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[Functional Neurosurgery]
MGH Functional Neurosurgical Service
mGH Neurosurgical Service
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The Functional and Stereotactic Neurosurgery Center provides comprehensive evaluation and care for patients with movement disorders, epilepsy, obsessive-compulsive disorder, and certain chronic pain syndromes. The center works closely with the Partners Parkinson and Movement Disorders Treatment Center, and the MGH Epilepsy Unit.
 
  • ABSTRACT
  • INTRODUCTION
  • How should patients be selected for surgery?
  • What evaluation is necessary to localize epileptic regions?
  • Imaging
  • PET scans
  • What procedures are appropriate for specific epilepsies?
  • Partial seizures
  • Focal seizures with secondary generalization
  • Infantile hemiplegia
  • How should outcome be assessed?
  • Directions for future research - should a controlled trial be done?
  • CONCLUSIONS and RECOMMENDATIONS
  • About NIH Consenus Development Conferences
  • SURGERY FOR EPILEPSY
    From: NIH Consensus Development Conference on Surgery for Epilepsy

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    National Institutes of Health Consensus Development Conference Statement March 19-21, 1990 This statement was originally published as: Surgery for Epilepsy . NIH Consensus Statement 1990 Mar 19- 21; 8(2):1-20.

    For making bibliographic reference to the statement in the electronic form displayed here, it is recommended that the following format be used: Surgery for Epilepsy. NIH Consens Statement Online 1990 Mar 19-21[cited year month day];8(2):1-20.
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    ABSTRACT


    The National Institutes of Health Consensus Development Conference on Surgery for Epilepsy brought together neurologists, neurosurgeons, psychologists, other health care providers, and the public to address issues regarding epilepsy surgery including patient selection and management, localization of seizure site onset, appropriate diagnostic techniques, and postoperative outcome assessment.

    The panel concluded that brain surgery is an alternative treatment when medication fails. Seizure frequency, severity type, possible brain damage or injury from frequent seizures, and effect on quality of life all must be considered in deciding to evaluate for surgery. An appropriate medication trial must have been conducted, using the correct drugs for the patient's seizure type at adequate doses and blood levels. Nonepileptic attacks must be ruled out, and diagnostic tests to detect any underlying cause should be performed.

    If surgery is considered, patients should be evaluated by a team including neurologists, neurosurgeons, neuropsychologists, social workers, and, if needed, psychiatrists. Assessment of outcome should include standardized methods of information collection. Measures assessing quality of life and overall health status can compare epilepsy to other chronic conditions. Assessment of economic and social impact on the patient's family should be included.
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    INTRODUCTION The full text of the panel's statement follows.

    Epilepsy is common. About 10 percent of all Americans will have at least one seizure at some time. Many people have one or a few attacks and then never have another one. For those with recurrent seizures, about 70 percent are satisfactorily controlled with antiepileptic drugs. Of the 150,000 people who develop epilepsy each year, 10 to 20 percent prove to have "medically intractable epilepsy." Many of these patients and their families have to deal with a chronic disorder that impairs the quality of life for all concerned.

    Brain surgery may be an alternative treatment if antiepileptic drugs fail, and it is being used more often. Several centers have reported success, and increasing numbers of patients are being referred for surgery, including many children. Improved technology has made it possible to identify more accurately where seizures originate in the brain (epileptic regions), and advances in surgery have made operative management safer. As a result, investigators have estimated that 2,000 to 5,000 new patients in the United States might be suitable for operations each year, compared with the present annual rate of about 500.

    Nevertheless, controlled trials have not been done, and there is disagreement among investigators about the choices and application of methods to evaluate patients for surgery, which procedures should be done, and how best to assess outcome. For these reasons, this consensus conference was organized.

    There is no precise definition of intractable epilepsy. Among the considerations are seizure frequency, seizure type, severity of attacks, and impact on quality of life. Before seizures are deemed intractable it is necessary to be certain that the correct drugs have been used in the correct amounts. Complex partial seizures are more likely to be intractable than tonic-clonic or other common forms of epilepsy. In uncontrolled complex partial seizures, the frequency of seizures varies from fewer than one a week to five or more each day. The clinical manifestations also vary in different patients. Some are not apparent to anyone but the patient; others disrupt daily activities and are socially embarrassing. If a patient falls during seizures that occur only a few times a year, repeated injuries and trips to emergency rooms can make life miserable. Even one seizure a year may disqualify a person from having a driver's license. Disability is also influenced by the reaction of the patient's family, friends, teachers, or employers. All of these factors have an impact on what is judged severe enough to warrant consideration of surgical therapy.

    There are other reasons to consider surgical therapy. For instance, repeated seizures may have adverse effects on the brain, leading to progressive cerebral degeneration and more severe clinical handicaps. Chronic use of antiepileptic drugs may cause toxic syndromes and may also have adverse effects on learning, scholastic achievement, development, and job performance.

    On the other hand, surgery has risks and costs that have to be considered. Before a patient is accepted for surgery, it is necessary to be certain of the diagnosis and the adequacy of previous drug therapy. Evaluation for surgery includes several methods: video- monitoring, brain imaging, different kinds of electroencephalography, and neuropsychological tests. The best combination of these studies has yet to be defined. Investigators do not agree about the preoperative need to identify areas of the brain that control speech. Similarly, there are differences of opinion about the specific surgical procedures that produce the best outcomes for different kinds of attacks. Anterior temporal lobe operations and other cortical resections involve the removal of epileptic regions from the temporal lobe and other areas of the brain and are done for complex partial seizures. Corpus callosotomy involves the severing of connections between the right and left sides of the brain and is used for some types of generalized attacks; corpus callosotomy and hemispherectomy can be used for seizures with childhood hemiplegia.

    This consensus conference was designed to address the following questions:

    1. How should patients be selected?
    2. What evaluation is necessary to localize epileptic regions?
    3. What procedures are appropriate for specific epilepsies?
    4. How should outcome be assessed?
    5. Directions for future research--should a controlled trial be done? If so, for what seizure types?

    To address these questions, the National Institute of Neurological Disorders and Stroke and the Office of Medical Applications of Research of the National Institutes of Health convened a Consensus Development Conference on Surgery for Epilepsy on March 19-21, 1990. After a day and a half of presentations by experts and discussion by the audience, a consensus panel drawn from specialists and generalists from the medical profession and related scientific disciplines, clinical investigators, and public representatives considered the evidence and came to the following conclusions.
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    HOW SHOULD PATIENTS BE SELECTED?

    Patients with unsatisfactory seizure control often seek alternative care. The number or severity of the seizures may be unacceptable to the patient, family, or treating physician. Other reasons for referral include the results of diagnostic tests that may show a structural focal brain lesion, unsatisfactory psychosocial adaptation due to poor seizure control, unacceptable sedation, or other drug side effects. Such patients, especially those with persistent complex partial seizures and some types of generalized seizures, may be candidates for surgical treatment. First, however, these patients should be referred to an adult or pediatric neurologist for further evaluation of diagnosis and treatment.

    Evaluation and medical treatment of these patients may take place under the supervision of a neurologist or in an epilepsy center that provides comprehensive diagnostic and treatment services designed for patients with intractable epilepsy. By "intractable" we mean that seizures have not been brought under acceptable control with the resources available to the primary care physician or neurologist.

    To be effective and comprehensive, the staff of a center should include the following: neurologists with special training and experience in epilepsy; neurosurgeons with experience in epilepsy surgery; neuropsychologists; and personnel trained to deal with social, psychological, and psychiatric problems and rehabilitation for school and work. Personnel to perform ancillary neurodiagnostic assessment must also be available, including closed-circuit TV and electroencephalography (EEG) monitoring telemetry; modern neurophysiological and EEG equipment; neuroimaging capabilities, including magnetic resonance imaging (MRI); and neuropsychological testing. Some centers also have positron emission tomography (PET), single photon emission computed tomography (SPECT), or other methods of evaluating cerebral blood flow and metabolism.

    Before a patient is considered for surgery, evaluation should be sufficient to ensure the following:

    • Nonepileptic attacks have been excluded and epilepsy is, in fact, present. Cardiogenic syncope, psychogenic seizures, and other nonepileptic states can closely mimic epileptic attacks.
    • The epileptic seizure type and syndrome have been clarified. Primary and secondary epilepsies, partial seizures, and tonic- clonic seizures respond to different antiepileptic drugs and different surgical procedures.
    • Diagnostic tests have been performed to define a metabolic or structural cause of the epileptic attacks.
    • The patient has had a reasonable trial of the appropriate antiepileptic drugs, with adequate monitoring of compliance and the effects of the treatment.
    • The patient and family have received detailed information about the specific seizure disorder, available drug treatments and side effects, and alternative treatments such as surgery. If, after this evaluation, seizures prove to be intractable or drug treatment is unsatisfactory, appropriate patients should be referred to an epilepsy center to be evaluated for surgery. Referrals should be made as soon as it is clear that medical treatment is unlikely to result in further benefit. Early referrals may prevent the development of chronic psychosocial and physical problems that result from uncontrolled seizures.

    Coexisting disorders may affect the decision to operate; they may include severe psychiatric disorders, profound developmental retardation, or progressive neurodegenerative diseases. After the initial evaluation and a full unsuccessful trial of medical therapy, surgery may be considered. Patients with partial seizures and secondarily generalized seizures (attacks that begin locally and spread to both sides of the brain) are potential candidates. Secondarily generalized seizures may take the form of atonic, tonic, or tonic-clonic attacks. Patients with seizures and childhood hemiplegia may also benefit from surgery. Patients with the following seizure types are potential candidates: complex partial seizures of temporal lobe origin or other focal seizures; generalized, atonic, akinetic, or myoclonic seizures; and partial seizures with childhood hemiplegia.
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    WHAT EVALUATION IS NECESSARY TO LOCALIZE EPILEPTIC FOCI?

    Precise clinical, electrophysiologic, and imaging data are necessary to carry out surgical therapy. Neurological assessment is necessary to identify and exclude other forms of neurological disease. In all cases, EEG and MRI are used. Additional tests are often necessary for precise localization. The following electrophysiological techniques are used in establishing the diagnosis and focality of an epileptic disorder:

    1. EEG is essential, sometimes with sleep deprivation or other activation techniques.
    2. EEG monitoring with video (video-EEG) is used widely in the evaluation of potential surgical candidates to exclude nonepileptic seizures and to define the electroclinical characteristics of the seizures. It is often used to establish and localize consistency and validity of the epileptogenic region.
    3. For precise cerebral localization, other more or less invasive techniques are used in some cases to establish a high degree of confidence in the electrical localization. These methods include sphenoidal leads, subdural and epidural electrodes and grids, and depth electrodes placed stereotaxically. Decisions about the need for these procedures must be individualized.
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    Brain Imaging Techniques

    Imaging techniques include x-ray computed tomography (CT), MRI, PET, and SPECT.

    CT has a limited role in the investigation of partial epilepsy because MRI is superior to CT in demonstrating brain tumors, vascular malformations, and focal brain atrophy. The diagnostic value of MRI in visualizing mesial temporal sclerosis and atrophy is under study. MRI is useful postoperatively to assess the extent of surgical resection.

    PET measures regional cerebral metabolism and blood flow. PET imaging has been quite successful in identifying the focus as an area of hypometabolism between attacks. This observation may be used in selecting patients with partial and secondarily generalized seizures for resective surgery. Because of the high costs and complexities of PET, this technology has been confined to a limited number of centers.

    SPECT can also be used for functional imaging of the brain because it demonstrates regional cerebral blood flow, which is linked to cerebral metabolism and can therefore be used to identify the epileptic focus. SPECT uses conventional and readily available equipment and radiopharmaceuticals. These compounds can be used to study both ictal and interictal states. In the past decade, this relatively affordable technology has become widely available. More work is needed to determine whether SPECT is as sensitive as PET in localizing the epileptic regions.

    Psychological tests are essential for the evaluation of varied cerebral functions, including memory and language. The intra-arterial amobarbital test is used to localize language function and to assess memory preoperatively.

    These diagnostic methods should be available at specialized epileptic centers. However, the data are insufficient to determine which particular patients require the more invasive and detailed techniques.

    Combining data from the major epilepsy centers would allow the development of a data bank or registry that should clarify many unanswered questions about the use of these diagnostic techniques.
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    WHAT PROCEDURES ARE APPROPRIATE FOR SPECIFIC EPILEPSIES?

    For 60 years, there has been continuous development of the surgical management of epilepsy. There have been many advances in the scientific understanding of epilepsy, in new technologies for localizing epileptic foci, and in methods for reducing operative risk. Neither randomized controlled trials nor large community-based clinical trials have been undertaken; nevertheless, several surgical approaches have been reported to be successful and rational in managing some types of intractable epilepsy. The data are not definitive and are primarily derived from single-institution studies. Surgery for epilepsy in patients with preoperatively detected neoplasms or vascular malformations depends as much on the nature and site of the lesion as on the seizure disorder.

    The following discussion relates specifically to surgical procedures performed with the primary goal of alleviating a seizure disorder rather than removing a specific brain lesion. Data collected to date suggest that patients in three general categories are suitable candidates for epilepsy surgery: partial seizures of temporal or extratemporal origin, secondarily generalized seizures, or unilateral, multifocal epilepsy associated with infantile hemiplegia.

    Patients With Partial Seizures

    The largest group of surgical candidates comprises patients with complex partial seizures of temporal lobe origin. Preoperative evaluation identifies those patients with tumors or vascular malformations and can determine whether the epileptic focus is deep (in the amygdala or hippocampus) or superficial (cortical).

    Appropriately directed, surgical resection of epileptogenic tissue has resulted in success rates of 55 to 70 percent of patients, when success was defined as no seizures (some auras may be present) for 5 years after surgery sometimes with some patients still taking anticonvulsant medication. In some patients, surgery also results in an improved psychosocial outcome, but this has not been studied adequately. Combined morbidity and mortality rates for surgery are below 5 percent. The charges for diagnostic evaluation and surgery vary from $25,000 in uncomplicated cases to over $100,000 in those who require extensive preoperative testing, with a median charge of $40-60,000.

    Partial seizures of frontal origin and from other extratemporal sites may also be treated surgically when the clinical manifestations and diagnostic studies indicate an epileptic region in a resectable area. Appropriately directed surgical resection of epileptogenic tissue may result in improvement (as defined above) in 30-50 percent of cases. The mortality rates are less than 2 percent, and the charges are slightly more than the cost of temporal lobe resection.
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    Patients With Secondarily Generalized Seizures

    Some patients with generalized seizures may be candidates for surgical management. Specifically, patients with the Lennox-Gastaut syndrome or drop-attacks may be helped by section of the corpus callosum, a procedure designed to prevent rapid bilateral generalization of epileptic discharges. The procedure is most frequently recommended in patients who are prone to violent falls that often result in head injury. The seizure disorder usually persists postoperatively but seizures may become less frequent, less disabling, and less violent. Evaluation and selection of candidates have not been standardized. There is also variability of surgical technique, particularly how completely the corpus callosum is sectioned. Postoperative mortality is low, but significant complications may occur in as many as 20 percent. The charge for the surgery is often higher than for lobectomy because the procedure as done in some centers requires two operations, but the charge for the preoperative evaluation is often less.
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    Seizures Associated With Infantile Hemiplegia

    In patients with intractable unilateral, multifocal epilepsy associated with infantile hemiplegia, hemispherectomy or callosotomy may be beneficial. These cases are rare, accounting for about 2 percent of all patients treated surgically for epilepsy. Success is measured not only by improvement in seizure frequency and type but also by improvement in behavior. Avoidance of complications (superficial cortical hemosiderosis and hydrocephalus) is a major consideration in the selection of surgical technique and has led to a current consensus for a "functional" hemispherectomy rather than one that is "anatomically complete." Success rates of 50 to 70 percent are balanced by combined mortality and morbidity rates that, in the past, reached 50 percent with anatomical hemispherectomy. Initial charges are similar to those for callosotomy but are increased by subsequent charges of dealing with late complications.
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    HOW SHOULD OUTCOME BE ASSESSED?

    Most studies that have assessed the outcome of either medical or surgical treatment of epilepsy have emphasized a single measure: seizure elimination or reduction in frequency. This measurement of seizure frequency needs to be clarified. For example, is a 50-percent reduction in a person who has two complex partial seizures a week equivalent to a 50-percent reduction in a person who has two seizures a year? We recommend the use of standardized methods to collect information about the frequency and kinds of seizures the patients are having.

    Although we recognize the importance of seizure frequency, we recommend that future studies should use "general measures" of outcome that would take advantage of validated and quantitative methods to assess the quality of life and health status of individuals. This could be achieved by a standardized survey to assess the following: short-term surgical mortality and morbidity or complications (e.g., death, paralysis, or infection in the postoperative period); physical health (symptoms, functioning, role activities, sleep-wake cycle, and mobility); mental health (psychiatric diagnoses as well as symptoms such as anxiety or depression); neuropsychological assessment, including cognitive functioning and memory, both verbal and nonverbal; social health (personal interactions, employment, sexuality, driver's license, and community interactions); and general health (health perceptions, including fear of death and pain, life satisfactions, and energy). Evaluation of children should include assessment of developmental progress and school performance.

    To evaluate each of the above, we recommend using general measures of health status and quality of life so that patients with epilepsy can be compared to patients with other chronic conditions. Epilepsy is a unique condition and we also recommend that, in addition to the general measures, supplemental information should be collected about the specific aspects of the quality of life of patients with seizures, as discussed above. This information should be gathered from family members in addition to the patients themselves. Because epilepsy affects the whole family, the family's well-being should be part of the assessment.

    The assessment of any treatment of epilepsy must include analysis of the economic impact on patients, families, and society. Economic impact includes expenditures on medical care directly (surgical and hospitalization costs, medication costs, costs of allied health personnel) as well as indirect costs such as contributed care by family members and whether a patient's income and productivity are affected positively or negatively in the future.

    Assessment must be done repeatedly for several years. Data from treatment centers should be pooled to achieve statistical power sufficient to test the efficacy of treatment, as assessed by the multiple outcome measures.

    We recognize that individuals will emphasize different outcomes. Some may be more concerned with the reduction in seizure frequency; others may be more concerned with the effect of treatment on memory or social function. Evaluation of any therapy for intractable epilepsy must explicitly consider these patient preferences.

    For all of these considerations, there is a need for a standardized method of data collection so that results from different treatment centers can be combined and compared.
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    DIRECTIONS FOR FUTURE RESEARCH--SHOULD A CONTROLLED TRIAL BE DONE? IF SO, FOR WHAT SEIZURE TYPES?

    • The panel is impressed that surgery is beneficial for selected patients, but the optimal timing of surgery is not known. Because of current referral patterns, patients considered for temporal lobe resection tend to have had uncontrolled (intractable) epilepsy for 10 to 20 years. We therefore recommend a controlled trial of early versus late surgery to determine whether early surgery or optimal medical treatment followed by later surgery of patients with complex partial seizures will result in better health status and quality of life and may prevent additional brain damage or chronic social disability.
    • Investigators differ in the selection of tests for preoperative evaluation. In particular, it is not known when more extensive diagnostic tests are needed, including ictal surface EEG recording, invasive intracranial electrode recording, PET, or SPECT. A program should be developed to assess the value of these tests, and should include the development and evaluation of algorithms. This would require standardization of definitions, data collection, and central analysis of the data.
    • We recommend development of an outcome assessment method that combines validated measures already used to assess general health status and function in a population of patients with other chronic conditions, with special items that are sensitive to the unique characteristics of people with epilepsy and those close to them, as described in the answer to question 4.
    • We recommend that psychiatric and behavioral functions be systematically assessed before surgery and during followup to determine whether there are specific contraindications to any particular surgical procedure and whether these procedures subsequently affect behavior.
    • In temporal lobe surgery for partial seizures, standard and "tailored" resections are used by different groups but the results are apparently similar. The circumstances in which each technique is maximally effective should be clarified by standardized data collection including documentation of extent of surgical resection and multivariate analysis so that an appropriate trial may ultimately be planned, if needed.
    • Because epilepsy surgery now may be used more often in children than in the past, we recommend additional studies to determine the effects of uncontrolled seizures and antiepileptic drug therapy on the developing brain. These studies might include, but not be limited to, evaluation of sequential neurodevelopmental assessment, anatomic and metabolic imaging procedures, cognitive-linguistic- academic achievement in school, and psychosocial adaptation of the child and family.
    • Surgical treatment of epilepsy might not be needed if we knew more about ways to prevent brain injury or if we had more effective and less toxic anticonvulsant drugs. It is therefore necessary to support fundamental research in the basic sciences of epilepsy: developmental neurobiology, neural science, cellular pathology, neuropharmacology, and preventive epidemiology.
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    CONCLUSIONS AND RECOMMENDATIONS
    • Most epilepsy surgery is performed by teams of committed physicians at sophisticated medical centers. The number of operations is increasing rapidly.
    • As currently used, surgery for intractable epilepsy is capable of stopping seizures or reducing their frequency. Effects on overall health status and quality of life have not been adequately studied.
    • Several different diagnostic studies and surgical techniques have been used but do not clearly differ in effectiveness.
    • Before surgery is performed, there are three absolute requirements. First, the diagnosis of epilepsy must be ascertained. Second, there must have been an adequate trial of drug therapy; that is, the correct drugs used in the correct dosage, carefully monitored for an appropriate time. Finally, the electroclinical syndrome must be defined.
    • As demand for surgery grows and it becomes available at more hospitals, quality of care must be maintained. Surgery should be performed at hospitals equipped with modern technology and staffed by multidisciplinary teams capable of preoperative diagnosis, selection of medical and surgical treatments, comprehensive postoperative evaluation, and ambulatory rehabilitative care. Rehabilitation should include the transition of patients to a seizure-free or almost seizure-free lifestyle with respect to psychological and social adjustment, education, and vocational training.
    • Physicians in any center or independent hospital that offers surgery for epilepsy should agree to use standardized data collection for all patients. The data should be maintained in a central registry, with respect for confidentiality. The data should include demographic information, diagnosis, clinical history, results of preoperative evaluation, and outcome assessment of quality of life and health status for at least 5 years. Outcome information should be provided to patients considering surgery so that expectations about the benefits and risks can be discussed and assessed.
    The Panel Members , Conference Speakers , and Conference Organizers
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    CONFERENCE SPONSORS

    National Institute of Neurological Disorders and Stroke. Murray Goldstein, M.D. Director

    Office of Medical Applications of Research. John H. Ferguson, M.D. Director
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    ABOUT THE NIH CONSENSUS DEVELOPMENT PROGRAM

    NIH Consensus Development Conferences are convened to evaluate available scientific information and resolve safety and efficacy issues related to a biomedical technology. The resultant NIH Consensus Statements are intended to advance understanding of the technology or issue in question and to be useful to health professionals and the public.

    NIH Consensus Statements are prepared by a nonadvocate, non-Federal panel of experts, based on

    1. presentations by investigators working in areas relevant to the consensus question during a 2-day public session;
    2. questions and statements from conference attendees during open discussion periods that are part of the public session; and
    3. closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government.

    Copies of this statement and bibliographies prepared by the National Library of Medicine are available from the Office of Medical Applications of Research, National Institutes of Health, Federal Building, Room 618, Bethesda, MD 20892.
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