Overcoming the effects of fluid shear stress in ovarian cancer cell lines: Doxorubicin alone or photodynamic priming to target platinum resistance.

Resistance to platinum-based chemotherapies remains a significant challenge in advanced-stage high-grade serous ovarian carcinoma, and patients with malignant ascites face the poorest outcomes. It is, therefore, important to understand the effects of ascites, including the associated fluid shear stress (FSS), on phenotypic changes and therapy response, specifically FSS-induced chemotherapy resistance and the underlying mechanisms in ovarian cancer. This study investigated the effects of FSS on response to cisplatin, a platinum-based chemotherapy, and doxorubicin, an anthracycline, both of which are commonly used to manage advanced-stage ovarian cancer. Consistent with prior research, OVCAR-3 and Caov-3 cells cultivated under FSS demonstrated significant resistance to cisplatin. Examination of the role of mitochondria revealed an increase in mitochondrial DNA copy number and intracellular ATP content in cultures grown under FSS, suggesting that changes in mitochondria number and metabolic activity may contribute to platinum resistance. Interestingly, no resistance to doxorubicin was observed under FSS, the first such observation of a lack of resistance under these conditions. Finally, this study demonstrated the potential of photodynamic priming using benzoporphyrin derivative, a clinically approved photosensitizer that localizes in part to mitochondria and endoplasmic reticula, to enhance the efficacy of cisplatin, but not doxorubicin, thereby overcoming FSS-induced platinum resistance.

Hyperkinetic and Hypokinetic Movement Disorders in SSPE: A Systematic Review of Case Reports and Case Series.

Background: Subacute Sclerosing Panencephalitis (SSPE) typically presents with periodic myoclonus; however, a spectrum of movement disorders including dystonia, chorea, tremor, and parkinsonism have also been described. This review aims to evaluate the array of movement disorders in SSPE, correlating them with neuroimaging findings, disease stages, and patient outcomes. Methods: A comprehensive review of published case reports and case series was conducted on patients with SSPE exhibiting movement disorders other than periodic myoclonus. PRISMA guidelines were followed, and the protocol was registered with PROSPERO (2023 CRD42023434650). A comprehensive search of multiple databases yielded 37 reports detailing 39 patients. Dyken's criteria were used for SSPE diagnosis, and the International Movement Disorders Society definitions were applied to categorize movement disorders. Results: The majority of patients were male, with an average age of 13.8 years. Approximately, 80% lacked a reliable vaccination history, and 39% had prior measles infections. Dystonia was the most common movement disorder (49%), followed by parkinsonism and choreoathetosis. Rapid disease progression was noted in 64% of cases, with a disease duration of ≤6 months in 72%. Neuroimaging showed T2/FLAIR MR hyperintensities, primarily periventricular, with 26% affecting the basal ganglia/thalamus. Brain biopsies revealed inflammatory and neurodegenerative changes. Over half of the patients (56%) reached an akinetic mute state or died. Conclusion: SSPE is associated with diverse movement disorders, predominantly hyperkinetic. The prevalence of dystonia suggests basal ganglia dysfunction.

Neuroimaging Abnormalities in Patients with Subacute Sclerosing Panencephalitis : Prospective Follow-up Study.

OBJECTIVE: This study aimed to assess the neuroimaging abnormalities and their progression in patients with Subacute sclerosing panencephalitis (SSPE) and identify clinical predictors of these imaging findings. METHODS: This prospective observational study evaluated clinical and neuroimaging features in patients with SSPE. Patients were categorized using Dyken's criteria, Jabbour's staging system, and the definition of fulminant SSPE. They underwent comprehensive clinical assessments, cerebrospinal fluid examination, Electroencephalogram (EEG), and Magnetic Resonance Imaging (MRI) scans. Treatment involved intrathecal interferon­α and antiepileptic medications. Functional disability was assessed using the modified Barthel index. Follow-ups were performed at 6 months, including reassessment of Modified Barthel Index (MBI) and Jabbour's staging and EEG and MRI scans. RESULTS: The mean age was 13.9 ± 6.7 years, with males comprising 81.5% (44/54) of the cohort. Fulminant SSPE was noted in 33% (18/54) of cases. Disease duration before presentation varied significantly between fulminant and non-fulminant forms (p = 0.001). Neuroimaging abnormalities were more prevalent in JS III stage patients, with diffuse cerebral atrophy being a significant finding (p = 0.011). Basal ganglia involvement correlated with movement disorders. The 6­month follow-up showed increased cerebral atrophy (p = 0.004). Increasing disease duration was an independent predictor of cerebral atrophy. An Intercomplex interval (ICI) of more than 10 minutes correlated with normal neuroimaging, 10 patients died within the study period, 8 of whom had fulminant SSPE. CONCLUSION: Parieto-occipital White matter hyperintensity (WMH) is the most prevalent and sensitive neuroimaging finding for the diagnosis of SSPE. Despite interferon treatment, cerebral atrophy progressed in both aggressive and fulminant SSPE. Increasing disease duration is an independent predictor of cerebral atrophy.

Treatment Outcome in Patients with Disseminated Cysticercosis: A Systematic Review of Case Reports and Case Series.

Disseminated cysticercosis is defined by multiple brain lesions and involvement of other body sites. Cysticidal treatment in disseminated cysticercosis is considered life-threatening. We conducted a systematic review of all published cases and case series to assess the safety and efficacy of cysticidal treatment. We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42022331895) to assess the safety and efficacy of cysticidal treatment. Using the search term "disseminated neurocysticercosis OR disseminated cysticercosis," databases like PubMed, Scopus, Embase, and Google Scholar were searched. Outcomes included death and secondary measures like clinical improvement and lesion reduction. We calculated the predictors of primary outcome (death) using the binary logistic regression analysis. We reviewed 222 published cases from 101 publications. Approximately 87% cases were reported from India. Of 222 cases, 134 (60%) received cysticidal treatment. Follow-up information was available from 180 patients, 11 of them died, and 169 showed clinical improvement. The death rate was 4% (5 out of 114) in patients treated with cysticidal drugs plus corticosteroids, in comparison with 13% (5 out of 38) in patients who were treated with corticosteroids alone. All patients using only praziquantel faced fatality. Death predictors identified were altered sensorium and lack of treatment with albendazole. We noted that the risk of death after cysticidal treatment is not as we expected, and a multicentric randomized controlled trial is needed to resolve this issue.

Clinical features, pathogenesis, pathology, neuroimaging, clinical course and outcome of measles inclusion-body encephalitis: a systematic review of published case reports and case series.

Measles inclusion-body encephalitis (MIBE) is rare, with insights largely from case studies. We systematically analyzed subacute Sclerosing Panencephalitis (SSPE) cases in immunocompromised patients, identifying distinctive clinical and neuroimaging features. These findings could facilitate MIBE diagnosis without the need for brain biopsies. Our systematic review on MIBE and HIV-related SSPE adhered to PRISMA guidelines and was registered with PROSPERO. We searched multiple databases and followed a detailed inclusion process with independent reviews and quality assessment. Data on patient demographics, clinical features, and outcomes were compiled. A review of 39 studies on 49 MIBE patients and 8 reports on HIV-positive SSPE patients was conducted. Acute lymphoblastic leukemia, HIV, organ transplants, and malignancies were common precursors to MIBE. Perinatal HIV was prevalent among SSPE cases. Seizures were the primary symptom in MIBE, often drug-resistant and progressing to status epilepticus or epilepsia partialis continua, whereas periodic myoclonus was universal in SSPE. Neuroimaging showed distinct patterns for each group, and histopathology confirmed measles virus presence in 39% of MIBE cases. MIBE patients typically progressed to coma and death. In conclusion, MIBE and SSPE in HIV-infected patients present with distinct clinical pictures but identical brain pathological abnormalities.

The spectrum of psychiatric manifestations in subacute sclerosing panencephalitis: A systematic review of published case reports and case series.

Data related to psychiatric manifestations in subacute sclerosing panencephalitis (SSPE) is currently available only in the form of isolated case reports. In this systematic review, we evaluated the spectrum of psychiatric manifestations and their impact on the course and outcome of SSPE. Data were obtained from 4 databases (PubMed, Embase, Scopus, and Google Scholar), with the most recent search conducted on March 27, 2023. The PRISMA guidelines were followed, and the PROSPERO registration number for the protocol is CRD42023408227. SSPE was diagnosed using Dyken's criteria. Extracted data were recorded in an Excel spreadsheet. To evaluate the quality of the data, the Joanna Briggs Institute Critical Appraisal tool was employed. Our search resulted in 30 published reports of 32 patients. The mean age was 17.9 years. Schizophrenia, catatonia, and poorly characterized psychotic illnesses were the 3 most common psychiatric presentations that were seen in 63% (20/32) of cases. Catatonia was seen in 4 patients. Affective disorders, mania, and depression were reported among 22% (7/32) cases. In approximately 81% (26/32) cases, the course of SSPE was acute fulminant. Treatment with antipsychotic drugs had poor or no response. Out of 17 patients, who received antipsychotic drugs, 6 patients noted severe extrapyramidal adverse effects. SSPE often masquerades as a psychiatric disorder. Unresponsive psychiatric symptoms, early extrapyramidal signs, and progressive encephalopathy indicate SSPE.

Occurrence and determinants of seizures and their impact on tuberculous meningitis: a prospective evaluation.

OBJECTIVE: To assess the incidence of seizures and the factors contributing to poor outcomes in patients with tuberculous meningitis (TBM). METHODS: In this prospective observational study, 129 patients with TBM were enrolled at the Department of Neurology, King George's Medical University, Uttar Pradesh, India, from April 2021 to April 2023. Detailed clinical history, neurological examinations, baseline laboratory tests, contrast-enhanced Magnetic resonance imaging (MRI) and electroencephalography (EEG) were obtained for all patients. Patients received anti-tuberculous therapy and, if necessary, anti-epileptic treatment. Patients were followed for 6 months, with outcomes evaluated using the Modified Rankin Scale (MRS). RESULTS: Of the 129 patients, 48 (37.2%) reported seizures. Advanced TBM stage (p = 0.040, OR = 2.50 95% CI:1.02-6.07), cortical involvement (p = .0.013, OR = 2.58 95% CI:1.20-5.51) and spike-wave discharges in the EEG (p = 0.001) were significantly associated with seizure occurrence. After multivariate analysis, only cortical involvement (p = 0.031, OR = 2.34, 95% CI:1.08-5.08) emerged as independent predictor of for seizures. Focal to bilateral seizures (p = 0.008, OR = 9.41, 95% CI: 1.76-74.04), status epilepticus (p = 0.002, OR = 8.00, 95% CI: 1.86-34.32), and rifampicin resistance (p = 0.022, OR = 9.25, 95% CI: 1.43-59.50) were significantly associated with poor outcomes at the 6-month mark. CONCLUSION: Seizures were significantly associated with advanced stage of the disease, cortical involvement on neuro-imaging and epileptiform pattern on EEG. Additionally, focal to bilateral seizures and status epilepticus adversely affected the outcome.

The spectrum of central nervous system manifestations in leprosy: a systematic review of published case reports and case series.

BACKGROUND: This systematic review aimed to investigate central nervous system (CNS) involvement in leprosy by analysing multiple cohort studies, individual cases and case series. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. PubMed, Scopus and Embase databases were searched up to 8 July 2023, using a predefined search strategy. Inclusion criteria included patients diagnosed with leprosy with evidence of CNS involvement. The quality of the included cases was evaluated using the Joanna Briggs Institute checklist. RESULTS: A total of 34 records were identified, including 18 cohort studies and 16 reports describing 27 isolated cases. Autopsies revealed macroscopic changes in the spinal cord, neurofibrillary tangles and senile plaques. Mycobacterium leprae was detected in neurons of the medulla oblongata and spinal cord using PCR and phenolic glycolipid 1 staining. Cerebrospinal fluid (CSF) analysis showed inflammatory changes, increased gamma globulins and detection of Mycobacterium leprae antigens and antibodies. In 21 patients (78%), spinal cord/brachial plexus abnormities were detected. In the majority, MRI revealed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity in the cervical cord. In patients with brainstem involvement, T2/FLAIR hyperintensity was noted in the cerebellar peduncles, facial nerve nuclei and/or other cranial nerve nuclei. Brain parenchymal involvement was noted in three patients. CONCLUSIONS: This systematic review provides evidence of CNS involvement in leprosy, based on autopsy findings, neuroimaging, CSF analysis and neurophysiological studies.

Exposure to select PFAS and PFAS mixtures alters response to platinum-based chemotherapy in endometrial cancer cell lines.

BACKGROUND: Exposure to per- and poly-fluoroalkyl substances (PFAS) has been associated with significant alterations in female reproductive health. These include changes in menstrual cyclicity, timing of menarche and menopause, and fertility outcomes, as well as increased risk of endometriosis, all of which may contribute to an increased risk of endometrial cancer. The effect of PFAS on endometrial cancer cells, specifically altered treatment response and biology, however, remains poorly studied. Like other gynecologic malignancies, a key contributor to lethality in endometrial cancer is resistance to chemotherapeutics, specifically to platinum-based agents that are used as the standard of care for patients with advanced-stage and/or recurrent disease. OBJECTIVES: To explore the effect of environmental exposures, specifically PFAS, on platinum-based chemotherapy response and mitochondrial function in endometrial cancer. METHODS: HEC-1 and Ishikawa endometrial cancer cells were exposed to sub-cytotoxic nanomolar and micromolar concentrations of PFAS/PFAS mixtures and were treated with platinum-based chemotherapy. Survival fraction was measured 48-h post-chemotherapy treatment. Mitochondrial membrane potential was evaluated in both cell lines following exposure to PFAS ± chemotherapy treatment. RESULTS: HEC-1 and Ishikawa cells displayed differing outcomes after PFAS exposure and chemotherapy treatment. Cells exposed to PFAS appeared to be less sensitive to carboplatin, with instances of increased survival fraction, indicative of platinum resistance, observed in HEC-1 cells. In Ishikawa cells treated with cisplatin, PFAS mixture exposure significantly decreased survival fraction. In both cell lines, increases in mitochondrial membrane potential were observed post-PFAS exposure ± chemotherapy treatment. DISCUSSION: Exposure of endometrial cancer cell lines to PFAS/PFAS mixtures had varying effects on response to platinum-based chemotherapies. Increased survival fraction post-PFAS + carboplatin treatment suggests platinum resistance, while decreased survival fraction post-PFAS mixture + cisplatin exposure suggests enhanced therapeutic efficacy. Regardless of chemotherapy sensitivity status, mitochondrial membrane potential findings suggest that PFAS exposure may affect endometrial cancer cell mitochondrial functioning and should be explored further.

Bilateral Vision Loss and Visual Hallucinations in Subacute Sclerosing Panencephalitis: A Case Report.

We report an interesting case of visual loss and visual hallucinations in a 37-year-old man. He presented with decreased vision in both eyes and visual hallucinations for the last one and a half months. He also had multiple focal to bilateral tonic-clonic seizures. On examination, there was no perception of light rays in both eyes. Fundus examination revealed disc oedema with peripapillary small haemorrhages in both eyes. Initially, the discs were hyperaemic, which turned pale in the subsequent examination at 1 month. Magnetic resonance imaging (MRI) of the brain revealed T2 hyperintensities in periventricular white matter and right fronto-parietal-occipital gray matter. His electroencephalogram showed intermittent slowing. His cerebrospinal fluid (CSF) examination showed five cells (all lymphocytes), protein 50 mg/dl, sugar 76 mg/dl (corresponding blood sugar 90 mg/dl). His CSF specimen was positive for anti-measles IgG antibodies. In conclusion, acute vision loss can rarely be the presenting symptom and, therefore, SSPE should also be considered in differential diagnoses of acute vision loss in measles-endemic regions.

Transient fluid flow improves photoimmunoconjugate delivery and photoimmunotherapy efficacy.

Circulating drugs in the peritoneal cavity is an effective strategy for advanced ovarian cancer treatment. Photoimmunotherapy, an emerging modality with potential for the treatment of ovarian cancer, involves near-infrared light activation of antibody-photosensitizer conjugates (photoimmunoconjugates) to generate cytotoxic reactive oxygen species. Here, a microfluidic cell culture model is used to study how fluid flow-induced shear stress affects photoimmunoconjugate delivery to ovarian cancer cells. Photoimmunoconjugates are composed of the antibody, cetuximab, conjugated to the photosensitizer, and benzoporphyrin derivative. Longitudinal tracking of photoimmunoconjugate treatment under flow conditions reveals enhancements in subcellular photosensitizer accumulation. Compared to static conditions, fluid flow-induced shear stress at 0.5 and 1 dyn/cm2 doubled the cellular delivery of photoimmunoconjugates. Fluid flow-mediated treatment with three different photosensitizer formulations (benzoporphyrin derivative, photoimmunoconjugates, and photoimmunoconjugate-coated liposomes) led to enhanced phototoxicity compared to static conditions. This study confirms the fundamental role of fluid flow-induced shear stress in the anti-cancer effects of photoimmunotherapy.

Multicenter comparison of head shape outcomes for three minimally invasive strip craniectomy techniques for sagittal craniosynostosis.

OBJECTIVE: A literature gap exists comparing whole head shape outcome following correction of sagittal craniosynostosis. The objective of this multicenter study was to provide an analysis of long-term results following three different endoscopic strip craniectomy techniques for correction of sagittal craniosynostosis: 1) spring-assisted strip craniectomy, 2) wide-strip craniectomy with biparietal and bitemporal barrel-stave wedge osteotomies plus helmet orthosis, and 3) narrow-strip craniectomy plus orthosis without barrel staves. METHODS: Pre- and postoperative 3D stereophotogrammetric images were collected from patients who underwent craniosynostosis surgery. Procedures were divided among institutions as follows: spring-assisted strip craniectomies were performed at Atrium Health Wake Forest Baptist Hospital; narrow-strip craniectomies were performed at St. Louis Children's Hospital by one craniofacial surgeon; and wide-vertex craniectomies were performed at St. Louis Children's Hospital prior to 2010, and then continued at Children's Medical Center Dallas. Pre- and postoperative 3D whole-head composite images were generated for each procedure to visually represent outcomes at final follow-up and compared with age-matched normal controls. RESULTS: Patients in the spring-assisted strip craniectomy group showed normalization of frontal bossing and skull height compared with age-matched controls, whereas patients undergoing wide-strip craniectomy showed greater correction of occipital protrusion. Patients in the narrow-strip craniectomy cohort had intermediate results between these outcomes. Nested aggregate head shapes showed good correction of head shapes from all techniques. CONCLUSIONS: This large, retrospective, multicenter study illustrated whole head shape outcomes from three different craniectomy procedures. Although each procedure showed some differences in loci of primary correction, all three surgical methods demonstrated good correction of primary scaphocephalic deformity.

Vision Loss in Subacute Sclerosing Panencephalitis: A Systematic Review of Case Reports and Case Series.

Vision loss is a presenting complaint in many patients with subacute sclerosing panencephalitis (SSPE). Data related to vision loss in SSPE is available only in the form of case reports. In this systematic review, we evaluated characteristics of vision loss, affected anatomic site, and patient course and outcome. We extracted data from four databases: PubMed, Embase, Scopus, and Google Scholar. The last search was done on October 26, 2022. We adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered with PROSPERO (CRD42022362652). Dyken's criteria were used for the diagnosis of SSPE. The data were recorded in an Excel sheet. The Joanna Briggs Institute Critical Appraisal tool was used to assess the quality of data. The mean age of patients with SSPE was 17.9 years. Males outnumbered females (60:34). In 73 patients (76%), duration of illness/onset of vision loss was less than 6 months. In 76% patients (n = 73), visual manifestations appeared before encephalopathy. Involvement of the retina (58 of 96, 60.4%), optic nerve (9 of 96, 9.3%), or cerebral cortex (29 of 96, 30.2%) was responsible for vision loss. T2/fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) parieto-occipital hyperintensities were the most frequent (71.4%) neuroimaging abnormality. Retinal biopsy revealed similar findings revealed by brain histopathology. All patients died and became akinetic mute during the follow-up period, which ranged from a few weeks to a few years. In conclusion, retinal involvement was the most common cause of vision loss. Vision loss often precedes encephalopathy. Cortical vision loss was associated invariably with T2/FLAIR MRI hyperintensities in the parieto-occipital region.

Spectrum of Serious Neurological and Psychiatric Adverse Events in Indian COVID-19 Vaccine Recipients: A Systematic Review of Case Reports and Case Series.

Indian data regarding serious neurological and psychiatric adverse events, following coronavirus disease 2019 (COVID-19) vaccination, are lacking. We, therefore, systematically evaluated cases of post-vaccinal serious neurological and psychiatric adverse reactions published from India. A systematic review of cases published from India, which were archived in PubMed, Scopus, and Google Scholar databases, was performed; pre-print databases along with ahead-of-print contents were searched in addition. Retrieved articles, as on June 27, 2022, were evaluated following PRISMA guidelines. EndNote 20 web tool was used to make a PRISMA flow chart. Individual patients' data were compiled in a tabular form. The protocol of the systematic review was registered with PROSPERO (CRD42022324183). A total of 64 records describing 136 instances of serious neurological and psychiatric adverse events were identified. More than 50% (36/64) reports were from the following four states, namely, Kerala, Uttar Pradesh, New Delhi, and West Bengal. The mean age of persons developing these complications was 44.89 ± 15.77 years. In the majority, adverse events occurred within 2 weeks of administration of the first dose of COVISHIELD vaccine. Immune-mediated central nervous system (CNS) disorders were identified in 54 instances. Guillain-Barre syndrome and other immune-mediated peripheral neuropathies were reported in 21 cases. Post-vaccinal herpes zoster was recorded in 31 vaccine recipients. Psychiatric adverse events were recorded in six patients. In Indian recipients of COVID-19 vaccine, a variety of serious neurological complications were reported. The overall risk appears minuscule. Immune-mediated central and peripheral neuronal demyelinations were the most frequently reported post-vaccinal adverse events. A large number of cases of herpes zoster have also been reported. Immune-mediated disorders responded well to immunotherapy.

Tumor Necrosis Factor-α, CD1A and CD1E Genetic Polymorphisms in Guillain-Barré Syndrome: A Study from India.

Background: Guillain-Barré Syndrome (GBS) is an acute acquired autoimmune inflammatory disorder of peripheral nerves and roots. The pathogenesis is essentially an aberrant post-infectious immune response in a genetically susceptible host milieu. Single nucleotide polymorphisms (SNP) in genes encoding the inflammatory mediators like TNF-α, CD1A and CD1E can influence their expression and level and the susceptibility and clinical course of disease in GBS. Objective: We tried to study the susceptibility of single nucleotide polymorphisms of TNF-α and CD1 genes in Guillain-Barré Syndrome in Indian population and determine the association in terms of genotype, allele and haplotype distribution along with individual subtype, severity and clinical outcome. Methodology: In this case-control study, we investigated the single nucleotide polymorphism pattern in the promoter region of TNF-α (-308 G/A), TNF-α (-863C/A), CD1A and CD1E genes using real-time polymerase chain reaction in 75 GBS patients and analysed in comparison with 75 age and sex-matched healthy controls. Results: The findings revealed that the allelic distribution of TNF-α (-308 G/A) *A allele was associated with GBS (P value 0.04, Odds Ratio 2.03, 95% Confidence Interval 1.01-4.07). There was no association found with genotype, haplotype combination and other allele distribution for GBS in the study. CD1A and CD1E SNPs did not reveal any susceptibility for GBS. The subtype analysis did not reveal any statistical significance, except for CD1A *G allele with AMAN subtype (P value 0.026). The haplotypic combinations and mutant allele of TNF-α (-308 G/A), TNF-α (-863C/A), CD1A and CD1E were significantly associated with severe GBS in the study. However, there was no association of any SNP for mortality and survival of GBS in the study. Conclusion: TNF-α (-308 G/A)*A allele might confer genetic susceptibility for GBS in Indian population. CD1 genetic polymorphism could not be considered for susceptibility to GBS. TNF-α and CD1 genetic polymorphism did not affect mortality in GBS.

Methods to Evaluate Changes in Mitochondrial Structure and Function in Cancer.

Mitochondria are regulators of key cellular processes, including energy production and redox homeostasis. Mitochondrial dysfunction is associated with various human diseases, including cancer. Importantly, both structural and functional changes can alter mitochondrial function. Morphologic and quantifiable changes in mitochondria can affect their function and contribute to disease. Structural mitochondrial changes include alterations in cristae morphology, mitochondrial DNA integrity and quantity, and dynamics, such as fission and fusion. Functional parameters related to mitochondrial biology include the production of reactive oxygen species, bioenergetic capacity, calcium retention, and membrane potential. Although these parameters can occur independently of one another, changes in mitochondrial structure and function are often interrelated. Thus, evaluating changes in both mitochondrial structure and function is crucial to understanding the molecular events involved in disease onset and progression. This review focuses on the relationship between alterations in mitochondrial structure and function and cancer, with a particular emphasis on gynecologic malignancies. Selecting methods with tractable parameters may be critical to identifying and targeting mitochondria-related therapeutic options. Methods to measure changes in mitochondrial structure and function, with the associated benefits and limitations, are summarized.

Impact of comorbid psychogenic non-epileptic seizures on migraine: An observational study.

Objectives: There is a bidirectional and complex interplay between psychiatric comorbidities and migraine. Migraine has been observed in 50-60% of patients with psychogenic non-epileptic seizures (PNES). Studies describe migraine as a medical comorbidity in PNES. However, there are limited studies on impact of PNES on migraine. We aim to see the impact of PNES on migraine. Materials and Methods: This cross-sectional and observational study was conducted at a tertiary-care center from June 2017 to May 2019. Fifty-two patients with migraine with PNES and 48 patients with migraine without PNES were included on the study. Migraine and PNES were diagnosed based on International Classification of Headache Disorders-3 (ICHD-3) and International League Against Epilepsy (ILAE) criteria, respectively. Headache intensity was assessed using visual analog scale. Comorbid depression, anxiety, and somatoform-symptom-disease were assessed using the Generalized Anxiety Disorder-7 Scale, Patient Health Questionnaire-9, and DSM-5 criteria, respectively. Results: Females were common in both groups and the difference was statistically insignificant. Headache frequency was significantly more in patients with migraine with PNES (P < 0.05). However, headache intensity was similar in both groups. Patients with headaches and PNES identified triggers less commonly except for stress. Depression and somatoform symptom disorder were significantly more common in patients with migraine with PNES. Abnormal neurocircuitry involving frontal, limbic, and thalamic regions due to comorbid PNES may cause central sensitization, resulting in frequent migraine headaches which is further augmented by coexisting depression and somatoform-symptom-disease. Conclusion: Migraine with PNES patients suffers more frequent headaches than patients with migraine without PNES. They differ in various headache triggers, with mental stress being the predominant trigger.

Case Report: An Unusual Case of Subacute Sclerosing Panencephalitis with Distinctive Clinical and Neuroimaging Features.

Subacute sclerosing panencephalitis (SSPE) is a relentlessly progressive brain disorder with invariable mortality. Subacute sclerosing panencephalitis is common in measles-endemic areas. We report an unusual SSPE patient with distinctive clinical and neuroimaging features. A 9-year-old boy came with a 5-month history of spontaneously dropping objects from both hands. Subsequently, he developed mental decline, a loss of interest in his surroundings, decreased verbal output, and inappropriate crying and laughing along with generalized periodic myoclonus. On examination, the child was akinetic mute. The child demonstrated intermittent generalized axial dystonic storm with flexion of upper limbs, an extension of lower limbs, and opisthotonos. Dystonic posturing was more dominant on the right side. Electroencephalography revealed periodic discharges. Cerebrospinal fluid antimeasles IgG antibody titer was markedly elevated. Magnetic resonance imaging revealed marked diffuse cerebral atrophy, and periventricular T2/fluid-attenuated inversion recovery hyperintensity. T2/fluid-attenuated inversion recovery images also revealed multiple cystic lesions present in the region of periventricular white matter. The patient was given a monthly injection of intrathecal interferon-α. The patient is currently continuing in the akinetic-mute stage. In conclusion, in this report, we described an unusual case of acute fulminant SSPE in which neuroimaging demonstrated unusual multiple small discrete cystic lesions in the cortical white matter. The pathological nature of these cystic lesions currently is not clear and needs to be explored.

Severe COVID-19-associated hyperinflammatory syndrome versus classic hemophagocytic lymphohistiocytosis: similarities, differences, and the way forward.

The hyperinflammatory immune response in severe COVID-19 infection shares features with secondary hemophagocytic lymphohistiocytosis (sHLH) in the form of fever, cytopenia, elevated inflammatory markers, and high mortality. There are contrasting opinions regarding utility of HLH 2004 or HScore in the diagnosis of severe COVID-19-related hyperinflammatory syndrome (COVID-HIS). This was a retrospective study of 47 patients of severe COVID-19 infection, suspected to have COVID-HIS and 22 patients of sHLH to other illnesses, to evaluate the diagnostic utility and limitations of HLH 2004 and/or HScore in context to COVID-HIS and to also evaluate the utility of Temple criteria for predicting severity and outcome in COVID-HIS. Clinical findings, hematological, and biochemical parameters along with the predictor of mortality were compared between two groups. Only 6.4% (3/47) of cases fulfilled ≥5/8 HLH 2004 criteria and only 40.52% (19/47) of patients showed HScore >169 in COVID-HIS group. 65.9% (31/47) satisfied the Temple criteria in COVID-HIS as compared with 40.9% (9/22) in the non-COVID group (p = 0.04). Serum ferritin (p = 0.02), lactate dehydrogenase (p = 0.02), direct bilirubin (p = 0.02), and C-reactive protein (p = 0.03) were associated with mortality in COVID-HIS. Both HScore and HLH-2004 criteria perform poorly for identifying COVID-HIS. Presence of bone marrow hemophagocytosis may help to identify about one-third of COVID-HIS missed by the Temple Criteria.

Obstetric outcomes in pregnant women with subacute sclerosing panencephalitis (SSPE): a systematic review of case reports and case series.

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a devastating brain disease caused by persistent infection by the measles virus. Several cases of SSPE in pregnant ladies have been described. This systematic review is focused on maternal and foetal outcomes among pregnant women with SSPE. METHODS: We searched four databases (PubMed, Embase, Scopus, and Google Scholar). We reviewed all relevant cases, published until 14 August 2022. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol was registered with PROSPERO (CRD42022348630). The search items that we used were "((Pregnancy) OR (delivery)) AND (Subacute sclerosing panencephalitis (SSPE))". Dyken's criteria were used for the diagnosis of SSPE in pregnant women. The extracted data was recorded in an Excel sheet. The Joanna Briggs Institute Critical Appraisal tool for case reports was used to assess the quality of published cases. RESULTS: We came across 19 reports describing details of 21 cases. The age of SSPE-affected women varied from 14 to 34 years (mean 23 years). In the majority (n=14), clinical manifestations were started in the antepartum period. Nine pregnant SSPE women presented with vision loss. After delivery, 13 SSPE-affected women died. On the contrary, 15 foetuses, though the majority were preterm, were alive. Five foetuses either died soon after birth or were still-born. CONCLUSION: In conclusion, SSPE in pregnancy is often missed, as it mimics eclampsia. SSPE in pregnancy usually has a devastating course. Universal early childhood measles vaccination is the only way to fight this menace.