Clinical epidemiology of posttraumatic epilepsy in a group of Chinese patients

ObjectiveTo explore the incidence, types of onset, and risk factors of posttraumatic epilepsy (PTE).MethodsThis is a retrospective follow-up study of patients discharged from the Affiliated Hospital of the Medical College of the Chinese People's Armed Police Forces between September 2004 and September 2008 with a diagnosis of traumatic brain injury (TBI).ResultsComplete clinical information was available on 2826 patients. Of the 2826 TBI patients, 141 developed PTE, providing an incidence rate of 5.0%. Twenty-four cases (0.8%) had posttraumatic seizures (PTS), of which 16 (66.7%) continued to experience after the acute phase of their TBI, accounting for 5.0% of the total PTE cases. A total of 125 cases (88.7%) were diagnosed as presenting with late-stage seizures, occurring from 10 days to three years after TBI (93/141 (66.0%) presented within six months after the TBI, 14/141 (9.9%) between six and twelve months, 22/141 (15.7%) between one and two years and only 12/141 (8.5%) between two and three years after the TBI. The severity of PTE was rated mild, medium, and severe in 3.6%, 6.9%, and 17% of the TBI patients. Multiple regression analysis was carried out to identify factors contributing to the risk of developing PTE. Five parameters contributed to the model: Older age, greater severity of brain injury, abnormal neuroimaging, surgical treatment, and early-stage seizures.ConclusionAge, severity of brain injury, neuroimaging results, treatment methods, and early-stage seizures are independent risk factors of PTE.     

Risk factors for posttraumatic epilepsy: A systematic review and meta-analysis

ObjectiveA systematic review and meta-analysis was performed to identify risk factors for posttraumatic epilepsy (PTE).MethodsTwo electronic databases (Medline and Embase) were searched to identify studies with a cohort, case-control, or cross-sectional design reporting on epidemiologic evidence regarding risk factors for PTE.ResultsMen had a higher risk of developing PTE than women [relative ratio (RR), 1.32; 95% confidence interval (CI), 1.10–1.59]. A history of alcohol abuse (RR, 2.18; 95% CI, 1.26–3.79), posttraumatic amnesia (RR, 1.31; 95% CI, 1.12–1.53), focal neurologic signs (RR, 1.42; 95% CI, 1.16–1.74), and loss of consciousness at initial traumatic brain injury (TBI) (RR, 1.62; 95% CI, 1.13–2.32) were associated with a greater risk of PTE. TBI-related abnormal neuroimaging findings, including skull fracture (RR, 2.27; 95% CI, 1.49–3.44), midline shift (RR, 1.46; 95% CI, 1.14–1.87), brain contusion (RR, 2.35; 95% CI, 1.69–3.28), subdural hemorrhage (RR, 2.00; 95% CI, 1.33–3.01), and intracranial hemorrhage (RR, 2.65; 95% CI, 1.83–3.82) were strong risk factors for PTE. The risk of developing PTE after skull fracture, mild brain injury, and severe brain injury peaked within the first year after TBI, and then gradually decreased. However, a high risk of PTE was sustained for > 10 years.ConclusionThe current meta-analysis identified potential risk factors for PTE. The results may contribute to better prevention strategies and treatments for PTE.     

Results of phase II levetiracetam trial following acute head injury in children at risk for posttraumatic epilepsy

Posttraumatic seizures develop in up to 20% of children following severe traumatic brain injury (TBI). Children ages 6–17 years with one or more risk factors for the development of posttraumatic epilepsy, including presence of intracranial hemorrhage, depressed skull fracture, penetrating injury, or occurrence of posttraumatic seizure were recruited into this phase II study. Treatment subjects received levetiracetam 55 mg/kg/day, b.i.d., for 30 days, starting within 8 h postinjury. The recruitment goal was 20 treated patients. Twenty patients who presented within 8–24 h post‐TBI and otherwise met eligibility criteria were recruited for observation. Follow‐up was for 2 years. Forty‐five patients screened within 8 h of head injury met eligibility criteria and 20 were recruited into the treatment arm. The most common risk factor present for pediatric inclusion following TBI was an immediate seizure. Medication compliance was 95%. No patients died; 19 of 20 treatment patients were retained and one observation patient was lost to follow‐up. The most common severe adverse events in treatment subjects were headache, fatigue, drowsiness, and irritability. There was no higher incidence of infection, mood changes, or behavior problems among treatment subjects compared to observation subjects. Only 1 (2.5%) of 40 subjects developed posttraumatic epilepsy (defined as seizures >7 days after trauma). This study demonstrates the feasibility of a pediatric posttraumatic epilepsy prevention study in an at‐risk traumatic brain injury population. Levetiracetam was safe and well tolerated in this population. This study sets the stage for implementation of a prospective study to prevent posttraumatic epilepsy in an at‐risk population.     

Functional outcome and health-related quality of life 10 years after moderate-to-severe traumatic brain injury

Objectives – To describe the functional outcome and health‐related quality of life (HRQL) 10 years after moderate‐to‐severe traumatic brain injury (TBI). Material and methods – A retrospective, population‐based study of 62 survivors of working‐age with moderate‐to‐severe TBI injured in 1995/1996, and hospitalized at the Trauma Referral Center in Eastern Norway. Functional status was measured by the Glasgow Outcome Scale‐Extended (GOS‐E). HRQL was assessed by the SF‐36 questionnaire. Results – The mean current‐age was 40.8 years. The frequency of epilepsy was 19% and the depression rate 31%. A majority had good recovery (48%) or moderate disability (44%). Employment rate was 58%. Functional and employment status were associated with initial injury severity in contrast to HRQL. Study patients had significantly lower scores in all SF‐36 dimensions when compared with the general Norwegian population. Conclusion – At 10‐years follow‐up, our study population is still in their most productive years and affected domains should be considered in long‐term follow‐up and intervention programs.     

Predicting posttraumatic epilepsy with MRI: prospective longitudinal morphologic study in adults

PURPOSE: Evaluation of morphologic risk factors for posttraumatic epilepsy (PTE) by using brain magnetic resonance imaging (MRI) in serial assessments 相似文献   

Epileptic spasms in paediatric post‐traumatic epilepsy at a tertiary referral centre

Aim. To recognize epileptic spasms (ES) as a seizure type after traumatic brain injury (TBI), accidental or non‐accidental, in infants and children. In the process, we aim to gain some insight into the mechanisms of epileptogenesis in ES. Methods. A retrospective electronic chart review was performed at the Children's Hospital of Michigan from 2002 to 2012. Electronic charts of 321 patients were reviewed for evidence of post‐traumatic epilepsy. Various clinical variables were collected including age at TBI, mechanism of trauma, severity of brain injury, electroencephalography/neuroimaging data, and seizure semiology. Results. Six (12.8%) of the 47 patients diagnosed with post‐traumatic epilepsy (PTE) had ES. Epileptic spasms occurred between two months to two years after TBI. All patients with ES had multiple irritative zones, manifesting as multifocal epileptiform discharges, unilateral or bilateral. Cognitive delay and epileptic encephalopathy were seen in all six patients, five of whom were free of spasms after treatment with vigabatrin or adrenocorticotropic hormone. Conclusion. The risk of PTE is 47/321(14.6%) and the specific risk of ES after TBI is 6/321 (1.8%). The risk of ES appears to be high if the age at which severe TBI occurred was during infancy. Non‐accidental head trauma is a risk factor of epileptic spasms. While posttraumatic epilepsy (not ES) may start 10 years after the head injury, ES starts within two years, according to our small cohort. The pathophysiology of ES is unknown, however, our data support a combination of previously proposed models in which the primary dysfunction is a focal or diffuse cortical abnormality, coupled with its abnormal interaction with the subcortical structures and brainstem at a critical maturation stage.     

外伤性癫痫危险因素分析

目的 调查颅脑创伤(TBI)患者外伤性癫痫(PTE)的发生率、发作类型、危险因素及其认知功能等.方法 对我院脑系科中心2004年9月至2007年9月之间好转出院的TBI病例进行回顾性调查和电话随访及回访.纳入资料完整及能随访的患者共2023例.结果 (1)2 023例TBI患者中有98例出现PTE,其发生率为4.84%,高发年龄段为51～70岁和10岁以下.65例(66.32%)患者的PTE发生于外伤后1年以内;(2)TBI病情重、高龄、皮层损伤、蛛网膜下腔出血、多次手术治疗及受伤早期痫性发作均可增加PTE的发病率;(3)PTE 患者认知障碍和性格发生变化的发生率高于非PTE患者(P＜0.05).结论 癫痫发生与TBI严重程度、受伤年龄、损伤部位、影像学表现、治疗方法和伤后临床表现等有关.

Abstract：

Objective The purpose of this study was to investigate the incidence of posttraumatic seizure and epilepsy,the seizure type of epilepsy,risk factors of epilepsy and Recognition function.Methods The TBI cases discharged after the improvement from September 2004 to Septemher 2007 were retrospectively investigated and visited by telephone and 2023 cases was brought into study.Results (1)98 cases suffered PTE and the incidence of PTE was 4.84%;the age of high incidence was 51～70 years old and less than 10 years old. 65 cases(66.32%)occurred in less than one year after trauma.(2)Serious injury,old age,cortical injury,subarachnoid hemorrhage,many surgical treatment and early epileptic seizure after injury would increase the incidence of PTE(P＜0.05).(3)The incidence of cognitive impairment was higher in patients with PTE than non-PTE patients(P＜0.05).Conclusion The risk of posttranmatic seizure and epilepsy is correlation with the severity of TBI,age,injury location,imaging findings,treatment methods and clinical manifestations after injury.     

Predictors and dynamics of posttraumatic epilepsy

Objectives - The goal of our study was to identify clinical, neurophysiological and neuroradiological variables in severe head trauma (SHT) with predictive value for posttraumatic epilepsy (PTE) and to evaluate the influence of each risk factor for the dynamics of epilepsy. Material and methods - We systematically compared 57 PTE patients with 50 age and sex-matched control patients with SHT and no PTE. Mean follow-up was 8 years.
Results - Of all PTE-patients 68.5% had their first seizure within 2 years after the trauma. Significant risk factors for PTE were focal signs in the first examination ( P <0.01), missile injuries ( P <0.01), frontal lesions ( P <0.01), intracerebral hemorrhage ( P <0.01), diffuse contusion ( P <0.01), prolonged posttraumatic amnesia ( P <0.001), depression fracture ( P <0.01) and cortical-subcortical lesions ( P <0.001). The combination of the last 3 variables conferred a particularly high risk for PTE (logistic regression analysis). Combined seizure pattern, high seizure frequency, AED-non-compliance and alcohol abuse predicted poor seizure control.
Conclusion -The risk for PTE is clearly determined by those variables which correlate with the severity, the extent of tissue loss and the penetrating nature of the brain trauma.     

Factors associated with persistent risk of depression in older people following discharge from an acute cardiac unit

BACKGROUND: This longitudinal study aims to describe the prevalence and characteristics associated with persistent risk of depression in a group of older, hospitalized patients. METHODS: We examined patients at two time-points: baseline and one month post-discharge from hospital. Patients in this study comprised those who had been admitted to the cardiology unit, with no cognitive impairment, aged 60 years and over, and those who were followed up at both time points (N = 155). Questionnaires administered included risk of depression (Geriatric Depression Scale-15; GDS-15), cognitive impairment (Mini-mental State Examination), social support (7-Item Subjective Social Support Index), co-morbidity (Charlson's Comorbidity Index), sociodemographic variables, physical functioning (Modified Barthel's Index) and clinical variables. RESULTS: The prevalence of risk of depression (GDS-15 score > or = 5) among older inpatients at baseline was 34%. At one month post-discharge this had fallen to 17% and this group was identified as those at persistent risk of depression. Factors associated with a risk of persistent depression were: hospitalization within the last six months; length of stay of four days or more; discharge diagnosis of angina; and impaired Subjective Social Support Score. CONCLUSION: Depression occurs commonly among older hospitalized patients and may resolve spontaneously. The identification of factors associated with persistent risk of depression can be helpful when looking at which patients may benefit most from screening and treatment for depression after discharge.     

Imaging biomarkers of posttraumatic epileptogenesis

Traumatic brain injury (TBI) affects 2.5 million people annually within the United States alone, with over 300 000 severe injuries resulting in emergency room visits and hospital admissions. Severe TBI can result in long‐term disability. Posttraumatic epilepsy (PTE) is one of the most debilitating consequences of TBI, with an estimated incidence that ranges from 2% to 50% based on severity of injury. Conducting studies of PTE poses many challenges, because many subjects with TBI never develop epilepsy, and it can be more than 10 years after TBI before seizures begin. One of the unmet needs in the study of PTE is an accurate biomarker of epileptogenesis, or a panel of biomarkers, which could provide early insights into which TBI patients are most susceptible to PTE, providing an opportunity for prophylactic anticonvulsant therapy and enabling more efficient large‐scale PTE studies. Several recent reviews have provided a comprehensive overview of this subject (Neurobiol Dis, 123, 2019, 3; Neurotherapeutics, 11, 2014, 231). In this review, we describe acute and chronic imaging methods that detect biomarkers for PTE and potential mechanisms of epileptogenesis. We also describe shortcomings in current acquisition methods, analysis, and interpretation that limit ongoing investigations that may be mitigated with advancements in imaging techniques and analysis.     

Risk factors for hallucinations in Parkinson's disease: Results from a large prospective cohort study

The aim of this study was to identify risk factors for the development of hallucinations in patients with Parkinson's disease (PD). A broad range of motor and nonmotor features was assessed at baseline and during the following 5 years in 386 PD patients. Cross‐sectional analyses of baseline data and longitudinal analyses of follow‐up data were performed to identify risk factors for hallucinations in PD. Twenty‐one percent of the patients had hallucinations at baseline, whereas 46% of the patients without hallucinations at baseline developed this feature during follow‐up. Univariate survival analysis showed that older age, female sex, less education, higher age at onset, and more severe motor and cognitive impairment, depression, daytimes sleepiness, autonomic dysfunction, and motor fluctuations and dyskinesias, as well as higher daily levodopa dose, were associated with the risk of developing hallucinations. This largely corresponds with the features that were associated with the presence of hallucinations at baseline. In a stepwise regression model, older age at onset, female sex, excessive daytime sleepiness, autonomic dysfunction, and dyskinesias emerged as independent risk factors for developing hallucinations. Female sex, autonomic dysfunction, motor fluctuations, and dyskinesias have not been reported as risk factors in previous studies. These findings lend support to the notion that hallucinations in PD are caused by a combination of risk factors that are associated with (the interaction between) older age and more advanced disease. The identification of female sex as a risk factor for developing of hallucinations in PD is a new finding and should be verified in future studies. © 2013 Movement Disorder Society     

Does Glucocorticoid Administration Prevent Late Seizures after Head Injury?

PURPOSE: Preventing posttraumatic epilepsy has been a difficult challenge. In this study we evaluated the association between glucocorticoid administration after traumatic brain injury (TBI) and posttraumatic seizures. METHODS: We examined a seizure-prevention trial database of 404 patients with severe TBI for exposure to glucocorticoids in the early (<1 week) posttraumatic period. After controlling for seizure risk, we compared the odds of developing first and second late posttraumatic seizures between those that received glucocorticoids and those that did not. RESULTS: Patients dosed with glucocorticoids within 1 day of their TBI were more likely to develop first late seizures than were those without [p = 0.04; hazard ratio = 1.74; 95% confidence interval (CI), 1.01-2.98]; whereas those receiving glucocorticoids > or =2 days after their injury had no similar association (p = 0.66; hazard ratio = 0.77; 95% CI, 0.23-2.56; p = 0.10 among the three groups). Receiving glucocorticoids within 1 day, or > or =2 days after TBI was not associated with second late seizure development. CONCLUSIONS: Glucocorticoid treatment after TBI is not associated with decreased late posttraumatic seizures, and early treatment is associated with increased seizure activity.     

Suicide among older psychiatric inpatients: an evidence-based study of a high-risk group.

OBJECTIVE: Older adults have elevated suicide rates, especially in the presence of a psychiatric disorder, yet not much is known about predictors for suicide within this high-risk group. The current study examines the characteristics associated with suicide among older adults who are admitted to a psychiatric hospital. METHOD: All persons aged 60 and older living in Denmark who were hospitalized with psychiatric disorders during 1990-2000 were included in the study. Using a case-control design and logistic regression analysis, the authors calculated the suicide risk associated with specific patient characteristics. RESULTS: Affective disorders were found to be associated with an almost twofold higher risk of suicide among psychiatric inpatients than other types of disorders (95% confidence interval [CI]: 1.5-2.6). Patients with dementia had a significantly lower risk ratio of 0.2 (95% CI: 0.1-0.3). In combination with other types of disorder, affective disorders were found to modify an increased risk of suicide. First versus later admission for depression was a better predictor for suicide than age at first hospitalization for depression (before or after age 60 years). More than half of suicides occurred either within the first week of admission or discharge (chi(2) [1] = 27.70, p <0.001) compared with the distribution of patient days. CONCLUSIONS: Our findings underline the important role of affective disorder in combination with other types of disorders. Assessment of suicide risk among older psychiatric inpatients should take current or previous episodes of affective illness into consideration and pay special heed to the time shortly after admission and discharge.     

Cognitive outcome after mild and moderate traumatic brain injury in older adults

This paper presents findings on the cognitive outcome of older adults sustaining mild traumatic brain injury (TBI). Results indicate that mild TBI patients who are 50 years or older, unlike those with moderate TBI, exhibit cognitive functioning that is comparable to noninjured controls by 1-2-months postinjury. However, these patients continue to report significant anxiety, depression, and somatic preoccupation despite their improvement on objective neuropsychological measures. The lowest postresuscitation Glasgow Coma Scale (GCS) score and the presence of intracranial pathology are more strongly associated with outcome than the durations of posttraumatic amnesia and impaired consciousness, possibly reflecting measurement issues in older persons who are likely to be injured in low velocity falls and to suffer delayed complications. A classification system that considers not only the GCS score but also the presence of intracranial pathology is sensitive to differences in the outcome of older adults, similar to the findings in young patients. The implications of these findings for older TBI patients and directions for research are discussed.     

Cognitive Outcome After Mild and Moderate Traumatic Brain Injury in Older Adults

This paper presents findings on the cognitive outcome of older adults sustaining mild traumatic brain injury (TBI). Results indicate that mild TBI patients who are 50 years or older, unlike those with moderate TBI, exhibit cognitive functioning that is comparable to noninjured controls by 1-2-months postinjury. However, these patients continue to report significant anxiety, depression, and somatic preoccupation despite their improvement on objective neuropsychological measures. The lowest postresuscitation Glasgow Coma Scale (GCS) score and the presence of intracranial pathology are more strongly associated with outcome than the durations of posttraumatic amnesia and impaired consciousness, possibly reflecting measurement issues in older persons who are likely to be injured in low velocity falls and to suffer delayed complications. A classification system that considers not only the GCS score but also the presence of intracranial pathology is sensitive to differences in the outcome of older adults, similar to the findings in young patients. The implications of these findings for older TBI patients and directions for research are discussed.     

Assessment of short- and long-term outcomes of patients hospitalized with intracerebral hemorrhage

The aim of this study was to assess short- and long-term outcomes of patients hospitalized with intracerebral hemorrhage (ICH) in South Carolina. Patients with a primary diagnosis of ICH (ICD-9-CM code 431) discharged during 2002 were identified in the South Carolina hospital discharge database. Kaplan-Meier estimates of recurrent stroke, myocardial infarct, vascular death, all-cause death, and composite events were calculated at 1 month, 6 months, and 1, 2, 3, and 4 years. Age- and race-specific survival curves were plotted. A total of 893 patients were discharged during 2002. Most were Caucasian (CA) (61.4%), followed by African American (AA) (37.4%). The mean age of patients in the AA group was 12 years younger than that of the CA group; of those in the AA group, 63.8% were < 65 years of age, and of those in the CA group, 27.4% were > 65 years of age. Kaplan-Meier estimates of cumulative risk increased with time over the 4-year period after discharge, and the risk of all-cause death was high (~40%-60%). Survival curves showed that the composite risk of recurrent stroke, myocardial infarct, or vascular death was higher for AA patients < 65 years of age compared to similarly aged CA patients, whereas the risk was higher for CA patients ≥65 years of age compared to similar age AA patients. The racial disparity in short- and long-term outcomes for ICH patients < 65 years of age in South Carolina highlights the need for improvements in stroke prevention, particularly among the AA population.     

Neuropharmacological insight into preventive intervention in posttraumatic epilepsy based on regulating glutamate homeostasis

Background

Posttraumatic epilepsy (PTE) is one of the most critical complications of traumatic brain injury (TBI), significantly increasing TBI patients' neuropsychiatric symptoms and mortality. The abnormal accumulation of glutamate caused by TBI and its secondary excitotoxicity are essential reasons for neural network reorganization and functional neural plasticity changes, contributing to the occurrence and development of PTE. Restoring glutamate balance in the early stage of TBI is expected to play a neuroprotective role and reduce the risk of PTE.

Aims

To provide a neuropharmacological insight for drug development to prevent PTE based on regulating glutamate homeostasis.

Methods

We discussed how TBI affects glutamate homeostasis and its relationship with PTE. Furthermore, we also summarized the research progress of molecular pathways for regulating glutamate homeostasis after TBI and pharmacological studies aim to prevent PTE by restoring glutamate balance.

Results

TBI can lead to the accumulation of glutamate in the brain, which increases the risk of PTE. Targeting the molecular pathways affecting glutamate homeostasis helps restore normal glutamate levels and is neuroprotective.

Discussion

Taking glutamate homeostasis regulation as a means for new drug development can avoid the side effects caused by direct inhibition of glutamate receptors, expecting to alleviate the diseases related to abnormal glutamate levels in the brain, such as PTE, Parkinson's disease, depression, and cognitive impairment.

Conclusion

It is a promising strategy to regulate glutamate homeostasis through pharmacological methods after TBI, thereby decreasing nerve injury and preventing PTE.     

Dysautonomia after severe traumatic brain injury

Background: Dysautonomia after traumatic brain injury (TBI) is characterized by episodes of increased heart rate, respiratory rate, temperature, blood pressure, muscle tone, decorticate or decerebrate posturing, and profuse sweating. This study addresses the incidence of dysautonomia after severe TBI, the clinical variables that are associated with dysautonomia, and the functional outcome of patients with dysautonomia. Methods: A historic cohort study in patients with severe TBI [Glasgow Coma Scale (GCS) ≤ 8 on admission]. Results: Seventy‐six of 119 patients survived and were eligible for follow‐up. The incidence of dysautonomia was 11.8%. Episodes of dysautonomia were prevalent during a mean period of 20.1 days (range 3–68) and were often initiated by discomfort. Patients with dysautonomia showed significant longer periods of coma (24.78 vs. 7.99 days) and mechanical ventilation (22.67 vs. 7.21 days). Dysautonomia was associated with diffuse axonal injury (DAI) [relative risk (RR) 20.83, CI 4.92–83.33] and the development of spasticity (RR 16.94, CI 3.96–71.42). Patients with dysautonomia experienced more secondary complications. They tended to have poorer outcome. Conclusions: Dysautonomia occurs in approximately 10% of patients surviving severe TBI and is associated with DAI and the development of spasticity at follow‐up. The initiation of dysautonomia by discomfort supports the Excitatory: Inhibitory Ratio model as pathophysiological mechanism.     

Traumatic brain injury: Risks of epilepsy and implications for medicolegal assessment

Traumatic brain injury (TBI) is a potentially preventable cause of epilepsy. Increasing incidence among army personnel and the high incidence among children and young people raise concern. This article presents a review of selected studies dealing with the risks of TBI and the risk of posttraumatic epilepsy in humans. The incidence of persons admitted to hospital with TBI has decreased in developed countries in recent years. However, there is little change in TBI-associated deaths, and the decrease in hospitalization may merely reflect that more people with head injury are cared for on an outpatient basis. It is clear that epilepsy is a frequent consequence of brain injury, even many years after the injury. However, several well-controlled studies have been unable to identify therapies that prevent the development of epilepsy after TBI. Posttraumatic epilepsy has significant implications for the affected individuals, family, and society. Despite several interventions used to prevent posttraumatic epilepsy, the only proven "intervention" to date is to prevent TBI from occurring.     

A potential model of pediatric posttraumatic epilepsy

Preclinical models of pediatric posttraumatic epilepsy (PTE) are lacking. We hypothesized that traumatic brain injury (TBI), induced by controlled cortical impact, in immature rats would cause electroencephalographic (EEG) epileptiform activity and behavioral seizures. TBI or sham craniotomy was performed on postnatal day 17. Using video-EEG monitoring 4–11 months post-TBI, most TBI rats (87.5%) showed EEG spiking and one had spontaneous, recurrent seizures. Controls showed neither EEG spikes nor electrographic/behavioral seizures. Late seizures were rare after TBI, but EEG spiking was common and may represent a surrogate for PTE.