Associate Professor, Director, Behavioral Medicine
Track Clinical Psychology Program, Department
of Psychology, Virginia Commonwealth University,
Richmond, VA, USA
Stretch the skin between the thumb and finger and insert the needle parallel with the surface about 3 mm into the superficial layers of the dermis anxiety lymph nodes buy discount prozac 10 mg online. The tip should remain visible through the skin anxiety research buy line prozac, and a raised blanched 3 mm bleb will appear if the injection has been given correctly depression symptoms holden caulfield order prozac discount. If no resistance is encountered depression definition and example discount prozac 40mg fast delivery, the tip is almost certainly too deep and needs to be repositioned depression economic definition cheap prozac online mastercard. Give the injection slowly and leave the injection site uncovered to facilitate healing depression fact sheet buy generic prozac 20mg online. Babies should become tuberculin positive within 6 weeks if vaccina tion was effective (routine testing to confirm this is not generally thought necessary) mood disorder powerpoint buy prozac 60 mg. Other problems: If the slow local reaction generally expected eventually turns into a discharg ing ulcer depression test goldberg cheap prozac online master card, this should be covered with a simple dry non-occlusive dressing (occlusive dressings can delay healing). For the management of anaphy laxis (an extremely rare occurrence), see the monograph on immunisation (q. Parents need to be approached in the antenatal period so that babies likely to benefit can be identified before birth and an agreement reached regarding the need for early vaccina tion. Early post-delivery discharge and the fragmentation of postnatal care have further dam aged the systems that used to exist for delivering and documenting such prophylaxis reliably in many Health Districts. Make a note of the batch number and the expiry date, as well as the date of administration. The peak extent of any induration induced (ignoring any associated erythema or redness) is documented to the nearest millimetre. Supplies are distributed within the United Kingdom by Farillon for the Department of Health. A Patient Group Direction cannot currently be used to authorise use because the products European marketing authorisation does not cover the United Kingdom. Performance of commercial blood tests for the diagnosis of latent tuberculosis infection in children and adolescents. Clinical management and diagnosis of tuberculosis, and measures for its prevention and control, 2011. Biochemistry Homocysteine is an intermediate in the breakdown of the amino acid methionine. Homocysteine has toxic effects on the brain (causing developmental delay, seizures and psychiatric disease) and predisposes to lens dislocation, thromboembolism, osteoporosis and marfanoid habitus. Betaine (N,N,N-trimethylglycine) is a small N-trimethylated amino acid that acts as a methyl group donor, allowing hepatic methyltransferases to convert homocysteine to the less toxic methionine. Classical homocystinuria: this autosomal recessive disorder results from cystathionine synthase deficiency. A few patients are detected by neonatal screening programmes, but most patients present with developmental delay, dislocated lenses, skeletal abnormalities or thromboembolic disease. Betaine lowers plasma and urine homocysteine concentrations and usually improves symptoms such as behaviour and seizures. Women with homocystinuria should continue with treatment during pregnancy to minimise the risk of thromboembolic disease and, possibly, the risk of fetal loss. Patients with these rare disorders can present in many different ways, including acute neonatal encephalopathy and developmental delay. Betaine is also used in defects of cobalamin metabolism if homocys tinuria persists despite pharmacological doses of vitamin B12 (q. The dose is then adjusted by monitoring the plasma homocysteine level, but doses in excess of 150 mg/kg/day seldom confer additional benefit. Monitoring Plasma methionine concentrations rise during treatment in classical homocystinuria, and mon itoring is recommended to ensure that potentially toxic levels (>1000 mol/l) do not develop. Clinicians need to be aware that acute cerebral oedema has (very rarely) been reported a few weeks after starting treatment. Supply A palatable strawberry-flavoured medicine is now available as a special from Special Products Ltd; 100 ml costs 40. Reconstitute the dry powder with 55 ml of purified water to obtain a liquid containing 50 mg/ml, and use within 28 days. It comes with three spoons allowing measurement of 1 g, 150 mg or 100 mg of powder. The required amount of powder is mixed with water, juice or milk (including formula milk) until completely dissolved and taken immediately. The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Long term treatment with betaine in methylenetetrahydrofolate reductase deficiency. See the website com mentary for a discussion of the relative merits of betamethasone and dexamethasone. Indications for antenatal use the seminal paper that first identified a strategy for preventing, rather than curing, surfactant deficiency was published >40years ago. The first clue came from the observation that experi mental lambs delivered prematurely failed to develop the respiratory problems seen in control animals if exposed to corticosteroids before delivery. It took 20 years for this strategy to gain general acceptance and, in the interim, a further 11 trials were mounted to replicate the original findings. Babies delivered <24 hours after prophylaxis is started derive only limited benefit, and it is now clear that benefit wanes after a week. Twins seem to benefit just as much as singleton babies, but because they were not separately identified in many trials, the available sample size is currently too small to establish this. Delaying further prophylaxis until delivery again seems immi nent can also work well (as long as delivery can then be delayed for at least 36 hours) as the Obstetrix trial showed in March 2009. No adverse late consequence of exposure to a single course of betamethasone could be detected when the children of the mothers recruited into the first trial in New Zealand were recontacted after 30 years. Women with hypertension and fetal growth retardation were excluded from many early trials, but we now know that these babies benefit too. Use (under prophylactic antibiotic cover) was also beneficial where there has been pre-labour rupture of membranes, but use in mothers with diabetes remains less well established, since treatment could affect diabetic control. Repetitive antenatal treatment slows fetal growth, but the effect was too small to be detectable at discharge in most trials and non-existent in the most recent trial. Oral treatment cannot be recommended on the basis of the only small trials conducted to date. While prophylaxis is of no proven benefit when delivery threatens before 24 weeks gestation, it should not be denied to those at risk of delivery at 23 weeks if requested. Repeat treatment: If delivery does not occur for 7 days and then again becomes likely in the next 7 days, consider giving another 12mg dose and try to delay delivery for 24 hours, since respiratory problems and their complications can be serious after delivery before 30 weeks gestation (and a reducible risk before 33 weeks). The only formulation routinely available in the United Kingdom is a 1ml ampoule containing 5. Impact of a rescue course of antenatal corticosteroids: a multicenter randomized placebo-controlled trial. Prenatal corticosteroid prophylaxis for women delivering at late preterm gestation. It is found in a wide range of foods including eggs, liver, kidneys and some vegetables. Biotin is a cofactor for four carboxylases: propionyl-CoA carboxylase, pyruvate carboxylase, 3-methylcrotonyl-CoA carboxylase and acetyl-CoA carboxylase. Holocarboxylase synthetase catalyses the covalent attach ment of biotin to these proteins. When carboxylases are degraded, biotin is liberated by the action of biotinidase and recycled. Pathology Deficiency of either holocarboxylase synthetase or biotinidase leads to multiple carboxylase deficiency. Holocarboxylase synthetase deficiency: these children present as neonates or infants with feeding problems, encephalopathy, metabolic acidosis and urinary organic acids compatible with the four carboxylase deficiencies. Mothers of patients are sometimes given 10 mg of biotin a day during any subsequent pregnancy, although it is not clear whether such prenatal treatment is actually necessary. Biotinidase deficiency: Children with this rare condition present in the first 2 years of life, usually with seizures or developmental delay. In both conditions, there is a good response to pharmacological doses of biotin, but if treatment is delayed, irreversible brain damage will often have occurred. Although screening at birth has not yet been initiated in the United Kingdom (as it has in some countries), it does have the potential to prevent most of these problems. It is not yet clear whether these children benefit from routine supplementation, but supplementation seems harmless enough in itself. There have been no convincing reports of benefit from biotin in patients with an isolated carboxylase deficiency. Treatment can usually be given by mouth, but a parenteral preparation is available. Supply the need for high-dose biotin treatment is so uncommon that there is no regular pharmaceutical preparation on the market. It is possible for hospital pharmacies to get 5mg tablets in packs of 30 (cost 19) and ampoules containing 5mg/ml (cost 6. A 5 mg/5 ml suspension of biotin is available from the Specials Laboratory with a 14-day expiry date. Clinical and neuropsychological outcome in 33 patients with biotinidase deficiency ascertained by nationwide newborn screening and family studies in Austria. Prenatal diagnosis of holocarboxylase synthetase deficiency by assay of the enzyme in chorionic villus material followed by prenatal treatment. Outcome in patients with profound biotinidase deficiency: relevance of newborn screening. Biotinidase deficiency: if you have to have an inherited metabolic disease, this is the one to have. Products Blood is not sterile, and viruses can be transmitted during transfusion, although the risk of cell associated virus transmission is now routinely minimised by prior leucodepletion. Malaria and other blood-borne parasites pose a significant risk in areas where these are endemic. Whole blood donations (~470ml) are collected into 63ml of citrate phosphate dextrose anti coagulant. Not only are these packs leucodepleted, but they also contain virtually no functional platelets. These packs can be stored for 5 weeks, but ideally, blood <7 days old should be supplied for neonatal use because the potassium and acid load are less and there will be fewer microaggregates. In addition, the oxygen-carrying capacity will be greater (the concentration of 2,3-diphosphoglycerate in the red cells falls with time). It is also irradiated if the baby is having, or has had, an intrauterine transfusion. If unmatched group O Rh D-negative blood ever needs to be used in an emergency, an attempt should be made to discuss this with a consul tant haematologist first. Symptomatic treatment with 1mg of chlorphenamine maleate intramuscularly (previously known as chlorpheniramine maleate) may be appropriate. Immediate signs include flushing, dyspnoea, fever, hypotension and oliguria, with haemoglobi naemia and haemoglobinuria. Stop the transfusion at once, take specimens for laboratory anal ysis, and watch for renal failure, hyperkalaemia and coagulopathy. Umbilical vein obstruction (as from a tight nuchal cord) can leave a baby hypovolaemic at birth. They are more reproducible, require less blood and provide an immediate sideward answer. Such differences can be minimised if free-flowing blood is collected from a warm, well-perfused heel. Indications for transfusion Symptomatic babies with a venous haematocrit of <40% at birth merit transfusion once a sample of blood has been collected from both the baby and the mother for diagnostic purposes. Watch for the hypovolaemic baby with a normal haematocrit immediately after birth; haematocrit values normally rise in the first 12 hours of life, but in such babies, there will be a fall. Acute loss is best managed by a prompt rapid transfusion, but chronic anaemia at birth is better managed by exchange transfusion. Since it is the fall in plasma volume rather than the fall in haemoglobin that poses the immediate threat after acute blood loss, 0. Up to 80% of preterm babies who weighed <1500g at birth will receive at least one blood transfusion during their neonatal career. Indications for transfusion in this group have largely been based on the haemoglobin concentration combined with the cardiorespiratory status of the baby. Multiple small transfusions from dif ferent donors are wasteful, and put the patient at increased risk. It is not usually necessary to calculate a specific replacement volume or give a covering diuretic. Terminal co-infusion into a line containing glucose is also safe and does not cause mea surable haemolysis, so it is better to do this than terminate the glucose infusion and precipitate reactive hypoglycaemia when it is not practicable to erect a separate intravenous line. Check the crossmatch particulars and the patients name, and record all the details in the case notes. Furosemide for packed red cell transfusion in preterm infants: a randomized controlled trial. Umbilical cord milking reduces the need for red cell transfusions and improves neonatal adaptation in infants born less than 29 weeks gestation: a randomised controlled trial. Minimal haemolysis in blood co-infused with amino acid and dextrose solutions in vitro. The safety and efficacy of red cell transfusions in neonates: a systematic review of randomized controlled trials. The first clinical trial of this type of drug in humans was published in 1995, and since then, endothelin-1 receptor antagonists have been tested in clinical trials involving heart failure, pulmonary arterial hypertension, resistant arterial hypertension, stroke and subarachnoid haemorrhage and various forms of cancer. Sporadic reports of use of bosentan to treat neonatal pulmonary hypertension, either with or without congenital heart disease, first appeared in 2008 when it was used in infants who were failing to respond to other, more widely used agents such as nitric oxide (q. To date, only one small randomised placebo-controlled trial has been undertaken using bosentan as an adjuvant therapy. Endothelin-1 is a 21-amino-acid protein that is one of the most potent vasoconstrictors in the pulmonary vasculature, and pulmonary hypertension is associated with an increased expression of endothelin-1 in vascular endothelial cells. The pharmacokinetic profile of bosentan in older children appears to be similar to that in adults, although pharmacokinetics in a neonatal population have yet to be studied. Fluid retention may be a sign of worsening pulmonary hypertension or a side effect of bosentan and requires a full cardiac assessment. Bosentan is contraindicated during pregnancy with reports of higher fetal demise and terato genic effects. Although the high protein binding should mean drug levels in milk are low, the potential for side effects is such that breastfeeding is contraindicated. Drug interactions Bosentan interacts with clarithromycin, fluconazole, rifampicin, sildenafil and warfarin. These may be split with a pill cutter and are stable for up to 4 weeks if stored in the original manufacturers bottle. The resulting suspension can be used to prepare an aliquot providing the correct dose. Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension.
Similarly depression gi symptoms order 40mg prozac with visa, long term cognitive outcome for patients with benign childhood epilepsy with cen trotemporal spikes (rolandic epilepsy) is thought to be good depression definition oxford cheap prozac 40 mg online, although mild neuropsychological dysfunction is found in childhood depression zoloft not working purchase prozac paypal. Thus anxiety lump in throat buy cheap prozac, cognitive dysfunction is often present across epilepsy syndromes anxiety 2 year old discount 10 mg prozac free shipping, but evidence for cognitive deteriation is limited to a subset of epilepsy syndromes depression chinese definition order prozac online. Neuroimaging has also found structural and functional brain abnormalities which support the hypothesis that uncontrolled (medication refractory) epilepsy is a progressive disease anxiety effects purchase prozac on line amex. While some data suggest extra-temporal atrophy may represent early cerebral damage depression eating buy generic prozac 10mg on line, increasing evidence suggests such abnormalities are pro gressive in nature and likely due to structural brain changes associated with ongo ing seizure activity. The metabolic abnormalities can normalize following treatment result ing in seizure freedom (Cendes et al. The forces affecting the extent and progression of impairment appears to reflect a combination of noxious and benefi cial factors impacting the brain. Neuropsychological Profiles Below, we summarize the neuropsychological findings for patients with both gen eralized epilepsy syndromes and focal epilepsies. Generalized Epilepsy Syndromes In general, generalized seizures are more likely to impair cognitive functions than are partial seizures, particularly for patients with multiple episodes of status-epilepticus (Dodrill 1986; Hennric Jokeit and Schacher 2004). In actuality, there is debate over whether seizures originate in the thalamus or the cortex (Holmes et al. It also known that frontal lobe structures play a significant role in generalized epilepsies (Pavone and Niedermeyer 2000). Accordingly, patients with generalized epilepsies have exhibited impairment in functions associated with the frontal lobes (executive functions), such as mental flexibility, working memory, and task shifting. The surgical evaluation process has allowed extensive data to be collected across electroneurophysiological, neuroana tomical (gross to molecular level), neurophysiological, neurological, neuropsychologi cal, psychiatric, psychological, quality of life, as well as a variety of psychosocial/ cultural variables. The goal for the collection and analysis of data has been to establish seizure focus and propagation as well as predict surgical outcome (seizure freedom, cognitive, psychiatric) to improve quality of life and reduce morbidity/mortality. Neuropsychological outcome is increasingly considered an important marker of successful seizure surgery outcome. Detailed below, prototypical neuropsychological profiles that have lateralizing/localizing value. We also summarize the more limited research on the various extratemporal epilepsies. The lateralization of dysfunction has been used to predict the side of seizure onset (see predicting side of seizure, below). However, the text-book pro file for temporal lobe epilepsy has not been found consistently (Barr et al. Indeed, nonverbal/visual memory defi cits associated with nondominant hemisphere dysfunction have been particularly difficult to establish. Language deficits and seizure lateralization: Seizure lateralization has been predicted by naming deficits (Busch et al. Hamberger and colleagues have also introduced an auditory naming task that may also have value in predicting preoperative seizure lateralization. However, these data are limited, and there are no consistent findings with respect to auditory naming failure and seizure lateralization (Hermann et al. However, pre-operative deficits in semantic fluency (category fluency) have not shown consistent value in seizure lateralization, since impaired scores are observed for patients with either dominant or nondominant temporal lobe epilepsy (Bartha et al. Semantic fluency requires both an executive component medi ated by frontal lobe regions. Similarly, performance on letter fluency tasks can be impaired preoperatively due to both frontal lobe and temporal lobe dysfunction (Helmstaedter et al. Thus, simply having a poor score on a semantic or phonemic verbal fluency task may not be of localizing or lateralizing value, but may be helpful for localizing (temporal vs frontal) if the component parts of the tests are examined. The nociferous cortex hypothesis of Wilder Penfield is sometimes invoked to explain this phenomenon (Penfield and Jasper 1954), in which epilepsy disrupts widespread neural networks. While current visual memory test scores and memory complaints are not strongly associated, most neu ropsychological studies do not adequately assess function of the right (nondominant) 466 M. Clinically, patients with these deficits have greater difficulty recognizing familiar individuals, which seems to contribute to compromised social functioning. A new approach to studying the neuropsychologic aspects of epilepsy has been to assess if distinct patient groups could be empirically derived based on similarities and differences in presurgical neuropsychological function (Hermann et al. While scores on measures of immediate and delayed memory, confrontation naming, executive control processes. Structural neuroimaging found the minimally impaired group exhibited hippocampal volume atrophy, but no other significant differences from the control group. In contrast to the primarily memory impaired group, the most pronounced defi cits were in executive and psychomotor speed. The third cluster tended to be the old est sample, having the longest duration of epilepsy, taking the most antiepileptic medications, and showing the greatest volumetric brain abnormalities. The material-specific pattern of memory dysfunction model may be impacted by other task parameters and disease-related variables. For example, material-specific findings may be easier to detect when examining both learning and recall patterns rather than only examining one trial learning (Jones-Gotman et al. Further, material-specific findings may be altered by side of seizure onset (Vannest et al. While this 16 Epilepsy and Seizures 467 review highlights considerable variability in the pre-surgical neuropsychological presentation of patients with epilepsy, patients experience better seizure control and better functional outcome when the prototypical neurocognitive profiles line up with other diagnostic findings. While it is increasingly appreciated that meaningful post operative neuropsychological deficits should mark a clear adverse comorbidity to neurosurgical treatment to be avoided. The role of the hippocampus versus extramesial temporal involvement for naming was recently demonstrated by Hamberger et al. Rather, patients whom are seizure-free can exhibit a post-operative improvement in performance. The improved performance is thought to reflect the pre-surgical widespread disruption of neural networks by epi lepsy (see Nociferous Cortex hypothesis below) (Helmstaedter et al. Resolution of seizures can result in significant improvement on neuropsychological tasks associated with frontal lobe function (Hermann et al. Other areas of impairment include: (1) cost estimation (Upton and Thompson 1996), (2) reasoning (Upton and Thompson 1999), determining temporal order (McAndrews and Milner 1991), and social cognition. For example, worse performance may be found on memory tasks requiring efficient encoding and/or retrieval (list learning tests). Post-operative decline in motor and neuropsychological functions can occur with unilateral frontal lobe resections (Helmstaedter et al. Referrals for surgical evaluation to epilepsy centers is rare, accounting for less than 10% of surgical patients, but do respond favorably to surgical treat ment for carefully selected patients (Binder et al. Defects in visual processing are common, and vary from visual field cuts to deficits in facial processing, color perception, object localization, object recognition (including letters/words), and other visuospatial/visuoconstructional skills (Kiper et al. Deficits in sensory discrimination, arithmetic, and language functioning (spelling, reading, etc. Patients with seizure onset involving the mesial occipital lobe exhibited more visual-field defects. Patients with seizure onset involving the parietal lobes tend to exhibit deficits in visuoperceptual/ visuospatial and/or visuoconstructional deficits (Siegel and Williamson 2000). Children with occipital lobe seizure onset exhibited academic problems, psychiatric disorders. Factors That May Obscure Neuropsychological Profiles in Presurgical Epilepsy Patients A variety of factors can obscure neuropsychological deficits attributable to the underlying epilepsy syndrome/pathology. As potential sources of error, these variables can obfuscate dysfunction due to underlying disease and/or effect from seizures, and lead to error in studying neu ropsychological functioning of patients with epilepsy. For example, topiramate may adversely affect attention, verbal fluency, and processing speed, which is entirely separate from the effects of the underlying neuropathology (Kockelmann et al. Adverse effects from medication could also lead to underestimating the patients level of cognitive function. Medical and psychiatric conditions comorbid with epilepsy can also introduce measurement error into neuropsychological assessment (Lezak et al. Seizures may develop following a head injury or be the presenting symptom of brain tumor(s), stroke, or encephalitis. The primary disease or injury contributes uniquely to the patients pattern of dysfunction, and there may be multifocal dys function related to brain tumor(s) as well as the cerebral dysfunction of epilepsy. Psychiatric comorbidities, particularly depression and anxiety symptoms, are higher for patients with epilepsy than the general public (Blumer et al. Scores on neuropsychological tests can be adversely affected by depression and anxiety (Lezak et al. Finally, there is growing awareness that acute ictal or inter-ictal epileptiform discharges can alter neuropsychological functioning. While the impact of epilep tiform activity can accentuate lateralized dysfunction in the case of focal seizure onset (Privitera et al. Problems with features of test design and selection can also muddle the interpre tation of neurocognitive data. For example, it is frequently argued that neuropsy chological tests are not particularly sensitive to nondominant mesial temporal functions, thought to reflect visual memory functions (Jones-Gottman 1996). For example, the Family Pictures subtest of the Wechsler Memory Scale, 3rd edition (Wechsler 1997) contributes to the Visual Memory index from this battery, yet vari ance of the test loads on a verbal factor (Dulay et al. Thus far, it has been extremely difficult to develop a visual memory test that does not allow for verbal processing/mediation of information. Similarly, more com plex list learning tasks place greater demands on executive systems than do less complex contextual memory tasks. Overall, prototypical neuropsychological profiles can be identified in some cases of epilepsy, but have not been identified in others. There are many potentially confounding factors that can make it challenging to obtain an accurate baseline measure of neuropsychological function in patients with epilepsy. We believe it is increasingly possible to recognize and control for variables that can potentially adversely affect neuropsychological function. In this manner, one may be able to better assess neuropsychological deficits and predict surgical outcome. Reasons for the variability are not entirely clear, but include center differences in patient selec tion, surgical techniques and outcome classification system used (Ojemann and Jung 2006). Recent long-term longitudinal data report 10-year seizure-free rates ranging from 37% to 80%. Overall, patients with mesial temporal sclerosis as the sole pathology is associated with the highest seizure freedom at 1 year (90+%), and are most likely to remain seizure-free at 10+ years after surgery. It can be viewed that epilepsy surgery has taken an intractable patient and made them responsive to medication. Variables Predicting Seizure Remission Factors that predict seizure remission have been an area of aggressive research. Neuropsychological variables have shown less predictive value, but significant vari ance to lateralizing seizure onset or predict seizure outcome has been demonstrated in some cases. In addition, it is important for the neuropsychologist to provide input to the epilepsy surgery pro gram regarding the potential neuropsychological risks with surgery. It can be the case in which a patient may present with neurological findings supportive of having a good seizure-free outcome, but at the risk of pronounced neuropsychological defi cits could out weight the potential benefits of a patient becoming seizure-free (Hermann and Loring 2008). A more detailed review of evidence-based neuropsychology for predicting neuropsychological outcome follows. The brain pathology underlying epilepsy can be the best predictor of seizure freedom. A panel of neurologists and neuropathologists in 2004 described and categorized these abnormalities (Palmini et al. Shorter duration of pre-operative epilepsy increases likelihood patient will be seizure-free (less likely to relapse) (see Table 16. Neuropsychological variables predicting seizure remission: Evidence-based Neuropsychology: In general, neuropsychological data are not helpful in predicting seizure outcome. However, some studies have shown neuropsychological data incre mentally improves prediction of seizure freedom (Hennessy et al. Overall, the multivariate prediction model provided accurate classification of 93% of the patients whom were seizure-free and not seizure-free. Predicting Side of Seizure Onset In general, electroneurophysiological and structural neuroimaging are the most powerful predictors of side of seizure onset. Neuropsychology Variables Predicting Side of Seizure Onset: Evidence-based Neuropsychology While neuropsychologial deficits have long been associated with side of surgery, only more recently has the incremental variance of neuropsychological data to determining side of surgery (side of seizure onset) been explored. Neuropsychological data do provide significant prediction to lateralizing side of seizure onset. It should also be noted that Wada test results also have predictive value (and may be more predictive) to lateralize side of seizure onset (Perrine et al. A constellation of variables have consistently shown to be predictive of neuropsychological outcome (see below). Among these, particularly strong predic tors are the neuropsychological presurgical test scores, which provide unique variance to predicting memory outcome, and form a cornerstone for evidence based neuropsychology practice and research. As an example, Chelune and Najm (2001) report a relative risk for a post-surgical memory deficit that is 4. Hippocampal Adequacy versus Hippocampal Functional Reserve Chelune (1995) detailed two perspectives for predicting post-surgical cognitive outcome from epilepsy surgery. One hypothesis was the functional reserve of the contralateral hippocampus predicted post-surgical memory outcome (functional reserve hypothesis). The second hypothesis, known as the functional adequacy model, predicted the functional adequacy of the ipsilateral hippocampus tissue resected would determine the risk for material specific memory decline. The functional reserve hypothesis was based primarily on studies documenting severe amnestic disorders of patients with bilateral mesial temporal lobe dysfunc tion and in several cases, bilateral temporal lobe resection (Scoville and Milner 1957). Additional support was provided by data from Wadas testing, as patients with poor memory when the contralateral. This has generally been supported, particularly the obser vation that patients with high pre-surgical memory functioning are at greater risk 476 M. The other 47% of patients exhibited impaired verbal memory (immediate and delayed), but average visual memory scores. Interestingly, only patients with early onset epilepsy (less than 6 years of age) exhibited a deficit in appreciating fearful facial expression. Long-term neuropsychological outcome data suggest individuals undergoing left temporal lobectomy may exhibit decline in verbal memory for up to 2 years after surgery (Alpherts et al. Individuals having a right temporal lobectomy had an overall increase in verbal memory scores at 6 months after surgery, but these gains were lost at 2 years after surgery. Relatively little memory change has been observed in memory from 2 to 6 years after surgery. In general, the risk for material specific memory decline decreases in patients with hippocampal sclerosis. In general, the better (more intact) a patients neuropsychological memory is prior to surgery, the greater the persons risk will be for memory decline. Among patients with verbal memory index scores of 79 or below, only 5% exhibited a decline of 10 or more points. Patients with Memory Index scores greater than 90 (mean of 100 and standard deviation of 15) at baseline have a 4. The relative incremental validity of Wadas test results over neuroimaging and neuropsychological data continue to be debated. Pre-surgical neuropsychological memory scores and Wadas test scores may not be redundant. Duration of epilepsy Patients with a longer duration of epilepsy are at less risk for post-surgical cognitive decline (but likely have poorer neuropsychological function prior to surgery). Other Points/Factoids for Predicting Neuropsychological Outcome from Epilepsy Surgery 1. This may refect the effect of the epileptic focus negative effect on ipsilateral brain function, and the so-called nociferous cortex hypothesis (Penfeld and Jasper 1954). Individuals exhibited no signifcant change in memory scores from 2 years to 6 years post-operative follow-up evaluations. Cognitive outcome is better for patients whom are seizure-free versus those patients who do not become seizure-free. Impact of Wadas (Intracarotid Amobarbital/Methohexital) Procedure for Predicting Outcome Wadas test is, arguably, the gold standard for evaluating the lateralized functional neuroanatomical organization of language and memory (Baxendale 2009). Predicting neuropsychological outcome from Wadas test remains an important variable for neuropsychologists to consider (Loring et al. Predicting outcome from Wadas test will be discussed in terms of language dominance and side of anticipated surgery (see Table 16. This test result is somewhat favorable, but there is considerable risk for verbal memory decline. Poor memory pre-operatively reduces relative risk of pronounced memory decline following surgical resection, and raises concern Wadas test was invalid. The relative potential benefit of seizure freedom and outcome must be balanced upon the functional level of the patient. Among patients with poor memory on neuropsychological functioning, but func tioning independently, surgical resection could worsen the amnestic syndrome, decreasing the patients functional independence. Language Dominant to Contralateral Side of Surgery Memory adequate with ipsilateral injection but poor for contralateral injection. This test result is also somewhat favorable, but there is risk for memory (visual and verbal) decline. This describes a test result in which the ipsilateral injection to the side of the proposed surgical resection (testing the contral ateral hemisphere language and memory function) results in poor memory functioning. Alternatively, injection of the contralateral hemisphere to the proposed resection (test ing ipsilateral hemisphere language and memory function) results in adequate memory. Traditionally, this test finding (so-called failing Wadas test) is generally considered to pose considerable neuropsychological risk to the patient with an amnestic syndrome following surgery being the worst case outcome (Loring et al. While decades of research establish patients with wrong way Wadas test results are at increased risk for memory decline, data suggest the risk of memory decline may be similar to those patients without structural pathology (Lacruz et al. The astute reader will recall that patients without structural pathology are at increased risk for memory decline. Thus, while having a wrong way Wada test result does not absolutely preclude surgical treatment, the risk of memory decline is greater.
Check estradiol and June 17 depression test for disability buy cheapest prozac, 2016 31 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People testosterone levels at 3 and 6 months and titrate dose accordingly anxiety x blood and bone lyrics generic prozac 20mg otc. For those patients using spironolactone depression definition with reference discount 40mg prozac overnight delivery, check renal function and K+ at 3 months and 6 months depression definition army generic prozac 60mg overnight delivery, then q 6-12 months anxiety frequent urination generic prozac 20mg on-line. While laboratory monitoring of hormone levels may seem complex anxiety 9dpo cheap prozac 40 mg amex, it is of similar difficulty to the monitoring of other similarly complex lab-monitored conditions managed by primary care providers bipolar depression journals purchase 20mg prozac, such as thyroid disorders mood disorder statistics 2012 cheap 60 mg prozac, anticoagulation, or diabetes. Once hormone levels have reached the target range for a specific patient, it is reasonable to monitor levels yearly, or only as needed as described below. As with other situations involving maintenance of hormone therapy (menopause, contraception), annual visits are sufficient for transgender women on a stable hormone regimen. Other reasons for measuring hormone levels in the maintenance phase include significant metabolic shifts such as the onset of diabetes or a thyroid disorder, substantial weight changes, subjective or objective evidence of virilization, or new symptoms potentially precipitated or exacerbated by hormone imbalances such as hot flashes or migraines. Such patients may also require more frequent office visits to manage coexisting conditions. Increased frequency of office visits may also be useful for patients with complex psychosocial situations to allow for the provision of ancillary or wraparound services. Current Endocrine Society recommendations include the measurement of only total testosterone and estradiol. This is consistent with Endocrine Society recommendations that only total testosterone be monitored in non-transgender men being managed for testosterone deficiency, except in cases of borderline testosterone levels. However, since testosterone is of particular concern is insuring maximal feminization, the calculation of bioavailable testosterone in transgender women may still be of value. As such in cases of patient concern or persistent virilized features in the presence of a female-range total testosterone, calculation of the bioavailable testosterone may help fine tune hormone regimens for optimal effect. Interpretation of laboratory results requires special attention in the context of transgender care. However, these specific ranges may vary between different laboratories and techniques. Furthermore, the interpretation of reference ranges supplied with lab result reports may not be applicable if the patient is registered under a gender that differs from their intended hormonal sex. For example, a transgender woman who is still registered as male will result in lab reference ranges reported for a male; clearly these ranges are not applicable for a transgender woman using feminizing hormone therapy. Providers are encouraged to consult with their local lab(s) to obtain hormone level reference ranges for both male and female norms, and then apply the correct range when interpreting results based on the current hormonal sex, rather than the sex of registration. Monitoring estradiol levels Historically estrogen levels have been monitored using the total serum estradiol. The 2009 Endocrine Society Guidelines recommend monitoring serum estradiol and maintaining levels at the June 17, 2016 32 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People mid-cycle range for non-transgender women. There is no evidence that higher estradiol levels in patients with adequate androgen suppression results in additional feminization or breast development. Maintaining estrogen levels in the physiologic range for menstruating non-transgender women minimizes risks and side effects, and makes sense clinically. Note that the use of conjugated estrogens (Premarin) or ethinyl estradiol (found in most combined oral contraceptives) are not accurately measured by estradiol assays and will typically result in low measured levels. In patients who have been using self-administered conjugated estrogens, or ethinyl estradiol, it is reasonable to check a total estrogens level, which may provide a more accurate estimate in these cases. There is some evidence that the use of oral estradiol results in higher serum levels of estrone due to first pass hepatic metabolism, as compared to parenteral forms. Monitoring testosterone levels Testosterone levels can be difficult to measure in non-transgender men due to rapid fluctuations in levels, relating to pulsatile release of gonadotropins, with higher levels in the morning hours. Monitoring hormone levels in patients using injected estrogen Pharmacokinetic studies of injected estrogen have been limited. Two earlier studies only examined single-dose pharmacokinetics and are therefore unable to be applied to steady-state dosing. When measuring hormone levels in patients using injected forms of estradiol, a mid-cycle level is often sufficient, however if the patient is experiencing cyclic symptoms such as migraines or mood swings, peak (1-2 days post injection) and trough levels of both estradiol and testosterone may reveal wide fluctuations in hormone levels over the dosing cycle; in these cases, consider changing to an oral or transdermal preparation, or reducing the injection interval (with concomitant reduction in dose, to maintain the same total dose administered over time). A single study suggests similar pharmacokinetics when estradiol is injected subcutaneously, rather than intramuscular. Several factors contribute to these differences, bone mass, muscle mass, number of myocytes, presence or lack of menstruation, and the erythropoetic effect of testosterone. While transgender women do not menstruate, those with female-range hormone levels will lack the erythropoetic effects of male-range testosterone, and it may be reasonable to use the female-range lower limit of normal when interpreting H&H. Conversely, the lack of menstruation, and potential for pulsatile undetected androgen activity in those with retained gonads make it reasonable to use the male-range upper limit of normal for H&H. Using the male-range upper limit of normal for alkaline phosphatase and creatinine may also be appropriate for transgender women due to retained bone and muscle mass or myocyte counts, respectively. This is of particular importance in transgender women using spironolactone who are registered as female, and may have a lab result flag showing an abnormal elevated creatinine. Lower and upper limits of normal to use when interpreting selected lab tests in transgender women using feminizing hormone therapy Lab measure Lower Limit of normal Upper Limit of normal Creatinine Not defined Male value Hemoglobin/Hematocrit Female value Male value Alkaline Phosphatase Not defined Male value Individualized dosing based on patient centered goals Some patients may desire limited hormone effects or a mix of masculine and feminine sex characteristics. Examples include retention of erectile function with otherwise maximum feminization, or minimal feminizing effects with the exception of body or facial hair elimination or breast growth. While manipulation of dosing regimens and choice of medication can allow patients June 17, 2016 34 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People to achieve this goal, it is important to have a clear discussion with patients regarding expectations and unknowns. Specifically, it is not possible to select in advance an exact hormone regimen that will predictably allow patients to arrive at a specified configuration of sex characteristics. Furthermore, individual genetic and physiologic variation can result in wide variations in both blood levels and response to therapy between different individuals using the same route and dose. At the same time, response to hormone therapy is also individualized and measures such as breast growth are variable in both degree and time course. Likely predictive factors of speed and degree of feminization include genetics, age at initiation of therapy, and body habitus. All transgender women who smoke should be counselled on tobacco risks and cessation options at every visit. Many transgender women may be unable or unwilling to quit smoking; this should not represent an absolute contraindication to estrogen therapy. After an in depth and careful informed consent discussion, it is reasonable to prescribe estrogen using a harm reduction approach, with a preferred route of transdermal estrogen. Loss of erectile function: Sildenafil (Viagra) and tadalafil (Cialis) can be used for preservation of erectile function at any stage or with any feminizing hormone regimen, in consideration of the typical contraindications and precautions when using this class of medication. It is reasonable check both total and bioavailable testosterone levels, and consider reduction of androgen blockade to allow an increase in testosterone, depending on patient goals. This study found no correlation between sexual desire and testosterone levels in the transgender women, though a significant correlation was found between hormones and desire in non-transgender women. Post-gonadectomy: Since estrogen dosing should be based on physiologic female levels, no reduction in estrogen dosing is required after gonadectomy. Some patients may choose to use a lower dose, which is appropriate as long as dosing is adequate to maintain bone density. Due to higher levels of co-occurring conditions in older individuals, there may also be higher risk of adverse effects. Nevertheless a large number of women have started hormones at advanced ages and safety and satisfaction have been reported as acceptable. Expected effects of this may be similar to non-transgender women experiencing menopause. Transgender women who retain their gonads but withdraw hormone therapy may experience return of virilization. A discussion of the pros and cons of this approach, with individualized and shared decision making is recommended. Pituitary adenoma (prolactinoma) and galactorrhea: Prolactin elevations and growth of pituitary prolactinomas are theoretical risks associated with estrogen therapy; several cases have been reported. Furthermore, Endocrine Society guidelines for the management of incidental prolactinomas are expectant management only, in the absence of suggestive visual or other symptoms (significant galactorrhea, headaches). As such it is recommended that prolactin be checked only in cases of visual disturbances, excessive galactorrhea, and be considered in cases of new onset headaches. It is noted that some transgender women experience a minimal amount of galactorrhea early in their hormone therapy course. The presence of non-bloody minimal galactorrhea from more than one duct and/or bilateral is almost certainly physiologic and would not warrant further evaluation. Venous thromboembolism: Data from studies of menopausal women suggest no increased risk of venous thromboembolism with the use of transdermal estradiol. A report of 11 transgender women with a history of activated protein C resistance (the mechanism of action implicated in the hypercoaguable state associated with the Factor-V Lieden mutation) using transdermal estradiol without anticoagulation found no clotting events after a mean of 64 months of therapy. Routine screening for prothrombotic mutations is not recommended in the absence of risk factors. June 17, 2016 37 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People Figure 7-1. Testosterone has been associated with overall immune suppression, and autoimmune conditions are more common in non-transgender women than men. Hormone dosing should begin low and advance slowly, monitoring for worsening symptoms, and in collaboration with any specialists who may be managing the autoimmune condition. Migraine: Migraines have a clear hormonal component and may be exacerbated by estrogen therapy. Patients with a history of migraines should consider starting with a low dose and titrating upward as tolerated. Oral or transdermal estrogen may be preferred to the potentially cyclic levels associated with injected estrogen. Mental health conditions: While hormones may contribute to mood disorders (such as in premenstrual dysphoric disorder or postpartum depression), there is no clear evidence that estrogen therapy is directly associated with the onset of or worsening of mental health conditions. In fact one study found that transgender women experience improvements in social functioning and reduced anxiety and depression once estrogen therapy is begun. It may be advisable to avoid injected estrogen due to the potentially cyclic levels, which could bring about or worsen existing mood symptoms. Estrogen therapy in patients with a prior history of cancer: An active estrogen-sensitive cancer is a contraindication to estrogen therapy. For patients with a prior history of estrogen sensitive cancer (breast, pituitary), consultation with an oncologist is recommended. While androgen deprivation is a mainstay of treatment for advanced prostate cancer, it is unclear if estrogen therapy may confer an independent protection or increased risk of prostate cancer. Perioperative use of feminizing hormones: No direct study of the risk of perioperative venous thromboembolism in users of bioidentical estrogens has been conducted. Guidelines from two British professional organizations make a weak recommendation to discontinue menopausal hormone therapy in the perioperative period, however both acknowledge that this may not be needed in the setting of proper prophylaxis. June 17, 2016 43 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People heparin or compression devices). Postoperative depression is a nontrivial concern and may have some basis in the drastic hormone shifts, including cessation of estrogens, experienced in the perioperative period. There is no evidence to suggest that transgender women who lack specific risk factors (smoking, personal or family history, excessive doses or use of synthetic estrogens) must cease estrogen therapy before and after surgical procedures, in particular with appropriate use of prophylaxis and an informed consent discussion of the pros and cons of discontinuing hormone therapy during this time. Possible alternatives include using a lower dose of estrogen, and/or changing to a transdermal route if not already in use. A comparison of the short term effects of oral conjugated equine estrogens versus transdermal estradiol on C-reactive protein, other serum markers of inflammation, and other hepatic proteins in naturally menopausal women. Differential effects of oral conjugated equine estrogen and transdermal estrogen on atherosclerotic vascular disease risk markers and endothelial function in healthy postmenopausal women. Mechanisms in endocrinology: epidemiology of hormonal contraceptives-related venous thromboembolism. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. A randomized, double-blind study of two combined oral contraceptives containing the same progestogen, but different estrogens. Spironolactone with physiological female steroids for presurgical therapy of male-to-female transsexualism. Hair loss in women: medical and cosmetic approaches to increase scalp hair fullness. June 17, 2016 44 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People 9. Adverse side effects of 5 reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients. Androgen-deprivation therapy and bone loss in prostate cancer patients: a clinical review. Cyproterone acetate induces a wide spectrum of acute liver damage including corticosteroid-responsive hepatitis: report of 22 cases. Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the womens health initiative randomized controlled trial. June 17, 2016 45 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People 23. Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg). Medroxyprogesterone acetate and estradiol cypionate injectable suspension (Cyclofem) monthly contraceptive injection: steady state pharmacokinetics. June 17, 2016 46 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People 37. Hypoactive sexual desire in transsexual women: prevalence and association with testosterone levels. Effects of cross-gender steroid hormone treatment on prolactin concentrations in humans. Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis. Single-dose pharmacokinetics of sublingual versus oral administration of micronized 17 beta-estradiol. Estrogen deficiency in severe postpartum depression: successful treatment with sublingual physiologic 17beta-estradiol: a preliminary study. Mortality and morbidity in transsexual patients with cross-gender hormone treatment. Incidence of thrombophilia and venous thrombosis in transsexuals under cross-sex hormone therapy. June 17, 2016 47 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People 51. Hormonal contraception in women with migraine: is progestogen-only contraception a better choice Do cosmetic surgeons consider estrogen containing drugs to be of significant risk in the development of thromboembolism Venous thrombo-embolism as a complication of cross-sex hormone treatment of male-to-female transsexual subjects: a review. June 17, 2016 48 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People 8. General effects include the development of facial hair, virilizing changes in voice, a redistribution of facial and body subcutaneous fat, increased muscle mass, increased body hair, change in sweat and odor patterns, frontal and temporal hairline recession, and possibly male pattern baldness. Sexual and gonadal effects include an increase in libido, clitoral growth, vaginal dryness, and cessation of menses. An ovulatory state is common, though not absolute and long-term fertility may be affected, though some transgender men are able to discontinue testosterone and achieve successful pregnancy. The general approach involves the use of one of several forms of parenteral testosterone. Prior use of oral methyltestosterone and other synthetics commonly encountered in bodybuilding communities has resulted in unsubstantiated concerns about negative hepatic effects of testosterone use in transgender men. Testosterone is available in a number of injected and topical preparations, which have been designed for use in non-transgender men with low androgen levels (see table). Since the label dosing (not included in table) for these medications are based on the treatment of men with low, but not no, testosterone, higher dosing may be needed in transgender men (see table) than are commonly used in non-transgender men. Furthermore, these dosage ranges do not necessarily represent a target or ideal dose. Dose increases should be based on patient response and/or monitored hormone levels. Specific absorption and activity varies and consultation with the individual compounding pharmacist is recommended. Testosterone undecanoate has been used extensively for transgender care outside of the U. Testosterone undecanoate has been associated with rare cases of pulmonary oil microembolism and anaphylaxis. All injections must be administered in an office or hospital setting by a trained and registered health care provider and monitored for 30 minutes afterwards for adverse reactions. Benefits of subcutaneous administration include a smaller and less painful needle, and may avoid scarring or fibrosis from long term (possibly > 50 years) intramuscular therapy (Grading: T O M). After application, the testosterone moves into the dermis, where it slowly releases over the course of the day. Care should be taken to avoid any contact of the gel with others, especially women and June 17, 2016 50 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People children. It is also recommended that the application site be washed at a later time if close skin-skin contact with another person is expected. Clinical response can be measured objectively by the presence of amenorrhea by 6 months.
Syndromes
Follow any diet your transplant team recommends.
Nervous system conditions, such as multiple sclerosis or stroke
Where are the blood vessels located?
Is the head growing more in a front-to-back pattern or in a side-to-side pattern?
Ultrasound of the eye
It is present at birth.
Skin biopsies of the vulvar area
Conditions that allow fluid to escape from the bloodstream
Appetite loss
Avoid surfaces that reflect light more, such as water, sand, concrete, and white-painted areas.
Long term effects of bilateral subthalamic nucleus stimulation on cognitive function bipolar depression in teenagers buy cheap prozac 10 mg on line, mood residual depression definition purchase generic prozac pills, and behaviour in Parkinsons disease mood disorder holistic medicine order prozac 60 mg with amex. Clinical correlates and cognitive under pinnings of verbal fluency impairment after chronic subthalamic stimulation in Parkinsons dis ease mood disorder related to pms purchase 10mg prozac free shipping. Effects of pallidotomy and bilateral subthalamic stimulation on cognitive function in Parkinsons disease: A controlled comparative study anxiety questionnaire for adults buy cheap prozac 20 mg. Dementia as the most common presentation of cortical-basal ganglionic degeneration mood disorder yahoo purchase 10mg prozac otc. Pallidal stimulation in dystonia: Effects on cognition depression podcast prozac 10 mg lowest price, mood depression symptoms cognitive cheap prozac 40mg fast delivery, and quality of life. Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons. Differential modulation of subcortical target and cortex during deep brain stimulation. Surgical therapies for Parkinsons disease; in Kurlan R (ed): Treatment of Movement Disorders. Differential modula tion of subcortical target and cortex during deep brain stimulation. Bilateral subthalamic nucleus stimulation for Parkinsons disease: A systematic review of the clinical literature. The neuropsychology of patients with clini cally diagnosed idiopathic normal pressure hydrocephalus. The clinical significance of neuropsychological changes following bilateral subthalamic nucleus deep brain stimulation for Parkinsons disease. Disease progression continues in patients with advanced Parkinsons disease and effective subthalamic nucleus stimulation. Clinical significance: A statistical approach to defining meaningful change in psychotherapy research. The impact of deep brain stimulation on executive function in Parkinsons disease. Functional magnetic resonance imaging during deep brain stimulation: a pilot study in four patients with Parkinsons disease. The long-term results of stereotaxic surgery and L-dopa therapy in patients with Parkinsons disease. The long-term results of stereotactic surgery and L-dopa in patients with Parkinsons disease. Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinsons disease. Apraxia in Parkinsons disease, progressive supranuclear palsy, multiple system atrophy and neuroleptic-induced Parkinsonism. Psychopathology in patients with degenerative cerebellar diseases: A comparison to Huntingtons disease. A prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome. Neuropsychological functioning in cor tical-basal ganglionic degeneration: Differentiation from Alzheimers disease. Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome. Effect of levodopa on cognitive function in Parkinsons disease with and without dementia and dementia with Lewy bodies. Neuropsychological functioning following bilateral subthalamic nucleus stimulation in Parkinsons disease. Comparison of dementia with Lewy bodies to Alzheimers disease and Parkinsons disease with dementia. Development and initial validation of a screening tool for Parkinson disease surgical candi dates. Cognitive sequelae of subthalamic nucleus deep brain stimulation in Parkinsons disease: a meta-analysis. Stimulation of the subthalamic nucleus in Parkinsons disease: Cognitive and affective changes are not linked to the motor outcome. Which elements are excited in electrical stimulation of mammalian central nervous system: A review. Manual for the administration of Neuropsychological test batleries for adults and children. The ups and downs of Parkinson disease: A prospective study of mood and anxiety fluctuations. Patient selection and assessment recommendations for deep brain stimulation in Tourettes syndrome. Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinsons disease. Surgical treatment of Parkinsons disease and other related movement disorders (current clinical neurology). Neuropsychological and quality of life outcome after thalamic stimulation for essential tremor. Assessing cognitive change in Parkinsons disease: Development of practice effect-corrected reliable change indices. Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia. Bilateral, pallidal, deep-brain stimulation in primary generalised dystonia: A prospective 3 year follow-up study. Chronic bilateral thalamic stimulation: A new therapeutic approach in intractable Tourette syndrome. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinsons disease. Presentation and management of psychosis in Parkinsons disease and dementia with Lewy bodies. Neuropsychological sequelae of subthalamic nucleus deep brain stimulation in Parkinsons disease: A critical review. Cognitive declines following bilateral subthalamic nucleus deep brain stimulation for the treat ment of Parkinsons disease. Bobholz and Shelley Gremley Abstract Demyelinating disorders are characterized by the destruction of the myelin sheaths of the nerves following normal myelin development. Types of demyelinating conditions can be generally characterized as immune-mediated diseases, infection mediated diseases, inherited disorders, and toxic disorders (see (Table 20. This chapter will begin with a brief description of demyelinating conditions representing these categories. The most common presenting complaints of demyelinating disorders are rapid motor and sensory changes. Untreated, these factors may compound physical and cognitive disability associated with the demyelinating disorder. Onset of symptoms is sudden and can include monoplegia (paralysis of a single limb) or hemiplegia (paralysis on one side of the body), headache, delirium, lethargy, coma, seizures, stiff neck, fever, ataxia, optic neuritis, transverse myelitis, vomiting, and weight loss. Patients who recover tend to show good functional recovery from a neurologic stand point; however, neuropsychological studies show that this apparent transient illness is associated with cognitive and social sequelae (Jacobs et al. This disorder is characterized by progressive inflammation of the white matter in the brain at multiple locations. Demyelination is most prominent in the occipital lobes and is a result of direct infection of oligodendrocytes, the cells responsible for creating the myelin sheath. Common symptoms include hemiparesis, aphasia, focal seizures, and visual disturbances. Patients with this disorder have a progressive myelopathy, sensory distur bance, bladder dysfunction, and optic neuritis. Inherited demyelinating disorders, or leukodystrophies, are characterized by specific gene defects that result in myelin abnormalities (Joy and Johnston 2001). More specifically, there is either inadequate myelin production or excess breakdown of myelin. Toxic optic neuropathy is defined by visual impairment do to damage to the optic nerve. This disorder is uncommon and is primarily associated with specific medications, occupational exposures, or tobacco and alcohol abuse. This eventually leads to thinning or complete loss of myelin, and this demyelinating process can cause changes in motor and sensory functioning, as well as changes in cognition. The functions most frequently affected include abstract conceptualization, recent memory, attention, and informa tion processing speed. Onset is also estimated to be approximately 5 years earlier for women (Olek 2005). The prevalence of the disease ranges between 2 and 150 per 100,000 depending on the country or specific population (Rosati 2001). It is also more common among people who live in northern latitudes during childhood. Climate, diet, geomagnetism, toxins, sunlight exposure, and infectious exposure have all been offered as possible reasons for these regional differences. This course is characterized by clearly defned relapses or unpredictable attacks followed by periods of remission or complete recovery of symptoms. Reported common triggers for relapse include warm weather, infections, and emotional and physical stress. The primary progressive subtype tends to affect people who are older at disease onset. A common hypothesis is that a viral infection or retroviral reactivation primes a susceptible immune system for an abnormal reaction later in life. Deficits in executive functioning, verbal abstraction, and visuospatial perception have also been found (Rao et al. Gremley for lunch yesterday) tends to be most affected, while implicit, semantic, and autobiographical memory are typically spared. While debated in the past, memory disruption is likely associated with encoding, storage, and retrieval operations. Working memory is generally thought to be the ability to hold information in memory for a short period, while manipulating that information. Deficits in working memory are thought to be related to deficits in processing speed since these functions related to one another. Furthermore, studies have 20 Multiple Sclerosis and Other Demyelinating Disorders 655 shown that individuals who have cognitive dysfunction are more likely to have problems with employment compared to those without cognitive deficits (Rao et al. Cognitive dysfunction has been associated with poorer performance on computerized assessment of driving skill and accident rates (Shawaryn et al. Correlates with Neuropsychological Deficits Some general trends have become apparent in the research examining correlates of neuropsychological dysfunction. Disease duration is also a relatively strong correlate of neuropsychological dysfunction, with longer periods of disease associated with increasing cognitive deficits (Thorton and Naftail 1997). Acute, sub-acute and chronic pain, including Trigeminal neuralgia, tonic spasms, continuous dysesthetic pain, acute radicular pain, and optic neuritis, muscle cramps, headache, and back pain may interfere with test performance. Worth noting is that disease modifying medications typically are not associated with cognitive side effects. Brain lesions and psychosocial issues are considered risk factors for mood disturbance, while physical disability does not appear to be closely associated with depression (Goldstein Consensus Group 2005). More recent imaging research has dem onstrated greater magnitude of correlation between measures of atrophy as measured by third ventricle dilation and cognitive dysfunction. Furthermore, this association appears to be strongly related to thalamic and neocortical atrophy. However, patients often present with cognitive dys function as their initial disease symptom and, for some, this can remain their primary symptom throughout their disease. Further analysis of these data also showed that there was slightly greater risk for men to have lower auditory memory than women (odds ratio of 1:76) but that sex differences were not apparent with the other factors examined. This study also showed an interaction between sex and disease course, as men were found to be 5. At other times, an evaluation is helpful in determining the reasons for difficulties at work and/or home, and in determining whether changes in treatment approach are necessary. Many times, a neuropsychological evaluation is needed to determine ones work capacity and/or application for disability. Therefore, the length and depth of the evaluation may differ based on the purpose of the assessment. Comprehensive test batteries are not always necessary to answer referral questions. In 2001, an international panel was convened in order to develop an ideal, minimal record of neuropsychological function (Benedict et al. The Brief Repeatable Battery assesses verbal memory, spatial memory, attention, and verbal fluency. The Basso Screening Battery assesses verbal learning, verbal fluency, and auditory attention, and the Screening Evaluation for Cognitive Impairment measures verbal memory, general verbal ability, and attention. Unlike the batteries of objective measures described above, this measure would assess subjective experi ence to assist the clinician in management of this symptom. A high rate of cognitive complaints would likely trigger more comprehensive neuropsychological evaluation to better appreciate the concerns and to assist with treatment plans. The clinician is encouraged to carefully consider the reason for evaluation and to assess accordingly. In cases where the referral question relates to the individuals ability to work or academic functions, a more comprehensive evaluation may be warranted. In contrast, some individuals are referred for evaluation to assess for cognitive problems or monitor course of symptoms. As with motor symptoms or sensory symptoms, neurologists are often requesting neuropsychological evalua tions to monitor cognitive symptoms. Often, a relatively briefer evaluation still targeting the areas vulnerable to decline may be considered. While it is important for the clinician to characterize the nature and severity of cognitive problems, consideration of other issues such as depression, sleep depriva tion, pain, and fatigue must be considered when developing treatment recommen dations. Studies examining the effects of disease modifying medications may help in prevention of cognitive decline (Fischer et al. However, more recently, efforts to manage the symp tom of cognitive dysfunction have focused on donepezil (Krupp et al. Cognitive impairment in early-onset multiple sclerosis: Pattern, predictors, and impact on everyday life in a 4-year followup. Cognitive dysfunction in early onset multiple sclerosis: A reappraisal after 10 years. Speed of presentation influences story recall in college students and persons with multiple sclerosis. Depressed mood in multiple sclerosis: Relationship to capacity demanding memory and attentional functioning. Demographic, clinical and cognitive characteristics of multiple sclerosis patients who continue to work. Risk of processing speed deficits among patients with relapsing and remitting and secondary progressive multiple sclerosis. Relative risk of cognitive impairment is mediated by disease course and sex in multiple sclerosis. The nature of memory impairments in multiple sclerosis: Acquisition versus retrieval. Speed of information processing as a key deficit in multiple sclerosis: Implications for rehabilitation. Neuropsychological effects of interferon beta-1a in relapsing-remitting multiple sclerosis. The effects of amantadine and pemoline on cognitive functioning in multiple sclerosis. A double-blind pilot study of the effect of Prokarin on fatigue in multiple sclerosis. Treatment for depression and its relationship to improvement of quality of life and psychological well-being in multiple sclerosis patients. Neuropsychological outcome after acute disseminated encephalomyelitis: impact of age at illness onset. Assessment of driving performance in patients with relapsing-remitting multiple sclerosis by a driving simulator. Factors influencing quality of life in multiple sclerosis patients: Disability, depressive mood, fatigue, and sleep quality. Comparative outcomes for individual cognitive-behavior therapy, supportive-expressive group psychotherapy, and sertraline for the treatment of depression in multiple sclerosis. Evidence-based cognitive rehabilitation for persons with Multiple Sclerosis: A review of the literature.
