Autoimmune Encephalitis: Insights Into Immune-Mediated Central Nervous System Injury.

Autoimmune encephalitis (AE) is a category of immune-mediated disorders of the central nervous system (CNS) affecting children and adults. It is characterized by the subacute onset of altered mentation, neurocognitive issues, refractory seizures/drug-resistant epilepsy, movement disorders, and/or autonomic dysfunction. AE is mediated by autoantibodies targeting specific surface components or intracytoplasmic antigens in the CNS, leading to functional or structural alterations. Multiple triggers that induce autoimmunity have been described, which are mainly parainfectious and paraneoplastic. The imaging features of AE often overlap with each other and with other common causes of encephalitis/encephalopathy (infections and toxic-metabolic etiologies). Limbic encephalitis is the most common imaging finding shared by most of these entities. Cortical, basal ganglia, diencephalon, and brainstem involvement may also be present. Cerebellar involvement is rare and is often a part of paraneoplastic degeneration. Owing to an improved understanding of AE, their incidence and detection have increased. Hence, in an appropriate setting, a high degree of suspicion is crucial when reporting clinical MRIs to ensure prompt treatment and better patient outcomes. In this review, we discuss the pathophysiology of AE and common etiologies encountered in clinical practice.

Imaging of pediatric glioneuronal and neuronal tumors.

Glioneuronal tumors (GNTs) are an expanding group of primary CNS neoplasms, commonly affecting children, adolescents and young adults. Most GNTs are relatively indolent, low-grade, WHO grade I lesions. In the pediatric age group, GNTs have their epicenter in the cerebral cortex and present with seizures. Alterations in the mitogen-activated protein kinase (MAPK) pathway, which regulates cell growth, are implicated in tumorigenesis. Imaging not only plays a key role in the characterization and pre-surgical evaluation of GNTs but is also crucial role in follow-up, especially with the increasing use of targeted inhibitors and immunotherapies. In this chapter, we review the clinical and imaging perspectives of common pediatric GNTs.

Enlarging and shrinking focal perivascular spaces.

BACKGROUND AND PURPOSE: Perivascular spaces (PVS) are interstitial fluid-filled spaces surrounding blood vessels traversing the deep gray nuclei and white matter of the brain. These are commonly encountered on CT and MR imaging and are generally asymptomatic and of no clinical significance. However, occasional changes in the size of focal PVS, for example, when enlarging, may mimic pathologies including neoplasms and infections, hence potentially confounding radiological interpretation. Given these potential diagnostic issues, we sought to better characterize common clinical and imaging features of focal PVS demonstrating size fluctuations. MATERIALS AND METHODS: Upon institutional approval, we retrospectively identified 4 cases demonstrating PVS with size changes at our institution. To supplement our cases, we also performed a literature review, which identified an additional 14 cases. Their clinical and imaging data were analyzed to identify characteristic features. RESULTS: Of the 18 total cases (including the 4 institutional cases), 10 cases increased and 8 decreased in size. These focal PVS ranged from 0.4-4.5 cm in size. Whereas a decrease in size did not represent a diagnostic issue, focal increase in size of PVS led to concerning differential diagnoses in at least 30% of the radiology reports. These enlarging PVS were most found in the basal ganglia and temporal lobe, and in patients with previous brain radiation treatment. CONCLUSION: Focal size change of PVS can occur, especially years after brain radiation treatment. Being cognizant of this benign finding is important to consider in the differential diagnosis to avoid undue patient anxiety or unnecessary medical intervention.

Diagnostic Imaging for Retinoblastoma Cancer Staging: Guide for Providing Essential Insights for Ophthalmologists and Oncologists.

Retinoblastoma is the most common cause of all intraocular pediatric malignancies. It is caused by the loss of RB1 tumor suppressor gene function, although some tumors occur due to MYCN oncogene amplification with normal RB1 genes. Nearly half of all retinoblastomas occur due to a hereditary germline RB1 pathogenic variant, most of which manifest with bilateral tumors. This germline RB1 mutation also predisposes to intracranial midline embryonal tumors. Accurate staging of retinoblastoma is crucial in providing optimal vision-, eye-, and life-saving treatment. The AJCC Cancer Staging Manual has undergone significant changes, resulting in a universally accepted system with a multidisciplinary approach for managing retinoblastoma. The authors discuss the role of MRI and other diagnostic imaging techniques in the pretreatment assessment and staging of retinoblastoma. A thorough overview of the prevailing imaging standards and evidence-based perspectives on the benefits and drawbacks of these techniques is provided. Published under a CC BY 4.0 license. Test Your Knowledge questions for this article are available in the supplemental material.

Uncovering the Uncommon: Institutional Insights Into the Clinical and Epidemiological Characteristics of Rarer Forms of Bladder Cancer Beyond Transitional Cell Carcinoma.

Introduction Non-transitional cell carcinomas of the bladder (NTCCB) represent a significant clinical challenge due to their rarity, heterogeneity, and poor prognosis. Despite their poor prognosis, the treatment of NTCCB has historically been based on the same principles used for transitional cell carcinomas (TCCs). Our study focuses on the management of non-transitional cell carcinomas and aims to identify areas where treatment outcomes can be improved based on our institutional experience. Materials and methods A retrospective analysis of patients with NTCCB who presented at Kasturba Hospital Manipal was conducted between 2012 to 2021. Patient data were collected, and demographic characteristics, presenting symptoms, history of other primary malignancies, comorbidities, location of the tumour, stage at presentation, histopathological subtype, site of systemic metastasis, and primary treatment given were analyzed descriptively. Median overall survival was determined by calculating the time from the initial diagnosis to the date of death. Results Among 31 patients with NTCCB, 15 (48%) presented with metastatic disease, five (16%) with locally advanced disease, and 11 (36%) with localized disease. The most common histopathological subtypes were squamous cell carcinoma and adenocarcinoma, as noted in 14 (45.2%) and 13 (41.9%) patients, respectively, followed by neuroendocrine tumours in two (6.5%), extra-adrenal phaeochromocytoma in one (3.3%), and sarcomatoid carcinoma in one (3.3%) patient, respectively. The lung was the most frequent site of systemic metastasis as noted in six (40%) patients, followed by the liver and skeletal system in three (20%) patients each, peritoneum in two (13.3%), cerebral cortex in one (6.7%), and non-regional lymph nodes in one (6.7%) patient. The primary treatment given included palliative chemotherapy in 14 (45.2%) patients, radical cystectomy with ileal conduit in 10 (32.3%), neoadjuvant chemotherapy only in four (12.9%), partial cystectomy in one (3.2%), pelvic exenteration with ileal conduit in one (3.2%), and peritoneal debulking with palliative chemotherapy in one (3.2%) patient. The overall median survival was 15 months, with a one-year survival rate of 67.4%. Conclusion NTCCB exhibits aggressive clinical behaviour and presents with nonspecific clinical features in the early stages, often leading to late diagnosis and an advanced tumour stage at presentation. Multi-institutional studies with larger patient cohorts are needed to recommend best clinical practices for early detection and optimal treatment strategies to improve patient survival.

Comparing Tubeless and Tubed Approaches in Percutaneous Nephrolithotomy for Moderate Renal Calculi: Outcomes on Safety, Efficacy, Pain Management, Recovery Time, and Cost-Effectiveness.

Introduction This study focuses on investigating the effect of routine nephrostomy tube placement in patients with moderate renal calculi of size 2.5 cm or less who undergo uncomplicated percutaneous nephrolithotomy (PCNL) procedures. Previous studies have not specified whether only uncomplicated cases were included in the analysis, which may affect the results. This study aims to provide a clearer understanding of the effect of routine nephrostomy tube placement on blood loss in a more homogeneous patient population. Materials and methods A prospective randomized controlled trial (RCT) was conducted at our department over 18 months, dividing 60 patients with a single renal or upper ureteric calculus of size ≤2.5 cm into two groups: 30 patients in each group (group 1: tubed PCNL, group 2: tubeless PCNL). The primary outcome was the drop in perioperative hemoglobin level and the number of packed cell transfusions necessary. The secondary outcome included the mean pain score, analgesic requirement, length of hospital stay, time to return to normal activities, and the total cost of the procedure. Results The two groups were comparable in age, gender, comorbidities, and stone size. The postoperative hemoglobin level was significantly lower in the tubeless PCNL group (9.56 ± 2.13 gm/dL) compared to the tube PCNL group (11.32 ± 2.35 gm/dL) (p = 0.0037), and two patients in the tubeless group required blood transfusion. The duration of surgery, pain scores, and analgesic requirement were comparable between the two groups. The total procedure cost was significantly lower in the tubeless group (p = 0.0019), and the duration of hospital stay and time to return to daily activities were significantly shorter in the tubeless group (p < 0.0001). Conclusions Tubeless PCNL is a safe and effective alternative to conventional tube PCNL, with the advantages of shorter hospital stay, faster recovery, and lower procedure costs. Tube PCNL is associated with less blood loss and the need for transfusions. Patient preferences and bleeding risk should be considered when choosing between the two procedures.

Interesting and unusual clinical presentations in leprosy at a referral center.

BACKGROUND: Leprosy is a disease of declining global endemicity but is still an important health-care problem in India. Pure neural leprosy is an important subset of presentations of leprosy in India. Leprosy is a known disease of the skin and nerves, but cases of pure neural involvement are relatively less. We hereby present 10 cases of pure neural leprosy in which the diagnosis of leprosy was difficult with routine methods. MATERIALS AND METHODS: The study was conducted at the main referral center and satellite clinics of our organization. A retrospective analysis of patient records for the last four years was undertaken to identify patients presenting with predominantly neurological manifestations and uncommon presentations including those without skin lesions. The medical records of the patients were used as source of data. All the patients were subjected to a detailed clinical examination and bacteriological examination with slit-skin smears. Investigations like nerve biopsy, electromyography, and nerve conduction studies were done in patients with diagnostic difficulties. RESULTS: Patients presented with neurological symptoms like paresthesias (60%), diminished sensations (40%), nonhealing ulcers (30%), and blisters (20%). All except one had thickened nerves on clinical examination. Slit-skin smear was negative in all but one patient. Nerve biopsy confirmed the diagnosis of leprosy in seven cases. CONCLUSION: Pure neural leprosy is difficult to diagnose with routine methods. The diagnosis should be considered, especially by neurologists and dermatologists, who are more likely to see such patients with predominant neural manifestations. The diagnosis should be confirmed with nerve biopsy to prevent delay in therapy and associated complications.

BCG immunotherapy as an adjunct to chemotherapy in BL-lL patients--its effect on clinical regression, reaction severity, nerve function, lepromin conversion, bacterial/antigen clearance and 'persister' M. leprae.

BACKGROUND AND OBJECTIVE: Multidrug therapy in leprosy has failed to eliminate the problem of persister bacilli. Clearance of bacterial antigens is extremely slow which could predispose to continued nerve damage even after release from treatment. In the present study the immunomodulatory efficacy of BCG vaccine administered post-MDT in BL-LL leprosy patients was investigated in depth with a view to determining if augmenting chemotherapy with immunotherapy would help in faster clearance of M. leprae/antigens, bring down the level of persisters and minimise the occurrence/severity of reaction and nerve damage. METHODS: This is a placebo-controlled study in treated BL-LL patients. The patients are matched with respect to age, sex, bacteriological index and history of reaction, stratified and allocated to the two groups. One group (Gr A) received two doses of BCG-MOSCOW (3-33 x 10(5) cells) and the other (Gr B) normal saline (0.85%), injected intra-dermally at 3 month intervals. The Primary outcomes assessed at the end of 6 months were bacterial/antigen clearance, lepromin conversion, granuloma clearance and the occurrence of persisters. The secondary outcomes were clinical regression, occurrence and severity of reaction and changes in nerve functions. MATERIAL: A total of 107 BL-LL patients comprised of 49 in Gr A and 58 in Gr B; of which 36 and 42 respectively completed the study as per protocol, and are included in the final analysis. FINDINGS: The study findings show that both the primary and the secondary out comes were comparable in the two groups. Two doses of BCG administered post-MDT (Gr A) did not significantly alter the level of persisters or help in hastening the bacterial/antigen clearance, clinical regression of lesions and granuloma clearance. Lepromin conversion rates were also comparable. While the frequency of lepra reaction/neuritis following the intervention was comparable, the severity of reactions was significantly higher in Gr A. On the positive side neural functions assessed by nerve conduction studies showed that deterioration of motor nerve conduction was significantly lower in the BCG arm. Since all patients developing moderate to severe reactions, immediately received a course of corticosteroids, it is possible that timely use of it might have helped.

The effect of corticosteroids usage on bacterial killing, clearance and nerve damage in leprosy; part 3--Study of two comparable groups of 100 multibacillary (MB) patients each, treated with MDT + steroids vs. MDT alone, assessed at 6 months post-release from 12 months MDT.

OBJECTIVE: To investigate effects of therapeutic usage of corticosteroids on M. leprae killing and clearance, on clearance of granuloma and on nerve damage in multibacillary (MB) leprosy patients. DESIGN: From a cohort of 400 untreated MB patients, a comparable group of 100 each receiving MDT + steroids (group A) vs MDT alone (group B) were assessed at 18 months as compared to month zero with respect to clinical and granuloma regression, M. leprae killing and clearance, and nerve functions. Analysis was performed using SPSS version 10.0. The significance of association was tested using Chi square and Fisher's exact tests. RESULTS: Regression of lesions assessed clinically and by histopathology was seen in 52% and 53% patients in group A and 46% and 63% in B respectively (P not significant). Clearance of bacteria assessed by bacteriological index (BI) in slit skin smears (SSS) and extent and intensity of antigen using anti-BCG staining were also comparable in the two groups. Multiplication of M. leprae in the mouse foot pad (MFP) indicating the presence of viable bacilli was seen in 14% and 16% of SSS positive BL-LLs patients in groups A and B respectively (P not significant). The occurrence of viable M. leprae was higher among patients with repeat reaction (19%) than single (11%). Using clinical tests (nerve palpation, monofilament and voluntary muscle testing), the proportion of sensory and motor nerves showing improvement or deterioration were similar in the two groups. However using nerve conduction studies, the overall proportion of nerves showing deterioration (22%) was significantly higher than improvement (9%) (P < 0.001). CONCLUSIONS: Treatment with MDT + corticosteroids does not adversely affect the clearance of granuloma, M. leprae and/or its antigens and M. leprae killing. However the continued presence of viable bacteria in > 14% of BL-LLs patients indicate that 12 months of MDT may be insufficient for complete bacterial killing. In both groups nerve conduction studies indicated that deterioration of nerves was high suggesting, MDT + corticosteroids was not very efficacious in the prevention or reversal of nerve damage. A better immuno-modulatory drug or a modified corticosteroid regime is needed.

The effect of corticosteroid usage on the bacterial killing, clearance and nerve damage in leprosy: a prospective cohort study: part 1--study design and baseline findings of 400 untreated multibacillary patients.

OBJECTIVE: To investigate possible adverse effects of therapeutic usage of corticosteroids on the killing and clearance of M. leprae and the clearance of granuloma, in patients with multibacillary (MB) leprosy. DESIGN: A cohort of 400 untreated MB patients were sub-grouped into those to be treated with corticosteroids (prednisolone 40 mg daily tapered to 5 mg over 12 weeks) along with MB-MDT for reaction and/or neuritis or silent neuropathy (SN) of <6 months duration (group A), and those with no reaction and to be treated with MDT only (group B). Clinical, bacteriological, histopathological and neurological test findings at fixed time points were compared. Analysis was performed using SPSS version 10.0. The significance of association was tested using Chi-square test. In the current report, we describe the study design and baseline findings of 400 untreated MB patients, with special emphasis on differences between patients in groups A and B. RESULTS: At baseline, applying Ridley-Jopling classification, 39% patients were BT, 20% BB, 24% BL, 12% sub-polar LL and 5% pure neural (PN). Overall, 60% patients were slit skin smear (SSS) negative and 33% presented with disability either grades 1 or 2. Overall 140/400 (35%) patients presented with reaction and/or neuritis and 11/400 (3%) presented with SN of <6 months duration. Comparing groups A and B, the percentage of patients presenting with DG2 was significantly higher in group A (43%). By clinical tests, monofilaments (MF) and voluntary muscle testing (VMT), the percentage of patients and nerves showing functional impairment was also significantly higher in group A. However, in the more sensitive nerve conduction velocity (NCV) test, the percentage of patients that showed nerve abnormalities was closely comparable; 94% and 91% in groups A and B respectively while number of affected nerves was higher in group A. CONCLUSION: At baseline, as recorded by NCV, peripheral nerve function abnormality was observed in almost all the MB patients regardless of reaction; but among those presenting with reaction or neuritis, the nerve damage was more severe and extensive.