Evaluation of the epidemiologic, clinical, radiologic, and treatment methods of patients with subacute and chronic meningitis.

BACKGROUND: Meningitis is known as a meningeal inflammation accompanied by pleocytosis in the cerebrospinal fluid (CSF), and can be classified into acute, subacute, and chronic meningitis based on symptoms duration of ≤ 5 days, ≥ 5 days and ≥ 4 weeks, respectively. Subacute and chronic meningitis are caused mainly by indolent infectious agents and noninfectious causes such as autoimmune, and neoplastic. In this study, we investigated the characteristics, diagnosis, and treatment of subacute and chronic meningitis. METHODS: We extracted the medical records of patients with chronic and subacute meningitis who were referred to three tertiary centers from Jun 2011 to Jun 2021. Initially, 2050 cases of meningitis were screened, and then 79 patients were included in the study. RESULTS: Headache (87.3%), nausea and vomiting (74.7%), fever (56.4%), and visual impairments (55.7%) were the most prevalent symptoms. The most common signs were nuchal rigidity (45.3%), altered mental status (26.9%), and papillary edema (37.5%). Brain computed tomography (CT) was normal in 68.6% of the patients while 22.9% of the cases had hydrocephalus. Brain magnetic resonance imaging (MRI) was normal in 60.0% of the patients. The most common abnormal MRI findings were leptomeningeal enhancement (16.0%) and hydrocephalus (16.0%). We had a 44.3% definite diagnosis with bacterial (n:25, 31.6%) and neoplastic (n:8, 10.1%) being the most prevalent etiologies. Mycobacterium tuberculosis (60%) and Brucella spp. (12%) were the most prevalent bacterial pathogens. CONCLUSIONS: The most common etiologies include infectious, neoplastic, and immunologic. Due to insidious presentation and uncommon etiologies, establishing a proper diagnosis, and providing timely targeted treatment for patients with subacute and chronic meningitis remains a challenge for clinicians.

Developing a novel prediction model in opioid overdose using machine learning; a pilot analytical study.

Background and Aims: The opioid epidemic has extended to many countries. Data regarding the accuracy of conventional prediction models including the Simplified Acute Physiologic Score (SAPS) II and acute physiology and chronic health evaluation (APACHE) II are scarce in opioid overdose cases. We evaluate the efficacy of adding quantitative electroencephalogram (qEEG) data to clinical and paraclinical data in the prediction of opioid overdose mortality using machine learning. Methods: In a prospective study, we collected clinical/paraclinical, and qEEG data of 32 opioid-poisoned patients. After preprocessing and Fast Fourier Transform analysis, absolute power was computed. Also, SAPS II was calculated. Eventually, data analysis was performed using SAPS II as a benchmark at three levels to predict the patient's course in comparison with SAPS II. First, the qEEG data set was used alone, secondly, the combination of the clinical/paraclinical, SAPS II, qEEG datasets, and the SAPS II-based model was included in the pool of classifier models. Results: Seven out of 32 (22%) died. SAPS II (cut-off of 50.5) had a sensitivity/specificity/positive/negative predictive values of 85.7%, 84.0%, 60.0%, and 95.5% in predicting mortality, respectively. Adding majority voting on random forest with qEEG and clinical data, improved the model sensitivity, specificity, and positive and negative predictive values to 71.4%, 96%, 83.3%, and 92.3% (not significant). The model fusion level has 40% less prediction error. Conclusion: Considering the higher specificity and negative predictive value in our proposed model, it could predict survival much better than mortality. The model would constitute an indicator for better care of opioid poisoned patients in low resources settings, where intensive care unit beds are limited.

Toxoplasmosis accelerates acquisition of epilepsy in rats undergoing chemical kindling.

Epilepsy is one of the most common neurologic disorders worldwide with no distinguishable cause in 60% of patients. One-third of the world population has been infected with Toxoplasma gondii. This intracellular parasite has high tropism for excitable cells including neurons. We assessed impact of acute and chronic T. gondii infection on epileptogenesis in pentylenetetrazole (PTZ) kindling model in male rats. T. gondii cysts were administered to rats by intraperitoneal (i.p.) injection. The presence of T. gondii cysts in the brain of rats was verified by hematoxylin-eosin staining. One and eight weeks after cysts injection, as acute and chronic phases of infection, PTZ (30mg/kg, i.p.) was injected to the rats every other day until manifestation of generalized seizures. Histologic findings confirmed cerebral toxoplasmosis in rats. The rats with acute or chronic Toxoplasma infection became kindled by lower number of PTZ injections (14.8±1 and 13.6±1 injections, respectively) compared to corresponding uninfected rats (18.7±1 and 16.9±1 injections, p<0.05). Toxoplasma infection increased the rate of kindling in rats. The chronically-infected rats achieved focal and also generalized seizures earlier than the rats with acute infection. Toxoplasmosis might be considered as a risk factor for acquisition of epilepsy.

Seroepidemiological study of Toxoplasma gondii infection in a population of Iranian epileptic patients.

Epilepsy is one of the most common neurologic disorders. Underlying cause of epilepsy is unknown in 60 % of the patients. Toxoplasma gondii is an intracellular parasite which is capable of forming tissue cysts in brain of chronically infected hosts including humans. Some epidemiological studies suggested an association between toxoplasmosis and acquisition of epilepsy. In this study we determined seroprevalence of latent Toxoplasma infection in a population of Iranian epileptic patients. Participants were classified in three groups as Iranian epileptic patients (IEP, n = 414), non-epileptic patients who had other neurologic disorders (NEP, n = 150), and healthy people without any neurologic disorders (HP, n = 63). The presence of anti-Toxoplasma IgG antibodies and IgG titer in the sera were determined by ELISA method. Anti-T. gondii IgG seroprevalence obtained 35.3 %, 34.7 % and 38.1 % in IEP, NEP and HP, respectively. The seroprevalence rate was not significantly different among the three groups (P = 0.88). Anti-T. gondii IgG titer was 55.7 ± 78, 52.4 ± 74 and 69.7 ± 92 IU/ml in IEP, NEP and HP, respectively. There was not any statistically significant difference in the antibody titer between the study groups (P = 0.32). The rate of T. gondii infection in epileptic patients was not higher than non-epileptic patients and healthy people in the Iranian population.

Contribution of dopamine neurotransmission in proconvulsant effect of Toxoplasma gondii infection in male mice.

Epilepsy is one of the most common neurologic disorders worldwide with no distinguishable cause in 60% of patients. One-third of world's population is infected with Toxoplasma gondii (T. gondii). This intracellular parasite has high tendency to excitable cells including neurons. We assessed seizure susceptibility and involvement of dopaminergic system in male mice with acute and chronic T. gondii infection. Mice were infected by intraperitoneal injection of T. gondii cysts. Acute and chronic stages of infection were determined by quantification of SAG1/BAG1 transcripts and level of repetitive REP-529 sequence in the brain of mice by real-time PCR. Threshold of clonic seizures was measured by tail vein infusion of pentylenetetrazole. The infected mice were pretreated with D1 and D2 dopamine receptor antagonists, and seizure threshold was measured. Moreover, seizure threshold was determined after treatment of toxoplasmosis by sulfamethoxazole and trimethoprim. SAG1 level reached the maximum at week 2 after infection and then declined. The maximum level of BAG1 was observed at the week 3 and preserved till the week 8. REP-529 was detected at first week after infection, reached maximum at the week 3 and kept at this level till the eighth week. Threshold of seizures significantly decreased in both acute and chronic phases of infection. D1 and D2 receptors antagonists inhibited proconvulsant effect of toxoplasmosis. Chemotherapy inhibited parasite growth and multiplication, and returned seizure susceptibility to the level of non-infected mice. Dopaminergic neurotransmission participates in proconvulsant effect of T. gondii. The effect of parasite is eliminated by antibiotic therapy. © 2017 Wiley Periodicals, Inc.

The Efficacy of Gabapentin in Patients with Central Post-stroke Pain.

Thalamic pain syndrome, a type of central post-stroke pain (CPSP), may develops after a hemorrhagic or ischemic stroke and results in impairment of the thalamus. There is limited experience about gabapentin in treatment of central pains like CPSP. In a prospective observational study, the intensity of pain was recorded using the Numeric Rating Scale (NRS) at the entrance to the study. Patients eligible for treating with gabapentin, received gabapentin 300 mg twice-daily. The pain intensity was measured at entrance to the study and after one month using NRS. Decrease of 3 points from the initial NRS considered being clinically significant. From a total of 180 primarily screened patients, 84 (44 men and 40 women) were recruited. There was a significant difference between pre-treatment and post-treatment NRS (5.9 ± 2.51 vs. 4.7 ± 3.01; 95% CI: 0.442-1.962, p = 0.002). Fisher's exact test showed no statistically significant effect of clinical and demographic characteristics of patients on their therapeutic response to gabapentin. Given the safety, efficacy, well tolerability and lack of interaction with other drugs we suggest gabapentin to be more considered as a first line therapy or as add-on therapy for reducing the pain severity in patients with thalamic syndrome.

Correlation between distribution of muscle weakness, electrophysiological findings and CTG expansion in myotonic dystrophy.

Myotonic dystrophy type 1 (DM-1) is a multi-system disorder affecting the muscles, brain, cardiovascular system, endocrine system, eyes and skin. Diagnosis is made by clinical, electrodiagnostic and genetic studies. This study aimed to determine the correlation between CTG expansion and distribution of muscle weakness and clinical and electrophysiological findings. Genetically confirmed DM-1 patients presenting to Shariati Hospital between 2005 and 2011 were included in this study. Clinical, electrodiagnostic and genetic testing was performed and the correlation between CTG expansion and distribution of muscle weakness and clinical and electromyographic findings was studied. Thirty-three genetically confirmed DM-1 patients were enrolled. Myotonia, bifacial weakness and distal upper limb weakness were seen in all patients. Diabetes mellitus was found in one patient (3%), cardiac disturbance in eight (24.2%), cataracts in eight (24.2%), hypogonadism in five (15.2%), frontal baldness in 13 (39.4%), temporalis wasting in 14 (42.4%), temporomandibular joint disorder in seven (21.2%) and mental retardation in eight (24.2%). The mean number of CTG repeats, measured by Southern blot, was 8780 (range 500-15,833). A negative correlation was found between CTG expansion and age of onset. Temporalis wasting and mental retardation were positively correlated with CTG expansion. No relationship was found between weakness distribution, electromyographic findings, other systemic features and CTG expansion. In this study of DM-1 in Iran, we found a correlation between CTG expansion and age of onset, temporalis wasting and mental disability. No correlation between CTG expansion and electrodiagnostic and other clinical findings were detected.

Association analysis of intractable epilepsy with C3435T and G2677T/A ABCB1 gene polymorphisms in Iranian patients.

OBJECTIVE: The results from studies investigating a possible association between ABCB1 polymorphism and drug-resistant epilepsy are so far inconsistent. Moreover, recent meta-analyses studies do not confirm any link between ABCB1 C3435T polymorphism and drug resistance. Yet, if patients with comparable clinical status (same type of epilepsy, antiepileptic drugs, epilepsy onset and gender) are evaluated, the link between ABCB1 polymorphisms and drug resistance may be unmasked. We studied the association between C3435T and G2677T/A ABCB1 gene polymorphisms and drug resistance in Iranian epilepsy patients. METHODS: Two hundred healthy subjects and 332 epilepsy patients (200 drug-responsive and 132 drug-resistant) were selected. Genotypes were determined by polymerase chain reaction followed by restriction fragment length polymorphism or the amplification refractory mutation system. RESULTS: The risk of drug resistance was higher in patients with a C/T genotype than in those with C/C or T/T genotypes at position 3435 in patients with cryptogenic epilepsy (p=0.01). A higher risk of drug resistance was observed in adult patients with a C/C genotype than in those with a T/T genotype at position 3435 (25.8% vs 15.8%, p=0.01). The risk of drug resistance was also higher in female patients with a C/C genotype than in those with a T/T genotype at position 3435 (26.8% vs 16.3%, p=0.04). No significant association was found between G2677T/A polymorphism and epilepsy drug resistance in the different subgroups of patients. CONCLUSION: Iranian adult female patients with a C/C genotype at position 3435 of the ABCB1 gene have a higher risk of resistance to antiepileptic drugs. Replication studies with large sample sizes are needed to confirm the results.

Association between ABCB1-T1236C polymorphism and drug-resistant epilepsy in Iranian female patients.

BACKGROUND: One third of epileptic patients are resistant to several anti-epileptic drugs (AED). P-glycoprotein (P-gp) is an efflux transporter encoded by ATP-binding cassette subfamily B member 1 (ABCB1) gene that excludes drugs from the cells and plays a significant role in AEDs resistance. Over-expression of P-gp could be a result of polymorphisms in ABCB1 gene. We studied the association of T129C and T1236C single-nucleotide polymorphisms (SNP) of ABCB1 gene with drug-resistant epilepsy in Iranian epileptics. METHODS: DNA samples were obtained from 200 healthy controls and 332 epileptic patients, of whom 200 were drug responsive and 132 drug resistant. The frequencies of the genotypes of the two SNP were determined by polymerase chain reaction followed by restriction fragment length polymorphism. RESULTS: No significant association was found between T129C and T1236C genotypes and drug-resistant epilepsy neither in adults nor in children. However, the risk of drug resistance was higher in female patients with 1236CC (P = 0.02) or CT (P = 0.008) genotype than in those with TT genotype. The risk of drug resistance was also higher in patients with symptomatic epilepsies with 1236CC (P = 0.02) or CT (P = 0.004) genotype than in those with TT genotype. The risk of drug resistance was lower in patients with idiopathic epilepsies with 129TT genotype (P = 0.001) than in those with CT genotype. CONCLUSION: Our results indicate that T1236C polymorphism is associated with drug resistance in Iranian female epileptic patients. Replication studies with large sample sizes are needed to confirm our results.

Complex I deficiency in Persian multiple sclerosis patients.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by the morphological hallmarks of inflammation, demyelination and axonal loss. Until now, little attention has been paid to the contribution of mitochondrial respiratory chain enzyme activities to MS. In this study, kinetic analysis of mitochondrial respiratory chain complex I enzyme (measured as NADH-ferricyanide reductase) was performed on intact mitochondria isolated from fresh skeletal muscle in MS patients (n = 10) and control subjects (n = 11). Mitochondrial DNA common deletion and deletions were also tested in MS patients. Our findings showed that complex I activities were significantly reduced (P = 0.007) in patients compared with control. However, we could not find deletion in mtDNA of patients with MS. The presupposition of relationship between MS and mitochondrial disorders is due to predominant maternal transmission of MS in affected parent-child pairs, pathoaetiological role of respiratory chain dysfunction in multisystem disorders and important role of it in neurodegenerative disorders, a number of patients such as LHON or other mtDNA abnormality with developed neurological symptoms indistinguishable from MS and similarity of clinical symptoms in mitochondrial disorders to those of MS. This study suggested that a biochemical defect in complex I activity may be involved in pathogenesis of MS.