Original Article
The Clinical Characteristics and Treatment Response in Children with West Syndrome in a Developing Country: A Retrospective Case Record Analysis
Journal of Child Neurology 1-8 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073815569304 jcn.sagepub.com
Sheffali Gulati, MD1, Puneet Jain, MD, DM1, Lakshminarayanan Kannan, MD, DM1, Rachna Sehgal, MD, DM1, and Biswaroop Chakrabarty, MD, DM1
Abstract This study describes the clinical characteristics, treatment, and outcome of children with West syndrome in a tertiary care hospital in north India. Overall, 310 case records diagnosed from January 2009 to June 2012 were reviewed. The median age of onset of spasms was 5 months (interquartile range ¼ 2.5-7 months). The predominant underlying etiology was perinatal cerebral ischemia (55%). Adrenocorticotropic hormone or oral steroids were received by 92% children, of whom 43% became seizure free. Median lag time for appropriate treatment initiation was significantly less in patients who became seizure free as compared to those with persisting seizures (11 vs 15 months, P ¼ .001) soon after receiving treatment of choice. Later age at onset of spasms was associated with a favorable seizure outcome (P ¼ .03). In a resource-limited setting, unawareness along with treatment costs and repeated visits to the hospital are significant obstacles to optimum management. Keywords West syndrome, epileptic encephalopathy, epileptic spasms, Lennox-Gastaut syndrome, hypsarrhythmia Received October 12, 2013. Received revised July 05, 2014. Accepted for publication December 22, 2014.
West syndrome was first described by W.J. West in 18411 and is characterized by a triad of epileptic spasms or salaam attacks, hypsarrhythmia on electroencephalogram (EEG), and developmental delay or regression. The typical onset is between 3 and 12 months of age. Hypsarrhythmia, the characteristic interictal EEG feature in West syndrome. is characterized by chaotic background EEG activity with nearly continuous, random, asynchronous, high-voltage slow waves and spikes arising from multiple foci.2 Early and aggressive treatment has implications for longterm neurodevelopmental outcome.3 The data from India on management and follow-up of patients with West syndrome are sparse.4-6 In a developing world scenario like that in India, there is dearth of expertise in identifying, diagnosing, and treating West syndrome. This is both at the level of parents and guardians (failure to identify these events as seizures) and health care services (lack of trained pediatric neurologists and low accessibility to EEG). The current center is one of the few tertiary-level public sector teaching hospitals in India where this condition is diagnosed and treated. Patients are referred from entire India and the neighboring countries. Being a public sector hospital, the cost of care is also very less and the patient
load is very high. Hence, patients from across the economic strata come here. Thus, data from a significantly large number of patients of West syndrome were collected over a short period of time. The purpose of this study was to describe the clinical characteristics, treatment received, and outcome of children with West syndrome.
Materials and Methods In this study, the medical records of patients who were diagnosed with West syndrome between January 2009 and June 2012 at a tertiary care hospital in North India were retrospectively reviewed. All the children diagnosed with West syndrome underwent thorough clinical examination and investigations, which included neuroimaging, EEG, and auditory and ophthalmologic evaluation. Metabolic
1
Division of Pediatric Neurology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
Corresponding Author: Sheffali Gulati, MD, Division of Pediatric Neurology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India. Email: [email protected]
Downloaded from jcn.sagepub.com at GEORGIAN COURT UNIV on March 21, 2015
2
Journal of Child Neurology
Children with West Syndrome
Treatmentnaïve paent
Paent already on treatment
Received hormonal therapy in the past
No idenfiable structural cause or insult
Trial of oral pyridoxine, bion, folinic acid, pyridoxal phosphate
No
Tuberous Sclerosis Complex
Valproate and clonazepam iniated
Assess for suitability of Vigabatrin
Screened for tuberculosis
Assess for suitability of ACTH No
Yes Spasms controlled
No Connuaon of the previous an-epilepcYes drugs
If yes, then Vigabatrin given
Yes
Oral steroids
ACTH
Drugs tried (not in any parcular sequence) Vigabatrin( if not tried before) Leveracetam Lamotrigine Topiramate Zonisamide
No
Paral/No response Dietary therapy offered
Figure 1. Treatment protocol for children with infantile spasms at the All India Institute of Medical Sciences, New Delhi. screening (arterial lactate and blood gas analysis, serum ammonia, tandem mass spectroscopy, and gas chromatography mass spectroscopy) and genetic tests (karyotyping) were done wherever necessary. The cases were classified as those with known (structural, metabolic, or genetic) and those with unknown etiology.7 The children were treated per the treatment protocol depicted in Figure 1. Those with no underlying etiology were sequentially given adequate trial of pyridoxine, biotin, pyridoxal phosphate, and folinic acid. All patients with a structural cause with no metabolic abnormality were offered intramuscular adrenocorticotropic hormone (ACTH) as first line of treatment except in cases of tuberous sclerosis complex, where vigabatrin was used as the initial drug of choice. ACTH was started at a dose of 20 to 30 U/d followed by 2 weekly increments of 20 U/d to a maximum dose of 80 U/d by the end of 6 weeks followed by gradual tapering. This was on the basis of dosage mentioned by the Finnish Consensus Group (3-6 units/kg/d).8 For those patients who could not afford ACTH treatment or had logistic problems in receiving daily injections, oral prednisolone (2 mg/kg/d) was started followed by increasing up to 3 mg/kg/d after 3 weeks and gradual tapering after further 3 weeks. Oral vigabatrin was started at a dose of 50 mg/kg/d, followed by 1 to 2 weekly hikes of 25 mg/kg/d with a maximum dose of 150 mg/kg/d by the end of 6 weeks. In nonresponders, it was tapered after 12 weeks, whereas in complete or partial responders it was continued for 6 months and then gradually tapered. Response to all the 3 first-line agents were assessed up to 6 weeks of starting therapy with dose escalation to maximum within that period, beyond which other antiepileptics or ketogenic diet were considered. The children were followed up on an outpatient basis in the pediatric neurology clinic. Pediatric neurology consultants (1 or 2) and senior residents (4-5) pursuing superspecialty fellowship in Pediatric Neurology
were attending the patients. The seizure frequency was assessed using parental seizure records. The clinical manifestations of the different seizure types were clarified with parents at each visit. The seizure response was classified as: (a) 100% seizure free, (b) 50% to 100% seizure reduction from the baseline, (c)
The Clinical Characteristics and Treatment Response in Children with West Syndrome in a Developing Country: A Retrospective Case Record Analysis
Journal of Child Neurology 1-8 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073815569304 jcn.sagepub.com
Sheffali Gulati, MD1, Puneet Jain, MD, DM1, Lakshminarayanan Kannan, MD, DM1, Rachna Sehgal, MD, DM1, and Biswaroop Chakrabarty, MD, DM1
Abstract This study describes the clinical characteristics, treatment, and outcome of children with West syndrome in a tertiary care hospital in north India. Overall, 310 case records diagnosed from January 2009 to June 2012 were reviewed. The median age of onset of spasms was 5 months (interquartile range ¼ 2.5-7 months). The predominant underlying etiology was perinatal cerebral ischemia (55%). Adrenocorticotropic hormone or oral steroids were received by 92% children, of whom 43% became seizure free. Median lag time for appropriate treatment initiation was significantly less in patients who became seizure free as compared to those with persisting seizures (11 vs 15 months, P ¼ .001) soon after receiving treatment of choice. Later age at onset of spasms was associated with a favorable seizure outcome (P ¼ .03). In a resource-limited setting, unawareness along with treatment costs and repeated visits to the hospital are significant obstacles to optimum management. Keywords West syndrome, epileptic encephalopathy, epileptic spasms, Lennox-Gastaut syndrome, hypsarrhythmia Received October 12, 2013. Received revised July 05, 2014. Accepted for publication December 22, 2014.
West syndrome was first described by W.J. West in 18411 and is characterized by a triad of epileptic spasms or salaam attacks, hypsarrhythmia on electroencephalogram (EEG), and developmental delay or regression. The typical onset is between 3 and 12 months of age. Hypsarrhythmia, the characteristic interictal EEG feature in West syndrome. is characterized by chaotic background EEG activity with nearly continuous, random, asynchronous, high-voltage slow waves and spikes arising from multiple foci.2 Early and aggressive treatment has implications for longterm neurodevelopmental outcome.3 The data from India on management and follow-up of patients with West syndrome are sparse.4-6 In a developing world scenario like that in India, there is dearth of expertise in identifying, diagnosing, and treating West syndrome. This is both at the level of parents and guardians (failure to identify these events as seizures) and health care services (lack of trained pediatric neurologists and low accessibility to EEG). The current center is one of the few tertiary-level public sector teaching hospitals in India where this condition is diagnosed and treated. Patients are referred from entire India and the neighboring countries. Being a public sector hospital, the cost of care is also very less and the patient
load is very high. Hence, patients from across the economic strata come here. Thus, data from a significantly large number of patients of West syndrome were collected over a short period of time. The purpose of this study was to describe the clinical characteristics, treatment received, and outcome of children with West syndrome.
Materials and Methods In this study, the medical records of patients who were diagnosed with West syndrome between January 2009 and June 2012 at a tertiary care hospital in North India were retrospectively reviewed. All the children diagnosed with West syndrome underwent thorough clinical examination and investigations, which included neuroimaging, EEG, and auditory and ophthalmologic evaluation. Metabolic
1
Division of Pediatric Neurology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
Corresponding Author: Sheffali Gulati, MD, Division of Pediatric Neurology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India. Email: [email protected]
Downloaded from jcn.sagepub.com at GEORGIAN COURT UNIV on March 21, 2015
2
Journal of Child Neurology
Children with West Syndrome
Treatmentnaïve paent
Paent already on treatment
Received hormonal therapy in the past
No idenfiable structural cause or insult
Trial of oral pyridoxine, bion, folinic acid, pyridoxal phosphate
No
Tuberous Sclerosis Complex
Valproate and clonazepam iniated
Assess for suitability of Vigabatrin
Screened for tuberculosis
Assess for suitability of ACTH No
Yes Spasms controlled
No Connuaon of the previous an-epilepcYes drugs
If yes, then Vigabatrin given
Yes
Oral steroids
ACTH
Drugs tried (not in any parcular sequence) Vigabatrin( if not tried before) Leveracetam Lamotrigine Topiramate Zonisamide
No
Paral/No response Dietary therapy offered
Figure 1. Treatment protocol for children with infantile spasms at the All India Institute of Medical Sciences, New Delhi. screening (arterial lactate and blood gas analysis, serum ammonia, tandem mass spectroscopy, and gas chromatography mass spectroscopy) and genetic tests (karyotyping) were done wherever necessary. The cases were classified as those with known (structural, metabolic, or genetic) and those with unknown etiology.7 The children were treated per the treatment protocol depicted in Figure 1. Those with no underlying etiology were sequentially given adequate trial of pyridoxine, biotin, pyridoxal phosphate, and folinic acid. All patients with a structural cause with no metabolic abnormality were offered intramuscular adrenocorticotropic hormone (ACTH) as first line of treatment except in cases of tuberous sclerosis complex, where vigabatrin was used as the initial drug of choice. ACTH was started at a dose of 20 to 30 U/d followed by 2 weekly increments of 20 U/d to a maximum dose of 80 U/d by the end of 6 weeks followed by gradual tapering. This was on the basis of dosage mentioned by the Finnish Consensus Group (3-6 units/kg/d).8 For those patients who could not afford ACTH treatment or had logistic problems in receiving daily injections, oral prednisolone (2 mg/kg/d) was started followed by increasing up to 3 mg/kg/d after 3 weeks and gradual tapering after further 3 weeks. Oral vigabatrin was started at a dose of 50 mg/kg/d, followed by 1 to 2 weekly hikes of 25 mg/kg/d with a maximum dose of 150 mg/kg/d by the end of 6 weeks. In nonresponders, it was tapered after 12 weeks, whereas in complete or partial responders it was continued for 6 months and then gradually tapered. Response to all the 3 first-line agents were assessed up to 6 weeks of starting therapy with dose escalation to maximum within that period, beyond which other antiepileptics or ketogenic diet were considered. The children were followed up on an outpatient basis in the pediatric neurology clinic. Pediatric neurology consultants (1 or 2) and senior residents (4-5) pursuing superspecialty fellowship in Pediatric Neurology
were attending the patients. The seizure frequency was assessed using parental seizure records. The clinical manifestations of the different seizure types were clarified with parents at each visit. The seizure response was classified as: (a) 100% seizure free, (b) 50% to 100% seizure reduction from the baseline, (c)
