Development of a Bioluminescent Imaging Mouse Model for SARS-CoV-2 Infection Based on a Pseudovirus System.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains widely pandemic around the world. Animal models that are sensitive to the virus are therefore urgently needed to evaluate potential vaccines and antiviral agents; however, SARS-CoV-2 requires biosafety level 3 containment. To overcome this, we developed an animal model using the intranasal administration of SARS-CoV-2 pseudovirus. As the pseudovirus contains the firefly luciferase reporter gene, infected tissues and the viral load could be monitored by in vivo bioluminescent imaging. We used the model to evaluate the protective efficacy of monoclonal antibodies and the tissue tropism of different variants. The model may also be a useful tool for the safe and convenient preliminary evaluation of the protective efficacy of vaccine candidates against SARS-CoV-2, as well as the treatment efficacy of anti-viral drugs.

Clinical practice guidelines for post-stroke depression in China

Post-stroke depression (PSD) is a very common complication that leads to increased physical disability, poor functional outcome, and higher mortality. Therefore, early detection and treatment are very important. Since there are currently no specific guidelines for this disorder in China, the purpose of this study was to develop PSD guidelines and provide suggestions for clinicians and related workers.

Clinical practice guidelines for post-stroke depression in China.

Post-stroke depression (PSD) is a very common complication that leads to increased physical disability, poor functional outcome, and higher mortality. Therefore, early detection and treatment are very important. Since there are currently no specific guidelines for this disorder in China, the purpose of this study was to develop PSD guidelines and provide suggestions for clinicians and related workers.

Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients: A 7-year Study in an Epilepsy Center in China.

BACKGROUND: It is important to choose an appropriate antiepileptic drug (AED) to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ) and valproate (VPA), have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy. METHODS: This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM), oxcarbazepine (OXC), lamotrigine (LTG), or levetiracetam (LEV), were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated. RESULTS: A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64-44.07). CBZ exhibited the highest 12-month remission rate (85.55%), which was significantly higher than those of TPM (69.38%, P = 0.006), LTG (70.79%, P = 0.001), LEV (72.54%, P = 0.005), and VPA (73.33%, P = 0.002). CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%), rashes (7.76%), abnormal hepatic function (6.24%), and drowsiness (6.24%). CONCLUSION: This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first seizure, 12-month remission rate, and retention rate.

Lamotrigine induced DIHS/DRESS: Manifestations, treatment, and outcome in 57 patients.

OBJECTIVE: To evaluate the clinical features, course, response to treatment, and outcome of lamotrigine induced drug-induced hypersensitivity syndrome (DIHS) or drug reaction with eosinophilia and systemic symptoms (DRESS). METHODS: A comprehensive PubMed and Scopus search (covering the period from January 1999 through April 2014) of the English and non-English literature (with English abstract) was conducted to identify published reports of severe cutaneous adverse reactions (SCARs) associated with lamotrigine therapy. RESULTS: This study population included 57 patients, of whom 38 (66.67%) were female and 19 (33.33%) were male. The latency period varied from 9 days to 120 days, with a mean of 27.58 ± 20.65 days. Multisystem involvement was present in 97.37% (37/38) patients. Systemic corticosteroids were administered to (61.29%) 19/31 patients. 35/38 (92.11%) patients recovered completely, one patient developed liver failure and needed liver transplant, one died from septic shock and one died from multiple organ failure. CONCLUSIONS: We found a greater predominance of women with LTG-DIHS/DRESS, and 68.42% patients were >18 years of age. The presenting symptoms in most of patients were fever, skin rash, liver involvement, hypereosinophilia, and lymphadenopathy. Lamotrigine is associated to a rather high risk of severe cutaneous adverse reactions and to the risk of dying from such reactions, likes many other anticonvulsants. Early recognition and withdrawal of the suspected agent may avoid irreversible damage to the organs will be life saving.

Evaluation of clinical features of elderly epilepsy in China.

Recent data indicate that the prevalence and incidence of epilepsy are high among the elderly, many of whom will have concomitant neurodegenerative, cerebrovascular, or neoplastic disease. The aim of this study is to evaluate the clinical characteristics of elderly patients with epilepsy in China. We retrospectively reviewed the clinical records of 104 outpatients over 50 years of age (average: 63.8 years). The results showed that in the total 104 outpatients, 53 men and 51 women were studied. Twenty-seven (26.0%) patients had idiopathic epilepsy syndromes, and 15 (14.4%) patients were considered cryptogenic. Sixty-two (59.6%) patients had remote symptomatic epilepsy. According to the known etiological factors, cerebrovascular disease (53.2%) is the most common underlying cause, followed by craniocerebral trauma (16.1%), primary or metastatic neoplastic disease (16.1%), and others (14.5%). The most common type of seizure in the group studied was partial seizures (51.9%), followed by generalized seizures (37.5%). Forty-three patients (41.3%) were used combination medication and 61 patients (58.7%) were used single medication. In conclusions, this study provides important data for clinical and research purposes in China. Further research is indicated to confirm the clinical findings of the elderly people with epilepsy by a larger epidemiological study.

Lamotrigine-induced severe cutaneous adverse reaction: Update data from 1999-2014.

We systematically reviewed and analyzed published patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) associated with lamotrigine therapy to identify characteristics of these reactions. We identified a total of 70 patients (42 SJS, five SJS/TEN, 23 TEN). The female to male ratio was 2.83:1 in the TEN group and 1.47:1 in the SJS group. Patients in the TEN group were younger than in the SJS group but this difference was not significant (28.35 versus 32.71 years, respectively; p=0.27). The median time to onset was 25.33 versus 18.42 days for SJS and TEN, respectively. The median dosage at onset was 36.46 versus 57.29mg, and final dosage 111.25 versus 97.92mg/day for SJS and TEN, respectively. The median final dosages did not significantly differ. Concomitant use of valproate acid was reported in 54.55% of the SJS patients and 50.00% of the TEN patients. Three fatal reactions were reported, of which two patients deteriorated rapidly and died within 12h of admission, indicating that this disease can develop rapidly before effective treatment. There was no significant difference between the SJS and TEN groups in any of the clinical factors examined which confirmed the opinion that SJS and TEN are part of a single disease spectrum.

Risk of a lamotrigine-related skin rash: current meta-analysis and postmarketing cohort analysis.

PURPOSE: We systematically reviewed studies to provide current evidence on the incidence and risk of skin rash in patients with LTG therapy. METHODS: PubMed and Scopus databases, up to 15 March 2014 were searched to identify relevant studies. Eligible studies included prospective studies, retrospective studies and postmarketing reports, which included data of skin rash in patients with LTG therapy. RESULTS: Forty-one articles met the entry criteria. A total of 4447 patients with LTG therapy from 26 prospective studies, 2977 patients from 8 retrospective studies, and 26,126 patients from 5/7 postmarketing reports were included. The overall incidence of skin rash with LTG therapy was 9.98% (444/4447) from prospective studies, 7.19% (214/2977) from retrospective studies, and 2.09% (547/26,126) from postmarketing reports. A meta-analysis of the risk of skin rash in 21 prospective studies, did not show a significant difference between patients with LTG and other drugs, including placebo, other ADEs or lithium (OR 0.99-2.41). In 6 respective studies, there was a significantly higher OR in patients with LTG compared with those with non-aromatic AEDs. However, there was no significant difference in rash risk between patients with LTG and aromatic AEDs. CONCLUSIONS: Our study showed that LTG significantly increased the risk of developing a skin rash compared to non-aromatic AEDs. Our results support the need for large prospective population-based studies and clinical trials to determine whether LTG increases the risk of developing a skin rash than compared to other drugs.

Changes and overlapping distribution in the expression of CB1/OX1-GPCRs in rat hippocampus by kainic acid-induced status epilepticus.

Status epilepticus (SE) is a life-threatening neurological disorder. It is important to discover new drugs to control SE without the development of pharmacoresistance. Focus on the cannabinoid receptor and cannabinoid-related compounds might be a good option. Cannabinoid receptor 1 (CB1) and orexin receptor 1 (OX1) both belong to the GPCR superfamily and display "cross-talk" interactions, however, there has been no study of the effect of OX1/CB1 in epilepsy. Therefore, we investigated the potential long-term effects of SE on CB1 and OX1 expression in rat hippocampus, aiming to elucidate whether they are involved in the causative mechanism of epilepsy and whether they might form a heterodimer. In this study, SE was induced with kainic acid, and results of immunohistochemistry and RT-PCR both showed that the expression of CB1 in the hippocampus increased after SE and was significantly higher compared to controls especially 1 week post-SE. However we did not find any significant difference in the expression of OX1 between the SE group and the controls at any time. Under immunofluorescence staining, we observed an overlapping distribution of CB1 and OX1 in the hippocampus. The increased expression of CB1 in the hippocampus indicates that CB1 may play an important role in the underlying mechanism of SE, but the effect of OX1 was not obvious. The overlapping distribution of CB1 and OX1 in the hippocampus indicates that they may form a heterodimer to exert their effect in epilepsy.

High prevalence of headaches in patients with epilepsy.

BACKGROUND: To examine the association between headaches and epilepsy. METHODS: Consecutive adult epileptic patients who went to the outpatient clinic of the Epilepsy Center of PLA General Hospital between February 01, 2012, and May 10, 2013, were recruited into this study. A total of 1109 patients with epilepsy completed a questionnaire regarding headaches. RESULTS: Overall, 60.1% of the patients (male: 57.2%; female: 63.8%) reported headaches within the last year. The age-weighted prevalence of interictal migraine was 11.7% (male 8.9%, female 15.3%), which is higher than that reported in a large population-based study (8.5%, male 5.4%, female 11.6%) using the same screening questions. The prevalence of postictal headaches was 34.1% (males 32.7%, females 35.2%), and the presence of preictal headaches was 4.5% (males 4.3%, females 5.2%). The prevalence of headache yesterday in the general population was 4.8% (male 3.0%, female 6.6%). Thus, the prevalence of headaches, including migraine, is higher in epileptic patients in China. CONCLUSIONS: The high prevalence of postictal headaches confirms the frequent triggering of a headache by a seizure. A much lower frequency of preictal headaches, a condition in which the real triggering effect of the headache on the seizure might be difficult to prove.

Comorbidity between headache and epilepsy in a Chinese epileptic center.

Here we investigated the characteristics and prevalence of headaches in patients with epilepsy in a Chinese epileptic center based on the International Classification of Headache Disorders, 2nd edition. We found that 60.14% (667/1109) of patients reported headaches. Headache was less prevalent in males (57.17%) than in females (63.75%). Interictal headaches were present in 34.62% of patients, and 139/1109 (12.53%) patients had interictal migraine, which was a higher percentage than reported in a large population-based study from the same area (9.3%) using the same screening question. In addition, 469 (70.31%) patients had postictal headache, migraine characteristics were present in 73.35% of these patients, and 15.35% also suffered from interictal migraine. Lastly, 8.85% patients had preictal headache. These results confirm that headache is very common in patients with epilepsy. Seizures often trigger postictal headaches with migraine features. The comorbidity of migraines and epilepsy should receive clinical attention, as it may influence antiepileptic drug choice, and the headache may require specific treatment.

Clinical factors associated with postictal headache in Chinese patients with partial epilepsy.

PURPOSE: To investigate the incidence of postictal headache (PIH) and the factors potentially related to the occurrence of PIH in a Chinese epileptic center. METHODS: Consecutive adult patients with epilepsy, referred to the outpatient clinic of the Epilepsy Center of the PLA General Hospital between February 01, 2012, and May 10, 2013, were recruited to this study. 854 patients with partial epilepsy completed a questionnaire regarding headache, 466 patients with temporal lobe epilepsy (TLE), 82 patients with occipital lobe epilepsy (OLE) and 306 patients with frontal lobe epilepsy (FLE). A semi-structured interview was performed in those who confirmed headache. RESULTS: PIH occurred in 328 (38.41%) of the subjects. By type of epilepsy, PIH was found in 164 (35.19%) of the patients with TLE, 46 (56.01%) of the patients with OLE, and 118 (38.56%) of the patients with FLE. The incidence of PIH in OLE was significantly higher than in TLE and FLE (P<0.05). It occurs more frequently after generalized tonic-clonic seizures than other seizure types. Logistic regression analysis revealed that age at onset, type of seizure and classification of epilepsy were each significantly related to the occurrence of PIH. CONCLUSION: The results of our study revealed possible relationships between PIH and the region of epileptic focus and area of spread of epileptic discharges.

Chinese specific characteristics of sporadic Creutzfeldt-Jakob disease: a retrospective analysis of 57 cases.

OBJECTIVE: Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal and transmissible neurodegenerative disorder. However, no studies have reported Chinese specific characteristics of sCJD. We aimed to identify differences in sCJD between Chinese patients and patients from other countries. METHODS: The data from 57 Chinese sCJD patients were retrospectively analyzed, including demographic data, clinical manifestations, laboratory examinations, electroencephalograms (EEGs), diffusion-weighted imaging (DWI) scans, positron emission tomography (PET) scans, and pathological results. RESULT: The disease was pathologically confirmed in 11 patients. 39 cases were diagnosed as probable sCJD, and 7 were possible. Of the total cases, 33 were male, and 24 were female. The onset age ranged from 36 to 75 years (mean: 55.5, median: 57). Disease onset before the age of 60 occurred in 57.9% of patients. The disease duration from onset to death ranged 5-22 months (mean: 11.6, median: 11), and 51.9% of patients died 7 to 12 months after disease onset. The majority of patients presented with sub-acute onset with progressive dementia. 3 of the 9 patients who took 14-3-3 protein analysis had positive results (33.3%). The sensitivity of EEG was 79.6% (43/54). For DWI and PET examinations, the sensitivities were 94% (47/50) and 94.1% (16/17), respectively. In seven patients who did not show typical hyper-intensities on the first DWI examination, abnormalities of hypo-metabolism in the cerebral cortex were clearly detected by PET. In 13 out of the 17 patients, PET detected extra abnormal regions in addition to the hyper-intense areas observed in DWI. CONCLUSION: This is the first study to indicate that Chinese sCJD patients have a much earlier onset age and a longer disease duration than other populations, which is most likely related to racial differences. The longer disease duration may also be a probable characteristic of Asian populations. PET had high sensitivity for the diagnosis of sCJD.

Rosai-Dorfman disease: a retrospective analysis of 13 cases.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare, idiopathic, histiocytic proliferative disorder, the infrequent occurrence of which limits in-depth studies. Consequently, many characteristics of this disease remain unknown, restricting early diagnosis and proper treatment. METHODS: In this study, the literature was reviewed and a retrospective analysis of the medical records of 13 patients with RDD conducted to investigate the demographic data, clinical data, laboratory and imaging results, treatment, and prognosis of this disease. RESULTS: Of the 13 cases in our sample, 10 (77%) were purely extranodal RDD, 2 (15%) were both nodal and extranodal, and 1 (8%) was purely nodal. The locations of the 10 purely extranodal RDD lesions included the central nervous system (n = 6, 60%), nasal cavity and paranasal sinuses (n = 3, 30%), and the cutis (n = 1, 10%). The locations of the central nervous system-related RDD lesions included the cerebral subdura (n = 2, 29%), the sellar region (n = 3, 14%), the cerebral parenchyma (n = 1, 14%) and the spinal subdura (n = 1, 14%). Ten patients (77%) had stable conditions, 3 (23%) experienced recurrence, and 2 (15%) experienced recurrence and lesion metastasis. CONCLUSIONS: RDD is rare, requiring knowledge of its clinical manifestations for a rapid and correct diagnosis. In light of the possibility of recurrence and lesion metastasis, long-term follow-up is needed. Treatment is still controversial. Future efforts should be directed at investigating the etiology and postoperative treatment for relapsing cases or those with subresected lesions.

Comparison of diffusion-weighted MRI with 18F-fluorodeoxyglucose-positron emission tomography/CT and electroencephalography in sporadic Creutzfeldt-Jakob disease.

18F-fluorodeoxyglucose-positron emission tomography/CT (18F-FDG PET/CT) scanning may be a useful tool for early diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), as it may reveal lowered cellular glucose transport and metabolism in the cortex, cerebellum and basal ganglia. The aim of the present study was to compare the findings from PET/CT, MRI and electroencephalography (EEG) for patients with sCJD, to explore whether typical sites or reliable patterns of regional metabolic change could be found and to evaluate the results of diagnostic imaging in the light of clinical symptomatology. Five patients with biopsy-confirmed sCJD and nine with probable sCJD (aged 36-68 years) were evaluated using PET/CT, diffusion-weighted (DW)-MRI and EEG. In 13 of the 14 patients (92.86%), PET/CT imaging detected extra regions with abnormalities in addition to the hyperintense areas shown with DW-MRI. Two patients with no abnormal DW-MRI findings in the basal ganglia had bilateral extrapyramidal signs accompanied by basal ganglia hypometabolism on PET. Eight patients (57.14%) had decreased FDG uptake in the thalamic nuclei on PET scans; however, DW-MRI did not identify corresponding hyperintense changes in the thalamic nuclei. In 11 patients (78.57%), DW-MRI revealed more regions with abnormalities than EEG, and 10 patients (71.43%) had DW-MRI abnormalities in the thalamic nuclei and basal ganglia that EEG was unable to detect. There was a high level of correspondence among the PET/CT, DW-MRI and EEG results, with PET revealing more abnormal regions than the other imaging modalities. In the absence of neuropathological findings, FDG-PET could improve the accuracy of sCJD diagnosis when combined with DW-MRI and EEG, particularly for differentiating sCJD from paraneoplastic syndromes. Our results suggest that PET/CT is able to detect sCJD at an earlier stage and with greater sensitivity than DW-MRI.

Antiepileptic drug-induced skin reactions: a retrospective study and analysis in 3793 Chinese patients with epilepsy.

OBJECTIVE: To evaluate the incidence and clinical characteristics of AED-related skin reactions, along with factors influencing these reactions, in a sample of 3793 Chinese epileptic patients. MATERIALS AND METHODS: Between February 1999 and April 2010, consecutive patients with epilepsy were studied retrospectively. A detailed survey of each patient's medical records concerning all treatment with AEDs was performed. RESULTS: A total of 3793 (2323 male) Chinese epileptic patients taking at least one AED were investigated. Overall, 137/3793 (3.61%) patients experienced a skin reaction following one out of 11 different of AEDs marketed in China. In this study, we found skin reactions from carbamazepine (CBZ) in 3.80% of exposures, from lamotrigine (LTG) in 11.11%, and from oxcarbazepine (OXC) in 8.92%. Skin reactions developed significantly more often in females than in males (4.97% vs. 2.76%), and a logistic regression analysis confirmed female gender as a factor linked to AED-related rashes (OR=1.84, p<0.001). LTG-induced rashes were more frequent in girls under age 13 than in women over the age of 13 (p<0.05). CONCLUSION: The incidence of skin reactions was somewhat higher for LTG, CBZ, and OXC, whereas valproic acid, levetiracetam, and topiramate were rarely associated with skin reactions. Caution should be exercised when prescribing certain AEDs, particularly CBZ, LTG, and OXC. Females have a higher risk for skin reactions compared to males, though further investigation is needed to discern the underlying mechanisms.

Influence of chemical structure on skin reactions induced by antiepileptic drugs--the role of the aromatic ring.

Here we assessed whether the presence of an aromatic ring as a commonality in chemical structures of AEDs can explain skin reaction. We found that 164 cases of skin reactions associated with the use of AEDs were reported. Aromatic AEDs were suspected in 88.41% (145/164) of patients with skin reactions versus 59.80% (2316/3873) of patients without skin reactions. The presence of an aromatic ring in the chemical structure was associated with a significant increased risk of skin reactions (adjusted ROR 3.50; 95% CI 2.29, 5.35). Among the aromatic AEDs, skin reactions were significantly associated with carbamazepine, lamotrigine, and oxarbazepine. These results confirm that the presence of an aromatic ring as a common feature in chemical structures of AEDs partly explains AED-skin reactions. Skin reactions were reported triple as frequently with aromatic AEDs than with non-aromatic AEDs.

Changes in extrafrontal integrity and cognition in frontal lobe epilepsy: a diffusion tensor imaging study.

We used diffusion tensor imaging to characterize microstructural changes and their associations with cognition in Chinese patients with frontal lobe epilepsy (FLE). We examined 18 adult patients with FLE and 20 healthy controls. Compared with normal controls, patients with FLE had increased mean diffusivity (MD) in the right frontal lobe and decreased fractional anisotropy (FA) in both thalami. Patients with FLE also had decreased FA in the right frontal lobe that correlated with patient age at seizure onset and increased MD in the left thalamus that correlated with duration of epilepsy. Patients with FLE performed significantly worse on nearly all cognitive tasks, and there was a positive correlation between Mini-Mental Status Examination scores and FA in the left frontal lobe and the left thalamus. Our results suggest that the thalamus might be an important extrafrontal structure involved in FLE and that a longer duration of epilepsy might result in more abnormalities in the thalamus. Our results also support the hypothesis that the left frontal lobe white matter and the thalamus contribute to cognitive impairment in patients with FLE.

[Clinical analysis of 47 misdiagnosed cases of atypical tuberculous meningitis].

OBJECTIVE: To improve the differential diagnosis of tuberculous meningitis (TBM) and reduced potential misdiagnosis of TBM. METHODS: The clinical data of 47 misdiagnosed cases of TBM between January, 1994 and June, 2009 were investigated retrospectively. The clinical presentations and causes for the misdiagnoses were analyzed. RESULTS: The 47 patients with misdiagnosed TBM included 28 male and 19 female patients with a mean age of 36.84∓16.41 years. Eight patients had an acute onset, 10 had a subacute onset, and 29 had chronic disease. The initial symptoms, in the descending order of their frequencies, included fever and headache (87.2%), anergia and dyskinesia (27.7%), cerebral nerve damage (23.4%), decreased level of consciousness (14.9%), and urinary and fecal incontinence (2%). Meningeal irritation was present in 25 cases and positive Babinksi sign was found in 19 cases. Elevated intracranial pressure occurred in 51.1% of the cases, and 16 cases showed papilloedema. Non-purulent CSF with elevated protein was found in 86.7%, decreased glucose in 50%, and decreased chlorinate in 53.3% of the cases. Eight out of 23 cases showed a positive result of PPD test. MRI identified abnormitis with meningeal enhancement in 15 cases, hydrocephalus in 7 cases and infarction in 14 cases. Tuberculoma was found in 2 cases, and spinal cord lesions were found 4 cases. All the patients received anti-tuberculosis therapy, which resulted in symptomatic improvement in 39 cases, fluctuated condition in 2 cases; 5 patients discontinued the treatment and 1 died. CONCLUSION: Early TBM often presents with atypical features and its differential diagnosis can be difficult. CSF monitoring and careful inspection of the radiographic data can be helpful in the diagnosis of suspected cases, for which early anti-TB treatment is an important means to reduce misdiagnosis.

Changes in extratemporal integrity and cognition in temporal lobe epilepsy: a diffusion tensor imaging study.

BACKGROUND: Diffusion tensor imaging (DTI) is a sensitive technique for studying cerebral white matter. Only a few studies have examined the association between changes in extratemporal integrity and cognition in temporal lobe epilepsy (TLE), especially in Chinese patients. AIM: We used DTI to characterize microstructural changes and investigate their associations with cognition in patients with temporal lobe epilepsy. PATIENTS AND METHODS: We studied 27 adult patients with TLE and 21 healthy controls. A standardized neuropsychological evaluation and diffusion tensor imaging examination were conducted on each subject. Eight patients were excluded because T2-weighted magnetic resonance imaging (MRI) results showed visible lesions. Furthermore, we determined mean diffusivity (MD) and fractional anisotropy (FA) values in the different regions of interest - normal-appearing white matter (NAWM) in the frontal lobe white matter, the occipital lobe white matter, the corpus callosum, the internal capsules, the external capsules; and normal-appearing gray matter (NAGM) in the caudate nucleus head, the putamens and the thalami. These diffusion measurements were compared between the two groups, and we examined the correlations between DTI values and clinical characteristics. In addition, multiple linear regression analysis was used to study the association of DTI values with cognitive function. RESULTS: Compared with normal controls, TLE patients demonstrated decreased FA in NAGM of both thalami and NAWM of the posterior limb of the left internal capsule (P<.01). In patients with temporal lobe epilepsy, right thalamus FA showed a tendency to correlate with age at seizure onset (ß=0.47, P=.045), and left thalamus MD showed a tendency to correlate with the duration of epilepsy (ß=0.54 P=.038). Patients with temporal lobe epilepsy showed significantly poorer performance on nearly all tasks concerning category fluency and other executive functions (P<.01). In patients with TLE, there was a positive correlation between category fluency scores and FA in the white matter of the left frontal lobe (ß=0.429, P=.041) and the right occipital lobe (ß=0.613, P=.001). CONCLUSIONS: Our results suggested that the thalamus might be a potentially important extratemporal structure involved in temporal lobe epilepsy. Moreover, a longer duration of epilepsy or an earlier age at onset may result in more abnormalities in the thalamus. Patients with temporal lobe epilepsy showed significantly poorer performance on nearly all tasks concerning category fluency and other executive functions. Our results showed that frontal lobe white matter contributed to category fluency impairment in patients with TLE, but other areas might also contribute to these impairments.