Risk Factors of Elevated Blood Ammonia Level in Epilepsy Patients Treated With Lamotrigine

Background The aim of this study was to explore the effect of lamotrigine (LTG) on blood ammonia level in patients with epilepsy and identify risk factors affecting blood ammonia level. Methods This study included 91 epilepsy patients who were treated with LTG at Department of Neurology, Zhongshan Hospital, Xiamen University from January 2011 to April 2016, and were followed up for three years. Blood samples were taken during the interictal state and analyzed for blood LTG and ammonia levels. Results Total 46.1% of the samples exceeded the median blood ammonia level, and 2.1% of patients had hyperammonemia. Blood ammonia level was positively correlated with LTG blood concentration. LTG combined with valproic acid (VPA) therapy, seizure within one year, and elevated neutrophils affected blood ammonia level. Conclusion Blood ammonia level was significantly correlated with plasma concentration of LTG. LTG combined with VPA therapy, seizure within one year, and elevated neutrophils may be risk factors for elevated blood ammonia level in epilepsy patients treated with LTG.

Pattern Recognition in Epileptic EEG Signals via Dynamic Mode Decomposition

In this paper, we propose a new method based on the dynamic mode decomposition (DMD) to find a distinctive contrast between the ictal and interictal patterns in epileptic electroencephalography (EEG) data. The features extracted from the method of DMD clearly capture the phase transition of a specific frequency among the channels corresponding to the ictal state and the channel corresponding to the interictal state, such as direct current shift (DC-shift or ictal slow shifts) and high-frequency oscillation (HFO). By performing classification tests with Electrocorticography (ECoG) recordings of one patient measured at different timings, it is shown that the captured phenomenon is the unique pattern that occurs in the ictal onset zone of the patient. We eventually explain how advantageously the DMD captures some specific characteristics to distinguish the ictal state and the interictal state. The method presented in this study allows simultaneous interpretation of changes in the channel correlation and particular information for activity related to an epileptic seizure so that it can be applied to identification and prediction of the ictal state and analysis of the mechanism on its dynamics.

Enhanced pre-ictal cortical responsivity in migraine patients assessed by visual chirp stimulation

Background Migraine is associated with altered sensory processing and cortical responsivity that may contribute to susceptibility to attacks by changing brain network excitability dynamics. To gain better insight into cortical responsivity changes in migraine we subjected patients to a short series of light inputs over a broad frequency range (“chirp” stimulation), designed to uncover dynamic features of visual cortex responsivity. Methods EEG responses to visual chirp stimulation (10–40 Hz) were measured in controls (n = 24) and patients with migraine with aura (n = 19) or migraine without aura (n = 20). Average EEG responses were assessed at (i) all EEG frequencies between 5 and 125 Hz, (ii) stimulation frequencies, and (iii) harmonic frequencies. We compared average responses in a low (10–18 Hz), medium (19–26 Hz) and high (27–40 Hz) frequency band. Results Responses to chirp stimulation were similar in controls and migraine subtypes. Eight measurements (n = 3 migraine with aura; n = 5 without aura) were assigned as “pre-ictal”, based on reported headache within 48 hours after investigation. Pre-ictally, an increased harmonic response to 22–32 Hz stimulation (beta band) was observed ( p = 0.001), compared to interictal state measurements. Conclusions We found chirp responses to be enhanced in the 48 hours prior to migraine headache onset. Visual chirp stimulation proved a simple and reliable technique with potential to detect changes in cortical responsivity associated with the onset of migraine attacks.

Ictal neck pain investigated in the interictal state – a search for the origin of pain

Background Neck pain is reported in more than 50% of migraine patients during migraine attacks and may be an important source to migraine pain. Objectives To investigate phenotypical differences between migraine patients with and without ictal neck pain in the interictal phase. Additionally, to prospectively examine the association between pericranial muscle tenderness and the impending migraine attack. Methods Migraine patients (n = 100) and controls (n = 46) underwent a semi-structured interview and sensory testing interictally. Pericranial muscle tenderness was determined using total tenderness score and local tenderness score. The occurrence of migraine attacks was then prospectively recorded for the following seven days. Results Patients with ictal neck pain had increased tenderness of pericranial neck muscles compared to migraine patients without ( p = 0.023). Ictal neck pain was not associated with migraine localization, tension-type headache, or markers of central sensitization. Prospective data of 84 patients showed that tenderness of trigeminal sensory innervated muscles increased the migraine attack rate ( p = 0.035). Conclusion The distinction of migraine patients based on the occurrence of ictal neck pain could indicate migraine subtypes and possible involvement of peripheral tissue in the pathophysiology. Whether treatment responses differ among these groups would be fascinating. Additionally, we found that cephalic muscle tenderness is a risk factor for an impending migraine attack.

Functional magnetic resonance imaging of regional impaired cerebrovascular reactivity for migraineurs in the interictal state

ABSTRACTThere is still an unmet need of mapping the potential impairment of cerebrovascular reactivity (CVR) in episodic migraineurs in the interictal state. We mapped CVR of 6 episodic migraineurs and 5 headache-free controls (HC) with blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) under carbon dioxide (CO2) challenge of 30-second epochs with elevated end-tidal partial pressure of CO2 (PETCO2) by 4-8mmHg. Three migraineurs have migraine without aura (MOA) and the other three have migraine with aura (MA). We found that only MOA subjects showed a reduced or negative BOLD response to CO2 at the red nucleus. All 3 MOA subjects were characterized by bilateral posterior communicating artery hypoplasia (bPCAH) identified by MR angiography (MRA). MOA and HC subjects did not show any significant difference in BOLD responses to CO2 challenge in cortical and white matter while MA subjects showed poor positive association between BOLD responses and PETCO2 in large territories of the cortex and white matter tracts. The combined use of fMRI under CO2 challenge and MRA presented a unique approach to investigate the mechanisms of episodic migraine in the interictal state demonstrating for the first time negative CVR at the red nucleus of the midbrain in patients with MOA. CVR maps obtained from both the midbrain and cortical regions provided various signatures to explore the differences between migraineurs and HC and between MOA and MA.

Triheptanoin alters [U-13C6]-glucose incorporation into glycolytic intermediates and increases TCA cycling by normalizing the activities of pyruvate dehydrogenase and oxoglutarate dehydrogenase in a chronic epilepsy mouse model

Triheptanoin is anticonvulsant in several seizure models. Here, we investigated changes in glucose metabolism by triheptanoin interictally in the chronic stage of the pilocarpine mouse epilepsy model. After injection of [U-13C6]-glucose (i.p.), enrichments of 13C in intermediates of glycolysis and the tricarboxylic acid (TCA) cycle were quantified in hippocampal extracts and maximal activities of enzymes in each pathway were measured. The enrichment of 13C glucose in plasma was similar across all groups. Despite this, we observed reductions in incorporation of 13C in several glycolytic intermediates compared to control mice suggesting glucose utilization may be impaired and/or glycogenolysis increased in the untreated interictal hippocampus. Triheptanoin prevented the interictal reductions of 13C incorporation in most glycolytic intermediates, suggesting it increased glucose utilization or – as an additional astrocytic fuel – it decreased glycogen breakdown. In the TCA cycle metabolites, the incorporation of 13C was reduced in the interictal state. Triheptanoin restored the correlation between 13C enrichments of pyruvate relative to most of the TCA cycle intermediates in “epileptic” mice. Triheptanoin also prevented the reductions of hippocampal pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase activities. Decreased glycogen breakdown and increased glucose utilization and metabolism via the TCA cycle in epileptogenic brain areas may contribute to triheptanoin's anticonvulsant effects.