Neurontin

Nishant Shah, MD

• Assistant Professor
• Department of Pediatrics
• Wayne State University
• Children? Hospital of Michigan Detroit
• Detroit, Michigan

Therapeutic options include medicine river animal hospital generic neurontin 800mg without prescription, for example medications for rheumatoid arthritis generic 100 mg neurontin with visa, weekly or twice weekly to a total dose of 6?8 Gy topical and intralesional corticosteroids and topical would be appropriate (Grade B) medicine side effects neurontin 600mg online. Psoriasis of the nails treated Radiotherapy with Grenz rays: a double-blind bilateral trial treatment 12mm kidney stone generic neurontin 400mg free shipping. Cochrane In all three trials symptoms tuberculosis neurontin 600mg free shipping, with a total of 46 participants symptoms ulcerative colitis discount 300 mg neurontin mastercard, a clinician Database Syst Rev 2013; 31: 1. The severity of eight Background symptoms were scored out of 3, giving a possible total score of 24. Improvement was reported in the most common type of eczema is known as 83 of 88 (94%) areas treated, for all dose fractionation atopic dermatitis or atopic eczema. In some cases the condition becomes chronic and Recommendations hyperkeratotic, or associated with lichenification, with exaggerated skin markings. Most infants who develop the condition outgrow it by their tenth birthday, while a minority of patients If there are no alternative options for chronic continue to have symptoms on and off throughout life. There is very limited recent recommendations used within this review are literature on its use. There was a1 significantly better response to active treatment at References one month but this difference was no longer apparent at three and six months. A double-blind study treated at Aarau, Switzerland, 22 with refractory of superficial radiotherapy in chronic palmar eczema and six with psoriasis of palms and/or soles eczema. Long-term results of radiotherapy in patients with chronic palmo-plantar eczema or psoriasis. Does Prevention of gynaecomastia and breast pain prophylactic breast irradiation prevent caused by androgen deprivation therapy in antiandrogen-induced gynaecomastia Evaluation of 253 patients in the randomized Int J Radiat Oncol Biol Phys 2012; 83(4): e519? Scandinavian trial spcg-7/sfuo-3. Tamoxifen as prophylaxis for prevention of gynaecomastia and breast pain associated with 10. Efficacy of tamoxifen and radiotherapy for An open, randomised, multicenter, phase 3 trial prevention and treatment of gynaecomastia and comparing the efficacy of two tamoxifen breast pain caused by bicalutamide in prostate schedules in preventing gynaecomastia induced cancer: a randomised controlled trial. Evaluation of tamoxifen and anastrozole in the Radiotherapeutic prophylaxis of estrogen- prevention of gynaecomastia and breast pain induced gynaecomastia: a study of late sequela. Prophylactic of radiation on prevention of gynaecomastia breast irradiation with a single dose of electron due to oestrogen therapy. Optimal prophylactic and definitive therapy for bicalutamide-induced gynaecomastia: results of a meta-analysis. In most cases, the absolute risk is very small organisations in Scotland, Wales and Northern and needs to be balanced against the risk of Ireland regarding potential national approaches. It is provided for use by appropriately qualified professionals, and the making of any decision regarding the applicability and suitability of the material in any particular circumstance is subject to the users professional judgement. Part I: the 100 top-cited papers in neurosurgical journals A review Fr a n c i s c o a. The number of citations a published article receives is a measure of its impact in the scientifc com- munity. This study identifes and characterizes the current 100 top-cited articles in journals specifcally dedicated to neurosurgery. Neurosurgical journals were identifed using the Institute for Scientifc Information Journal Citation Reports. A search was performed using Institute for Scientifc Information Web of Science for articles appearing in each of these journals. The 100 most cited manuscripts in neurosurgical journals appeared in 3 of 13 journals dedicated to neurosurgery. These included 79 in the Journal of Neurosurgery, 11 in the Journal of Neurology, Neurosurgery and Psychiatry, and 10 in Neurosurgery. Representation varied widely across neurosurgi- cal disciplines, with cerebrovascular diseases leading (43 articles), followed by trauma (27 articles), stereotactic and functional neurosurgery (13 articles), and neurooncology (12 articles). The study types included 5 randomized trials, 5 cooperative studies, 1 observational cohort study, 69 case series, 8 review articles, and 12 animal studies. Thirty ar- ticles dealt with surgical management and 12 with nonsurgical management. There were 15 studies of natural history of disease or outcomes after trauma, 11 classifcation or grading scales, and 10 studies of human pathophysiology. The most cited articles in neurosurgical journals are trials evaluating surgical or medical therapies, descriptions of novel techniques, or systems for classifying or grading disease. The time of publication, feld of study, nature of the work, and the journal in which the work appears are possible determinants of the likelihood of citation and impact. These are the studies that cal community is the number of times that article has A have helped defne the way that our discipline is been cited (the citation count). The purpose of this study practiced by serving as the foundation for new methods, is to identify, using the citation count, works that have procedures, or concepts. A surrogate for measuring the made key contributions in the feld and are driving or have driven the practice of neurosurgery. The study and anal- British Journal of Neurosurgery ysis of citation indexes, or bibliometrics, have resulted in Clinical Neurology and Neurosurgery the development of various metrics to assess the impact Journal of Neurology, Neurosurgery and Psychiatry of scientifc journals or individual investigators based on the number of citations to their respective works. In the Journal of Neurosurgery present study, we take advantage of these tools, not read- Minimally Invasive Neurosurgery ily available in the past, to identify the important works Neurosurgery in neurosurgery. In this frst part, Neurosurgical Review we identify the 100 top-cited articles published in neu- rosurgical journals since 1950 and provide an analysis of Neurosurgery Quarterly the felds and types of study represented in these articles. The source of the data of citations to these articles made by other neurosurgical presented in this study is the web-based bibliometric data- journals. We identifed 11 the most cited articles in all 13 neurosurgical journals neurosurgical journals by searching the Journal Citation were sorted by the citation counts. The citation counts ranged from 287 to 1515, and tifed a journal specializing in neurosurgical anesthesiol- the years of publication ranged from 1956 to 2001, with 77 ogy, which was excluded from our analysis. The journals having been published between 1976 and 1995, 19 before Surgical Neurology and Acta Neurochirurgica, not cap- 1976, and 4 after 1995. A search In the following sections, the numbers in parentheses was then performed on Web of Science of each journal represent the ranking of the articles in terms of number under Publication Name, and results were sorted by the of citations. The journal Spine was also considered for inclusion, Field of Study and 32 articles were found in Spine that had been cited over 265 times (a cutoff value corresponding to the num- the articles were categorized as studies concerning ber of citations for the 100th most cited article in the Jour- cerebrovascular disease, trauma, tumors, or functional nal of Neurosurgery). Spinal cord injury was included under primarily by a neurosurgeon; thus, despite the overlap trauma, and stereotaxy, epilepsy, and pain were included and relevance of the topics covered in Spine with neuro- under functional neurosurgery. Ninety-fve of the articles surgery, the journal was not considered a neurosurgical fell under 1 of these 4 categories; in addition, 5 articles journal for the purposes of this study. Highly cited neuro- were about syringomyelia, hydrocephalus, infection, and surgical papers appearing in general medical journals are spine surgery (Table 4). These was compiled in August 2009, and the numbers presented included 19 articles on the management of intracranial thus refect the citation counts at that time. Wada J, Rasmussen T: Intracarotid injection of sodium amytal for the lateralization of cerebral speech dominance. Guglielmi G, Vinuela F, Dion J, Duckwiler G: Electrothrombosis of saccular aneurysms via endovascular approach. Locksley H: Natural history of subarachnoid hemorrhage, intracranial aneurysms and arteriovenous malformations. Ojemann G, Ojemann J, Lettich E, Berger M: Cortical language localization in left, dominant hemisphere. Vinuela F, Duckwiler G, Mawad M: Guglielmi detachable coil embolization of acute intracranial aneurysm: perioperative anatomi- 516 cal and clinical outcome in 403 patients. Guglielmi G, Vinuela F, Sepetka I, Macellari V: Electrothrombosis of saccular aneurysms via endovascular approach. J Neurosurg 84:203?214, 1996 (continued) J Neurosurg / Volume 112 / February 2010 225 F. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C: A prospective study of acute cerebrovascular disease in the community: 469 the Oxfordshire Community Stroke Project?1981-86. Incidence, case fatality rates and overall outcome at one year of cerebral infarction, primary intracerebral and subarachnoid haemorrhage. Perret G, Nishioka H: Report on the cooperative study of intracranial aneurysms and subarachnoid hemorrhage. An analysis of 545 cases of cranio-cerebral arteriovenous malformations and fstulae reported to the coopera- tive study. Aaslid R, Huber P, Nornes H: Evaluation of cerebrovascular spasm with transcranial Doppler ultrasound. Guglielmi G, Vinuela F, Duckwiler G, Dion J, Lylyk P, Berenstein A, Strother C, Graves V, Halbach V, Nichols D, Hopkins N, Fer- 385 guson R, Sepetka I: Endovascular treatment of posterior circulation aneurysms by electrothrombosis using electrically detach- able coils. Bouma G, Muizelaar J, Choi S, Newlon P, Young H: Cerebral circulation and metabolism after severe traumatic brain injury: the 383 elusive role of ischemia. J Neurosurg 54:289?299, 1981 (continued) 226 J Neurosurg / Volume 112 / February 2010 Highly cited works in neurosurgery. Jennett B, Teasdale G, Braakman R, Minderhoud J, Heiden J, Kurze T: Prognosis of patients with severe head injury. Neurosur- 319 gery 4:283?289, 1979 (continued) J Neurosurg / Volume 112 / February 2010 227 F. Lasjaunias P, Chiu M, Terbrugge K, Tolia A, Hurth M, Bernstein M: Neurological manifestations of intracranial dural arteriovenous 306 malformations. Marmarou A, Shulman K, Lamorgese J: Compartmental analysis of compliance and outfow resistance of the cerebrospinal fuid 304 system. Yoshida S, Inoh S, Asano T, Sano K, Kubota M, Shimazaki H, Ueta N: Effect of transient ischemia on free fatty acids and phos- 302 pholipids in the gerbil brain. Ferguson G: Physical factors in the initiation, growth, and rupture of human intracranial saccular aneurysms. Shiozaki T, Sugimoto H, Taneda M, Yoshida H, Iwai A, Yoshioka T, Sugimoto T: Effect of mild hypothermia on uncontrollable in- 295 tracranial hypertension after severe head injury. J Neurosurg 58:11?17, 1983 228 J Neurosurg / Volume 112 / February 2010 Highly cited works in neurosurgery. Three articles were on movement 1981?1985 20 17 1 2 disorders, including pallidotomy (No. Three 1986?1990 24 18 3 3 articles described techniques for functional localization, 1991?1995 20 19 0 1 including the Amytal test for lateralizing language domi- 1996?2000 3 2 0 1 nance (No. Results from 2006?present 0 0 0 0 microvascular decompression were presented in 2 articles, total 100 79 11 10 1 for hemifacial spasm (No. In addition, there were experiences reported on the use of in- radiosurgical treatment (Nos. There were 12 tumor studies in the top 100 cited Three articles were studies of normal vascular physiol- articles. Five of these were on glial tumors, including 1 ogy, including 2 studies performed on animals (Nos. Glasgow Outcome Scale or Glasgow Coma Scale and 1 for the Simpson grading system for extent of meningioma Type of Study resection. There were 5 randomized trials, 5 cooperative stud- There were 21 articles that were categorized as labora- ies, and 1 observational cohort. This included 12 animal studies: 1 histologi- articles that consisted of case series, some of which were cal study of an animal model of glial tumors; 1 surgical topic reviews or laboratory studies that were supplement- study of coiling; 1 study of vasospasm; 6 pathophysiology ed by patient data. There agement, nonsurgical management, natural history, clas- were 7 human studies: 4 pathology studies of dementia sifcations, reviews, and laboratory studies. There were also 2 ex vivo models: care unit management, medication-based therapies, and 1 of aneurysms using a glass model and 1 of the shaken- nonsurgical diagnostic studies. Five studies were structured as ran- radiation therapy, 3 articles were on surgical or endovas- domized, controlled trials, and 6 articles were prospec- cular techniques for functional localization, and 2 were tive multiinstitutional cooperative studies or population- about new stereotactic technologies. Nine studies described medical management of has accumulated as a measure of impact is that such a neurosurgical problems, including 7 studies on head trau- method favors older publications and older journals. Ninety of the 100 articles head trauma included 4 randomized trials and 3 prospec- appeared in these 2 journals. The presence of only 1 article published since 1997 trauma when the emphasis was not on therapy or diagnos- is likely accounted for by not enough time having elapsed tic techniques. This included 6 studies of prognostic fac- for important studies to accumulate citations, or could tors related to outcomes following head trauma, of which refect the referral of more recent high-impact papers to 2 addressed the effects of minor head trauma. In contrast, the relatively small 8 studies on the natural history of cerebrovascular dis- number of contributions from papers in the 1950?1975 230 J Neurosurg / Volume 112 / February 2010 Highly cited works in neurosurgery. Part I epochs may relate to a number of variables, including loss First, inherent problems of citation analyses have of immediacy and awareness, and limitations in biblio- been described, including that such methods favor older metric databases for tracking older articles. Fur- tion and analysis because they have appeared in textbook thermore, we suggest that the presence of only 19 papers rather than manuscript form, for example, the founding between 1950 and 1975 may be related to limitations of work of microneurosurgery by Yasargil,11 documented in the database for tracking citations to older articles. This limitation has been identifed as being even more pronounced with newer bibliometric sources We noted an overrepresentation of cerebrovascular 1,3 such as Google Scholar and Scopus. It is not entirely clear why neurosurgery or neurosurgical in their titles, as well there is an overweighting of cerebrovascular papers and as 2 related journals without either term. However, it is worth noting that all 100 top-cited cular neurosurgery has attracted some of the most aca- articles were found in only 3 journals. In ad- this study also omits neurosurgical articles that have been dition, as neurooncology lends itself to laboratory study, published in general medical journals, such as those with perhaps the preponderance of highly cited studies in this higher impact and broader readership such as the New domain are skewed toward the basic sciences and are England Journal of Medicine, Journal of the American more likely to be published in nonneurosurgical journals, Medical Association, or Lancet. For example, not one refecting the notion that the major progress and advances article on the list of the 100 most cited articles in neuro- in brain tumors may still be largely found in the labora- 2 surgery journals concerned carotid endarterectomy, one tory rather than in the operating room. An There has been variable interest in functional neu- appraisal of the most highly cited neurosurgical articles rosurgery over time. The interest in functional neurosur- in all journals including the general medicine journals is gery waned in the late 1960s, when advances in medical addressed in the companion part of this study. This area of sources for citations, although they are weaker at tracking neurosurgery is in active growth and should exert a great- older publications. Spine as a subspecialty is virtually absent among the topics addressed in the top 100 cited papers, despite com- Conclusions prising a large proportion of most neurosurgical prac- Identifying the most cited articles in neurosurgical tices. The ress in neurosurgery, where our feld has been, and where involvement of neurosurgeons in modern spinal surgery, it is headed.

Then ders silent treatment neurontin 400 mg line, the term neurometabolic diseases is in- one to two cells are biopsied and examined while the creasingly used (Moser 1998) treatment diabetes trusted 300 mg neurontin. After the results logical mechanisms of these disorders include are known only the healthy embryos are implanted in energy failure treatment nerve damage generic neurontin 800 mg overnight delivery, substrate deficiency medicine garden best neurontin 800 mg, intoxication symptoms urinary tract infection neurontin 400mg, the uterus symptoms esophageal cancer buy genuine neurontin. An im- it is performed are cystic fibrosis, spinal muscular portant decision to be made is whether the disor- atrophy, haemophilia and fragile X syndrome. In gener- droxyglutaric aciduria and D-2-hydroxyglu- al, metabolic diseases are recessive disorders without taric aciduria clinical symptoms in heterozygous individuals. Most neurometabolic dis- logical signs and symptoms in the majority of inborn orders show progressive neurological features errors of metabolism. From a clinical point of view, the following three categories can be distinguished: 122 Chapter 3 Causes of Congenital Malformations Table 3. Many inborn errors of metab- Johnston 2001), clinically characterized by a severe olism fall into this category. In many patients, multisystem disorders are: the corpus callosum is absent (Dobyns 1989). In a) Congenital disorders of N- and O-linked gly- Lesch?Nyhan syndrome, hyperuricemia and a char- cosylation acteristic neurobehavioural syndrome with motor b) Mitochondrial encephalomyopathies dysfunction and self-injurious behaviour is found c) Lysosomal storage disorders (Jinnah and Friedmann 2001). Pyruvate dehydroge- eases caused by defects in the synthesis of the glycan nase deficiency is the best studied neurometabolic moiety of glycoconjugates or in the attachment of disorder (Brown et al. In addition to many examples of disorders in the metabolism of organic other organs, the brain is affected in 10 of the 11 acids are fumarase deficiency (Remes et al. Altering the sterol content of membranes may identified (Jaeken and Carchon 2001). Perturbations in cholesterol home- ing to pontocerebellar hypoplasia, is shown in Clini- ostasis may result from a defect in the normal Sonic cal Case 3. O-linked glycosylation defects form the hedgehog signalling network and cholesterol biosyn- underlying mechanism of certain lissencephalies thesis (Cohen and Shiota 2002; Chap. Mevalonic such as Walker?Warburg syndrome, Fukuyama con- aciduria, caused by deficiency of mevalonate kinase, genital muscular dystrophy and muscle?eye?brain an enzyme located proximally in the cholesterol disease (Barkovich et al. The patient showed pro- Disorders of Cholesterol Biosynthesis found psychomotor retardation,ataxia,a dysmorphic Defects of cholesterol biosynthesis (Fig. Abnormal sterols are known orders all show complex malformation syndromes 124 Chapter 3 Causes of Congenital Malformations Clinical Case 3. Microscopic ex- Congenital Disorders amination of the brain stem revealed severe atrophy of Glycosylation of the inferior olives (Fig. Distinct dentate nu- synthesis of the glycoconjugates or in the attachment clei were found. In the of glycans to macromolecules (Jaeken and Matthijs cerebrum, some nodular heterotopia were found 2001; Jaeken et al. This case was kindly provided by Gerard van Noort (Laboratory for Pathology East-Netherlands, En- schede,The Netherlands). A 15-year-old boy, with psy- chomotor retardation of unknown aetiology and se- vere scoliosis,died after a severe bronchopneumonia. At autopsy,an extensive necrotic bronchopneumonia References and signs of aspiration were found. The endocard showed fibrosis and the liver was steatotic and mildly Jaeken J, Matthijs G (2001) Congenital disorders of glycosyla- fibrotic (Fig. Brain examina- D (eds) the Metabolic & Molecular Bases of Inherited Dis- tion showed no obvious malformations of the cere- ease,8th ed. The cerebellar atrophy was present in findings in two patients with the carbohydrate-deficient gly- the vermis as well as in the hemispheres. Cardiac malformations are common form erythroderma and limb defects, is character- (Liu et al. Desmosterolosis shows a variable phenotype poplasia, especially of the vermis (Cherstvoy et al. Their enzymatic abilities include roles as oxi- disease, originally descibed as occurring only in chil- dases, in ether lipid synthesis, and in cholesterol and dren older than 1 year of age and in adults (van der dolichol biosynthesis. Moreover,typical in- sum disease, which are now thought to represent volvement of the pontine tegmental white matter was variants with different severity of the same disorder observed. The disease Myelination is the final phase in the development of is chronically progressive, with in most patients the cerebral white matter. Death occurs after a outwards from the oligodendrocyte cell body, are be- variable period of a few months to a few decades. Primary absence of central myelina- the developing brain is vulnerable to various vascu- tion has not been described so far. The cause of is- presence of myelin even at adult age (Koeppen and chemia or hypoxia may be maternal, placental, fetal Robitaille 2002). Early in gestation, prototype of a central hypomyelinating disorder general hypoxia may lead to very severe brain (Fig. They include dis- utero or before the adult features of the hemisphere eases such as globoid cell leukodystrophy (Krabbe are manifest (Friede 1989; Norman et al. This term is often used more widely, leukodystrophy (Ruggieri 1997; Aicardi 1998). Early particularly by neuroradiologists, who include uni- in the disease course, their clinical picture is general- lateral enlargement of the lateral ventricles. Hydra- ly dominated by bilateral and slowly progressive mo- nencephaly means the destruction of the cerebral tor manifestations such as spasticity and ataxia. Cog- hemispheres, usually the bilateral territories of sup- nitive and behavioural deterioration and epileptic ply of the internal carotid arteries, combined with phenomena usually appear at a later time and remain hydrocephalus due to aqueduct stenosis (Fig. In both types of brain injury a varying part of the basal Congenital white matter hypoplasia has also been re- ganglia and the thalamus are also involved (Norman ported without evidence of demyelination, dysmyeli- et al. When the fetus survives such serious 128 Chapter 3 Causes of Congenital Malformations Clinical Case 3. The girl was the first child of Zellweger Syndrome nonconsanguineous parents, born at 40. Her weight was 2,500 g (P5), and her head Zellweger syndrome is an early lethal multisystem circumference was 33 cm (P3). There were dysmor- disorder with deficient peroxisomes,and is character- phic signs: a broad nasal bridge, low-set ears, a high ized by cerebrohepatorenal malformations due to forehead, a small chin, Simian crease, joint contrac- defective b-oxidation of very long chain fatty acids tures of the lower limbs and bilateral congenital (Moser et al. X-ray examination of the knees showed fatty acids in plasma or cultivated fibroblasts (Gould stippled patellar calcifications. There was include dysmorphic facies, deafness, congenital severe epilepsy and poor psychomotor development. Material for further molecu- dase and glycolate oxidase, by the presence of phy- lar biological examination was not available. A McGraw-Hill,New York,pp 3181?3218 periventricular cavity was found on the left side. The polymicrogyric Increased level and impaired degradation of very-long-chain fatty acids and their use in prenatal diagnosis. The plump infe- D (eds) the Metabolic & Molecular Bases of Inherited Dis- rior olives showed an abnormal gyration pattern with ease,8th ed. Thijssen,Nijmegen) lesions, additionally polymicrogyria and other mal- dated the appearance of polymicrogyria in mono- formations may be seen,the extent of the lesion again zygotic twins to the 13th to 16th weeks of gestation. Bordarier and Robain (1995) described a case of An important cause of intrauterine ischemic cere- dizygotic twins in which both parts showed cerebral bral damage may be seen in monochorionic twins damage. Although shortage of blood in one fetus and surplus of blood in classically seen in very low birthweight infants with the other (Clinical Case 3. There are several reports less than 24 weeks of gestation or in sick premature of polymicrogyria in monozygotic twins (Norman neonates owing to disturbed autoregulation of cere- 1980; Barth and van der Harten 1985; Larroche et al. On microscopic examination, there was se- cephalic leukoencephalopathy with subcortical cysts vere diffuse degeneration of the myelin in the cen- and vanishing white matter, the gene defects have trum semiovale and to a lesser degree in the cerebral been identified (Leegwater et al. In the severely af- childhood, but onsets in early infancy, have also been fected parts of the brain, complete absence of myelin described. The youngest case reported so far is pre- with relatively little myelin debris was observed. The neuro- mutated in leukoencephalopathy with vanishing white mat- logical status of the baby deteriorated progressively ter. The first child in this family, a can cause leukoencephalopathy with vanishing white mat- ter. No cerebral aqueduct could be Porencephaly is a severe brain malformation, usually identified. At occurring early in gestation owing to general hypoxia autopsy, brain weight was 280 g. The second child of healthy ly torn corpus callosum,extremely reduced cerebellar parents with a normal first child presented with a hemispheres and absent pyramids (Fig. The term periventricular leuko- periventricular haemorrhage may extend into the malacia is used for the state in which the periventric- ventricle and ultimately give rise to hydrocephalus by ular white matter is destroyed and resorbed during blocking the narrow ventricular and arachnoidal the perinatal period in premature infants. It may also ex- and physiological circumstances of the premature in- tend into the brain parenchyma and even give rise to fant. Studies on the anatomy of the vascular supply to infarction of the adjacent white matter. The latter will the white matter suggested that the deep white mat- usually be haemorrhagic by obstruction of the drain- ter represented a watershed territory in this period ing veins (de Vries et al. Another important factor, con- During the last trimester of pregnancy (26?36 tributing to the vulnerability of the prenatal white weeks of gestation), the developing white matter is matter, may be the intrinsic vulnerability of the especially vulnerable to hypoxic?ischemic injuries. Owing to abnormal blood shunting between the pla- centae in monochorionic biamniotic twins, perfusion failure may occur. This may result in cerebral damage, the extent of which is dependent on the state of de- velopment of the fetus. Polymicrogyria is commonly one of the characteristic malformations (Barth and van der Harten 1985; Larroche et al. This was the second preg- nancy of nonsanguineous parents with one healthy child of 1 year old. Of the monozygotic twins, the fe- male patient was severely affected, the second twin was completely normal. During pregnancy,dispropor- tionate growth was noted and fetal movements were almost absent. At 27 weeks of gestation, polyhydram- nios was recognized on ultrasound examination, and 2,000 ml of amniotic fluid was removed through am- nion punctures in two sessions. The patient was born at 29 weeks of gestation and died a few minutes after birth owing to lung hypoplasia. The second of the twins was briefly admitted to the neonatal intensive care unit,but did well and showed no congenital mal- formations. There was only one umbilical artery in the first twin and a velamentous insertion of its umbilical cord. There was hyperextension of the neck and multiple joint contractures were evident. There was clinodactyly and camptodactyly, the knees were extended with genua recurvata. On the left side a pes equinovarus was present, and on the right side a pes calcaneovarus. Brain weight was polymicrogyric cortex (c) in a case of twin-to-twin transfu- 120 g (normal range 174?38 g). Microscopic examination showed that the References polymicrogyric cortex was severely disrupted. Acta Ectopic groups of neuroglial cells were found in the Neuropathol (Berl) 67:345?349 meninges. Biol Neonate 65:343?352 134 Chapter 3 Causes of Congenital Malformations have glutamate receptors and may be damaged by ex- cess glutamate release when neural tissue is damaged by ischemia (Kinney and Back 1998; McDonald et al. The lesions appear yellow owing to calci- um deposition and may become cavitated and cystic. The term telencephalic leukoencephalopathy is used to describe diffuse reactive changes throughout the white matter of the cerebral hemispheres without focal infarction or cyst formation. In multicystic leukoencephalopathy, the white matter contains many large cysts which may almost completely re- place it (Clinical Case 3. The most frequent is subventricular haem- orrhage, but if isolated it most often has no conse- quences (Volpe 2001a). The left hemisphere is more frequent- plexus haemorrhages most often are of no conse- ly affected than the right, probably owing to haemo- quence. Perinatal-stroke risk factors in- the vein of Galen are rare and other arteriovenous clude cardiac, blood, homocystein and lipid disor- malformations only rarely provoke intrauterine ders, infections, maternal and placental diseases, and problems. Besides rare haemorrhages, malformation iatrogenic interventions such as catheterization and of the vein of Galen may also lead to important cere- extracorporeal membrane oxygenation (Nelson and bral damage and ultimately brain atrophy due to is- Lynch 2004). Large parts of the neocortex were also severely necrotic with Multicystic leukoencephalopathy is the most severe sparing of the occipital lobes. The top of each sulcus form of white matter damage (Volpe 2001; Squier affected was always better preserved than its base. The lesions of the grey matter both sides,the hippocampus and the subiculum were in this case are typical for an episode of complete as- almost completely necrotic. They consist of severe loss of Purkinje cells and of some cells in the dentate necrosis of the deep brain nuclei, the neocortex and nuclei was found. The reason for the perinatal as- almost completely necrotic except for part of the phyxia was not entirely clear, but was probably pla- occipital white matter, leading to porencephaly. After an uneventful preg- distinct intima fibrosis and calcification of the inner nancy,birth at full term at home presented unexpect- part of the media (Fig. Deteriorating heart tones resulted in the transport of the mother to the hospital. Owing to traffic problems, transport took more than 1 h, after which a boy was born with low Apgar scores. Epileptic References fits were present from the first day but no sponta- Squier W (2002) Pathology of fetal and neonatal brain damage: neous movements were noted. The selective vulnerability of neuronal groups may explain the parasagittal cerebral injury at the 136 Chapter 3 Causes of Congenital Malformations Clinical Case 3.

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Signs Hypoesthesia of medial thigh region treatment wpw buy discount neurontin 800mg line, weakness and at- Relief rophy in adductor muscles medications causing thrombocytopenia buy generic neurontin 400mg online. Diabetes or any Laboratory Findings other systemic disease will be treated appropriately medicine everyday therapy cheap neurontin online mastercard. Surgical decompression of the lateral femoral cutaneous nerve as it passes under the inguinal ligament is asthma medications 7 letters neurontin 800 mg without a prescription, on rare Usual Course occasions medications for ibs buy cheap neurontin 800mg on-line, helpful in the patient who has failed conser- Constant aching pain that persists unless the cause is vative therapy treatment zenker diverticulum generic 400 mg neurontin mastercard. Essential Features Complications Hypoesthesia and paresthesia in upper anterolateral Progressive loss of sensory and motor functions in obtu- thigh. Differential Diagnosis Social and Physical Disability Radiculopathy of L2 or L3; upper lumbosacral plexus When severe, may impede ambulation and physical ac- lesion due to infection or tumor; entrapment of superior tivity involving hip. Page 198 Pathology Usual Course Obturator hernia; osteitis pubis, often secondary to lower Constant aching pain which persists unless cause is suc- urinary tract infection or surgery; lateral pelvic neoplasm cessfully treated. Complications Essential Features Progressive sensory and motor loss in femoral nerve or Pain in groin and medial thigh; with time the develop- its branches depending upon site of lesion. Social and Physical Disability Major gait disturbance if quadriceps femoris is paretic. Differential Diagnosis Tumor or inflammation involving L2-L4 roots, psoas Pathology muscle, pelvic side wall. X4a Neoplasm Differential Diagnosis Neoplasm or infection impinging upon femoral nerve, L2-L4 roots, psoas muscle, or pelvic sidewall. X6b Arthropathy Anterior surface of thigh, anteromedial surface of leg, medial aspect of foot to base of first toe. Definition Main Features Pain in the distribution of the sciatic nerve due to pa- Constant aching pain in anterior thigh, knee, medial leg, thology of the nerve itself. The pain may involve only a portion of the sensory field due to pathology in only one branch of the Site nerve. There may be sensory loss in similar areas and Lower extremity; may vary from gluteal crease to toes weakness of the quadriceps femoris, sartorius, and asso- depending upon level of nerve injury. If the disorder is secondary to femoral hernia, pain is increased by increase in intra-abdominal pressure. Main Features Trauma to the saphenous nerve may result in an isolated Continuous or lancinating pain or both, referred to the sensory deficit in the knee or leg with local pain. Hypoesthesia in anterior thigh, medial leg, and foot or portion thereof; weakness and atrophy in sartorius or Associated Symptoms quadriceps femoris muscles if lesion proximal to upper Weakness and sensory loss in muscles and other tissues thigh. There may be local tenderness at the site of nerve innervated by the damaged portion of the nerve; secon- injury. Laboratory Tests None Usual Course If a progressing lesion is the cause of the pain, the pa- Usual Course tient will have an increasing neurological deficit and Pain initially when walking, relieved by rest. If a static intraneural lesion is the sively severe and frequent lancinating pain in the toes cause of the pain, the neurological deficit is fixed and associated with constant metatarsal ache. Often associated with abnormal postures (narrow shoes or high Relief heels) or deformities of the foot and alleviated by treat- Remove offending lesion impinging upon nerve. Complications Relief Progressive neurological deficit in the territory of the Orthotic devices to force plantar flexion, i. Pathology Pathology Compression of interdigital nerve by metatarsal heads Varying degrees of myelin and axonal damage within and transverse metatarsal ligament; development of in- nerve. Essential Features Pain in region of metatarsal heads exacerbated by Essential Features weight-bearing. Differential Diagnosis Differential Diagnosis Myelopathy, radiculopathy, lumbosacral plexus lesion Sciatic or peroneal neuropathy, plantar fasciitis, metatar- involving L4-S 1 segments. Aching myofascial pain arising from trigger points lo- cated in one of the three gluteal muscles. Main Features Constant aching pain, often lancinating; often worse at Site night or during exercise; perceived in the region of the Gluteus maximus, medius, or minimus muscles. Page 200 System the sacroiliac joint or pain in the posterior leg and foot, Musculoskeletal system. Gluteus Maximus: Trigger points Site in this muscle may refer pain to any part of the buttock Buttock from sacrum to greater femoral trochanter with or coccyx areas. Gluteus Medius: Trigger points in this or without posterior thigh, leg, foot, groin, or perineum. Those in the or in which the piriformis prevents excessive medial posterior portion refer pain downward into the lower rotation by acting as a lateral rotator of the thigh during part of the buttock, the posterior part of the thigh, and twisting and bending movements. The knee joint is not aware of the injury until hours or days after the inci- spared in this distribution. Symptoms are particularly aggravated by sitting to that of sciatica and also of other low back pain condi- (which places pressure on the piriformis muscle) and by tions involving the gluteal musculature. Placing the hip in external rotation may de- located in the anterior portion refer pain similarly except crease pain. Course: without appropriate intervention, that it is distributed along the lateral rather than posterior persistent pain. Aggravating Factors A foot with a long second and short first metatarsal Associated Symptoms bone. It can act as a perpetuating factor for all the gluteal Paresthesias in the same distribution as the pain; other muscles, especially the gluteus medius. Straight leg raising is usually dyspareunia, pain on passing constipated stool, impo- restricted because of tightness in the hamstring and glu- tence. Signs Pathology On external palpation through a relaxed gluteus maxi- See myofascial pain syndromes. On Trigger points of the gluteal musculature very often internal palpation during rectal or vaginal examination: function as satellite trigger points of those located in the piriformis muscle tenderness and firmness (medial trig- quadratus lumborum muscle. Reproduction of buttock Differential Diagnosis pain with stretching the piriformis muscle during hip Sacroiliac joint dysfunction, sciatic neuritis, piriformis flexion, abduction, and internal rotation while lying su- syndrome. Painful hip abduction against resistance while sit- Code ting (Pace Abduction Test). Pain in the buttock and posterior thigh due to myofascial Bone scan (Tc-99m methylene diphosphonate) is usually injury of the piriformis muscle itself or dysfunction of normal but has been reported to show increased piri- Page 201 formis muscle uptake acutely. Selected nerve conduction studies Essential Features may demonstrate nerve entrapment. Buttock pain with or without thigh pain, which is aggra- vated by sitting or activity. Posterolateral ten- sponds well to appropriate interventions, particularly in derness and firmness on rectal or vaginal examination. Relief Correction of biomechanical factors (leg length discrep- Differential Diagnosis ancy, hip abductor or lateral rotator weakness, etc. Pro- Lumbosacral radiculopathy, lumbar plexopathy, proxi- longed stretching of piriformis muscle using hip flexion, mal hamstring tendinitis, ischial bursitis, trochanteric abduction, and internal rotation. Facilitation of stretch- bursitis, sacroiliitis, facet syndrome, spinal stenosis (if ing by: reciprocal inhibition and postisometric relaxation bilateral symptoms). May occur concurrently with lum- techniques; massage; acupressure (ischemic compres- bar spine, sacroiliac, and/or hip joint pathology. Xlf procaine/Xylocaine) to region of lateral attachment of piriformis on femoral greater trochanter (lateral trigger References point), or to tender areas medial to sciatic nerve near Travell, J. The lower extremities, piri- sacrum (medial trigger point) with rectal/vaginal moni- formis, and other short lateral rotators. If previous measures fail, surgical transection of & Wilkins, Baltimore, 1992, pp. Social and Physical Disabilities Difficulty sitting for prolonged periods and difficulty with physical activities such as prolonged walking, standing, bending, lifting, or twisting compromise both sedentary and physically demanding occupations. Main Features Metastases to the hip joint region produce continuous System aching or throbbing pain in the groin with radiation Nervous system. In some cases peripheral causes have through to the buttock and down the medial thigh to the been described; the spinal cord is probably also in- knee. A me- tastatic deposit to the femoral shaft produces local pain, Main Features which is also aggravated by weight-bearing. Sometimes re- Pain at rest due to tumor infiltration of bone usually re- lieved by activity, though it may be worse following sponds reasonably well to nonsteroidal anti- exercise. Pain due to ments may be florid or almost imperceptible, and in the hip movement or weight-bearing responds poorly to latter case, the patient may never have noticed them. They consist of irregular, involuntary, and sometimes writhing movement of the toes, and they cannot be imi- Signs and Laboratory Findings tated voluntarily. They can be suppressed for a minute or There may be tenderness in the groin and in the region two by voluntary effort and then return when the patient of the greater trochanter. There is not usually a relation between the formity unless a pathological fracture has occurred. Complications the major complication is a pathological fracture of the Relief femoral neck or the femoral shaft. Pathology Precise pathology unknown, but nerve root lesions have Summary of Essential Features and Diagnostic been described, and spinal cord damage. There is usually tenderness in the groin and increased pain on internal and external rota- References tion. Differential Diagnosis the differential diagnosis includes upper lumbar plexo- Nathan, P. Psychiatry, 41 (1978) pathy, avascular necrosis of the femoral head, and septic 934-939. Definition Usual Course Pain in the limbs, usually constant and aching in the feet, Unremitting. Pathology Site Degenerative changes appear in the dorsal root ganglion the distal portion of the limbs, more often in the feet cells or motor neurons of the spinal cord with resulting than in the hands, and across the joint spaces. Cold, damp, and changes in the weather appear to cause an increase in the symptom. Rest, simple analgesics the pain arises in association with peroneal muscular such as paracetamol (acetaminophen) and nonsteroidal atrophy. Age anti-inflammatory drugs, and transcutaneous electrical of Onset: the illness normally appears in childhood and stimulation help to ease the pain. Relief is also associ- adolescence, with a reported age range for prevalence ated with warmth, massage, lying down, sleep, and dis- from 10-84 years. The sex linked form is less common than the other Conduction velocities in motor nerves may be de- types. Pain Quality: pain is relatively rare in the disease, creased, or denervation may be evident. It may be continuous or intermittent but is aggra- Essential Features vated by activity, stress, cold, and damp. This aching Pain in the relevant distribution in patients affected by pain appears most often as a complication of surgical the typical muscle disorder. Anxiety and Pain affecting joints only fatigue appear in association with the pain. There is Pain affecting the belly of the muscle distal muscle wasting with the classical inverted 205. Definition System Severe, sharp, or aching pain syndrome arising from Musculoskeletal system. The patient characteris- tically finds it impossible to sleep on the affected side. Cases are often secondary to systemic Aggravated by climbing stairs, extension of the back inflammatory disease, such as ankylosing spondylitis, from flexion with knees straight. Relief Usual Course Injection into the ischial bursa with local anesthetic and Usually of sudden onset. The pain tends to be severe and steroid; doughnut cushion as used for treatment of persistent. Local infiltration of local anesthetic and steroid into the area of the greatest tenderness produces excellent pain Pathology relief. Essential Features Recurring pain in ischial region aggravated by sitting or Pathology lying, relieved by injection. Inflammatory process of bursa caused by repeated trauma or generalized inflammation such as rheumatoid Differential Diagnosis arthritis. X3 Local pain aggravated by climbing stairs, extension of the back from flexion with knees straight. Aching or burning pain in the high lateral part of the thigh and in the buttock caused by inflammation of the Code 634. Definition Pain due to primary or secondary degenerative process involving the hip joint. Treatment with qui- Pain due to a degenerative process of one or more of the nine, calcium supplements, diphenhydramine, diphenyl three compartments of the knee joint. X8 ology, aggravating and relieving features, signs, usual course, physical disability, pathology, and differential diagnosis as for osteoarthritis (I-11). Main Features Pain with insidious onset in the plantar region of the System foot, especially worse when initiating walking. Main Features Signs Severe aching cramps in the calves of the legs, often Tenderness along the plantar fascia when ankle is dorsi- preventing the patient from sleep or waking him or her flexed. Page 206 Radiographic Findings Pathology Often associated with calcaneal spur when chronic. Fifteen percent have some form of systemic rheumatic disease, usually a seronegative form of spondylarthritis. Relief Arch supports, local injection of corticosteroid, oral non- Differential Diagnosis steroidal anti-inflammatory agents. Many of the terms were already es- process by which the terms were first delivered and the tablished in the literature.

The primary event is dete- Without prompt treatment symptoms gastritis purchase neurontin with mastercard, permanent rioration of articular cartilage and medications not to take when pregnant discount 100mg neurontin amex, even- joint damage can rapidly result medications pictures order cheap neurontin line. The bone-on-bone teria usually infect the joint through contact is the primary cause of pain treatment for piles neurontin 100mg sale, as hematogenous spread or secondary to there are many nerve endings at the artic- osteomyelitis medicine descriptions purchase 600mg neurontin free shipping. The diagno- It can be occasionally due to trauma or sis is made by clinical assessment in con- skin infection medicine keri hilson lyrics order neurontin 100mg otc. This tures of a hip joint tumor are outlined in and w alkers are a results in the destruc- Table 1. In characterizing hip tumors, it is tion of articular carti- useful to consider the following three com m on part of the lage and the subchon- parameters:5 nonsurgical dral bone. Anatomic location and site of the treatm ent for mities, such as swan tumor; neck, boutonniere, 2. Large, aggressive lesions mer toes and flexion with irregular margins or soft-tissue contractures, are often inspected. Pain is characteristically felt in der, and a moth-eaten appearance is the groin or thigh, but may occur in the characteristic of aggressive lesions; lumbar spine or knee. The most slow-expanding lesions, the periosteal definitive diagnostic tool, however, is a sleeve may remain intact and continue biopsy. Biopsies are indicated in cases of new bone formation during the expan- suspected malignancy, selected benign sion. This leads to the appearance of a tumors or in cases of an uncertain diagno- Codmans triangle or lamellar sis. In rapidly growing Trauma tumors that extend beyond the Trauma to the hip can result in a hip frac- periosteal sleeve, the radiograph has a ture, dislocation, or both. Clinically, the limb is shortened, is interruption of blood supply to the internally rotated and adducted. Alcoholism and steroid Trauma to the hip also can result in use are the two most common causes of fractures. Neurom uscular Problem s the two nerves most likely to cause pain or numbness around the hip are the sciatic and lateral femoral cutaneous nerves. The sci- atic nerve includes motor and sen- sory components that originate from the L4-S3 nerve roots. It passes through the sciatic notch, where it is susceptible to compres- sion by the piriformis muscle (Figure 1). Typical symptoms include a dull ache in the buttock, which may radiate down the poste- rior thigh. This pain may be diffi- cult to distinguish from radicular pain caused by nerve root com- pression in the lumbosacral spine. It can be compressed as it passes under the inguinal ligament, espe- Strains and tendonitis are common causes cially in obese patients and those with of hip pain related to soft-tissue injury. This condi- strain is an acute injury to a muscle or ten- tion is known as meralgia paresthetica, don. In contrast, tendonitis denotes and causes numbness or pain over the acute inflammatory tendon changes sec- anterolateral thigh (Figure 2). In the anterior hip, the Neuromuscular hip conditions also can muscles most likely to be acutely or be classified as either intrinsic or extrinsic chronically injured are the rectus abdo- disorders. Most often, the injuries occur intrinsic neuromuscular hip disorders, the at the muscle-tendon junction. Spinal muscle imbalance, resulting from hip flexion during anterior sitting is the posi- adductors and flexors overpowering the tion that raises the intradiscal pressure to hip abductors and extensors. The intrinsic the greatest degree and suggests disc dis- neuromuscular disorders associated with ease. An abnormal neurologic Extrinsic neuromuscular dysfunctions examination of the lower extremities sug- secondarily involving the hip joint com- gests radiculopathy. The history and physical, therefore, luxation/dislocation plays a secondary may need to be focused on bladder and role, contractures frequently develop. Some of these disorders are associated with spasticity, and others have flaccid Conclusion paralysis as the dominant feature. It is beyond the Most importantly, one needs to consider scope of this article to describe each of the location of the pain and inquire about these conditions in detail. The 34 Adult Hip Pain information gathered from the history will instances, orthopedic consultation may be guide the physician in choosing certain necessary. Clinical Orthopedics helpful to further understand the distin- and Related Research 1999; 368:135-40. We are nd What to expect during the test located in the Gateway Building, 2 floor, 1200 East. Depending on the type of exam, images are the following information about your test. Your technologist (804) 828-6828 to schedule your test or if you have any performing the test will let you know what time questions about your nuclear medicine exam. You will lie down If you have unexplained bone pain, a bone scan may help while the camera takes scans of your bones from determine the cause. Drinking extra fluids may help bones (osteomyelitis) the tracer leave your body faster. The inf o rm a tio n pro vided in these guidelinesis im po rta nt o rprim a ry hea lthca re pro vidersin the f eldso f pedia trics, o nco lo gy, interna lm edicine, f a m ily pra ctice, a nd gyneco lo gy, a swella ssubspecia listsin m a ny f elds Im plem enta tio n o f these guidelinesisintended to increa se a wa renesso po tentia lla the ef ectsa nd to sta nda rdize a nd enha nce f o llo w- up ca re pro vided to survivo rso pedia tric m a ligna nciesthro ugho uttheirliespa n. M o nro via, C : C hildren sO nco lo gy G ro up; O cto ber 2 va ila ble o n- line: v i v o G uide line s M e t h odolog y L a ndierW, B ha tia S, Eshelm a n D o rte K, Sweeney T, Hester L, D a rling J rm stro ng F la tt, C o nstine L S, F reem a n C R riedm a n D L, G reen D M, M a rina N, M ea do ws T, Neglia J P, O ef f ngerK C, R o biso n L L, R uccio ne K S, Skla rC, Hudso n M M evelo pm ento f risk- ba sed guidelines o rpedia tricca ncersurvivo rs : the C hildren sO nco lo gy G ro up lo ng- term f o llo w- up guidelines ro m the C hildren sO nco lo gy G ro up L a the Ef ectsC o m m ittee a nd Nursing D iscipline. H e alt h Links Backg round and A p p licat ion Eshelm a n D, L a ndierW, Sweeney T, Hester L, F o rte K a rling J Hudso n M M a cilita ting ca re f o rchildho o d ca ncersurvivo rs : integra ting C hildren sO nco lo gy G ro up lo ng- term f o llo w- up guidelinesa nd hea lth linksin clinica lpra ctice. The Inf o rm a tio na lC o ntentisno tintended to substitute f o rm edica la dvice, m edica lca re, dia gno siso rtrea tm ento bta ined f ro m a physicia n o rhea lthca re pro vider To ca ncersurvivo rs i children, theirpa rentso rlega lgua rdia ns : Plea se seek the a dvice o a physicia n o ro therqua lif ed hea lthca re pro viderwith a ny questio nsyo u m a y ha ve rega rding a m edica lco nditio n a nd do no trely o n the Inf o rm a tio na lC o ntent. The C hildren sO nco lo gy G ro up isa resea rch o rga niza tio n a nd do esno tpro vide individua lized m edica lca re o rtrea tm ent To physicia nsa nd o therhea lthca re pro viders: the Inf o rm a tio na lC o ntentisno tintended to repla ce yo urindependentclinica ljudgm ent, m edica la dvice, o rto exclude o therlegitim a the criteria f o rscreening, hea lth co unseling, o rinterventio n f o rspecif cco m plica tio nso f childho o d ca ncertrea tm ent. Neitheristhe Inf o rm a tio na lC o ntentintended to exclude o therrea so na ble a lterna tive f o llo w- up pro cedures. The Inf o rm a tio na lC o ntentispro vided a sa co urtesy, butno tintended a sa so le so urce o guida nce in the eva lua tio n o childho o d ca ncersurvivo rs. The C hildren s O nco lo gy G ro up reco gnizestha tspecif cpa tientca re decisio nsa re the prero ga tive o the pa tient a m ily, a nd hea lthca re pro vider No endo rsem ento f a ny specif ctests, pro ducts, o rpro ceduresism a de by Inf o rm a tio na lC o ntent, the C hildren sO nco lo gy G ro up, o ra f f lia ted pa rty o rm em bero the C hildren sO nco lo gy G ro up. N o C l aim to A ccu racyor C om pl eteness: W hile the C hildren sO nco lo gy G ro up ha sm a de every a ttem ptto a ssure tha tthe Inf o rm a tio na lC o ntentisa ccura the a nd co m plete a so the da the o f publica tio n, no wa rra nty o rrepresenta tio n, expresso rim plied, ism a de a sto the a ccura cy, relia bility, co m pleteness, releva nce, o rtim elinesso such Inf o rm a tio na lC o ntent N o L iabil ityon P artof C hil dren s O ncol og y rou p and R el ated P arties/ g reem entto I ndem nifyand H ol d H arm l ess the C hil dren s O ncol og y rou p and R el ated P arties: No lia bility is a ssum ed by the C hildren sO nco lo gy G ro up o ra ny a f f lia ted pa rty o rm em berthereo f o rda m a ge resulting f ro m the use, review, o ra ccesso the Inf o rm a tio na lC o ntent. Yo u a gree to the f o llo wing term so f indem nif ca tio n: i Indem nif ed Pa rties include a utho rsa nd co ntributo rsto the Inf o rm a tio na lC o ntent, a llo f cers, directo rs, representa tives, em plo yees, a gents, a nd m em berso the C hildren sO nco lo gy G ro up a nd a f f lia ted o rga niza tio ns ii by using, reviewing, o ra ccessing the Inf o rm a tio na lC o ntent, yo u a gree, a tyo uro wn expense, to indem niy, def end a nd ho ld ha rm less Indem nif ed Pa rties ro m a ny a nd a lllo sses, lia bilities, o rda m a ges including a tto rneys eesa nd co sts resulting f ro m a ny a nd a llcla im s, ca useso a ctio n, suits, pro ceedings, o rdem a ndsrela ted to o ra rising o uto f use, review o ra ccesso f the Inf o rm a tio na lC o ntent P roprietaryR ig hts: the Inf o rm a tio na lC o ntentissubjectto pro tectio n underthe co pyrightla w a nd o therintellectua lpro perty la w in the United Sta tesa nd wo rldwide. The C hildren sO nco lo gy G ro up reta insexclusive co pyrighta nd o therright, title, a nd interestto the Inf o rm a tio na lC o ntenta nd cla im sa llintellectua lpro perty rightsa va ila ble underla w. C ha ng, M L ucile Pa cka rdC hildren sHo spita lSta nf o rdUniversity O to la ryngo lo gy D o ugla s C ipka la, M Sa intVincentHo spita la ndHea lth C a re C enter Pedia tricO nco lo gy Sa tkira nS. C o hen, M a na - a rber/ Ha rva rdC a ncerC enter Pedia tricEndo crino lo gy Thyro id L illia nR M ea cha m, M to C hildren sHea lthca re o tla nta Eglesto n Pedia tricEndo crino lo gy L ilibeth R. To rno, M C hildren sHo spita lo O ra nge C o unty Pedia tricO nco lo gy Sta ceyUrba ch, M Ho spita l o rSick C hildren Pedia tricEndo crino lo gy G rego ryC. C o hen, M a na - a rber/ Ha rva rdC a ncerC enter Pedia tricEndo crino lo gy L o uisS. PerkinsM M S C hildren sHo spita lsa ndC linicso M inneso ta M innea po lis Pedia tricO nco lo gy Sha ntiR a m a cha ndra n, M S, R C P, M Pa eds Perth C hildren sHo spita l Hem a to po ieticC ellTra nspla nta tio n L inda S. Huh, M M nderso nC a ncerC enter Pedia tricO nco lo gy Sue C K a ste, O St ude C hildren sR esea rch Ho spita l Pedia tricR a dio lo gy Va lera e O L ewisM M nderso nC a ncerC enter O rtho pedicO nco lo gy J illL. R a nda ll M C S Prim a ryC hildren sHo spita l O rtho pedicO nco lo gy K a ren W a silewskiM a sker M to C hildren sHea lthca re o tla nta Eglesto n Pedia tricO nco lo gy C a rm en W ilso n, PhD St ude C hildren sR esea rch Ho spita l Epidem io lo gy Neuro co gnitive Lyn a lsa m o, PhD Ya le University Psycho lo gy Psycho so cia l Pia a nerjee, PhD St ude C hildren sR esea rch Ho spita l Neuro psycho lo gy M a tthew itsko, PhD Virginia C o m m o nwea lth University/ M a sseyC a ncerC enter Pedia tricPsycho lo gy R ebecca o ster PhD W a shingto nUniversityScho o lo M edicine Pedia tricPsycho lo gy M a tthew Ho cking, PhD C hildren sHo spita lo Phila delphia Psycho lo gy L a ura a nzen, PhD Ho spita l o rSick C hildren Neuro psycho lo gy Nina S. W o o dm a n, M Universityo Io wa / Ho ldenC o m prehensive C a ncerC enter a m ilyM edicine O ra l enta l Sha ro nC a stellino, M M Sc C hildren sHea lthca re o tla nta Eglesto n Pedia tricO nco lo gy C a thleenM C o o k, M Ea stC a ro lina University Pedia tricO nco lo gy K a renE. Turco tte, M Universityo M inneso ta / M a so nicC a ncerC enter Pedia tricO nco lo gy Tung T. Pro m o teshea lthy liestyles a re def ned a sthera py- rela ted co m plica tio nso ra dverse ef ectstha tpersisto ra rise a f ter b. Pro vides o ro ngo ing m o nito ring o hea lth sta tus co m pletio n o f trea tm ent o ra pedia tricm a ligna ncy. Pro videstim ely interventio n f o rla the ef ects these guidelinesrepresenta sta tem ento f co nsensus ro m a pa nelo f expertsin the la the ocu s ef ectso pedia tricca ncertrea tm ent. The guidelinesa re bo th evidence- ba sed utilizing these guidelinesa re intended f o ruse esta blished a sso cia tio nsbetween thera peuticexpo suresa nd la the ef ectsto identiy high- c, a nd pro vide a f ra m ewo rk f o ro ngo ing la the ef ectsm o nito ring risk ca tego ries a nd gro unded in the co llective clinica lexperience o f experts m a tching the in childho o d ca ncersurvivo rs v e v i d m a gnitude o the risk with the intensity o f the screening reco m m enda tio ns g v i v o Since thera peuticinterventio ns o ra specif cpedia tricm a ligna ncy m a y va ry co nsidera bly T arg etP opu l ation ba sed o n the pa tient sa ge, presenting f ea tures, a nd trea tm entera, a thera py- ba sed design wa scho sen to perm itm o dula r o rm a tting o f the guidelinesby thera peuticexpo sure. M edica lcita tio nssuppo rting the a sso cia tio n o f ea ch la the ef ectwith o o ngo ing issuesrela ted to the lo ng- term f o llo w- up needso thispa tientpo pula tio n is a specif cthera peuticexpo sure a re included. R evisio nswere m a de ba sed ca re f o rsurvivo rso f childho o d, a do lescent, a nd yo ung a dultca ncers. The revised dra f twa sthen sento utto a dditio na lm ultidisciplina ry to putthe reco m m enda tio nsin perspective, a vo id o ver testing, a ddresspo tentia la nxieties, a nd experts o r urtherreview. The C hildren sO nco lo gy guidelinessubsequently underwentco m prehensive review a nd sco ring by a pa nelo expertsin G ro up itsel do esno tpro vide individua lized trea tm enta dvice to survivo rso rtheir a m ilies, a nd the la the ef ectso pedia tricm a ligna ncies, co m prised o m ultidisciplina ry representa tives ro m stro ngly reco m m endsdiscussing thisinf o rm a tio n with a qua lif ed m edica lpro f essio na l the C O L a the Ef ectsC o m m ittee. Ea ch Hea lth L ink underwenttwo levelso f G ro up Nursing D iscipline a nd L a the Ef ectsC o m m ittee a nd a re m a inta ined a nd upda ted by review; f rstby the Nursing C linica lPra ctice Subco m m ittee to veriy a ccura cy o co ntenta nd the C hildren sO nco lo gy G ro up sL o ng- Term F o llo w- Up G uidelinesC o re C o m m ittee a nd its reco m m enda tio ns, a nd then by m em berso the L a the Ef ectsC o m m ittee to pro vide expert a sso cia ted Ta sk F o rces llC hildren sO nco lo gy G ro up m em bersha ve co m plied with the m edica lreview) a nd Pa tient dvo ca cy C o m m ittee to pro vide f eedba ck rega rding presenta tio n C O co nf icto f interestpo licy, which requiresdisclo sure o f a ny po tentia lf na ncia lo ro ther o co ntentto the la y public co nf icting interests P re- R el ease R eview E vidence C ol l ection the initia lversio n o the guidelines Versio n 1 ? C hildren sO nco lo gy G ro up the ffe ts Pertinentinf o rm a tio n f ro m the published m edica llitera ture o verthe pa st yea rs upda ted a s u i d s wa srelea sed to the C hildren sO nco lo gy G ro up m em bership in M a rch o f O cto ber wa sretrieved a nd reviewed during the develo pm enta nd upda ting o f these o ra six- m o nth tria lperio d. R evisions R ef erences ro m the biblio gra phieso f selected a rticleswere used to bro a den the sea rch. The guidelineswere initia lly relea sed to the public Versio n 1 ? u r M ethods w - u i d s o n the C hildren sO nco lo gy G ro up W ebsite in Septem ber In 2, the lea dership o f the C hildren sO nco lo gy G ro up L a the Ef ectsC o m m ittee a nd Nursing o llo wing thisrelea se, cla rif ca tio n rega rding the a pplica bility o the guidelinesto the D iscipline a ppo inted a 7 m em berta sk f o rce, with representa tio n f ro m the L a the Ef ects a do lescenta nd yo ung a dultpo pula tio nso ca ncersurvivo rswa srequested. In respo nse, C o m m ittee, Nursing D iscipline, a nd Pa tient dvo ca cy C o m m ittee. The ta sk f o rce wa sco nvened a dditio na lm ino rm o dif ca tio nswere m a de a nd the title o the guidelineswa scha nged. A to review a nd sum m a rize the m edica llitera ture a nd develo p a dra f to f clinica lpra ctice revised versio n Versio n 1 ? w - u i d s fo u r s o f C guidelinesto directlo ng- term f o llo w- up ca re f o rpedia tricca ncersurvivo rs. These ta sk f o rcesa re the o rigina ldra f twentthro ugh severa litera tio nswithin the ta sk f o rce prio rto initia lreview. Ta sk f o rce m em bersa re a ssigned a cco rding to theirrespective were a ssigned a cco rding to a m o dif ed versio n o the Na tio na lC o m prehensive C a ncerNetwo rk a rea so expertise a nd clinica linteresta nd m em bership isupda ted every 2 yea rs listo f C a tego rieso C o nsensus, a s o llo ws these ta sk f o rcesa nd theirm em bership isincluded in the C o ntributo rs sectio n o f this C ateg ory tatem entof C onsensu s do cum ent, ref ecting co ntributio nsa nd reco m m enda tio nsreleva ntto the currentrelea se o these guidelines Versio n 5 ? O cto ber There isunio rm co nsensuso the pa neltha t 1 There ishigh- levelevidence linking the la the ef ectwith the thera peutic A llrevisio nspro po sed by the ta sk f o rceswere eva lua ted by a pa nelo f experts, a nd i expo sure a ccepted, a ssigned a sco re see Sco ring Expla na tio n sectio n o f Pref a ce). Pro po sed revisio ns 2 the screening reco m m enda tio n isa ppro pria the ba sed o n the co llective tha twere rejected by the expertpa nelwere returned with expla na tio n to the releva ntta sk clinica lexperience o pa nelm em bers f o rce cha ir. I desired, ta sk f o rce cha irswere given a n o ppo rtunity to respo nd by pro viding a dditio na ljustif ca tio n a nd resubm itting the rejected ta sk f o rce reco m m enda tio n( s o r urther There isunio rm co nsensuso the pa neltha t co nsidera tio n by the expertpa nel There islo wer levelevidence linking the la the ef ectwith the thera peutic expo sure P l an for U pdates 2 the screening reco m m enda tio n isa ppro pria the ba sed o n the co llective the m ultidisciplina ry ta sk f o rcesdescribed a bo ve willco ntinue to m o nito rthe litera ture a nd clinica lexperience o pa nelm em bers repo rtto the C O L o ng- Term F o llo w- Up G uideline C o re C o m m ittee during ea ch guideline 2 There isno n- unio rm co nsensuso the pa neltha t review/ upda the cycle. Perio dicrevisio nsto these guidelinesa re pla nned a snew inf o rm a tio n 1 There islo wer levelevidence linking the la the ef ectwith the thera peutic beco m esa va ila ble, a nd a tlea stevery 5 yea rs. C linicia nsa re a dvised to check the C hildren s O nco lo gy G ro up website perio dica lly f o rthe la testupda tesa nd revisio nsto the guidelines expo sure which willbe po sted a t v i v o the screening reco m m enda tio n isa ppro pria the ba sed o n the co llective clinica lexperience o pa nelm em bers S coring xpl anation 3 There ism a jo rdisa greem enttha tthe reco m m enda tio n isa ppro pria te. These guidelinesrepresenta sta tem ento f co nsensus ro m a m ultidisciplina ry pa nelo f U niform consensu s Nea r una nim o usa greem ento the pa nelwith so m e po ssible neutra lpo sitio ns expertsin the la the ef ectso f pedia tricca ncertrea tm ent. The guidelineso utline m inim um N on- u niform consensu s : the m a jo rityo pa nelm em bersa gree with the reco m m enda tio n; ho wever there reco m m enda tio ns o rspecif chea lth screening eva lua tio nsin o rderto detectpo tentia lla the isreco gnitio na m o ng pa nelm em berstha tgiventhe qua lityo evidence, clinicia nsm a ycho o se to a do pt ef ectsa rising a sa resulto f thera peuticexpo suresreceived during trea tm ento f childho o d, di erenta ppro a ches a do lescent, a nd yo ung a dultca ncers H ig h- evel evidence Evidence derived ro m high qua lityca se co ntro lo rco ho rtstudies L ow er evel evidence Evidence derived ro m no n- a na lyticstudiesca se repo rtsca se seriesa ndclinica l Ea ch sco re rela testo the strength o f the a sso cia tio n o f the identif ed la the ef ectwith experience. Thisisdue to the f a cttha tthere a re no ra ndo m ized clinica ltria ls a nd C a tego ry 2 reco m m enda tio nsa re designa ted a s 2 there isunio rm ity o co nsensus no ne f o rthco m ing in the f o reseea ble f uture) o n which to ba se reco m m enda tio ns o rperio dic a m o ng the reviewersrega rding strength o evidence a nd a ppro pria tenesso the screening screening eva lua tio nsin thispo pula tio n; theref o re, the guidelinessho uld no tbe m isco nstrued reco m m enda tio n) o r 2 there isno n- unio rm co nsensusa m o ng the reviewersrega rding a srepresenting co nventio na l evidence- ba sed clinica lpra ctice guidelines o r sta nda rdso strength o evidence a nd a ppro pria tenesso the screening reco m m enda tio n) ca re. R a thertha n subm itting reco m m enda tio nsrepresenting m a jo rdisa greem ents, item ssco red Ea ch item wa ssco red ba sed o n the levelo f evidence currently a va ila ble to suppo rtit. C o nsidera tio nsin this Screening a nd f o llo w- up reco m m enda tio nsa re o rga nized by thera peuticexpo sure a nd rega rd include the pra ctica lity a nd ef f ciency o a pplying these bro a d guidelinesin individua l included thro ugho utthe guidelines. Pedia tricca ncersurvivo rsrepresenta rela tively sm a llbut clinica lsitua tio ns. Studiesto a ddressguideline im plem enta tio n a nd ref nem enta re a to p gro wing po pula tio n a thigh risk f o rva rio usthera py- rela ted co m plica tio ns ltho ugh severa l prio rity o the C O L o ng- Term F o llo w- Up G uideline C o re C o m m ittee; studieso ea sibility o f wellco nducted studieso n la rge po pula tio nso f childho o d ca ncersurvivo rsha ve dem o nstra ted guideline use ha ve been repo rted in lim ited institutio nsa nd o thersa re currently underwa y a sso cia tio nsbetween specif cexpo suresa nd la the ef ects, the size o f the survivo rpo pula tio n Issuesbeing a ddressed include descriptio n o a nticipa ted ba rriersto a pplica tio n o the a nd the ra the o f o ccurrence o f la the ef ectsdo esno ta llo w f o rclinica lstudiestha two uld a ssess reco m m enda tio nsin the guidelinesa nd develo pm ento review criteria f o rm ea suring cha nges the im pa cto f screening reco m m enda tio nso n the m o rbidity a nd m o rta lity a sso cia ted with the in ca re when the guidelinesa re im plem ented. Theref o re, sco ring o f ea ch expo sure ref ectsthe expertpa nel sa ssessm ento f the evidence esta blishing the ef f ca cy o screening f o rla the co m plica tio nsin pedia tricca ncer levelo f litera ture suppo rtlinking the thera peuticexpo sure with the la the ef ectco upled with a n survivo rs. W hile m o stclinicia nsbelieve tha to ngo ing surveilla nce f o rthese la the co m plica tio ns a ssessm ento f the a ppro pria tenesso f the reco m m ended screening m o da lity in identiying the isim po rta ntin o rderto a llo w f o rea rly detectio n a nd interventio n f o rco m plica tio nstha tm a y po tentia lla the ef ectba sed o n the pa nel sco llective clinica lexperience. W hile reco gnizing tha tthe length a nd identif ca tio n o a nd interventio n f o rla the o nsetthera py- rela ted co m plica tio nsin thisa trisk depth o these guidelinesisim po rta ntin o rderto pro vide clinica lly- releva nt, evidence- ba sed po pula tio n, po tentia lly reducing o ra m elio ra ting the im pa cto f la the co m plica tio nso n the hea lth reco m m enda tio nsa nd suppo rting hea lth educa tio n m a teria ls, clinicia n tim e lim ita tio nsa nd sta tuso f survivo rs. In a dditio n, o ngo ing hea lthca re tha tpro m o teshea lthy liestyle cho icesa nd the ef o rtrequired to identiy the specif creco m m enda tio nsreleva ntto individua lsurvivo rs pro videso ngo ing m o nito ring o f hea lth sta tusisim po rta nt o ra llca ncersurvivo rs ha ve been identif ed a sba rriersto theirclinica la pplica tio n. Theref o re, the C O L o ng- Term Po tentia lha rm so f guideline im plem enta tio n include increa sed pa tienta nxiety rela ted to o llo w- Up G uideline C o re C o m m ittee ha spa rtnered with the B a ylo rScho o lo M edicine to enha nced a wa renesso f po ssible co m plica tio ns, a swella sthe po tentia l o r a lse- po sitive develo p a web- ba sed intera ce, kno wn a s Pa sspo rt o rC a re, tha tgenera tesindividua lized screening eva lua tio ns, lea ding to unnecessa ry f urtherwo rkup. In a dditio n, co stso f lo ng- expo sure- ba sed reco m m enda tio ns ro m these guidelinesin a clinicia n- o cused f o rm a t o rea se term f o llo w- up ca re m a y be pro hibitive f o rso m e survivo rs, pa rticula rly tho se la cking o pa tientspecif ca pplica tio n o the guidelinesin the clinica lsetting. The Pa sspo rt o rC a re hea lth insura nce, o rtho se with insura nce tha tdo esno tco verthe reco m m ended screening a pplica tio n isa va ila ble to C hildren sO nco lo gy m em berinstitutio nsa tno co st o ra dditio na l eva lua tio ns inf o rm a tio n, plea se co nta ctM a rcE. Ho ro witz, M o rSusa n K ra use P atientP references Ultim a tely, a swith a llclinica lguidelines, decisio nsrega rding screening a nd clinica l u nding ou rce m a na gem ent o ra ny specif cpa tientsho uld be individua lly ta ilo red, ta king into co nsidera tio n Thiswo rk wa ssuppo rted by the C hildren sO nco lo gy G ro up C ha ir s ra nt U1 C a nd the pa tient strea tm enthisto ry, risk f a cto rs, co - m o rbidities, a nd liestyle. These guidelinesa re the Na tio na lC linica lTria lsNetwo rk G ro up O pera tio nsC enter ra nt U1 C ro m the theref o re no tintended to repla ce clinica ljudgm ento rto exclude o therrea so na ble a lterna tive Na tio na lC a ncerInstitute. The Versio n 5 upda te, including typesetting, wa ssuppo rted by the f o llo w- up pro cedures. The C hildren sO nco lo gy G ro up reco gnizestha tspecif cpa tientca re St a ldrick s o unda tio n. A s c t, a u n u l t C s a re o rga nized a cco rding to thera peuticexpo sures Sco re a ssigned by expertpa nelrepresenting the strength o da ta a rra nged by co lum n a s o llo ws f ro m the litera ture linking a specif cla the ef ectwith a thera peutic S ection N u m ber Unique identif er o rea ch guideline sectio n. T herapeu tic A g ent Thera peuticinterventio n f o rm a ligna ncy, including chem o thera py See Sco ring Expla na tio n in the Pref a ce f o rm o re inf o rm a tio n. Included a re m edica lcita tio nstha tpro vide evidence f o r psycho so cia la ssessm ent. R eco m m enda tio n f o rm inim um f requency the a sso cia tio n o the thera peuticinterventio n with the specif c o f perio diceva lua tio nsisba sed o n risk f a cto rsa nd m a gnitude o f risk, trea tm entco m plica tio n a nd/ o reva lua tio n o predispo sing risk f a cto rs a ssuppo rted by the m edica llitera ture a nd/ o rthe co m bined clinica l In a dditio n, so m e genera lreview a rticlesha ve been included in the experience o f the reviewersa nd pa nelo f experts R ef erence sectio n f o rclinicia n co nvenience. H eal th C ou nsel ing H eal th L ink s: Hea lth educa tio n m a teria lsdevelo ped specif ca lly to C ancer S creening Sectio ns co nta in preventive screening reco m m enda tio ns o r F u rther a cco m pa ny these guidelines. Title( s o f Hea lth L ink( s releva ntto R ecom m endations co m m o n a dulto nsetca ncers, o rga nized by co lum n a s o llo ws C onsiderations ea ch guideline sectio n a re ref erenced in thisco lum n.