Electrolytes Play a Role in Detecting Cisplatin-Induced Kidney Complications and May Even Prevent Them-Retrospective Analysis.

Background and Objective: Cisplatin is a chemotherapy drug used to treat several types of malignancies. It is a platinum-based compound that interferes with cell division and DNA replication. Cisplatin has been associated with renal damage. This study evaluates the early detection of nephrotoxicity through routine laboratory tests. Materials and Methods: This is a retrospective chart review based on the Saudi Ministry of National Guard Hospital (MNGHA). We evaluated deferential laboratory tests for cancer patients treated with cisplatin between April 2015 and July 2019. The evaluation included age, sex, WBC, platelets, electrolytes, co-morbidities and interaction with radiology. Results: The review qualified 254 patients for evaluation. Around 29 patients (11.5%) had developed kidney function abnormality. These patients presented with abnormally low magnesium 9 (31%), potassium 6 (20.7%), sodium 19 (65.5%) and calcium 20 (69%). Interestingly, the whole sample size had abnormal electrolytes presenting magnesium 78 (30.8%), potassium 30 (11.9%), sodium 147 (58.1%) and calcium 106 (41.9%). Some pathological features were detected, such as hypomagnesemia, hypocalcemia and hypokalemia. In addition, infections that needed antibiotics were dominant in patients treated with cisplatin alone, representing 50% of this group. Conclusions: We report that an average of 15% of patients with electrolyte abnormalities develop renal toxicity and reduced function. Moreover, electrolytes may serve as an early indicator for renal damage as part of chemotherapy complication. This indication represents 15% of renal toxicity cases. Changes in electrolyte levels have been reported with cisplatin. Specifically, it has been linked to hypomagnesemia, hypocalcemia and hypokalemia. This study will help reduce the risk of dialysis or the need for kidney transplant. It is also important to manage any underlying conditions and control patients' intake of electrolytes.

Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review.

Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential role in the disease pathogenesis, and are an essential target for therapy. Three generations of mTOR inhibitors have been developed and are clinically used for immunosuppression and chemotherapy for multiple cancers. Only a few mTOR inhibitors have been investigated for the treatment of medulloblastoma and other pediatric tumors. The first-generation mTOR, sirolimus, temsirolimus, and everolimus, went through phase I clinical trials. The second-generation mTOR, AZD8055 and sapanisertib, suppressed medulloblastoma cell growth; however, limited studies have investigated possible resistance pathways. No clinical trials have been found to treat medulloblastoma using third-generation mTOR inhibitors. This systematic review highlights the mechanisms of resistance of mTOR inhibitors in medulloblastoma and includes IDO1, T cells, Mnk2, and eIF4E, as they prolong malignant cell survival. The findings promote the importance of combination therapy in medulloblastoma due to its highly resistant nature.

Spinal dural arteriovenous fistula: a comprehensive review of the history, classification systems, management, and prognosis.

Spinal dural arteriovenous fistulas account for the majority of spinal vascular malformations. They are typically located in the thoracolumbar region and are diagnosed in the middle-aged and elderly populations. Although spinal dural arteriovenous fistulas have been postulated to be acquired, their exact development remains uncertain. Typically, the arteriovenous shunt is situated close to the spinal nerve root, inside the dura mater, where the blood from the radiculomeningeal artery and radicular vein intermix. Throughout history, there have been multiple classification systems of spinal arteriovenous shunts since 1967. Those were mainly based on the evolution of diagnostic studies as well as the treatment of these lesions. Such classification systems have undergone significant changes over the years. Unlike intracranial dural arteriovenous fistula, spinal dural arteriovenous fistula is progressive in nature. The neurological manifestations, due to venous congestion, tend to be insidious as well as non-specific. These include sensory deficits, such as paresthesia, bilateral and/or unilateral radicular pain affecting the lower limbs, and gait disturbances. Spinal dural arteriovenous fistulas can be suspected on magnetic resonance imaging/magnetic resonance angiography and confirmed by digital subtraction angiography (DSA). The management includes surgery, endovascular therapy, and in selected cases, radiotherapy. The treatment goal of spinal dural arteriovenous fistula is to halt the progression of the disease. The prognosis depends on both the duration of symptoms as well as the clinical condition prior to therapy. The present article comprehensively reviews the pathophysiology, changes in classification systems, natural history, clinical manifestations, radiological features, management, and prognosis.

The Response of Synthetic Adrenocorticotropic Hormone (ACTH) Treatment in Pediatric Drug-Resistant Epilepsy Other Than Infantile Epileptic Spasms Syndrome: A Retrospective Observational Study.

INTRODUCTION:  Adrenocorticotropic hormone (ACTH) is a tropic hormone naturally secreted by the anterior pituitary gland to stimulate the secretion of cortisol and androgens. ACTH is used in non-tuberous sclerosis infantile epileptic spasms syndrome (IESS), and it has shown significant, promising results in epilepsy syndromes with possible inflammatory processes. However, many studies have also demonstrated a promising potential even in other types of drug-resistant epilepsy.  Material and method: This study is a retrospective observational study that follows the clinical characteristics and outcomes of nine pediatric patients with drug-resistant epilepsy treated with short-term synthetic ACTH in Saudi Arabia. The response was assessed during the ACTH infusion and after three months. RESULTS: During infusion, six of the nine (66%) patients had a short-term (within two weeks) favorable response, with a more than 50% reduction in seizure frequency. Four of the nine (44%) patients had complete responses with seizure freedom. After three months, four patients (44%) had a three-month seizure frequency reduction of more than 30% attributed to ACTH, including one patient with an IESS history who had a 70% reduction in seizure frequency. Of the four patients who had a complete response, three (75%) had a seizure relapse after tapering in the following three months.  Conclusion: This case series adds to the literature to suggest ACTH treatment of drug-resistant epilepsies other than IESS might benefit some patients in the acute setting but they are less likely to maintain a sustained treatment response. Randomized and large sample size studies are necessary to assess treatment response and accurately aid in appropriate patient selection.

Intracranial dural arteriovenous fistula: a comprehensive review of the history, management, and future prospective.

Dural arteriovenous fistulas (DAVF) are abnormal acquired intracranial vascular malformations consisting of pathological connections located within the dura between the pial arteries and the veno vasora, comprising the walls of the dural sinuses, bridging veins, or transosseous emissary veins. Dural arteriovenous fistulas are distinguished from arteriovenous malformations by their arterial supply from the vessels that perfuse the dura mater and lack of a parenchymal nidus. They are most commonly situated at the transverse and cavernous sinuses. The mechanism of development behind dural arteriovenous fistula can be explained by the molecular and anatomical factors. Multiple classification systems have been proposed throughout history including; Djindjian and Merland, Cognard, and Borden classification systems. The aggressiveness of the clinical course in intracranial dural arteriovenous fistula can be predicted through the angiographic patterns of venous drainage, more specifically, the presence of cortical venous drainage, the presence of venous ectasia, and the aggressiveness of clinical presentation. Intracranial dural arteriovenous fistulas might be discovered incidentally. However, if symptomatic, the clinical presentation ranges from mild neurological deficits to severe, lethal intracranial hemorrhage. Angiography is the imaging of choice to investigate, diagnose, and plan treatment for intracranial dural arteriovenous fistula. The management algorithm of intracranial dural arteriovenous fistula can be broadly divided into conservative, surgical, endovascular, and/or radiosurgical options. With the advent of endovascular therapies, surgery has fallen out of favor for managing intracranial dural arteriovenous fistulas. In the present article, the pathophysiology, classifications, natural history, clinical manifestations, radiological features, management, and complications are comprehensively reviewed.

Primary spinal cord glioblastoma: A rare cause of paraplegia.

Background: Primary spinal glioblastomas are extremely rare neoplasms and account for only 0.2% of glioblastoma cases. Due to the rare incidence of spinal cord glioblastoma in the literature, its natural history/ outcome remains undetermined. The present article describes the clinical presentation, radiological/pathological characteristics, and outcome of the primary spinal cord glioblastoma. Case Description: Two young patients initially presented with paresis that rapidly progressed to paraplegia. Nondermatomal sensory deficits were also noted, mainly affecting the lower limbs. Neuroradiological imaging revealed an extensive intramedullary spinal cord lesion, with no evidence of concurrent intracranial space-occupying lesions. Thoracic laminectomy, followed by tumor debulking and/or biopsy, was performed. The histomorphology was suggestive of glioblastoma, the World Health Organization grade 4 (Isocitrate Dehydrogenase-wild type). They were discharged in stable condition and were started on chemoradiotherapy, with clinicoradiological follow-up. One patient passed away after 9 months of initial presentation. The other patient was alive at 6-month follow-up. Conclusion: Primary spinal glioblastoma is a rare and challenging tumor. Patients commonly present with a progressive paresis, resulting in paraplegia, regardless of the surgical resection extent, and received adjuvant chemotherapy. Therefore, primary spinal cord glioblastoma should be considered in patients reporting a rapid lower limb weakness with neuroradiological evidence of extensive, exophytic intramedullary lesion of the spine. A biopsy-proven histopathological diagnosis is of indisputable importance to establish the final diagnosis and plan treatment options.

Social Anxiety and Obsessive-Compulsive Disorder Are Common Among Persons With Multiple Sclerosis at King Abdulaziz Medical City, Riyadh.

Background Multiple sclerosis (MS) is associated with a physical disability and disturbed psychosocial functioning in young people. Many psychological and psychiatric comorbidities have been reported in MS. Objective To determine the frequency of social anxiety disorder (SAD) and obsessive-compulsive disorder (OCD) among MS patients and their relation to MS severity. Methods A cross-sectional survey was conducted in an adult MS cohort. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Social Phobia Inventory (SPIN) were used to determine the presence and severity of OCD and SAD. The Statistical Package for the Social Sciences (SPSS) version 22 (IBM Corp., Armonk, NY) was used for statistical analysis. The Mann-Whitney U test and logistic regression were used to assess the association of the two diseases with the severity of MS. Results A total of 145 persons with MS (pwMS) were studied. The mean age was 33.5 (±8.5) years; the mean duration of MS was 7.2 (± 5.1) years. The majority (74.1%) were women; 57.3% were married; 63% had a college education; 50% belonged to the higher middle-class socioeconomic strata. Relapsing-remitting multiple sclerosis was the most common type of MS (92.2%). The mean Expanded Disability Status Scale (EDSS) score was 2.24 (±2.19). SAD was reported by 26.9%, and OCD was reported by 31% of the cohort. PwMS with walking difficulty but not wheelchair-bound had a statistically significant increased risk of SAD (p = 0.036). There was no direct association between MS-related disability and OCD. However, pwMS with SAD were more likely to have concomitant OCD (t=4.68, p-value <0.001, 95% CI: 0.47-1.16). Increasing disability was associated with higher chances of developing social anxiety and, in turn, OCD (t=3.39, p-value <0.001, 95% CI: 0.66-2.52). Conclusions Social anxiety and obsessive-compulsive disorders were present in nearly one-third of pwMS. Impaired walking but not wheelchair dependence was associated with social anxiety. PwMS with SAD were more likely to have obsessive-compulsive disorder.