The most frequent side effects of the use of SGLT2 inhibitors are genitourinary tract infections. Since our patient presents with recurrent UTIs, the least indicated drug for the control of her diabetes would be option 4.

The most frequent side effects of the use of SGLT2 inhibitors are genitourinary tract infections. Since our patient presents with recurrent UTIs, the least indicated drug for the control of her diabetes would be [HIDDEN].

A 55-year-old woman, type 2 diabetic and obese, on treatment with metformin, with Hb A1c of 8%, has a history of repeated urinary tract infections. Which of the following therapeutic options to associate with metformin do you consider the LEAST appropriate?

Clinical experience with exenatide in obese North Indian patients with type 2 diabetes mellitus.

To share our clinical experience with exenatide in obese North Indian subjects with type 2 diabetes. We share our experience with use of exenatide in 74 patients treated at Indraprastha Apollo Hospital, a tertiary care centre in New Delhi, India Subjects included obese / overweight subjects (mean weight and BMI; 97.67 ± 5.6 kg and 34.56 kg/m(2)) with known history of type 2 DM (Mean: 9 ± 5.6 years) and maintaining suboptimal glycemic control (HbA1c >7%) on oral antidiabetic agents, with or without basal insulin. Metformin and sulphonylureas were continued (with dose adjustment if indicated), as was basal insulin (glargine / detemir). TZDs and DPP4 inhibitors were discontinued. The dose of exenatide was increased to 10 mcg twice a day after 4-12 weeks. 56 patients completed minimum 3 month therapy. 42 patients completed 6 months, 32, 9 months and 25 completed 12 months. Data of patients who had completed at-least 3 months of therapy was included for analysis. 69.77, 67.44, and 13.95% of the patients were receiving metformin, secretagogues or thiazolidinediones alone or in combination; 17.76% of the patients were on basal insulin. The change in fasting and post-prandial blood glucose levels were significant at 3, 6, 9 and 12 months with p-value <0.05. The mean weight loss at one, three, and six months and one year was 1.7 ± 1.3, 3.8 ± 2.5, 6.3 ± 3.4, and 8.3 ± 4.3 kg, respectively (P <0.05). The mean HbA1c (baseline: 8.8 ± 1.3%) at 3, 6 months and at one year was 7.8 ± 0.9, 7.7 ± 0.8 and 7.2 ± 0.8 (P <0.05). Thirty-five percent of the patients had a 'good' A1c value (< 7%) at the end of 12 months. 13 patients discontinued exenatide (three due to lack of response, six due to cost of therapy and four due to severe nausea). Nausea was the most common side effect, occurring in 95% patients within 1 month, although the incidence declined with passage of time. Clinical use of Exenatide is associated with significant improvement in glycemic control and major weight loss (8.3±4.3 kg at 1 year) in obese subjects with type 2 diabetes. Nausea is the most common side effect. In conclusion, exenatide is a effective and useful option for treatment of type 2 diabetes in obese Indian subjects.

Antihyperglycemic Drug Use in Long-Stay Nursing Home Residents with Diabetes Mellitus.

About 29.2% of American adults ≥ 65 years of age have diabetes mellitus, but details regarding diabetes management especially among nursing home residents are dated. Evaluate the prevalence of antihyperglycemic agents in residents with diabetes mellitus and describe resident characteristics using major drug classes. cross-sectional study. virtually all United States nursing homes. 141,636 residents with diabetes mellitus. Minimum Data Set (2016) and Medicare Part D claims determined use of metformin, sulfonylureas, meglitinide analogs, alpha-glucosidase inhibitors, TZDs, DPP4 inhibitors, SGLT2 inhibitors, GLP1 agonists, as monotherapy and with basal insulin. Seventy-two percent received antihyperglycemic drugs [most common: basal insulins (53.9% total; 46.9% with other non-insulin agents), metformin (35.5% total; 14.2% monotherapy), sulfonylureas (19.6% total; 6.3% monotherapy), and DPP4 inhibitors (12.2% total; 2.2% monotherapy)]. Sixty-three percent of meglitinide monotherapy versus 34.1% of metformin monotherapy users; and 38.3% meglitinide-basal insulin versus 22.2% metformin-basal insulin users were ≥85 years. Obesity was greater among users of GLP1 agonists compared to those receiving other agents (monotherapy: 60.5% versus 33-42%; with basal insulin: 76.2% versus 50-58%). End-stage renal disease was least prevalent among metformin users (monotherapy: 6.6%; with basal insulin: 8.8%) and most common among meglitinide monotherapy (19.6%) and GLP1 agonists with basal insulin (22%) users. There is heterogeneity of diabetes treatment in nursing homes. Use of antihyperglycemic drugs with a higher risk of hypoglycemia, such as insulin with sulfonylureas or meglitinides, continue in nursing home residents.

Insulin Therapy in Type 2 Diabetes.

Since the discovery of insulin, it was the only drug available for the treatment of diabetes until the development of sulfonylureas and biguanides 50 years later. But even with the availability of oral glucose-lowering drugs, insulin supplementation was often needed to achieve good glucose control in type 2 diabetes. Insulin NPH became the basal insulin therapy of choice and adding NPH to metformin and/or sulfonylureas became the standard of care until basal insulin analogs were developed and new glucose-lowering drugs became available. The advantages in cost-benefit of insulin analogs and their combination with new glucose-lowering drugs are still a matter of debate. There is no general agreement on how to avoid inertia by prescribing insulin therapy in type 2 diabetes when really needed, as reflected by the diversity of recommendations in the current clinical practice guidelines. When necessary for this review, a systematic search of the evidence was done in PubMed and Cochrane databases. Adding new oral glucose-lowering drugs to insulin such as DPP-4 inhibitors lead to a modest HbA1c reduction without weight gain and no increase in hypoglycemia. When SGLT-2 inhibitors are added instead, there is a slightly higher HbA1c reduction, but with body weight and blood pressure reduction. The downside is the increase in genital tract infections. GLP-1 receptor agonists have become the best alternative when basal insulin fails, particularly using fixed ratio combinations. Rapid-acting insulins via the inhaled route may also become an alternative for insulin supplementation and/or intensification. "Smart insulins" are under investigation and may become available for clinical use in the near future. Aggressive weight loss strategies together with the new glucose-lowering drugs which do not cause hypoglycemia nor weight gain should limit the number of patients with type 2 diabetes needing insulin. Nevertheless, because of therapeutic inertia and the progressive nature of the disease, many need at least a basal insulin supplementation and insulin analogs are the best choice as they become more affordable. Fixed ratio combinations with GLP1 receptor agonists are a good choice for intensification of insulin therapy.

[Short-term Glucose Lowering Effects of Sodium-glucose Cotransporter 2 Inhibitors Confirmed by Flash Glucose Monitoring in Two Outpatients with Type 1 Diabetes].

Case 1 was a 41-year-old man with type 1 diabetes. He presented with poor glycemic control [hemoglobin A1c (HbA1c) of 8-9%] despite treatment with more than 20 units/day of insulin and 150 mg of miglitol. Before administration of sodium glucose cotransporter 2 (SGLT2) inhibitor, hyperglycemia was noted mainly at night by Flash Glucose Monitoring (FGM). Administration of ipragliflozin at 50 mg improved the hyperglycemia mainly at night (mean blood glucose, before administration: 205 mg/dl, day 6 of treatment: 119 mg/dl). Two months later, the HbA1c improved to 7.2% without hypoglycemia or ketosis. Case 2 was a 46-year-old woman with type 1 diabetes. She was morbidly obese and presented with poor glycemic control (HbA1c: 9-11%) although she was being treated with more than 50 units/day of insulin and 2,250 mg of metformin. Before administration of SGLT2 inhibitor, hyperglycemia was noted to be mainly nocturnal by FGM. Administration of dapagliflozin at 5 mg improved the hyperglycemia mainly at night on day 2 with improvement in the mean blood glucose level from 188 mg/dl before administration to 128 mg/dl on day 5. Four months later, the HbA1c improved to 8.0% without hypoglycemia and ketosis, and her body weight decreased from 92.1 to 89.8 kg. The hypoglycemic effect of SGLT2 inhibitors is independent of insulin. These agents also have various other effects, including weight loss, improvement of blood pressure and lipid metabolism. Here we report the short-term glucose lowering effects of two SGLT2 inhibitors, as confirmed by FGM, in two outpatients with type 1 diabetes.

Approach Toward Diabetes Treatment in the Elderly.

Concomitant diseases in elderly individuals with diabetes (renal failure, heart failure, ischemic heart disease, stroke, urinary incontinence, cognitive impairment, dementia, sarcopenia, and osteoporosis) make diabetes management difficult. Therefore, other comorbid conditions should be taken into account in elderly diabetics when considering a treatment approach. The use of oral antidiabetic agents in individuals older than 75 years may be limited. Although the diabetes treatment is not any different in healthy elderly patients, hypoglycemia is one of the most feared conditions, especially in the elderly. Therefore, metformin, DPP-IV inhibitors, and SGLT2 inhibitors should be considered in the first place with less risk of hypoglycemia. Low-dose sulfonylureas may also be used in selected cases. The use of new antidiabetic drugs, such as GLP-1 anologues and SGLT2 inhibitors, has strengthened our ability to cope with the risk of hypoglycemia and cardiovascular events, which are the two most important drawbacks in the treatment of elderly people with diabetes. Insulin treatment should be individualized, and the most rare injection regimens should be used. In case of failure of OAD, basal insulin should be added to the current treatment, and if necessary, a basal + plus regimen should be planned by adding bolus insulin 1/2/3 times per day to the meals. As a result, in elderly diabetics, an inadequate treatment or excessive treatment and individualizing the treatment should be the most appropriate approach.

Fournier Gangrene Associated With Sodium-Glucose Cotransporter-2 Inhibitors: A Review of Spontaneous Postmarketing Cases.

Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors has been associated with Fournier gangrene (FG), a rare urologic emergency characterized by necrotizing infection of the external genitalia, perineum, and perianal region. To describe and compare reported cases of FG in diabetic adults receiving treatment with SGLT2 inhibitors or other antiglycemic agents. Descriptive case series. U.S. Food and Drug Administration (FDA) Adverse Event Reporting System and published case reports. Adults receiving SGLT2 inhibitors or other antiglycemic agents. Clinical and laboratory data. The FDA identified 55 unique cases of FG in patients receiving SGLT2 inhibitors between 1 March 2013 and 31 January 2019. The patients ranged in age from 33 to 87 years; 39 were men, and 16 were women. Time to onset after initiation of SGLT2-inhibitor therapy ranged from 5 days to 49 months. All patients had surgical debridement and were severely ill. Reported complications included diabetic ketoacidosis (n = 8), sepsis or septic shock (n = 9), and acute kidney injury (n = 4). Eight patients had fecal diversion surgery, 2 patients developed necrotizing fasciitis of a lower extremity that required amputation, and 1 patient required a lower-extremity bypass procedure because of gangrenous toes. Three patients died. For comparison, the FDA identified 19 FG cases associated with other antiglycemic agents between 1984 and 31 January 2019: metformin (n = 8), insulin glargine (n = 6), short-acting insulin (n = 2), sitagliptin plus metformin (n = 2), and dulaglutide (n = 1). These patients ranged in age from 42 to 79 years; 12 were men, and 7 were women. Two patients died. Inability to establish causality or incidence, variable quality of reports, possible underreporting, and confounding by indication. FG is a newly identified safety concern in patients receiving SGLT2 inhibitors. Physicians prescribing these agents should be aware of this possible complication and have a high index of suspicion to recognize it in its early stages. None.

Self-Induced Euglycemic Diabetic Ketoacidosis: When to Stop the Drip.

Diabetic ketoacidosis (DKA) is a well-known, serious complication that many patients with type 1 and 2 diabetes face due to either a relative or absolute insulin deficiency. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have gained increased popularity due to their diabetic, cardiovascular, and renal benefits. An associated complication of SGLT2 inhibitors is euglycemic DKA. A 56-year-old male with a history of type 2 diabetes mellitus and peripheral neuropathy presented with right foot pain secondary to a diabetic foot ulcer. The ulcer was present for one year, but the patient noticed increased pain and purulent discharge over the three days prior to presentation. While being treated inpatient for the foot ulcers, the patient repeatedly refused to receive standard hospital diabetes management of insulin injections. He instead insisted to take his home medications against medical advice, which were metformin and Glyxambi® (empagliflozin/linagliptin, Boehringer Ingelheim, Ingelheim am Rhein, Germany). His diabetic foot ulcer was medically managed with IV antibiotics.  On day 4 of admission, his anion gap increased to 23 mEq/L, and serum bicarbonate (CO2) decreased to 8 mEq/L, raising concerns of diabetic ketoacidosis. His glucose was 141 mg/dL, his beta-hydroxybutyrate was high at 5.5 mmol/L. An arterial blood gas (ABG) test demonstrated anion gap metabolic acidosis with secondary respiratory alkalosis. A urinalysis demonstrated glucose 1000 mg/dL and ketones of 150 mg/dL. The patient was diagnosed with euglycemic DKA. Due to the patient having normal glucose levels, an insulin drip and a 5% dextrose with 0.45% normal saline drip were started. Basic metabolic profiles were ordered every four hours, with glucose checks every hour. Once the anion gap was closed and his urinary ketones disappeared, the patient transitioned to subcutaneous insulin. He was able to be discharged home with basal subcutaneous insulin and metformin with instructions to avoid SGLT2 inhibitors in the future.  Unfortunately, there are currently no guidelines from endocrinology or internal medicine societies regarding the management of euglycemic DKA. As the typical DKA diagnostic criteria of elevated blood glucose level are not present, it is easy to overlook euglycemic DKA. As these SGLT2 inhibitors become more prevalent, careful monitoring of all potential side effects as well as the contraindications are prudent to successful management of complex disease states.

Canagliflozin

Canagliflozin, sold under the brand name Invokana among others, is a medication used to treat type 2 diabetes. It is a third-line medication to be tried after metformin, a first-line medication for type 2 diabetes. It is used together with exercise and diet. It is not recommended in type 1 diabetes. It is taken by mouth. Common side effects include vaginal yeast infections, nausea, constipation, and urinary tract infections. Serious side effects may include low blood sugar, Fournier's gangrene, leg amputation, kidney problems, high blood potassium, and low blood pressure. Diabetic ketoacidosis may occur despite nearly normal blood sugar levels. Use in pregnancy and breastfeeding is not recommended. Canagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor. It works by increasing the amount of glucose lost in the urine.

Type 2 diabetes

, there is insufficient data to recommend nonnutritive sweeteners, which may help reduce caloric intake. Medications Blood sugar control There are several classes of anti-diabetic medications available. Metformin is generally recommended as a first line treatment as there is some evidence that it decreases mortality; however, this conclusion is questioned. Metformin should not be used in those with severe kidney or liver problems. A second oral agent of another class or insulin may be added if metformin is not sufficient after three months. Other classes of medications include: sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, SGLT2 inhibitors, and glucagon-like peptide-1 analogs. As of 2015 there was no significant difference between these agents. A 2018 review found that SGLT2 inhibitors and GLP-1 agonists, but not DPP-4 inhibitors, were associated with lower mortality than placebo or no treatment.

Empagliflozin/linagliptin/metformin

Empagliflozin/linagliptin/metformin, sold under the brand name Trijardy XR, is a drug combination used for the treatment of type 2 diabetes. It is a combination of empagliflozin, linagliptin, and metformin. Empagliflozin/linagliptin/metformin was approved for use in the United States in January 2020. Adverse effects To lessen the risk of developing ketoacidosis (a serious condition in which the body produces high levels of blood acids called ketones) after surgery, the FDA has approved changes to the prescribing information for SGLT2 inhibitor diabetes medicines to recommend they be stopped temporarily before scheduled surgery. Empagliflozin should each be stopped at least three days before scheduled surgery. Symptoms of ketoacidosis include nausea, vomiting, abdominal pain, tiredness, and trouble breathing. History The combination preparation was developed and marketed by Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company. References External links

Dapagliflozin-associated euglycemic diabetic ketoacidosis in a patient with type 2 diabetes mellitus: A case report.

Rare cases of euglycemic diabetic ketoacidosis (eu-DKA) have been reported after the administration of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. No reports have described eu-DKA complicated by hypernatremia due to SGLT-2 inhibitors. A 76-year-old woman with a 40-year history of type 2 diabetes mellitus (DM), for which metformin (1000 mg/day) and dapagliflozin (10 mg/day) were prescribed, presented with malaise, fever, and oliguria. On presentation, her white blood cell count (11,800/μL), serum creatinine (3.2 mg/dL), and C-reactive protein (54 mg/L) were abnormal. Bilateral pyeloureteritis and diffuse paralytic ileus were present. She received intravenous antibiotics and total parenteral nutrition, and was asked to fast. Her renal function and ileus briefly improved. Oral hypoglycemic agents, metformin and dapagliflozin, along with enteral feeding were reinstituted on day 3 of hospitalization. However, on day 6 of hospitalization, the patient developed an altered state of consciousness including confusion, lethargy, and stupor. Several laboratory abnormalities suggestive of ketoacidosis with euglycemia were noted. The patient was diagnosed with eu-DKA accompanied by severe hypernatremia (corrected serum Na concentration, 163 mEq/L) and hypokalemia following dapagliflozin re-administration. The patient was treated with indicated intravenous fluid therapy. Dapagliflozin use was discontinued. The patient's mental status and laboratory findings improved gradually, and she was discharged on maintenance doses of insulin and metformin on day 14 of hospitalization. Acute illnesses such as diffuse paralytic ileus and urinary tract infection, and dietary restrictions or fasting in patients with DM can be considered potential predisposing factors for SGLT-2 inhibitor-associated eu-DKA. For patients with diabetes in the setting of acute morbidity, timely resumption of the SGLT-2 inhibitor therapy should be carefully determined. In addition, eu-DKA due to SGLT-2 inhibitor use may be accompanied by electrolyte disturbances such as hypernatremia and hypokalemia.

SGLT2-inhibitors are effective and safe in the elderly: The SOLD study.

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) may have important benefits for the elderly with type 2 diabetes (T2D), however some safety concerns still limit their use in patients over 70 years of age. The SOLD study (SGLT2i in Older Diabetic patients) is a multicenter study, aimed to evaluate the effectiveness and safety of SGLT2i in the older diabetic patients in a real-life setting. We analyzed a population of 739 adults (mean age 75.4 ± 3.9 years, M/F 420/319) with T2D, which started a SGLT2i-based treatment after the age of 70, with at least one year of follow-up. Data were collected at baseline, at 6 and 12 months of follow-up. SGLT2i (37.5% Empagliflozin, 35.7% Dapagliflozin, 26.1% Canagliflozin, 0.7% Ertugliflozin) were an add-on therapy to Metformin in 88.6%, to basal insulin in 36.1% and to other antidiabetic drugs in 29.6% of cases. 565 subjects completed the follow up, while 174 (23.5%) discontinued treatment due to adverse events which were SGLT2i related. A statistically significant reduction of glycated hemoglobin (baseline vs 12 months: 7.8 ± 1.1 vs 7.1 ± 0.8%, p < 0.001) and body mass index values (baseline vs 12 months: 29.2 ± 4.7 vs 28.1 ± 4.5 kg/m<sup2</sup, p < 0.001) were evident during follow-up. Overall, estimated glomerular filtration rate remained stable over time, with significant reduction of urinary albumin excretion. In the subgroup of patients which were ≥ 80 years, a significant improvement in glycated hemoglobin values without renal function alterations was evident. Overall discontinuation rate during the follow-up period was different across age groups, being urinary tract infections and worsening of renal function the most common cause. SGLT2i are well-tolerated and safe in the elderly and appear as an effective therapeutic option, though some caution is also suggested, especially in more fragile subjects.

Fixed-Dose Combination of Canagliflozin and Metformin for the Treatment of Type 2 Diabetes: An Overview.

Metformin is recommended as a first-line therapy for patients with type 2 diabetes mellitus (T2DM). However, many patients do not achieve glycemic goals with metformin monotherapy and require subsequent combination therapy with other antihyperglycemic agents (AHAs). For newly diagnosed patients with high blood glucose, initial combination therapy may be required to achieve glycemic control. The American Association for Clinical Endocrinologists algorithm for the treatment of T2DM recommends metformin plus a sodium glucose co-transporter 2 (SGLT2) inhibitor as the first oral combination in patients who present with HbA1c ≥7.5%. Canagliflozin, an SGLT2 inhibitor, lowers the renal threshold for glucose and increases urinary glucose excretion leading to a mild osmotic diuresis and a net caloric loss. The effect of canagliflozin is insulin-independent and complementary to other AHAs, including metformin. A fixed-dose combination (FDC) of canagliflozin and metformin is also available with variable dosing, which may be attractive to some patients owing to the potential for reduced pill burden and costs. This article reviews the efficacy and safety of canagliflozin in combination with metformin based on data from the canagliflozin phase 3 clinical program. As initial combination therapy in drug-naïve patients or as dual therapy with metformin or triple therapy in combination with metformin and other AHAs, canagliflozin 100 and 300 mg improved glycemic control and provided reductions in body weight and systolic blood pressure that were sustained for up to 104 weeks. Canagliflozin was generally well tolerated across studies in combination with metformin. An increased incidence of adverse events (AEs) related to the mechanism of SGLT2 inhibition (i.e., genital mycotic infections, urinary tract infections, osmotic diuresis-related AEs) was observed with canagliflozin. Canagliflozin was associated with a low incidence of hypoglycemia when not used in conjunction with AHAs associated with hypoglycemia (i.e., insulin or sulfonylurea). Together, these results support the use of a canagliflozin and metformin FDC as a treatment approach for a broad range of patients with T2DM. Janssen Scientific Affairs, LLC.

SGLT2 inhibitor

Medical uses The gliflozins are used to treat type 2 diabetes mellitus but are most often used as second- or third-line agents instead of first-line because there are other medications on the market that have much longer safety record and are less expensive than gliflozins. Gliflozins may be a good option for patients who are failing with metformin monotherapy, especially if reducing weight is part of the underlying treatment. They are often used in combination therapy, for example the dual therapy metformin plus gliflozin and the triple therapy metformin, sulfonylurea and gliflozin.

InternalMed_Harrison

lost 5–7% of their body weight during the 3 years of the study. Studies in Finnish and Chinese populations noted similar efficacy of diet and exercise in preventing or delaying type 2 DM. A number of agents, including α-glucosidase inhibitors, metformin, thiazolidinediones, GLP-1 receptor pathway modifiers, and orlistat, prevent or delay type 2 DM but are not approved for this purpose. Individuals with a strong family history of type 2 DM and individuals with IFG or IGT should be strongly encouraged to maintain a normal BMI and engage in regular physical activity. Pharmacologic therapy for individuals with prediabetes is currently controversial because its cost-effectiveness and safety profile are not known. The ADA has suggested that metformin be considered in individuals with both IFG and IGT who are at very high risk for progression to diabetes (age <60 years, BMI ≥35 kg/m2, family history of diabetes in first-degree relative, and women with a history of GDM). Individuals with IFG,

Empagliflozin

Treatment guidelines Guidelines by the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) recommend SGLT-2 inhibitors like empagliflozin as second-line medications after metformin for type2 diabetes in people with heart failure or chronic kidney disease. For type2 diabetes with established cardiovascular disease, the guidelines recommend either a SGLT-2 inhibitor or a GLP-1 agonist as second-line medications after metformin. In all other type2 diabetes cases, SGLT-2 inhibitors like empagliflozin can be appropriate second-line options if blood glucose control or weight loss are treatment priorities. They are less appropriate if cost is a major factor. In the United Kingdom empagliflozin is typically only recommended together with metformin if a sulfonylurea cannot be taken.

Combination therapy in type 2 diabetes mellitus: adding empagliflozin to basal insulin.

Type 2 diabetes mellitus (T2DM) management is complex, with few patients successfully achieving recommended glycemic targets with monotherapy, most progressing to combination therapy, and many eventually requiring insulin. Sodium glucose cotransporter 2 (SGLT2) inhibitors are an emerging class of antidiabetes agents with an insulin-independent mechanism of action, making them suitable for use in combination with any other class of antidiabetes agents, including insulin. This review evaluates a 78-week, randomized, double-blind, placebo-controlled trial investigating the impact of empagliflozin, an SGLT2 inhibitor, as add-on to basal insulin in patients with inadequate glycemic control on basal insulin, with or without metformin and/or a sulfonylurea. Empagliflozin added on to basal insulin resulted in significant and sustained reductions in glycated hemoglobin (HbA1c) levels compared with placebo. Empagliflozin has previously been shown to induce weight loss, and was associated with sustained weight loss in this study. This combination therapy was well tolerated, with similar levels of hypoglycemic adverse events in the empagliflozin and placebo groups over the 78-week treatment period. Urinary tract infections and genital infections, side effects associated with SGLT2 inhibitors, were reported more commonly in the empagliflozin group; however, such events led to treatment discontinuation in very few patients. These findings suggest that, with their complementary mechanisms of action, empagliflozin added on to basal insulin may be a useful treatment option in patients on basal insulin who need additional glycemic control without weight gain.

Ertugliflozin

Ertugliflozin, sold under the brand name Steglatro, is a medication for the treatment of type 2 diabetes. The most common side effects include fungal infections of the vagina and other infections of the female reproductive system. Ertugliflozin is a sodium/glucose cotransporter 2 (SGLT2) inhibitor and is in the class of drugs known as gliflozins. In the United States, it was approved by the Food and Drug Administration for use as a monotherapy and as a fixed dose combination with either sitagliptin or with metformin. In the European Union, it was approved in March 2018, for use as a monotherapy or combination therapy. In September 2020, The New England Journal of Medicine reported that ertugliflozin was shown to be essentially non-inferior to placebo. A combination with metformin is marketed as Segluromet and a combination with sitagliptin is marketed as Steglujan.

Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors: A Clinician's Guide.

This comprehensive review covers the historical background, physiology, application in type 2 diabetes, novel uses, cardiovascular benefits, side effects and contraindications of sodium-glucose cotransporter-2 (SGLT2) inhibitors. SGLT2 inhibitors are an insulin-independent class of oral antihyperglycemic medication that clinicians use in the treatment of type 2 diabetes. Multiple landmark clinical trials support the effectiveness of SGLT2 inhibitors in reducing blood glucose levels, but it is important to understand when to properly utilize them. SGLT2 inhibitors are the most beneficial as an adjunct medication in addition to metformin in patients with a history of cardiovascular or renal disease who need further hemoglobin A1c reduction. The novel mechanism of action also demands clinicians be aware of the side effects not typically experienced with other oral antihyperglycemic drugs, such as genital tract infections, lower leg amputations, electrolyte disturbances and bone fractures. On top of their benefits in type 2 diabetes, novel uses for SGLT2 inhibitors are being uncovered. Diabetic patients with non-alcoholic fatty liver disease, who are at an increased risk of cirrhosis and hepatocellular carcinoma, experience a clinically significant reduction in serum alanine aminotransferase levels. SGLT2 inhibitors are also effective at lowering body weight in obese individuals and decreasing systolic blood pressure. Dual SGLT1/SGLT2 inhibitors are currently being investigated as possibly the first oral medication for type 1 diabetes.

Empagliflozin/metformin

Empagliflozin/metformin, sold under the brand name Synjardy among others, is a fixed-dose combination anti-diabetic medication used to treat type 2 diabetes. It contains empagliflozin and metformin hydrochloride. It is taken by mouth. The most common side effects include hypoglycaemia (low blood sugar levels) when the medicine is taken with a sulphonylurea or insulin, infections of the urinary tract and genitals, and increased urination. It was approved for use in the European Union in May 2015, for use in the United States in August 2015, and for use in Australia in May 2020.

[Therapeutic options for a type 2 diabetic patient not well controlled with metformin plus basal insulin].

In a patient with type 2 diabetes not well controlled with a basal insulin - metformin combination, several therapeutic options may be considered: intensifying insulin therapy with different schemes (appropriate titration using a more favourable basal insulin analogue, adding one, two or three rapid-acting insulin analogues, shift to two or three premix insulin injections), adding a dipeptidyl peptidase-4 inhibitor (gliptin) or an inhibitor of sodium-glucose cotransporters type 2 (gliflozin), or combining a glucagon-like peptide-1 receptor agonist with basal insulin. The choice should be made according the individual profile and preference of the patient, in a personalized approach, taking into account the advantages and disadvantages of each therapeutic solution.

Appropriate Use of SGLT2s and GLP-1 RAs With Insulin to Reduce CVD Risk in Patients With Diabetes -- Other Issues -- Use of SGLT2 Inhibitors and GLP-1RAs with Insulin in Patients with Type 2 Diabetes

As stated above by the ADA guidelines, insulin is effective and preferred in patients with catabolic diabetes. In the absence of catabolic symptoms (weight loss or hemoglobin A1C greater than 10%), GLP-1RAs are an alternative to insulin. When hemoglobin A1C is markedly elevated but less than 10%, both basal insulin or a GLP-1RA can be used as add-on therapy to metformin, as they have been shown to have good glycemic efficacy in these patients. [49] GLP-1RAs have shown at-least comparable glycemic efficacy when compared to basal insulin with the added benefit of weight loss which is usually desirable in most of these patients. [49] For patients with moderately elevated hemoglobin A1C levels and established cardiac or renal disease, SGLT2 inhibitors or GLP-1RA should be added to metformin therapy before adding insulin or other agents due to their documented efficacy in improving cardiovascular mortality and slowing the progressive renal disease. In patients with a risk of hypoglycemia, GLP-1RA, SGLT2 inhibitors, and dipeptidyl peptidase 4 (DPP-4) inhibitors are the treatment of choice as they do not increase the risk of hypoglycemia as opposed to insulin.

Merck & Co.

Details of Merck's major products are as follows: Januvia (sitagliptin) is a dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. In 2013, Januvia was the second largest selling diabetes drug worldwide. Januvia is commonly paired with the generic anti-diabetes drug metformin. It has been popular due in part because unlike many other diabetes drugs, it causes little or no weight gain and is not associated with hypoglycemic episodes. Merck also sells a single pill combination drug containing both Januvia and metformin under the trade name Janumet. There has been some concern that treatment with Januvia and other DPP-IV inhibitors may be associated with a modestly increased risk of pancreatitis.

InternalMed_Harrison

As with any therapy, the benefits of efforts directed toward glycemic control must be balanced against the risks of treatment (Table 418-5). Side effects of intensive treatment include an increased frequency of serious hypoglycemia, weight gain, increased economic costs, and greater demands on the patient. In the DCCT, quality of life was very similar in 2417 the intensive and standard therapy groups. The most serious complication of therapy for DM is hypoglycemia, and its treatment with oral glucose or glucagon injection is discussed in Chap. 420. Severe, recurrent hypoglycemia warrants examination of treatment regimen and glycemic goal for the individual patient. Weight gain occurs with most (insulin, insulin secretagogues, thiazolidinediones) but not all (metformin, α-glucosidase inhibitors, GLP-1 receptor agonists, DPP-IV inhibitors) therapies. The weight gain is partially due to the anabolic effects of insulin and the reduction in glucosuria. As a result of recent controversies

InternalMed_Harrison

Considerable clinical experience exists with metformin and sulfonylureas because they have been available for several decades. It is assumed that the α-glucosidase inhibitors, GLP-1 agonists, DPP-IV inhibitors, thiazolidinediones, and SLGT2 inhibitors will reduce DM-related complications by improving glycemic control, but longterm data are not yet available. The thiazolidinediones are theoretically attractive because they target a fundamental abnormality in type 2 DM, namely insulin resistance. However, all of these agents are currently more costly than metformin and sulfonylureas. Patient with type 2 diabetes Individualized glycemic goal Medical nutrition therapy, increased physical activity, weight loss + metformin

[Therapeutic behavior to follow in the following clinical case: treatment of type 2 diabetes].

A 62-year old woman with obesity, high blood pressure and type 2 diabetes mellitus (DM2) was referred to a Vascular Risk Unit of the Internal Medicine Department due to elevated HbA1C (8.1%) in spite of having taken metformin (850 mg/12h) and glipizide (10 mg/12 h) regularly. She tries to exercise daily (walking 30 min) and has lost weight (from 5 to 12 kg) several times, but always regains what she has lost. Furthermore, she monitors her glucose levels in fasting every two weeks and generally has between 120 and 160 mg/dL. Her high blood pressure is being treated with enalapril/HCTZ and she also takes aspirin 100mg/day and simvastatin 20 mg/day. It is seen in her family background that one brother died suddenly at 50 years of age. Her physical examination shows a BMI of 32.4 Kg/m(2), and she has no edemas in the lower limbs. Her BP is 154/82 mmHg and creatinine 0.9 mg/dL. She has no microalbuminuria and her liver function is normal. What treatment do you think would be the more appropriate? 1 - Add glitazones. 2 - Add incretin mimetics (GLP 1/ DPP-4). 3 - Slow acting insulin.

Changes in treatment of hyperglycemia in a hypertensive type 2 diabetes population as renal function declines.

Cardiovascular complications associated with expensive noninsulin agents for type 2 diabetes are the focus of concern in light of the risk of kidney dysfunction with aging. Head-to-head comparisons are unavailable to guide the choice of new drugs for hyperglycemia in patients with type 2 diabetes, decreased estimated glomerular filtration rate (eGFR) and increased cardiovascular risk. A first approach would be to document current medication choices. All prescriptions for 10 151 patients (5623 males/4528 females) with both type 2 diabetes and hypertension seen two or  more times during a 5-year period (2007-12) at Joslin Diabetes Center were evaluated. {mean age 64 years [interquartile range (IQR) 64-65)], body mass index 31 kg/m<sup2</sup (IQR 30-32) and mean eGFR 78 mL/min/1.73 m<sup2</sup (IQR 78, 78)}. Insulin was used in >60% of patients, metformin in 50% and sulfonylurea derivatives in 25%. Dipeptidyl peptidase 4 (DPP4) and acarbose class drugs were prescribed in 10% of patients, GLP-1 in 8% and other classes [including thiazolidinediones (TZD)] in <5%. Patients were grouped into four drug <bCategories</b none, 447 (4%); insulin only, 3836 (38%); other than insulin, 2910 (29%) and insulin combinations, 2955 (29%). Common combinations included insulin/metformin [<in</i = 2493 (25%)], insulin/sulfonylureas [706 (7%)], metformin/sulfonylureas [2017 (20%)], metformin/GLP1 [949 ( 9%)], metformin/DPP4 [895 (9%)] and metformin/TZD [500 (5%)]. Insulin use increased to 70% from 35% as eGFR dropped to <30 mL/min/1.73 m<sup2</sup; use of insulin combined with other drugs dropped to 12% from 31% and the use of other drugs alone without insulin dropped similarly to 12% from 30%. Reduced renal function was associated with increased use of insulin and decreased use of other anti-diabetic agents in a statistically significant progression. BMI and gender did not influence medication choice.

Antidiabetic medication and risk of dementia in patients with type 2 diabetes: a nested case-control study.

Diabetes is a risk factor for dementia, but whether antidiabetic medication decreases the risk is unclear. We examined the association between antidiabetic medication and dementia. We performed a nested case-control study within a cohort of all 176 250 patients registered with type 2 diabetes in the Danish National Diabetes Register between 1995 and 2012. This population was followed for dementia diagnosis or anti-dementia medication use until May 2018. Using risk-set sampling, each dementia case (n = 11 619) was matched on follow-up time and calender year of dementia with four controls randomly selected among cohort members without dementia (n = 46 476). Ever use and mean daily defined dose of antidiabetic medication was categorized in types (insulin, metformin, sulfonylurea and glinides combined, glitazone, dipeptidyl peptidase 4 (DPP4) inhibitors, glucagon-like peptide 1 (GLP1) analogs, sodium-glucose transport protein 2 (SGLT2) inhibitors and acarbose). Conditional logistic regression models were fitted to calculate odds ratios (ORs) for dementia associated with antidiabetic medication use, adjusting for potential confounders. Use of metformin, DPP4 inhibitors, GLP1 analogs, and SGLT2 inhibitors were associated with lower odds of dementia after multible adjustments (ORs of 0.94 (95% confidence interval (CI): 0.89-0.99), 0.80 (95% CI 0.74-0.88), 0.58 (95% CI: 0.50-0.67), and 0.58 (95% CI: 0.42-0.81), respectively), with a gradual decrease in odds of dementia for each increase in daily defined dose. Analyses of the most frequent treatment regimes did not show any synergistic effects of combined treatment. Use of metformin, DPP4 inhibitors, GLP1 analogs and SGLT2 inhibitors was associated with lower risk of dementia in patients with diabetes.

A 74-year-old woman with diabetes.

Ms M, a 74-year-old woman with type 2 diabetes of 6 years' duration, has a glycated hemoglobin (HbA1C) value of 7.4% despite taking 3 oral antidiabetic medications, as well as coexistent hypertension and abdominal obesity. She has no known microvascular or macrovascular complications of diabetes and is otherwise healthy. She is reluctant to commence insulin treatment as she dislikes the idea of injections and wonders if there are any alternate options if she is to get her HbA(1C) value below 7%. The natural history of type 2 diabetes, reasons why many patients begin requiring insulin over time, rationale for tight glycemic control, and therapeutic options for Ms M are discussed.

Cost-effectiveness of intensification with SGLT2 inhibitors for type 2 diabetes.

Using a US payer perspective, this study aimed to compare the lifetime cost-effectiveness of adding sodium-glucose cotransporter 2 (SGLT2) inhibitors vs switching to glucagon-like peptide 1 receptor agonists (GLP-1 RAs) among patients with type 2 diabetes who were not at glycated hemoglobin A1c target after dual therapy with metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors. The cost-effectiveness analysis was performed with the validated IQVIA Core Diabetes Model. Treatment effects were obtained from randomized clinical trials with economic data based on published literature. Risk of treatment-emergent adverse events and complications were simulated using submodels informed by published risk equations adjusted for patient characteristics, physiological parameters, and history of complications. Outcomes included cumulative incidence of micro- and macrovascular complications, life-years (LYs), quality-adjusted life-years (QALYs), and total costs. Scenario analyses were performed to assess robustness of results to variations in clinical and cost inputs and assumptions. Over a lifetime time horizon, adding an SGLT2 inhibitor dominated the strategy of switching to a GLP-1 RA, improving survival by 0.049 LYs and 0.026 QALYs, and was associated with cost savings of $9511. The majority of the scenario analyses confirmed dominance of the DPP-4 inhibitor + SGLT2 inhibitor pathway vs the GLP-1 RA pathway. The probabilistic sensitivity analysis reinforced the base-case finding of cost savings while gaining QALYs. Intensification with an SGLT2 inhibitor on top of a DPP-4 inhibitor demonstrated slightly better efficacy and cost savings compared with switching to a GLP-1 RA in patients not at glycemic goal with metformin and a DPP-4 inhibitor.

Second-line Glucose-Lowering Therapy in Type 2 Diabetes Mellitus.

There is consensus that metformin should be the first-line pharmacological therapy for type 2 diabetes. Although new evidence on effective treatments for type 2 diabetes is rapidly evolving, there is uncertainty regarding the optimal choice of second-line therapy. Our aim was to review the current major guidelines for second-line therapy in type 2 diabetes, along with findings from the recent cardiovascular outcome trials, focusing on two particularly promising classes of glucose-lowering drugs, sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP1 RAs). In the recent randomized controlled trials, two SGLT2 inhibitors (i.e., empagliflozin and canagliflozin) and two GLP1 RAs (i.e., liraglutide and albiglutide) reduced cardiovascular events in patients with type 2 diabetes, of whom most had established atherosclerotic cardiovascular disease. Some clinical guidelines have changed their recommendations for second-line therapy based on these findings. The first choice for a second-line therapy by the new American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) guidelines is SGLT2 inhibitors or GLP1 RAs for patients with atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease. For patients without these conditions, the ADA/EASD lists five options of noninsulin second-line therapy without a suggested hierarchy of use. On the other hand, the 2019 consensus statement from the American Association of Clinical Endocrinologists/American College of Endocrinology lists nine hierarchical options, with GLP1 RAs as the first recommended therapy, followed by SGLT2 inhibitors and dipeptidyl peptidase 4 (DPP4) inhibitors, and sulfonylurea as the last option. The American College of Physicians recommends four oral treatment options, which do not include GLP1 RAs. The International Diabetes Federation recommends sulfonylureas, DPP4 inhibitors, or SGLT2 inhibitors as preferred second-line drugs with GLP1 RAs as an alternative in obese patients. The World Health Organization strongly recommends sulfonylureas in low-resource settings. The National Institute for Health and Care Excellence in the UK recommends DPP4 inhibitors, thiazolidinediones, or sulfonylureas, with use of SGLT2 inhibitors only under special circumstances. Clinical guidelines for the choice of second-line therapy in type 2 diabetes are inconsistent. A comprehensive assessment of the risks and benefits of second-line therapy is needed to address knowledge gaps that underlie core clinical practice.

[DPP-4 or SGLT2 inhibitor added to metformin alone in type 2 diabetes].

After failure of a monotherapy with metformin, dipeptidyl peptidase-4 inhibitors (gliptins) and sodium-glucose cotransporters type 2 (gliflozins) offer an alternative to the add-on of a sulphonylurea, especially in diabetic patients at risk of hypoglycaemia. The choice between a gliptin and a gliflozin may be guided by the individual patient characteristics : rather a gliptin in a patient without obesity or severe hyperglycaemia, in an elderly patient, with a frailty profile or with renal impairment; rather a gliflozin in an obese patient, with hypertension, hyperuricaemia, antecedents of cardiovascular disease (especially heart failure), without advanced renal insufficiency and with a low risk of urinary/genital infections or events linked to dehydration such as hypotension.


Germinal tumors are the most frequent in children in the pineal region. They usually capitate homogeneously and cause triventricular hydrocephalus and Parinaud. Glioblastomas usually occur in adults at the lobar level, medulloblastomas are the most frequent malignant tumors at the posterior fossa level in children (vermis and roof of the IV ventricle) but rare at the pineal level and meningiomas are rare in children and also in the pineal region.

Germinal tumors are the most frequent in children in the pineal region. They usually capitate homogeneously and cause triventricular hydrocephalus and Parinaud. Glioblastomas usually occur in adults at the lobar level, medulloblastomas are the most frequent malignant tumors at the posterior fossa level in children (vermis and roof of the IV ventricle) but [HIDDEN] at the pineal level and meningiomas are rare in children and also in the pineal region.

A 13-year-old boy presents with subacute headache and diplopia. Neurologic examination shows vertical gaze palsy and MRI shows a contrast-enhancing lesion in the pineal region obstructing the aqueduct of Sylvius. The most likely diagnosis is:

Neuro-oncology

5. Pituitary Region Tumors A wide variety of tumors can occur in and around the sella turcica. The most common tumors in this region are craniopharyngiomas, pituitary adenomas, meningiomas, and optic chiasm gliomas. Visual impairment is a common presenting symptom, due to compression or invasion of the optic chiasm. 6. Germ Cell and Pineal Region Tumors Most tumors of the pineal region are either germinomas or pineal cell tumors, and are tumors of adolescents and young adults. Presentation relates to the location in the nervous system. 7. Medulloblastoma and Other Primitive Neuroectodermal Tumors Medulloblastoma and other primitive neuroectodermal tumors (PNETs) are a group of highly aggressive central nervous system tumors with a tendency to spread via cerebrospinal fluid pathways. These typically are tumors of childhood and young adulthood. 8. Meningiomas and Other Meningeal Tumors

[Unilateral supranuclear abducens palsy in a pineal tumor].

A 13-year-old boy complained of frequent headaches and diplopia on rightward gaze. A CT scan demonstrated hydrocephalus and a non-homogeneous enhancing mass in the pineal area, leading to a diagnosis of pineal tumor. The physical examination revealed no abnormalities. On neurological examination, there were a right homonymous hemianopsia and slight choked disc in both optic fundi. His right eye was slightly adducted on primary gaze. On right lateral gaze, his right eye could not move beyond the midline and showed gaze paretic nystagmus, whereas his left eye could move fully in all directions. The abducens palsy could be overcome by the oculocephalic maneuver or caloric test. Interestingly, his right eye could abduct when his left eye was covered. From these finding, this was labelled a supranuclear abducens palsy. The convergent nystagmus was observed. Rightward OKN (quick phase to right) of the right eye was abolished with and without the left eye covered, while leftward OKN of the right eye was preserved. Pursuit to right was disturbed. After removal of the tumor, the gaze palsies disappeared. It is postulated that the supranuclear lateral gaze palsy was caused by impairment of supranuclear control by involvement of lateral gaze pathways to gaze center coursing near the oculomotor nucleus.

Pineal mixed germ cell tumor with a synchronous sellar lesion in the sixth decade.

Intracranial germ cell tumors (GCTs) typically affect children and adolescents. We here report on a 59-year-old male patient presenting with diplopia, polydipsia and polyuria. On clinical examination, slight restriction of the upward gaze was seen on the left side. Computed tomography demonstrated calcifications in the pineal region and enhanced neurohypophysis. Magnetic resonance imaging displayed a heterogeneous pineal mass of 3-cm diameter, which was multicystic with an enhanced cyst wall, and also swelling of the pituitary stalk. The pineal lesion of the tumor, which included calcifications and keratinaceous components, was totally excised using an occipital transtentorial approach. Histopathological examination showed it to be a mixed GCT with germinoma and mature teratoma components. Postoperative chemoradiotherapy provided complete disappearance of the suprasellar lesion. To our knowledge, this is the first case of mixed bifocal GCT in an older adult reported in the literature, although a few cases of tumors with a single histological component have been reported. Hence, our case further underlines the possibility of the occurrence of GCTs in older adults and advocates the consideration of GCTs in the differential diagnosis of such cases for appropriate management.

Fast-developing fatal diffuse leptomeningeal dissemination of a pineal germinoma in a young child: a case report and literature review.

Intracranial germinomas are uncommon and constitute less than 1% of all intracranial tumors. They usually arise in the midline of the brain, most commonly in the pineal region. Pineal germinomas tend to spread through the cerebrospinal fluid (CSF). However, pineal germinomas with fast-developing diffuse subarachnoid/leptomeningeal dissemination are extremely rare, especially in young children. The case of a 4-year-old boy with a pineal germinoma who died of diffuse subarachnoid/leptomeningeal dissemination 1 month after radiotherapy is reported. A PubMed search with specific key terms was used to review cases of pineal germinomas with metastasis. The patient presented with a two-week history of worsening headache, visual disturbances and nonprojectile vomiting. Parinaud's sign was positive on physical examination. Head computed tomography (CT)/magnetic resonance imaging (MRI) revealed a lesion in the pineal region with eccentric calcification and obvious supratentorial hydrocephalus. Pineal germinoma was suspected. A ventriculoperitoneal (VP) shunt followed by focal radiotherapy ameliorated the headaches and visual disturbances. The patient was discharged home without further treatment due to financial difficulties. One month after discharge, he was readmitted due to worsening headache, vomiting and lethargy. MRI showed a decrease in the size of the pineal lesion but revealed a diffuse leptomeningeal enhancement including the sulcus, basal cistern, prepontine cistern, and supravermian cistern. The patient's condition deteriorated rapidly, and he died 26 hours after readmission. The characteristics of pineal germinomas with metastasis are reported based on a review of the literature. Metastases in pineal germinomas predominately occur in adolescents or young adults, most commonly as spinal "drop metastases." Dissemination usually develops several years after the initial tumor diagnosis and has a relatively good clinical prognosis. However, fast widespread subarachnoid/leptomeningeal dissemination and sudden death may occur in a young child before salvage treatment, as in the presented case.

An unusual location for a choroid plexus papilloma: the pineal region.

Choroid plexus papillomas (CPP) are rare benign neoplasms of the central nervous system that occur most often in children during the first decade of life. They occur most often in the lateral ventricle. It is extremely rare for a CPP to occur in the pineal region. We describe the case of a child with a CPP located in the pineal region, who was initially diagnosed with obstructive hydrocephalus by cranial computed tomography (CT). A 9-year-old female patient presented with complaints of visual disturbance, nausea, and vomiting. Magnetic resonance imaging (MRI) showed a poor contrast-enhanced pineal-localized lesion. Anatomical variations within the patient caused her surgery to proceed using a supratentorial-occipital interhemispheric approach. The tumor was totally removed, and a histological examination revealed the tumor to be a typical CPP. The patient received follow-up neurological and ophthalmologic examinations at 3, 6, 9, 12, 24, and 36 months postoperatively, which demonstrated her progressive improvement. CPPs may have a wide range of locations and resulting symptoms. However, the pineal region is a rarely encountered location, particularly for pediatric patients. It is of great value to correctly differentiate neoplasms such as germ cell tumors, pineocytomas, meningiomas, and astrocytomas, so that patients receive the correct diagnosis and treatment approach.

Neuroophthalmic Manifestations of Intracranial Tumours in Children.

All children between 0 and 16 years presenting with brain tumours confirmed by Magnetic Resonance Imaging (MRI) and treated surgically in our institute were included in this study. The aim of this study is to evaluate the neuroophthalmic and clinical characteristics of intracranial space occupying lesions in children. Neuroophthalmic manifestations along with location of the tumour by contrast-enhanced MRI, type of surgical intervention, and postoperative histopathological diagnosis were evaluated. In pediatric brain tumours, male preponderance was seen and supratentorial location was more common in general, while in older children, infratentorial tumours were more common than supratentorial tumours. Headache, vomiting, and cerebellar signs were the commonest neurological features. Diminution of vision, diplopia, and strabismus were the commonest ophthalmic symptoms. Papilledema, ophthalmoparesis, and nystagmus were the most frequent ophthalmological signs. Neurological manifestations of seizures, altered sensorium and motor deficits were more frequently seen in supratentorial tumours, while cranial nerve involvement and ataxia were seen in infratentorial tumours. Ophthalmological manifestations including diplopia, strabismus, ophthalmoparesis, and nystagmus were more frequently seen in infratentorial tumours. Astrocytoma was the most frequent histopathological diagnosis followed by medulloblastoma. Diagnosis of pediatric intracranial tumours is complex and requires a multidisciplinary approach for prompt management. An ophthalmologist should have a high index of suspicion for brain tumours especially in patients presenting with common ocular symptoms like diminution of vision, diplopia, and strabismus without any neurological symptoms.

Medulloblastoma

The cumulative relative survival rate for all age groups and histology follow-up was 60%, 52%, and 47% at 5 years, 10 years, and 20 years, respectively, with children doing better than adults. Signs and symptoms Signs and symptoms are mainly due to secondary increased intracranial pressure due to blockage of the fourth ventricle and tumors are usually present for 1 to 5 months before diagnosis is made. The child typically becomes listless, with repeated episodes of vomiting, and a morning headache, which may lead to a misdiagnosis of gastrointestinal disease or migraine. Soon after, the child will develop a stumbling gait, truncal ataxia, frequent falls, diplopia, papilledema, and sixth cranial nerve palsy. Positional vertigo and nystagmus are also frequent, and facial sensory loss or motor weakness may be present. Decerebrate attacks appear late in the disease.

Germ Cell Seminoma -- History and Physical

Pineal region tumors usually present with signs and symptoms of increased intracranial pressure (headache, nausea, vomiting, papilledema) due to obstructive hydrocephalus. Neuroophthalmological abnormalities are also present, which include diplopia and Parinaud syndrome characterized by upward gaze paralysis, loss of light perception, loss of convergence, and nystagmus. [4]

Pineal Region Meningioma in a Very Young Child.

Meningiomas in childhood are infrequently seen. Furthermore, they are extremely rare at a pineal location with few reported cases above 5-years of age. We present a very young child with a large pineal region meningioma which mimicked the usually occurring pathologies at this site. A 2.5-year-old child presented with symptoms of raised intracranial pressure. MRI demonstrated a homogenously enhancing pineal lesion with small cystic areas. After an initial cerebrospinal fluid evaluation for germ cell tumors, the child underwent excision of the lesion by the Krause approach. The tumor showed no definitive dural attachment, had well-defined arachnoid interface, and was completely excised. The final histopathology was meningioma. Although unusual, we highlight the importance of considering meningiomas among the childhood pineal region lesions, given their good outcome with total resection. Also, pertinent brief literature of the pediatric pineal region meningiomas has been provided. An assessment of preoperative and intraoperative features (clear arachnoid plane) along with adjuncts such as frozen studies can help discern various entities of this region, and decide the extent of excision.

Sphenoid wing meningioma

Tumors found in the external third of the sphenoid are of two types: en-plaque and globoid meningiomas. En plaque meningiomas characteristically lead to slowly increasing proptosis with the eye angled downward. Much of this is due to reactive orbital hyperostosis. With invasion of the tumor into the orbit, diplopia is common. Patients with globoid meningiomas often present only with signs of increased intracranial pressure. This leads to various other symptoms including headache and a swollen optic disc. The differential diagnosis for sphenoid wing meningioma includes other types of tumors such as optic nerve sheath meningioma, cranial osteosarcoma, metastases, and also sarcoidosis. Following the physical exam, the diagnosis is confirmed with neuro-imaging. Either a head CT or MRI with contrast such as gadolinium is useful, as meningiomas often show homogenous enhancement. Angiography looking for signs like stretched arteries may be used to supplement evaluation of vascular

InternalMed_Harrison

A large number of tumors can arise in the region of the pineal gland. These typically present with headache, visual symptoms, and hydrocephalus. Patients may have Parinaud syndrome characterized by impaired upgaze and accommodation. Some pineal tumors such as pineocytomas and benign teratomas can be treated simply by surgical resection. Germinomas respond to irradiation, whereas pineoblastomas and malignant germ cell tumors require craniospinal radiation and chemotherapy. Meningiomas are diagnosed with increasing frequency as more people undergo neuroimaging for various indications. They are now the most common primary brain tumor, accounting for approximately 35% of the total. Their incidence increases with age. They tend to be more common in women and in patients with neurofibromatosis type 2. They also occur more commonly in patients with a past history of cranial irradiation.

Central neurocytomas of uncommon locations: report of two cases.

We report two patients with central neurocytomas at an uncommon location in the brain. The first, a 58-year-old man presenting with signs and symptoms of increased intracranial pressure, had a tumor located at the pineal region. The second, a 21-year-old woman with tumor in the aqueductal region had worsening migraine-like headaches and diplopia. Both patients had obstructive hydrocephalus treated by neuroendoscopic third ventriculostomy and biopsy of the tumors. No additional treatment was done. We conclude that neurocytomas should be considered in the differential diagnosis of tumors located in the pineal and aqueductal regions.

Pediatrics_Nelson

Brain tumors are the second most common neoplasm in children. About 50% arise from within the posterior fossa. Tumors that arise in the posterior fossa or brainstem produce progressive ataxia with headache that may be acute or gradual in onset. There is a progressive worsening over days, weeks, or months, typically with associated signs and symptoms of elevated intracranial pressure. The ataxia and dysmetria may result from primary cerebellar invasion or from obstruction of the CSF pathways (aqueduct of Sylvius or fourth ventricle) with resultant hydrocephalus. The most common tumors in this region include medulloblastoma, ependymoma, cerebellar astrocytoma, and brainstem glioma.

Pediatrics_Nelson

If an intracranial lesion is suspected, magnetic resonance imaging (MRI) is currently the examination of choice (Fig. 157-1). Examination of CSF by cytocentrifuge histologic testing is essential to determine the presence of metastatic disease in primitive neuroectodermal tumors, germ cell tumors, and pineal region tumors. A lumbar puncture should not be performed before imaging has been obtained to evaluate for evidence of increased intracranial pressure. If a tumor is Figure 157-1 Magnetic resonance imaging scan of a 9-year-old boy showing a heterogeneously enhancing fourth ventricular mass (arrow). It was resected, and pathology revealed medulloblastoma.

[Problems on recurrence after removal of teratoma in pineal region--an experience of recurrence of pineal teratoma 4 years after tumor removal].

A case of teratoma in the pineal region which recurred 4 years after the first tumor removal was reported in this paper. When the patient was 5 years old, she, complained of headache and vomiting, and visited our hospital. As a heterogeneous mass with no enhancement effect was found in the pineal region by CT scan, she was admitted on November 9, 1976. There was no abnormalities on physical examination but neurological examination revealed slight disturbance of conjugate upward gaze (Parinaud's sign). Left vertebral angiogram demonstrated posterior superior displacement of posterior choroidal artery and downward displacement of Rosenthal vein, but early venous filling and tumor stain were not seen. Under preoperative diagnosis of a teratoma in the pineal region, the first operation (left occipital craniotomy and total removal of the tumor) was performed on November 24, 1975. Microscopic examinations revealed that the removed tumor was a mature teratoma in the pineal region. Postoperative course was uneventful and discharged on December 20, 1975. The follow-up study was continued at outside clinic after discharge. There was no signs of recurrence until 3 years after the first operation, but on January, 1981 (4 years after the first operation), she suffered from severe headache and vomiting again and re-admitted to our hospital on February 3, 1981. There was no remarkable neurological deficits except for the mild intracranial hypertensive sign and no changes of findings on angiogram. But CT findings were markedly characteristic. It revealed a heterogenous mass with remarkable enhancement effect in the pineal region and ventricular enlargement. Because a mixed type (teratomatous and germinomatous) of pineal tumors was suspected from the CT findings, irradiation was done after V-P shunt. The tumor was reduced to half size after the first course of 2000 rads irradiation, but there is no more reduction of the size of the tumor following the second course of 2000 rads (total 4000 rads) irradiation. Against the residual tumor, tumor removal was performed on June 2, 1981. Microscopically, the most part of the resected tumor showed fibrous changes caused by irradiation and partially teratomatous compartment. From this result (radiosensitivity and histology) the authors assumed that the recurred tumor could be a mixed type (germinoma and teratoma) of pineal tumor. Postoperative course was uneventful except for a transient disturbance of conjugate upward gaze and she was discharged on June 25, 1981. And now, there is no signs of recurrence 12 months after the second operation. Conclusively, it will be stressed that we should continue follow-up study the case even after total removal of teratoma, especially in the pineal region. Moreover, it was considered that there is a possibility of the changes of the histological features on recurrence of the pineal teratoma. When germinomatous compartment is suspected, irradiation is the first choice and then microsurgical operation should be done against residual tumor.

[A case of pineal teratoma arising from hydrocephalus of unknown cause].

We report a case of "functional aqueductal stenosis" which reveals dilatation of the lateral and 3rd ventricles without stenosis at the aqueduct in MRI. This case shows a pineal teratoma which presents one year later with symptoms of hydrocephalus caused by "functional aqueductal stenosis". A seven-year-old boy was admitted to our department owing to headache and vomiting. CT and MRI showed hydrocephalus. The lateral and 3rd ventricles were dilated while the 4th ventricle was normal. Furthermore, tumoral obstruction of the aqueduct was not found. After a ventriculoperitoneal shunt, he recovered well without neurological deficits. One year later, symptoms of precocious puberty, that is the appearance of public hair and deepening of his voice, were found. A follow-up MRI demonstrated a pineal region tumor. Although human chorionic gonadotropin level in the serum and urine was transiently elevated, it normalized before surgery. The operation was performed by the occipital transtentorial approach and the tumor was totally removed. Histological examination proved this tumor to be a mature teratoma, showing three germ cell layers. About two weeks later, he was discharged without any neurological deficit. In this case, although hydrocephalus occurred, MRI didn't demonstrate aqueductal obstruction caused by the tumor. However, one year later, a pineal region tumor was confirmed by MRI. This suggests that hydrocephalus might have some association with the appearance of the pineal region tumor. Therefore, it is necessary to be aware of the possibility of the occurrence of tumors whenever we encounter "functional aqueductal obstruction", when MRI doesn't demonstrate aqueductal obstruction caused by a tumor.

Unusual clinical presentation of a presumed pineal germinoma with two disseminated lesions.

We report a case of a presumed pineal germinoma in a 28-year-old man. Although the pineal body, the presumed primary lesion, was small, there were two disseminated tumors, one in the posterior fossa and the other in the left parietal region. The initial symptom was cerebellar ataxia. These two disseminated tumors had attachments to the inferior surface of the cerebellar tentorium and the dura mater of the parietal convexity, respectively, and they were fed by external carotid artery branches, like meningiomas. Neither angiography nor magnetic resonance imaging could provide the differential diagnosis between germinoma and meningioma. Computed tomographic scanning revealed slight enlargement of the pineal body suggestive of a germinoma.

Glioblastoma multiforme of the pineal region: case report.

pineal region tumors are uncommon, and comprise more frequently three categories: germ cell, parenchymal cell and glial tumors. Most pineal gliomas are low-grade astrocytomas. Glioblastoma multiforme, the most aggressive and common brain tumor, is extremely rare at this location with only few cases reported. a 29-year-old woman with a two month history of headache, nuchal pain, fever, nausea and seizures and physical examination showing nuchal rigidity, generalized hypotony, hypotrophy and hyper-reflexia, Babinski sign and left VI cranial par palsy. CT scan examination revealed a ill-defined hypodense lesion at the pineal region with heterogeneous contrast enhancement. MRI showed a lesion at the pineal region infiltrating the right thalamic region. The patient underwent a right craniotomy with partial resection of the mass. The histological examination of paraffin-embedded material defined the diagnosis of glioblastoma multiforme. Post-operative radiotherapy was indicated but the patient refused the treatment and died two months afterwards. in spite of its rarity at this location, glioblastoma multiforme should be considered in the differential diagnosis of aggressive lesions at the pineal region.

Neurology_Adams

When any of the several clinical syndromes caused by metastatic tumor is fully developed, diagnosis is relatively easy. If only headache and vomiting are present, a common problem is to attribute them to migraine or tension headache. One should invoke such explanations only if the patient has the standard symptoms of one of these conditions. CT with contrast will detect practically all sizable (1 cm) metastases though MRI with gadolinium is much more sensitive especially for cerebellar and subcentimeter lesions, and will expose associated leptomeningeal disease. Multiple nodular deposits of tumor in the brain on imaging studies most clearly distinguish metastatic cancer from other tumors but this pattern may also occur with brain abscesses, brain lymphoma, and glioblastoma.

Neuro-otology symptoms as the early sign in pediatric patient with a pineal gland tumor: a case report.

Patients with pineal tumors are often asymptomatic and the symptoms depend on the location of the mass. In fact, around 3%-8% of pediatric brain tumor cases are pineal tumors. Children with pineal tumors may present with dizziness and vertigo as early signs. These symptoms are common conditions among 5-15 years old children and could probably lead to misdiagnoses. We present a case of 14-year-old who came to the emergency room of DR. Soetomo Hospital Surabaya with neurotologic symptoms. After a series of radiographic and laboratory examinations, he was diagnosed with germinoma. A ventriculoperitoneal shunt was performed in the emergency room and intravenous dexamethasone was administered.

Pineal region lesion masquerading choroid plexus papilloma: case report.

Choroid plexus papillomas (CPPs) are rare intracranial neoplasms, especially in the third ventricle. We report a patient with a posterior third ventricular CPP extending into the pineal that radiographically and clinically presented as a pineal region lesion. In a 51-year-old female with headache and upward gaze impairment radiological examination showed a mass in the pineal region obstructing the aqueduct of Sylvius and causing hydrocephalus. After ventriculoperitoneal shunting the tumor was approached through the infratentorial-supracerebellar approach and pathological examination revealed a typical CPP. This case represents an unusual presentation of an intracranial CPP. This entity should be considered an extremely rare cause of a lesion in the pineal region.

Clinical diagnostic dilemma of intracranial germinoma manifesting as wide skull base extension.

The aims of this study were to present an uncommon intracranial germinoma manifesting as skull base extension and analyze its clinical characteristics to give valuable insight into such uncommon radiologic variant. This is a clinical study of a 15-year-old girl with intracranial germinoma manifesting as skull base extension. Clinical characteristics, magnetic resonance imaging scan observations, pathologic findings, and flow of the treatment procedure were presented and analyzed. She had a 5-month history of diuresis and diplopia. magnetic resonance imaging observation displayed a neoplasm located in the right-side central skull base and suprasellar area with wide extension into the cavernous sinus, intraorbital region, ethmoidal sinus, sphenoid sinus, and pituitary fossa. After administration of contrast medium, strong and heterogeneous enhancement of the mass was observed, with a dural tail sign along the right cerebellar tentorial. Right pterional approach was performed, and intraoperative histologic examination suspected the diagnosis of germinoma; partial resection was achieved, and postoperative radiotherapy was administered. Cranial nerve palsy improved greatly 6 months postoperatively. Although highly unusual, germinoma should be included in the differential diagnosis of all masses with extension along the midline region of skull base, especially when it happens in young female patients.

[Medulloblastoma originating from the superior cerebellar peduncle: a case report].

A rare case of medulloblastoma originating from the superior cerebellar peduncle is reported. After tilting her neck to the right, a 4-year-old girl experienced a left-side hemiparesis for 3 months. Computed tomography (CT) scan and magnetic resonance image (MRI) showed an enhanced mass in the left tentorial incisura. The preoperative diagnosis was trochlear nerve neurinoma or tentorial meningioma, while the postoperative pathological diagnosis was medulloblastoma. Since medulloblastoma is thought to originate from the external granular layer, it is speculated that the external granular layer migrated through the superior cerebellar peduncle and changed to medulloblastoma.

Immature teratoma of the tectum mesencephali with histopathological detection of rudimentary eye anlage in a 3-year-old boy: Report of a rare case.

Intracranial teratoma is a rare neoplasm derived from omnipotent germinal cells that can contain mesoderm, endoderm and/or ectoderm layer tissue. Histologically teratomas are characterized by abnormal structures like teeth or bone that can be further subdivided into mature and immature according to the presence of incompletely differentiated tissue. Characteristic intracranial teratomas are space-occupying lesions in the pineal region and often present with hydrocephalic symptoms due to aqueduct stenosis. A 3-year-old boy presented with a peracute hemiparesis, fatigue and speech deficit. MRI diagnostics showed a cystic, partially solid, inhomogeneous contrast-enhancing formation at the top of the tectum mesencephali with consecutive aqueduct compression. The patient underwent a sub-occipital craniotomy via a supracerebellar approach and complete resection was achieved. The histopathological examination mainly showed mature tissue of ectodermal, mesodermal and endodermal origin. However, small areas of undifferentiated neuroectodermal tissue within an optic vesicle formation were detected, leading to the diagnosis of an immature teratoma. In due course, the patient was discharged in good health without neurological deficits. To our knowledge, optic vesicle-containing intracranial germ cell tumors are extremely rare. Here we report a unique case with immature neuroectodermal tissue within an optic vesicle formation in an otherwise mature teratoma.

Neurology_Adams

Vomiting appears in a relatively small number of patients with a tumor syndrome and usually accompanies the headache when the latter is severe. It is more frequent with tumors of the posterior fossa. The most persistent vomiting (lasting several weeks) that we have observed has been in patients with low brainstem gliomas, fourth ventricular ependymomas, and subtentorial meningiomas. Some patients may vomit unexpectedly and forcibly without preceding nausea (“projectile vomiting”), a sign that is fairly specific to tumor in children, but others suffer nausea and severe discomfort. Usually the vomiting is not related to the ingestion of food, and, often, it occurs before breakfast.

Spontaneous regression of germinoma in the pineal region before endoscopic surgery: a pitfall of modern strategy for pineal germ cell tumors.

Since its introduction in the neurosurgical field, neuroendoscopy has played an important role in the treatment of pineal germ cell tumors. The authors report a case of pineal germinoma revealing spontaneous regression before neuroendoscopic surgery. A 15-year-old boy presented with chronic headache, deterioration of his visual acuity, and diplopia. Head magnetic resonance imaging (MRI) revealed a large tumor in the pineal region and triventricular hydrocephalus due to occlusion of the aqueduct. As levels of tumor markers in serum and cerebrospinal fluid, including those of alpha-fetoprotein, carcinoembryonic antigen, human chorionic gonadotropin (hCG), and the beta-subunit of hCG, were all within the normal ranges, endoscopic surgery for biopsy and third ventriculocisternostomy was performed. Under endoscopic view, the tumor was revealed to be smaller than expected from preoperative images. MRI obtained 14 days after admission disclosed marked shrinkage of the tumor. The histopathological diagnosis was pure germinoma, and the patient underwent chemotherapy combined with fractionated radiotherapy. The tumor disappeared, and the patient did not show any signs of relapse. Spontaneous regression is a very rare phenomenon in malignant brain tumors, and in the literature it has been uncommonly described in pineal germ cell tumors. Our case disclosed a pitfall of modern strategy for this pathology with neuroendoscopy. Dilated ventricles and a certain amount of lesion are factors for safe endoscopic biopsy of pineal tumors. Radiographic images shortly before surgery are warranted, especially in patients whose symptoms of intracranial hypertension have already improved before surgery.

A suprasellar cystic germ cell tumor initially diagnosed as an arachnoid cyst.

We report here the case of a suprasellar cystic germ cell tumor (GCT) initially diagnosed as an arachnoid cyst. A 10-year-old boy experienced headache, dizziness, and diplopia, and was shown to have an approximately 2 cm suprasellar cyst. Two months after endoscopic third ventriculostomy was performed, a 5-6 cm cystic mass with an internal enhancing component was observed in the suprasellar cistern. Serum human chorionic gonadotropin levels were slightly increased in the serum and cerebrospinal fluid (55 and 162 IU/L, respectively) but were strikingly elevated in the cystic fluid (14,040 IU/L). The patient showed complete remission, with only a very small cystic lesion remaining after surgery, chemotherapy, and radiation treatment for a suprasellar mixed GCT. However, follow-up after treatment was complicated by moyamoya syndrome and cerebral infarction. GCT can be considered as a rare differential diagnosis in the case of a suprasellar cystic mass. Evaluation of tumor markers and close follow-up will be necessary.

A Novel Dissection Method Using a Flexible Neuroendoscope for Resection of Tumors Around the Aqueduct of Sylvius.

Flexible endoscopes have both a wide range of movement and a wide field of view and are therefore widely used for endoscopic third ventriculostomy and biopsy. However, tumor resection around the aqueduct of Sylvius using flexible endoscopes has scarcely been reported. We report 2 cases of tumor resection around the aqueduct of Sylvius. The first case is a 38-year-old man presenting with progressive headache, nausea, and diplopia. Magnetic resonance imaging (MRI) revealed a 1.4 cm nonenhancing mass at the entry of the aqueduct of Sylvius and occlusive hydrocephalus. We performed tumor resection and endoscopic third ventriculostomy (ETV) simultaneously. His symptoms disappeared after the operation. Final pathologic diagnosis was ancient schwannoma. The second case is a 78-year-old woman presenting with progressive disturbance of consciousness (coma). MRI showed 0.7 cm nonenhancing mass at the entry of the aqueduct of Sylvius and occlusive hydrocephalus. We performed tumor resection and ETV similarly. Her consciousness improved after the operation. Final tumor diagnosis was cavernous malformation. In both cases there was no additional neurologic deficit after the surgery. By using a flexible endoscope for tumor dissection, resection of a tumor without a neck, which cannot be removed through aspiration alone, becomes possible. To our knowledge, the presented cases are the first to describe the effectiveness of complete resection of a tumor in the third ventricle using flexible endoscopy.

Neurology_Adams

The majority of affected patients are children 4 to 8 years of age, and males outnumber females 3:2 or 3:1 in most reported series. As a rule, symptoms have been present for 1 to 5 months before the diagnosis is made. The clinical picture is fairly distinctive and derives from secondary hydrocephalus and raised intracranial pressure as a result of blockage of the fourth ventricle. Typically, the child becomes listless, vomits repeatedly, and has a morning headache. The first diagnosis that suggests itself may be gastrointestinal disease or abdominal migraine. Soon, however, a stumbling gait, frequent falls, and diplopia as well as strabismus lead to a neurologic examination and the discovery of papilledema or sixth nerve palsies. However, when the tumor is located in the lateral cerebellum or in the cerebrum, as it usually is in adults, signs of raised intracranial pressure may be delayed. Dizziness (positional) and nystagmus are then frequent. A small proportion of children have a

Lung carcinoma metastasis presenting as a pineal region tumor.

The pineal region is an unusual site for brain metastasis and most metastatic pineal lesions are asymptomatic. A 53 year-old man presented with severe headache, limitation of upward gaze and diplopia. The patient's neurological examination was unremarkable. Magnetic resonance imaging (MRI) scans of the brain demonstrated a 1.5 x 2 cm well demarcated solitary mass in the pineal region with hydrocephalus. Surgery was performed and adenocarcinoma was diagnosed. A systemic investigation revealed adenocarcinoma of the lung as primary lesion. Although rare, metastatic tumor should be considered in the differential diagnosis of pineal region tumors.

[The ophthalmologic signs in cerebellum tumor. Preliminary report].

The aim of the study was an analysi The study included 14 pati The symptoms found before surger 1. The natural dynamic of the tum

Calcifying pseudoneoplasm of the neuraxis (CaPNoN): an unusual cause of third nerve palsy in a teenager.

An 18-year-old part-time teacher presented with headache and diplopia. Physical examination showed partial left oculomotor palsy. Neurology examination was otherwise unremarkable. Cross-sectional imaging was arranged for investigation of third nerve palsy. On CT scan, the lesion was calcified, and on MRI, hypointense on <iT</i <sub1</sub and <iT</i <sub2</sub weightedimages with thin rim enhancement, resembling an atypical meningioma. CT angiogram showed no vascular connection. Following worsening diplopia and a slight increase in lesion size on follow-up MRI, the patient was re-reviewed in our regional skull base multidisciplinary team meeting, where a decision for excision was made. Pre-operatively, the absence of a vascular connection was confirmed on catheter angiogram. Histopathological examination demonstrated features typical of calcified pseudoneoplasm of the neuraxis, with extensive metaplastic calcification with stroma containing variable fibrovascular tissue and focal inflammatory cell infiltrates, spindle and epithelioid cells, and psammoma bodies at the rim of the lesion. Following surgery, the patient had persisting diplopia. He remains under clinical review. As surgical resection is considered curative, no further imaging follow-up is planned.