Epilepsy: habilitation and rehabilitation

Epilepsy: Habilitation and Rehabilitation Warren A. Marks, Angel Hernandez, and Marsha Gabriel Rehabilitation represents not only a distinct field of medicine, but also a philosophical and practical treatment approach that can be applied to a variety of chronic disorders. Neurology encompasses many chronic disorders, making it ideal for the application of rehabilitation principles in daily practice. Epilepsy offers a unique opportunity to incorporate rehabilitation principles into the management of a complex medical disorder. Epilepsy is an evolving disease process that changes with the maturation of the central nervous system. The rehabilitative model provides the framework for a dynamic treatment plan to meet the changing needs of the child with epilepsy through the social and developmental changes of childhood, adolescence, and adulthood. The development of epilepsy may complicate the recovery from many acute and chronic conditions that affect the central nervous system. The rehabilitation process must address these many aspects of the disease process and its sequelae. This makes neurologists uniquely qualified to manage the rehabilitation team. The impact of the therapeutic milieu on the recovery process may be as important as any specific medical or surgical intervention. © 2003 Elsevier Inc. All rights reserved.

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EHABILITATION IS the process of restoring someone or something to its original condition. The traditional medical model considers seizures and posttraumatic epilepsy to be complications or sequelae of some other injurious brain process. In recent years, however, increased attention has been paid to the global effects of epilepsy on the individual and the family unit. Most attention has focused on the cognitive side effects of anticonvulsant medications or the aftereffects of epilepsy surgery. Recognition of the adverse effects of epilepsy and its treatment on daily functioning allows for a rehabilitative approach to the treatment of these patients. CURRENT CONCEPTS IN EPILEPSY REHABILITATION

Neurologic disorders are unique in their potential for adverse outcomes on societal integration, due to the very target organ of dysfunction and to the common negative effects of treatment regimens. Epilepsy is perhaps the prime example of a disorder that can negatively affect social, cognitive, and emotional development, and for which the treatment can sometimes be as troubling as the disorder itself. For children, the interactions between epilepsy, underlying etiology, and treatment are even more complex than in the adult.1 Learning is a pyramid process of assimilating new knowledge and integrating it with other previously acquired information. If the foundation is weak, then weighing down the top part of the structure will eventually lead to collapse. Any process that adversely affects early development may lead to subsequent developmental and social disabilities. For children, this can be seen as school and or social failure and ultimately an inability to fully Seminars in Pediatric Neurology, Vol 10, No 2 (June), 2003: pp 151-158

integrate as a productive and successful member of society. More than restoring lost luster, habilitation is the process of guiding someone to an anticipated potential. Current concepts of epilepsy present the opportunity to view its treatment in a new light. Several recent articles have offered insight to the importance of a “latent period” between initial insult and the subsequent development of epilepsy in both animal models2 and human experience.3 The nature of this initial insult varies widely from a first seizure to an inflicted internal (meningitis, encephalitis) or external brain trauma. The latent period is, therefore, also a window of opportunity for habilitation. This is analogous to the habilitation approach of providing developmental learning opportunities during early childhood in an attempt to lessen the need for rehabilitation later in childhood and beyond. The latent period between insult and epilepsy potentially offers opportunities for both neuroprotection and antiepileptogenesis.4 Although many drugs may be neuroprotective or antiepileptic (seizure-preventing), none has been shown to be antiepileptogenic, that is, able to prevent the actual development of epilepsy in a susceptible individual.4 Although valproate has some neuroprotective properties and phenobarbital, MK 801, and benzodiazepines offer some

From the Department of Neurology, Cooks Children’s Medical Center, Fort Worth, TX. Address reprint requests to Warren A. Marks, MD, Department of Neurology, Cooks Children’s Medical Center, 901 Seventh Ave., Suite 120, Fort Worth, TX 76104. © 2003 Elsevier Inc. All rights reserved. 1071-9091/03/1002-0000$30.00/0 doi:10.1016/S1071-9091(03)00023-8 151

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promise of antiepileptogenesis in rats, no antiepileptic medication has yet been found to be antiepileptogenic in humans.5-7 The subsequent development of epilepsy in susceptible individuals invokes specific rehabilitation needs. Although medications are the mainstay of epilepsy treatment, social, educational and behavioral programs are vital to the ultimate success of any treatment plan. Providing the appropriately stimulating environment may be a highly effective tool for improving outcome after a variety of brain injuries, inducing many positive structural and biochemical changes in the brain.8,9 This article explores the impact of epilepsy on the rehabilitation process, as well as the role of the rehabilitation process on the treatment of epilepsy. Many readers will likely find that they are already incorporating many rehabilitation principles into their practice management for patients with epilepsy and other chronic neurologic conditions. As with every other aspect of professional practice, technology is significantly impacting the treatment of patients with epilepsy. Newer and more sophisticated diagnostic and treatment approaches are rapidly expanding the scientific basis of our understanding and treatment of epilepsy. At the same time, however, the explosion of information, and sometimes misinformation, available via the Internet has significantly impacted the relationship of physician, patient, and family. As highlighted by the recent consensus statement from the American Academy of Pediatrics, nowhere is the rehabilitation more applicable than during the transition of individuals with epilepsy from pediatric to adult health care systems.10 By nature, pediatrics is more family-oriented, with sophisticated pediatric hospitals widely invested in many support systems, including child-life programs and in-hospital classrooms. For adolescents with special health care needs, including epilepsy and its frequently accompanying developmental and behavioral disabilities, this transition can be difficult. This problem is further compounded by the lack of medical insurance, and therefore lack of access to providers, which often plagues this patient population. NATURAL HISTORY AND TREATMENT DECISIONS

Approximately 5% of children in the United States can be expected to experience a seizure by

age 20; one-fourth of these patients will meet criteria for the diagnosis of epilepsy.11 In 75% of the cases, epilepsy begins before age 19 years.12 Seizure type and epilepsy syndrome are key elements forming the scientific basis for treating seizures. The International League Against Epilepsy (ILAE) classification system has helped elucidate the natural history of many epileptic syndromes.13 This information is one critical factor in the development of an overall management strategy for the child with epilepsy. Therefore, the decision to recommend medication for an individual with epilepsy may seem relatively straightforward. Nonetheless, controversy persists about the appropriateness of pharmacologic treatment or nontreatment of many self-limited epileptic syndromes. The decision to treat must take many factors into account besides the predicted natural history of the epilepsy syndrome. Pharmacologic efficacy must balance the benefits of treatment against the potential adverse effects of any chosen medication. Many factors are involved in the selection of an appropriate anticonvulsant medication. Treatment must be individualized based on a number of personal, family, and socioeconomic variables. Since 1994 there has been a virtual explosion of a new generation of anticonvulsants. Some of these represent novel compounds, whereas others are modified and hopefully improved versions of more traditional medications.14 There remains a paucity of reliable data regarding the effectiveness and long-term tolerability of these medications in children. There has been a recent surge of clinical research trials evaluating specifically the safety, efficacy, and tolerability of anticonvulsants in children. Acquired or symptomatic epilepsy syndromes, occurring as a consequence of illness (meningitis, encephalitis, tumors) or traumatic brain injury, entail somewhat different sets of social and rehabilitation issues. Here seizures are often the complicating factor and not the primary disability. Nonetheless, treatment of the seizure disorder has many of the same implications. The negative psychoeducational effects of anticonvulsants may be exaggerated in the child with preexisting or acquired cognitive limitations. Traumatic brain injury is defined as an external force resulting in damage to the brain. Although we typically consider this to be externally induced

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trauma, such as a blow to the head or a shaking injury, for the purpose’s of this discussion, we take a much broader conceptual approach. Our definition of trauma must be expanded to include any acquired insult to the brain that may result in acute or chronic functional changes in cerebral function. This includes not only blunt and penetrating trauma, but also medical and biochemical derangements including meningitis and encephalitis, stroke, and electrolyte and other metabolic derangements. This predisposing insult may render the brain a more susceptible substrate for seizures as well as the potentially negative effects of antiepileptic medications. Seizures occurring in the context of an acquired problem, such as meningitis, stroke, or traumatic brain injury, are an extreme source of anxiety for families. Repetitive or prolonged clinical seizures have negative immediate consequences on the management of the patient with a brain injury from trauma or infection. Increases in metabolic demand with elevations of and consequent glucose utilization increase metabolic lactic acid production, leading to regional acidosis and increased cellular dysfunction.15 The choice of anticonvulsants in this setting is limited by the drugs rapidity of onset and route of administration. Despite the numerous new anticonvulsants available, initial management choices for acute intravenous administration are still limited to benzodiazepines, phenobarbital, phenytoin, and valproate. Acute seizures in the context of traumatic brain injury may predict the later development of epilepsy, although the incidence is lower in children than adults (10% versus 36%).11 Obviously, the need for acute or chronic anticonvulsant therapy has significant implications for the rehabilitation process. To date, there is no convincing evidence that prophylactic treatment with antiepileptic medications is antiepileptogenic. During the recovery process from a traumatic brain injury, patients typically progress through a series of fairly well-described cognitive stages that have been applied to both children and adults.16 Progress on through these stages of recovery may be masked, if not actually altered, by the administration of medications, including anticonvulsants. The long-term implications of early medication use have not been established. Improvements in functional outcome measures should ultimately prove invaluable in helping monitor effective epilepsy treatment in the rehabilitation setting. Anticonvul-

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sant medications can have both positive and negative behavioral consequences, cognitive consequences range from neutral to negative and are often dose-related. Studies in healthy adult volunteers as well as those with epilepsy have generally confirmed that the cognitive effects of phenytoin, carbamazepine, and valproate are similar and minimal, particularly when used as monotherapy and when blood levels are maintained in the generally accepted ranges.14 Lamotrigine and gabapentin have generally shown less negative cognitive effects.17 Phenobarbital and benzodiazepines are well recognized to have negative effects.18 Topiramate has negative effects that may be further exacerbated by more rapid titration.17 The very limited information available in children indicates that the effects of phenytoin, carbamazepine, and valproate are similar to the findings in adults.14,17,18 Treatment decisions made for infants and young children may have life-long implications. The issue of medicating infants is even more controversial due to the lack of any reliable testing tools for assessing the cognitive effects on short- and longterm development. This has been further complicated by the notion that untreated early, even febrile, seizures may lead to the later development of mesial temporal sclerosis and the potential for medically refractory seizures in adulthood.19 This may occur even without evidence of atrophy or other abnormalities detectable on magnetic resonance imaging (MRI).20 Despite this controversy, only two medications, phenobarbital and valproate, have had any formal testing for the treatment of febrile seizures. Phenobarbital,21 but not diazepam,22 has been demonstrated to have negative effects on children with febrile seizures. Although patients with complicating factors are at higher risk for future seizures,23 no antiepileptic medication has been shown to affect the future development of epilepsy even in this selected population. Treatment decisions must be made in conjunction with families. In addition to the medical recommendations to treat or not treat based purely on the available scientific literature, many social factors can influence treatment decisions. First and foremost of these is a family’s sense of confidence in the physician. This will be coupled with their relative tolerance for having their child have seizures versus being on chronic medication therapy. The successful rehabilitation of the child in-

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cludes being treated normally by family and society. In infancy and early childhood, obviously more parental implications must be dealt with. Shore24 found that parents were concerned about their children’s loss of intelligence, possible death, and the possibility of a brain tumor. School-age children have their own issues; however, they are often not able or willing to verbalize their responses to internal (anxiety) or external stress (peer pressure). Many experience fears of seizures, feelings of helplessness, and alienation.25,26 Studies identifying the psychosocial effects of epilepsy in children and adolescents are limited. There are even fewer studies outlining effective treatment programs for these psychosocial consequences. Patient education has been shown to improve compliance, to allay fears, and to avoid damaging “self-management” practices, including the use of recreational drugs.27 Educational and social performance can be enhanced by effective treatment of epilepsy. However, these benefits must be balanced with the potential adverse cognitive and behavioral effects of the medications. It is difficult to conduct research separating the effects of medication on behavior and cognition from the sequelae of epilepsy alone. Yet there is a growing body of literature suggesting that the underlying epilepsy has a significant negative impact on cognition and contributes to psychopathology.28 Even presumed “benign” epileptic syndromes, such as absence seizures, have been found to be associated with a higher incidence of learning disabilities.29 Often, the behavioral consequences of disease and treatment are more disabling than the seizures themselves.30 Participation in extracurricular activities is a vital part of social development. Limitations on participation must be considered. These problems are obviously not unique to epilepsy; asthma is the most common childhood illness that restricts full participation in athletics and other activities. Children and adolescents with epilepsy have a higher degree of social and emotional retardation than do those with asthma and other nonneurologic disorders.31-33 Reliable “quality-of-life indicators” have not been fully developed and tested for children and adolescents.34 Driving is a “right of passage” for many adolescents. Any disorder that impairs awareness poses restrictions on the ability to achieve this important measure of independence. Restrictions vary by

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state, but generally require being seizure-free for 6 months to 2 years. For some adolescents this can be an important tool for improving compliance during this very difficult time. There continue to be safety and medicolegal concerns about the potential reaction-slowing and judgment-impairing effects of medications. These effects may be compounded by the concurrent use of other substances, including prescriptions and over-the counter medications or herbal and other nontraditional remedies. The use of recreational substances, including alcohol and hallucinogenic substances, expands during this very critical time as well. Much of this use is out of the control of the physician and treatment team. An unexpected benefit of the recent push for more restrictive licensure requirements in inexperienced drivers occurring in many states, including adolescents, is that it may lessen the social burden of not driving for some youngsters with chronic disorders, including epilepsy. These problems are clearly exacerbated in the youngster with medical refractory epilepsy. Here the decision paradigm shifts from “whether to treat” into the realm of “how to successfully balance the effects and side effects of disease and treatment.” MEDICALLY REFRACTORY EPILEPSY

Most epilepsy patients can achieve seizure control with a single antiepileptic drug. However, despite the recent advances in pharmacologic management of epilepsy, 37% of patients with epilepsy continue to have breakthrough seizures.35 When adding antiepileptic drugs finding the correct combination is very important to increase the chances of seizure freedom especially because about 50% of patients with well-controlled seizures may experience unacceptable side effects from their medications. This problem is further exacerbated with polytherapy. In addition, there are significant comorbidities that must be taken into consideration. Some of these relate directly to the etiology of the epilepsy (eg, cerebral palsy, stroke, meningitis), whereas others may be a consequence of incompletely controlled seizures, or social restriction. Still others may be due to medication effects, even in the context of continued functioning. Childhood onset of seizures has been linked over time to decreased brain volume as measured by MRI, in addition to cognitive decline.36 Children undergoing surgical

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resection often have new acquired deficits that bring to bear the typical images of the more traditional rehabilitation process. When two or more medications fail, alternative therapies should be discussed, because prognosis is poor with additional antiepileptic drug use.35 Patients with pharmacoresistant seizures, or those who experience unacceptable side effects, have limited nonpharmacologic alternatives. Some of the alternatives treatments for these children include resective or ablative surgery, vagal nerve stimulator, and Ketogenic diet. Each of these options presents an additional set of rehabilitation issues. Resective or ablative surgery is well-selected children with intractable epilepsy may reduce or eliminate seizures.37-39 Surgical outcome, as measured by seizure reduction, is dependent on multiple factors, including duration of epilepsy, type of surgery performed, epileptic syndrome, presence or absence of a lesion, and location of epileptogenic focus. The duration of epilepsy in children is important, because it ultimately affects development. Prognosis is better when electrographic focus correlates with a lesional focus and a temporal rather than extratemporal focus. Extratemporal resections and hemispherectomies are performed most often in children under age 12, with the highest percentage done in children under age 2 .40 The most commonly identified pathologic correlates are cortical dysplasias and low-grade neoplasms. Vascular malformation and cortical infarction are less common etiologies. Success rates, as determined by reduction of seizure frequency, are less favorable with extratemporal resections. The seizure outcome is largely dependent on how well circumscribed the lesion is. The need for significant postoperative rehabilitation is dependent on the location of the lesion and the extent of the surgical resection. The nature of the specific deficit will determine the rehabilitation needs of the individual. Children with frontal lobe resective surgery may have higher IQ scores than those with temporal lobe resections, but also demonstrate greater impairment in manual motor coordination. Favorable results may be obtained even in the absence of complete seizure control.41 Temporal lobe resection for hippocampal sclerosis is the most common epilepsy surgery performed in adults,42 but is less common in children.43,44 Success rates, as determined by seizure frequency

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reduction of 70% to 80%, are seen in both children and adults.41 The most frequent complication is homonymous superior quadrantanopsia, which tends to be asymptomatic. There are limited data in children in regard to neuropsychological impact, but it is thought to be similar that of adults. IQ remains largely unchanged, but language and memory, especially the acquisition and retention of new verbal information after dominant hemisphere resections, are affected.45 Children with frontal lobe resections tends to have preserved IQ but more motor manipulation deficits.46 Patients with intractable epilepsy due to unilateral hemispheric syndromes may be good candidates for hemispherectomy. Typically patients have cortical dysplasias, prenatal or perinatal porencephalic cysts, Rasmussen encephalitis, hemimegalencephaly, or Sturge–Weber syndrome. Complete seizure freedom may be achieved in 50% to 80% of patients.47-49 Hemispherectomies performed early in life may actually decrease the severity of motor deficits, with an increased likelihood of independent ambulation. Language deficits are present despite early transfer of some function to the previously nondominant hemisphere. The mechanism of this process remains unknown. Patients with nonlocalizing epilepsy are more problematic. Corpus callosotomy provides a palliative option for patients with Lennox–Gastaut syndrome and intractable atonic seizures. It can be an alternative for other types of primary and secondarily generalized epilepsies. It is generally is effective in 60% to 80% of cases, with an average seizure frequency reduction of 70%.50 This can provide a significant improvement in the quality of life. Long-term sequelae necessitating rehabilitation include the disconnection syndrome, affecting interhemispheric communication between cortical, visual, and tactile sensory functions and verbal expression, among other problems. These longterm problems limit the overall acceptability of this procedure, especially with the increased availability of vagal nerve stimulation and the ketogenic diet. Since its approval in 1997, more than 4000 pediatric patients have had vagal nerve stimulators implanted. Recent adult and pediatric studies have demonstrated statistically significant reduction in seizure frequency and better quality of life.51 Approximately 30% of children demonstrated a 75%

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reduction in seizure frequency at 6 months and greater than 90% reduction at 12 months. Quality of life (QOL) was improved in 86%, and correlated with a shorter duration of epilepsy before implant and onset of seizures after 1 year of age. Improvement in QOL has not been completely correlated with a significant decrease in seizure frequency, but was affected by other factors, including improved alertness.52-54 Vagal nerve stimulation has also been associated with improved behavioral changes independent of complete seizure control.56 Undoubtedly, more study is needed in this area. The ketogenic diet is high in fat and limits carbohydrate and protein intake. Patients with refractory epilepsy can often achieve more than a 50% reduction in seizure frequency, depending on epileptic syndrome, with overall improvement in quality of life. Patient and family selection is critical to a successful trial on the ketogenic diet, to reduce the chance of discontinuation of the diet or noncompliance. A team approach with intense family education has been vital to the success of this therapeutic approach.56 Although many children on the ketogenic diet are severely developmentally disabled, the issue of noncompliance may still be present. THE TEAM APPROACH

Rehabilitation represents not only a distinct field of medicine, but also a philosophical and practical treatment approach that can be applied to various chronic disorders. Neurology encompasses many chronic disorders, making it ideal for the application of rehabilitation principles in daily practice. Epilepsy offers a unique opportunity to incorporate rehabilitation principles into the management of a complex medical disorder. The importance of the therapeutic milieu in the recovery may be as important as any specific medical or surgical intervention.57 During the rehabilitation process for patients with epilepsy, it is important to consider many factors, including the primary disease process and the treatment, including the potential neuropsychological effects of surgery and the potential negative cognitive effects of anticonvulsant medications. Future research will answer many of the lingering questions about long-term prognosis and the prospects for neuroprotection and antiepileptogenesis. The successful treatment of epilepsy requires a team approach. The rehabilitation process involves

an ongoing partnership between the physician, care team, patient, and family. Similarly, the treatment of chronic disorders is a dynamic process that involves the commitment of several partners to develop and implement a successful treatment strategy. The physician’s primary roles include (1) establishing the appropriate diagnoses; (2) educating the family regarding the potential treatment options available; (3) Counseling the family toward the selection of an appropriate treatment regimen, and developing back-up plans in the event of less than fully successful first approach; and (4) monitoring and adjusting of the treatment plan, which includes knowing when to expand the team. The individual and family are the primary focus of the treatment team. Making sure that the patient, family, physician, and treatment team have common goals and expectations is the key to a successful rehabilitation experience. The team can be expanded or contracted in response to the complexity of the epilepsy and the needs of the patient and family. The physician and patient can be considered the core of the team. Nurses and social workers provide education and support. Use of the ketogenic diet entails specialized nutritionists. Epilepsy surgery requires the additional expertise of medical and surgical epileptologists and electrophysiology technicians. Neuropsychologists, psychologists, and counselors have a vital role in assessment and support. Rehabilitation therapists are often needed to habilitate or rehabilitate specific developmental or acquired functional deficits. For children, specialists and teachers must also be part of the rehabilitation team. Actively involving the family in the decisionmaking process and educating them about the disease process improves therapeutic compliance. Improving communication allows for earlier detection of adverse events and adjustment of the treatment regimen. CONCLUSIONS

Epilepsy is an evolutionary disease process that changes with the maturation of the central nervous system. The rehabilitative model provides the framework for a dynamic treatment plan to meet the changing needs of the child with epilepsy through the social and developmental changes of childhood and adolescence.

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The development of epilepsy may complicate the recovery from many acute and chronic conditions that affect the central nervous system. The rehabilitation process must address these many

aspects of the disease process and its sequelae, including epilepsy. This makes neurologists uniquely qualified to manage the rehabilitation team.

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47. Carson BS, Javedan SP, Freeman JM, et al: Hemispherectomy: A hemidecortication approach and review of 52 cases. J Neurosurg 84:903-911, 1996 48. Peacock WJ, Wehby-Grant MC, Shields WD, et al: Hemispherectomy for intractable seizures in children: a report of 58 cases. Childs Nerv Syst 12:376-384, 1996 49. Montes JL, Farmer JP, Andermann F, et al: Hemispherectomy, in Wyllie E (ed): The Treatment of Epilepsy: Principles and Practice. Baltimore, MD, Lippincott Williams & Wilkins, 2001, pp 1147-1159 50. Rougier A, Claverie B, Pedespan JM, et al: Callosotomy for intractable epilepsy. J Neursurg Sci 41:51-57, 1997 51. Schachter SC, Wheless JW: Vagus nerve stimulation therapy 5 years after approval: A comprehensive update. Neurology 59(suppl 4):S1-61, 2002 52. Helmers SL, Wheless JW, Frost M, et al: Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: Retrospective study. J Child Neurol 16:843-848, 2001 53. Murphy JV, Wheless JW, Schmoll CM: Left vagal nerve stimulation in 6 patients with hypothalamic hamartomas. Pediatr Neurol 23:167-168, 2000 54. Patwardhan RV, Stong B, Bebin EM, et al: Efficacy of vagal nerve stimulation in children with medically refractory epilepsy. Neurosurgery 47:1353-1357, 2000 55. Rush AJ, George MS, Sackeim HA, et al: Vagus nerve stimulation for treatment-resistant depressions: a multicenter study. Biopsychiatry 47:276-286, 2000 56. Freeman JM, Freeman JB, Kelly MY, et al: The Ketogenic diet: a treatment for epilepsy, 3rd edition. Demos. 2000 57. Greenwood RS, Parent JM: et al. Damage control: The influence of environment on recovery from brain injury. Ann Neurol 59:1203–1303, 2002