Elevated Intracranial Pressure Associated With Exogenous Hormonal Therapy Used for Gender Affirmation.

BACKGROUND: Addison disease, corticosteroid withdrawal, and taking synthetic growth hormone have been linked with development of intracranial hypertension, but there is still debate on whether administration of other exogenous hormones plays a role in precipitating elevated pressure. The growing use of hormonal therapy for gender affirmation provides an opportunity to explore this possibility. METHODS: All transgender patients taking exogenous hormones for female-to-male (FTM) and male-to-female (MTF) transitions who were diagnosed with intracranial hypertension at Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital and Beth Israel Deaconess Medical Center between August 2014 and November 2018 were included in a retrospective review. Visual acuity, type, and dose of exogenous hormone, visual field testing, clinical exam, results of neuroimaging and lumbar puncture, and treatment modalities were catalogued and analyzed. RESULTS: Six transgender individuals were identified. Five were FTM, with an average hormone treatment time of 18.4 months, and one was MTF who had been treated with hormones for 4 years. The average age of all patients was 23.5 years. The average time between onset of symptoms and presentation was 5 months. Fifty percent of the patients reported pulse-synchronous tinnitus, 83% reported positional headache, 33% reported transient visual obscurations, and 16% reported diplopia. Lumbar punctures performed on 4 of the patients revealed elevated opening pressures and normal cerebrospinal fluid constituents. MRI findings consistent with elevated intracranial pressure (ICP) were present in the other 2 patients in whom lumbar puncture was unsuccessful. Four patients were treated with acetazolamide and one was treated with topiramate, with an average follow-up time of 15.7 months. All patients demonstrated bilateral optic disc swelling, and all maintained normal acuity and color vision. Performance on visual field testing was not significantly affected in any patient. CONCLUSIONS: This is the largest reported series to date of gender-transitioning patients with intracranial hypertension, including one novel MTF conversion. These observations warrant further investigation into the possible link of exogenous hormonal therapy and elevated ICP and any mechanisms or confounders underlying this potential association.

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.

Benign Intracranial Hypertension Necessitating Ventriculoperitoneal Shunt Insertion Secondary to Growth Hormone Therapy

Presentation Constant bilateral frontal headache associated with early morning awakenings, two episodes of vomiting and blurred vision. Diagnosis Benign Intracranial Hypertension. Treatment Repeat Lumbar Punctures were performed. GH was stopped and acetazolamide commenced. Later requiring VP shunt due to refractory symptoms with full resolution of symptoms. Conclusion Surgical management involving shunt procedures are reserved for refractory cases and are highly effective at resolving intractable symptoms.

Cerebral venous thrombosis requiring invasive treatment for elevated intracranial pressure in women with combined hormonal contraceptive intake: risk factors, anatomical distribution, and clinical presentation.

OBJECTIVE Women taking combined hormonal contraceptives (CHCs) are generally considered to be at low risk for cerebral venous thrombosis (CVT). When it does occur, however, intensive care and neurosurgical management may, in rare cases, be needed for the control of elevated intracranial pressure (ICP). The use of nonsurgical strategies such as barbiturate coma and induced hypothermia has never been reported in this context. The objective of this study is to determine predictive factors for invasive or surgical ICP treatment and the potential complications of nonsurgical strategies in this population. METHODS The authors conducted a 2-center, retrospective chart review of 168 cases of CVT in women between 2000 and 2012. Eligible patients were classified as having had a mild or a severe clinical course, the latter category including all patients who underwent invasive or surgical ICP treatment and all who had an unfavorable outcome (modified Rankin Scale score ≥ 3 or Glasgow Outcome Scale score ≤ 3). The Mann-Whitney U-test was used for continuous parameters and Fisher's exact test for categorical parameters, and odds ratios were calculated with statistical significance set at p ≤ 0.05. RESULTS Of the 168 patients, 57 (age range 16-49 years) were determined to be eligible for the study. Six patients (10.5%) required invasive or surgical ICP treatment. Three patients (5.3%) developed refractory ICP > 30 mm Hg despite early surgical decompression; 2 of them (3.5%) were treated with barbiturate coma and induced hypothermia, with documented infectious, thromboembolic, and hemorrhagic complications. Coma on admission, thrombosis of the deep venous system with consecutive hydrocephalus, intraventricular hemorrhage, and hemorrhagic venous infarction were associated with a higher frequency of surgical intervention. Coma, quadriparesis on admission, and hydrocephalus were more commonly seen among women with unfavorable outcomes. Thrombosis of the transverse sinus was less common in patients with an unfavorable outcome, with similar distribution in patients needing invasive or surgical ICP treatment. CONCLUSIONS The need for invasive or surgical ICP treatment in women taking CHCs who have CVT is partly predictable on the basis of the clinical and radiological findings on admission. The use of nonsurgical treatments for refractory ICP, such as barbiturate coma and induced hypothermia, is associated with systemic infectious and hematological complications and may worsen morbidity in this patient population. The significance of these factors should be studied in larger multicenter cohorts.

Intracranial hypertension secondary to high dose cytosine arabinoside - A case study.

We report a rare case of intracranial hypertension following high dose cytosine arabinoside (HiDAC) in a 20-year-old man, with precursor B-cell acute lymphoblastic leukemia (ALL). A five drug induction protocol for ALL was initiated; post induction consolidation was with HiDAC (3 g/m2 IV every 12 h on days 1, 3 and 5). Post consolidation, cytogenetic remission was attained and he received an intensification and maintenance regimen for ALL, for a period of approximately 24 months. Four months following the completion of his treatment, the patient relapsed within the central nervous system (CNS). Intravenous salvage chemotherapy was initiated using a combination of fludarabine 30 mg/m2, followed by cytarabine 2 g/m2 4 h later on days 1 through 5 (FA). On day # 23 of FA, he developed a severe headache. A gadolinium-enhanced brain magnetic resonance imaging (MRI) revealed increased intracranial pressure. On day # 25, ophthalmology examination suggested bilateral papilledema. He was started on acetazolamide 250 mg twice daily. He had spontaneous resolution of his symptoms. The patient had no recurrence of papilledema or any other neurological symptoms. Intracranial hypertension secondary to HiDAC, is an exceedingly rare complication and is not regularly associated as a common side effect of cytarabine administration. Prompt action in diagnosing and treating intracranial hypertension will save the patient from consequences, such as loss of vision, that are prevalent in this condition.

Delayed Development of Intracranial Hypertension After Discontinuation of Tetracycline Treatment for Acne Vulgaris.

A 14-year-old girl presented with a history of left-sided headache and acute bilateral blurred vision. She had a remote history of oral tetracycline use for the treatment of acne vulgaris, which had been discontinued for 1 month. The patient was diagnosed with drug-induced intracranial hypertension (IH) and treated with oral acetazolamide with subsequent resolution of symptoms. IH, a known rare complication of the tetracycline class of antibiotics, can also have a delayed presentation after discontinuation of the medication.

The effect of ketamine on intracranial and cerebral perfusion pressure and health outcomes: a systematic review.

STUDY OBJECTIVE: We synthesize the available evidence on the effect of ketamine on intracranial and cerebral perfusion pressures, neurologic outcomes, ICU length of stay, and mortality. METHODS: We developed a systematic search strategy and applied it to 6 electronic reference databases. We completed a gray literature search and searched medical journals as well as the bibliographies of relevant articles. We included randomized and nonrandomized prospective studies that compared the effect of ketamine with another intravenous sedative in intubated patients and reported at least 1 outcome of interest. Two authors independently performed title, abstract, and full-text reviews, and abstracted data from all studies, using standardized forms. Data from randomized controlled trials and prospective studies were synthesized in a qualitative manner because the study designs, patient populations, reported outcomes, and follow-up periods were heterogeneous. We used the Jadad score and Cochrane Risk of Bias tool to assess study quality. RESULTS: We retrieved 4,896 titles, of which 10 studies met our inclusion criteria, reporting data on 953 patients. One study was deemed at low risk of bias in all quality assessment domains. All others were at high risk in at least 1 domain. Two of 8 studies reported small reductions in intracranial pressure within 10 minutes of ketamine administration, and 2 studies reported an increase. None of the studies reported significant differences in cerebral perfusion pressure, neurologic outcomes, ICU length of stay, or mortality. CONCLUSION: According to the available literature, the use of ketamine in critically ill patients does not appear to adversely affect patient outcomes.

Symptomatic intracranial hypertension and prolonged hypocalcemia following treatment of Paget's disease of the skull with zoledronic acid.

Skull involvement in Paget's disease of bone can lead to neurological symptoms, prompting treatment. Intravenous zoledronic acid (ZA) has emerged as an effective and safe treatment option for patients with Paget's, leading to sustained remission and improved quality of life. A previously untreated 61-year-old female presented with 2-year history of facial asymmetry with progressive hearing impairment. Serum calcium levels were normal with upper normal levels of PTH and low 25OHD levels. Serum alkaline phosphatase was markedly increased and bone scan showed extensive pagetic involvement of the skull. Head CT and MRI revealed hydrocephalus with cerebellar tonsillar herniation, platybasia and basilar invagination. In the absence of clinical signs or symptoms of intracranial hypertension, she was treated with intravenous ZA after 15-day supplementation with calcium and vitamin D. Twelve hours after the infusion, the patient became confused, agitated and disoriented and developed urinary incontinence; cortical sulci became effaced on CT indicating increased intracranial pressure. Over the following days, she developed frank hypocalcemia requiring intravenous calcium infusion and calcitriol. Neurological status returned to normal within 24 h of onset, except for urinary incontinence. Nine months later she remained incontinent and still required calcitriol to maintain normocalcemia. Zoledronic acid is a first-line option for the treatment of Paget's disease, yet there can be complications in particular clinical scenarios such as pagetic hydrocephalus, as seen in this case. Plentiful supplementation of calcium and vitamin D before bisphosphonate therapy is paramount in order to minimize the risk of prolonged post-treatment hypocalcemia.

Pretreatment with midazolam blunts the rise in intracranial pressure associated with ketamine sedation for lumbar puncture in children.

OBJECTIVE: Ketamine has a long history of use during pediatric procedural sedation. Concerns about raising intracranial pressure may limit use in certain situations. Whereas some data suggest that benzodiazepine coadministration may blunt this response, pediatric data during procedural sedation do not exist. We evaluated the effects of midazolam pretreatment on intracranial pressure during ketamine sedation in children. DESIGN: Prospective, randomized clinical study. SETTING: Outpatient Medical Observation unit at Kosair Children's Hospital. PATIENTS: A total of 25 oncology patients in whom sedated lumbar puncture was scheduled. INTERVENTIONS: Patients alternated between sedation in Group A (midazolam/ketamine prior to lumbar puncture) or Group B (ketamine only prior to lumbar puncture). Opening pressure, medication doses, sedation depth, and complications were recorded. A control group of non-ketamine-sedated patients (Group C) was added to differentiate drug vs. disease-specific opening pressure changes. Between-group differences were compared by linear mixed effects model or contingency table with p < 0.05 considered significant. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients aged 82 ± 49 months were sedated 84 times. Thirty-five sedations were in Group A, 39 in Group B, and 10 in Group C. Mean (95% confidence interval) adjusted opening pressure in Group A (22.0 [12.3, 22.2] cm H2O) was lower than Group B (26.5 [24.0, 29.2] cm H2O, p = 0.013). Opening pressure in Group C (17.3 [12.3, 22.2] cm H2O) was lower than in Group B (p = 0.002) but not in Group A (p = 0.096). Ketamine doses were similar between Groups A and B (1.4 ± 0.6 mg/kg vs. 1.4 ± 0.4 mg/kg, p = NS). Mean midazolam pretreatment dose was 0.09 ± 0.02 mg/kg and did not correlate with measured opening pressure. Four patients, all in Group B, experienced significant emergence reactions. CONCLUSION: While pretreatment with midazolam is associated with a reduction in intracranial pressure compared with sedation with ketamine alone, ketamine-containing regimens are associated with higher opening pressures than non-ketamine-containing regimens.

[Dynamics of intracerebral and cerebral perfusion pressure during major abdominal surgery].

UNLABELLED: Purpose of the study was to compare an influence of anaesthesia with sevoflurane and propofol on intracerebral and cerebral perfusion pressure by data of ophthalmo-dynamometry of the central retinal vein. MATERIALS AND METHODS: The article deals with study of 75 patients which were undergoing major abdominal surgery. Combined anaesthesia with sevoflurane and fentanyl and total intravenous anaesthesia with propofol and fentanyl were used during the operations. Subgroups were identified in the groups of patients depended on the basic intracerebral pressure (ICP); subgroup of patients with normal ICP (< or = 12 mmHg) and subgroup of patients with intracerebral hypertension (ICP > 12 mmHg) RESULTS: Intracerebral pressure increased by 56% and cerebral perfusion pressure decreased by 35% in patients with intracerebral hypertension during the application of combined anaesthesia with sevoflurane. ICP decreased to normal parameters during application of total intravenous anaesthesia with propofol in patients with intracerebral hypertension. There was no changes of intracerebral and cerepral perfusion pressure (CPP) in patients without cerebral hypertension. Awaking time in patients with intracerebral hypertension was longer by 1.6 times after anaesthesia with sevoflurane than after anaesthesia with propofol. CONCLUSION: Combined inhalation anaesthesia with sevoflurane causes the increasing of ICP and decreasing of CPP and increasing of awaking time. Total intravenous anaesthesia with propofol and fentanyl provides stable cerebral haemodynamics. Total intravenous anaesthesia with propofol is a technique of choice in patients with underling intracerebral hypertension.

Intracranial Hypertension Associated With Testosterone Therapy In Female-To-Male Transgender Patients: A Case Report And Literature Review.

We highlight a case of intracranial hypertension secondary to exogenous testosterone in a female-to-male transgender patient and present a systematic review of similar cases. Our review identified 19 female-to-male transgender individuals with intracranial hypertension. The mean age was 24.2 years and most common presenting symptom was headache (78.9% of patients). The most frequently associated ocular symptoms were transient visual obscurations (42.1%) and blurred vision (21.1%). Onset of symptoms occurred concurrently with exogenous testosterone therapy in 89.5% of the patients. The most common treatments were acetazolamide (89.5%), topiramate (31.6%), and alteration in hormone regimen (21.1%); four cases required surgery. These findings aid clinicians treating intracranial hypertension in patients undergoing gender affirmation therapy in a conscientious, patient-centered manner.

Fulminant intracranial hypertension secondary to oxytetracycline requiring urgent ventriculo-peritoneal shunt insertion.

Idiopathic intracranial hypertension is a syndrome that presents with headaches and visual loss. Its pathogenesis is unknown. Treatment options include acetazolamide, therapeutic lumbar punctures or permanent CSF diversion. We present the only reported case of acute drug-induced intracranial hypertension secondary to oxytetracycline requiring urgent cerebrospinal fluid diversion. The patient's rapid visual failure progressed daily despite discontinuation of the drug and required an urgent ventriculo-peritoneal (VP) shunt insertion. Patients should be counselled about the rare potential risk of developing intracranial hypertension when commencing oxytetracycline. Rapid visual failure in IIH is a neurosurgical emergency necessitating urgent ventriculoperitoneal shunt insertion.

Intracranial hypertension and papilloedema as a complication to low antiretroviral therapy adherence in a man living with chronic HIV.

We describe a 61-year-old man living with HIV on antiretroviral therapy (ART), who presented with headache, dizziness and blurred vision. Latest CD4+ cell count 3 months prior to admission was 570×106 cells/mL and HIV viral load <20 copies/mL. The patient was diagnosed with cerebrospinal fluid (CSF) lymphocytic pleocytosis, raised intracranial pressure and papilloedema. Neuroimaging showed normal ventricular volume and no mass lesions, suggesting (1) neuroinfection (2) idiopathic intracranial hypertension or (3) retroviral rebound syndrome (RRS) as possible causes. Neuroinfection was ruled out and idiopathic intracranial hypertension seemed unlikely. Elevated plasma HIV RNA level was detected consistent with reduced ART adherence prior to admission. RRS is a virological rebound after ART interruption, which can mimic the acute retroviral syndrome of acute primary infection. To the best of our knowledge, we describe the second case of RRS presenting as CSF lymphocytic pleocytosis and elevated intracranial pressure after low ART adherence.

[Acute intracranial hypertension during xenon anesthesia in a patient with a giant brainstem tumor and cerebrospinal fluid flow obstruction: a case report].

Today there are prospects for the wide use of xenon for anesthesia or analgesic sedation in neurosurgical patients, but clinical trials of and experience in using the agent in neurosurgery are scanty. The paper reports the first case of acute intracranial hypertension during xenon anesthesia in a patient with a giant brain base tumor and cerebrospinal fluid flow obstruction in the presence of subcompensated intracranial hypertension. Comparison of intracranial pressure, blood pressure, cerebral perfusion pressure, and linear blood flow velocity suggests the nature of the effect of xenon on cerebral vascular tone, cerebral blood flow, and its autoregulation. Based on the findings, the authors discuss whether xenon may be used in patients with intracranial hypertension.

Drug-Induced Intracranial Hypertension: A Systematic Review and Critical Assessment of Drug-Induced Causes.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition with increased intracranial pressure of unknown etiology. Its presenting symptoms include persistent headache, pulsatile tinnitus, and visual obscuration. It tends to occur in obese women of childbearing age, and its greatest risk is irreversible loss of vision. Some of the commonly used medications in dermatology, especially those for acne vulgaris, have been associated with IIH. However, the creation of specific risk categories for drugs as a guide for clinicians has never been performed. OBJECTIVE: The aim of this study was to critically assess all published cases of IIH and identify high-risk drugs associated with drug-induced intracranial hypertension (DIIH), to assist dermatologists and other physicians with patient education and monitoring of symptoms of secondary intracranial hypertension. METHODS: MEDLINE, EMBASE, and Cochrane Review Databases were searched for all cases of IIH thought to be drug-related between January 1900 and June 2019. A total of 5117 articles were identified, and 235 articles were found to be relevant. All cases were assessed to satisfy the modified Dandy criteria for diagnosis of IIH, and the likelihood of each case being a 'definite' adverse drug reaction (ADR) was determined using the Koh algorithm for ADR. An association category (from weakly associated [Category I] to strongly associated [Category V]) was assigned based on the number of cases meeting these two criteria. RESULTS: There were 259 verifiable cases of DIIH. Vitamin A derivatives, tetracycline-class antibiotics, recombinant growth hormone, and lithium were found to be most strongly associated with DIIH (Categories IV and V). Corticosteroids were moderately associated with DIIH (Category III). Drugs that were weakly associated with DIIH (Categories I and II) include cyclosporine, progestin-only contraceptives, combined oral contraceptives, second- and third-generation fluoroquinolones, sulfenazone, gonadotropin-releasing hormones and luteinizing hormone-releasing hormone agonist, nalidixic acid, amiodarone, stanozolol, danazol, divalproic acid, sulfasalazine, ketoconazole, and ustekinumab. CONCLUSION: We suggest using the term 'drug-induced intracranial hypertension' (DIIH) and propose a set of diagnostic criteria for DIIH. Our review attempts to identify DIIH-associated drugs based on a strict diagnostic and drug-causality algorithm, then stratify them into appropriate risks categories. This may ultimately assist physicians in counselling patients about the risk of DIIH when prescribing medications and recognizing this uncommon yet sight-threatening condition.

A new experimental mouse model of water intoxication with sustained increased intracranial pressure and mild hyponatremia without side effects of antidiuretics.

The most used experimental mouse model of hyponatremia and elevated intracranial pressure (ICP) is intraperitoneal injection of water in combination with antidiuretics. This model of water intoxication (WI) results in extreme pathological changes and death within 1 h. To improve preclinical studies of the pathophysiology of elevated ICP, we characterized diuresis, cardiovascular parameters, blood ionogram and effects of antidiuretics in this model. We subsequently developed a new mouse model with mild hyponatremia and sustained increased ICP. To investigate the classical protocol (severe WI), C57BL/6mice were anesthetized and received an intraperitoneal injection of 20% body weight of MilliQ water with or without 0.4 µg·kg-1 desmopressin acetate (dDAVP). Corresponding Sham groups were also studied. In the new WI protocol (mild WI), 10% body weight of a solution containing 6.5 mM NaHCO3, 1.125 mM KCl and 29.75 mM NaCl was intraperitoneally injected. By severe WI, ICP and mean arterial pressure increased until brain stem herniation occurred (23 ± 3 min after injection). The cardiovascular effects were accelerated by dDAVP. Severe WI induced a halt to urine production irrespective of the use of dDAVP. Following the new mild WI protocol, ICP also increased but was sustained at a pathologically high level without inducing herniation. Mean arterial pressure and urine production were not affected during mild WI. In conclusion, the new mild WI protocol is a superior experimental model to study the pathophysiological effects of elevated ICP induced by water intoxication.