Idiopathic Intracranial Hypertension in Female-to-Male Transgender Patients on Exogenous Testosterone Therapy.

PURPOSE: To present four female-to-male (FTM) transgender patients on testosterone therapy diagnosed with idiopathic intracranial hypertension (IIH). METHODS: The authors report 4 consecutive FTM transgender patients on exogenous testosterone diagnosed with IIH at a single institution. RESULTS: Patient 1 presented with progressive blurred vision and a central scotoma 10 weeks after starting testosterone cypionate injections for hormonal gender transition. Bilateral grade 5 papilledema was present; the patient underwent bilateral optic nerve sheath fenestration with improved vision and resolution of edema. Patient 2 presented with transient vision loss, pulsatile tinnitus, and blurred vision 13 months after starting testosterone cypionate injections. The patient had grade 4 and 3 disc edema of the right and left eyes, respectively. Patient 3 presented with headaches and pulsatile tinnitus and was on testosterone injections at an unknown dose. The examination revealed grade 1 and 2 disc edema of the right and left eyes, respectively. Patient 4 presented with decreased vision, transient visual obscurations, and daily migraines while using topical testosterone gel every other day. Color vision was reduced, and lumbar puncture revealed elevated intracranial pressure. All patients had neuroimaging findings consistent with increased intracranial pressure. CONCLUSIONS: Testosterone therapy plays an essential role in FTM hormonal transitioning and may play a role in IIH. Patients undergoing testosterone therapy for gender transition should be informed of the possibility of developing IIH while on treatment, with obesity possibly increasing this risk. Comprehensive eye examinations should be considered in these patients before initiating hormone therapy.

Pseudotumour cerebri due to phenytoin in a child.

Pseudotumour cerebri is a manifestation of intracranial hypertension in an otherwise normal individual. We hereby report phenytoin-induced pseudotumour cerebri in a 9-year-old boy who received phenytoin as a prophylactic anticonvulsant following surgical removal of unifocal Langerhans cell histiocytosis involving the right frontal bone. The child was evaluated for headache and diplopia after starting phenytoin and on evaluation was found to have bilateral sixth nerve palsy. The only abnormality detected was an elevated cerebrospinal fluid pressure. Withdrawal of phenytoin resulted in complete resolution of symptoms. Despite meticulous literature search, we found only 1 other report of phenytoin induced pseudotumour cerebri. We report this case to highlight the need to consider this entity whenever a patient presents with new onset or persistent headache and visual symptoms soon after starting a medication since a high degree of suspicion is needed to arrive at the diagnosis and to take appropriate steps before it progresses to harmful complications such as vision loss.

Shifting gears to differentiation agents in acute promyelocytic leukemia with resource constraints-a cohort study.

BACKGROUND: Treatment of acute promyelocytic leukaemia has emerged as a major success in hemato-oncology. While literature from the developed world boasts of outstanding outcomes, there is a paucity of data from the developing world. This study aimed to assess complications and outcomes of acute promyelocytic leukaemia in a resource-constrained setting. METHODS: We retrospectively collected data from patients diagnosed with APL from January 2016 to December 2020. RESULTS: Sixty-four patients were treated-32 in both the Sanz high and low-risk groups. In the Sanz low-risk group, 12.5% of patients received ATRA with daunorubicin and 81.25% received ATRA with ATO. In the Sanz high-risk group, 18.8% of patients received ATRA with daunorubicin, 34.3% received ATRA with daunorubicin and ATO while 40.6% received ATRA with ATO. 56.25% of patients developed differentiation syndrome. The incidence was higher in Sanz high-risk group as compared to Sanz low-risk group. 57.4% of patients had an infection at the time of presentation. 62.5% of patients developed neutropenic fever during treatment. 17.2% of patients developed pseudotumor cerebri. The 4-year EFS and OS were 71.25 and 73.13%, respectively. Sanz low-risk group had a better 4-year EFS and OS as compared to the Sanz high-risk group. Haemoglobin at presentation and Sanz high-risk group were associated with poorer outcomes with a hazard ratio of 0.8 and 3.1, respectively. Outcomes in high-risk patients were better with the use of ATRA + ATO + daunorubicin. CONCLUSION: In the Indian population, APL patients have a high incidence of differentiation syndrome, pseudotumor cerebri, and infections during induction. CR, EFS, and OS compared to the developed world can be achieved with optimal therapy. Low haemoglobin at presentation and Sanz high-risk group were associated with poorer outcomes. ATRA, ATO, and daunorubicin combination is the preferred protocol for treating high-risk patients.

Papilledema and idiopathic intracranial hypertension due to the possible potentiation of ATRA by posaconazole in a case of acute promyelocytic leukemia.

INTRODUCTION: Idiopathic intracranial hypertension (IIH) (pseudotumor cerebri) is a rare side effect of all-trans retinoic acid (ATRA). IIH cases have been observed after the concomitant use of ATRA with azole group antimicrobials such as fluconazole and voriconazole. Here, we discuss about the diagnosis and treatment process of the IIH emerging in a young acute promyelocytic leukemia (APL) case with the ATRA impact, which can be increased by posaconazole. CASE: A 19-year-old male patient was diagnosed with APL. Headache and blurred vision were developed on the 12th day of the AIDA (ATRA, 45 mg/m2/day, oral and idarubicin 12 mg/m2, on days 2, 4, 6, 8, intravenous) protocol and posaconazole proflaxis. He was diagnosed IIH along with the existing eye findings and imagings. MANAGEMENT & OUTCOME: ATRA treatment and posaconazole were interrupted. Systemic acetazolamide and dexamethasone treatment were initiated. After significant clinical response was observed, ATRA treatment was resumed without posaconazole and a similar clinical condition did not recur. DISCUSSION: The combined use of ATRA and azole group drugs increases the risk of developing IIH. Patients with APL who developed IIH during the concomitant use of ATRA and fluconazole or voriconazole have been reported. To the best of our knowledge, our case is the first APL case with a IIH who treated with ATRA-based therapy and used posaconazole. In case of development of side effects, drugs should be interrupted and this combination should be avoided if possible after appropriate approach and clinical improvement.

Increased Incidence of Pseudotumor Cerebri Syndrome Among Users of Tetracycline Antibiotics.

BACKGROUND: To determine whether the use of a tetracycline-class antibiotic is associated with an increased risk of developing pseudotumor cerebri syndrome (PTCS). METHODS: We identified patients in the University of Utah Health system who were prescribed a tetracycline-class antibiotic and determined what percentage of those individuals were subsequently diagnosed with PTCS secondary to tetracycline use. We compared this calculation to the number of patients with PTCS unrelated to tetracycline use. RESULTS: Between 2007 and 2014, a total of 960 patients in the University system between the ages of 12 and 50 were prescribed a tetracycline antibiotic. Among those, 45 were diagnosed with tetracycline-induced PTCS. We estimate the incidence of tetracycline-induced PTCS to be 63.9 per 100,000 person-years. By comparison, the incidence of idiopathic intracranial hypertension (IIH) is estimated to be less than one per 100,000 person-years (Calculated Risk Ratio = 178). CONCLUSIONS: Although a causative link between tetracycline use and pseudotumor cerebri has yet to be firmly established, our study suggests that the incidence of pseudotumor cerebri among tetracycline users is significantly higher than the incidence of IIH in the general population.

Doxycycline-induced idiopathic intracranial hypertension in a patient with Lyme disease.

ABSTRACT: Doxycycline is widely used to treat early and disseminated Lyme disease. Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a rare but serious adverse reaction to this medication. This article reviews the pathophysiology, presentation, diagnosis, and treatment of a patient with disseminated Lyme disease complicated by doxycycline-induced IIH.

Pseudotumor cerebri syndrome with different types of hormonal contraceptives in women of child-bearing age.

BACKGROUND AND PURPOSE: There is a lack of comparative safety data on the risk of pseudotumor cerebri syndrome (PTCS) associated with different hormonal contraceptives. We sought to quantify the risk of PTCS associated with eight different types of hormonal contraceptives compared with oral levonorgestrel. METHODS: We conducted a retrospective cohort study, with a case-control analysis of 4 871 504 women aged 15-45 years in the period 2008-2015, using IQVIA Ambulatory Electronic Medical Records data in the USA. Patients who used nine different contraceptive agents including intrauterine levonorgestrel, medroxyprogesterone injection, etonogestrel/ethinyl estradiol vaginal ring and combination oral contraceptives (COCs) that contained ethinyl estradiol and the progestins levonorgestrel, norgestimate, desogestrel, norethindrone and drospirenone, were included. Diagnosis of PTCS was defined using the first International Classification of Diseases, 9th or 10th revision, code for intracranial hypertension in patients who had also received an imaging code in the 30 days prior to the index date. RESULTS: A total of 3323 PTCS cases and 13 292 matched controls were identified. No increase in risk was found when analysing intrauterine levonorgestrel or COCs containing desogestrel, norethindrone, drospirenone, norgestimate or norgestrel versus COC levonorgestrel. The adjusted incidence rate ratio for etonogestrel/etonogestrel/ethinyl estradiol vaginal ring and medroxyprogesterone suspension compared with levonorgestrel COC was 4.45 [95% confidence interval (CI) 1.98-9.96] and 2.20 (95% CI 1.33-3.64), respectively. CONCLUSIONS: This study found an elevated risk for PTCS among users of etonogestrel vaginal ring and medroxyprogesterone suspension when compared with oral levonorgestrel. Future studies are needed to confirm these findings.

Benign intracranial hypertension in a patient treated with ustekinumab for psoriasis.

Ustekinumab is a monoclonal antibody, which binds the p40 subunit of IL-12 and IL-23 so they are unable to bind to their receptors, ultimately reducing T-cell-mediated inflammation in psoriasis. Studies and cases have focused on the risk of infection and malignancy associated with the use of biologics medications; however, there have been limited data available on the potential neurological adverse effects of biologics. We report the case of a 44-year-old female with a longstanding history of psoriasis who developed benign intracranial hypertension while on ustekinumab for her psoriasis.

Magnetic Resonance Imaging Findings of All-Trans Retinoic Acid-induced Pseudotumor Cerebri in a Child With Acute Promyelocytic Leukemia.

Pseudotumor cerebri (PTC), also known as idiopathic or benign intracranial hypertension, is characterized by elevated intracranial pressure without any evidence of organic central nervous system disorders. PTC is a rare but well-known adverse event associated with all-trans retinoic acid (ATRA) treatment. Persistent blindness in about 10% of affected patients is caused by PTC; therefore, prompt and accurate diagnosis is required. Recently, magnetic resonance imaging (MRI) findings, including empty sella, flattening of the posterior aspect of the globe, and distention of the perioptic subarachnoid space, have been found to be of high diagnostic value in PTC, but there apparently have been no reports about MRI findings in ATRA-induced PTC. We report here an 11-year-old boy with acute promyelocytic leukemia who developed ATRA-induced PTC during leukemia treatment. MRI findings beneficial for the diagnosis of PTC were observed.

Herpes simplex encephalitis and pseudotumour cerebri due to isotretinoin.

Isotretinoin can have significant adverse reactions on multiple systems. We report a unique case of pseudotumour cerebri and herpes encephalitis resulting due to isotretinoin. A 19-year-old female patient was admitted to our clinic, presenting with headache, nausea, vomiting and fever since three days. She had used isotretinoin for the last two months. The patient's neurological examination revealed the presence of neck stiffnes and a body temperature of 39,0◦C. MRI showed high signal localized to the temporal lobe and insula on the right and widened cerebrospinal fluid signal intensity on either side of the optic nerve. Electroencephalogram sharp and wave paroxysms on the right temporo-parietal region. Lumbar puncture showed an opening pressure of 320 mm H2O. The cerebrospinal fluid displayed the presence of 4-5 lymphocytes. On these grounds, the diagnosis of pseudotumour cerebri and herpes encephalitis was made. It is thus suggested that the physicians must keep in mind that pseudotumour cerebri and herpes encephalitis are possible adverse effects of isotretinoin.

Idiopathic Intracranial Hypertension Induced by Topical Application of Vitamin A.

A 21-year-old nonobese woman developed headaches and papilledema while excessively using 3 topical preparations of vitamin A. Neuroimaging studies were unremarkable and opening pressure on lumbar puncture was 300 mm H2O with normal cerebrospinal fluid composition. After discontinuation of the topical vitamin A preparations, the symptoms and signs of increased intracranial pressure resolved. The association of intracranial hypertension and topical vitamin A application has only been reported once previously.

Pseudotumor cerebri associated with cyclosporine use in severe atopic dermatitis.

Cyclosporine use can cause neurologic complications in 0.5% to 35% of cases, although the appearance of pseudotumor cerebri (PC) is exceptional. PC secondary to the use of cyclosporine is described mainly in individuals who have received a bone marrow transplant. We report the first case, to our knowledge, of PC secondary to the use of cyclosporine in a child with severe atopic dermatitis, with satisfactory resolution and without vision sequelae.

Pseudotumour cerebri in acute promyelocytic leukemia on treatment with all-trans-retinoic acid (ATRA) - an experience from a tertiary care centre.

Acute promyelocytic leukemia (APML) is considered to be sensitive to all-trans-retinoic acid (ATRA) which acts as a differentiating agent. ATRA is considered to be a well-tolerated agent and is known to achieve complete remission in acute promyelocytic leukemia. However, a few cases on long term all-trans-retinoic acid (ATRA) use can develop pseudotumor cerebri. Out of 32 patients with APML who were treated in our Centre over a 4-year-period, we encountered 6 patients who developed ATRA-related pseudotumor cerebri while on maintenance treatment. The patients ranged from 12 to 40 years of age. 3 patients complained of unbearable headache, 2 of diplopia and 1 of gross reduction in visual acuity. CT scans and MRI did not reveal any intracranial lesions. Cerebrospinal fluid (CSF) examination was normal with CSF manometry revealing a high CSF pressure (average of 345mmH2O). Fundoscopy revealed papilledema in 5 patients and optic atrophy in 1 patient. The patients were successfully managed with decrease dose/discontinuation of ATRA, use of acetazolamide, corticosteroids and therapeutic CSF drainage.

Efficacy and Side Effects of Topiramate in Treatment of Children With Pseudotumor Cerebri Syndrome.

BACKGROUND: Topiramate is often considered as a second-line medication for the treatment of pseudotumor cerebri syndrome (PTCS), but limited studies exist that evaluate its efficacy in children. METHODS: Retrospective study of patients aged <21 years with PTCS who were treated with topiramate alone or in combination with acetazolamide was performed. Data regarding clinical courses and visual outcomes were recorded. RESULTS: A total of 46 patients were identified. Three (6.5%) patients were treated with topiramate alone, 31 (67.4%) transitioned to topiramate from acetazolamide, and 12 (26.1%) took both topiramate and acetazolamide concurrently. The median time to resolution of papilledema on topiramate was 0.57 years (interquartile range 0.32 to 0.84). Among eyes with papilledema graded on the Frisen scale at topiramate initiation, 40 of 57 (70.2%) were grade 1, nine of 57 (15.8%) were grade 2, and eight of 57 (14.0%) were grade 3. Twenty-seven of 46 (58.7%) reported headache improvement after starting topiramate. The mean dose of topiramate was 1.3 ± 0.8 mg/kg/day. The most common side effect was patient report of cognitive slowing (10 of 46 [21.7%]). All patients on topiramate monotherapy who were compliant with treatment and follow-up had resolution of papilledema with no evidence of visual function loss. CONCLUSIONS: Topiramate can effectively treat PTCS in children with mild to moderate papilledema or in those unable to tolerate acetazolamide. More research is needed to assess the efficacy of topiramate for higher grade papilledema.

Intravitreal bevacizumab in the treatment of peripapillary choroidal neovascular membrane secondary to idiopathic intracranial hypertension.

A 14 year-old Caucasian boy with idiopathic intracranial hypertension (IIH) presented with blurred vision in his left eye. Visual acuity was 20/20, right eye, and 20/80, left eye, and funduscopy revealed bilateral papilledema. In addition, there was peripapillary choroidal neovascular membrane (PPCNVM) in the left eye. Oral acetazolamide improved the symptoms and signs of IIH, but seven weeks later, acuity remained 20/80, left eye, with an increase in subretinal hemorrhage. Two weeks following an intravitreal injection of bevacizumab, visual acuity on the left had improved to 20/30 with resolution of subretinal hemorrhage and fibrosis of PPCNVM. After an additional 2 weeks, visual acuity improved to 20/20, and there has been no sign of recurrence over 3.5 years of follow-up.