Pharmacometrics models with hidden Markovian dynamics
AbstractThe aim of this paper is to provide an overview of pharmacometric models that involve some latent process with Markovian dynamics. Such models include hidden Markov models which may be useful for describing the dynamics of a disease state that jumps from one state to another at discrete times. On the contrary, diffusion models are continuous-time and continuous-state Markov models that are relevant for modelling non observed phenomena that fluctuate continuously and randomly over time. We show that an extension of these models to mixed effects models is straightforward in a population context. We then show how the forward –backward algorithm used for inference in hidden Markov models and the extended Kalman filter used for inference in diffusion models can be combined with standard inference algorithms in mixed effects models for estimating the parameters of the model. The use of these models is illustrated with tw o applications: a hidden Markov model for describing the epileptic activity of a large number of patients and a stochastic differential equation based model for describing the pharmacokinetics of theophyllin.
We present the case of a girl who underwent VPH for hemimegalencephaly in early infancy. Postoperatively, she developed unexpected seizures of mesio-temporal origin. Stereo-EEG provided arguments for an amygdalar origin. High-resolution MRI with tractography confirmed the presence of the amygdalo-fugal pathway to be responsible of epileptic discharges propagation. She became seizure-free after temporal resection.
We describe a patient with a long history of seizures and a remote status epilepticus event. On magnetic resonance imaging, a presumed left temporal lobe tumor was observed. On neurosurgical consultation, the lesion was identified as a chronic mesial temporal lobe herniation. The patient lacked history that would suggest risk of cerebral herniation. Accurately identifying the patient ’s chronic temporal lobe herniation radiographically likely saved this patient from unnecessary surgery or biopsy and allowed the patient to receive appropriate conservative care.
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ConclusionsThe multidimensional evaluation revealed that higher levels of anxiety and depression are associated with worse quality of life in real clinical practice in patients with epilepsy, especially in females and drug-resistant epilepsy. In addition, sleep disturbances are associated with particular aspects of the quality of life. Further studies with longitudinal follow-up would be useful to adequately manage these comorbidities in patients with epilepsy.
AbstractAlthough depressive symptoms are the most common psychiatric comorbidity in epilepsy, they remain underestimated and untreated in a large proportion of patients. The purpose of this study was to evaluate depression severity and related clinical features in people with epilepsy using a well-reliable self-report index of mood, the Beck Depression Inventory-II (BDI-II). One-hundred seventeen adult patients with epilepsy were recruited from a tertiary epilepsy center and completed the BDI-II. A single-item analysis of the 21 questions of the BDI-II was computed and differences between women and men in each depressive s...
ConclusionThe SINO SEEG electrode implantation assisted by surgical robot-assistant system manufactured in China is safe, accurate and mature.
In conclusion, automated subﬁeld volumetry for patients with hippocampal sclerosis moderately reflects their subfield atrophy and might be useful to predict the postsurgical change of memory function in these patients.PMID:34521044 | DOI:10.1016/j.eplepsyres.2021.106759
Expert Rev Neurother. 2021 Sep 14. doi: 10.1080/14737175.2021.1981288. Online ahead of print.ABSTRACTINTRODUCTION: Mosaic variants arising in brain tissue are increasingly being recognized as a hidden cause of focal epilepsy. This knowledge gain has been driven by new, highly sensitive genetic technologies and genome-wide analysis of brain tissue from surgical resection or autopsy in a small proportion of patients with focal epilepsy. Recently reported novel strategies to detect mosaic variants limited to brain have exploited trace brain DNA obtained from cerebrospinal fluid liquid biopsies or stereo-electroencephalography...
Curr Neuropharmacol. 2021 Sep 13. doi: 10.2174/1570159X19666210913120637. Online ahead of print.ABSTRACTEpilepsy is a devastating neurological disorder. Current anti-convulsant drugs are only effective in about 70% of patients, while the rest remain drug-resistant. Thus, alternative methods have been explored to control seizures in these drug-resistant patients. One such method may be through the utilization of fruit phytochemicals. These phytochemicals have been reported to have beneficial properties such as anti-convulsant, anti-oxidant and anti-inflammatory activities. However, some fruits may also elicit harmful effect...
ConclusionThe diagnosis of SPS can get delayed in a patient with history of epilepsy. Although SPS and epilepsy are often linked by anti-GAD antibodies as common etiology, it is possible that epilepsy surgery might be a trigger for development of SPS in a small subset. Development of autoimmunity to neuronal GAD65 protein, exposed during surgery, is suspected in pathogenesis.