Temporal lobe epilepsy (TLE) is a chronic neurological condition characterized by recurrent seizures (epilepsy) which originate in the temporal lobe of the brain. The seizures involve sensory changes, for example smelling an unusual odour that is not there, and disturbance of memory.
The most common cause is mesial temporal sclerosis.
Water homeostasis has been shown crucial for regulation of neuronal excitability. The control of water movement is achieved through a family of small integral membrane channel proteins called aquaporins (AQPs). Despite the fact that changes in water homeostasis occur in sclerotic hippocampi of people with temporal lobe epilepsy (TLE) , the expression of AQPs in the epileptic brain is not fully characterised 1).
Soluble human epoxide hydrolase 2 is increased in both lateral and medial temporal tissues in temporal lobe epilepsy. Further studies should be conducted as inhibition of this enzyme has resulted in a significant decrease in or stopping of seizures and attenuated neuro-inflammation in experimental epilepsy models in the current literature 2).
In order to understand the pathophysiology of temporal lobe epilepsy (TLE), and thus to develop new pharmacological treatments, in vivo animal models that present features similar to those seen in TLE patients have been developed during the last four decades. Some of these models are based on the systemic administration of chemoconvulsants to induce an initial precipitating injury (status epilepticus) that is followed by the appearance of recurrent seizures originating from limbic structures.
Kainic acid and pilocarpine models, have been widely employed in basic epilepsy research. Their behavioral, electroencephalographic and neuropathologic features and response of these models to antiepileptic drugs and the impact they might have in developing new treatments are explained in the work of Lévesque et al. 3).
The transition to the ictal stage is accompanied by increasing global synchronization and a more ordered spectral content of the signals, indicated by lower spectral entropy. The interictal connectivity imbalance (lower ipsilateral connectivity) is sustained during the seizure, irrespective of any appreciable imbalance in the spectral entropy of the mesial recordings 4).
Fractional anisotropy asymmetry (FAA) values can be potentially used to identify the seizures of origin of TLE and to help understand the relationship between fiber tracts with the side of seizure origin of TLE 5).
The area of predominant perifocal 18F positron emission tomography hypometabolism and reduced [11C]flumazenil (11C-FMZ) -binding on PETscans is currently considered to contain the epileptogenic zone and corresponds anatomically to the area localizing epileptogenicity in patients with temporal lobe epilepsy (TLE).
Drug resistant epilepsy is a major clinical challenge affecting about 30% of temporal lobe epilepsy (TLE) patients.
The reasons for failure of surgical treatment for mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) remain unclear.
Surgical resection is the gold standard treatment for drug-resistant focal epilepsy, including mesial temporal lobe epilepsy (MTLE) and other focal cortical lesions with correlated electrophysiological features.
Surgical approaches for medically refractory mesial temporal lobe epilepsy (MTLE) that previously have been reported include anterior temporal lobectomy (ATL), transcortical selective amygdalohippocampectomy, transsylvian amygdalohippocampectomy, and subtemporal amygdalohippocampectomy.
Each approach has its advantages and potential pitfalls.
Anterior temporal lobectomy
The extent of pre-surgical perifocal PET abnormalities, the extent of their resection, and the extent of non-resected abnormalities were not useful predictors of individual freedom from seizures in patients with TLE 6).
Seizure, cognitive, and psychiatric outcomes were reviewed after 389 surgeries performed between 1990 and 2015 on patients aged 15-67 years at a tertiary center. Three surgical approaches were used: anterior temporal lobectomy (ATL; n = 209), transcortical selective amygdalohippocampectomy (SAH; n = 144), and transsylvian SAH (n = 36).
With an average follow-up of 8.7 years (range = 1.0-25.2), seizure outcome was classified as Engel I in 83.7% and Engel Ia in 57.1% of patients. The histological classification of HS was type 1 for 75.3% of patients, type 2 for 18.7%, and type 3 for 1.2%. Two factors were significantly associated with seizure recurrence: past history of status epilepticus and preoperative intracranial electroencephalographic recording. In contrast, neither HS type, the presence of a dual pathology, nor surgical approach was associated with seizure outcome. Risk of cognitive impairment was 3.12 (95% confidence interval = 1.27-7.70), greater in patients after ATL than in patients after transcortical SAH. A presurgical psychiatric history and postoperative cognitive impairment were associated with poor psychiatric outcome.
The SAH and ATL approaches have similar beneficial effects on seizure control, whereas transcortical SAH tends to minimize cognitive deterioration after surgery. Variation in postsurgical outcome with the class of HS should be investigated further 7).
A certain number of patients suffer significant decline in verbal memory after hippocampectomy. To prevent this disabling complication, a reliable test for predicting postoperative memory decline is greatly desired. Therefore, Tani et al., assessed the value of electrical stimulation of the parahippocampal gyrus (PHG) as a provocation test of verbal memory decline after hippocampectomy on the dominant side.
Eleven right-handed, Japanese-speaking patients with medically intractable left temporal lobe epilepsy (TLE) participated in the study. Before surgery, they underwent provocative testing via electrical stimulation of the left PHG during a verbal encoding task. Their pre- and posthippocampectomy memory function was evaluated according to the Wechsler Memory Scale-Revised (WMS-R) and/or Mini-Mental State Examination (MMSE) before and 6 months after surgery. The relationship between postsurgical memory decline and results of the provocative test was evaluated.
Left hippocampectomy was performed in 7 of the 11 patients. In 3 patients with a positive provocative recognition test, verbal memory function, as assessed by the WMS-R, decreased after hippocampectomy, whereas in 4 patients with a negative provocative recognition test, verbal memory function, as assessed by the WMS-R or MMSE, was preserved.
Results of the present study suggest that electrical stimulation of the PHG is a reliable provocative test to predict posthippocampectomy verbal memory decline 8).
Eighty patients with temporal lobe epilepsy were randomly assigned to surgery (40 patients) or treatment with antiepileptic drugs for one year (40 patients). Optimal medical therapy and primary outcomes were assessed by epileptologists who were unaware of the patients’ treatment assignments. The primary outcome was freedom from seizures that impair awareness of self and surroundings. Secondary outcomes were the frequency and severity of seizures, the quality of life, disability, and death.
At one year, the cumulative proportion of patients who were free of seizures impairing awareness was 58 percent in the surgical group and 8 percent in the medical group (P<0.001). The patients in the surgical group had fewer seizures impairing awareness and a significantly better quality of life (P<0.001 for both comparisons) than the patients in the medical group. Four patients (10 percent) had adverse effects of surgery. One patient in the medical group died.
In temporal-lobe epilepsy, surgery is superior to prolonged medical therapy. Randomized trials of surgery for epilepsy are feasible and appear to yield precise estimates of treatment effects 9).