ABSTRACT
OBJECTIVES: To examine the clinical characteristics and prognosis of cerebral venous sinus thrombosis (CVST) that presented as pseudotumor cerebri (PTC) patients with JAK2V617F mutation. METHODS: Medical records of all consecutive patients that presented with PTC and a JAK2V617F mutation who were treated were retrospectively reviewed. Data regarding demographics and ocular presenting symptoms and signs, neurological signs, hematological factors treatment, and prognosis were collected. RESULTS: The most common presenting symptoms were headache (5 patients, 83.3%) and visual obscurations (5 patients, 83.3%). CVST of the sagittal sinus and sigmoid sinus were the most common site of thrombus. Platelet count and hemoglobin count were higher than normal during follow-up. There was significant change in the disk edema degree as well as decline in retinal nerve fiber layer (RNFL) thickness (P < 0.001, P < 0.001, Matched pairs). There was no significant change in visual acuity (VA) or mean deviation (MD) during follow-up (P = 0.95, 0.64, respectively, Matched pairs). CONCLUSIONS: Pseudotumor cerebri resulting from CSVT in our patients with JAK2V617F mutation was frequent in young patients and needed medical and surgical treatment, without improvement in visual functions and in third caused poor visual outcome. Therefore, we believe that a screening test for JAK2V617F mutation should be considered for patients with CVST without known risk factor presenting with PTC, especially when sagittal sinus or sigmoid sinus involvement or thrombocytosis or high hemoglobin are found upon presentation. This might lead to more aggressive management which may improve the visual prognosis of those young patients.
Subject(s)
Janus Kinase 2/genetics , Pseudotumor Cerebri/genetics , Sinus Thrombosis, Intracranial/complications , Adult , Child , Female , Genetic Predisposition to Disease , Humans , Male , Mutation , Pseudotumor Cerebri/diagnosis , Pseudotumor Cerebri/etiology , Sinus Thrombosis, Intracranial/diagnosisSubject(s)
Pseudotumor Cerebri/genetics , Acetazolamide/therapeutic use , Adolescent , Carbonic Anhydrase Inhibitors/therapeutic use , Child , Female , Genetic Predisposition to Disease , Headache Disorders/etiology , Humans , Male , Materia Medica/adverse effects , Neuroimaging , Papilledema/etiology , Pseudotumor Cerebri/chemically induced , Pseudotumor Cerebri/drug therapy , Siblings , Weight GainABSTRACT
PURPOSE: Idiopathic intracranial hypertension (IIH) is a condition of increased intracranial pressure of unknown aetiology. Patients with IIH usually suffer from headache and visual disturbances. High intracranial pressure despite normal ventricle size and negative MRI indicate perturbed water flux across cellular membranes, which is provided by the brain water channel aquaporin-4 (AQP4). IIH could be associated with malfunctioning intracerebral water homeostasis and cerebrospinal fluid (CSF) reabsorption based on functional or regulatory alterations of AQP4. METHODS: Clinical data, blood and CSF samples were collected from 28 patients with IIH. Clinical characteristics were assessed, and a genetic association study was performed by sequencing the AQP4 gene on chromosome 18. Genetic data were compared with 52 healthy controls and matched by age, sex and ethnicity. Chi-square test and linear discriminant analysis (LDA) were used in the search of a genotype-phenotype association. RESULTS: While the majority of patients responded to medical treatment, four required shunt application. All, except one, had a good visual outcome. The 24 AQP4 gene SNPs showed no association with IIH. Full cross-validation of the LDA modelling resulted in only 55.1% correct classification of the cases and controls, with a corresponding estimated p-value 0.37. CONCLUSIONS: Our genetic case-control study did not indicate an association between AQP4 gene variants and IIH. However, the theory of an etiopathogenic link between IIH and AQP4 is tempting, and discussed in this article. Association studies with large sample size are difficult to perform owing is the rarity of the condition.
Subject(s)
Aquaporin 4/genetics , Polymorphism, Single Nucleotide , Pseudotumor Cerebri/genetics , Adult , Case-Control Studies , Cerebrospinal Fluid Shunts , Chromosomes, Human, Pair 18/genetics , Diuretics/therapeutic use , Female , Genetic Association Studies , Humans , Intracranial Pressure , Male , Middle Aged , Norway , Pseudotumor Cerebri/therapy , Ventriculoperitoneal Shunt , Young AdultABSTRACT
An 18-year-old woman with Gitelman syndrome (GS) associated with idiopathic intracranial hypertension (IIH) is described. She was obese and showed a 10 kg gain in body weight over a period of 8 months. She presented with headache, vomiting, and diplopia. She had bilateral papilledema, and right abducens palsy. CSF examination demonstrated high pressure (over 320 mmH(2)O) with normal cytochemistry. Brain MRI was normal. She showed mild alkalosis, hypokalemia, hypomagnesemia, increased plasma renin activity, and normal blood pressure. Two heterozygous mutations in the SLC12A3 gene were identified. Therefore, she was diagnosed as GS with IIH. We should keep in mind the possible occurrence of IIH in GS.
Subject(s)
Gitelman Syndrome/complications , Pseudotumor Cerebri/complications , Adolescent , Amino Acid Substitution , Base Sequence , DNA Mutational Analysis , Exons , Female , Gitelman Syndrome/diagnosis , Gitelman Syndrome/genetics , Heterozygote , Humans , Mutation, Missense , Pseudotumor Cerebri/diagnosis , Pseudotumor Cerebri/genetics , Receptors, Drug/genetics , Solute Carrier Family 12, Member 3 , Symporters/geneticsABSTRACT
Pseudotumor cerebri with or without venous sinus thrombosis is a rare clinical presentation of Behçet disease in childhood. We present here a case of childhood pseudotumor cerebri without a previous diagnosis of Behçet disease. The detailed history and physical examination of the case led to the diagnosis of neuro-Behçet disease. The investigation of predisposition to thrombosis revealed heterozygous factor V Leiden mutation along with the high lipoprotein(a) level. The symptoms resolved dramatically by treatment with the combination of immunosuppression and anticoagulation with regard to the detected factor V Leiden mutation and high lipoprotein(a) level. After a symptom-free period of 9 months, the cerebral vein thrombosis recurred. We present this case to draw attention to this rare cause of pseudotumor cerebri in childhood and to emphasize the importance of additional thrombotic risk factors regarding the potential recurrence of thrombotic events in Behçet disease.
Subject(s)
Behcet Syndrome/genetics , Pseudotumor Cerebri/genetics , Sinus Thrombosis, Intracranial/genetics , Age of Onset , Behcet Syndrome/complications , Behcet Syndrome/epidemiology , Child , Factor V/genetics , Female , Humans , Lipoprotein(a)/blood , Pseudotumor Cerebri/drug therapy , Pseudotumor Cerebri/epidemiology , Recurrence , Sinus Thrombosis, Intracranial/drug therapy , Sinus Thrombosis, Intracranial/epidemiology , Treatment OutcomeABSTRACT
Facial nerve palsies are uncommon in infants. We report on 10-week-old monozygotic twins, diagnosed with cystic fibrosis by newborn screening, who developed facial palsy and increased intracranial pressure. Cranial imaging and cerebrospinal fluid analysis produced normal results. Levels of serum vitamin A were below normal range. Low levels of vitamin A are associated with facial nerve paralysis, and are at least partly implicated in the development of increased intracranial pressure in infants with cystic fibrosis.
Subject(s)
Cystic Fibrosis/diagnosis , Diseases in Twins/diagnosis , Facial Paralysis/diagnosis , Pseudotumor Cerebri/diagnosis , Vitamin A Deficiency/diagnosis , Cystic Fibrosis/complications , Cystic Fibrosis/genetics , Diseases in Twins/etiology , Diseases in Twins/genetics , Facial Paralysis/etiology , Facial Paralysis/genetics , Humans , Infant , Male , Pseudotumor Cerebri/etiology , Pseudotumor Cerebri/genetics , Vitamin A Deficiency/complications , Vitamin A Deficiency/geneticsABSTRACT
Familial occurrence of Idiopathic intracranial hypertension has been rarely reported in the literature. Idiopathic intracranial hypertension, both with and without papilloedema is only described in two families before, though one had a probable diagnosis. We report a family of mother and her two daughters. A 37 year old woman was diagnosed with idiopathic intracranial hypertension. Her 7 year old, younger daughter presented a year later with similar symptoms. She did not respond to medical treatment and required Lumbo-peritoneal shunt, Ventriculo-peritoneal shunt and bilateral sub-temporal decompression. Her elder daughter later presented with headaches and idiopathic intracranial hypertension without papilloedema was diagnosed at the age of 13 years. Further insight into the patterns of inheritance is required and other family members should be offered screening, even if papilloedema is not present.
Subject(s)
Cerebrospinal Fluid Shunts/methods , Pseudotumor Cerebri/genetics , Adolescent , Adult , Child , Humans , Male , Papilledema/etiology , Papilledema/genetics , Pseudotumor Cerebri/surgery , Ventriculoperitoneal Shunt/methodsABSTRACT
Alagille syndrome is an autosomal dominant condition with incomplete penetrance that is associated mostly with hepatic, cardiac, and skeletal abnormalities. In addition, the association of Alagille syndrome with ocular abnormalities is well known and is considered one of the characteristic features of this condition. Most commonly, posterior embryotoxon, glaucoma, or retinopathy has been identified in these children. The authors present 2 patients with Alagille syndrome who, before the age of 3 years old, developed idiopathic intracranial hypertension with documented increased intracranial pressure by lumbar puncture and papilledema, which was responsive to acetazolamide.
Subject(s)
Alagille Syndrome/physiopathology , Papilledema/physiopathology , Pseudotumor Cerebri/physiopathology , Acetazolamide/pharmacology , Acetazolamide/therapeutic use , Age of Onset , Alagille Syndrome/genetics , Alagille Syndrome/pathology , Cerebrospinal Fluid Pressure/physiology , Child, Preschool , Diuretics/pharmacology , Diuretics/therapeutic use , Female , Humans , Infant , Male , Papilledema/diagnosis , Papilledema/drug therapy , Pseudotumor Cerebri/diagnosis , Pseudotumor Cerebri/genetics , Spinal Puncture/methodsABSTRACT
The association of chronic migraine (CM) with an idiopathic intracranial hypertension without papilledema (IIHWOP), although much more prevalent than expected in clinical series of CM sufferers, is not included among the risk factors for migraine progression. We discuss the available evidence supporting the existence of a pathogenetic link between CM and idiopathic intracranial hypertensive disorders and suggest a causative role for IIHWOP in migraine progression.
Subject(s)
Migraine Disorders/complications , Migraine Disorders/physiopathology , Papilledema/complications , Pseudotumor Cerebri/complications , Disease Progression , Female , Humans , Migraine Disorders/epidemiology , Migraine Disorders/genetics , Papilledema/genetics , Pseudotumor Cerebri/genetics , Risk FactorsABSTRACT
This article is a case report of a 17-year-old male who presented with a headache and blurry vision. He subsequently was noted to have papilledema on a fundoscopic examination and an initial normal magnetic resonance imaging and computed tomography of his head; his condition was, therefore, diagnosed as pseudotumor cerebri. A subsequent magnetic resonance venography of his head revealed venous thrombosis, and other investigations revealed an elevated factor VIII level as well as a mutation at the MTHFR locus, consistent with an elevated risk for hypercoagulability. In addition, he admitted to steroid usage for purposes of performance enhancement in baseball. The patient's condition eventually improved with acetazolamide and serial lumbar punctures. Steroids have been linked to predisposition to hypercoagulable states, but there are no reports identified by these authors that link performance-enhancing steroids with pseudotumor cerebri as a result of a coagulation dyscrasia.
Subject(s)
Pseudotumor Cerebri/chemically induced , Steroids/adverse effects , Venous Thrombosis/chemically induced , Adolescent , Headache/etiology , Humans , Intracranial Pressure , Magnetic Resonance Imaging , Male , Pseudotumor Cerebri/diagnosis , Pseudotumor Cerebri/genetics , Treatment Outcome , Venous Thrombosis/drug therapy , Vision Disorders/etiologyABSTRACT
OBJECTIVE: To evaluate racial differences in idiopathic intracranial hypertension (IIH). METHODS: Medical records of all consecutive patients with definite IIH seen between 1989 and 2006 were reviewed. Demographics, associated factors, and visual function at presentation and follow-up were collected. Black patients were compared to non-black patients. RESULTS: We included 450 patients (197 black, 253 non-black). Obesity, systemic hypertension, anemia, and sleep apnea were more common in black patients than in non-black patients (p = 0.01). CSF opening pressure was higher in black patients (40 vs 34 cm CSF, p < 0.001). Visual acuity, visual field loss, and degree of papilledema at presentation and follow-up were worse in black patients (p = 0.01). Diagnostic and therapeutic measures were similar between black patients and non-black patients, except for optic nerve sheath fenestration (p = 0.01) and lumbar puncture (p = 0.03), both more commonly performed on black patients. The relative risk of severe visual loss for black patients compared with non-black patients was 3.5 (95% CI 2.0 to 5.8, p < 0.001) in at least one eye and 4.8 (95% CI 2.1 to 10.9, p < 0.001) in both eyes. Logistic regression analysis supported race, anemia, body mass index, and male gender as independent risk factors for severe visual loss and suggested that racial differences may be partially accounted for by differences in CSF opening pressure, body mass index, and frequency of anemia. CONCLUSION: Black patients with idiopathic intracranial hypertension (IIH) were more likely than non-black patients with IIH to have severe visual loss in at least one eye. This difference did not appear to result from diagnosis, treatment, or access to care, but may partially relate to differences in other risk factors. Black patients have a more aggressive disease and may need closer follow-up and lower thresholds for early intervention.
Subject(s)
Black People , Pseudotumor Cerebri/epidemiology , Pseudotumor Cerebri/pathology , White People , Adolescent , Adult , Black People/genetics , Child , Female , Humans , Male , Middle Aged , Pseudotumor Cerebri/genetics , Retrospective Studies , Risk Factors , Vision Disorders/epidemiology , Vision Disorders/genetics , Vision Disorders/pathology , White People/geneticsSubject(s)
Eye Diseases/genetics , Eye Diseases/physiopathology , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/physiopathology , Neurology/trends , Animals , Cranial Nerve Diseases/complications , Cranial Nerve Diseases/physiopathology , Humans , Neurodegenerative Diseases/complications , Ocular Motility Disorders/genetics , Ocular Motility Disorders/physiopathology , Optic Atrophy, Hereditary, Leber/genetics , Optic Atrophy, Hereditary, Leber/physiopathology , Optic Neuritis/genetics , Optic Neuritis/physiopathology , Prion Diseases/complications , Prion Diseases/physiopathology , Pseudotumor Cerebri/genetics , Pseudotumor Cerebri/physiopathologyABSTRACT
We report a case of Gitelman syndrome (GS) in a dizygotic twin who presented at 12 years of age with growth delay, metabolic alkalosis, hypomagnesemia and hypokalemia with inappropriate kaliuresis, and idiopathic intracranial hypertension with bilateral papilledema (pseudotumor cerebri). The patient, her twin sister, and her mother also presented with cerebral cavernous malformations. Based on the early onset and normocalciuria, Bartter syndrome was diagnosed first. However, mutation analysis showed that the proband is a compound heterozygote for 2 mutations in SLC12A3: a substitution of serine by leucine at amino acid position 555 (p.Ser555Leu) and a novel guanine to cytosine transition at the 5' splice site of intron 22 (c.2633+1G>C), providing the molecular diagnosis of GS. These mutations were not detected in 200 normal chromosomes and cosegregated within the family. Analysis of complementary DNA showed that the heterozygous nucleotide change c.2633+1G>C caused the appearance of 2 RNA molecules, 1 normal transcript and 1 skipping the entire exon 22 (r.2521_2634del). Supplementation with potassium and magnesium improved clinical symptoms and resulted in catch-up growth, but vision remained impaired. Three similar associations of Bartter syndrome/GS with pseudotumor cerebri were found in the literature, suggesting that electrolyte abnormalities and secondary aldosteronism may have a role in idiopathic intracranial hypertension. This study provides further evidence for the phenotypical heterogeneity of GS and its association with severe manifestations in children. It also shows the independent segregation of familial cavernomatosis and GS.
Subject(s)
Diseases in Twins/genetics , Gitelman Syndrome/genetics , Protein Splicing/genetics , Pseudotumor Cerebri/genetics , Receptors, Drug/genetics , Symporters/genetics , Alkalosis/genetics , Bartter Syndrome/genetics , Child , DNA Mutational Analysis , Diuretics , Female , Growth Disorders/genetics , Humans , Hypokalemia/genetics , Magnesium Deficiency/genetics , Magnetic Resonance Imaging , Mutation , Pedigree , Pseudotumor Cerebri/complications , Pseudotumor Cerebri/diagnosis , Solute Carrier Family 12, Member 3 , SyndromeABSTRACT
En la literatura médica son cada vez más frecuentes los trabajos que relacionan la hipertensión intracraneal benigna (HIB) y los estados protrombóticos. Recientemente se ha relacionado la resistencia a la proteína C activada y la mutación para el factor V de Leiden (FVL), con patología tromboembólica. La alta prevalencia del FVL ha originado que se relacione este factor procoagulante en patología trombótica del territorio cerebrovascular. La alteración de la reabsorción del líquido cefalorraquídeo por los microtrombos que se formarían en las vellosidades aracnoideas explicaría la fisiopatología de la HIB y el FVL. En este sentido aportamos 2 pacientes con diagnóstico de HIB que presentaron como único factor de riesgo heterocigosis para el FVL
Benign idiopathic intracranial hypertension (BIH) in association with prothrombotic conditions has been reported with increasing frequency in the medical literature. Recently, activated protein C resistance (APCR) has been identified as a factor in some cases. Because of its high prevalence, factor V Leiden mutation (FVL) is the most frequent coagulation abnormality associated with cerebral venous thrombosis. Reduced craniospinal fluid reabsorption due to damaged arachnoid villi secondary to microthrombus formation has been proposed as an explanation for the physiopathology of BIH and FVL. We describe two patients with a diagnosis of BIH, in whom the only risk factor was heterozygosity for FVL mutation
Subject(s)
Male , Child , Humans , Factor V/genetics , Pseudotumor Cerebri/genetics , Heterozygote , MutationABSTRACT
Benign idiopathic intracranial hypertension (BIH) in association with prothrombotic conditions has been reported with increasing frequency in the medical literature. Recently, activated protein C resistance (APCR) has been identified as a factor in some cases. Because of its high prevalence, factor V Leiden mutation (FVL) is the most frequent coagulation abnormality associated with cerebral venous thrombosis. Reduced craniospinal fluid reabsorption due to damaged arachnoid villi secondary to microthrombus formation has been proposed as an explanation for the physiopathology of BIH and FVL. We describe two patients with a diagnosis of BIH, in whom the only risk factor was heterozygosity for FVL mutation.
Subject(s)
Factor V/genetics , Pseudotumor Cerebri/genetics , Child , Heterozygote , Humans , Male , MutationABSTRACT
We studied thrombophilia, hypofibrinolysis, and polycystic-ovary syndrome (PCOS) in 65 women consecutively referred because of idiopathic intracranial hypertension (IIH) as a means of better understanding the origin of IIH, with the ultimate goal of developing novel medical therapies for IIH. Our hypothesis: IIH results in part from inadequate drainage of cerebrospinal fluid (CSF) resulting from thrombotic obstruction to CSF resorption-outflow, favored by thrombophilia-hypofibrinolysis. We conducted the polymerase chain reaction (PCR) and assessed serologic coagulation measures in 65 women (64 of them white) with IIH, PCR in 102 healthy white female controls (72 children, 30 age-matched adults), and serologic measures in the 30 adults. Of the 65 patients, 37 (57%) were found to have PCOS; 16 (43%) were obese (BMI > or = 30 to < 40), and 19 (51%) were extremely obese (BMI > or = 40). Of the 65 women with IIH, 25 (38%) were homozygous for the thrombophilic C677T MTHFR mutation, compared with 14% of controls (14/102) ( P = .0002). Thrombophilic high concentrations of factor VIII (>150%) were present in 9 of 65 (14%) IIH cases, compared with 0 of 30 controls (0%) (Fisher's p [p f ] = .053). An increased concentration of lipoprotein A (> or = 35 mg/dL), associated with hypofibrinolysis, was present in 19 of 65 IIH cases (29%), compared with 3 of 30 controls (10%) (p f = .039). IIH occurred in 18 of 65 IIH patients taking estrogen-progestin contraceptives (28%), in 6 patients taking hormone-replacement therapy (9%), and in 5 pregnant subjects (8%). We speculate that PCOS, associated with obesity and extreme obesity, is a treatable promoter of IIH. We also speculate that if thrombophilia-hypofibrinolysis and subsequent thrombosis are associated with reduced CSF resorption in the arachnoid villi of the brain, thrombophilia and hypofibrinolysis-often exacerbated by thrombophilic exogenous estrogens, pregnancy, or the paradoxical hyperestrogenemia of PCOS-are treatable promoters of IIH.
Subject(s)
Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/diagnosis , Pseudotumor Cerebri/diagnosis , Pseudotumor Cerebri/etiology , Thrombophilia/complications , Thrombophilia/diagnosis , Adolescent , Adult , Blood Coagulation Tests , Estrogens/blood , Female , Fibrinolysis , Humans , Magnetic Resonance Imaging , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Middle Aged , Obesity/complications , Obesity/diagnosis , Polycystic Ovary Syndrome/genetics , Pregnancy , Pseudotumor Cerebri/genetics , Thrombophilia/geneticsSubject(s)
Bone Density/genetics , Receptors, LDL/genetics , Adult , Female , Genes, Dominant , Humans , LDL-Receptor Related Proteins , Low Density Lipoprotein Receptor-Related Protein-5 , Male , Mandible/abnormalities , Mutation, Missense , Palate, Hard/abnormalities , Pedigree , Pseudotumor Cerebri/genetics , Radiography , Skull/diagnostic imaging , Skull/pathology , SyndromeABSTRACT
Hypopituitarism associated with pituitary mass in childhood is most frequently the consequence of craniopharyngioma or Rathke's cleft cyst. We report a patient with an intrasellar pseudotumor associated with hypopituitarism, which led us to a misdiagnosis of intrasellar craniopharyngioma. After spontaneous involution of the mass, diagnosis was revised. DNA analysis showed a deletion in the Prophet of Pit-1 (PROP-1) gene, a pituitary transcription factor. It is important to recognize that a PROP-1 deletion can cause pituitary pseudotumor that can be mistaken for a craniopharyngioma or Rathke's pouch cyst.
Subject(s)
Gene Deletion , Homeodomain Proteins/genetics , Pituitary Neoplasms/genetics , Pseudotumor Cerebri/genetics , Child , DNA/analysis , DNA/genetics , Growth/physiology , Growth Hormone/therapeutic use , Humans , Hydrocortisone/therapeutic use , Magnetic Resonance Imaging , Male , Pituitary Hormones/blood , Pituitary Neoplasms/blood , Pituitary Neoplasms/pathology , Pseudotumor Cerebri/blood , Pseudotumor Cerebri/pathology , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Approximately 30 patients with familial hypomagnesemia-hypercalciuria have been reported. We describe an 8-year-old girl with cardinal findings of familial hypomagnesemia-hypercalciuria (hypomagnesemia, hypermagnesiuria, hypercalciuria, renal insufficiency, hyperuricemia, elevated serum parathormone, hyposthenuria and nephrocalcinosis), who received combination therapy consisting of magnesium salts, thiazide diuretic and potassium supplementation. At the 4-year follow-up investigation under this treatment, the patient was found to have cerebral pseudotumor (increased intracranial pressure with normal or small ventricles on neuroimaging, no evidence of an intracranial mass and normal cerebrospinal fluid composition) with papilledema and visual field defects. Thiazide therapy was terminated and the cerebral pseudotumor disappeared. The authors hypothesize that cerebral pseudotumor in this patient was related to severe hypocalcemia, as a consequence of profound hypomagnesemia induced by protracted thiazide treatment. To our knowledge, this is the first report of a child with familial hypomagnesemia-hypercalciuria who developed pseudotumor cerebri after thiazide therapy.