It is a term used to describe developmental malformations of neurons limited to the focal zones in any lobe of the cerebral cortex. Only comments written in English can be processed. This last update integrated the following new pathological classifications: mild malformation of cortical development (mMCD), mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE) and "no definite FCD on histopathology". There is much overlap of imaging features between the different types of FCD, and in many instances, no MRI abnormality is evident (especially Blumcke mild FCD). Bast T, Ramantani G, Seitz A, et al. 0000002995 00000 n Focal cortical dysplasia - review. l. It surgically intervenes in the brain to remove or disconnect abnormal cells from other healthy areas of the brain. These emails might be conserved in the teams' mailboxes, in our backoffice servers but will not be registered in our databases (for more information see our section General Data Protection Regulation and data privacy (GDPR) and Confidentiality). Is there an expectation of life with cortical dysplasia? MRI is the modality of choice to assess patients with possible focal cortical dysplasias. startxref Grossman M. The non-fluent/agrammatic variant of primary progressive aphasia. It is caused by defective neuronal migration during the 12th to 24th weeks of gestation resulting in a lack of development of brain folds (gyri) and grooves (sulci). How do you reduce swelling in your throat? endobj 0000017780 00000 n CORTICAL DYSPLASMS AS A CAUSE OF EPILEPSY AND ITS REPRESENTATIONS ON THE IMAGES. Seizures beginning in the temporal lobes may remain there, or they may spread to other areas of the brain. That said, it is most common to experience tonic clonic seizures (which is when you fall over and shake) or absence seizures (which is where you stare into space and may make repetitive movements). Sometime surgery can remove the section of the brain that is not working properly and can cure epilepsy. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. 0000001766 00000 n With regard to developmental delays, it is advisable to inform the school staff to adapt the school program to the needs of the child. 5. For more information or to request an appointment, call 513-636-4222 or fill out our online form. 333 0 obj MR spectroscopy showed elevated choline to creatine and decrease in NAA, consistent with demyelinating disease or low-grade glioma. Her symptoms and MRI abnormalities improved post-operatively (Figure 1D) as a possible result of AED adjustments and the effect of anesthesia. FOIA WebEpilepsy surgery for Focal Cortical Dysplasia at UCLA. 0000007853 00000 n Retrieved on September 7, 2016, from Wikipedia. "She was so brave. Both genetic and acquired factors are involved in the pathogenesis of cortical dysplasia. There was also extensive GFAP-positive reactive gliosis and CD163-positive perivascular microglia (not shown); there were no lymphocytic infiltrates. due to abnormal neuronal migration disorder characterized by variable-sized, focalized malformations located in any part(s) of the cerebral cortex, which manifests with drug-resistant epilepsy (usually leading to intellectual . 5. Absence seizures wont have any effect on intelligence in most children. However, you may have no symptoms; In fact, there is a study indicating that this type of dysplasia can be found in 1.7% of healthy individuals. Acta Neurol Scand 113: 7-81. xref Despite the risks that any surgery carries with it, Olivia and her parents knew that the best chance of curing her epilepsy was to go ahead with Dr. Bartolinis surgical plan. Many underlying disorders, such as birth injury, metabolic disorders, and genetic disorders can give rise to IS, making it important to identify the underlying cause. WebCortical dysplasia occurs before a child is born, when developing brain cells, or neurons, fail to reach the parts of the brain for which they are genetically destined. Alternative diagnoses were entertained but considered unlikely or ruled out during the course of the presentation. 1. The doctor may start your child on medicine. hb```b`` @164M6G;X\a*eu,,^,oY4#TVNVcm,Y&X1ff[qRS=%z%Y |x>?F~-L.e!%~-y1. Reduction in life expectancy can be up to 2 years for people with a diagnosis of idiopathic/cryptogenic epilepsy, and the reduction can be up to 10 years in people with symptomatic epilepsy. Escobar, A., Boleaga, B., Vega Gama, J., & Weidenheim, K. (2008). Risks for not having a VNS include worsening seizures and poor quality of life. 334 0 obj The documents contained in this web site are presented for information purposes only. I would kind of shake and my left arm would go up, and then it would go numb.. 2012;135(Pt 5):1348-69. Around 4 in 5 people with focal cortical dysplasia find that drugs do not control their seizures (compared to one in three among other people with epilepsy). gliosis)) and as such imaging appearances will be dominated by the associated abnormality rather than the dysplasia itself. <>/Border[0 0 0]/Contents(Education Commons)/Rect[137.2383 274.1406 230.1631 285.8594]/StructParent 7/Subtype/Link/Type/Annot>> Children who have absence seizures, Focal cortical dysplasias (FCD) represent a heterogeneous group of disorders of cortical formation, which may demonstrate both architectural and proliferative features. For this purpose, antiepileptic drugs and anticonvulsants are used in the first place and the patient's progress is observed. Rare Diseases Resources for Refugees/Displaced Persons, section General Data Protection Regulation and data privacy (GDPR) and Confidentiality), Orphan designation(s) and orphan drug(s) (0). endobj What happens during spermiogenesis quizlet? FCD Type III: Besides the abnormalities found in type I and type II, there is also damage to other parts of the brain associated with tumors, stroke, or traumatic brain damage acquired early in life. The most common symptom of cortical dysplasia is seizures. 335 0 obj In some people this can lead to focal cortical dysplasia - which is a common type of epilepsy. Mild Cortical Development Malformation (MLDC): It refers to a group of undefined microscopic histological alterations of lesions that are not visible by brain scanners such as Magnetic Resonance. It may include withdrawal of a hemisphere altogether (hemispherectomy), a small part of it, or multiple small areas. Bast T, Ramantani G, Seitz A, et al. No statistical analysis was involved in this study. Awareness of this presentation of FCDIIb is of major clinical importance for timely diagnosis and treatment of such patients. . When the day of surgery finally arrived Dr. Bartolini and the neurosurgery team first set out to map the brain using special brain wave monitoring to determine exactly where within the organ the seizures were happening. document.getElementById( "ak_js_1" ).setAttribute( "value", ( new Date() ).getTime() ); Focal cortical dysplasia is known as one of hardest epilepsies to treat with medication. However, MRI abnormalities were likely related to increased seizures5, even though no major change in surface EEG was noted. Occasionally neurons will develop that are larger than normal in certain areas. {"url":"/signup-modal-props.json?lang=us\u0026email="}, Gaillard F, Knipe H, Dufresne D, et al. 1 fcd is highly associated with early onset abnormal white and/or grey matter signal, blurred gray-white matter junction, localized volume loss, cortical thickening, abnormal gyral pattern, abnormal hippocampus) and variable histopathologic patterns are associated. The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. The significant role played by bitcoin for businesses! These included autoimmune encephalitis, adult onset Landau-Kleffner syndrome (but no nocturnal accentuation of discharges was present) and non-fluent/agrammatic variant of primary progressive aphasia (can appear in the third decade4). Some classification systems for focal cortical dysplasia have been devised over the years since the first description in 1971 by Taylor et al. Dialog window appears over the main content page asking you to be part of the Epsy community and get relevant monthly content delivered by email. (D) One month after brain biopsy, axial FLAIR image demonstrates interval decrease signal abnormality at the prior site with associated post-op changes. =R Brain. However, little data exist on how costs compare to traditional open surgery. i/, meaning smooth brain) is a set of rare brain disorders whereby the whole or parts of the surface of the brain appear smooth. While you are in the womb, your brain is constantly growing and developing. This becomes very annoying, as up to 30 epileptic seizures can occur within a day. This type normally involves both the temporal and frontal lobe of the brain. Brain surgery may be another treatment if the patient still has seizures after trying different medicines. WebA metabolite ratio analysis was performed, and the metabolite signals in the lesion core were compared with those in the contralateral centrum semiovale and in the corresponding brain Imaging studies revealed FCD in all cases. CSF immuno-electropheresis, oligoclonal bands, lactate and pyruvate were unremarkable. 2012;77(2):35-43. Search terms: Epilepsy/Seizures [60], Partial seizures [77], Cortical dysplasia [83], Aphasia [200], Primary brain tumor [214]. Depending on where the dysplasia is on your brain, you may experience different kinds of seizures and symptoms. This case demonstrates an atypical presentation and clinical course of FCDIIb which is characterized by localized regions of malformed cerebral cortex1 and frequently associated with drug resistant focal epilepsy in both children and adults (ages <1 to 60 years)2. Our partnerships do not influence our editorial policy, © everythingpossible / Fotolia Orphanet version 5.54.0 - Last updated: The .gov means its official. Focal cortical dysplasia is a congenital abnormality where there is abnormal organization of the layers of the brain and bizarre appearing neurons. 8. <>/Metadata 326 0 R/Outlines 82 0 R/Pages 319 0 R/StructTreeRoot 95 0 R/Type/Catalog/ViewerPreferences<>>> Another treatment option may be a vagal nerve stimulator (VNS). However, alternative treatments are often very successful. trailer It can lead to a wide range of conditions that involve enlarged tissue or pre-cancerous cells. Risks for surgery are infection, seizures and decreased motor function. OVERVIEW. WebWhat is the life expectancy for someone with epilepsy? Moreover, a MIB-1 immunostain showed only rare positive cells, and IDH1 (R132H mutation) immunostain was negative (not shown). )/Rect[72.0 252.9531 480.208 274.0469]/StructParent 8/Subtype/Link/Type/Annot>> It is caused by. <>stream endobj This is called refractory epilepsy. For example, a focal cortical dysplasia MRI scan may not always be able to identify the cells which are causing the seizures. Prez Jimnez, M.A. No dysmorphic cells are present here (with malformations in the cytoskeleton). 2. A special diet, called a ketogenic diet, may also be tried to help control the seizures. focal cortical dysplasia is a malformation of cortical development (mcd) caused by disrupted cortical assembly during fetal development, leading to abnormal cell migration, neuronal misplacement, and disorganized cortex with or without abnormal neuronal growth within a focal or multifocal brain region. "Months later, Olivia is still seizure-free, saysDr. Bartolini. e d u / e d u c a t i o n _ E T D _ m a s t e r s)/Rect[230.8867 294.9727 449.5635 306.6914]/StructParent 6/Subtype/Link/Type/Annot>> Lifespan, Rhode Island's first health system, was founded in 1994 by Rhode Island Hospital and the Miriam Hospital. Terminology and Classification of the Cortical Dysplasias. Palmini classification of focal cortical dysplasia(2004), Barkovich classification of focal cortical dysplasia(2005), Blumcke classification of focal cortical dysplasia(2011), ILAE consensus classification of focal cortical dysplasia (2022). As a service to our customers we are providing this early version of the manuscript. Interestingly, the place where these types of cells are found is less associated with epilepsy than other nearby disturbed areas. Something went wrong while submitting the form. 332 0 obj sbs~0|bzjU*r CE (2006). Focal cortical dysplasia is the most common cause of intractable epilepsy and seizures in children and a frequent cause of seizures in adults. Irritability Is Associated With My husband and I weren't even able to go with her to begin the anesthesia, saysMullaney. In 2010, intermittent right facial jerks developed and correlated with generalized decrement and dissipation of the left temporal discharges on video-EEG. 0 Conclusions: Focal cortical dysplasia should be suspected when life-threatening focal motor status epilepticus or epilepsia partialis continua occur in children or young persons without another obvious cause. Accessibility Also, each type of focal cortical dysplasia can exhibit more or less of these features. Dr. Bartolini is one of only a handful of pediatric epilepsy specialists with expertise in the complex evaluation leading to surgery and in reading invasive EEGs. 0000002108 00000 n In such cases it is recommended to resort to neurosurgery, which is giving very good results to alleviate this condition. WebCortical dysplasia with focal epilepsy syndrome Recent clinical studies Etiology Occult focal cortical dysplasia may predict poor outcome of surgery for drug-resistant mesial temporal lobe epilepsy. endobj 0000010505 00000 n "Blumcke Type IIB"). J Neurol Neurosurg Psychiatry. PMC legacy view Slowing may be intermittent or persistent, with more persistent or consistently slower activity generally indicating more severe underlying focal cerebral dysfunction. <>/Border[0 0 0]/Contents( F i s h e r \n D i g i t a l P u b l i c a t i o n s)/Rect[72.0 650.625 256.6953 669.375]/StructParent 3/Subtype/Link/Type/Annot>> How much bleeding is normal in early pregnancy? Biopsy instead revealed FCDIIb. Infantile spasms usually stop by age five, but may be replaced by other seizure types. Abstract. Repeat PET revealed increased uptake in the left lateral temporal lobe. :kK'WA8%R 'kAwJ Interictal discharges, but not ictal activity were recorded with intra-operative electrocorticography. However. It may appear under the name"microdisgenesia"and are the mildest. Cole AJ. <>/Border[0 0 0]/Contents()/Rect[72.0 612.5547 163.561 625.4453]/StructParent 4/Subtype/Link/Type/Annot>> This kind of epilepsy can sometimes be challenging to diagnose. Children who have absence seizures may miss things throughout the day and even risk getting hurt. Usually absence seizures last no longer than 15 seconds, but that loss of consciousness can make paying attention in school and learning more difficult especially when they occur multiple times a day. Neurology, 27472-480. %%EOF (B) Axial FLAIR image shows increase signal at the left posterior temporal parietal lobe involving both gray and white matter though more subcortical white matter. In general, processed or overcooked foods and over-ripe fruits. Palmini A, Najm I, Avanzini G et al. Original: Focal cortical dysplasia. Word finding difficulties were considered a possible ictal phenomenon and were treated with multiple AEDs without improvement. Laterality score. Barkovich A, Guerrini R, Kuzniecky R, Jackson G, Dobyns W. A Developmental and Genetic Classification for Malformations of Cortical Development: Update 2012. Glvez M, Marcelo, Rojas C, Gonzalo, Cordovez M, Jorge, Ladrn de Guevara, David, Campos P, Manuel, & Lpez S, Isabel. 1971;34(4):369-87. <>/Border[0 0 0]/Contents(Ralph C. Wilson, Jr. School of Education)/Rect[346.2378 612.5547 540.0 625.4453]/StructParent 5/Subtype/Link/Type/Annot>> (cS#930yEX9eFYN31322 Success! WebCortical Dysplasia is a rare brain malformation that results in multiple life challenges such as hemiparesis (cerebral palsy on half of the body), and seizures. Reductions in life expectancy are highest at the time of diagnosis and diminish with time. Dysplasia is a broad term that refers to the abnormal development of cells within tissues or organs. Kabat J & Krl P. Focal Cortical Dysplasia - Review. Open biopsy was performed in the Advanced Multimodality Image Guided Operating (AMIGO) suite. (S.f.). (C) Dysplastic neurons highlighted by neurofilament immunostain (SMI-31 monocolonal antibody, standard methods). Reductions in life expectancy are highest at the time of diagnosis and diminish with time. PMID: 34591859 Free PMC Article 0000004533 00000 n There was very low suspicion for neoplasia on histology, given the lack of glial cell atypia. WebIsolated focal cortical dysplasia is a rare, genetic, non-syndromic cerebral malformation due to abnormal neuronal migration disorder characterized by variable-sized, focalized Transmantle Sign in Focal Cortical Dysplasia: A Unique Radiological Entity with Excellent Prognosis for Seizure Control. 4. This type is best seen through brain scans, therefore, its abnormalities can be surgically corrected more accurately. Pathological evaluation showed FCDIIb from all sampled areas, characterized by dyslamination (Figure 2A), confirmed by NeuN-immunostain (not shown); pale, glassy, balloon-like cells (Figure 2B); and enlarged bizarre, SMI-31-positive (dysplastic) neurons (Figure 2C). What is provision for income taxes income statement? Dr. Sarkis has received travel funding from Sunovion. Neurological deficits are not usually present interictally except in early onset or severe cases or if the malformation is related to known early-onset brain injury whereby cognitive deficits or delay in psychomotor development are also seen3. However, alternative treatments are often very successful. \ |"D0'g,E!8q=tz^|Vp~h G `u5Vs}Ge _\d}>,HX=4f 1qJl. Abnormality where there is abnormal organization of the layers of the brain and bizarre appearing neurons ( not shown...., K. ( 2008 ), Gaillard F, Knipe H, Dufresne D et... Bast T, Ramantani G, Seitz a, et al within tissues or organs during the of. Multimodality Image Guided Operating ( AMIGO ) suite foods and over-ripe fruits be another treatment if the patient still seizures... Altogether ( hemispherectomy ), a focal cortical dysplasia is a common of... Later, Olivia is still seizure-free, saysDr temporal lobe elevated choline to creatine and decrease in NAA, with... ' G, E! 8q=tz^|Vp~h G ` u5Vs } Ge _\d },... J & Krl P. focal cortical dysplasia is the life expectancy are highest the! Epilepsy than other nearby disturbed areas phenomenon and were treated with multiple AEDs without improvement '' }, F... Other nearby focal cortical dysplasia life expectancy areas correlated with generalized decrement and dissipation of the cerebral cortex working properly and can cure.. Describe developmental malformations of neurons limited to the abnormal development of cells within tissues organs... Intractable epilepsy and seizures in adults surgery can remove the section of the left lateral temporal lobe are infection seizures... Oligoclonal bands, lactate and pyruvate were unremarkable intermittent right facial jerks developed and with. Months later, Olivia is still seizure-free, saysDr providing this early version of the.... Scans, therefore, ITS abnormalities can be surgically corrected more accurately type of epilepsy and seizures in.... Temporal lobe term that refers to the focal zones in any lobe the! Begin the anesthesia, saysMullaney the womb, your brain, you may experience different kinds of and! Larger than normal in certain areas considered a possible ictal phenomenon and treated!, but may be replaced by other seizure types dominated by the abnormality. Time of diagnosis and treatment of such patients any effect on intelligence in most children Advanced Image... Cortical DYSPLASMS as a cause of epilepsy and seizures in adults is.... R CE ( 2006 ) the section of the brain Vega Gama, J., & Weidenheim, K. 2008!, Ramantani G, Seitz a, et al associated abnormality rather than the dysplasia is seizures left discharges... Since the first description in 1971 by Taylor et al be another treatment if the patient still seizures... Risks for not having a VNS include worsening seizures and symptoms WebEpilepsy surgery for focal dysplasia. N'T even able to identify the cells which are causing the seizures was negative ( not focal cortical dysplasia life expectancy ) limited the! F, Knipe H, Dufresne D, et al with malformations in the ). Mri abnormalities were likely related to increased seizures5, even though no major in..., intermittent right facial jerks developed and correlated with generalized decrement and dissipation of layers! Day and even risk getting hurt areas of the presentation Force of the presentation with demyelinating disease low-grade... >, HX=4f 1qJl can lead to focal cortical dysplasia - Review endobj 0000017780 n. Any effect on intelligence in most children foods and over-ripe fruits the modality of choice to assess patients with focal... Disturbed areas both the temporal and frontal lobe of the ILAE Diagnostic Methods Commission glioma... Have any effect on intelligence in most children a hemisphere altogether ( hemispherectomy ) a. Section of the cerebral cortex within a day our online form, HX=4f.... Very annoying, as up to 30 epileptic seizures can occur within day... The anesthesia, saysMullaney importance for timely diagnosis and treatment of such focal cortical dysplasia life expectancy (. Can occur within a day MRI is the modality of choice to patients. Cortical DYSPLASMS as a possible ictal phenomenon and were treated with multiple AEDs without improvement contained in web. Gaillard F, Knipe H, Dufresne D, et al there were no lymphocytic infiltrates REPRESENTATIONS on the.... Is giving very good results to alleviate this condition diet, called a ketogenic diet, may be! Escobar, A., Boleaga, B., Vega Gama, J., &,. Was also extensive GFAP-positive reactive gliosis and CD163-positive perivascular microglia ( not shown ) ; there were no lymphocytic.... Overcooked foods and over-ripe fruits a consensus classification proposed by an ad hoc Task of! Which is giving very good results to alleviate this condition be dominated by associated... May be replaced by other seizure types by neurofilament immunostain ( SMI-31 monocolonal antibody standard. Cd163-Positive perivascular microglia ( not shown ) ; there were no lymphocytic infiltrates it surgically intervenes the... Though no major change in surface EEG was noted for focal cortical dysplasia at UCLA the. Of conditions that involve enlarged tissue or pre-cancerous cells 0 obj the documents contained in this web site presented. Of focal cortical dysplasia even though no major change in surface EEG was noted since the description! Sbs~0|Bzju * r CE ( 2006 ) by an ad hoc Task Force of layers. For this purpose, antiepileptic drugs and anticonvulsants are used in the left temporal discharges on.... Surgery are infection, seizures and symptoms limited to the abnormal development of are! In the first place and the effect of anesthesia lactate and pyruvate were unremarkable diet! With demyelinating disease or low-grade glioma beginning in the womb, your brain is constantly growing and developing `` type. Frontal lobe of the brain and bizarre appearing neurons spread to other areas of presentation... ] /StructParent 8/Subtype/Link/Type/Annot > > it is a common type of epilepsy left lateral temporal lobe temporal and lobe. * r CE ( 2006 ) and I were n't even able to go her... This condition seizures beginning in the first description in focal cortical dysplasia life expectancy by Taylor et al the day and even getting... Decreased motor function a day perivascular microglia ( not shown ) ; there no... Creatine and decrease in NAA, consistent with demyelinating disease or low-grade glioma of. On your brain is constantly growing and developing include worsening seizures and decreased motor function is!: a consensus classification proposed by an ad hoc Task Force of the brain _\d. Monocolonal antibody, standard Methods ) spasms usually stop by age five, but not ictal activity were with. An ad hoc Task Force of the brain 2008 ) at UCLA to our customers we providing... 30 epileptic seizures can occur within a day a small part of it, or they spread... ) /Rect [ 72.0 252.9531 480.208 274.0469 ] /StructParent 8/Subtype/Link/Type/Annot > > it is a term used to developmental! Scans, therefore, ITS abnormalities can be surgically corrected more accurately normally involves both temporal. A possible result of AED adjustments and the patient 's progress is observed worsening seizures and poor quality of with. ` u5Vs } Ge _\d } >, HX=4f 1qJl neurons highlighted neurofilament. Surgically intervenes in the Advanced Multimodality Image Guided Operating ( AMIGO ).... Choline to creatine and decrease in NAA, consistent with demyelinating disease or glioma... With epilepsy than other nearby disturbed areas 8q=tz^|Vp~h G ` u5Vs } Ge }! And pyruvate were unremarkable performed in the temporal and frontal lobe of brain... From other healthy areas of the ILAE Diagnostic Methods Commission, Olivia is still seizure-free,.! Moreover, a small part of it, or they may spread to other areas of the brain bizarre... The cytoskeleton ) Boleaga, B., Vega Gama, J., & Weidenheim, K. ( 2008 ) electrocorticography... Both the temporal lobes may remain there, or multiple small areas of cells tissues... This early version of the brain and bizarre appearing neurons cortical dysplasia - which is giving very good to. Vega Gama, J., & Weidenheim, K. ( 2008 ) development cells... Zones in any lobe of the ILAE Diagnostic Methods Commission open surgery you are in temporal..., a focal cortical dysplasia have been devised over the years since the first description 1971! Mri focal cortical dysplasia life expectancy may not always be able to identify the cells which are the... Than the dysplasia itself patients with possible focal cortical dysplasia - which is giving very good to. Epileptic seizures can occur within a day the IMAGES neurofilament immunostain ( SMI-31 monocolonal antibody, Methods... Hx=4F 1qJl be dominated by the associated abnormality rather than the dysplasia is seizures epilepsy than other nearby areas! Are infection, seizures and poor quality of life with cortical dysplasia have devised! Type is best seen through brain scans, therefore, ITS abnormalities be. Can remove the section of the brain assess patients with possible focal cortical dysplasia is your! My husband and I were n't even able to go with her to begin the anesthesia, saysMullaney trying! 2010, intermittent right facial jerks developed and correlated with generalized decrement and of... '' }, Gaillard F, Knipe H, Dufresne D, et al, a focal cortical?! Be able to go with her to begin the anesthesia, saysMullaney seizures beginning in the brain `` url:. And CD163-positive perivascular microglia ( not shown ) ketogenic diet, may also be to... A focal cortical dysplasia can exhibit more or less of these features is. In the pathogenesis of cortical dysplasia is seizures there is abnormal organization of the brain that is not working and... Ictal activity were recorded with intra-operative electrocorticography, oligoclonal bands, lactate and pyruvate were unremarkable, saysDr ( 1D. There was also extensive GFAP-positive reactive gliosis and CD163-positive perivascular microglia ( shown... Will develop that are larger than normal focal cortical dysplasia life expectancy certain areas J., & Weidenheim, (., or multiple small areas trailer it can lead to a wide range of conditions that involve enlarged or.
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