Association of Head Injury with Late-Onset Epilepsy

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Online-Only Supplement

Association of Head Injury with Late-Onset Epilepsy: Results from the Atherosclerosis Risk in Communities (ARIC) Cohort

A.L.C. Schneider,R. F. Gottesman, G. L. Krauss, J. Gugger, R. Diaz-Arrastia, A. Kucharska- Newton, J. Huang, E. L. Johnson

Table of Contents

eTable 1. Self-reported head injury questions ... 2 eTable 2. ICD-9 and ICD-10 codes used to define head injury ... 3 eTable 3. Adapted Department of Defense head injury severity classification using ICD codes ... 4 eTable 4. Number of Individuals with specific ICD codes used to define head injury ... 5 eTable 5. ICD-9 and ICD-10 codes used to define late-onset epilepsy (LOE) ... 8 eTable 6. Number of Individuals with specific ICD codes used to define late-onset epilepsy (LOE) ... 9 eTable 7. Unadjusted and adjusted models of the hazard ratio for risk of late-onset epilepsy (LOE) after any head injury and after 1, and 2+ head injuries, excluding 737 individuals later diagnosed with dementia ... 11 eTable 8. Unadjusted and adjusted models of the hazard ratio for risk of late-onset epilepsy (LOE) after 0, 1, and 2+ head injuries stratified by most severe injury (among subpopulation of 1,345 head injury cases identified using ICD codes) ... 13

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eTable 1. Self-reported head injury questions.

ARIC Visit 3 (1993-1995)

1. Have you ever had a head injury which led you to see a physician or seek hospital care?

2. How many times has this happened?

3. How many of these head injuries resulted in your losing consciousness, no matter how briefly?

4.In what year was your head injury for which you sought medical care?

ARIC Visit 4 (1996-1998)

1. Have you ever had a major head injury? That is, one that resulted in your losing consciousness, no matter how briefly, or that led you to see a physician or seek hospital care?

2. How many times has this happened?

3. How many head injuries resulted in your losing consciousness, no matter how briefly?

4. In what year was your head injury for which you lost consciousness sought medical care?

ARIC Brain MRI Visit (2004-2006)*

1. Have you ever had a head injury that resulted in loss of consciousness (knocked out)?

2. How many times?

3. In what year or how old were you when this first occurred?

4. In what year or how old were you when this last occurred?

ARIC Visit 5 (2011-2013)*

1. Have you ever had a head injury that resulted in loss of consciousness?

2. Have you had a head injury with extended loss of consciousness (>5 minutes)?

3. Have you had a head injury that resulted in long-term problems or dysfunction?

ARIC Visit 6 (2016-2017)

1. Have you ever had a head injury that resulted in loss of consciousness?

2. Have you had a head injury with extended loss of consciousness (>5 minutes)?

3. Have you had a head injury that resulted in long-term problems or dysfunction?

*Questions asked in a subgroup of ARIC participants selected for brain magnetic resonance imaging (MRI) scans.

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eTable 2. ICD-9 and ICD-10 codes used to define head injury.

ICD-9 Codes

800.xx Fracture of vault of skull 801.xx Fracture of base of skull

803.xx Other and unqualified skull fractures

804.xx Multiple fractures involving skull or face with other bones 850.xx Concussion

851.xx Cerebral laceration and contusion

852.xx Subarachnoid, subdural, and extradural hemorrhage following injury

853.xx Other and unspecified intracranial hemorrhage following injury 854.xx Intracranial injury of other and unspecified nature

959.01 Head injury, unspecified

ICD-10 Codes

S02.0 Fracture of vault of skull S02.1X Fracture of base of skull

S02.8 Fractures of other unspecified skull and facial bones S02.91 Unspecified fracture of skull

S04.02 Injury of optic chiasm

S04.03X Injury of optic tract and pathways S04.04X Injury of visual cortex

S06.X Intracranial injuries, concussion, traumatic cerebral edema, diffuse and focal traumatic brain injury, traumatic epidural, subdural, and subarachnoid hemorrhage

S07.1 Crushing injury of skull

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eTable 3. Adapted Department of Defense Head Injury Severity Classification Using ICD-9 Codes.

Mild 800; 801; 803; 804 (.0, .00, .01, .02, .06, .09, .5, .50, .51, .52) 850 (.0, .1, .11, .5, .9)

310.2 959.01

Moderate/Severe 800; 801; 803; 804 (.03, .04, .05, .1, .10-.16, .19, .2, .20-.26, .29, .3, .30-.36, .39, .4, .40-.46, .49, .53, .54, .55, .56, .59) 850 (.12, .2, .3, .4)

851 (.0, .00-.06, .09, .2, .20-.26, .29, .4, .40-.46, .49, .6, .60- .66, .69, .8, .80-.86, .89)

852 (.0, .00-.06, .09, .2, .20-.26, .29, .4, .40-.46, .49, .64, .65, .84, .85)

853; 854 (.0, .00-.06, .09)

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eTable 4. Number of Individuals with specific ICD codes used to define head injury among the subset of 1,345 head injury cases identified using ICD-9 codes.

ICD Code Used to Identify Head Injury Head Injury Severity Category

Number of Individuals with ICD

Code in Medical Records 800.00 - Closed fracture of vault of skull without

mention of intracranial injury, unspecified state of consciousness

Mild 2

801.00 - Closed fracture of vault of skull without mention of intracranial injury, unspecified state of consciousness

Mild 23

801.01 - Closed fracture of vault of skull without mention of intracranial injury, with no loss of consciousness

Mild 18

801.02 - Closed fracture of vault of skull without mention of intracranial injury, with brief [less than one hour] loss of consciousness

Mild 2

801.26 - Closed fracture of base of skull with subarachnoid, subdural, and extradural hemorrhage, with loss of consciousness of unspecified duration

Moderate/Severe 7

801.31 - Closed fracture of base of skull with other and unspecified intracranial hemorrhage, with no loss of consciousness

Moderate/Severe 2

801.41 - Closed fracture of base of skull with intracranial injury of other and unspecified nature, with no loss of consciousness

Moderate/Severe 1

803.01 - Other closed skull fracture without mention of intracranial injury, with no loss of consciousness

Mild 2

850.0 - Concussion with no loss of consciousness

Mild 110

850.1 - Concussion with brief loss of consciousness

Mild 29

850.5 - Concussion with loss of consciousness of unspecified duration

Mild 32

850.9 - Concussion, unspecified Mild 93

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850.11 - Concussion, with loss of consciousness of 30 minutes or less

Mild 12

851.41 - Cerebellar or brain stem contusion without mention of open intracranial wound, no loss of consciousness

Moderate/Severe 2

851.80 - Other and unspecified cerebral laceration and contusion, without mention of open intracranial wound, unspecified state of consciousness

Moderate/Severe 20

851.81 - Other and unspecified cerebral laceration and contusion, without mention of open intracranial wound, with no loss of consciousness

Moderate/Severe 28

852.00 - Subarachnoid hemorrhage following injury without mention of open cranial wound, unspecified state of consciousness

Moderate/Severe 64

852.01 - Subarachnoid hemorrhage following injury without mention of open cranial wound, with no loss of consciousness

Moderate/Severe 42

852.20 - Subdural hemorrhage following injury without mention of open cranial wound,

unspecified state of consciousness

Moderate/Severe 309

852.21 - Subdural hemorrhage following injury without mention of open cranial wound, with no loss of consciousness

Moderate/Severe 143

852.24 - Subdural hemorrhage following injury without mention of open cranial wound, with prolonged [more than 24 hours] loss of consciousness and return to pre-existing conscious level

Moderate/Severe 16

852.40 - Extradural hemorrhage following injury without mention of open cranial wound,

unspecified state of consciousness

Moderate/Severe 18

852.41 - Extradural hemorrhage following injury without mention of open cranial wound, with no loss of consciousness

Moderate/Severe 10

853.00 - Other and unspecified intracranial hemorrhage following injury without mention of

Moderate/Severe 71

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open intracranial wound, unspecified state of consciousness

853.01 - Other and unspecified intracranial hemorrhage following injury without mention of open intracranial wound, with no loss of

consciousness

Moderate/Severe 31

853.02 - Other and unspecified intracranial hemorrhage following injury without mention of open intracranial wound, with brief [less than one hour] loss of consciousness

Moderate/Severe 8

853.04 - Other and unspecified intracranial hemorrhage following injury without mention of open intracranial wound, with prolonged [more than 24 hours] loss of consciousness and return to pre-existing conscious level

Moderate/Severe 1

854.00 - Intracranial injury of other and unspecified nature without mention of open intracranial wound, unspecified state of consciousness

Moderate/Severe 222

854.01 - Intracranial injury of other and unspecified nature without mention of open intracranial wound, with no loss of

consciousness

Moderate/Severe 41

854.09 - Intracranial injury of other and unspecified nature without mention of open intracranial wound, with concussion, unspecified

Moderate/Severe 3

959.01 - Head injury, unspecified Mild 2208

Note: The number of individuals with codes sums to more than the number with head injury as each individual could have more than one code used at different visits.

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eTable 5. ICD-9 and ICD-10 codes used to define late-onset epilepsy (LOE).

ICD-9 Codes

345.0x Generalized nonconvulsive epilepsy 345.1x Generalized convulsive epilepsy 345.2 Petit mal status

345.3 Grand mal status

345.4x Localization-related (focal) (partial) epilepsy with complex partial seizures 345.5x Localization-related (focal) (partial) epilepsy with simple partial seizures 345.7x Epilepsia partialis continua

345.8x Other forms of epilepsy and recurrent seizures 345.9x Epilepsy unspecified

780.39 Other convulsions

ICD-10 Codes

G40.0xx Localization-related (focal) (partial) epilepsy

G40.1xx Localization-related (focal) (partial) epilepsy with complex partial seizures G40.2xx Localization-related (focal) (partial) epilepsy with spimple partial seizures G40.3xx Generalized idiopathic epilepsy

G40.4xx Other generalized epilepsy and epileptic syndromes G40.8xx Other epilepsy and recurrent seizures

G40.9xx Epilepsy, unspecified R56.1 Post-traumatic seizures

R56.9 Seizure (convulsive), convulsions NOS

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eTable 6. Number of Individuals with specific ICD codes used to define late-onset epilepsy (LOE).

ICD Code Used to Identify LOE Number of Individuals

with ICD Code in Medical Records

345.1 - Generalized convulsive epilepsy 51

345.11 - Generalized convulsive epilepsy, with intractable epilepsy

16

345.3 - Grand mal status 1

345.4 - Localization-related (focal) (partial) epilepsy with complex partial seizures

23

345.41 - Localization-related (focal) (partial) epilepsy and epileptic syndromes with complex partial seizures, with intractable epilepsy

10

345.5 - Localization-related (focal) (partial) epilepsy with simple partial seizures

19

345.51 - Localization-related (focal) (partial) epilepsy with simple partial seizures, with intractable epilepsy

7 345.71 – Epilepsia partialis continua, with intractable epilepsy 1 345.8 - Other forms of epilepsy and recurrent seizures 14 345.81 - Other forms of epilepsy and recurrent seizures, with

intractable epilepsy

1

345.9 - Epilepsy unspecified 87

345.91 - Epilepsy unspecified, with intractable epilepsy 8

780.39 - Other convulsions 180

G40.109 - Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, not intractable, without status epilepticus

2

G40.219 - Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, intractable, without status epilepticus

4

G40.309 - Generalized idiopathic epilepsy and epileptic syndromes, not intractable, without status epilepticus

7

G40.409 - Other generalized epilepsy and epileptic syndromes, not intractable, without status epilepticus

8

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G40.802 - Other epilepsy, not intractable, without status epilepticus

3

G40.89 - Other seizures 31

G40.901 - Epilepsy, unspecified, not intractable, with status epilepticus

6

G40.909 - Epilepsy, unspecified, not intractable, without status epilepticus

64

R56.1 - Post-traumatic seizures 3

R56.9 – Unspecified convulsions 98

Note: The number of individuals with codes sums to more than the number with LOE as each individual could have more than one code used at different visits.

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eTable 7. Unadjusted and adjusted models of the hazard ratio for risk of late-onset epilepsy (LOE) after any head injury and after 1, and 2+ head injuries, excluding 737 individuals later diagnosed with dementia.

Model Hazard Ratio 95% Confidence Interval

Any Head Injury Unadjusted

No head injury 1 Reference

Head injury 2.05 1.42-2.97

Model 1*: adjusted for demographics

Head injury 2.07 1.42-3.01

Model 2**: fully adjusted

Head injury 1.91 1.31-2.79

Head Injury Frequency Unadjusted

0 Head injuries 1 Reference

1 Head injury 1.70 1.12-2.57

2+ Head injuries 3.90 2.20-6.92

Model 1*: adjusted for demographics

1 Head injury 1.72 1.13-2.62

2+ Head injuries 3.93 2.19-7.03

Model 2**: fully adjusted

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1 Head injury 1.62 1.06-2.47

2+ Head injuries 3.36 1.87-6.06

*Model 1 is adjusted for visit 1 age, sex, race/field center, and education level.

**Model 2 is adjusted for variables in Model 2 + body mass index, smoking, alcohol use, APOE ε4 genotype, hypertension, diabetes, history of stroke.

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eTable 8. Unadjusted and adjusted models of the hazard ratio for risk of late-onset epilepsy (LOE) after 0, 1, and 2+ head injuries stratified by most severe injury (among subpopulation of 1,345 head injury cases identified using ICD codes).

Model Hazard Ratio 95% Confidence

Interval Unadjusted:

1 Mild head injury 2.56 1.71-3.82

1 Moderate/severe head injury 3.33 1.38-7.52

2+ Mild head injuries 6.29 4.15-9.53

2+ Moderate/severe head injuries 9.39 5.74-15.36 Model 1*: adjusted for demographics

2+ Moderate/severe head injuries 10.32 6.28-16.98 Model 2**: fully adjusted

2+ Moderate/severe head injuries 6.28 3.78-10.44

*Model 1 is adjusted for visit 1 age, sex, race/field center, and education level.

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**Model 2 is adjusted for variables in Model 1 + body mass index, smoking, alcohol use, APOE ε4 genotype, hypertension, diabetes, history of stroke, and history of dementia.