Intracranial Hypotension Syndrome Research Articles

Continuous intrathecal infusion of nivolumab in advanced melanoma with leptomeningeal disease.

9522 Background: The prognosis of melanoma patients with leptomeningeal disease (LMD) remains poor (median OS of 3.5 months). Intrathecal (IT) drug administration could bypass the blood-cerebrospinal fluid (CSF) barrier and has been explored in many cancers using chemotherapies or monoclonal antibodies. According to a recent phase I trial (PMID36997799), nivolumab IT delivery appears safe while its efficacy remains to be further investigated. Methods: We retrospectively reviewed melanoma patients with LMD treated with continuous IT administration of nivolumab (after decision in multidisciplinary tumor boards) at 2 institutions from February 2021 to October 2023. Patients received 10 to 13.5 mg/day of IT nivolumab delivered through a catheter (cath) connected to an implanted pump. Nivolumab concentrations were monitored in spinal CSF via an independent access port. All patients were enrolled in the MelBase cohort. Results: 11 patients (5 females, median age 52) were treated with continuous IT nivolumab with median (IQR) time to follow-up of 2.5 (1.1-6.3) months (m). Nivolumab was delivered through a spinal (n=10) and ventricular (n=1) cath. All patients had progressed on systemic immunotherapy (ipilimumab + nivolumab n=10, nivolumab n=1). Five patients had symptomatic LMD. All patients were ECOG 0 or 1 except one patient ECOG 3 (due to neurological deficit). Primary tumors were cutaneous (n=8), mucosal (n=1) and unknown (n=2). Tumors were BRAFV600 (n=10) and NRASQ61-mutated (n=1). All but 3 patients had stable extracranial disease. Concomitant systemic therapies were the following: corticosteroids (n=5), intravenous nivolumab (first 3 months of IT therapy) (n=1), and targeted therapies (n=4). The median duration of IT treatment was 1.5 (0.5-2.7) m. The median overall survival (OS) was 2.5 (1.1-NA) m. OS at 3, 12 and 19 m were 36.4 % (16.6-79.5), 27.3 % (10.4-71.6) and 13.6 % (10.4-71.6), respectively. Three patients had prolonged survival (19 m n=2, 12 m n=1). Treatment-related adverse events (all reversible) occurred in 5 patients: hemorrhage on cath path (n=1, grade 2), immune-mediated meningoencephalitis (n=1, grade 3), intracranial hypotension syndrome (n=3, grade 2). Steady state was obtained after 3 weeks of continuous IT infusion. Pharmacokinetics data are summarized in Table. Conclusions: Survival data are slightly inferior to those previously published. However 3 patients had prolonged survival (>=1 year). Median nivolumab concentrations in CSF were comparable to through plasma concentrations at steady state after 3mg/kg IV infusion. High plasma concentrations suggest rapid clearance of nivolumab from the CSF, possibly related to reverse transcytosis of immunoglobulins. [Table: see text]

Blood Patch for Post-Surgical Cerebrospinal Fluid Leak: A Case Report

Intracranial hypotension syndrome may occur secondary to Cerebrospinal Fluid Leak (CSFL). Its etiology can be iatrogenic, traumatic or spontaneous. The most common cause is related to incidental or intentional punctures during anesthetic approaches. It is a rare complication during lumbar spine surgery. The clinical manifestations of this syndrome are characterized by orthostatic headache as the most frequent symptom, accompanied by a wide variety of manifestations, which frequently result in a disability for daily life activities and a delayed recovery. Diagnosis is made through a detailed medical history, the presence of symptoms and signs, and additional imaging studies. Initial treatment is conservative; however, using a hematic patch is recommended for a significant number of patients as the next step, reserving surgical treatment for cases that are not resolved with these measures. This paper presents the clinical case of a 56-year-old female patient diagnosed with CSF fistula following a surgical procedure, which is treated by applying a blood patch with complete remission of symptoms; similarly, a therapeutic algorithm is proposed for the diagnosis of CSFL.

Brain MRI features of postdural puncture headache

BackgroundPostdural puncture headache (PDPH) is a relatively common acute complication that occurs following regional anesthesia and is among the clinical features of secondary intracranial hypotension syndrome (IHS).The aim of this...

Evaluation and management of orthostatic headache in hypermobility disorders.

Headache is a frequent symptom among patients with hypermobility spectrum disorders. This mini review focuses specifically on a challenging aspect of headache evaluation in all patients, but especially those with hypermobility - the orthostatic headache. While the differential for an orthostatic headache is overall limited, patients with hypermobility disorders have risk factors for all of the most commonly encountered orthostatic headache disorders. The most common conditions to produce orthostatic headaches are discussed - spontaneous intracranial hypotension, cervicogenic headache, and postural orthostatic tachycardia syndrome. Less common etiologies of orthostatic headache pertinent to any patient are presented in table format.

Abstract 284: Renal Contrast Excretion After Myelography: A Valuable Tool in The Diagnosis of Cerebrospinal‐Venous Fistulae

Introduction Cerebrospinal‐venous fistulae (CSF‐VFs) represent a pathologic, low‐flow direct connection between the intrathecal space, usually at the level of a diverticular dilation of a nerve root sleeve, and the thoracolumbar venous system. They can cause CSF hypovolemia resulting in an often‐debilitating intracranial hypotension syndrome. Lateral decubitus CT or DSA myelography (CTM, DSM) are the gold‐standard modalities for diagnosing these entities. Their high spatial and temporal resolution allows visualization of the abnormal connection between the two spaces. Yet, the small size and low flow make CSF‐VFs radiographically subtle, and may not be consistently visualized even after a correctly‐performed CTM/DSM, requiring repeated invasive procedures to definitively establish or exclude their presence. Opacification of the renal excretory system 30‐60 minutes after lateral decubitus myelograms is thought to be a highly sensitive and specific indirect sign of the presence of a CSF‐VF 1,2, as this amount of time is considered insufficient to allow arachnoid reabsorption of contrast. Renal pelvises hyperdensity or its absence after a negative decubitus CTM/DSM can prompt further myelographic investigation or definitively rule out the presence of a CSF‐VF on the side of the examination, respectively. Methods We present three patients with severely symptomatic CSF‐VFs treated at our hospital between 2021 and 2023. All patients were females (range: 50‐60 years old). All three patients underwent bilateral diagnostic lateral decubitus DSM/CTM. Exams were performed at least 72 hours apart in order to allow complete clearance of intrathecal contrast. After each myelographic acquisition, patients remained in the lateral decubitus position until abdominal CT imaging was performed at 30 and 45 minutes to detect the presence of contrast in the renal collecting system. Results Patients 1 and 2, had a CSF‐VF between nerve root dural diverticula and the azygos system that was directly visualized on lateral decubitus CTM (patient 1: right T10‐T11, patient 2: left T8‐T9). Contrast was detectable in the renal pelvises after myelography was performed on the affected side, and not detectable after the contralateral investigation. One fistula was treated via CT‐guided targeted blood patch and fibrin glue injection and the other via endovascular Onyx embolization of the tributary Intercostal veins. Patient 3 had an extremely slow flow CSF‐VF at the right T11‐12 level that was identified only after 5 right‐sided decubitus myelograms with both modalities. The repeated exams were based on the presence of contrast in the renal pelvises after each right‐sided procedure and on the absence of renal opacification after the left‐sided myelograms. Eventually, a CSF‐VF was identified. Successful Onyx embolization of the foraminal veins of the R T11‐12 levels was performed. All three patients had complete resolution of symptoms. Conclusion Contrast presence in the renal excretory system after a lateral decubitus CTM/DSM is a potentially highly sensitive and specific indirect diagnostic sign that can establish or exclude the presence of a CSF‐VF on the examined side. It could be particularly helpful when the fistula is not initially detected, as it can prompt aggressive continuation of the myelographic work‐up. Similarly, it can exclude its presence on one side, sparing the patient invasive and low yield diagnostic procedures.

Surgical management of spontaneous intracranial hypotension syndrome: a literature review.

Spontaneous intracranial hypotension (SIH) is a highly disabling but often misdiagnosed disorder. The optimal management options for patients with SIH remain uncertain. The aim of this study was to review studies reporting the management of SIH with a special emphasis on the surgical treatment of SIH including clinical trials, case series and case reports related to the issue of various neurosurgical procedures performed for SIH treatment. The clinical outcomes of patients diagnosed with SIH treated with either only surgery or with surgery as the primary method of treatment were analysed. The PubMed, Scopus and Google Scholar databases were searched according to the established criteria. The literature search revealed seven clinical trials, five case series and eight case reports regarding surgical treatment of patients diagnosed with SIH. Manuscripts reporting at least five individuals treated surgically for SIH were considered as case series. In most published articles, surgery provided clinical benefit, resulting in a success rate of 82.6-100% for complete relief of SIH symptoms. Our literature review has revealed that SIH can be diagnosed reliably by MRI and cisternography. The identification of the location of SIH is mandatory for its successful surgical treatment. The clinical outcome is related to the location of SIH in the spinal canal. Most often, cerebrospinal fluid leakage occurs in the thoracic region. Surgical treatment is very effective and the obtained treatment results are complete and permanent. of the location of SIH is mandatory for its successful surgical treatment. The clinical outcome is related to the location of SIH in the spinal canal. Most often, cerebrospinal fluid leakage occurs in the thoracic region. Surgical treatment is very effective and the obtained treatment results are complete and permanent.

Intracranial hypotension syndrome in a pediatric patient with Marfan syndrome

Intracranial hypotension syndrome (IHS) is attributed to reduced cerebrospinal fluid (CSF) pressure. It may be spontaneous or secondary to a history of trauma or systemic disease. We present the case of an 11-year-old boy, with medical history of Marfan syndrome, with orthostatic headache and persistent vomiting (12 hours) following a fall on the sacrococcygeal region. Magnetic resonance showed extradural fluid collections at dorsal and lumbosacral levels, compatible with CSF leak. The condition was resolved with treatment, but the patient had two new episodes during the follow-up period. Thus, an epidural blood patch was performed two years after the first episode. Although HIS is uncommon in children, it should be suspected in patients with orthostatic headache, particularly if the patient presents a connectivopathy. Few studies have assessed the management of HIS in paediatric age. The case presented here and the reviewed available literature provides further data for these type of cases.

Patología del líquido cefalorraquídeo. Hidrocefalia, pseudotumor cerebral y síndrome de presión baja

Cerebrospinal fluid (CSF) pathology refers to primary abnormalities of the CSF and its circulation. Hydrocephalus is the pathological increase in the size of the cerebral ventricles due to an increase in CSF, the result of an imbalance between formation (normally constant) and drainage, due to defects in reabsorption or circulation; hydrocephalus is thus classified as communicating or noncommunicating. Hydrocephalus can occur in children (the majority congenital) and adults. A special type of chronic hydrocephalus in adults is normal pressure hydrocephalus and its famous Hakim-Adams triad. Pseudotumor cerebri and idiopathic intracranial hypertension (IIH) are characterized by symptoms of intracranial hypertension (IH) with elevation of CSF opening pressure; the main problem is potential vision loss. Intracranial hypotension syndrome is caused by leakage of CSF through the thecal sac, frequently after a lumbar puncture. It is normally characterized by orthostatic headache, decreased CSF pressure, and meningeal uptake on magnetic resonance imaging tests.

Тугоухость и деменция – сопряженность развития: неизбежность и возможная обратимость, желаемое и действительное

In people over 65 years of age, hearing disorders occur in 30% of cases. Hearing impairment affects the psychoemotional status of patients, exacerbating the progression of cognitive deficits. One of the variants of frontotemporal dementia (FTD) is pathogenetically caused by intracranial hypotension syndrome (IHS). The incidence of IHS is estimated to be approximately 2–5 cases per 100,000 inhabitants. One of the complications of SVH is dementia with sagging brain syndrome (BSD), clinically similar to FTD. IHS is regularly accompanied by cochleovestibular disorders, among which audiological deviations prevail. To confirm IHS, positional audiometry is of great importance. Unlike typical FTD, for which effective therapy is unknown, BSD treatment results are positive in 81% of cases. The authors of the publication note an improvement in concentration of attention, analytical ability, and daytime activity in their patients after the course of treatment of IHS. For earlier detection, or confirmation, of the mentioned pathology at the diagnostic stage, the authors propose an increase in the number of studies due to audiometric tests.

Prof Cerebrospinal CNS-Leaks: State of the Art in Imaging Diagnosis with Special Focus on Intrathecal MRI Paramagnetic Contrast Agents Procedures

MR imaging has proved invaluable in anatomic depiction of the cerebrospinal fluid (CSF) spaces and the surrounding neural and non-neural tissue, although there are still some clinical situations (i.e., cases of CSF-flow alterations, communicating or non-communicating cyst masses bordering CSF pathways, or craniospinal CSF leaks) in which further imaging tests may be required for a definitive diagnosis. This paper will review the state-of-the-art imaging in these processes, including Radionuclide Cisternography, plain Computed Tomography (CT) and enhanced-CT Cisternography/ myelography, as well as Magnetic Resonance Imaging (MRI) and contrast-enhanced Cisternography/myelography, emphasizing the latest CT and MR imaging refinement advances and proposing tailored specific approaches for two well-established clinical syndromes, namely CSF rhinorrhea and intracranial hypotension syndrome.

Prenatal intracranial hypotension syndrome in congenital cephalocele: Insights into pathophysiologic mechanisms and importance of defect coverage.

To compare specific fetal cranial and cerebral findings indicative of prenatal intracranial hypotension (PICH) syndrome between open and closed cephaloceles. Two groups of fetuses with cephalocele who underwent magnetic resonance imaging scan were selected based on the defect coverage: covered ("closed cephalocele" group, n=4) and uncovered by skin ("open cephalocele" group, n=8). The presence of signs associated with PICH syndrome was evaluated and findings compared between groups. Cases from the open cephalocele group showed statistically significant differences in comparison with the closed cephalocele group regarding reduction of the interpeduncular angle (p=0.006), reduced amount of cerebrospinal fluid in the subarachnoid space (p=0.01), collapsed/severely reduced fourth ventricle (p=0.03), cephalocele content (p=0.03), and identification of a vector traction (p=0.03). There were no differences in the presence of cerebellar tonsillar descent, obstructive ventriculomegaly, and presence of the lemon sign. In comparison with gestational age-matched controls, only the biparietal diameter but not the head circumference was significantly smaller in both the open and closed cephalocele groups (p<0.05). Congenital cephaloceles present distinct imaging behavior depending on the defect coverage. Therefore, the classification of cephalocele should include, in addition to location and content, the presence or absence of skin fully covering the defect.

Spontaneous intracranial hypotension syndrome presented with sixth cranial nerve palsy: a case report

Introduction Spontaneous intracranial hypotension (SIH) is a secondary cause of headache often misdiagnosed and underdiagnosed disorder. The main presentation is orthostatic headache. An uncommon symptom is cranial nerve palsy. We described a case of SIH that presented to our service with sixth cranial nerve palsy. Case Report Female, 39 years old, no relevant medical past or history of trauma, awoke due intense holocranial headache, associated with vomiting and photophobia, worsening in orthostasis. In the general emergency department, she was release with prescription of analgesics and topiramate, without resolution. After a week, the patient reported diplopia and was referred to our service, a tertiary center. In admission, she kept an intense orthostatic headache and in neurologic examination she presented right sixth nerve palsy, no other deficits. Laboratorial tests were normal, including metabolic and infectious marks. Cerebrospinal fluid (CSF) opening pressure was low (50 mmH2O) and analysis showed elevated protein levels (158mg/dl). MRI showed diffuse pachymeningeal enhancement and venous sinus distension, mainly in superior sagittal venous sinus. CT myelogram detected a spinal CSF leak in transition C1-C2. Initially, performed hydration and bed rest, while patient with partial improvement of headache. An epidural blood patch was then performed using 15ml of autologous blood with compatible contrast and lidocaine. There was complete resolution of pain after the procedure and four weeks later complete resolution of right sixth nerve palsy. Discussion According to International Classification of Headaches Disorders, third edition (ICHD-3), the headache attributed to SIH is descripted as a headache has developed in temporal relation to low CSF pressure (&lt;60mm H2O) and/or evidence of CSF leakage on imaging. (To see the complete abstract, please, check out the PDF).

Surgical treatment of spinal CSF-venous fistulas: a systematic review

CSF-venous fistula is a relatively new and unexplored cause of spontaneous intracranial hypotension syndrome (SIH). The syndrome was first described in 1974 in a patient with chronic lumbar puncture-associated headache after digital subtraction myelography. After 40 years, CSF-venous fistula was considered as the cause of the SIH syndrome in patients with orthostatic headache. CSF-venous fistula is a pathological connection of the subarachnoid space and the adjacent epidural vein or veins. It is one of the top three causes of SIH along with dural defects and meningeal diverticulum. Despite the insufficient assessment of the prevalence of CSF-venous fistulas, some authors consider the syndrome to be the cause of 25 % of the cases. Positional headaches, as well as headaches associated with cough and Valsalva maneuver, are the most common symptoms in patients with CSF-venous fistulas. These patients are characterized by typical MRI signs of intracranial hypotension, such as a clear visualization of pachymeninx, venous congestion, an increase in the size of the pituitary gland, brain sagging syndrome, tonsillar herniation, etc. However, due to the rarity of this disease, algorithms for its diagnosis and treatment have not been established. Management of patients is usually limited to conservative treatment as the first-line method. This includes EBP alone or in combination with fibrin glue. Open surgery for ligation or coagulation of the fistula is used in cases of failed conservative treatment. Endovascular occlusion of the draining vein is a relatively new and less common treatment. The article presents a systematic review of the literature and analysis of the clinical results of various types of treatment for CSF-venous fistulas (EBP, surgical excision and endovascular embolization).

Headache and neuroimaging findings in conditions of cerebrospinal fluid (CSF) circulation disorders: in hydrocephalus, pseudotumor cerebri, and CSF hypotension syndrome

The authors wish in this narrative minireview show and comment on some neuroimaging findings encountered in patients with conditions of cerebrospinal fluid circulation disorders, such as in the hydrocephalus, pseudotumor cerebri, and CSF hypotension syndrome. The MRI of a young woman with a clinical diagnosis of post-dural puncture headache, performed on the fourth postpartum day after cesarean delivery, evolving with headache and diplopia, is shown. Non-contrast-enhanced sagittal T1 magnetic resonance imaging shows that the cerebellar tonsils are at the level of the foramen magnum, therefore still within normal limits, but, despite that, the opening of the cerebral aqueduct in the third ventricle is below the imaginary line connecting the anterior clinoid to the vein of Galen, therefore considered abnormally lower than the expected anatomical position. The axial T1-weighted images with post-contrast fat suppression also show impregnation and thickening of the dura mater. There is also mild engorgement of the cerebral venous sinuses, best demonstrated on T1 with post-contrast fat suppression, which is also identified on post-contrast magnetic resonance angiography, with no signs of venous thrombosis. We conclude that the diagnosis of a patient with intracranial hypotension syndrome can be suspected or confirmed with typical neuroimaging findings.

Successful treatment of intractable pseudomeningocele with FXIII deficiency by surgery and FXIII replacement therapy: A case report

Pseudomeningocele is an extradural cystic collection of cerebrospinal fluid (CSF) and is rare and typically asymptomatic. However, pseudomeningocele is sometimes associated with symptoms. Whether symptomatic pseudomeningocele is best treated conservatively or surgically remains controversial. Factor XIII (FXIII) is a blood coagulation factor that also promotes fibroblast proliferation during wound healing. Although treatment of postsurgical CSF leakage with FXIII has been reported, there have been no reports on surgical treatment and FXIII replacement therapy of pseudomeningocele with FXIII deficiency. We report a case of pseudomeningocele with FXIII deficiency that was successfully treated by surgery and FXIII replacement therapy. The patient presented with symptoms of intracranial hypotension syndrome that had started a few months after laminectomy for thoracic ossification of the ligamentum flavum 2 years earlier. Magnetic resonance imaging and delayed computed tomography myelography confirmed a diagnosis of pseudomeningocele. Epidural blood patch treatment was performed twice but did not result in improvement. Furthermore, the FXIII level decreased to 56%, so the patient was also diagnosed as having acquired FXIII deficiency. We elected to treat the patient by surgery with FXIII replacement therapy. The dural injury was repaired using an artificial dura mater patch, fibrin glue, and polyglycolic acid sheets. The FXIII level was 74%–135% during the perioperative period. The patient had a good postoperative course. Postoperative magnetic resonance images showed resolution of the pseudomeningocele. There was no recurrence during 6 months of follow-up. Perioperative FXIII replacement may be a useful treatment for pseudomeningocele with FXIII deficiency.

MRI Diagnostics of Intracranial hypotension Syndrome on the Example of Clinical Observation

Intracranial hypotension is a clinical and radiological syndrome, manifested by a decrease in the volume or pressure of the cerebrospinal fluid caused by various reasons, one of the main clinical manifestations of which are orthostatic headaches. The gold standard in the radiation diagnosis of this condition is magnetic resonance imaging (MRI). Increasing the awareness of radiologists about this pathology, its manifestations on MRI, will allow more often to diagnose this syndrome and choose the tactics of further treatment. This publication presents its own clinical observation — a patient with intracranial hypotension syndrome, on his example, MR and clinical manifestations are considered, and some data on the etiology and pathogenetic mechanisms of the described pathological process are also given.

Japanese Guideline for Traumatic Intracranial Hypotension:Interpretation and Current Situation

Since the 2000s, "intracranial hypotension syndrome associated with trauma" has become a social problem in relation to litigation and compensation issues in Japan. To address this problem, guidelines for correct diagnosis have been developed. The basic pathogenesis of this disease is cerebrospinal fluid leakage caused by fragile tissue injury due to trauma. In order to improve the treatment outcome of this disease, it is important to prove the CSF leakage directly, using diagnostic imaging based on the guidelines, rather than diagnosing it based on clinical manifestations alone. For management, an epidural blood patch(EBP)should be used only after careful consideration. As such, rest and adequate fluid replacement should generally be given first. However, in cases with concomitant subdural hematoma, the order of hematoma irrigation and EBP should be determined according to the condition and urgency of each patient. In addition, it is necessary to standardize the formal name of this condition in papers to ensure rigorous academic discussion.

Intracranial Hypotension, Subdural Haematoma and Sjogren Syndrome.

Intracranial Hypotension, Subdural Haematoma and Sjogren Syndrome.

Prenatal intracranial hypotension syndrome: new insights into the mechanisms of fenestration of septi pellucidi and ventriculomegaly in fetuses with open spinal dysraphism

Objective To study the prevalence of abnormalities of the septi pellucidi (SP) in a cohort of fetuses with open spinal dysraphism (OSD) and to determine whether this condition is secondary to obstructive ventriculomegaly and, therefore, part of the natural history of prenatal intracranial hypotension (PICH) syndrome. Methods Magnetic resonance imaging (MRI) studies from fetuses with OSD were analyzed. The SP were assessed using axial and coronal T2-weighted images of the fetal brain and classified as intact, partially absent, or completely absent. Additionally, the correlation between the presence or absence of the SP and the size of the lateral ventricles, degree of cerebellar tonsillar herniation, collapse of the fourth ventricle, and interpeduncular angle was investigated. Results A total of 32 fetuses with OSD were studied. Mean gestational age at the time of the fetal MRI was 25.5 ± 3.9 weeks (range, 19–35) and mean ventricular size was 16.2 ± 4.2 mm (range, 8–26). Twenty-three (71.9%) fetuses had cerebellar tonsillar herniation. The IPA was completely collapsed in 23 cases (71.9%), reduced in seven (21.9%), and unreadable in two (6.3%). Twenty (62.5%) fetuses presented with intact SP, 10 (31.3%) with partially absent SP (incomplete fenestration), and two (6.3%) with completely absent SP (complete fenestration). Fenestration of the SP correlated significantly with the degree of ventriculomegaly (Pearson’s correlation coefficient =0.459; p = .01). However, there was no correlation with the IPA, collapse of the fourth ventricle, and cerebellar tonsillar herniation. Conclusions More than one-third of the fetuses with OSD had fenestration of the SP. The most probable etiology is increased intraventricular pressure leading to local necrosis of the SP. As fenestration of the SP is a secondary event associated with PICH syndrome, this condition should not be considered a contraindication for intrauterine repair of the spinal defect. Instead, it should be seen as an indicator of the severity of the intraventricular pressure.

Clinical Presentation, Investigation Findings, and Treatment Outcomes of Spontaneous Intracranial Hypotension Syndrome

Spontaneous intracranial hypotension (SIH) is a highly disabling but often misdiagnosed disorder. The best management options for patients with SIH are still uncertain. To provide an objective summary of the available evidence on the clinical presentation, investigations findings, and treatment outcomes for SIH. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline-compliant systematic review and meta-analysis of the literature on SIH. Three databases were searched from inception to April 30, 2020: PubMed/MEDLINE, Embase, and Cochrane. The following search terms were used in each database: spontaneous intracranial hypotension, low CSF syndrome, low CSF pressure syndrome, low CSF volume syndrome, intracranial hypotension, low CSF pressure, low CSF volume, CSF hypovolemia, CSF hypovolaemia, spontaneous spinal CSF leak, spinal CSF leak, and CSF leak syndrome. Original studies in English language reporting 10 or more patients with SIH were selected by consensus. Data on clinical presentation, investigations findings, and treatment outcomes were collected and summarized by multiple observers. Random-effect meta-analyses were used to calculate pooled estimates of means and proportions. The predetermined main outcomes were the pooled estimate proportions of symptoms of SIH, imaging findings (brain and spinal imaging), and treatment outcomes (conservative, epidural blood patches, and surgical). Of 6878 articles, 144 met the selection criteria and reported on average 53 patients with SIH each (range, 10-568 patients). The most common symptoms were orthostatic headache (92% [95% CI, 87%-96%]), nausea (54% [95% CI, 46%-62%]), and neck pain/stiffness (43% [95% CI, 32%-53%]). Brain magnetic resonance imaging was the most sensitive investigation, with diffuse pachymeningeal enhancement identified in 73% (95% CI, 67%-80%) of patients. Brain magnetic resonance imaging findings were normal in 19% (95% CI, 13%-24%) of patients. Spinal neuroimaging identified extradural cerebrospinal fluid in 48% to 76% of patients. Digital subtraction myelography and magnetic resonance myelography with intrathecal gadolinium had high sensitivity in identifying the exact leak site. Lumbar puncture opening pressures were low, normal (60-200 mm H2O), and high in 67% (95% CI, 54%-80%), 32% (95% CI, 20%-44%), and 3% (95% CI, 1%-6%), respectively. Conservative treatment was effective in 28% (95% CI, 18%-37%) of patients and a single epidural blood patch was successful in 64% (95% CI, 56%-72%). Large epidural blood patches (>20 mL) had better success rates than small epidural blood patches (77% [95% CI, 63%-91%] and 66% [95% CI, 55%-77%], respectively). Spontaneous intracranial hypotension should not be excluded on the basis of a nonorthostatic headache, normal neuroimaging findings, or normal lumbar puncture opening pressure. Despite the heterogeneous nature of the studies available in the literature and the lack of controlled interventional studies, this systematic review offers a comprehensive and objective summary of the evidence on SIH that could be useful in guiding clinical practice and future research.