Popping the balloon: Abrupt onset of a spinal CSF leak and spontaneous intracranial hypotension in idiopathic intracranial hypertension, a case report.

OBJECTIVES: Spontaneous intracranial hypotension (SIH) is a debilitating neurologic condition that is often thought of as separate from idiopathic intracranial hypertension (IIH). The unique case presented here details a spontaneous spinal cerebrospinal fluid (CSF) leak that developed abruptly following a CSF pressure elevating maneuver in a patient with pre-existing intracranial hypertension, raising the possibility of a causative link between the two conditions. RESULTS: A 40-year-old woman with symptomatic IIH developed a dural tear of a thoracic spinal nerve root sleeve during an episode of Valsalva maneuver leading to a CSF leak and development of symptomatic SIH. This was successfully treated with epidural blood and fibrin glue patch and the patient is now symptom-free. DISCUSSION: The implication of a possible causative link between elevated CSF pressure and subsequent development of dural rupture and SIH raises important questions regarding the pathophysiology of SIH in some cases. Furthermore, it suggests that there could be a potential prophylactic benefit of CSF pressure lowering medications in preventing the development of SIH in patients with IIH.

Intracranial Pressure Monitoring in Poor-Grade Patients with Aneurysmal Subarachnoid Hemorrhage Treated by Coiling.

OBJECTIVE: The main objective of the present study was to analyze the intracranial pressure (ICP) and cerebral perfusion pressure (CPP) changes during coiling. We also evaluated the prevalence of rebleeding and outcomes for patients monitored before and after coiling. METHODS: Ninety-nine consecutive poor-grade patients with aneurysmal subarachnoid hemorrhage (aSAH; World Federation of Neurological Surgeons grade IV and V) were enrolled in our prospective observational study. For 31 patients, ICP and CPP monitoring was started immediately after the diagnosis of aSAH, and the values were recorded every 15 minutes during coiling (early ICP group). For 68 patients, ICP and CPP monitoring began after coiling (late ICP group). The outcomes were evaluated at 90 days using the modified Rankin scale. RESULTS: At the beginning of coiling, the ICP was >20 mm Hg in 10 patients (35.7%). The median ICP was 18 mm Hg (range, 5-60 mm Hg). The CPP was <60 mm Hg in 6 patients (24%). The median CPP was 70 mm Hg (range, 30-101 mm Hg). Despite medical treatment and/or cerebrospinal fluid drainage, 51.6% of the patients monitored during coiling had at least one episode of intracranial hypertension (defined as ICP >20 mm Hg), and 51.6% had at least one episode of reduced CPP (defined as CPP <60 mm Hg). Early monitoring (before aneurysm repair) was not associated with rebleeding. At 90 days, the functional recovery was better in the early ICP group (P = 0.004). CONCLUSIONS: During coiling, patients with poor-grade aSAH can experience episodes of intracranial hypertension and reduced CPP. Early and appropriate treatment of elevated ICP was not associated with rebleeding and might have improved the outcomes.

Clinical significance of Epstein-Barr virus in the cerebrospinal fluid of immunocompetent patients.

INTRODUCTION: Polymerase chain reaction (PCR)-based testing of cerebrospinal fluid (CSF) samples has greatly facilitated the diagnosis of central nervous system (CNS) infections. However, the clinical significance of Epstein-Barr virus (EBV) DNA in CSF of individuals with suspected CNS infection remains unclear. We wanted to gain a better understanding of EBV as an infectious agent in immunocompetent patients with CNS disorders. METHODS: We identified cases of EBV-associated CNS infections and reviewed their clinical and laboratory characteristics. The study population was drawn from patients with EBV PCR positivity in CSF who visited Pusan National University Hospital between 2010 and 2019. RESULTS: Of the 780 CSF samples examined during the 10-year study period, 42 (5.4 %) were positive for EBV DNA; 9 of the patients (21.4 %) were diagnosed with non-CNS infectious diseases, such as optic neuritis, Guillain-Barré syndrome, and idiopathic intracranial hypotension, and the other 33 cases were classified as CNS infections (22 as encephalitis and 11 as meningitis). Intensive care unit admission (13/33 patients, 39.3 %) and presence of severe neurological sequelae at discharge (8/33 patients, 24.2 %) were relatively frequent. In 10 patients (30.3 %), the following pathogens were detected in CSF in addition to EBV: varicella-zoster virus (n = 3), cytomegalovirus (n = 2), herpes simplex virus 1 (n = 1), herpes simplex virus 2 (n = 1), Streptococcus pneumomiae (n = 2), and Enterococcus faecalis (n = 1). The EBV-only group (n = 23) and the co-infection group (n = 10) did not differ in age, gender, laboratory data, results of brain imaging studies, clinical manifestations, or prognosis; however, the co-infected patients had higher CSF protein levels. CONCLUSION: EBV DNA in CSF is occasionally found in the immunocompetent population; the virus was commonly associated with encephalitis and poor prognosis, and frequently found together with other microbes in CSF.

Insights into the natural history of spontaneous intracranial hypotension from infusion testing.

OBJECTIVE: To assess the pathophysiologic changes in patients with spontaneous intracranial hypotension (SIH) based on measures of CSF dynamics, and on the duration of symptoms, in a retrospective case-controlled study. METHODS: We included consecutive patients investigated for SIH at our department from January 2012 to February 2018. CSF leak was considered confirmed if extrathecal contrast spillage was seen on imaging (CT or MRI) after intrathecal contrast application, or dural breach was detected by direct intraoperative visualization. We divided patients with a confirmed CSF leak into 3 groups depending on the symptom duration, as follows: ≤10, 11-52, and >52 weeks. Clinical characteristics and measures of CSF fluid dynamics obtained by computerized lumbar infusion testing were analyzed over time and compared with a reference population. RESULTS: Among the 137 patients included, 69 had a confirmed CSF leak. Whereas 93.1% with <10 weeks of symptoms displayed typical orthostatic headache, only 62.5% with >10 weeks of symptoms did (p = 0.004). Analysis of infusion tests revealed differences between groups with different symptom duration for CSF outflow resistance (p < 0.001), lumbar baseline pressure (p = 0.013), lumbar plateau pressure (p < 0.001), baseline pressure amplitude (p = 0.021), plateau pressure amplitude (p = 0.001), pressure-volume index (p = 0.001), elastance (p < 0.001), and CSF production rate (p = 0.001). Compared to the reference population, only patients with acute symptoms showed a significantly altered CSF dynamics profile. CONCLUSION: A CSF leak dramatically alters CSF dynamics acutely, but the pattern changes over time. There is an association between the clinical presentation and changes in CSF dynamics.

Delayed Iatrogenic Intracranial Hypotension After Thoracotomy.

We report a case of intracranial hypotension (IH) after thoracotomy. A 56-year-old woman presented 10 days after a left upper lobectomy with severe headache due to pneumocephalus and pneumorrhachis, which resolved on conservative treatment. Two months later, the patient was readmitted in an unconscious state with characteristics of IH and "sagging brain." Subsequent magnetic resonance imaging revealed a fistula at the level of the left Th5 pedicle. The patient underwent operation with closure of the fistula and recovered without complications. The presence of pneumocephalus and pneumorrhachis after thoracotomy should raise the suspicion of a persistent subarachnoid-pleural fistula to prevent IH and "sagging brain."

Is "normal tension glaucoma" glaucoma?

Primary open angle glaucoma (POAG) represents a distinct disease entity with elevated intraocular pressure (IOP) as the main risk factor, even though the reasons for why the IOP is elevated remains to be elucidated. It is considered that normal tension glaucoma (NTG) is a subtype of POAG, comprising a special form of glaucomatous neurodegeneration or glaucomatous optic neuropathy (GON) almost exactly the same as that seen in POAG, but the IOP, as named, remains in the statistically normal range. Actually the disease entity of NTG has been a profound confusion and it is difficult to be accurately conceptualized. One of the reasons is that the IOP is closely linked to the occurrence of GON in POAG but not in NTG, and for the latter, it seems that GON is secondary to a number of local or systemic disorders. In recent years, increasing evidences suggest that NTG or IOP independent GON is a non-glaucomatous disease with different disease entities from POAG and with more diverse and complex etiologies. Here we hypothesized that NTG, at least for those with recognizable primary diseases, is not a glaucomatous disease; instead, it represents a group of disorders with GON as a characteristic clinical feature or phenotype.

Capacity to Compensate for Central Hypovolemia and Effects of Menstrual Cycle Phases.

BACKGROUND: Tolerance to central hypovolemia is dictated by exhaustion of the physiological capacity to compensate called the compensatory reserve. Such physiological compromise can have detrimental impact on performance in aerospace environments as well as survival from hemorrhage on the battlefield. We induced central hypovolemia using progressively stepwise lower body negative pressure (LBNP) in women during various phases of the menstrual cycle to test the hypothesis that similar tolerance across all menstrual cycle phases would be reflected by similar changes in compensatory reserve.METHODS: Based on self-reporting of the last menstrual period, 40 healthy women, matched by demographics, were classified into 1 of 5 menstrual cycle phases: early follicular (EF, Days 1-7; N = 10), late follicular and ovulatory (LF, Days 9-15, N = 6), early luteal (EL, Days 16-18, N = 6), midluteal (ML, Days 19-25, N = 8), and late luteal (LL, Days 26-30, N = 10). All subjects had a 28-30 d menstrual cycle and were not taking oral contraceptives. Tolerance to central hypovolemia was measured as time (seconds) from baseline to the onset of presyncopal symptoms induced by LBNP.RESULTS: Time to presyncope as well as hemodynamic and compensatory reserve responses were statistically indistinguishable across all menstrual cycle phases.DISCUSSION: Consistent with our hypothesis, compensatory reserve with associated hemodynamic responses and tolerance to central hypovolemia was not affected by menstrual cycle phases. Our findings indicate experimental comparisons of responses to central hypovolemia involving the participation of healthy women with normal menstrual cycles and not taking oral contraceptives can be conducted independent of menstrual cycle phase.Convertino VA, Schlotman TE, Stacey W, Hinojosa-Laborde C. Capacity to compensate for central hypovolemia and effects of menstrual cycle phases. Aerosp Med Hum Perform. 2019; 90(4):378-383.

A clinical analysis on 40 cases of spontaneous intracranial hypotension syndrome.

OBJECTIVE: To investigate clinical and imaging features of 40 patients with spontaneous intracranial hypotension (SIH). METHODS: 40 cases of spontaneous intracranial hypotension (SIH) diagnosed in our hospital from June 2013 to September 2017 were collected and retrospectively analyzed. RESULTS: In our study, the male to female ratio was 2:3. The average age of onset was 43.0 ± 15.0 years. There were 12 (30.0%) patients with clear incentives, mostly catching cold. The average length of hospital stay was 11.2 ± 6.3 days. All the patients showed orthostatic headaches, 62.5% patients with nausea or vomiting, 40.0% patients with neck stiffness, 17.5% patients with dizziness and vertigo, 10.0% patients with numbness and weakness of limbs, 5% patients with neck discomfort, and 2.5% patients with visual symptoms (visual impairment, photophobia, diplopia). 24 patients underwent CT scans which showed no abnormalities in 20 cases (83.3%), subdural fluid accumulation in 3 cases (12.5%), and subdural haematoma in 1 case (2.5%). Cranial contrast-enhanced MR scans showed diffuse pachymeningeal enhancement (95.83%, 23/24), signs of pituitary hyperaemia in 5 cases (20.8%), subdural fluid accumulation and subdural hematoma in 4 cases (16.7%), sagging of the brain in 3 cases (12.5%), and engorgement of venous structures in 1 case (4.1%). Six patients underwent plain and contrast-enhanced spinal MR scans which showed varying degrees of dural thickening and enhanced performance in all the patients. 92.5% (37/40) of patients had cerebrospinal fluid pressure <60 mmH2O on lumbar puncture. 97.5% of patients underwent conservative treatment with drugs and had a good outcome. CONCLUSION: Orthostatic headache and cranial MRI diffuse pachymeningeal enhancement are characteristic features of SIH. Cranial contrast-enhanced MR scan is recognized as the first and non-invasive investigation in the diagnosis of SIH. Most patients had cerebrospinal fluid pressure <60 mmH2O. The vast majority of patients improved with fluid replacement.

A Review of Spontaneous Intracranial Hypotension.

PURPOSE OF REVIEW: Spontaneous intracranial hypotension (SIH) is an underdiagnosed phenomenon predominantly presenting with low cerebrospinal fluid (CSF) pressure and postural headache in setting of CSF leak. The goal of this paper is to provide updates on the pathology, diagnosis, and management of SIH. The utility of multiple imaging modalities and the use of epidural blood patches and fibrin glue polymers are explored. RECENT FINDINGS: In regard to diagnosis, new non-invasive modalities in detection of SIH including transorbital ultrasound and serum biomarkers are found. In addition, increased efficacy of large volume and repeated placement of multiple epidural blood patches (EBP) are seen. In addition, the management of refractory SIH using fibrin glue polymers has proved efficacious in recent case series. While the diagnosis may be challenging for clinicians, future research in SIH is leading to more rapid detection methods. Future studies may target optimal use of EBP in comparison to fibrin glue polymers, in addition to new developments in increased understanding of SIH physiology and phenotype.

Spontaneous intracranial hypotension associated with pachymeningeal enhancement in a patient with systemic lupus erythematosus (SLE): an extremely rare presenting feature.

A 16-years-old girl presented to our institution with history of severe bilateral headache for 5 days associated with vomiting. She also had fever for 2 months without any localising symptoms and skin lesions for 1 month. Examination revealed erythematous rash over bridge of nose and ear lobes, ulcer over hard palate and tenderness of small joints of both hands. Systemic examination was unremarkable except for bilateral papilloedema. Investigations revealed anaemia, leucopenia and elevated erythrocyte sedimentation rate. Cranial imaging revealed diffuse pachymeningeal enhancement with subdural effusion. Lumbar puncture revealed no abnormal findings in cerebrospinal fluid except low opening pressure. Antinuclear antibody was 4+ with anti-Sm antibody positive. She was diagnosed to have spontaneous intracranial hypotension associated with pachymeningeal enhancement secondary to systemic lupus erythematosus. She showed dramatic improvement with steroid and azathioprine therapy. She continues to be asymptomatic after 2 years of follow-up.

Intracranial hypotension and hypertension: reversible Chiari malformation due to dynamic cerebrospinal fluid abnormalities in Gorham-Stout disease. Case report.

Gorham-Stout disease (GSD) is an intractable disease characterized by massive osteolysis caused by abnormal lymphangiogenesis in bone. In rare cases of GSD, CSF abnormalities develop. The authors present the case of a 19-year-old woman with GSD presenting with orthostatic headache due to intracranial hypotension (5 cm H2O). The clinical course of this case was very unusual. Orthostatic headache was associated with a CSF leak from the thigh after pathological fractures of the femur and pelvis. The chronic CSF leak led to acquired Chiari malformation (CM) with syringomyelia. After an epidural blood patch, her neurological status improved; however, after the complete arrest of the CSF leak from the thigh, she presented with severe nonpostural headache and progressive visual acuity loss with optic papilledema. A ventriculoperitoneal shunt was placed to treat intracranial hypertension (50 cm H2O). Headache improved and optic papilledema decreased after shunt surgery. This case shows that dynamic CSF abnormalities may lead to reversible CM in patients with GSD. Sealing a CSF leak rather than performing suboccipital decompression is recommended for acquired CM resulting from a CSF leak.

Magnetic resonance imaging provides evidence of glymphatic drainage from human brain to cervical lymph nodes.

Pre-clinical research in rodents provides evidence that the central nervous system (CNS) has functional lymphatic vessels. In-vivo observations in humans, however, are not demonstrated. We here show data on CNS lymphatic drainage to cervical lymph nodes in-vivo by magnetic resonance imaging (MRI) enhanced with an intrathecal contrast agent as a cerebrospinal fluid (CSF) tracer. Standardized MRI of the intracranial compartment and the neck were acquired before and up to 24-48 hours following intrathecal contrast agent administration in 19 individuals. Contrast enhancement was radiologically confirmed by signal changes in CSF nearby inferior frontal gyrus, brain parenchyma of inferior frontal gyrus, parahippocampal gyrus, thalamus and pons, and parenchyma of cervical lymph node, and with sagittal sinus and neck muscle serving as reference tissue for cranial and neck MRI acquisitions, respectively. Time series of changes in signal intensity shows that contrast enhancement within CSF precedes glymphatic enhancement and peaks at 4-6 hours following intrathecal injection. Cervical lymph node enhancement coincides in time with peak glymphatic enhancement, with peak after 24 hours. Our findings provide in-vivo evidence of CSF tracer drainage to cervical lymph nodes in humans. The time course of lymph node enhancement coincided with brain glymphatic enhancement rather than with CSF enhancement.

Chest Pain as a Manifestation of Intracranial Hypotension: Report of Four Cases.

BACKGROUND: Chest pain has not been recognized as a manifestation of intracranial hypotension secondary to cerebrospinal fluid leakage. CASE REPORT: We report on 4 patients with intracranial hypotension diagnosed by the pattern of headaches, temporal proximity to dural puncture, magnetic resonance imaging findings, and resolution of symptoms after epidural blood patch who presented with chest pain. The chest pain was episodic, located in the sternal and interscapular region for the first 3 patients, with no radiation to any other region and no clear relationship to exertion. The fourth patient had episodic chest pain located in the subclavicular and suprascapular region. Two patients reported dyspnea with chest pain. Underlying coronary artery ischemia was excluded using a combination of the electrocardiogram and cardiac enzyme assays. The pain resolved after epidural blood patch treatment. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Clinicians should be aware of chest pain that can be seen with intracranial hypotension and cerebrospinal leakage to ensure appropriate diagnostic tests and treatment.

Spontaneous Intracranial Hypotension: 10 Myths and Misperceptions.

OBJECTIVE: To discuss common myths and misperceptions about spontaneous intracranial hypotension (SIH), focusing on common issues related to diagnosis and treatment, and to review the evidence that contradicts and clarifies these myths. BACKGROUND: Recognition of SIH has increased in recent years. With increasing recognition, however, has come an increased demand for management by neurologists and headache specialists, some of whom have little prior experience with the condition. This dearth of practical experience, and lack of awareness of recent investigations into SIH, produces heterogeneity in diagnostic and treatment pathways, driven in part by outdated, confusing, or unsubstantiated conceptions of the condition. We sought to address this heterogeneity by identifying 10 myths and misperceptions that we frequently encounter when receiving referrals for suspected or confirmed SIH, and to review the literature addressing these topics. METHODS: Ten topics relevant to diagnosis and treatment SIH were generated by the authors. A search for studies addressing SIH was conducted using PubMed and EMBASE, limited to English language only, peer reviewed publications from inception to 2018. Individual case reports were excluded. The resulting studies were reviewed for relevance to the topics in question. RESULTS: The search generated 557 studies addressing SIH; 75 case reports were excluded. Fifty-four studies were considered to be of high relevance to the topics addressed, and were included in the data synthesis. The topics are presented in the form of a narrative review. CONCLUSIONS: The understanding of SIH has evolved over the recent decades, leading to improvements in knowledge about the pathophysiology of the condition, diagnostic strategies, and expanded treatments. Awareness of these changes, and dispelling outdated misconceptions about SIH, is critical to providing appropriate care for patients and guiding future investigations going forward.

Prevalence of hyperdense paraspinal vein sign in patients with spontaneous intracranial hypotension without dural CSF leak on standard CT myelography.

PURPOSE: A recently identified and treatable cause of spontaneous intracranial hypotension (SIH) is cerebrospinal fluid (CSF)-venous fistula, and a recently described computed tomography myelogram (CTM) finding highly compatible with but not diagnostic of this entity is the hyperdense paraspinal vein sign. We aimed to retrospectively measure the prevalence of the hyperdense paraspinal vein sign on CTMs in SIH patients without dural CSF leak, in comparison with control groups. METHODS: Three CTM groups were identified: 1) SIH study group, which included dural CSF leak-negative standard CTMs performed for SIH, with early and delayed imaging; 2) Early control CTMs, which were performed for indications other than SIH, with imaging shortly after intrathecal contrast administration; 3) Delayed control CTMs, which included delayed imaging. CTMs were retrospectively reviewed for the hyperdense paraspinal vein sign by experienced neuroradiologists, blinded to the group assignment. All CTMs deemed by a single reader to be positive for the hyperdense paraspinal vein sign were independently reviewed by two additional neuroradiologists; findings were considered positive only if consensus was present among all three readers. For positive cases, noncontrast CTs and prior CTMs, if available, were reviewed for the presence of the sign. RESULTS: Seven of 101 (7%) SIH patients had contrast in a spinal/paraspinal vein consistent with the hyperdense paraspinal vein sign; no patient in either control group (total n=54) demonstrated the hyperdense paraspinal vein sign (P = 0.0463). The finding occurred only at thoracic levels. Each patient had a single level of involvement. Six (86%) occurred on the right. Four occurred in female patients (57%). The sign was seen on early images in 3 of 7 cases (43%) and on both early and delayed images in 4 of 7 cases (57%). In 2 of 7 patients (29%), a noncontrast CT covering the relevant location was available and negative for the sign. A prior CTM was available in 2 of 7 patients (29%), and in both cases the hyperdense paraspinal vein sign was also evident. CONCLUSION: The prevalence of the hyperdense paraspinal vein sign in SIH patients with dural CSF leak-negative standard CTM was 7%. As the sign was not seen in control groups, this sign is highly compatible with the presence of CSF-venous fistula. Since the CTMs were not specifically dedicated to identifying hyperdense paraspinal veins (i.e., they were not dynamic and were not preceded by digital subtraction myelography), the true prevalence of the sign may be higher. Radiologists should scrutinize conventional CTMs for this sign, especially in patients in whom a traditional dural CSF leak is not identified.

Factors affecting cerebrospinal fluid opening pressure in patients with spontaneous intracranial hypotension.

OBJECTIVE: Spontaneous intracranial hypotension (SIH) is recognized far more commonly than ever before. Though usually characterized by low cerebrospinal fluid (CSF) pressure, some patients with SIH are observed to have normal pressure values. In this study, we aimed to confirm the proportion of patients with normal CSF opening pressure (CSF OP) and explore the factors affecting CSF OP in SIH patients. METHODS: We retrospectively reviewed 206 consecutive SIH patients and analyzed their clinical and imaging variables (including demographic data, body mass index (BMI), duration of symptoms, and brain imaging findings). Univariate and multivariate analyses were performed to identify the potential factors affecting CSF OP. RESULTS: In a total of 114 (55.3%) cases the CSF OP was ≤60 mmH2O (1 mmH2O=9.806 65 Pa), in 90 (43.7%) cases it was between 60 and 200 mmH2O, and in 2 (1.0%) cases it was >200 mmH2O. Univariate analysis showed that the duration of symptoms (P<0.001), BMI (P<0.001), and age (P=0.024) were positively correlated with CSF OP. However, multivariate analysis suggested that only the duration of symptoms (P<0.001) and BMI (P<0.001) were strongly correlated with CSF OP. A relatively high R2 of 0.681 was obtained for the multivariate model. CONCLUSIONS: Our study indicated that in patients without a low CSF OP, a diagnosis of SIH should not be excluded. BMI and the duration of symptoms can influence CSF OP in SIH patients, and other potential factors need further investigation.

Reversible Holmes' tremor due to spontaneous intracranial hypotension.

Holmes' tremor is a low-frequency hand tremor and has varying amplitude at different phases of motion. It is usually unilateral and does not respond satisfactorily to drugs and thus considered irreversible. Structural lesions in the thalamus and brainstem or cerebellum are usually responsible for Holmes' tremor. We present a 23-year-old woman who presented with unilateral Holmes' tremor. She also had hypersomnolence and headache in the sitting posture. Her brain imaging showed brain sagging and deep brain swelling due to spontaneous intracranial hypotension (SIH). She was managed conservatively and had a total clinical and radiological recovery. The brain sagging with the consequent distortion of the midbrain and diencephalon was responsible for this clinical presentation. SIH may be considered as one of the reversible causes of Holmes' tremor.