By N. Armon. Bennett College.

Air Entry Effective tidal volume is assessed by chest expansion and auscultation of breath sounds generic 5 mg finasteride. Stridor indicates upper (extra thoracic) airway obstruction and may be because of the tongue discount finasteride 1 mg amex, laryngomalacia buy 5 mg finasteride visa, vocal cord paralysis 5 mg finasteride with mastercard, hemangioma, tumor, cysts, infection, edema, or aspiration of a foreign body. Wheezing indicates intrathoracic obstruction due to conditions such as bronchiolitis, asthma, pulmonary edema, or an intrathoracic foreign body. Circulatory Status Circulation is assessed to find out if the cardiac output meets the tissue demands. Shock is defined as circulatory dysfunction in which there is inadequate delivery of oxygen and substrates to meet the metabolic demands of tissues. Heart rate changes alone may be too early a sign of derangement and are often nonspecific. By the time hypotension develops it may be very late and the shock is classified as decompensated shock. Heart Rate Tachycardia is a common response to a variety of stresses including shock. One must be aware that a bounding pulse does not necessarily denote good perfusion. The loss of central pulse is a premorbid sign and is to be treated as cardiac arrest. Temperature: When the ambient temperature is warm, the extremities should be warm. Assessment of the temperature of the trunk and the extremities should be done simultaneously as cooling occurs from the periphery to the center. Color: Color of the skin reflects skin perfusion and indirectly respiratory and circulatory status. Skin of palm and fingers may be pink (normal), pale, cyanosed, mottled or ashen grey depending on the degree of compromise. The extremity being tested should be raised above the level of the heart to make sure that only venous refill is not being tested. Brain: Brain perfusion can be assessed by features already described in appearance, i. Renal: Urine output may not be useful in initial assessment in a critically ill child, but is useful in monitoring the child and in evaluation of renal perfusion. Blood pressure: Shock can be present with normal, increased or decreased blood pressure. Progression to irreversible/refractory shock or multiple organ failure or death rapidly follows. Lower limit (5th percentile) of blood pressure is: Newborn 60 mm Hg systolic Up to 1 year 70 mm Hg systolic 2 to 10 years 70 + (2 × age in years) mm Hg Beyond 10 years 90 mm Hg systolic Pulse Oximetry Oxygen saturation assessment is an important adjunct to identify oxygenation state in an acutely ill child. Based on the appearance, breathing and circulatory status, the physiologic status of a critically ill child is classified as: 1. Cardiorespiratory failure is characterized by agonal respirations, bradycardia and cyanosis. Based on this physiologic status the severity of the compromise is classified and the child is managed further accordingly. For example; if a fluid bolus has been given then assess the child for any improvement as indicated by improved capillary refill, stronger pulses, improved urine output and a lower heart rate. Stabilization Depending on the physiologic status of the child, the following stabilization measures can be undertaken. Airway It should be assessed whether the airway is maintainable or unmaintainable. If the airway is unmaintainable, nasopharyngeal or oropharyngeal airway or intubation is required. The patency of the airway is to be assessed and excessive secretions should be cleared. Breathing Hundred percent oxygen should be provided to any critically ill child irrespective of the physiologic status. If the child has Respiratory Distress the child is kept with the caregiver, is allowed to maintain a position of comfort, and oxygen is provided in a non-threatening manner. Turbulent airflow leads to increased airway resistance; hence the child should be kept calm. In case of inadequate chest expansion or respiratory arrest, bag and mask ventilation should be given with 100 % oxygen. Tracheostomy or cricothyrotomy may be required in cases of complete upper airway obstruction caused by diphtheria, severe orofacial injuries or laryngeal fractures. Circulation Once airway and breathing have been stabilized, vascular access is to be secured. Any drug can be infused using this route provided it is followed by a flush of fluid to get the drug in the central circulation. Blood products should be administered only when specifically indicated for replacement o f blood loss or for replacement of components. When the circulation does not improve with fluid boluses alone, inotropes are used. During stabilization the priority is to address the Airway first followed by Breathing and Circulation. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular Care: Part 10: Pediatric advanced life support. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Cerebral resuscitation after traumatic brain injury and cardiopulmonary arrest in infants and children in the new millennium. Critical illness causes alteration of physiologic status and biochemical parameters. The relationship between physiologic status and mortality risk may change as new treatment protocols, therapeutic interventions and monitoring strategies are introduced. Contribution of each variable and its ranges to mortality prediction were evaluated and the system was derived. The physiologic variables and their ranges were re-evaluated, eliminating some ranges that did not contribute significantly to mortality risk. A formal, operational method for assessing mental status is also included to account for frequent use of sedation and paralysis. The likely reasons for this could be difference in patient profile and greater load of severity of illness managed with lesser resources, both physical and human and also difference in quality of care. But there is no clear-cut threshold that directly predicts mortality and categorization of patients into different levels of risk is not possible. Score Probability of death (%) 5 9 10 15 15 23 20 35 25 49 30 63 35 75 How to Use the Score? This information is useful for optimum interventions and treatment to improve the outcome of critical illness. Tissue oxygenation is determined by the formula: O2 delivered = O2 carrying capacity of blood × cardiac output = ( Hb in gm × 1. In adults, the stroke volume can increase significantly while in the pediatric age group there are minimal stroke volume reserves and increased heart rate compensates maximally. If the demands increase beyond the compensatory mechanisms (decompensation), tissue oxygenation is jeopardized and anaerobic metabolism ensues with generation of lactate–the cascade of metabolic acidosis–negative inotropism–circulatory maldistribution is stimulated and ends up in multi-organ failure. In a stressful condition this failure cascade can be prevented or at least delayed, by timely oxygen supplementation. Oxygen is a life saving drug; and being a medication it carries a recommended dose. Overuse of oxygen can lead to serious longstanding side effects; so while using it, exact indications need to be defined and it should be used judiciously. Adequate tissue oxygen supply is the end result of adequate ventilation through the upper airways, lower airways and lung parenchyma; optimum perfusion across alveolar and capillary membrane, proper flow of blood across heart and pulmonary vasculature, uninterrupted systematic distribution of blood by cardiovascular system to all tissues and adequate oxygen carrying capacity of blood. Commonly the terms hypoxia and hypoxemia are used interchangeably but there is a theoretical difference where hypoxia indicates tissue under-oxygenation, while hypoxemia indicates decreased oxygen content of blood. A patient may be hypoxic but not hypoxemic as in severe septic shock and vice versa as in hemodynamically stable cyanotic heart disease.

Up to this point most of the interventions can be performed in a peripheral setting purchase finasteride online. Both nitroprusside and nitroglycerin lower systemic vascular resistence in children and are useful afterload reducing agents finasteride 1 mg otc. Close monitoring and volume augmentation are frequently required when vasodilators are used to decrease pulmonary vascular resistance generic 5 mg finasteride overnight delivery. Amrinone and milrinone are newer inotropic agents with properties of afterload reduction and myocardial diastolic relaxation(lusotropic effect) safe 5mg finasteride. Cold shock with normal blood pressure: • 1° goals: Titrate epinephrine, ScvO2 > 70%, Hgb > 10 g/dL • 2° goals: Add vasodilator (Nitrosovasodilators, milrinone, imrinone and others) with volume loading, consider levosimendan 60 Minutes Cold shock with low blood pressure: • 1° goals: Titrate epinephrine, ScvO2 > 70%, Hgb > 10 g/dL • 2° goals: Add norepinephrine Add dobutamine if ScvO2 > 70%, Consider milrinone, enoximone or levosimendan Vasopressin In severe warm shock with hypotension resistant to noradrenaline,vasopressin may be tried. Vasopressin therapy should be considered in warm shock unresponsive to fluid and norepinephrine. Vasopressin does not use catecholamine receptors, and its efficacy is therefore not affected by ongoing alpha-adrenergic receptor down-regulation. Additionally, V1 receptors are found in the kidney, myometrium, bladder, adipocytes, hepatocytes, ≤ platelets, spleen, and testis. V1-receptor activation mediates vasoconstriction by receptor-coupled activation of phospholipase. Blood flow within the coronaries, as well as the cerebral, pulmonary, and renal vascular beds, is preserved, promoting shunting to those areas. This regional vasodilation is likely the result of a complex interplay of vasopressin activity at V1 and endothelial V3 and oxytocin receptor sites producing an increase in nitric oxide release. In addition to these direct effects, vasopressin may also enhance or restore catecholamine sensitivity. Synthetic vasopressin (8-arginine vasopressin) acts at the same receptor sites as endogenous vasopressin, producing an identical physiologic response. Nitric oxide inhibitors and methylene blue are considered investigational therapies. It is not currently recommended for treatment of cardiogenic shock, hence it should not be used without ScvO2/cardiac output monitoring. Because vasopressin is destroyed by gastric trypsin, it must be administered parenterally. Vasopressin is rapidly degraded by enzymes in the liver and kidneys, with elimination half- life of approximately 10 to 35 minutes. For continuous intravenous infusion, it should be diluted with normal saline or 5% dextrose to a final concentration of 0. Administration through central venous access is recommended to minimize the risk of extravasation. Studies of vasopressin in adults with vasodilatory shock have used infusion rates of 0. It has been suggested that vasopressin infusions may be tapered over a 2 to 3 hour period, once blood pressure and the doses of concomitant catecholamine infusions are stabilized. Vasopressin has been shown to increase mean arterial pressure, systemic vascular resistance, and urine output in patients with vasodilatory septic shock and hyporesponsiveness to catecholamines. When employing measurements to assist in identifying acceptable cardiac output in children with systemic arterial hypoxemia such as cyanotic congenital heart disease or severe pulmonary disease, arterial-venous oxygen content difference is a better marker than mixed venous hemoglobin saturation with oxygen. As noted above, blood pressure by itself is not a reliable endpoint for resuscitation. Early fluid resuscitation based on weight with 40-60 mL/kg or higher may be needed. Decreased cardiac output and increased systemic vascular resistance tends to be most common hemodynamic profile. Pediatric recommendations include greater use of physical examination therapeutic endpoints. Issue of high-dose steroids for therapy of septic shock remains unsettled, although recommendation include use of steroids for catecholamine unresponsive shock in presence of a suspected or proven adrenal insufficiency. Goldstein B, Giroir B, Randolph A, et al; and the Members of the International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics* Pediatr Crit Care Med 2005;6:2-8. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Task Force Committee Members: Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock. Comparison of the three fluid solutions for resuscitation in dengue shock N Engl J Med 2005;353(9):877-89. Maitland K, Pamba A, English M, Peshu N, Marsh K, Newton C, Levin M Randomized trial of volume expansion with albumin or saline in children with severe malaria:preliminary evidence of albumin benefit. Early reversal of pediatric- neonatal septic shock by community physicians is associated with improved outcome. Acute management of dengue shock syndrome: A randomized double- blind comparison of 4 intravenous fluid regimens in the first hour. Reduction in case fatality rate from meningococcal disease associated with improved healthcare delivery. Mortality rates in pediatric septic shock with and without multiple organ failure. Aggressive management of dengue shock syndrome may decrease mortality rate: A suggested protocol. Acute management of dengue shock syndrome: A randomized double- blind comparison of 4 intravenous fluid regimens in the first hour. Pharmacokinetics and pharmacodynamics of milrinone lactate in pediatric patients with septic shock. Amrinone in pediatric refractory septic shock: An open-label pharmaco- dynamic study. Low serum cortisol in combination with high adrenocorticotrophic hormone concentrations are associated with poor outcome in children with severe meningococcal disease. Admission cortisol and adrenocorticotrophic hormone levels in children with meningococcal disease: Evidence of adrenal insufficiency? Hemodynamic and metabolic effects of low dose vasopressin infusion in vasodilatory Septic shock. The cloned vasopressin V1a receptor stimulates phospholipase A2, phospholipase C, and phospholipase D through activation of receptor-operated calcium channels. The human V3 pituitary vasopressin receptor: Ligand binding profile and density-dependent signaling pathways. Experience with phenylephrine as a component of pharmacologic support of septic shock. The effects of norepinephrine on hemodynamics and renal function in severe septic shock. Multi-center, randomized, double blind, placebo-controlled, double bind study of nitric oxide inhibitor 546C88: effect on survival in patients with septic shock. Methylene blue revisited: Management of hypotension in a pediatric patient with bacterial endocarditis. Clinical validation of cardiac output measurement using femoral artery thermodilution with direct Fick in ventilated children and adults Intens Care Med 1997;23(9):987-91. Intravenous arginine-vasopressin in children with vasodilatory shock after cardiac surgery. Intractable hypotension in septic shock: Successful treatment with vasopressin in an infant. Matok I, Vard A, Efrati O, Rubinshtein M, Vishne T, Leibovitch L, Adam M, Barzilay Z, Paret G. Terlipressin as rescue therapy for intractable hypotension due to septic shock in children. Hemodynamic and metabolic effects of low-dose vasopressin infusions in vasodilatory septic shock. Use of vasopressin in refractory hypotension in children with vasodilatory shock: Five cases and a review of the literature.

Therefore purchase 5 mg finasteride, the disease is diagnosed by the excretion of Thymosin is the hormone secreted from thymus generic 1mg finasteride free shipping. At birth it weighs about 10 g generic finasteride 5mg without a prescription, which increases in size to about Other Local Hormones 30 g during adolescence generic 5mg finasteride otc. It converts by the reticular epithelial cells of thymus (for details, angiotensinogen to angiotensin I, which is further con­ refer Chapter 18). Hence, thymus has the central position in the deve­ Erythropoietin is the glycoprotein hormone containing lopment of cellular immunity. For details of T cell 165 amino acids secreted mainly from interstitial cells development, refer ‘Immunity’. Though local hormones act locally in the tissue where they are produced, some of them have systemic effects. Female Reproductive System: Functional Anatomy, Oogenesis and Follicular Development 69. Ovarian Hormones and Control of Ovarian Functions Part D: Physiology of Conception, Pregnancy, Lactation and Contraception 71. Physiology of Contraception “To live, to love are signs of infinite things, Love is glory from eternity’s spheres. Abased, disfigured, mocked by baser mights That steal his name and shape and ecstasy, He is still the Godhead by which all can change. Describe the mechanism of sex differentiation and development in males and females. List the abnormalities of sex differentiation and understand the physiological basis of their causation. Apply the knowledge of sex determination and differentiation in understanding the physiology of reproductive system. Reproduction serves a primary goal of the nature in preservation and perpetuation of the species. The crea- tion of two sexually complete and different individuals in same species, known as sexual dimorphism is the cen- tral scheme of the nature to achieve its principal inten- tion of continuation of species through reproduction. Therefore, to appre- ciate the physiology of reproduction one should study the process of sex differentiation, development of gonads, gonadal functions, physiology of puberty and sexual mat- uration, the principles of functioning of the female and Fig. Sex Determination Sex Chromosomes Normal Chromosomal Pattern Gender is determined by the genetic inheritance of two In a normal human being, there are 46 (23 pairs) chromo- chromosomes, called sex chromosomes. The two sex somes: 22 pairs are autosomes and one pair is sex chro- chromosomes are the X chromosome, the larger one, and mosome (Fig. Females possess two X chromosomes and males have In Males one X and one Y chromosome. Hence, ideally, This is a relatively easy method to demonstrate sex chro- births of male and female children should have been matin (Barr body) in leucocytes or mucosal cells of the in equal proportion. When two X chromosomes are present, one X chromo- Y chromosomes are lighter than the sperm that con- some is functional and other X chromosome which is tain X chromosome as Y chromosome is smaller in size nonfunctional condenses to form sex chromatin. Thus, presence of Barr body generally indicates female mosomes swim faster in female genital tract and reach sex. Thus, the opportunity for these chromo- somes to fertilize ovum is more than the sperm with X Sex Differentiation chromosomes. The process of sex differentiation includes the pattern of Genetic Male development of the gonads, genital ducts, and the exter- nal genitalia. The differentiation of gender starts from sixth week of intrauterine life and continues even after birth till the When a sperm containing X chromosome fertilizes an complete maturation of the gonad of either gender is ovum, the resultant zygote develops into a genetic female achieved. Sex Determination Cell Lines of Development: Following fertilization, two Karyotyping different cell lines develop in the indifferent gonad. The one cell line forms the granulosa cells of the ovar- nique used for determining sex chromosome composition ian follicle and the Sertoli cells of the testicular semi- by employing tissue culture visualization of all chromo- niferous tubules. The differences in shape and size of chromosomes germ cells and promote their maturation, and finally in males and females help in concrete determination of guide their development into the genital duct system. Hence, instead of male gonads ovaries develop when both the sex chromosomes are X. Gonadal Sex Male Gonadal Sex In a normal genetic male, the seminiferous tubule starts to form at 6–7 weeks of gestation. The other cell line of the indifferent gonad (the inter- In a normal genetic female, the differentiation of indif- stitial cells) forms theca cells in the ovary and Leydig ferent gonad into the female gonads (ovaries) starts after cells in the testis. Both the X chromosomes in the germ cells are acti- characteristics and spermatogenesis. The germ cells then undergo divisions to form oogonia that continue to proliferate. Immediately after the start of meiosis, oogonia are Gonadal Sex and Phenotypic Sex surrounded by granulosa cells. The presence of Y chromosomes deter- prophase of meiosis for many years until ovulation mines the maleness of the individual, without which nei- ther testis nor the male genital pattern develop. Estrogen secreted from the granulosa cells help in the mining region of the Y) which is located on the distal female development. These are glycopro- system develops, and in the absence of any hormonal tein antigens present on the surface of all male cells. Both these antigens are involved in rejection of male the development of brain is also linked to the phenotypic tissue by the female recipients. Virilization of the genital duct and external genitalia ducts develop which gives rise to epididymis, vas defer- requires the presence of an androgen hormone recep- ens, seminal vesicles, and ejaculatory ducts. Therefore, X chromosomal gene ance of Leydig cells in the testis that secrete testoster- also contributes to the development of maleness. Note, in male, Müllerian duct degenerates, and in female, Wolffian duct degenerates. Chapter 65: Sex Diferentiation and Development, Puberty and Menopause 581 Flowchart 65. Wolffian ducts on each side, the Müllerian ducts arise, which develops into fallopian tubes and uterus. This differentiation is com- genitalia in the early part of life, which is influenced by exposures to androgens. It is proposed that the pattern of hypothalamic control of pleted by 18–20 weeks of gestation. The concentration then declines gradually to a low level the common chromosomal abnormalities are Turner’s during puberty and a lower concentration of about syndrome, Klinefelter’s syndrome, testicular feminization 2–5 ng/mL is maintained through rest of life. Note the small breast, webbed neck and short stature in a female with this syndrome; (B) Klinefelter syndrome. Thus, the syndrome usually presents with primary hypogonadism and infertility in male. It is characterized by diminished sexual development, dwarfism, and webbing of the neck in patients with no Superfemales gonadal tissue or rudimentary gonads (Fig. It results from nondisjunction of one of the X chromo- analysis for some other causes. At puberty though breasts develop normally, the growth of pubic and Klinefelter’s Syndrome axillary hairs is scanty. Though the external genitalia are of female type, there the syndrome is otherwise called seminiferous tubule is no development of uterus. The gonads are testis, with immature seminiferous nine features in an apparent male with small testes tubules. The patient is genetically female, but the presence of Though testes are present, spermatogenesis does not an extra Y chromosome causes development of the occur. They have male genitalia and at puberty male charac- This is a rare condition in which both testes and ovaries teristics develop due to adequate testosterone. But, seminiferous tubules are not properly developed the testis on the opposite side. Male external genital development occurs in genetic females exposed to androgen during 8th to 13th week of gestation. Source of androgen is usually congenital virilizing adre- Though other chromosomal abnormalities are not com- nal hyperplasia of fetus or virilizing ovarian tumor of mon, they do occur. Sometimes it may be iatrogenically-induced following Transposition of a part of one chromosome to other chro- treatment of mother with androgens or progestational mosome is possible. In a typical female pseudohermaphrodite, the indivi- of their father’s Y chromosome into the father’s X chromo- dual possesses ovaries, oviducts, but there is varying some during meiosis. They receive X chromosome from their degrees of masculine differentiation of external geni- mother and transpositioned X chromosome from father. Nondisjunction of Chromosome Nondisjunction of chromosome 21 (an autosome) is not 2.

Fluoxetine is ofen said to have that in other depressive disorders; the drugs are rapidly efective at an ‘activating’ efect and may be useful in fatigued or lethargic low doses and are efective for anxiety order cheap finasteride on line, fears generic 5mg finasteride with amex, irritability generic 1 mg finasteride amex, insomnia safe finasteride 5 mg, patients, and those with psychomotor retardation. The drugs afected include amitriptyline, nortriptyline, increased anxiety, fu-like symptoms and electric shock-like sensa- doxepine, clomipramine, mianserin, nomifensine, bupropion and, tions. Tese can best be avoided by gradual dose reduction rath- to a lesser extent, citalopram and paroxetine. Sodium valproate is a broad-spectrum inhibitor of drug metabo- lism which has been associated with a 50–60% elevation in plasma amitriptyline and nortriptyline concentrations. Neither paroxetine and psychological therapy than to treatment with either modal- nor sertraline afects plasma concentrations of carbamazepine or ity alone. Tere are sever- during which patients’ unhelpful beliefs about themselves and the al reports of plasma phenytoin concentrations increasing to toxic world they interact with are explored. Evidence for interaction is ofen con- A 2008 Cochrane review of psychological treatments for epilepsy ficting, and dosage may need adjustment depending on levels. Pharmacodynamic interactions The following points relate to the pharmacodynamic efects of an- tidepressant medication as used in general psychiatric practice (i. While these fndings are not specif- Electroconvulsive therapy, transcranial ic to patients with epilepsy, the same general principles are felt to magnetic stimulation and vagal nerve apply. Gastrointestinal employed (albeit rarely) in patients with severe depression, treat- symptoms such as abdominal cramps, nausea and diarrhoea are ment-resistant mania and, on a very occasional basis, in psychosis. Hypertension should be examined for in patients tak- Transcranial magnetic stimulation was postulated as a treatment ing venlafaxine, particularly at higher doses, and this medication for epilepsy, but controlled studies have not found evidence of should be avoided in patients at risk of cardiac arrhythmia. A va- efectiveness in reducing seizures, although it has been shown to riety of sexual disturbances may occur and should be asked about, have a mild antidepressant efect [94]. Comedication ilepsy although its clinical utility in clinical practice remains to be with oxcarbazepine, carbamazepine or diuretics will exacerbate determined [95]. Despite this, some patients remain sy to cause prolonged or persisting hallucinatory states. The hallucinatory experiences and produce clinical benefts in patients with treatment-resistant ofen have religious content. Tey demonstrated a 12-month remission rate of 30% can be much more prolonged (occasionally continuing for months and response rate of 60%. Postictal psychosis The concept of postictal psychosis can be dated back to the work of Psychoses of epilepsy Jackson [103] on ‘temporary mental disorders afer epileptic parox- Both psychotic symptoms and syndromes have been the subject of ysms’. Despite this, and the fact that it is the most frequent psychotic considerable research over the past century. Much of this has been condition seen in patients with epilepsy, it did not become the focus carried out by psychiatrists, whose approach has been to examine of attention until recently [104,105]. Tere continues to be no uni- these phenomena empirically through the lens of descriptive psy- versally agreed defnition, although that used by Kanemoto et al. Researchers from the feld of Common fndings among the diferent case series include (i) de- neurology have taken a more biological approach by attempting to lay between the onset of psychiatric symptoms and the time of last map specifc hallucinatory symptoms as well as more difuse psy- seizure; (ii) relatively short duration of psychosis; (iii) afect-laden chotic states to their underlying electrophysiological cause. What has emerged from this body of research is that secondary generalized tonic–clonic seizures preceding the onset of while it is clear that patients with epilepsy can experience a range of postictal psychosis; (vi) the onset of postictal psychosis afer a long primary or ‘functional’ mental disorders in the absence of epileptic duration of epilepsy (for a mean period of more than 10 years); and activity, it is also the case that a variety of hallucinated or frankly (vii) a prompt response to low-dose antipsychotics or benzodiaze- psychotic states are peculiar to patients with epilepsy and may be pines [107]. Up to 25% of patients with postictal psychosis may go caused by either ongoing epileptic activity (ictal psychosis), the ces- on to develop a chronic interictal psychosis [100]. Mood was markedly abnormal (elevat- patients (>65 years) presenting with delirium of any cause to the ed, depressed or both) in three-quarters, half had paranoid delu- emergency room. Delirium in these patients was initially attributed to another cause A further interesting point to raise is that it is likely that at least in over 80% of cases and led to increased length of stay and a higher some cases of apparently ‘postictal psychosis’ are not in fact ‘pos- mortality rate. Stevens [122] sums up what are still contemporary views: ‘It curring as an indirect afer-efect of seizure activity and, secondly, would be correct to say that nearly two thirds of all the adult ep- an atypical peri-ictal type, occurring as a direct manifestation of ileptics studied who were known to have had psychotic episodes limbic epileptic discharges (i. Finally, Pol- which required hospitalization also had a diagnosis of psychomotor lack et al. An interesting recent development of the bidirectional relationship ‘construct’ between epilepsy and psychopathology is the extension of this relationship to include psychosis. In analysis 1 they compared 5195 Defnition patients with schizophrenia with 20 776 controls without this disor- As Sachdev [114] has pointed out in his review on epileptic psycho- der. Analysis 2 compared 11 527 patients with epilepsy with 46 000 ses, most studies have lacked a precise defnition of either ‘psycho- controls. Defnitions for interictal psychosis need to exclude schizophrenia cohort than in the non-schizophrenia cohort with an peri-ictal psychosis, allow for the subcategories of drug-induced adjusted hazard ratio of 5. In analysis 2, the incidence of schizo- and the possibility of ‘alternative’ psychosis, and be present in the phrenia was higher in the epilepsy cohort than in the non-epilepsy absence of seizure discharges. Tey are not infrequent and can be comparison cohort with an adjusted hazard ratio of 7. The efect clinically more signifcant than the peri-ictal psychoses in terms of of schizophrenia on subsequent epilepsy was greater for women, severity and duration. Teir conclusion was Prevalence that there was a strong bidirectional relationship between the two Tere is a great deal of variance in prevalence estimates for psy- disorders and that the two conditions may share a common cause. During the Psychopathology in interictal psychosis: comparison follow-up period episodes remitted within a month in 11% and with schizophrenia lasted 6 months or more in 34. Several studies have not found signifcant difer- ‘the delusions and hallucinations of patients with the psychosis of ences 116], and more recent attempts to relate psychopathology to epilepsy are empathiseable’ (i. In one of the Other key features were said to be the absence of negative symp- largest population-based studies to date, Qin et al. Interictal manic while people with a history of epilepsy were two to three times more or bipolar presentations are considered rare. Notable exceptions likely to develop schizophrenia or schizophrenia-like psychosis include Flor-Henry’s [128] series, in which an afective psychosis than those without, there did not appear to be a diference accord- occurred in 40% of patients, and the prevalence rate of 70% for de- ing to the type of epilepsy. Tat said, there remains a strong clinical pressive psychosis reported by Fenton [129]. However, phrenia of epilepsy appears to conform to the usual schizophrenic this risk can be a particular issue for those who are seizure-free es- categories’ and Perez et al. This position Further problems associated with antipsychotic drug treatment would appear supported by the ‘bidirectional’ studies described in patients with epilepsy include (i) variation in the individually earlier. In cases where postictal psy- of haloperidol, chlorpromazine, clozapine, olanzapine, risperidone chosis is thought to be caused by ongoing limbic status epilepticus, and quetiapine. Tese interactions can be very marked (by up to acute therapy with benzodiazepines is usually advised, sometimes 50% on occasions) and clinically important. Valproate has few in- with additional antipsychotic therapy if the psychosis is forid. It is important to en- Postoperative psychiatric disorders sure that patients are nursed with the appropriate level of supervi- The literature on psychiatric disorder following surgery for med- sion in a contained environment and protected from causing harm ically intractable epilepsy is extensive and can be difcult to in- to themselves or others. In patients with a chronic interictal psychosis, antipsychotic For the interested reader a systematic review is provided by Cleary drug therapy is needed in most cases. What is clear is that epilepsy surgery can make existing antipsychotic drugs, such as risperidone, olanzapine, amisulpride, psychiatric disorder worse and trigger de novo psychopathology in sulpiride and quetiapine, in relatively low doses, are sufcient to those who had no previous psychiatric history. Despite this, a re- control symptoms, although on occasion combinations of antipsy- cent survey found that only 16% of adult epileptologists and 13% of chotic drugs (e. Re- starting doses, usual treatment dose and maximum doses as ob- cently published data from Queen Square [138] provide clinically served in routine psychiatric practice are outlined in Table 19. The key fndings are as follows: (in patients who previously had not had seizures) ranging from 1 Preoperatively, 29% (n = 81) had a current or past history of approximately 0. In one recent review, seizure incidence for the 2 Postoperatively, 105 (38%) patients experienced clinically sig- diferent atypical antipsychotics was given as 0. Another study found that a patients with preoperative psychiatric disorder continued to ex- set of all antipsychotics (olanzapine, quetiapine, clozapine, risperi- perience signifcant psychiatric symptoms during this time; 12% done, ziprasidone and aripiprazole) was not signifcantly associated required psychiatric hospitalisation and one patient committed with an increased risk of seizures afer the removal of both olan- suicide. The risk with clozapine 3 Patients with a preoperative psychiatric history had more than increased in a dose-dependent manner from 1. Pacia and Devinski [135], 4 For patients with both a preoperative and postoperative psychi- in a post-marketing study of more than 5000 patients on clozapine, atric disorder (n = 54), the most frequent postoperative psychi- showed a lower rate (1. Psychiatric Features of Epilepsy and their Management 269 Forty-nine per cent of cases presented within 6 months and in with no such history. Laterality 6 Patients with a preoperative psychiatric history had nearly or site of resection, histopathology and seizure outcome were not half the odds of achieving seizure freedom during the 4-year signifcantly correlated to pre- and/or post-surgical diagnoses of follow-up period whereas there was no relationship between de astheno-emotional disorder. In fact, the majority the prevalence of the astheno-emotional disorder was equivalent of de novo psychopathology occurred in the context of seizure to the preoperative rate [147,148]. In their prospective study of 72 consecutive patients who un- tres during 1996–2001.