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Response to rehabilitation of children and adolescents with epilepsy
Epilepsy & Behavior 20 (2011) 79–82
Contents lists available at ScienceDirect
Epilepsy & Behavior j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h
Response to rehabilitation of children and adolescents with epilepsy Matteo Chiappedi a,b, Ettore Beghi c,d,⁎, Oreste Ferrari-Ginevra e, Alessandro Ghezzo f, Emanuela Maggioni d, Flavia Mattana c, Patrizia Spelta g, Maria Chiara Stefanini h, Paolo Biserni a, Pietro Tonali i a
Fondazione Don Carlo Gnocchi ONLUS, Centro Medico “Santa Maria alle Fonti,” Salice Terme (PV), Italy Department of Neurological Science, University of Pavia, Pavia, Italy Istituto di Ricerche Farmacologiche “Mario Negri,” Milan, Italy d Fondazione Don Carlo Gnocchi ONLUS, IRCCS “Santa Maria Nascente,” Milan, Italy e Fondazione Don Carlo Gnocchi ONLUS, Centro Medico “Santa Maria al Castello,” Pessano con Bornago (MI), Italy f Fondazione Don Carlo Gnocchi ONLUS, Centro Medico “Bignamini,” Falconara (AN), Italy g Fondazione Don Carlo Gnocchi ONLUS, Centro Medico “Santa Maria alla Rotonda,” Inverigo (Como), Italy h Fondazione Don Carlo Gnocchi ONLUS, Centro Medico “Santa Maria della Pace,” Rome, Italy i Istituto di Neurologia, Università Cattolica del Sacro Cuore, Rome, Italy b c
a r t i c l e
i n f o
Article history: Received 20 July 2010 Revised 27 October 2010 Accepted 27 October 2010 Available online 3 December 2010 Keywords: Adolescent Child Epilepsy Rehabilitation
a b s t r a c t One hundred fifty-six children and adolescents with epilepsy from six Italian rehabilitation units were retrospectively enrolled to define the proportion of patients with epileptogenic developmental disorders who benefit from comprehensive rehabilitation programs and to identify factors predicting treatment response. The rehabilitation programs were classified as neuromotor, psychomotor, and speech and language. For each program, the response was coded as present or absent according to the caring physician's judgment. Selected demographic and clinical variables were correlated to treatment response. Neuromotor rehabilitation was performed in 86 cases (55%), psychomotor rehabilitation in 54 cases (34%), and speech and language rehabilitation in 40 cases (26%). Response rates were 58, 74, and 90%, respectively. Independent negative predictors of treatment response included severity of functional impairment (odds ratio= 0.02, 95% confidence interval= 0.01–0.14) and daily seizures (odds ratio = 0.22, 95% confidence interval= 0.08–0.58). © 2010 Elsevier Inc. All rights reserved.
1. Introduction Children and adolescents with functional disabilities are usually involved in comprehensive rehabilitation programs aimed at improving their adjustment to everyday life and, ultimately, their quality of life [1]. However, the response to these treatments is often unclear, a source of frustration for the patients and their families, and not cost-effective for health care administrators (i.e., costs are possibly too high to justify results obtained). In this context, epilepsy (a common complication of developmental encephalopathies) is thought to represent an impediment to the effects of rehabilitation because of the recurrence of seizures and the adverse effects of drugs. Other significant comorbidities, some of them directly related to epilepsy (such as mental retardation and sensory deficits), must be also taken into account and imply functional impairment and social restriction [2]. Behavioral problems can affect social outcome profoundly, and it is still a matter of debate how far they can be correlated with such factors as type of epileptic syndrome, underlying neurodevelopmental condition, epileptiform discharges, and medical or surgical treatment [3]. Assessment of rehabilitation outcome ⁎ Corresponding author. Istituto di Ricerche Farmacologiche "Mario Negri," Via G. la Masa 19, 20156 Milan, Italy. Fax: + 39 02 39001916. E-mail address: [email protected] (E. Beghi). 1525-5050/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2010.10.029
is even more complicated by the subjective interpretation of the severity of the functional impairment and the response to the available treatments. For these reasons, an observational study of a cohort of children and adolescents with developmental disorders and epilepsy was undertaken with a twofold purpose: (1) to define the proportion of cases thought to benefit from comprehensive rehabilitation programs, and (2) to identify factors predicting treatment response. 2. Methods The study was conducted in six rehabilitation units affiliated with the Don Gnocchi Foundation, a national network of private institutions devoted to the care and rehabilitation of clinical conditions causing functional disability. These units are located in northern and central Italy (Milan, Inverigo, Pessano, Salice Terme, Falconara, Rome) and serve the local population, providing unselected access to children and adolescents with developmental disorders with or without epilepsy. Patients with epilepsy were retrospectively traced through the centers’ medical records among those receiving at least a full rehabilitation cycle (see also below). Conforming to a standard definition [4], epilepsy was defined by the occurrence of at least two unprovoked seizures with or without treatment. Where present, the underlying epileptogenic condition (which was the source of the main diagnostic code) was recorded
80
M. Chiappedi et al. / Epilepsy & Behavior 20 (2011) 79–82
along with a number of demographic (age and gender) and clinical (ICD9-CM code, seizure frequency, disease severity, presence of a structural lesion, presence and degree of cognitive deficit, and number and type of antiepileptic drugs) variables. The rehabilitation program was specified and classified as neuromotor, psychomotor, or speech and language. Neuromotor rehabilitation in this study refers to physical therapy, with the specific goal of improving motor function and promoting development. Psychomotor rehabilitation aims at improving a child's development in a more general manner, using a mixture of motor, cognitive, and relational training. It combines different playbased techniques to improve knowledge of oneself and of the world, through motor functioning, with a consequent ability to establish a relationship with the human and nonhuman environment [5]. Speech and language rehabilitation is intended to increase a child's communicative skills, both verbal (“normal” speech therapy) and nonverbal (mainly using augmentative and alternative communication techniques), and sometimes also learning abilities (for older children and adolescents with learning disturbances). Every child was given a specific treatment program, usually including two to four sessions (45 minutes each) per week, using highly individualized sets of activities. Home exercises and parental and/or teacher counseling were provided depending on specific needs. Treatment length was not pre-defined, but chosen according to the specific characteristics of the patient (including age, underlying clinical condition, and personal skills) and meant to be sufficient to see an effect of rehabilitation in that specific patient. Children in our study were highly varied in many terms (including main diagnosis, comorbidities, age, seizure type, and frequency), so that no single validated assessment tool was able to reliably classify treatment outcome for all of them. Therefore, based on the subjective assessment of the caring physician, the response to the rehabilitation program was assessed and coded as “Present” or “Absent.” The response was considered “present” when, according to the physician's judgment, the child had acquired in a specific domain more skills than expected in the elapsed time according to his or her age. As the assessment of treatment response could be influenced by the subjective interpretation of the caring physician, interrater agreement was previously tested using the κ statistic and found to be satisfactory after proper training (κ ranging from 0.62 to 0.89 in Alimentary, Social, Movement, Communication, and Self-Management domains [Beghi et al., submitted]). The clinical judgment of the caring physician was used to rate global impairment and classify it as mild, moderate, severe, or profound. Data collection for the study fulfilled all legal requirements regarding data protection. In line with Italian legislation, as this was an observational study and the retrieval of the information on each patient and its transfer into a Web database were performed without identification of the case, ethical approval was not required. Descriptive statistics were applied to the demographic and clinical variables. Student's t test and the χ2 test for heterogeneity and trend were used as appropriate. A multivariate analysis of treatment response was also performed using a logistic regression model with forward stepwise (conditional) method to test the independent contribution of each demographic and clinical variable after adjusting for center and treatment duration. Some variables were dichotomized; these included cognitive deficit (severe/profound vs other), seizure frequency (daily vs other), severity of impairment (severe vs other), and number of drugs (3+ vs other). The data were analyzed with the SPSS Version 13.0 statistical package (Chicago, IL, USA) and are presented as means with SD, percentages, and odds ratios (ORs) with 95% confidence intervals (CIs). 3. Results
Table 1 Main diagnoses according to ICD9-CM. ICD9-CM group
Number (%) of cases
Cerebral palsy (343) Congenital anomalies (740–759) Mental disorders diagnosed in childhood (312–316) Other psychoses (295–299) Mental retardation (317–319) Hereditary and degenerative diseases of the central nervous system (330–337) Inflammatory diseases of the central nervous system (320–327) Other nonpsychotic mental disorders (306–311) Other paralytic syndromes (344)
73 (46.8) 22 (14.1) 21 (13.5) 16 (10.3) 12 (7.7) 6 (3.8)
most represented main diagnosis was cerebral palsy, followed by congenital anomalies, mental disorders diagnosed in childhood, and other psychoses (which includes Autism Spectrum Disorders) (Table 1). One hundred seventeen patients (75%) had a documented structural lesion, and 97 (62%), a severe disability. Cognitive deficit was severe or profound in 97 cases (62%). Fifty-two patients (35%) had one or more seizures per month, and 33 (22%), one or more
Table 2 Response to rehabilitation program by demographic and clinical characteristics of the sample. Variable Center 1 2 3 4 5 6 Gender Boys Girls Age, yearsa b5 5–9 10–14 15+ Severity of impairmentb Mild Moderate Severe Structural lesionb,c No Yes Cognitive deficit No Borderline Mild Moderate Severe Profound Seizure frequencyb,d b1/month 1–4/month 1–5/week Daily N1/day Number of drugsa None 1 2 3+ a
The study sample included 156 patients, 86 boys and 70 girls, aged 2 months to 19 years (mean = 7.6 years, SD = 6.4). The general characteristics of the sample are summarized in Tables 1 and 2. The
3 (1.9) 2 (1.3) 1 (0.6)
b c d
P b 0.005 (trend). P b 0.0005 (trend). Nonspecified in 8 cases. Nonspecified in 6 cases.
Number (%) of cases
Number (%) of responders
38 40 16 11 31 20
(24.4) (25.6) (10.3) (7.1) (19.9) (12.8)
23 (60.5) 28 (70.0) 11 (68.8) 7 (63.6) 20 (64.5) 12 (60.0)
86 (55.1) 70 (44.9)
54 (62.8) 47 (67.1)
16 70 43 27
12 (75.0) 53 (75.7) 24 (55.8) 12 (44.4)
(10.3) (44.9) (21.6) (17.3)
13 (8.3) 46 (29.5) 97 (62.2)
13 (100.0) 44 (95.7) 44 (45.4)
38 118
33 (86.8) 68 (57.6)
7 9 7 36 61 36
(4.5) (5.8) (4.5) (23.1) (39.1) (23.1)
5 (71.4) 9 (100.0) 7 (100.0) 32 (88.9) 40 (65.6) 8 (22.2)
98 14 5 13 20
(65.3) (9.3) (3.3) (8.7) (13.3)
75 (76.5) 11 (78.6) 2 (40.0) 4 (30.8) 7 (35.0)
7 87 41 21
(4.5) (55.8) (26.3) (13.5)
3 (42.9) 62 (71.3) 29 (70.7) 7 (13.5)
M. Chiappedi et al. / Epilepsy & Behavior 20 (2011) 79–82 Table 3 Response to the rehabilitation program by type of treatment. Treatment Neuromotora No Yes Psychomotor No Yes Speechb No Yes a b
Number (%) of cases
Number (%) of responders
70 86
51 (72.9) 50 (58.1)
103 53
62 (60.2) 39 (73.6)
116 40
65 (56.0) 36 (90.0)
P b 0.05. P b 0.0005.
seizures per day. One hundred forty-nine patients (96%) received one or more antiepileptic drugs. Valproate was the most common (96 patients), followed by phenobarbital (23 patients), carbamazepine (22 patients), lamotrigine (18 patients), and vigabatrin (14 patients). The proportion of cases responding to the rehabilitation programs varied significantly with age, severity of disability, presence of structural lesion, cognitive impairment, seizure frequency, and number of antiepileptic drugs (Table 2). Neuromotor rehabilitation was performed in 86 cases (55%), followed by psychomotor rehabilitation (53 cases, 34%) and speech and language rehabilitation (40 cases, 26%) (Table 3). Eleven patients received both psychomotor and speech and language rehabilitation (7%), whereas six received both neuromotor and speech and language rehabilitation (3.8%). Response rates to neuromotor, psychomotor, and speech and language rehabilitation were 58, 74, and 90%, respectively. In the multivariate analysis model, negative predictors of treatment response included only severity of impairment (OR = 0.02, 95% CI = 0.01–0.14) and daily seizures (OR = 0.22, 95% CI = 0.08–0.58).
4. Discussion As demonstrated in the study described here, children and adolescents with epilepsy seen in rehabilitation units are affected mostly by developmental disorders associated with physical, cognitive, psychological, and behavioral difficulties. This is consistent with published findings describing the relevant psychosocial impact of epilepsy in childhood [6]. In our cases, neuromotor rehabilitation was the most common therapeutic approach, followed by psychomotor rehabilitation and speech and language rehabilitation. Patients responding to the rehabilitation programs varied with age, severity of disability, presence of structural lesion, cognitive impairment, seizure frequency, and number of antiepileptic drugs. However, the only independent predictors of treatment response were severity of functional impairment and daily seizures. Cognitive deficit, a relevant component of severe disability, has been found to hamper the effects of rehabilitation in children and adolescents with head injury [7]; different factors (such as age at onset of seizures, type of epileptic syndrome, treatment with multiple antiepileptic drugs) causing educational underachievement in children with epilepsy have been reported to act through the induction of cognitive deficits [8]. High seizure frequency is likely to affect the level of participation required for rehabilitation to be effective and to induce a loss of mental abilities, in terms of both IQ and specific neuropsychological functions [9]. Interestingly, the number of concurrent antiepileptic drugs was not an independent negative predictor. Although the most common drugs were valproate, phenobarbital, and carbamazepine, that is, compounds thought to affect cognitive functions [10], their action was perhaps confounded by the severity of the disease, as already hypothesized by Sabbagh et al. [11] for school placement of children with epilepsy.
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An inverse correlation was found between efficacy of rehabilitation and age (see Table 2). However, this was not confirmed by multivariate analysis, which perhaps indicates that older children seen in rehabilitation units are mostly represented by patients with severe functional impairment and frequent seizures. Response was highest (90%) to speech and language rehabilitation, followed by psychomotor (74%) and neuromotor (58%) rehabilitation. These results can be explained by the differing indications of the three rehabilitation programs and by the heterogeneity of the target populations. Patients requiring speech and language rehabilitation were affected by milder epileptogenic conditions than those needing psychomotor and neuromotor rehabilitation. Neuromotor rehabilitation was performed in 70.1% of cases with severe functional impairment compared with 23.1% of those with mild functional impairment. The opposite was true for speech and language rehabilitation (9.3% vs 61.5%). None of the rehabilitation programs was found to be affected by seizure frequency. Thus, greater functional impairment, but not seizure frequency, seems to predict the failure of neuromotor and speech and language rehabilitation; in contrast, psychomotor rehabilitation was not apparently correlated with overall disease severity. The aim of rehabilitation is to maximize a patient's participation in his or her social setting [12] and to minimize stress and distress for the patient's family and caregivers. However, participation of an individual in a rehabilitation program is affected by the degree of functional impairment. In this context, the response to a rehabilitation program is maximized in patients already thought to respond. This explains why in our cohort, speech and language rehabilitation was offered more frequently to the less severely impaired patients. Thus, a successful outcome will include identification, prevention, and reduction of the cognitive, psychological, and social disabilities affecting children with developmental disorders. In contrast, the increased use of neuromotor rehabilitation in patients with severe functional impairment can only be explained as an attempt to prevent long-term complications and to provide a “basic” support to the patient and the family. In this context, neuromotor rehabilitation is the only program to be enacted to meet the patients’ and families’ demand even if the a priori expectation of success is fairly low. The study has several limitations. First, it is based on a wide definition of the rehabilitative options, without a single specific and evidence-based treatment. Second, nearly two-thirds of our patients had severe or profound cognitive deficits and severe functional impairments, and less compromised patients are therefore underrepresented. Third, our rehabilitation programs were highly individualized, and this is a possible source of bias in the interpretation of our results for lack of standardization. Last, even if the raters represent institutions with different geographic locations and have different personal and academic backgrounds, they all belong to a single foundation, so that these data may not be applicable to other settings. In conclusion, patients with epileptogenic developmental disorders have a differing response to neuromotor, psychomotor, and speech and language rehabilitation, neuromotor being the least and speech and language the most successful. As the efficacy of these therapeutic strategies is perhaps explained by the differing degree of functional impairment, one must also consider the cost-effectiveness of each of them, whose real indication should be seriously reconsidered to maximize its potential efficacy and limit its use in patients already thought to be nonresponders. In these patients, alternative therapeutic approaches should be explored.
References [1] Bishop M, Allen CA. The impact of epilepsy on quality of life: a qualitative analysis. Epilepsy Behav 2003;4:226–33. [2] Marks WA, Hernandez A, Gabriel M. Epilepsy: habilitation and rehabilitation. Semin Pediatr Neurol 2003;10:151–8. [3] Besag FM. Behavioral aspects of pediatric epilepsy syndromes. Epilepsy Behav 2004;5(Suppl 1):S3–S13.
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[4] Commission on Epidemiology and Prognosis, International League Against Epilepsy. Guidelines for epidemiological studies on epilepsy. Epilepsia 1993;34:592–6. [5] Dupré E. Patologie de l'emotivité et de l'imagination. Paris: Payot; 1925. [6] Sillanpaa M, Helen Cross J. The psychosocial impact of epilepsy in childhood. Epilepsy Behav 2009;15(Suppl 1):S5–S10. [7] Livingston MG, McCabe RJ. Psychosocial consequences of head injury in children and adolescents: implications for rehabilitation. Pediatrician 1990;17:255–61. [8] Bulteau C, Jambaque I, Viguier D, Kieffer V, Dellatolas G, Dulac O. Epileptic syndrome, cognitive assessment and school placement: a study of 251 children. Dev Med Child Neurol 2000;42:319–27.
[9] Dodrill CB. Neuropsychological effects of seizures. Epilepsy Behav 2004;5(Suppl 1): S21–4. [10] Brunbech L, Sabers A. Effect of antiepileptic drugs on cognitive function in individuals with epilepsy: a comparative review of newer versus older agents. Drugs 2002;62:593–604. [11] Sabbagh SE, Soria C, Escolano S, Bulteau C, Dellatolas G. Impact of epilepsy characteristics and behavioral problems on school placement in children. Epilepsy Behav 2006;9:573–8. [12] International classification of functioning, disability and health: version for children and youth. Geneva: World Health Organization; 2007.
Contents lists available at ScienceDirect
Epilepsy & Behavior j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h
Response to rehabilitation of children and adolescents with epilepsy Matteo Chiappedi a,b, Ettore Beghi c,d,⁎, Oreste Ferrari-Ginevra e, Alessandro Ghezzo f, Emanuela Maggioni d, Flavia Mattana c, Patrizia Spelta g, Maria Chiara Stefanini h, Paolo Biserni a, Pietro Tonali i a
Fondazione Don Carlo Gnocchi ONLUS, Centro Medico “Santa Maria alle Fonti,” Salice Terme (PV), Italy Department of Neurological Science, University of Pavia, Pavia, Italy Istituto di Ricerche Farmacologiche “Mario Negri,” Milan, Italy d Fondazione Don Carlo Gnocchi ONLUS, IRCCS “Santa Maria Nascente,” Milan, Italy e Fondazione Don Carlo Gnocchi ONLUS, Centro Medico “Santa Maria al Castello,” Pessano con Bornago (MI), Italy f Fondazione Don Carlo Gnocchi ONLUS, Centro Medico “Bignamini,” Falconara (AN), Italy g Fondazione Don Carlo Gnocchi ONLUS, Centro Medico “Santa Maria alla Rotonda,” Inverigo (Como), Italy h Fondazione Don Carlo Gnocchi ONLUS, Centro Medico “Santa Maria della Pace,” Rome, Italy i Istituto di Neurologia, Università Cattolica del Sacro Cuore, Rome, Italy b c
a r t i c l e
i n f o
Article history: Received 20 July 2010 Revised 27 October 2010 Accepted 27 October 2010 Available online 3 December 2010 Keywords: Adolescent Child Epilepsy Rehabilitation
a b s t r a c t One hundred fifty-six children and adolescents with epilepsy from six Italian rehabilitation units were retrospectively enrolled to define the proportion of patients with epileptogenic developmental disorders who benefit from comprehensive rehabilitation programs and to identify factors predicting treatment response. The rehabilitation programs were classified as neuromotor, psychomotor, and speech and language. For each program, the response was coded as present or absent according to the caring physician's judgment. Selected demographic and clinical variables were correlated to treatment response. Neuromotor rehabilitation was performed in 86 cases (55%), psychomotor rehabilitation in 54 cases (34%), and speech and language rehabilitation in 40 cases (26%). Response rates were 58, 74, and 90%, respectively. Independent negative predictors of treatment response included severity of functional impairment (odds ratio= 0.02, 95% confidence interval= 0.01–0.14) and daily seizures (odds ratio = 0.22, 95% confidence interval= 0.08–0.58). © 2010 Elsevier Inc. All rights reserved.
1. Introduction Children and adolescents with functional disabilities are usually involved in comprehensive rehabilitation programs aimed at improving their adjustment to everyday life and, ultimately, their quality of life [1]. However, the response to these treatments is often unclear, a source of frustration for the patients and their families, and not cost-effective for health care administrators (i.e., costs are possibly too high to justify results obtained). In this context, epilepsy (a common complication of developmental encephalopathies) is thought to represent an impediment to the effects of rehabilitation because of the recurrence of seizures and the adverse effects of drugs. Other significant comorbidities, some of them directly related to epilepsy (such as mental retardation and sensory deficits), must be also taken into account and imply functional impairment and social restriction [2]. Behavioral problems can affect social outcome profoundly, and it is still a matter of debate how far they can be correlated with such factors as type of epileptic syndrome, underlying neurodevelopmental condition, epileptiform discharges, and medical or surgical treatment [3]. Assessment of rehabilitation outcome ⁎ Corresponding author. Istituto di Ricerche Farmacologiche "Mario Negri," Via G. la Masa 19, 20156 Milan, Italy. Fax: + 39 02 39001916. E-mail address: [email protected] (E. Beghi). 1525-5050/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2010.10.029
is even more complicated by the subjective interpretation of the severity of the functional impairment and the response to the available treatments. For these reasons, an observational study of a cohort of children and adolescents with developmental disorders and epilepsy was undertaken with a twofold purpose: (1) to define the proportion of cases thought to benefit from comprehensive rehabilitation programs, and (2) to identify factors predicting treatment response. 2. Methods The study was conducted in six rehabilitation units affiliated with the Don Gnocchi Foundation, a national network of private institutions devoted to the care and rehabilitation of clinical conditions causing functional disability. These units are located in northern and central Italy (Milan, Inverigo, Pessano, Salice Terme, Falconara, Rome) and serve the local population, providing unselected access to children and adolescents with developmental disorders with or without epilepsy. Patients with epilepsy were retrospectively traced through the centers’ medical records among those receiving at least a full rehabilitation cycle (see also below). Conforming to a standard definition [4], epilepsy was defined by the occurrence of at least two unprovoked seizures with or without treatment. Where present, the underlying epileptogenic condition (which was the source of the main diagnostic code) was recorded
80
M. Chiappedi et al. / Epilepsy & Behavior 20 (2011) 79–82
along with a number of demographic (age and gender) and clinical (ICD9-CM code, seizure frequency, disease severity, presence of a structural lesion, presence and degree of cognitive deficit, and number and type of antiepileptic drugs) variables. The rehabilitation program was specified and classified as neuromotor, psychomotor, or speech and language. Neuromotor rehabilitation in this study refers to physical therapy, with the specific goal of improving motor function and promoting development. Psychomotor rehabilitation aims at improving a child's development in a more general manner, using a mixture of motor, cognitive, and relational training. It combines different playbased techniques to improve knowledge of oneself and of the world, through motor functioning, with a consequent ability to establish a relationship with the human and nonhuman environment [5]. Speech and language rehabilitation is intended to increase a child's communicative skills, both verbal (“normal” speech therapy) and nonverbal (mainly using augmentative and alternative communication techniques), and sometimes also learning abilities (for older children and adolescents with learning disturbances). Every child was given a specific treatment program, usually including two to four sessions (45 minutes each) per week, using highly individualized sets of activities. Home exercises and parental and/or teacher counseling were provided depending on specific needs. Treatment length was not pre-defined, but chosen according to the specific characteristics of the patient (including age, underlying clinical condition, and personal skills) and meant to be sufficient to see an effect of rehabilitation in that specific patient. Children in our study were highly varied in many terms (including main diagnosis, comorbidities, age, seizure type, and frequency), so that no single validated assessment tool was able to reliably classify treatment outcome for all of them. Therefore, based on the subjective assessment of the caring physician, the response to the rehabilitation program was assessed and coded as “Present” or “Absent.” The response was considered “present” when, according to the physician's judgment, the child had acquired in a specific domain more skills than expected in the elapsed time according to his or her age. As the assessment of treatment response could be influenced by the subjective interpretation of the caring physician, interrater agreement was previously tested using the κ statistic and found to be satisfactory after proper training (κ ranging from 0.62 to 0.89 in Alimentary, Social, Movement, Communication, and Self-Management domains [Beghi et al., submitted]). The clinical judgment of the caring physician was used to rate global impairment and classify it as mild, moderate, severe, or profound. Data collection for the study fulfilled all legal requirements regarding data protection. In line with Italian legislation, as this was an observational study and the retrieval of the information on each patient and its transfer into a Web database were performed without identification of the case, ethical approval was not required. Descriptive statistics were applied to the demographic and clinical variables. Student's t test and the χ2 test for heterogeneity and trend were used as appropriate. A multivariate analysis of treatment response was also performed using a logistic regression model with forward stepwise (conditional) method to test the independent contribution of each demographic and clinical variable after adjusting for center and treatment duration. Some variables were dichotomized; these included cognitive deficit (severe/profound vs other), seizure frequency (daily vs other), severity of impairment (severe vs other), and number of drugs (3+ vs other). The data were analyzed with the SPSS Version 13.0 statistical package (Chicago, IL, USA) and are presented as means with SD, percentages, and odds ratios (ORs) with 95% confidence intervals (CIs). 3. Results
Table 1 Main diagnoses according to ICD9-CM. ICD9-CM group
Number (%) of cases
Cerebral palsy (343) Congenital anomalies (740–759) Mental disorders diagnosed in childhood (312–316) Other psychoses (295–299) Mental retardation (317–319) Hereditary and degenerative diseases of the central nervous system (330–337) Inflammatory diseases of the central nervous system (320–327) Other nonpsychotic mental disorders (306–311) Other paralytic syndromes (344)
73 (46.8) 22 (14.1) 21 (13.5) 16 (10.3) 12 (7.7) 6 (3.8)
most represented main diagnosis was cerebral palsy, followed by congenital anomalies, mental disorders diagnosed in childhood, and other psychoses (which includes Autism Spectrum Disorders) (Table 1). One hundred seventeen patients (75%) had a documented structural lesion, and 97 (62%), a severe disability. Cognitive deficit was severe or profound in 97 cases (62%). Fifty-two patients (35%) had one or more seizures per month, and 33 (22%), one or more
Table 2 Response to rehabilitation program by demographic and clinical characteristics of the sample. Variable Center 1 2 3 4 5 6 Gender Boys Girls Age, yearsa b5 5–9 10–14 15+ Severity of impairmentb Mild Moderate Severe Structural lesionb,c No Yes Cognitive deficit No Borderline Mild Moderate Severe Profound Seizure frequencyb,d b1/month 1–4/month 1–5/week Daily N1/day Number of drugsa None 1 2 3+ a
The study sample included 156 patients, 86 boys and 70 girls, aged 2 months to 19 years (mean = 7.6 years, SD = 6.4). The general characteristics of the sample are summarized in Tables 1 and 2. The
3 (1.9) 2 (1.3) 1 (0.6)
b c d
P b 0.005 (trend). P b 0.0005 (trend). Nonspecified in 8 cases. Nonspecified in 6 cases.
Number (%) of cases
Number (%) of responders
38 40 16 11 31 20
(24.4) (25.6) (10.3) (7.1) (19.9) (12.8)
23 (60.5) 28 (70.0) 11 (68.8) 7 (63.6) 20 (64.5) 12 (60.0)
86 (55.1) 70 (44.9)
54 (62.8) 47 (67.1)
16 70 43 27
12 (75.0) 53 (75.7) 24 (55.8) 12 (44.4)
(10.3) (44.9) (21.6) (17.3)
13 (8.3) 46 (29.5) 97 (62.2)
13 (100.0) 44 (95.7) 44 (45.4)
38 118
33 (86.8) 68 (57.6)
7 9 7 36 61 36
(4.5) (5.8) (4.5) (23.1) (39.1) (23.1)
5 (71.4) 9 (100.0) 7 (100.0) 32 (88.9) 40 (65.6) 8 (22.2)
98 14 5 13 20
(65.3) (9.3) (3.3) (8.7) (13.3)
75 (76.5) 11 (78.6) 2 (40.0) 4 (30.8) 7 (35.0)
7 87 41 21
(4.5) (55.8) (26.3) (13.5)
3 (42.9) 62 (71.3) 29 (70.7) 7 (13.5)
M. Chiappedi et al. / Epilepsy & Behavior 20 (2011) 79–82 Table 3 Response to the rehabilitation program by type of treatment. Treatment Neuromotora No Yes Psychomotor No Yes Speechb No Yes a b
Number (%) of cases
Number (%) of responders
70 86
51 (72.9) 50 (58.1)
103 53
62 (60.2) 39 (73.6)
116 40
65 (56.0) 36 (90.0)
P b 0.05. P b 0.0005.
seizures per day. One hundred forty-nine patients (96%) received one or more antiepileptic drugs. Valproate was the most common (96 patients), followed by phenobarbital (23 patients), carbamazepine (22 patients), lamotrigine (18 patients), and vigabatrin (14 patients). The proportion of cases responding to the rehabilitation programs varied significantly with age, severity of disability, presence of structural lesion, cognitive impairment, seizure frequency, and number of antiepileptic drugs (Table 2). Neuromotor rehabilitation was performed in 86 cases (55%), followed by psychomotor rehabilitation (53 cases, 34%) and speech and language rehabilitation (40 cases, 26%) (Table 3). Eleven patients received both psychomotor and speech and language rehabilitation (7%), whereas six received both neuromotor and speech and language rehabilitation (3.8%). Response rates to neuromotor, psychomotor, and speech and language rehabilitation were 58, 74, and 90%, respectively. In the multivariate analysis model, negative predictors of treatment response included only severity of impairment (OR = 0.02, 95% CI = 0.01–0.14) and daily seizures (OR = 0.22, 95% CI = 0.08–0.58).
4. Discussion As demonstrated in the study described here, children and adolescents with epilepsy seen in rehabilitation units are affected mostly by developmental disorders associated with physical, cognitive, psychological, and behavioral difficulties. This is consistent with published findings describing the relevant psychosocial impact of epilepsy in childhood [6]. In our cases, neuromotor rehabilitation was the most common therapeutic approach, followed by psychomotor rehabilitation and speech and language rehabilitation. Patients responding to the rehabilitation programs varied with age, severity of disability, presence of structural lesion, cognitive impairment, seizure frequency, and number of antiepileptic drugs. However, the only independent predictors of treatment response were severity of functional impairment and daily seizures. Cognitive deficit, a relevant component of severe disability, has been found to hamper the effects of rehabilitation in children and adolescents with head injury [7]; different factors (such as age at onset of seizures, type of epileptic syndrome, treatment with multiple antiepileptic drugs) causing educational underachievement in children with epilepsy have been reported to act through the induction of cognitive deficits [8]. High seizure frequency is likely to affect the level of participation required for rehabilitation to be effective and to induce a loss of mental abilities, in terms of both IQ and specific neuropsychological functions [9]. Interestingly, the number of concurrent antiepileptic drugs was not an independent negative predictor. Although the most common drugs were valproate, phenobarbital, and carbamazepine, that is, compounds thought to affect cognitive functions [10], their action was perhaps confounded by the severity of the disease, as already hypothesized by Sabbagh et al. [11] for school placement of children with epilepsy.
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An inverse correlation was found between efficacy of rehabilitation and age (see Table 2). However, this was not confirmed by multivariate analysis, which perhaps indicates that older children seen in rehabilitation units are mostly represented by patients with severe functional impairment and frequent seizures. Response was highest (90%) to speech and language rehabilitation, followed by psychomotor (74%) and neuromotor (58%) rehabilitation. These results can be explained by the differing indications of the three rehabilitation programs and by the heterogeneity of the target populations. Patients requiring speech and language rehabilitation were affected by milder epileptogenic conditions than those needing psychomotor and neuromotor rehabilitation. Neuromotor rehabilitation was performed in 70.1% of cases with severe functional impairment compared with 23.1% of those with mild functional impairment. The opposite was true for speech and language rehabilitation (9.3% vs 61.5%). None of the rehabilitation programs was found to be affected by seizure frequency. Thus, greater functional impairment, but not seizure frequency, seems to predict the failure of neuromotor and speech and language rehabilitation; in contrast, psychomotor rehabilitation was not apparently correlated with overall disease severity. The aim of rehabilitation is to maximize a patient's participation in his or her social setting [12] and to minimize stress and distress for the patient's family and caregivers. However, participation of an individual in a rehabilitation program is affected by the degree of functional impairment. In this context, the response to a rehabilitation program is maximized in patients already thought to respond. This explains why in our cohort, speech and language rehabilitation was offered more frequently to the less severely impaired patients. Thus, a successful outcome will include identification, prevention, and reduction of the cognitive, psychological, and social disabilities affecting children with developmental disorders. In contrast, the increased use of neuromotor rehabilitation in patients with severe functional impairment can only be explained as an attempt to prevent long-term complications and to provide a “basic” support to the patient and the family. In this context, neuromotor rehabilitation is the only program to be enacted to meet the patients’ and families’ demand even if the a priori expectation of success is fairly low. The study has several limitations. First, it is based on a wide definition of the rehabilitative options, without a single specific and evidence-based treatment. Second, nearly two-thirds of our patients had severe or profound cognitive deficits and severe functional impairments, and less compromised patients are therefore underrepresented. Third, our rehabilitation programs were highly individualized, and this is a possible source of bias in the interpretation of our results for lack of standardization. Last, even if the raters represent institutions with different geographic locations and have different personal and academic backgrounds, they all belong to a single foundation, so that these data may not be applicable to other settings. In conclusion, patients with epileptogenic developmental disorders have a differing response to neuromotor, psychomotor, and speech and language rehabilitation, neuromotor being the least and speech and language the most successful. As the efficacy of these therapeutic strategies is perhaps explained by the differing degree of functional impairment, one must also consider the cost-effectiveness of each of them, whose real indication should be seriously reconsidered to maximize its potential efficacy and limit its use in patients already thought to be nonresponders. In these patients, alternative therapeutic approaches should be explored.
References [1] Bishop M, Allen CA. The impact of epilepsy on quality of life: a qualitative analysis. Epilepsy Behav 2003;4:226–33. [2] Marks WA, Hernandez A, Gabriel M. Epilepsy: habilitation and rehabilitation. Semin Pediatr Neurol 2003;10:151–8. [3] Besag FM. Behavioral aspects of pediatric epilepsy syndromes. Epilepsy Behav 2004;5(Suppl 1):S3–S13.
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[4] Commission on Epidemiology and Prognosis, International League Against Epilepsy. Guidelines for epidemiological studies on epilepsy. Epilepsia 1993;34:592–6. [5] Dupré E. Patologie de l'emotivité et de l'imagination. Paris: Payot; 1925. [6] Sillanpaa M, Helen Cross J. The psychosocial impact of epilepsy in childhood. Epilepsy Behav 2009;15(Suppl 1):S5–S10. [7] Livingston MG, McCabe RJ. Psychosocial consequences of head injury in children and adolescents: implications for rehabilitation. Pediatrician 1990;17:255–61. [8] Bulteau C, Jambaque I, Viguier D, Kieffer V, Dellatolas G, Dulac O. Epileptic syndrome, cognitive assessment and school placement: a study of 251 children. Dev Med Child Neurol 2000;42:319–27.
[9] Dodrill CB. Neuropsychological effects of seizures. Epilepsy Behav 2004;5(Suppl 1): S21–4. [10] Brunbech L, Sabers A. Effect of antiepileptic drugs on cognitive function in individuals with epilepsy: a comparative review of newer versus older agents. Drugs 2002;62:593–604. [11] Sabbagh SE, Soria C, Escolano S, Bulteau C, Dellatolas G. Impact of epilepsy characteristics and behavioral problems on school placement in children. Epilepsy Behav 2006;9:573–8. [12] International classification of functioning, disability and health: version for children and youth. Geneva: World Health Organization; 2007.