Normal CSF Flow Research Articles

679 Epidural Hypertension Theory in Patients With Lumbar Spinal Stenosis

INTRODUCTION: Laminectomy is the standard of treatment in Lumbar Spinal Stenosis(LSS). Multiple studies (Mariconda;Boden;Schonstrom;Matsumoto;Herno;Webber.) have not found relationship between spinal canal widening and symptoms improvement in LSS. Neurogenic compression and rootlets hypoxia theories try to explain pathophysiology of LSS. We propose Epidural Hypertension (EH) as a new paradigm that explains dynamic stress of neural structures involved in LSS. METHODS: Group A: single-segment LSS diagnosed by magnetic resonance (n = 4). Group B: Patients without LSS requiring surgery for another diagnosis (spinal cord stimulation, foraminotomy) (n = 3). Laminectomy was performed, previously, flavum ligament was meticulously dissected and a pressure microsensor was inserted in epidural space in stenotic segment. EP was measured in 0 and 50° extension in order to extrapolate EP in standing position. RESULTS: EP in LSS patients was 18,5 mmHg at 0° (IQR 16.5-37.5 mmHg) and 26 mmHg at 50° (IQR 20-34.5 mmHg). In patients without LSS, EP was 8mmHg at 0° (IQR 1-8 mmHg) and 3 mmHg at 50° (IQR 1-12 mmHg). We found differences using Wilcoxon's test. EP was greater in patients with LSS at 0° (p = 0.031) y 50° (p = 0.034). CONCLUSIONS: EH may play a foundamental role in pathophysiology of LSS. In Patients without LSS we found a drop in EP at 50° possibly secondary to caudal CSF displacement. In LSS patients we found a raise in EP at 50° possibly secondary to spinal canal narrowing impeding normal CSF flow increasing hydrostatic pressure in the stenotic segment. This results might be the first step to consider EH as a treatment target in LSS and determine its relationship with LSS symptoms.

Chiari malformation and syringomyelia.

Chiari malformation was first described over a century ago, and consists of posterior fossa anomalies that generally share the feature of cerebellar tonsillar descent through the foramen magnum. Our understanding of this disorder was initially based on autopsy studies, and has been greatly enhanced by the advent of MRI. The surgical management of Chiari anomalies has also evolved in a parallel fashion. Although the exact surgical technique varies among individual surgeons, the goals of surgery remain constant and consist of relieving brainstem compression and cranial nerve distortion, restoring the normal flow of CSF across the foramen magnum, and reducing the size of any associated syrinx cavity. Syrinx cavities are most commonly associated with Chiari anomalies, yet primary spinal syringomyelia (PSS) can be caused by traumatic, infectious, degenerative, and other etiologies that cause at least a partial CSF flow obstruction in the spinal subarachnoid space. As with syringomyelia associated with Chiari anomalies, the main goal of PSS surgery is to reestablish CSF flow across the area of obstruction. In addition to MRI, myelography with CT can be very helpful in the evaluation and management of these patients by identifying focal regions of CSF obstruction that may be amenable to surgical intervention. Future directions for the treatment of Chiari anomalies and syringomyelia include the application of advanced imaging techniques, more widespread use of genetic evaluation, large-scale outcome studies, and the further refinement of surgical technique.

Leptomeningeal Metastases.

Treatment options for leptomeningeal metastases are expanding with greater tolerability and efficacy than in the past. Improved knowledge of molecular subtypes of some cancers can guide in choosing more effective therapeutic options; however, physicians should be mindful that these molecular types can be different in the central nervous system compared to the rest of the body. This is particularly true in breast and lung cancer, in which some patients now can live for many months or even years after diagnosis of leptomeningeal metastases. Options for intrathecal therapies are expanding, but physicians should be mindful that this is a passive delivery system that relies on normal CSF flow, so therapies will not penetrate bulky or parenchymal disease sites, especially in the presence of abnormal CSF flow. When chemotherapeutic options are lacking or unsuccessful, focal radiosurgery which can provide symptomatic relief and proton craniospinal radiation remain effective options. Hopefully more formal studies will be conducted in the future to verify which treatments are indeed most effective for particular types of cancer.

Surgical Outcome after Posterior Fossa Decompression with and without Duraplasty in Adult Chiari Malformation Type-I

Background Data: Adult Chiari malformation is a heterogeneous group of conditions, with the underlying commonality of disruption of normal CSF flow through the foramen magnum. Some cases are congenital, but others are acquired. The optimal surgical treatment of adult Chiari malformation type-I is unclear. Purpose: To evaluate the operative and postoperative results of extradural and intradural approaches in the treatment of Chiari malformation type-I.Study Design: A descriptive retrospective clinical case study. Patients and Methods: Twenty patients underwent surgery for adult Chiari malformation type-I. They were divided into two groups; posterior fossa decompression group and posterior fossa decompression with duroplasty group. Each group included 10 patients. They were operated between 2008and 2015. Participants were evaluated pre-operatively and post-operatively every three months. Operative time, hospital stay and complications were assessed. The clinical outcomes were compared between the two groups using The Chicago Chiari Outcome Scale. Results: No statistically significant differences were found between the decompression and duroplasty groups with regard to demographics, preoperative symptoms, radiographic characteristics, and clinical outcomes. However, the operative time, hospital stay and aseptic meningitis were higher in the duroplasty group.Conclusion: The clinical outcome of posterior fossa decompression is nearly identical to that of posterior fossa decompression with duroplasty in adult patients with Chiari type-I; however, the operative time, hospital stay and complication rate is higher in duroplasty group. (2016ESJ113)

Minimally Invasive (Metrx) Resection of Intradural Spinal Lesions. A Series of 33 Consecutive Cases with Results and Complications

Spinal intradural lesions have been classically treated using open surgical techniques from a direct posterior translaminar approach. This despite the localization of the lesion with respect to the spinal cord. This “one size fits all” strategy works for many lesions, but is very limiting for others, particularly ventrally located lesions. Minimally invasive techniques allow for more flexibility in approach trajectories of almost 180° from one side to the other, while allowing for standard microsurgical techniques intradurally. The approaches are much reduced in size, are faster, and have minimal blood loss, with less muscle destruction. Retrospective patient record review from 2004-2013. Inclusion criteria include intradural spinal pathologies treated using the minimal access techniques with clinical and radiological follow up. 33 cases included in this study in 32 patients (17 male and 15 female) Ave age 50.4 years (20-80). 7 cases were in the cervical spine, 11 in the thoracic spine, and 15 cases were in the lumbosacral spine. Extramedullary pathologies All patients has postoperative MRI: 2 patients with intramedullary lesions: minimum residual teratoma stable at 5 years, AA with progressive disease but alive at 14 months after surgery. Extramedullary: 2 patients with drop mets from ependymoma stable at 8 and 43 months after surgery. 1 patient with recurrent meningioma in the T1 foramen, successfully treated the radiotherapy. 1 patient with tumor left stuck to the anterior spinal artery at C6 with stable disease. Remaining 24 patients with no residual disease. 2 patients with arachnoid cysts had normal CSF flow. Clinical complications (4 cases) Conclusions: 1. Use of minimal access surgical techniques appears to be a safe alternative to standard open approaches. Advantages are rapidity of access and closure, less blood loss, faster recovery postoperatively. 2. These techniques allow standard microsurgical techniques for lesion resection, and may enhance resection with more favorable surgical trajectories. These techniques can be used for highly selective intramedullary lesions.

Prognostic utility of neuraxis imaging in leptomeningeal metastasis (LM): A retrospective case series.

2037 Background: Correlate imaging of the central nervous system that includes both brain and spine MRI and radio-isotope cerebrospinal fluid [CSF] flow studies with survival in a retrospective case series of patients with LM. Methods: 240 adult patients with LM (125 non-brain solid tumor patients with positive CSF cytology; 40 non-brain solid tumor patients with negative CSF cytology and MRI consistent with LM; 50 lymphoma and 25 leukemia patients with positive CSF flow cytometry), all considered appropriate for LM-directed treatment, underwent prior to treatment brain and entire spine MRI and radio-isotope CSF flow studies. Results: Median overall survival was significantly shortened in patients with large volume MRI defined disease (defined as measurable tumor > 5 x 10 mm in orthogonal diameters) and in patients with non-corrected CSF flow obstruction irrespective of primary tumor histology. Additionally, cause of death differed wherein patients with large volume of disease or uncorrected obstructed CSF flow more often died of progressive LM disease whereas patients with normal or small volume disease and patients with normal or re-established CSF flow more often died of progressive systemic disease. Conclusions: Neuraxis imaging utilizing brain and spine MRI as well as radio-isotope CSF flow studies appears to have prognostic significance and may be predictive of median overall survival in this large cohort of patients with LM all of whom were considered for treatment with LM.

337 Cerebrospinal Fluid Flow Quantification of the Cerebral Aqueduct in Children and Adults with Two-Dimentional Cine Phase-Contrast Cine MR Imaging

Background and AimsCerebrospinal fluid (CSF) is known mainly involved in the intracranial homeostatic balance. Disruption of CSF flow may cause distinctive diseases. Therefore, the characterization of normal CSF flow dynamics...

Pilot study of systemic and intrathecal mafosfamide followed by conformal radiation for infants with intracranial central nervous system tumors: a pediatric brain tumor consortium study (PBTC-001)

A pilot study to investigate the feasibility of the addition of intrathecal (IT) mafosfamide to a regimen of concomitant multi-agent systemic chemotherapy followed by conformal radiation therapy (RT) for children <3 years with newly diagnosed embryonal CNS tumors was performed. Ninety-three newly diagnosed infants and children (<3 years) with embryonal CNS tumors were enrolled. Twenty weeks of systemic multi-agent chemotherapy commenced within 35 days of surgery. Patients without CSF flow obstruction (n = 71) received IT mafosfamide (14 mg) with chemotherapy. Localized (M(0)) patients with SD or better subsequently received RT followed by 20 additional weeks of chemotherapy. Second look surgery was encouraged prior to RT if there was an incomplete surgical resection at diagnosis. 71 evaluable patients with normal CSF flow received IT Mafosfamide with systemic chemotherapy; patients with M + disease were removed from protocol therapy at 20 weeks and those with PD at the time of progression. One and 5-year progression free survival (PFS) and overall survival (OS) for the cohort of 71 evaluable patients were 52 ± 6.5 % and 33 ± 13 %, and 67 ± 6.2 % and 51 ± 11 %, respectively. The 1-year Progression Free Survival (PFS) for M0 patients with medulloblastoma (MB, n = 20), supratentorial primitive neuroectodermal tumor (PNET, n = 9), and atypical teratoid rhabdoid tumor (ATRT, n = 12) was 80 ± 7 %, 67 ± 15 % and 27 ± 13 % and 5-year PFS was 65 ± 19 %, 37 ± 29 %, and 0 ± 0 %, respectively. The addition of IT mafosfamide to systemic chemotherapy in infants with embryonal CNS tumors was feasible. The PFS for M0 patients appears comparable to or better than most prior historical comparisons and was excellent for those receiving conformal radiotherapy.

Guidelines for the Management of Obstructive Hydrocephalus From Suprasellar-Prepontine Arachnoid Cysts Using Endoscopic Third Ventriculocystocisternostomy

Intracranial endoscopy has emerged as an innovative surgical tool for various intracranial procedures, but its use remains limited to neurosurgeons trained in this minimally invasive technique. Complex, skull base arachnoid cysts represent one entity that is challenging to treat because of adjacent critical neurovascular structures; however, the advent of intracranial endoscopic techniques has revolutionized treatment. Arachnoid cysts located in the suprasellar-prepontine skull base region can cause obstructive hydrocephalus or symptomatic mass effect and require urgent decompression. These patients may present with nonfocal symptoms that can quickly lead to a life-threatening condition if not accurately diagnosed and treated. The authors present a summary of the world literature of suprasellar-prepontine arachnoid cysts (SPACs) to ascertain clinical presentations and provide class III evidentiary treatment guidelines for this uniquely challenging type of arachnoid cyst. Urgent endoscopic third ventriculostomy results in normalization of intracranial pressure, return of normal CSF flow, and relief of symptoms.

Hydrocephalus associated with cystic dilation of the foramina of Magendie and Luschka

Cystic malformations in the posterior cranial fossa result from developmental failure in the paleocerebellum and meninges. The authors present the case of an infant with hydrocephalus associated with cystic dilation of the foramina of Magendie and Luschka. This 7-month-old female infant presented with sudden onset of tonic-clonic seizures. Computed tomography revealed tetraventricular hydrocephalus. Magnetic resonance imaging demonstrated a cyst communicating with the fourth ventricle and projecting to the cisterna magna and the cerebellopontine cisterns through the foramina of Magendie and Luschka. A suboccipital craniotomy was performed for removal of the cyst wall, and the transparent membrane covering the foramen of Magendie was removed under a microscope. After the surgery, the patient's hydrocephalus improved and a phase contrast cine MR imaging study showed evidence of normal CSF flow at the level of the third and fourth ventricles. Three weeks later, however, the hydrocephalus recurred. An endoscopic third ventriculocisternostomy was performed to address the possibility of stagnant CSF flow in the posterior cranial fossa, but the hydrocephalus continued. Finally the patient underwent placement of a ventriculoperitoneal shunt, resulting in improvement of her symptoms and resolution of the hydrocephalus. On the basis of this experience and previously published reports, the authors speculate that the cystic malformation in their patient could be classified in a continuum of persistent Blake pouch cysts. Hydrocephalus was caused by a combination of obstruction of CSF flow at the outlets of the fourth ventricle and disequilibrium between CSF production and absorption capacity.

Resolution of Acute Hydrocephalus and Migration of Neurocysticercosis Cyst with External Ventricular Drainage

Neurocysticercosis is endemic in the developing world, but is becoming more common in the US due to immigration. A 24-year-old man presented with acute hydrocephalus and headaches, nausea, and vomiting. Head CT revealed a 3rd ventricular cyst and immunological studies were suggestive of neurocysticercosis. EVD placement resulted in migration of the cyst interiorly and superiorly with return of normal CSF flow by MRI and resolution of symptoms. Review of this condition is important given increasing incidence in the United States.

Cine phase-contrast MRI evaluation of normal aqueductal csf flow according to sex and age

The aim of this study was cerebrospinal flow quantification in the cerebral aqueduct using cine phase-contrast magnetic resonance imaging (MRI) technique in both sexes and five different age groups to provide normative data. Sixty subjects with no cerebral pathology were included in this study. Subjects were divided into five age groups: < or =14 years, 15-24 years, 25-34 years, 35-44 years, and > or =45 years. Phase, rephase, and magnitude images were acquired by 1.5 T MR unit at the level of cerebral aqueduct with spoiled gradient echo through-plane, which is a cine phase-contrast sequence. At this level, peak flow velocity (cm/s), average flow rate (cm/ s), average flow (L/min), volumes in cranial and caudal directions (mL), and net volumes (mL) were studied. There was a statistically significant difference in peak flow between the age group of < or =14 years and the older age groups. There were no statistically significant differences in average velocity, cranial and caudal volume, net volume, and average flow parameters among different age groups. Statistically significant differences were not detected in flow parameters between sexes. When using cine-phase contrast MRI in the cerebral aqueduct, only the peak velocity showed a statistically significant difference between age groups; it was higher in subjects aged < or =14 years than those in older age groups. When performing age-dependent clinical studies including adolescents, this should be taken into consideration.

Normal Pressure Hydrocephalus Presenting as Othello Syndrome: Case Presentation and Review of the Literature

Normal pressure hydrocephalus (NPH), an obstruction in the normal flow of CSF through the subarachnoid space, typically presents with a classic “triad” of cognitive impairment, a gait disturbance, and urinary incontinence (1). The etiology of NPH includes subarachnoid spaceoccupying lesion or hemorrhage, chronic meningoencephalitis, changes following acute bacterial meningitis or spinal anesthesia, and carcinomatosis of the meninges (2). Usually, the underlying cause cannot be identified. Idiopathic NPH is clinically diagnosed in most patients during the sixth or seventh decade of life (3). The cognitive impairment in NPH most often manifests as subcortical dementia, though psychiatric and mood symptoms, most often depression, have been described. Most observations of psychiatric sequelae of NPH have been limited to case reports and have included frontal lobe symptoms such as apathy and akinetic mutism, as well as reports of mania, aggression, mood cycling, and psychosis (4–8). In this article, we report a case of NPH presenting as paranoid psychosis with delusional jealousy, otherwise known as the “Othello syndrome.” Case Presentation

HTLV-1 Adult T Cell Leukemia-Lymphoma Presenting with Refractory Hypercalcemia, Cranial Neuropathy and Diagnosis by Flow Cytometry and Cytogenetic Findings.

Introduction: ATLL) is a postthymic lymphoproliferative neoplasm of T cells caused by human T-cell lymphotropic virus (HTLV-1). Most cases are found in Japan, the Caribbean basin, and West Africa.ATLL is essentially a disease of adults, characterized by generalized lymphadenopathy, hepatosplenomegaly, skin lesions, and hypercalcemia. The prognosis of most patients is quite poor, with a median survival time of only 13 months, even with combination chemotherapy. The acute form had a significantly shorter survival (2 months) than lymphoma type (13 months)Advanced performance status, high lactic dehydrogenase, age > 40 years, increased total involved lesions and hypercalcemia, are associated with shortened survival (p<0.01). Hypercalcemia is observed in >80% of ATL. CASE Report:A 43 years old carribean male presented with refractory hypercalcemia 18 g/dl wihtout hematological manifestations,lymphadenopathy or hepatosplenomegaly. He had normal skeletal survey,serum immunoglobulins,immunofixation.The patient also had normal PTH,PTHrp,Vitamin D3,angiotensin converting enzyme levels and 24 hour urinary calcium.The patient had Hemoglobin 13.5 and absolute lymphocytosis 5000–6000/cubic mm.Peripheral smear showed clover T cells Bone marrow had normal morphology but flow cytometry revealed T cells immunoreactive for CD3, CD4,CD8, CD5, and CD25 and were nonimmunoreactive for CD7 .The patient developed visual disturbances, swllowing difficulty and facial palsy during hospital stay.MRI brain was normal but CSF flow cytometry was positive for CD2, CD3, CD4, CD8,CD5, and CD25 and were negative for CD7. Cytogenetic studies showed complex karyotype with: 47, XY,add(4)(p12),+add(4)(p12),add(5)(q11.2),add(7)(q31),–12,Add(12)(q22),der(13)t(5;13)(q11.2;q22),add(14)(q32),add(17)(q23) +mar1(11)/48,idem,+mar1(5)/46,XY(4).A Hyperdiploid male karyotype with monosomy for chromosome No.12,unbalanced translocation involving the long chromosome Nos. 5 and 13, additional material on long arm of 5,7, 12, 14(14q+chromosome) and 17 Complex karyotypes with numerical and structural abnormalities with six or more breaks involving the long arms of chromosomes Nos. 1, 3,6,7,12 and 14q 32 and the short arm of chromosome Nos. 10, 17 and 21 are reported in ATLL .T cell gene rearrangement confirmed the diagnosis.The patient had history of Strongyloides stercoralis infection 8 years ago.He was HIV negativebut had HTLV-1 antibodies(gp19,gp21).He was treated with EPOCH regimen along with intrathecal treatment with normal repeat cytology and CSF flow cytometry.The patientis planned for allogeneic transplant after completion of chemotherapy.Discussion: Adult T-cell lymphoma virus type 1, is implicated diseases including HTLV 1 associated myelopathy,Strongyloides stercoralis hyperinfection, and adult T leukemia/lymphoma. The virus activates a subset of T helper Th1cells with suppression of the Th2 lymphocytes and a reduction of Th2 cytokine production of IL-4, IL-5, IL-10 and IL-13 with an inadequate immune response to invading parasitic infections such as Strongyloides stercoralis. Dual positivity for CD4 and CD8 cells thus confers better prognosis. [Display omitted]

Relationship of Cine Phase-Contrast MRI to Outcome after Decompression for Chiari I Malformation.

BACKGROUND Many patients with symptomatic Chiari I malformation experience symptom recurrence after surgical decompression. Identification of predictors of outcome is needed to better select patients most likely to benefit from surgical intervention. We examined whether CSF flow dynamics assessed by cine phase-contrast MRI could independently predict response to posterior fossa decompression for Chiari I malformation. METHODS Pre and postoperative CSF flow dynamics were assessed by cine phase contrast magnetic resonance imaging in 130 consecutive patients receiving posterior fossa decompression for Chiari I malformation between 1997 and 2003. CSF flow was classified as “abnormal CSF flow” if biphasic flow was either absent or decreased through the aqueduct, fourth ventricle and its outlets, the foramen magnum, or ventral or dorsal to the cervical spinal cord. If no evidence of decreased flow was noted CSF flow was classified as “normal.” The association between pre-operative CSF flow dynamics, all recorded variables, and long-term outcome was assessed utilizing multivariate proportional hazards regression analysis. RESULTS All patients had tonsil herniation > 5mm below the foramen magnum (average 11 ± 5mm). Abnormal hindbrain CSF flow was observed in 81% of patients (43% complete obstruction, 38% reduced flow). Normal CSF flow was observed in 19% of patients. In multivariate analysis, patients with normal preoperative hindbrain CSF flow were 4.8-fold more likely to experience symptom recurrence following surgery (RR, 4.85; 95%CI, 1.88–12.5, P < 0.001) regardless of degree of tonsillar ectopia or presence of syringomyelia. Isolated frontal headache (RR, 4.16; 95%CI, 1.7–9.8, P < 0.05) and scoliosis (RR, 9.2; 95% CI, 1.7–10.5, P < 0.001) were also independent risk factors for symptom recurrence. CONCLUSIONS Normal preoperative hindbrain CSF flow was an independent risk factor for treatment failure after decompression for Chiari I malformation regardless of the degree of tonsilar ectopia. Cine phase-contrast MRI may be a valuable tool in identifying patients less likely to respond to surgical decompression for Chiari I malformation.

111Indium-diethylenetriamine pentaacetic acid cerebrospinal fluid flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases.

Abnormal CSF flow can impair the distribution of intrathecally administered drugs. We examined the relationship between 111indium-diethylenetriamine pentaacetic acid (111In-DTPA) CSF flow studies and methotrexate levels in ventricular and lumbar CSF and correlated these findings with outcome in patients with leptomeningeal metastases (LM). Seven men and 10 women with LM (10 solid tumors, 6 lymphoma, 1 leukemia) received 12 mg methotrexate and 0.5 mCi 111In-DTPA by intra-Ommaya injection; images were obtained immediately and after 4, 24, and 48 hours. Ventricular and lumbar CSF methotrexate and radioactivity levels were measured 6 hours after injection. Thirteen patients had abnormal CSF flow studies, 9 with multiple sites of obstruction. CSF flow obstruction was observed at ventricular outlets in 13 patients, cerebral convexities in 9 and in the spine in 2. With one exception, all obstructions were explicable by tumor deposits on MRIs. For all patients, ventricular and lumbar methotrexate and radioactivity levels correlated closely. Three patients with a normal CSF flow study are alive at 15+, 7.5+, and 3.9+ months from treatment. Of 12 with abnormal CSF flow studies, 11 are dead a median of 2 months from diagnosis. Two patients had diffusely delayed flow studies and both developed methotrexate leukoencephalopathy. CSF flow studies using 111In-DTPA reliably predict distribution of intrathecal methotrexate. Abnormal flow studies correlate with structural abnormalities, are an unfavorable prognostic factor, and may predict intrathecal chemotherapy toxicity.

Radioisotope CSF flow studies in leptomeningeal metastases.

Leptomeningeal metastases is a frequent neuro-oncologic complication in patients with cancer. Radionuclide CSF flow studies provide a unique method of evaluating CSF compartments in patients with leptomeningeal metastases. Radionuclide CSF flow studies are performed by injecting (111)Indium-DTPA into either the ventricular or lumbar CSF compartment. (111)Indium-DTPA is entrained by CSF and flows through CSF compartments based on normal CSF physiology. Normal times to appearance of (111)Indium-DTPA following intraventricular injection in either adults or children are as follows: ventricles (median 1 minute); cisterna magna/basal cisterns (5); cervical (15); thoracic (20); and lumbar (30) spinal subarachnoid spaces; and sylvian cisterns (50). Normal times to appearance of (111)Indium-DTPA following intralumbar injection are as follows: lumbar (1); thoracic (22.5); cervical (32.5) spinal subarachnoid spaces; cisterna magna/basal cisterns (37.5); sylvian cisterns (65); ventricles (1,440); and cerebral convexities (1,440). In 30 consecutive patients, 47% of patients had documented compartmentalization of CSF by (111)Indium-DTPA CSF flow studies. 13% had base of brain obstruction of whom 50% responded with re-establishment of normal CSF flow and 33% had spinal subarachnoid space block of whom 40% following therapy had re-establishment of normal CSF flow. In 61 consecutive patients, 33% of patients had abnormal spinal CSF flow studies which better demonstrated interruption of CSF flow when compared to CT myelography and spine MR. In 40 patients, all with CSF block, 20 of whom responded to therapy with re-establishment of normal CSF flow as compared to 20 with refractory CSF block, significant differences were seen in median survival and cause of death favoring patients with normal or restored CSF flow. Radioisotope CSF flow studies in patients with leptomeningeal metastasis appear to have two practical uses. First, radioisotope CSF flow studies by documenting normal CSF flow predict for homogeneous distribution of intra-CSF chemotherapy. Secondly, in patients with CSF flow obstruction refractory to site of obstruction therapy, limited survival, rapid leptomeningeal disease progression and death due to progressive CNS disease is predicted.

Carcinomatous meningitis secondary to breast cancer: predictors of response to combined modality therapy.

To identify the factors predictive of response and increased survival in patients with leptomeningeal metastases (LM) from breast cancer receiving multi-modal therapy. Leptomeningeal metastases (LM) are being diagnosed with increasing frequency as anti-cancer therapies become more effective and result in prolonged patient survival. 32 women (range 28 to 74 years; median 49) with LM due to metastatic breast cancer were treated. Neurologic presentation included: cranial neuropathies (10 patients); headache (10); cauda equina syndrome (6); ataxia (6); meningismus (3); radioculopathy (2); myelopathy (2); confusion (2); and seizure (1). All patients underwent radiographic evaluation of the extent of CNS disease followed by radiotherapy (21 women) and intraventricular chemotherapy: (methotrexate 32 women; cytarabine 22; thio-TEPA 11). CNS imaging (cranial MR, spine MR and radionuclide ventriculography) demonstrated: interrupted CSF flow (21); subarachnoid nodules (8); parenchymal brain metastases (6); hydrocephalus (4); and epidural spinal cord compression (1). Cytologic responses were seen in 14 women to first-, 7 to second- and 3 to third-line chemotherapy. Treatment-related toxicity included 21 women with aseptic meningitis and 10 women with thrombocytopenia or neutropenia (5 related to intraventricular chemotherapy). Median survival was 7.5 months (range 1.5 to 16), 18 women died of progressive LM or combined LM and systemic disease progression. Women with persistent interruption of CSF flow fared worse than women with normal CSF flow (median survival 3 versus 10 months; p < 0.0001). LM in women with metastatic breast cancer may be palliated with combined modality therapy, however, success of therapy and survival is based upon pre-treatment CNS extent of disease evaluation.

Idiopathic syringomyelia and the importance of occult arachnoid webs, pouches and cysts

Syringomyelia is the condition in which longitudinal cavities are found within the spinal cord. The use of drainage procedures has been widely practised with good short term results. However, the long-term results in some large series have been less favourable. There are many associated conditions and in most forms a blockage to the normal flow of CSF, either at the foramen magnum or in the spinal canal, can be identified. Most surgeons would now direct their efforts to the establishment of normal CSF flow rather than a shunting procedure. In a certain group of patients, even with the advent of sophisticated MRI, no associated abnormality or CSF block is easily identified. This type of syringomyelia is often termed idiopathic. We report 10 patients with symptomatic syringomyelia without readily recognized predisposing factors. In eight patients preoperative myelography revealed a block to the flow of contrast compatible with subarachnoid obstruction. Eight patients underwent laminectomy and division of the obstructing arachnoid webs. Five experienced good improvement and three only moderate improvement. Two of the patients underwent syrinx shunting procedures only, which resulted in a worsening of their symptoms. At operation one patient was found to have an arachnoid cyst. We believe that patients with idiopathic symptomatic syringomyelia may need myelography to identify such arachnoid abnormalities. Subsequent surgery should be directed at the establishment of normal CSF flow by laminectomy and excision of the offending lesion.

Prognostic significance of sup 111 Indium-DTPA CSF flow studies in leptomeningeal metastases

We assessed the clinical significance of interruption of CSF flow documented by radionuclide ventriculography (111Indium-DTPA CSF flow study) in patients with leptomeningeal metastases. Forty patients (25 men and 15 women) ranging in age from 6 to 70 years (median 38.5 years) with cytologically documented leptomeningeal metastases were demonstrated to have interruption of CSF flow by radionuclide ventriculography. All patients were treated with radiotherapy (30 Gy in 10 fractions) to the site of CSF obstruction after which intra-CSF chemotherapy (methotrexate or cytarabine followed by cytarabine or thio-TEPA if clinically indicated) was administered. Twenty patients (group 1) after radiotherapy to the site of CSF flow block demonstrated reestablishment of normal CSF flow. By contrast, 20 patients (group 2) treated in a similar manner had persistent CSF flow obstruction. All patients were treated with intraventricular chemotherapy. Median survival was 6 months in group 1 (range 3 to 15 months) compared with 1.75 months in group 2 (range 1 to 4 months) (p < 0.0001). Cause of death differed between groups with 20% of group 1 patients dying of progressive leptomeningeal disease compared with 70% of group 2 patients (p < 0.0006). In patients with leptomeningeal metastases and CSF flow obstruction, 111Indium-DTPA CSF flow studies predict patient survival and are useful in determining which patients would be candidates for intra-CSF chemotherapy administration.