Population Pharmacokinetics of Topiramate in Patients with Epilepsy Using Nonparametric Modeling.

BACKGROUND: Topiramate (TPM) is used for the treatment of various epileptic seizures and the prevention of migraine. This study aimed to develop a population pharmacokinetic model and identify covariates that influence TPM behavior in patients with epilepsy in Kuwait. METHODS: Data were collected retrospectively from 108 patients (2 years old and above) with epilepsy who were treated with oral TPM and 174 TPM blood samples from 3 hospitals in Kuwait from 2009 to 2016. Data were randomly divided into 2 groups for model development and validation. The population pharmacokinetic model was built using the nonparametric modeling algorithm (Pmetrics). The model was evaluated internally through the visual predictive check method and externally using a new data set. RESULTS: A 1-compartment model with first-order elimination fitted the data well. Covariates showing a significant effect on the elimination rate constant were renal function and coadministration of carbamazepine (CBZ). The mean estimated clearance was 2.11 L/h; this was 50% higher for patients coadministered with CBZ. Age and sex were essential covariates for the volume of distribution (V). The visual predictive check of the final model could predict the measured concentrations. External validation further confirmed the favorable predictive performance of the model with low bias and imprecision for predicting the concentration in a particular population. CONCLUSIONS: TPM elimination was increased with CBZ coadministration and was affected by renal function. Meanwhile, age and sex were the main predictors for V. The predictive performance of the final model proved to be valid internally and externally.

Yet Another Atypical Presentation of Anti-GQ1b Antibody Syndrome.

Variants of Guillain-Barre syndrome such as Bickerstaff encephalitis and Miller-Fisher syndrome have been reported. We report a 15-year-old boy who presented, after a prodromal illness, with 3-day progressive limb weakness, diplopia, and acute urinary retention. Clinically, he had horizontal gaze-evoked and upbeat nystagmus, bilateral extensor plantars in addition to quadriparesis and areflexia. Magnetic resonance imaging of the brain and spine was unremarkable and cerebral spinal fluid analysis showed lymphocytic pleocytosis. Nerve conduction study revealed symmetrical axonal neuropathy. Anti-GQ1b antibody was positive. A combination of IV methylprednisone followed by IVIg was instituted which led to remarkable clinical recovery. This case underpins the importance of recognizing atypical presentations of acute autonomic dysfunction and central nervous system features such as nystagmus, which may be associated with anti-GQ1b antibody syndrome. Features mimicking myelitis and brainstem encephalitis may pose diagnostic and therapeutic dilemma among the treating physicians.

Adherence to first-line disease-modifying therapy for multiple sclerosis in kuwait.

The aim of this retrospective study was to determine the rate of nonadherence to disease-modifying therapies (DMTs) among multiple sclerosis (MS) patients in Kuwait and to identify reasons for patient discontinuation of long-term therapy. Using a newly established MS registry at our institution, we collected data on MS patients' demographics, clinical characteristics, disability measures, and continuation or discontinuation of first-line DMTs. Reasons for nonadherence were divided into four categories: adverse events, inconvenience, perceived lack of efficacy, and physician-documented disease progression. Of 212 eligible patients, 40.1% were found to be nonadherent to first-line DMTs. In the nonadherent group, the female-to-male ratio was 1.75:1 and the mean age at disease onset was 26.8 years. Of this group, 69.4% of patients had a relapsing-remitting course, 18.8% had a secondary progressive course, and 11.8% had clinically isolated syndrome. Compared with the adherent group, the nonadherent group had a shorter mean disease duration (P = .014) and a greater likelihood of having Expanded Disability Status Scale (EDSS) scores of 3 or lower (67.1% vs. 48.0%; P = .007). Inconvenience was the most common reason for nonadherence (32.9%), followed by perceived lack of efficacy (25.9%), adverse events (23.5%), and physician-documented disease progression (17.7%). In summary, the rate of nonadherence to first-line DMTs in MS patients at our institution is considered high. Most nonadherent patients had a short disease duration and low EDSS scores. Inconvenience and perceived lack of efficacy were the most common reasons for nonadherence. The results demonstrate a need to improve treatment adherence among MS patients in Kuwait through providing better patient education, improving communication between patients and health-care providers, defining therapy expectations, and instituting new therapeutic techniques.

Risk factors, management and outcome of subtypes of ischemic stroke: a stroke registry from the Arabian Gulf.

BACKGROUND: Data on the determinants and outcome of ischemic stroke (IS) from the Arabian Gulf countries (AGC) are still scanty. The aim of this study was to characterize IS in six large stroke centers on the Arabian peninsula. METHODS: IS subtypes were evaluated in four AGC from January 2006 to December 2007 in a large prospective multicenter hospital-based stroke registry including demographics, baseline risk factors, outcome and management. RESULTS: A total of 780 patients with IS were included. Mean age was 58.9 years (63.7% males). Large-artery atherosclerosis (LAA) (38.1%) was the most common subtype followed by lacunar stroke (LS)(34.7%), cardioembolic stroke (CE)(13.5%) and other determined causes (7%). LAA and CE were both more commonly observed over the age of 70. LAA showed a higher male preponderance, and the highest prevalence of hypertension, diabetes, obesity and ischemic heart disease among all subtypes. Obesity was a risk factor for both LAA and CE. Anterior circulation stroke was significantly more affected in LAA (21.2%), CE (19%) and LS (15.1%) subtype of stroke than in posterior circulation strokes (4.4%, 2.9% and 2.8%, respectively) (p<0.05). Only 0.8% of patients received thrombolysis. The 90-day outcome was worst in LAA and least affected in LS. The over-all 90-day mortality was 2.1%. CONCLUSIONS: Demographically, our data are different from those in Western registries but the distribution of stroke subtypes is comparable. Compared to Asian registries the ratio LS versus LAA was much lower. For the first time these data allow to study the IS profile in this population.