially when used in combination with benzodiazepines. Infants metabolize phenobarbital more rapidly than older children and often require higher doses adjusted for body weight. Nevertheless, the pharmacokinetics of phenobarbital are more predictable than those of phenytoin in infants. Otherwise, the type of neuroimaging used in infants and children with status epilepticus should be individualized, depending on history and physical findings. Most commonly, pentobarbital is used as a continuous infusion to treat refractory status epilepticus. There are differing opinions on when to begin to wean therapy, but it is generally recommended that about 12 hours of seizure cessation be attained before weaning the infusion. A midazolam infusion has also been shown to be effective in refractory status epilepticus in some children (0. There is an 84% incidence of an acute systemic illness and a 30% incidence of dehydration reported in infants and children with cerebral sinovenous thrombosis. Infants typically present with seizures and lethargy, whereas older children may present with acute focal neurologic deficits or diffuse symptoms (headache, lethargy, or seizures). Because of the impact of making a specific vascular diagnosis on the management strategy, angiography is often recommended in children with idiopathic stroke. In pediatric and neonatal stroke, extracerebral risk factors contribute to about 75% of cases, but the spectrum of risk factors differs from those seen in adults. DeVeber133 grouped the most common risk factors for childhood ischemic stroke into vascular, intravascular, and embolic categories (Box 60-2). The most common vascular risk factor has been reported to be transient cerebral arteriopathy. Echocardiography is thus essential in the diagnostic workup for stroke in children. Treatment In the acute setting, antithrombotic therapy has been increasingly used in the therapy for pediatric stroke. Strater and colleagues140 compared treatment with low-molecular-weight heparin versus aspirin in 135 children with stroke across a variety of causes (including idiopathic, cardiac, vascular, and infectious) and found no difference in efficacy or safety when used to prevent stroke recurrence. In endocarditis, anticoagulation is not recommended because of the risk of rupture of occult mycotic aneurysms. Thrombolytic therapy has been subjected to very limited study in children, although cases describing the use of tissue plasminogen activator and cerebral balloon angioplasty in acute stroke in children with dramatic results are being reported. This includes numerous successful clinical trials as compared with thrombolytic therapy. Although these studies are beyond the scope of this chapter, they are reviewed by Campbell et al. Several clot retrieval systems are available including the Solitaire, Merci, and Revive. This is a promising approach, but at this juncture it can only be suggested that there may be a role for clot retrieval in children in selected patients managed by a highly experienced team. The management of systemic hypertension in the setting of pediatric stroke can be complicated by the variety of underlying disorders. In adults with thrombotic or hemorrhagic stroke and systemic hypertension, it is generally recommended that mean arterial blood pressure not be aggressively reduced below 130 mm Hg. Anecdotal reports of successful treatment with a variety of therapies including mild hypothermia and decompressive craniectomy have been reported. In children, normal saline or 5% dextrose in normal saline should be used in the initial 24 hours, carefully monitoring blood glucose concentration, followed by the addition of dextrose or initiation of hyperalimentation after 24 hours. In infants, either 5% or 10% dextrose in normal saline should be used, with insulin titrated to treat hyperglycemia. A glucose value of 200 mg/dL is a reasonable threshold in the absence of clear-cut evidence. Bacterial cell wall lipopolysaccharides of gram-negative bacteria and pneumococcal cell wall components stimulate a marked inflammatory response, with local production of tumor necrosis factor alpha, interleukin-1, prostaglandin E, and other mediators, leading to neutrophil infiltration, increased vascular permeability, and thrombosis. Inflammation of spinal nerves and roots produces meningeal signs, and inflammation of the cranial nerves produces optic, oculomotor, facial, and auditory neuropathies.

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