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.

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.

Immune-dysregulation in subacute sclerosing panencephalitis: An exploratory case-control study.

Subacute sclerosing panencephalitis (SSPE) is a chronic progressive neurological condition caused by a defective measles virus. It is postulated that immune-dysregulation might result in persistent infection (immune evasion) as well as initiation of autoimmune phenomenon (via natural killer cells) leading to panencephalitis. The primary objective of this case-control study was to analyse the pattern of immune dysregulation in cases with SSPE. The secondary objective was to assess the correlation between the measured immunological variables and disability/death at 6 months. This was an exploratory case-control study conducted at a tertiary-care referral-facility from January 2020 to September 2021. Thirty consecutive patients fulfilling the Dyken's criteria for SSPE and 30 age-and-sex-matched healthy controls were enrolled. Immunological profile constituted by lymphocyte subset analysis, immunoglobulin levels and complement levels were done in all cases and controls. Cases were staged as per Jabbour's system; disability was assessed using the modified Rankin Scale (mRS). Patients with SSPE had a mean age of 14.76 years (±6.9 years). There were 25 males and 5 females; 6.7% cases belonged to Jabbour's first stage, 40% to second stage and 53.3% to third stage. At least 1/4th had evidence of measles vaccination. Levels of absolute lymphocyte count, B-cells, T cells, helper T-cells, and cytotoxic T-cells were significantly higher in cases. IgG, IgM, and IgE levels were significantly higher while IgD levels were significantly lower in cases. At baseline, 13.3% of cases had a mRS score of 0-2 and 86.7% had a score of 3-6; at 6 months 10% had a mRS score 0-2 (favorable outcome) while 90% had a mRS score 3-6 (poor outcome). Higher IgE levels were found to correlate significantly with favorable outcome. Immune-dysregulation may play a significant role in shaping one's response to measles infection as well as in determining vaccine-efficacy.

Phenomenology, quality of life, and predictors of reversibility in patients with drug-induced movement disorders: a prospective study.

BACKGROUND: Drug-induced movement disorders (DIMDs) form an important subgroup of secondary movement disorders, which despite conferring a significant iatrogenic burden, tend to be under-recognized and inappropriately managed. OBJECTIVE: We aimed to look into phenomenology, predictors of reversibility, and its impact on the quality of life of DIMD patients. METHODS: We conducted the study in the Department of Neurology at a tertiary-care centre in India. The institutional ethics-committee approved the study. We assessed 55-consecutive DIMD patients at presentation to our movement disorder clinic. Subsequently, they followed up to evaluate improvement in severity-scales (UPDRS, UDRS, BARS, AIMS) and quality of life (EuroQol-5D-5L). Wilcoxan-signed-rank test compared the scales at presentation and follow-up. Binary-logistic-regrerssion revealed the independent predictors of reversibility. RESULTS: Fourteen patients (25.45%) had acute-subacute DIMD and 41 (74.55%) had tardive DIMD. Tardive-DIMD occurred more commonly in the elderly (age 50.73±16.92 years, p<0.001). Drug-induced-Parkinsonism (DIP) was the most common MD, followed by tardivedyskinesia. Risperidone and levosulpiride were the commonest culprit drugs. Patients in both the groups showed a statistically significant response to drug-dose reduction /withdrawal based on follow-up assessment on clinical-rating-scales and quality of life scores (EQ-5D-5L). DIMD was reversible in 71.42% of acute-subacute DIMD and 24.40% of patients with chronic DIMD (p=0.001). Binary-logistic-regression analysis showed acute-subacute DIMDs and DIP as independent predictors of reversibility. CONCLUSION: DIP is the commonest and often reversible drug-induced movement disorder. Levosulpiride is notorious for causing DIMD in the elderly, requiring strict pharmacovigilance.

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.

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.

Pediatric Tissue Expansion: Analysis of the National Surgical Quality Improvement Program-Pediatric.

INTRODUCTION: Tissue expansion (TE) in pediatric surgery provides vascularized tissue to attain functional and esthetic goals in a broad range of reconstructive procedures. Our study evaluates the demographic, operative, and short-term outcomes of TE in pediatric patients utilizing the American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database and highlights factors associated with postoperative complications. MATERIALS AND METHODS: Retrospective review of a large multicenter database of 402 pediatric patients that underwent TE within the NSQIP-P database from 2013 to 2020 at freestanding general acute care children's hospitals, children's hospitals within a larger hospital, specialty children's hospitals, or general acute care hospitals with a pediatric wing. Patient demographics, clinical risk factors, operative information, and postoperative outcomes were collected with an odds ratio analysis of risk factors. RESULTS: Patients were majority female (55.5%), White (63.2%), and non-Hispanic (67.4%). The minority were born prematurely (11.9%) and had congenital malformations (16.7%). Complications occurred in 5.7%, unplanned readmission in 4.5%, and unplanned operation in 6.5% of patients. Complications lead to readmission in 2.5% and return to the operating room in 3.2% of patients. American Society of Anesthesiology (ASA) score III-IV, congenital malformations, >1-day hospital stay, and pulmonary, neurologic, and hematologic comorbidities were associated with the greatest increase in odds of complication. CONCLUSION: This study utilizes the NSQIP-P to provide a comprehensive multicenter view of pediatric patients undergoing TE. Increased understanding of risk factors for complications allows for guidance in patient selection and helps in achieving favorable surgical outcomes.

Open Versus Minimally Invasive Approach for Craniosynostosis: Analysis of the National Surgical Quality Improvement Program-Pediatric.

OBJECTIVE: This multicenter study aimed to compare demographic, operative, and short-term outcomes data between open and minimally invasive surgical approaches for craniosynostosis repair utilizing the American College of Surgeon's National Surgical Quality Improvement Program Pediatric (NSQIP-P) database and highlight surgical disparities among races and ethnicities. DESIGN: Retrospective review of large multicenter database. SETTING: Freestanding general acute care children's hospitals, children's hospitals within a larger hospital, specialty children's hospitals, or general acute care hospitals with a pediatric wing. PATIENTS AND PARTICIPANTS: A total of 4931 pediatric patients underwent craniosynostosis correction within the NSQIP-P database from 2013 to 2019. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Demographic information included age at surgery, sex, race, and ethnicity. Operative and outcomes measures included operative time, anesthesia time, days until discharge, postoperative complications, blood transfusions, 30-day readmission, and 30-day unplanned return to operating room. RESULTS: Patients who underwent minimally invasive surgery had significantly shorter operative and anesthesia times (p < .001; p < .001), fewer days until discharge (p < .001), fewer postoperative complications (p < .05), and less blood transfusions (p < .001). The proportion of White patients was significantly higher in the minimally invasive surgery group (p < .01), whereas Black and Hispanic patients had a significantly higher proportion in the open surgery group (p < .001; p < .001). Additionally, the percentage of patients undergoing minimally invasive surgery increased from 3.8% in 2014 to over 13% in 2019. CONCLUSIONS: This study adds to a growing consensus that minimally invasive surgery has significantly decreased operative time, anesthesia time, transfusion rates, length of hospital stay, and postoperative complications compared to open surgery. Racial and ethnic surgical disparities showed larger proportions of Black and Hispanic populations undergoing open procedures.

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.

Tuberculous myelitis: a prospective follow-up study.

BACKGROUND: Prospective studies regarding tuberculous myelitis are lacking. We aimed to prospectively evaluate patients with tuberculous myelitis to identify the features that distinguish tuberculous myelitis from other myelitis. METHODS: This was a prospective study. Patients presenting with paraparesis/quadriparesis, and MRI showing myelitis were included. All patients were subjected to clinical, neuroimaging, and laboratory evaluation. Diagnosis of definite tuberculous myelitis was made if GeneXpert test in CSF was positive. Probable tuberculous myelitis was diagnosed if there was evidence of tuberculosis elsewhere in the body. Patients were treated with methylprednisolone and antituberculosis treatment. Patients were followed for 6 months. We compared the clinical, laboratory, and neuroimaging parameters and response to treatment of tuberculous myelitis with other myelitis. P values were adjusted using the Benjamini-Hochberg (BH) procedure to control false discovery rate. RESULTS: We enrolled 52 patients. Eighteen (34.6%) patients had tuberculous myelitis. Headache (P = 0.018) was significantly more common in tuberculous myelitis. The CSF protein (P < 0.001), and CSF cell count (P < 0.001) were significantly higher in tuberculous myelitis. On neuroimaging, a LETM was common in tuberculous myelitis. Spinal meningeal enhancement (14; 77.8%), extra-axial collection, and CSF loculation (6; 33.4%), arachnoiditis (3;16.7%), and concomitant spinal tuberculoma (2;11.1%) were other common imaging features of tuberculous myelitis. Tuberculous myelitis patients showed a better response (P = 0.025) to treatment. CONCLUSION: Tuberculous myelitis was seen in approximately 35% of all myelitis cases, in a high tuberculosis endemic zone. Headache, markedly elevated CSF protein and spinal meningeal enhancement were distinguishing features. Tuberculous myelitis patients responded well to corticosteroids.

Correlation of serotype-specific strain in patients with dengue virus infection with neurological manifestations and its outcome.

INTRODUCTION: Neurological manifestation of dengue virus infection is a rare entity. Serotypes commonly associated with neurological manifestation are DENV-2 and DENV-3. We plan to detect the serotypes related to the neurological presentation in dengue infection and its correlation with different neurological complications and outcome. METHODS: In this case-control study, consecutive dengue cases with different neurological manifestations were enrolled along with age and sex-matched controls (dengue patients without neurological complication). Serotyping using RT-PCR of samples of cases and controls were done. Level of correlation was analyzed with various parameters and outcomes. RESULTS: In cases out of 33 samples, 6 sample serotypes were detected, which were composed of DENV-1 (n = 2) and DENV-2 (n = 4). In controls, DENV-1 (n = 5), DENV-2 (n = 6), and DENV-3 (n = 3) were detected. When statistically correlated, no significant association was found in cases and controls with dengue virus serotype. The frequency of serotype 2 was higher in hypokalemic paralysis cases than non-hypokalemic paralysis cases and the difference was significant (p < 0.05). The outcome was good (mRS < 3) in all the cases where serotypes were detected, but on statistical correlation, it was not found significant (p > 0.05). CONCLUSION: DENV-1 and DENV-2 are associated with neurological manifestation of dengue infection, which is different from the existing literature, where DENV-2 and DENV-3 are reported. The detection of DENV serotype will help in predicting and best management of neurological complication. The serotype 2 of dengue virus is more commonly associated with dengue-associated hypokalemic paralysis than other neurological complication (p < 0.05). There is no significant association of serotypes with outcome or mortality.

Craniofacial Fibrous Dysplasia of the Skull Assisted by Virtual Surgical Planning.

Craniofacial fibrous dysplasia (FD) involves thickening of the skull and facial bones, causing asymmetry and distortion of overlying soft tissues. Surgical contouring is often performed with rotary bur or osteotome, with the goal of matching contralateral unaffected anatomy. This is made technically challenging by having no direct visualization of contralateral structures, and the desire to control depth of resection to match the contour of the unaffected side. In our report, a 13-year-old male presented for surgical evaluation of craniofacial FD affecting the right parietal/temporal bones. A novel virtual surgical planning approach of premade drilling template with numerous pilot guide holes was used to assist bone debulking. The pilot holes allowed precise burring of the dysplastic bone. The patient achieved excellent calvarial contour symmetry without unintended intracranial extension. We believe that virtual surgical planning and drilling depth guides are effective tools in the reconstruction of craniofacial FD.

Where Are We Headed? Diagnosing Abnormal Head Shapes Through Virtual Care Visits.

PURPOSE: Since the beginning of the coronavirus disease 2019 pandemic in early March, there has been a push to expand virtual patient care visits instead of in-person clinic visits. Studies have found that telemedicine can provide efficient triaging, reduction in emergency room visits, and conservation of health care resources and personnel. Although virtual patient care has been implicated in providing similar outcomes to traditional face-to-face care in patients affected with coronavirus disease 2019, there are a lack of studies on the effectiveness of virtual care visits (VCVs) for patients with craniosynostosis or deformational plagiocephaly. This study aims to develop an understanding of whether physicians can accurately diagnose pediatric patients with craniosynostosis or deformational plagiocephaly via VCVs, and whether they can determine if affected patients will benefit from helmet correction or if surgical treatment is required. METHODS: An Institutional Review Board-approved retrospective chart analysis over a 4-month period (March 1, 2020 to June 30, 2020) was performed analyzing all pediatric patients (<18 years old) who underwent virtual care calls for diagnosis and treatment of abnormal head shape. Patients were referred to UT Physicians Pediatric Surgery clinic for evaluation by a member of the Texas Cleft-Craniofacial Team (2 surgeons or 1 physician's assistant). Variables such as patient demographics, diagnosis, and need for confirmation were pulled and recorded from Allscripts Electronic Medical Records software. RESULTS: Thirty-five patients were identified who fit our search criteria. Out of these patients, eleven (31.43%) cases were diagnosed with craniosynostosis, twenty-two (62.86%) cases were diagnosed with deformational plagiocephaly, and 2 (5.71%) cases were diagnosed as being normocephalic. Median age at virtual care evaluation was 14.10 months (Interquartile Range [IQR] 5.729, 27.542) for patients diagnosed with craniosynostosis and 6.51 months (IQR 4.669, 7.068) for patients diagnosed with deformational plagiocephaly. All eleven (100%) patients diagnosed with craniosynostosis were referred for a confirmatory computed tomography scan before undergoing surgical intervention and saw an alleviation in head shape postoperatively. Eighteen (81.82%) of patients diagnosed with deformational plagiocephaly were recommended to undergo conservative treatment and the remaining 4 (18.18%) were recommended for helmet therapy. Two cases were unable to be diagnosed virtually. These patients needed a follow-up visit in person to establish a diagnosis and plan of treatment. CONCLUSIONS: Virtual care visits are increasing in frequency and this includes consultations for abnormal head shapes. Our experience demonstrates that the majority of patients can be evaluated safely in this modality, with only 5.71% requiring additional imaging or in-person visits to confirm the diagnosis. Our study underscores the feasibility of virtually diagnosing and recommending a plan for treatment in pediatric patients with abnormal head shapes. This information can be implemented to further our knowledge on the accuracy of diagnosis and treatment options for patients with craniosynostosis and deformational plagiocephaly. Further analyses are needed to quantify the financial and patient-reported outcomes of VCVs for these patients.

Select Per- and Polyfluoroalkyl Substances (PFAS) Induce Resistance to Carboplatin in Ovarian Cancer Cell Lines.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants associated with adverse reproductive outcomes including reproductive cancers in women. PFAS can alter normal ovarian function, but the effects of PFAS on ovarian cancer progression and therapy response remain understudied. Ovarian cancer is the most lethal gynecologic malignancy, and a major barrier to effective treatment is resistance to platinum-based chemotherapy. Platinum resistance may arise from exposure to external stimuli such as environmental contaminants. This study evaluated PFAS and PFAS mixture exposures to two human ovarian cancer cell lines to evaluate the ability of PFAS exposure to affect survival fraction following treatment with carboplatin. This is the first study to demonstrate that, at sub-cytotoxic concentrations, select PFAS and PFAS mixtures increased survival fraction in ovarian cancer cells following carboplatin treatment, indicative of platinum resistance. A concomitant increase in mitochondrial membrane potential, measured by the JC-1 fluorescent probe, was observed in PFAS-exposed and PFAS + carboplatin-treated cells, suggesting a potential role for altered mitochondrial function that requires further investigation.

Subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a slowly progressive brain disorder caused by mutant measles virus. SSPE affects younger age groups. SSPE incidence is proportional to that of measles. High-income countries have seen substantial decline in SSPE incidence following universal vaccination against measles. SSPE virus differs from wild measles virus. Measles virus genome recovered from the autopsied brain tissues demonstrates clustered mutations in virus genome particularly in the M gene. These mutations destroy the structure and functioning of the encoded proteins. Complete infectious virus particle has rarely been recovered from the brain. Human neurons lack required receptor for entry of measles virus inside the neurons. Recent in vitro studies suggest that mutations in F protein confer hyperfusogenic properties to measles virus facilitating transneuronal viral spread. The inflammatory response in the brain leads to extensive tissue damage. Clinically, SSPE is characterized by florid panencephalitis. Clinically, SSPE is characterized by cognitive decline, periodic myoclonus, gait abnormalities, vision loss, and ultimately to a vegetative state. Chorioretinitis is a common ocular abnormality. Electroencephalography (EEG) shows characteristic periodic discharges. Neuroimaging demonstrates periventricular white matter signal abnormalities. In advanced stages, there is marked cerebral atrophy. Definitive diagnosis requires demonstration of elevated measles antibody titers in cerebrospinal fluid (CSF). Many drugs have been used to stabilize the course of the disease but without evidence from randomized clinical trials. Six percent of patients may experience prolonged spontaneous remission. Fusion inhibitor peptide may, in the future, be exploited to treat SSPE. A universal vaccination against measles is the only proven way to tackle this menace currently.

Quantitative assessment of lesion load and efficacy of 3 cycles of albendazole in disseminated cysticercosis: a prospective evaluation.

BACKGROUND: The management of disseminated cysticercosis is unclear and largely considered hazardous. The role of albendazole remains controversial in such patients. METHODS: A tertiary care, University hospital-based prospective intervention study was conducted from December 2015 to December 2017. Patients with disseminated cysticercosis, defined as the presence of multiple viable neurocysticerci (≥ 3) in the brain along with involvement of an additional extra site, were included in the study. Patients with cysticercal encephalitis were excluded. A detailed evaluation, including ophthalmoscopy, ocular B scans, ultrasound abdomen, and X-rays were done. Albendazole was administered at a dose of 15 mg/kg/day in 3 cycles of 28 days each. All patients were also given adjuvant corticosteroids and anti-epileptic drugs. Clinical and radiological follow up was carried out at a difference of 3 months between each treatment cycle. For radiological quantification, lesions were counted at 10 pre-specified levels. Statistical analysis was done to estimate the difference in seizure frequency and lesion load. RESULTS: Twenty-nine patients (21 with > 20 lesions; 8 with ≤ 20 lesions) were given albendazole as per the protocol. There was a significant reduction in the occurrence of seizures (P < 0.001) and headache (P < 0.001). A significant reduction in lesion load from baseline to third follow-up was seen in the estimations done at different levels (P < 0.001). No patient developed serious side-effect warranting cessation of therapy. CONCLUSION: Cyclical use of albendazole appears efficacious in treating disseminated cysticercosis. The method of quantification described may be used in future studies for objective assessment. TRIAL REGISTRATION: ISRCTN11630542; 28th September 2019; Retrospectively registered.

Pathological, ultrasonographic, and electrophysiological characterization of clinically diagnosed cases of pure neuritic leprosy.

A subset of neuritic form of leprosy, called pure neuritic leprosy (PNL), seen in a minority of leprosy patients, is characterized by peripheral neuropathy without skin lesions and an absence of acid-fast bacilli on skin smears. Patients with PNL are often started on drug therapy without confirmation of diagnosis. We, therefore, did a prospective study of clinically diagnosed PNL patients with correlation of ultrasonographic and biopsy findings. A total of 100 consecutive patients with PNL, diagnosed according to the consensus case definition, were included in the study. All patients underwent nerve conduction study, peripheral nerve ultrasonography, and sural nerve biopsy. Multiple mononeuropathies were present in 75% of cases, mononeuropathy in 18%, and polyneuropathy in the remaining 7%. Compared to clinical examination, ultrasonographic assessment of the peripheral nerves was not only better at the detection of thickening but also helped in characterization of their fascicular architecture, echogenicity, and vascularity. A total of 32 cases were confirmed on nerve biopsy, out of which 75% had demonstrable lepra bacilli. Cranial nerve involvement, presence of trophic ulcers, and bilateral thickening of the great auricular nerve were significantly associated with the positivity of lepra bacilli. A significant improvement in the disability score happened after multidrug therapy. A comprehensive electrophysiologic, ultrasonographic, and histological evaluation may be helpful in establishing a diagnosis of PNL with greater confidence, while ruling out other non-leprosy diagnoses.

Platelet dysfunction and coagulation assessment in patients of tuberculous meningitis.

INTRODUCTION: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. As reported in various studies, stroke is common among patients with TBM, with a prevalence of 17-54%. The present study assessed platelet dysfunction and coagulation abnormality in patients with TBM. METHODS: This was a prospective observational study that included 123 consecutive patients with TBM. In addition to clinical and radiological parameters, the complete platelet function and coagulation function were studied. The patients were followed up to 6 months. RESULTS: A significant correlation between platelet abnormality and stroke in patients with TBM was reported in this study. Results of the univariate analysis revealed that haematological parameters such as mean platelet volume (MPV) (p < 0.001), platelet distribution width (PDW)(p < 0.001), platelet-large cell ratio (P-LCR) (p < 0.001), and platelet aggregometry (PAg) (p < 0.001) were significantly associated with infarct. However, other haematological parameters such as bleeding time (p = 0.712), clotting time (p = 0.362), activated partial thromboplastin time (p = 0.094), INR (p = 0.420), protein C (p = 0.988), and protein S (p = 0.579) were not significantly associated with infarct. During follow-up at 3 and 6 months, parameters such as MPV (p < 0.001), PDW (p < 0.001), and P-LCR (p < 0.001) were significantly associated with infarct. CONCLUSION: The present study concluded that platelet abnormalities in patients with TBM contribute to infarct and are associated with poor clinical outcomes. This study suggested the role of antiplatelet agents in preventing stroke in patients with TBM.

Photodynamic therapy: Promoting in vitro efficacy of photodynamic therapy by liposomal formulations of a photosensitizing agent.

OBJECTIVE: A relatively low level of lysosomal photodamage has been shown capable of promoting the efficacy of photodamage simultaneously or subsequently directed to mitochondrial/ER sites. The procedure has hitherto involved the use of two photosensitizing agents that require irradiation at two different wavelengths and different formulation techniques. This, together with different pharmacokinetic profiles of the photosensitizers, adds a layer of complexity to a protocol that we have sought to circumvent. In this study, liposomal formulations were used to direct photodamage created by benzoporphyrin derivative (BPD, Verteporfin) to lysosomes, mitochondria and the ER. This resulted in the development of an optimal targeting profile using a single agent and a single wavelength of activating irradiation. MATERIALS/METHODS: These studies were carried out in monolayer cultures of OVCAR5 tumor cells. BPD localization was modified by lipid anchoring and formulation in liposomes, and was assessed by fluorescence microscopy. Irradiation was carried out at 690 ± 10 nm with photodamage assessed also using fluorescent probes and microscopy. RESULTS: BPD normally localizes in a wide variety of sub-cellular loci that include both mitochondria and the ER, but lysosomes are spared from photodamage. Using a liposomal formulation containing BPD anchored to a lipid resulted in the targeting of lysosomes. A mixture of liposomes containing "free" and "anchored" BPD was shown to significantly promote photokilling. Eliminating cholesterol from the formulation of the anchored product enhanced lysosomal photodamage; prior studies had revealed that excess cholesterol can have a cytoprotective effect when lysosomes are the PDT target. DISCUSSION: The ability of a liposomal formulation to change localization patterns permits directing photodynamic therapy toward specific sub-cellular loci, thereby promoting photokilling. Incorporating chemotherapeutic agents into such formulations could represent a logical next step in assessing the ability of directed photodamage to enhance tumor eradication. Lasers Surg. Med. 50:499-505, 2018. © 2018 Wiley Periodicals, Inc.

Cortical laminar necrosis in dengue encephalitis-a case report.

BACKGROUND: Dengue encephalitis is a rare neurological manifestation of dengue fever. Its clinical presentation is similar to other viral encephalitides and encephalopathy. No single specific finding on magnetic resonance imaging of dengue encephalitis has yet been documented. They are highly variable and atypical. CASE PRESENTATION: A 15-year boy presented with fever, the headache and altered sensorium of 12-day duration. On neurological examination, his Glasgow Coma Scale score was 10 (E3M4V3). There was no focal neurological deficit. Laboratory evaluation revealed leukopenia and marked thrombocytopenia. Dengue virus IgM antibody was positive both in serum and cerebrospinal fluid. Magnetic resonance imaging of the brain revealed signal changes in bilateral parietooccipital and left frontal regions (left hemisphere more involved than the right hemisphere). There was gyriform enhancement bilateral parietooccipital regions consistent with cortical laminar necrosis. Bilaterally diffuse subcortical white matter was also involved and subtle T2 hyperintensity involving both basal ganglia was noted. Gradient echo sequence revealed presence of hemorrhage in the subcortical white matter. Patient was treated conservatively and received platelet transfusion. Patient became fully conscious after 7 days. CONCLUSION: In a patient with highly suggestive dengue e\ephalitis, we describe an unusual magnetic resonance imaging finding. This report is possibly the first instance of cortical laminar necrosis in such a setting.