Clinical utility of brain biopsy for presumed CNS relapse of systemic lymphoma.

OBJECTIVE: The objective of this study was to determine the frequency with which brain biopsy for presumed CNS relapse of systemic hematological malignancies yields new, actionable diagnostic information. Hematological malignancies represent a disparate group of genetic and histopathological disorders. Proclivity for brain involvement is dependent on the unique entity and may occur synchronously or metasynchronously with the systemic lesion. Diffuse large B-cell lymphomas (DLBCLs) have a high propensity for brain involvement. Patients in remission from systemic DLBCL may present with a lesion suspicious for brain relapse. These patients often undergo brain biopsy. The authors' a priori hypothesis was that brain biopsy in patients with a history of systemic DLBCL and a new brain MRI lesion would have lower diagnostic utility compared with patients with non-DLBCL systemic malignancies. METHODS: The authors performed a retrospective review of patients who underwent brain biopsy between 2000 and 2019. Inclusion criteria were patients ≥ 18 years of age with a prior systemic hematological malignancy in remission presenting with a new brain MRI lesion concerning for CNS relapse. Patients with a history of any CNS neoplasms, demyelinating disorders, or active systemic disease were excluded. The main outcome was the proportion of patients with a distinct histopathological brain diagnosis compared with the systemic malignancy. The authors secondarily assessed overall survival, procedure-related morbidity, and 30-day mortality. RESULTS: Sixty patients met inclusion criteria (40 males and 20 females); the median age at brain biopsy was 67 years (range 23-88 years). The median follow-up was 8.5 months (range 0.1-231 months). Thirty-nine (65.0%) patients had DLBCL and 21 (35%) had non-DLBCL malignancies. Thirty-five of 36 (97.2%) patients with prior systemic DLBCL and a diagnostic biopsy had histopathological confirmation of the original systemic disease versus 0 of 21 patients with non-DLBCL systemic malignancies (p < 0.001). Morbidity and 30-day mortality were 8.3% and 10.0%, respectively; 2 of 6 30-day mortalities were directly attributable to the biopsy. The median overall survival following brain biopsy was 10.8 months. CONCLUSIONS: Patients with a history of systemic DLBCL and presumed CNS relapse gained minimal clinical benefit from brain biopsy but were at high risk of morbidity and mortality. In patients with a history of non-DLBCL systemic malignancies, brain biopsy remained critical given the high likelihood for discovery of distinct diagnostic entities. It was determined that patients with a prior systemic DLBCL and presumed brain relapse should likely receive empirical therapy obviating treatment delay and the risks of brain biopsy.

Correction to: Comparative multidimensional molecular analyses of pediatric diffuse intrinsic pontine glioma reveals distinct molecular subtypes.

The original version of this article unfortunately contained a mistake.

In Utero Restoration of Hindbrain Herniation in Fetal Myelomeningocele as Part of Prenatal Regenerative Therapy Program at Mayo Clinic.

OBJECTIVE: To assess our initial experience with prenatal restoration of hindbrain herniation following in utero repair of myelomeningocele (MMC). PATIENTS AND METHODS: Three consecutive patients with prenatally diagnosed MMC (between January 1, 2018 and September 30, 2018) were managed with open in utero surgery. As per institutional review board approval and following a protocol designed at the Mayo Clinic Maternal & Fetal Center, fetal intervention was offered between 19 0/7 and 25 6/7 weeks of gestation. Prenatal improvement of hindbrain herniation was the declared restorative end point. Obstetrical and perinatal outcomes were also assessed. RESULTS: Diagnosis of MMC was confirmed upon referral between 20 and 21 weeks' gestation by using fetal ultrasound and magnetic resonance imaging. In all cases reported here, the spinal defect was lumbosacral with evidence of hindbrain herniation. Open in utero MMC repair was performed between 24 and 25 weeks' gestation with no notable perioperative complications. Postprocedure fetal magnetic resonance imaging performed 6 weeks after in utero repair documented improvement of hindbrain herniation. Deliveries were at 37 weeks by cesarean section without complications. Most recent postnatal follow-ups were unremarkable at both 11 months (baby 1) and 3 months of age (baby 2), with mild ventriculomegaly. Antenatal and postnatal follow-up of baby 3 at 1 month of age was also unremarkable. CONCLUSION: Our study highlights the prenatal restoration of hindbrain herniation following in utero MMC repair in all cases presented here as an example of a prenatal regenerative therapy program in our institution.

Validating the management paradigm for pediatric spinal aneurysmal bone cysts to optimize long-term outcomes: an institutional experience.

BACKGROUND: The optimal clinical management and outcomes of rare pediatric spinal aneurysmal bone cysts (spABC) is largely anecdotal. Current practice is based on bigger adult series, although given the disparities in spine growth of adults versus children, what impact this difference may have on long-term outcomes has yet to be substantiated. Correspondingly, the aim of this study was to describe the clinical course of all pediatric spABC cases managed at our institution to better understand this. METHODS: A retrospective cohort study of all pediatric spABC cases presenting to our institution between 1993 and 2017 was performed using a predetermined set of selection criteria. Primary outcomes of interest were treatment modalities and their outcomes, recurrence status, and functional status. RESULTS: A total of 24 pediatric spABC cases satisfied all criteria. Median age of diagnosis was 13.5 years, with 15 females and 9 males. Radicular pain was the presenting symptom in 21 (88%) cases. Diagnostic biopsy was pursued in 9 (38%) cases, pre-operative embolization in 8 (33%) cases, surgical intervention in 23 (96%) cases, and sclerotherapy in 2 (8%) cases. In terms of surgery, there were no intraoperative complications, and gross total resection (GTR) was achieved in 14 of the 23 (61%) cases. Overall, there were 5 (21%) cases which experienced recurrence by a median time of 8 months after initial surgery, all of which had initial subtotal resection. Median follow-up was 5 years, by which all patients demonstrated excellent functional status. CONCLUSIONS: There are a number of feasible therapeutic modalities and combinations that can be utilized to maximize control of pediatric spABCs and optimize long-term function similar to that of adults, irrespective of developing versus developed spines. The incidence of recurrence is not negligible, and therefore, rigorous long-term surveillance is highly encouraged, particularly within the first post-operative year following mono-modal non-GTR treatment.

Progressive hydrocephalus despite early complete reversal of hindbrain herniation after prenatal open myelomeningocele repair.

OBJECTIVE: Open prenatal myelomeningocele (MMC) repair is typically associated with reversal of in utero hindbrain herniation (HBH) and has been posited to be associated with a reduction in both postoperative prenatal and immediate postnatal hydrocephalus (HCP) risks. However, the long-term postnatal risk of HCP following HBH reversal in these cases has not been well defined. The authors describe the results of a long-term HCP surveillance in a cohort of patients who underwent prenatal MMC repair at their institution. METHODS: A retrospective review of all prenatal MMC repair operations performed at the Mayo Clinic between 2012 and 2017 was conducted. Pertinent data regarding the clinical courses of these patients before and after MMC repair were summarized. Outcomes of interest were occurrences of HBH and HCP and the need for intervention. RESULTS: A total of 9 prenatal MMC repair cases were identified. There were 7 cases in which MRI clearly demonstrated prenatal HBH, and of these 86% (6/7) had evidence of HBH reversal after repair and prior to delivery. After a mean postnatal follow-up of 20 months, there were 3 cases of postnatal HCP requiring intervention. One case that failed to show complete HBH reversal after MMC repair required early ventriculoperitoneal shunting. The other 2 cases were of progressive, gradual-onset HCP despite complete prenatal HBH reversal, requiring endoscopic third ventriculostomy with choroid plexus cauterization at ages 5 and 7 months. CONCLUSIONS: Although prenatal MMC repair can achieve HBH reversal in a majority of well-selected cases, the prevention of postnatal HCP requiring intervention appears not to be predicated on this outcome alone. In fact, it appears that in a subset of cases in which HBH reversal is achieved, patients can experience a progressive, gradual-onset HCP within the 1st year of life. These findings support continued rigorous postnatal surveillance of all prenatal MMC repair patients, irrespective of postoperative HBH outcome.

A1 segment hypoplasia associated with cerebral infarction after anterior communicating artery aneurysm rupture.

BACKGROUND: Congenital hypoplasia or absence of the A1 segment of the anterior cerebral artery (ACA) has been associated with increased incidence of berry aneurysms at the anterior communicating artery (Acom) complex. It is not known, however, whether this anatomic variant also predisposes patients to complications after aneurysmal subarachnoid hemorrhage. METHODS: Patients were included for analysis if they presented to our institution for clipping or coiling of an Acom aneurysm between the years of 2001 and 2013. Patients were deemed to have cerebral infarction if a new hypodensity in a vascular distribution was visualized on CT imaging. The association between A1 segmental abnormalities and radiologic infarction was subsequently evaluated in a risk-adjusted manner using stepwise multivariable logistic regression analysis. RESULTS: Of 145 patients who presented with aneurysmal subarachnoid hemorrhage after rupture of an Acom aneurysm, 31 (21.4%) had a hypoplastic or absent A1 segment. On univariate analysis, there was a trend toward an increased rate of radiologic infarction in patients with A1 segment abnormalities (OR=2.11, 95% CI: 0.93-4.79; P=0.0757). On multivariable analysis, a hypoplastic or absent A1 segment was significantly associated with an increased rate of radiologic infarction (OR=2.54, 95% CI: 1.02-6.43; P=0.0466). CONCLUSIONS: Our results suggest that a hypoplastic or absent A1 segment is associated with cerebral infarction following subarachnoid hemorrhage from ruptured Acom aneurysms, indicating a potential need for heightened vigilance and a reduced threshold for therapeutic intervention in patients harboring this abnormality.

Gastrostomy tube placement increases the risk of ventriculoperitoneal shunt infection: a multiinstitutional study.

OBJECTIVEGastrostomy tube placement can temporarily seed the peritoneal cavity with bacteria and thus theoretically increases the risk of shunt infection when the two procedures are performed contemporaneously. The authors hypothesized that gastrostomy tube placement would not increase the risk of ventriculoperitoneal shunt infection. The object of this study was to test this hypothesis by utilizing a large patient cohort combined from multiple institutions.METHODSA retrospective study of all adult patients admitted to five institutions with a diagnosis of aneurysmal subarachnoid hemorrhage between January 2005 and January 2015 was performed. The primary outcome of interest was ventriculoperitoneal shunt infection. Variables, including gastrostomy tube placement, were tested for their association with this outcome. Standard statistical methods were utilized.RESULTSThe overall cohort consisted of 432 patients, 47% of whom had undergone placement of a gastrostomy tube. The overall shunt infection rate was 9%. The only variable that predicted shunt infection was gastrostomy tube placement (p = 0.03, OR 2.09, 95% CI 1.07-4.08), which remained significant in the multivariate analysis (p = 0.04, OR 2.03, 95% CI 1.04-3.97). The greatest proportion of shunts that became infected had been placed more than 2 weeks (25%) and 1-2 weeks (18%) prior to gastrostomy tube placement, but the temporal relationship between shunt and gastrostomy was not a significant predictor of shunt infection.CONCLUSIONSGastrostomy tube placement significantly increases the risk of ventriculoperitoneal shunt infection.

Ventriculostomy and Risk of Upward Herniation in Patients with Obstructive Hydrocephalus from Posterior Fossa Mass Lesions.

BACKGROUND: Patients with posterior fossa lesions causing obstructive hydrocephalus present a unique clinical challenge, as relief of hydrocephalus can improve symptoms, but the perceived risk of upward herniation must also be weighed against the risk of worsening or continued hydrocephalus and its consequences. The aim of our study was to evaluate for clinically relevant upward herniation following external ventricular drainage (EVD) in patients with obstructive hydrocephalus due to posterior fossa lesions. METHODS: We performed a retrospective review of patients undergoing urgent/emergent EVD placement at our institution between 2007 and 2014, evaluating the radiographic and clinical changes following treatment of obstructive hydrocephalus. RESULTS: Even prior to EVD placement, radiographic upward herniation was present in 22 of 25 (88%) patients. The average Glasgow Coma Scale of patients before and after EVD placement was 10 and 11, respectively. Radiographic worsening of upward herniation occurred in two patients, and upward herniation in general persisted in 21 patients. Clinical worsening occurred in two patients (8%), though in all others the clinical examination remained stable (44%) or improved (48%) following EVD placement. Of the patients who had a worsening clinical exam, other variables likely also contributed to their decline, and cerebrospinal fluid diversion was likely not the main factor that prompted the clinical change. CONCLUSIONS: Radiographic presence of upward herniation was often present prior to EVD placement. Clinically relevant upward herniation was rare, with only two patients worsening after the procedure, in the presence of other clinical confounders that likely contributed as well.

Identical Twins Discordant for Metopic Craniosynostosis: Evidence of Epigenetic Influences.

Craniosynostosis, or premature fusion of the cranial sutures, occurs in approximately 1 in 2500 live births. The genetic causes and molecular basis of these disorders have greatly expanded over the last 2 decades, with numerous causative and contributory mutations having been identified. The role of fibroblast growth factor receptor (FGFR) mutations in the etiology of certain eponymous forms of craniosynostosis is now well elucidated; the most common syndromes associated with craniosynostosis are Pfeifer (FGFR1, FGFR2), Apert (FGFR2), Crouzon (FGFR2), Saethre-Chotzen (TWIST1), Jackson-Weiss (FGFR2), Greig (GL13), and Muenke (FGFR3) syndromes. Although pathological expression of these mutations often results in bilateral coronal craniosynostosis, single suture fusions (typically unilateral coronal synostosis) or multiple suture craniosynostosis are possible.The majority of patients diagnosed with craniosynostosis lack an identifiable syndrome or genetic mutation. The etiopathogenesis of these "nonsyndromic" forms of craniosynostosis is believed to involve a complex interplay of genetics, epigenetics, and environmental factors. Evaluation of genes implicated in nonsyndromic craniosynostosis has been conflicting; some evidence demonstrates an interplay between genetic and epigenetic influences while others do not. Certain environmental factors such as teratogenic levels of retinoic acid, maternal metabolic and hematologic disorders, and head growth constraint in utero may increase the likelihood of developing craniosynostosis, but these associations are again tenuous.The authors present 1 of 2 genetically confirmed identical twins discordant for metopic craniosynostosis. The implications of this case are clear: epigenetic influences, environmental influences, or both played a role in the development of this premature suture fusion.

Increased Operative Time for Benign Cranial Nerve Tumor Resection Correlates with Increased Morbidity Postoperatively.

OBJECTIVES: Operative time, previously identified as a risk factor for postoperative morbidity, is examined in patients undergoing benign cranial nerve tumor resection. DESIGN/SETTING/PARTICIPANTS: This retrospective cohort analysis included patients enrolled in the ACS-NSQIP registry from 2007 through 2013 with a diagnosis of a benign cranial nerve neoplasm. MAIN OUTCOME MEASURES: Primary outcomes included postoperative morbidity and mortality. Readmission and reoperation served as secondary outcomes. RESULTS: A total of 565 patients were identified. Mean (median) operative time was 398 (370) minutes. The 30-day complication, readmission, and return to the operating room rates were 9.9%, 9.9%, and 7.3%, respectively, on unadjusted analyses. CSF leak requiring reoperation or readmission occurred at a rate of 3.1%. On multivariable regression analysis, operations greater than 413 minutes were associated with an increased odds of overall complication (OR 4.26, 95% CI 2.08-8.72), return to the operating room (OR 2.65, 95% CI 1.23-5.67), and increased length of stay(1.6 days, 95% CI 0.94-2.23 days). Each additional minute of operative time was associated with an increased odds of overall complication (OR 1.004, 95% CI 1.002-1.006) and increased length of stay (0.006 days, 95% CI 0.004-0.008). CONCLUSION: Increased operative time in patients undergoing surgical resection of a benign cranial nerve neoplasm was associated with an increased rate of complications.

Risk of Ventriculostomy-Associated Hemorrhage in Patients with Aneurysmal Subarachnoid Hemorrhage Treated with Anticoagulant Thromboprophylaxis.

BACKGROUND: Patients with subarachnoid hemorrhage (SAH) frequently need a ventriculostomy for treatment of hydrocephalus. In some ICU practices, a ventriculostomy is considered a relative contraindication for subcutaneous heparin. We studied the risk of ventriculostomy-associated hemorrhage and deep venous thrombosis (DVT) in patients with anticoagulant prophylaxis. METHODS: This is a retrospective study of 241 consecutive patients with SAH and ventriculostomies treated at Mayo Clinic, Rochester from 2001 to 2014. DVT and pulmonary emboli (PE) prevention included subcutaneous or intravenous heparin, enoxaparin, dalteparin, and warfarin. The incidence of PE and DVT were noted within 30 days of hospital admission. Hemorrhages were classified as minor or major based on size and mass effect. RESULTS: Fifty-three (22 %) of the 241 patients were on prophylactic doses of anticoagulation while in the intensive care unit. Three of 53 patients on prophylactic anticoagulation had minor hemorrhages and none had major hemorrhages. Four (7.5 %) of 53 patients who received prophylactic anticoagulation versus 34 (18 %) of 188 patients who did not receive prophylactic anticoagulation developed DVT (p = 0.09). One of 10 patients on therapeutic anticoagulation had a major and fatal hemorrhage. CONCLUSION: In our cohort, the risk of VTE was reduced by more than half in patients receiving chemoprophylaxis. Ventriculostomy-associated hemorrhages were rare and minor. Anticoagulant thromboprophylaxis is mostly safe and required in aneurysmal SAH.

Is Patient Age Associated with Perioperative Outcomes After Surgical Resection of Benign Cranial Nerve Neoplasms?

OBJECTIVE: Previous studies have demonstrated that increasing age is associated with decreased rates of operative management and gross total resection in patients with vestibular schwannomas. METHODS: The American College of Surgeons National Surgical Quality Improvement Program data registry was used for this retrospective cohort analysis. Patients enrolled in the registry from 2007 to 2013 with a diagnosis of a benign neoplasm of a cranial nerve were included. The association between age and postoperative morbidity and mortality was evaluated by the use of multivariable logistic regression analyses. RESULTS: Of 565 patients included for analysis, the mean (median) age was 51 (53) years. Three clusters were evaluated: <50, 50-69, and ≥70 years. Mortality (0% vs. 1.03% vs. 4.55%, P = 0.012), stroke (0% vs. 0.69% vs. 6.82%, P < 0.001), and ventilator weaning failure (0.43% vs. 2.41% vs. 6.82%, P = 0.014) increased with age. Mean age was significantly greater among patients who died (70.60 vs. 50.87 years, P = 0.002) or had a stroke (68.00 vs. 50.89 years, P = 0.006), cardiac arrest (71.50 vs. 50.89 years, P = 0.038), or coma (74.00 vs. 50.96 years, P = 0.020) and those who failed ventilator weaning (62.55 vs. 50.82, P = 0.006). Age as both a continuous (odds ratio 1.10, 95% confidence interval 1.03-1.18) and categorical variable (age 70+ years odds ratio 78.88, 95% confidence interval 3.41-1825.57) was associated with an increased odds of composite morbidity. CONCLUSIONS: In patients undergoing surgery for benign cranial nerve neoplasms, increasing age is associated with increased mortality, stroke, coma, and ventilator weaning failure. Composite complication rates are significantly greater in patients ≥70 years, with a near 80-fold increased risk of complications.

Prompt Recognition and Management of Postoperative Intracranial Hypotension-Associated Venous Congestion: A Case Report.

BACKGROUND: Postoperative intracranial hypotension-associated venous congestion (PIHV) is an uncommon cause of clinical deterioration after a neurosurgical procedure that is often unrecognized until late in its course. Functional outcomes range from remarkable neurological recovery to death. Little is understood about the reason for deterioration in certain patients compared with improvement in others. A 68-year-old man with a progressive cervical myelopathy underwent an uncomplicated cervical decompression and alignment restoration at our hospital and suffered violent generalized tonic-clonic seizures intraoperatively and postoperatively. A postoperative head CT showed a right parietal hematoma, but no other cranial findings. A subsequent MRI demonstrated what we describe as early PIHV with symmetric T2 signal changes in the bilateral deep gray structures. No diffusion restriction corresponded to these areas. A CT myelogram revealed a considerable CSF collection within the operative bed. Upon returning to the operating room to localize the source of the leak, a large dural tear was identified off of midline with a bone chip alongside the defect. The defect was repaired, and the patient remained comatose for over a week postoperatively. He made a remarkable gradual recovery, and after a month in the hospital and rehabilitation, he returned home with relatively minimal neurological deficits. CONCLUSIONS: We postulate that if caught early and treated aggressively, neurologic injury resulting from PIHV may be reversible despite initially ominous imaging. Neurosurgeons and neurointensivists should therefore be compelled to search for dural defects and return to the operating room for immediate repair.

Prognostic and Mechanistic Factors Characterizing Seizure-Associated Crossed Cerebellar Diaschisis.

BACKGROUND: Crossed cerebellar diaschisis is a rare finding of hemispheric cerebellar depression following contralateral cerebral injury, hypothesized to result from excessive neuronal excitatory synaptic activity along cortico-pontine-cerebellar pathways. The phenomenon is typically observed following ischemic stroke, but has also been characterized during seizure activity--in particular, status epilepticus (SE). Neurological outcome has varied widely in published reports, with some patients achieving full neurologic recovery, while others experience persistent disability. METHODS: Case report and literature review. RESULTS: We present a 54-year-old man found unresponsive with a right hemispheric syndrome several days after discharge following amygdalohippocampectomy for refractory right temporal lobe epilepsy. Prolonged electroencephalogram demonstrated one subclinical right frontal seizure, along with right frontal periodic lateralized epileptiform discharges, presumed to be associated with SE preceding his admission. Initial MRI demonstrated restricted diffusion on diffusion weighted imaging in the right cerebral hemisphere, ipsilateral thalamus, and contralateral cerebellum. A head CT one week later showed diffuse sulcal effacement with loss of gray-white differentiation in the right frontal and insular regions with low attenuation changes of right thalamus. An MRI showed worsened diffusion restriction, despite a corresponding increase in perfusion. The patient remained paretic at discharge and follow-up. Follow-up MRI at 2 months demonstrated pronounced right cerebral and left cerebellar atrophy, loss of gray matter in much of the right cerebrum, and scattered areas of T2 hyperintensity, consistent with permanent right fronto-temporal neuronal loss. CONCLUSIONS: Collectively, these observations indicate that imaging findings of persistent cerebral restricted diffusion and cytotoxic edema in the subacute post-ictal period may predict irreversible neuronal injury and poor long-term outcome-even when accompanied by evidence of cortical hyperperfusion and recovery of second- and third-order neurons along the involved circuit.

Comparative multidimensional molecular analyses of pediatric diffuse intrinsic pontine glioma reveals distinct molecular subtypes.

Diffuse intrinsic pontine glioma (DIPG) is a highly morbid form of pediatric brainstem glioma. Here, we present the first comprehensive protein, mRNA, and methylation profiles of fresh-frozen DIPG specimens (n = 14), normal brain tissue (n = 10), and other pediatric brain tumors (n = 17). Protein profiling identified 2,305 unique proteins indicating distinct DIPG protein expression patterns compared to other pediatric brain tumors. Western blot and immunohistochemistry validated upregulation of Clusterin (CLU), Elongation Factor 2 (EF2), and Talin-1 (TLN1) in DIPGs studied. Comparisons to mRNA expression profiles generated from tumor and adjacent normal brain tissue indicated two DIPG subgroups, characterized by upregulation of Myc (N-Myc) or Hedgehog (Hh) signaling. We validated upregulation of PTCH, a membrane receptor in the Hh signaling pathway, in a subgroup of DIPG specimens. DNA methylation analysis indicated global hypomethylation of DIPG compared to adjacent normal tissue specimens, with differential methylation of 24 genes involved in Hh and Myc pathways, correlating with protein and mRNA expression patterns. Sequencing analysis showed c.83A>T mutations in the H3F3A or HIST1H3B gene in 77 % of our DIPG cohort. Supervised analysis revealed a unique methylation pattern in mutated specimens compared to the wild-type DIPG samples. This study presents the first comprehensive multidimensional protein, mRNA, and methylation profiling of pediatric brain tumor specimens, detecting the presence of two subgroups within our DIPG cohort. This multidimensional analysis of DIPG provides increased analytical power to more fully explore molecular signatures of DIPGs, with implications for evaluating potential molecular subtypes and biomarker discovery for assessing response to therapy.

Pathophysiology of primary spinal syringomyelia.

OBJECT: The pathogenesis of syringomyelia in patients with an associated spinal lesion is incompletely understood. The authors hypothesized that in primary spinal syringomyelia, a subarachnoid block effectively shortens the length of the spinal subarachnoid space (SAS), reducing compliance and the ability of the spinal theca to dampen the subarachnoid CSF pressure waves produced by brain expansion during cardiac systole. This creates exaggerated spinal subarachnoid pressure waves during every heartbeat that act on the spinal cord above the block to drive CSF into the spinal cord and create a syrinx. After a syrinx is formed, enlarged subarachnoid pressure waves compress the external surface of the spinal cord, propel the syrinx fluid, and promote syrinx progression. METHODS: To elucidate the pathophysiology, the authors prospectively studied 36 adult patients with spinal lesions obstructing the spinal SAS. Testing before surgery included clinical examination; evaluation of anatomy on T1-weighted MRI; measurement of lumbar and cervical subarachnoid mean and pulse pressures at rest, during Valsalva maneuver, during jugular compression, and after removal of CSF (CSF compliance measurement); and evaluation with CT myelography. During surgery, pressure measurements from the SAS above the level of the lesion and the lumbar intrathecal space below the lesion were obtained, and cardiac-gated ultrasonography was performed. One week after surgery, CT myelography was repeated. Three months after surgery, clinical examination, T1-weighted MRI, and CSF pressure recordings (cervical and lumbar) were repeated. Clinical examination and MRI studies were repeated annually thereafter. Findings in patients were compared with those obtained in a group of 18 healthy individuals who had already undergone T1-weighted MRI, cine MRI, and cervical and lumbar subarachnoid pressure testing. RESULTS: In syringomyelia patients compared with healthy volunteers, cervical subarachnoid pulse pressure was increased (2.7 ± 1.2 vs 1.6 ± 0.6 mm Hg, respectively; p = 0.004), pressure transmission to the thecal sac below the block was reduced, and spinal CSF compliance was decreased. Intraoperative ultrasonography confirmed that pulse pressure waves compressed the outer surface of the spinal cord superior to regions of obstruction of the subarachnoid space. CONCLUSIONS: These findings are consistent with the theory that a spinal subarachnoid block increases spinal subarachnoid pulse pressure above the block, producing a pressure differential across the obstructed segment of the SAS, which results in syrinx formation and progression. These findings are similar to the results of the authors' previous studies that examined the pathophysiology of syringomyelia associated with obstruction of the SAS at the foramen magnum in the Chiari Type I malformation and indicate that a common mechanism, rather than different, separate mechanisms, underlies syrinx formation in these two entities. Clinical trial registration no.: NCT00011245.