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1 Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Pujar SS, Martinos MM, Cortina-Borja M, et al, on behalf of the North London Epilepsy Research Network. Long-term prognosis after childhood convulsive status epilepticus: a prospective cohort study. Lancet Child Adolesc Health 2017; published online Dec 5.
2 Long-term prognosis after childhood status epilepticus- supplementary appendix This supplement contains the following items: Table S1. Clinical and demographic characteristics at the time of CSE of the follow-up cohort and those not followed-up 2 Figure S1. Venn diagram showing the number of subjects participating in neurological, neurocognitive, and neuroimaging assessment for the study 3 Table S2. Predictors on univariable analyses of incident (new-onset) epilepsy and intellectual disability following childhood CSE 4 Table S3. Details of seizure and aetiology classification, neuroimaging findings and seizure outcome at follow-up in subjects with incident epilepsy post-cse 5 Figure S2. Incidence of temporal lobe epilepsy (TLE) and epilepsy of non-tle semiology following childhood CSE 6 Table S4. Predictors of active epilepsy at follow-up post-cse in childhood 7 Figure S3. Prevalence of epilepsy, motor and intellectual disability at follow-up in childhood CSE cohort 8 Table S5. Educational outcomes in childhood CSE cohort 9 Table S6. CSE recurrence during follow-up according to CSE category 10 Figure S4. Clinical profile of children with and without clinically significant MRI abnormalities post-cse 11 1
3 Demographic/ Clinical Characteristics Followed-up (Total = 134) N (%) No follow-up (Total = 69) N (%) Difference in percentages (95% CI) Gender Male Female 67 (50) 67 (50) 35 (50 7) 34 (49 3) -0 7 (-14 9, 13 5) Median age at CSE, months (range) 32 7 (1-192) 31 8 ( ) Neurological impairment before the CSE episode Absent Present 59 (44) 75 (56) 33 (47 8) 36 (52 2) -3 8 (-17 9, 10 4) CSE category Prolonged febrile seizures 35 (26) 21 (30 5) -4 3 (-17 8, 8 2) Acute symptomatic 15 (11) 11 (16) -4 7 (-16, 4 6) Idiopathic epilepsy related 15 (11) 13 (19) -7 6 (-19 2, 2 2) Cryptogenic epilepsy related 4 (3) 2 (3) 0 0 (-7 2, 5) Remote symptomatic 53 (40) 19 (27 5) 12 (-1 9, 24 5) Unclassified 12 (9) 3 (4) 4 6 (-3 9, 11 3) CSE occurrence First-ever (Incident) Previous CSE (Recurrence) 106 (79) 28 (21) 57 (82 6) 12 (17 4) 3 5 (-8 7, 14) Seizure duration min >60 min 56 (41 8) 78 (58 2) 29 (42) 40 (58) -0 2 (-14 5, 13 6) Seizure character Continuous Intermittent 70 (52 2) 64 (47 8) 29 (42) 40 (58) 10 2 (-4 2, 23 9) Seizure type Focal-onset 9 (6 7) 5 (7 2) -0 5 (-9 7, 6 4) Secondarily generalised 39 (29 1) 26 (37 7) -8 6 (-22 3, 4 7) Primary generalised 86 (64 2) 38 (55 1) 9 1 (-4 9, 23 1) Ethnicity White 54 (40 3) 20 (29) 11 3 (-2 7, 23 9) Black 22 (16 4) 18 (26 1) -9 7 (-22 3, 1 8) Asian 41 (30 6) 21 (30 4) 0 2 (-13 5, 12 8) Mixed 7 (5 2) 4 (5 8) -0 6 (-9 2, 5 7) Other 10 (7 5) 6 (8 7) -1 2 (-10 8, 6 1) Socioeconomic status (Median IMD 2004 scores) P value on Mann-Whitney U test Table S1. Clinical and demographic characteristics at the time of CSE of the follow-up cohort and those not followed-up 2
4 Figure S1. Venn diagram showing the number of subjects participating in neurological, neurocognitive, and neuroimaging assessment for the study 3
5 Clinical and demographic characteristics Epilepsy Intellectual disability Complete case (N = 73) Imputed dataset (N = 116) Complete case (N = 80) Imputed dataset (N = 125) OR (95% CI) P OR (95% CI) P OR (95% CI) P OR (95% CI) P Age at CSE (months) 1 01 (0 999, 1 03) (0 99, 1 02) (0 97, 1 02) (0 98, 1 02) 0 99 Previous CSE* (0 4, 64 6) (0 3, 44 3) 0 28 Afebrile at CSE 8 4 (2 6, 26 4) < (1 8, 15 3) (0 6, 14 3) (0 5, 12 2) 0 25 Time to first treatment (min) 0 99 (0 96, 1 04) (0 97, 1 04) (0 87, 1 002) (0 91, 1 04) 0 44 CSE duration (min) 0 99 (0 98, 1 01) (0 98, 1 01) (0 99, 1 01) (0 99, 1 01) 0 68 Intermittent v continuous CSE 0 8 (0 3, 2 2) (0 4, 3 1) (0 3, 7 0) (0 3, 5 6) 0 67 CSE onset (focal v generalised) 1 2 (0 4, 3 5) (0 5, 3 6) (0 7, 17 8) (0 5, 11 4) 0 29 Epilepsy at baseline NA NA NA NA 8 0 (1 1, 59 6) (1 0, 43 0) Motor abnormality at baseline* 2 9 (0 4, 22 4) (0 4, 12 7) Abnormal cognition at baseline 2 5 (0 6, 10 4) (0 5, 8 3) 0 30 NA NA NA NA OR Odds Ratio *Zero cells NA Not Applicable Table S2. Predictors on univariable analyses of incident (new-onset) epilepsy and intellectual disability following childhood CSE 4
6 CSE category Prolonged febrile seizures (N=35) Acute symptomatic (N=15) Remote symptomatic (N=11) Unclassified (N=12) Age at CSE Interval between CSE & epilepsy onset Seizure/epilepsy type Direct aetiology MRI findings Epilepsy outcome at follow-up 10m 17m Generalised convulsive Presumed genetic Normal Terminal remission 4y 8m 7m Generalised convulsive Unknown Normal Terminal remission 1y 55m Dyscognitive focal seizures Focal onset with secondary generalisation Structural/metabolic Left mesial temporal sclerosis Terminal remission 3y 4m 3m Focal onset with secondary generalisation Presumed genetic Normal Terminal remission 2y 3m 2m Focal onset with secondary generalisation Undetermined Normal Terminal remission 1y 6m 13m Focal onset with secondary generalisation Generalized other motor Structural/metabolic Normal Terminal remission 7y 6m 2m Focal onset with secondary generalisation Structural/metabolic Normal Active 4y 6m 8m Dyscognitive focal seizures Focal onset with secondary generalisation Structural/metabolic Left mesial temporal sclerosis Terminal remission 12y 8m 6m Focal onset with secondary generalisation Structural/metabolic Focal cortical dysplasia Terminal remission 2y 3m 1m Focal onset with secondary generalisation Structural/metabolic Prominent ventricles and sulci Terminal remission 2y 1m 3m Focal autonomic Structural/metabolic Periventricular leucomalacia Terminal remission 2y 10m 0m Generalised convulsive Undetermined Uncooperative Active 2y 8m 2m Convulsive undetermined Undetermined Normal Terminal remission 6y 4m 1m Dyscognitive focal seizures Focal onset with secondary generalisation 3y 10m 2m Dyscognitive focal seizures Focal onset with secondary generalisation Structural/metabolic Left mesial temporal sclerosis Active Undetermined Declined MRI Terminal remission 2y 3m 10m Focal onset with secondary generalisation Undetermined Normal Active 4y 5m 3m Focal onset with secondary generalisation Undetermined Normal Terminal remission 3m 33m Focal onset with secondary generalisation Unknown Delayed myelination Active Table S3. Details of seizure and aetiology classification, neuroimaging findings and seizure outcome at follow-up in subjects with incident epilepsy post-cse 5
7 TLE Temporal lobe epilepsy Figure S2. Incidence of temporal lobe epilepsy (TLE) and epilepsy of non-tle semiology following childhood CSE 6
8 Clinical and demographic characteristics Complete case (N=134) Imputed dataset (N=203) Univariable Multivariable Univariable Multivariable OR (95% CI) P OR (95% CI) P OR (95% CI) P OR (95% CI) P Age at CSE (months) 1 02 (1 01, 1 03) (0 99, 1 02) (1 006, 1 02) (0 99, 1 02) 0 69 Previous CSE 5 8 (2 4, 14 3) < (0 3, 3 2) (2 4, 13 2) < (0 3, 2 9) 0 99 Afebrile at CSE 4 8 (2 1, 10 9) < (0 6, 5 4) (1 8, 8 5) < (0 6, 5 0) 0 32 Epilepsy at baseline 34 6 (11 0, 108 5) < (1 8, 39 0) (8 4, 59 4) < (2 1, 34 6) Motor abnormality at baseline 17 7 (7 1, 44 1) < (0 4, 7 7) (5 2, 30 0) < (0 7, 9 4) 0 17 Abnormal cognition at baseline 27 2 (8 8, 84 2) < (0 5, 17 7) (4 6, 36 5) < (0 3, 8 6) 0 66 OR Odds Ratio Table S4. Predictors of active epilepsy at follow-up post-cse in childhood 7
9 Figure S3. Prevalence of epilepsy, motor and intellectual disability at follow-up in childhood CSE cohort 8
10 Prolonged febrile seizures Acute symptomatic Idiopathic & cryptogenic Remote symptomatic Unclassified All CSE None 28 (80.0, ) 13 (86.7, ) 1 (5.3, ) 4 (7.6, ) 8 (66.7, ) 54 (40.3, ) Additional support in mainstream class 5 (14.3, ) 2 (13.3, ) 1 (5.3, ) 3 (5.7, ) 0 (0, ) 11 (8.2, ) Statement of special educational needs 2 (5.7, ) 0 (0, ) 17 (89.5, ) 46 (86.8, ) 4 (33.3, ) 69 (51.5, ) Total Table S5. Educational outcomes in childhood CSE cohort 9
11 CSE category CSE recurrence during follow-up Previous CSE Number at risk During NLSTEPSS After NLSTEPSS All recurrences Prolonged febrile seizures (N= 35) Incident cases 35 4 (11 4, ) 6 (17 1, ) 10 (28 6, ) Previous CSE All cases 35 4 (11 4, ) 6 (17 1, ) 10 (28 6, ) Acute symptomatic (N=15) Incident cases 15 1 (6 7, ) 0 (0, ) 1 (6 7, ) Previous CSE All cases 15 1 (6 7, ) 0 (0, ) 1 (6 7, ) Idiopathic & cryptogenic (N= 19) Incident cases 11 2 (18 2, ) 4 (36 4, ) 6 (54 6, ) Previous CSE 8 1 (12 5, ) 5 (62 5, ) 6 (75, ) All cases 19 3 (15 8, ) 9 (47 4, ) 12 (63 2, ) Remote symptomatic (N= 53) Incident cases 35 7 (20, ) 9 (25 7, ) 16 (45 7, ) Previous CSE 18 6 (33 3, ) 8 (44 4, ) 14 (77 8, ) All cases (24 5, ) 17 (32, ) 30 (56 6, ) Unclassified (N= 12) Incident cases 10 1 (10, ) 4 (40, ) 5 (50, ) Previous CSE 2 0 (0, ) 0 (0, ) 0 (0, ) All cases 12 1 (8 3, ) 4 (33 3, ) 5 (41 7, ) All CSE (N= 134) Incident cases (14 2, ) 23 (21 7, ) 38 (35 9, ) Previous CSE 28 7 (25, ) 13 (46 4, ) 20 (71 4, ) All cases (16 4, ) 36 (26 9, ) 58 (43 3, ) Table S6. CSE recurrence during follow-up according to CSE category 10
12 Figure S4. Clinical profile of children with and without clinically significant MRI abnormalities post-cse 11
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