Brain Edema and Disorders of Cerebrospinal Fluid Circulation

Joseph Jankovic MD , in Bradley and Daroff's Neurology in Clinical Practice , 2022

Gap Junctions on Ependymal and Pial Surfaces

Lining the cerebral ventricles (other than over the choroid plexus) is a layer of ciliated ependymal cells connected by gap junctions. Pial cells lining the surface of the brain, which form the limiting glial membrane, the glial limitans, also have gap junctions. Fluid, electrolytes, and large protein molecules move through the gap junctions, allowing exchange between the CSF and ISF. Intrathecal administration of antibiotics and chemotherapeutic agents has been used to bypass the BBB.

Blood vessels penetrate the brain from the surface. As they enter the brain, they are invested with pia mater. The space between the penetrating blood vessels and the brain, prior to the point where only brain tissue surrounds the vessels, is called the Virchow-Robin space. After injection of substances intrathecally, the large proteins in the CSF space penetrate into the brain from the surface via the Virchow-Robin spaces. These perivascular routes may be involved in the spread of infection into the brain from the subarachnoid space in meningitis.

Arachnoiditis

Robert F. Heary , ... Giancarlo Barolat , in Spine Surgery (Third Edition), 2005

Pathogenesis

The arachnoid is an avascular membrane that lies between two vascular membranes, the pia mater and the dura mater. A chronic infection or irritation can cause the arachnoid membrane to become thickened and adherent to both the dura mater and the pia mater. 26 The pia-arachnoid carries the blood vessels to the spinal cord, and this layer contains mesenchymal cells. In 1951, Smolik and Nash 34 recognized that when the outer arachnoid layer is injured, both the blood vessels and mesenchymal cells lend themselves to extensive proliferation. The ensuing reaction between the pia-arachnoid and the dura mater leads to obliterative arachnoiditis. 34 Arachnoiditis may affect the spinal cord or the cauda equina.

The pathogenesis of arachnoiditis is similar to the response of other serous membranes such as the peritoneum and pericardium. After the arachnoid layer is exposed to an insult, an inflammatory response that is characterized by a fibrinous exudate with a negligible inflammatory cellular exudate occurs together with neovascularization, leading to fibrosis. 7, 27 When this process occurs at the level of the spinal cord, vascular occlusive changes occur that reduce the blood supply to the spinal cord. 19, 21, 26, 32 The small perforating blood vessels that supply the outer portions of the white matter may be obliterated and result in necrosis and cavitation of the spinal cord parenchyma. 19, 32 Furthermore, obliteration of the venous drainage of the spinal cord may occur. 32 Ransford and Harries 26 postulated that in addition to causing the embarrassment of the blood supply of the spinal cord, arachnoiditis may cause secondary changes as a result of frank mechanical compression of neural tissue or diminished cerebrospinal fluid (CSF) circulation.

In the first half of the twentieth century, arachnoiditis was most often attributed to infectious causes. This led to changes throughout the neuraxis. More recently, lumbar arachnoiditis of noninfectious origin has become more prevalent than arachnoiditis at the spinal cord level. Lumbar arachnoiditis affects the nerve roots at the level of the cauda equina. Therefore the majority of recent experimental studies on arachnoiditis have focused on the cauda equina region.

In a classic description of lumbosacral arachnoiditis, Burton 3 described three stages in its pathogenesis. The first stage, radiculitis, consists of an inflamed pia-arachnoid with associated hyperemia and swelling of the nerve roots of the cauda equina. In the second stage, arachnoiditis, a progression of fibroblast proliferation and collagen deposition occurs. During this stage, nerve root swelling decreases, and the nerve roots adhere to each other and to the pia-arachnoid. In the third and final stage, adhesive arachnoiditis, marked proliferation of the pia-arachnoid occurs, with dense collagen deposition within the thecal sac. There is complete nerve root encapsulation, as well as hypoxemia of the nerve roots and progressive nerve root atrophy. 3

Yamagami et al. 36 induced experimental arachnoiditis at the level of the cauda equina in 105 rats. They found that the development of arachnoiditis and neural degeneration directly corresponded to the magnitude of extradural inflammation and wound healing processes that occurred after laminectomy with or without retained foreign bodies. These investigators postulated that a diminished nutritional supply may be responsible for the pathologic changes in arachnoiditis. Adhesions of the arachnoid cause the nerve roots of the cauda equina to lump together, and in so doing, these nerve roots are isolated from contact with the CSF, which results in both circulatory and nutritional disturbances in the nerve roots. 36 In another study, McLaurin et al. 21 induced experimental arachnoiditis in dogs. The adhesive arachnoiditis produced a nearly solid ring of dense collagenous tissue that extended from the pia to the dura. The vessels of the subarachnoid space were embedded in this fibrous tissue and appeared to be constricted by it. 21

The end stage of arachnoiditis, adhesive arachnoiditis, is the stage most associated with significant clinical morbidity. In this stage, the nerve roots are completely covered with collagen and become an integral part of the dural membrane. The thecal sac can appear to be an empty tube devoid of identifiable nerve fibers. 4 Many of the nerve roots passing through these sclerotic meninges degenerate and become atrophic. 19 At this stage of arachnoiditis, a lumbar puncture or surgical opening of the dura mater may lead to sectioning of the atrophic nerve fibers. 4

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Vein of Galen Aneurysmal Malformation

H. Richard Winn MD , in Youmans and Winn Neurological Surgery , 2017

Pial Arteriovenous Malformation with Vein of Galen Aneurysmal Dilation

Pial AVM with VGAD is a pial or parenchymal AVM that drains into the dilated vein of Galen or its tributary. Dilation of the vein of Galen is secondary to outflow obstruction. Outflow obstruction can be functional, due to high flow fistulas, or mechanical, due to progressive occlusion of the jugular bulb and the sigmoid sinus, or both. Progressive occlusion of the dural sinus is frequently observed in pediatric fistulous malformations of the brain, including VGAM. The etiology of this outflow obstruction is unknown but may be related to underdevelopment of the jugular bulb, abnormal skull base maturation, and kinking or thrombosis at the tentorial or dural edge at the skull base due to high-flow angiopathy of the venous system. Because of this outflow restriction, the vein of Galen dilates and blood flow refluxes into other normal cerebral veins (internal cerebral, vermian, hippocampal, basal vein, medial ventricular, internal parietal, or internal occipital veins, or other normal tributaries of the vein of Galen). Patency of the embryonic sinuses, such as the falcine sinus and the occipital sinus, is often seen in both VGAD and VGAM.

Pial AVM with VGAD usually manifests in childhood or young adulthood as intracerebral hemorrhage, focal neurological deficit, or seizures. High-output cardiac failure or hydrodynamic disorder can also occur in young children. Angiographic differentiation between VGAM and VGAD can sometimes be difficult. Demonstration of transmesencephalic feeders by magnetic resonance imaging (MRI) or angiography confirms the pial nature of the lesion 8 and thus the VGAD. Transmesencephalic feeders are projected below the P2 segment of the posterior cerebral artery on the lateral view of vertebral artery angiograms. 8 For treatment, transvenous occlusion of the vein of Galen is contraindicated in VGAD because it may produce hemorrhage or venous infarct of the deep cerebral veins, the outflow of which is occluded.

Pain Due to Tumors of the Skull Base

LASZLO MECHTLER MD , in Cancer Pain, 2006

Pain Related to Leptomeningeal Metastases

Leptomeningeal metastases (LM) occur when tumor cells infiltrate the arachnoid and the pia mater (leptomeninges), causing focal or multifocal infiltration. LM develop in approximately 5–8% of patients with non-Hodgkin lymphoma and up to 70% of patients with leukemia. Adenocarcinomas are the most common solid tumors causing LM, including, in decreasing order of frequency, breast, lung, melanoma, and gastrointestinal cancers. Untreated primary central nervous system tumors, such as medulloblastoma, ependymoma, and glioblastoma multiforme also have a high frequency of leptomeningeal seeding. The clinical features of LM are referable to the cerebrum, cranial nerves, and spinal nerve roots. Features of cranial nerve involvement, in order of frequency, are oculomotor palsies, facial weakness, hearing loss, vision loss, facial numbness, and tongue deviation. Headache and encephalopathy are common. Pain is the initial symptom in 25% of patients, and may occur in 40% of patients with LM infiltration. 36, 37 In most cases the pain is a dull, constant headache and may be one of two types: either with or without neck stiffness and back pain, the latter usually localizing to the lower back and buttocks. The pain results from traction on tumor-infiltrated nerves in the meninges. A clue that cranial nerve involvement is secondary to LM rather than to epidural tumor at the base of the brain is that multiple cranial nerves are usually affected. If the involvement is bilateral, it is even more likely that the pathology lies in the subarachnoid space rather than at the base of the brain.

CT continues to be used as a screening tool in the metastatic work-up for many cancer patients, but it is relatively insensitive compared to MRI, particularly in the detection of LM. MRI depicts LM well, particularly when magnetization transfer or post-contrast T1-weighted or FLAIR techniques are used. 38 Examination of the CSF is the most important test for LM. Only 3% of initial lumbar punctures yield normal CSF, but positive cytology is seen on initial CSF examination in 54% of LM patients, and the yield increases to above 90% when three separate spinal taps are performed. 39 The best yield is obtained when the CSF is taken from the symptomatic area. LM should be suspected when headaches are posturally induced or occur upon awakening, especially in cancer patients with normal CT or MR scans.

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Microsurgical Treatment of Spinal Vascular Malformations

H. Richard Winn MD , in Youmans and Winn Neurological Surgery , 2017

Perimedullary (Pial) Arteriovenous Fistulas

Previously described as type IV lesions, intradural AVFs are the result of a direct connection between an anterior or posterior spinal artery and the coronal venous plexus. As a result, they lie within the subarachnoid space and may be ventral or dorsal to the cord. These AVFs have been categorized by Merland and colleagues into three additional subtypes. 24,31 Type I lesions are defined by slow flow and relatively mild venous hypertension. Type II fistulas are composed of multiple feeding branches arising from the anterior spinal artery, thereby resulting in a higher flow lesion. Type III fistulas are characterized as giant fistulas with prominent dilation of the venous network. Among this group, progressively larger fistulas are defined by higher flow, increased pressure, and a greater incidence of clinically significant symptoms due to compression of the spinal cord, hemorrhage, or venous hypertension.

The eye

Torsten Liem DO Osteopath GOsC (GB) , in Cranial Osteopathy (Second Edition), 2004

The optic nerve sheaths (see Fig. 14.21)

The optic nerve is enclosed by the dura mater, the arachnoid mater and the pia mater.

•

The outer sheath of the optic nerve is formed by the dura mater, which blends with the sclera at the posterior surface of the eyeball. The outer sheath is continuous with the periosteum of the orbit. The dura mater protects the optic nerve and offers the eyeball support against the traction exerted by the extraocular muscles.

•

The inner sheaths of the optic nerve are formed by the arachnoid mater and the pia mater. The pia mater directly invests the optic nerve and passes septa into the nerve; these septa incompletely surround the bundles of nerve fibers. The pia mater is continuous with the choroid of the eyeball. The arachnoid mater is interposed between the dura mater and the pia mater and enables the optic nerve to shift minimally in its dural sheath. The fluid-filled intervaginal space corresponds to the CSF-filled subarachnoid space and very probably communicates with the latter. The intervaginal space terminates blindly at the eyeball. In the eye the arachnoid mater is a lamellar space between the choroid and the sclera.

The path of the optic nerve may be subdivided into four sections:

1.

The intraocular part (2 mm). The intraocular part consists of unmyelinated fibers located in the wall of the eyeball. Immediately after passing through the sclera the fibers acquire a myelin sheath.

2.

The intraorbital part (2.5 to 3 cm). This extends from where the nerve exits the eyeball as far as the optic canal. The optic nerve is surrounded by the four rectus muscles of the eye. The ophthalmic artery, the ciliary ganglion, the ciliary nerves and the ciliary vessels are located close to the optic nerve. A short distance behind the eyeball the central retinal vessels enter the optic nerve. At the entrance to the optic canal the optic nerve is surrounded by the funnel-shaped common tendinous ring. The nasociliary nerve, the abducent nerve as well as orthosympathetic fibers for the ciliary ganglion also pass through the common tendinous ring.

3.

The intracanalicular part (5 mm). Together with the ophthalmic artery, the optic nerve passes through the optic canal. It runs superiorly and medial to the artery. The optic canal is formed from the two original roots of the lesser wing of the sphenoid bone. In the optic canal the optic nerve travels in close proximity to the sphenoidal sinus and the ethmoidal air cells.

4.

The intracranial part (13 mm). This runs in the chiasmatic cistern in a posterior and medial direction to reach the optic chiasm. Here the optic nerve is sheathed only by the pia mater. Via the optic chiasm it is influenced by the pressure of the cerebrospinal fluid. The optic nerve also runs in close proximity to the internal carotid artery and its branches, the cavernous sinus, and the pituitary stalk.

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Sonography of the Fetal Central Nervous System

Luc De Catte , ... Michael Aertsen , in Fetal Medicine (Third Edition), 2020

Arachnoid Cysts

Arachnoid cysts result from an abnormal splitting of the arachnoid web and the inner layer the pia mater and subsequent entrapment of CSF. They account for about 1% of all intracranial masses in children. 227 Most of the arachnoid cysts are located supratentorially; 50% to 60% are located in the middle cranial fossa. They are also found in the quadrigeminal cistern (5%–10%), suprasellar cistern (5%–10%), cerebral convexity (5%) or posterior fossa (5%–10%). 227,228

On ultrasound, they appear as well-delineated, unilocular, regularly shaped hypoechoic masses without colour Doppler signal located on the surface of the brain.

In 25% of the cases, the diagnosis of arachnoid cysts is made in the second trimester; the remaining 75% are diagnosed between 28 and 34 weeks of gestation. Supratentorial cysts are picked up later in gestation than the ones in the posterior fossa. 229

The differential diagnosis includes porencephalic cysts, which are usually unilateral and communicating with the lateral ventricular system. 230 Additionally, CPCs are common intraventricular findings, and glioependymal cysts are located in the parenchyma of the brain. 231,232 Aneurysms of the vein of Galen and other vascular anomalies are easily differentiated by colour Doppler analysis. Rare conditions to differentiate are Rathke cleft cysts, schizencephaly, teratoma and IVH. In the posterior fossa, the differential diagnosis includes MCM, Blake pouch cysts and DWM.

Fetal MRI does not modify the diagnosis in the majority of cases, 141 but it is able to differentiate the AC from other cystic lesions. 229 In addition, MRI may be more precise in locating the lesion and determining its relationship with the surrounding structures, especially when located in the posterior fossa(Fig. 28.42). Finally, MRI more easily detects additional anomalies such as heterotopias and CC dysgenesis. 233 Postnatal workup mainly consists of a neurosonogram to confirm the location, size and number of the lesions and MRI to exclude associated cerebral anomalies.

The prognosis of a fetus with an arachnoid cyst depends particularly on the brain integrity rather than on the volume or location of the cyst. 234 The presence of a normal CC, absence of extra-CNS anomalies, a slowly growing cyst, the absence of VM and the location near the Sylvian fissure are favourable variables. Outcome of isolated arachnoid cysts is generally good. Neurologic symptoms reflect the anatomical localisation of the AC and the effect on CSF flow. Associated underlying abnormalities can give rise to symptoms, not directly related to the cyst itself (Table 28.15).

The natural history of AC varies from regression, stabilisation, slow growth towards acute enlargement of cyst, subdural effusion after rupture of cyst and subdural or intracystic bleeding, with or without trauma.

There is a debate in the literature between shunting and open microsurgical or endoscopic fenestration with cystoventriculostomy or cystocisternostomy. In a prospective long-term survey, a restrictive attitude to surgery for intracranial AC in the absence of objectively verified symptoms or signs of obstructions was advocated.

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Metastatic Disease and the Nervous System

Jasmin Jo , David Schiff , in Aminoff's Neurology and General Medicine (Sixth Edition), 2021

Leptomeninges

Definition

Leptomeningeal metastasis or neoplastic meningitis refers to the dissemination of cancer cells to the CSF, pia, and arachnoid mater. Depending on the underlying malignancy, this condition may be termed leptomeningeal carcinomatosis, lymphomatous meningitis, or leukemic meningitis. 14

Epidemiology

Leptomeningeal carcinomatosis is diagnosed in 5 to 10 percent of patients with solid cancers and 5 to 20 percent of those with hematologic malignancies. It also occurs in 1 to 2 percent of patients with primary brain tumors. The most common solid tumor sources are breast (12 to 34%), lung (10 to 26%) carcinomas, and melanoma (17 to 25%), while the most common hematologic tumor sources are acute lymphoblastic leukemia (10%), acute myeloid leukemia (5 to 10%), primary CNS or ocular lymphoma (20%), and non-Hodgkin's lymphoma (20%). The median age of diagnosis is 56 years and median KPS is 70. More than 70 percent of patients with leptomeningeal disease have advanced and uncontrolled systemic disease. Approximately 19 percent of cancer patients with neurologic signs and symptoms have evidence of leptomeningeal metastases on autopsy studies. 14

Pathophysiology

Leptomeningeal seeding occurs through several mechanisms, including hematogenous spread via Batson plexus or arterial dissemination, direct extension from adjacent structures, and migration from systemic tumors along perineural or perivascular spaces. Once tumor cells reach the leptomeninges, they can spread throughout the CNS via the CSF, resulting in multifocal neuraxis seeding. Tumor infiltration is most prominent in the skull base, the posterior surface of the spinal cord, and cauda equina, producing cranial nerve palsies and radiculopathies. Tumor deposits may result in obstruction of CSF flow, leading to hydrocephalus and sometimes to increased ICP. Blood vessels crossing the subarachnoid space may become occluded, leading to cerebral or spinal infarction. 14

Clinical Features

Clinical manifestations of leptomeningeal metastases can be classified into three categories: cerebral involvement resulting in headache, altered mental status, nausea, vomiting, gait disturbance, and cerebellar signs; cranial nerve involvement presenting with diplopia, visual loss, hearing changes, and facial weakness; and spinal symptoms including weakness, paresthesias, radicular neck or back pain, and bowel or bladder dysfunction. The majority of patients present with multifocal symptoms.

Diagnostic Studies

Gadolinium-enhanced MRI of the entire neuraxis is warranted to evaluate the extent of CNS disease and plan treatment. Neuroimaging should precede lumbar puncture as intracranial hypotension from lumbar puncture may produce pachymeningeal enhancement that mimics leptomeningeal metastases.

MRI findings that are highly suggestive of leptomeningeal metastases include linear or nodular enhancement of leptomeninges, which is often visible in the cerebral sulci, cerebellar folia, basal cisterns, and cauda equina; enhancement of the subependyma, and cranial or spinal nerves; and hydrocephalus (Fig. 26-7). A high-clinical suspicion of leptomeningeal metastases coupled with consistent MRI findings is sufficient to establish the diagnosis, even in the absence of malignant cells on CSF cytology. 14

Figure 26-7. Leptomeningeal metastasis from breast carcinoma. Postcontrast MRI demonstrates leptomeningeal enhancement along the left superior cerebellar surface in A, the margin of the frontal horn of the right lateral ventricle in B, and the left foramen of Luschka in C.

While identifying malignant cells in the CSF is the gold standard for diagnosis, its sensitivity is low. To minimize false-negative studies, the following measures are recommended: withdrawal of at least 10.5 ml of CSF for analysis; immediate processing of the sample; obtaining CSF from a site adjacent to the affected CNS region; and repeated CSF sampling and analysis. The sensitivity of CSF cytology is 71 percent for the first sample, 86 percent after two samples, 90 percent following three samples, and up to 93 percent after more than three samples. Flow cytometry analysis improves this sensitivity for patients with hematologic malignancies. Other CSF parameters suggestive of leptomeningeal metastases are elevated opening pressure, elevated leukocyte count, increased protein content, and decreased glucose level. CSF flow block develops at various levels in 30 to 70 percent of patients with leptomeningeal metastases and can be seen with radionuclide studies. Several organ-specific biomarkers in the CSF such as CA 15-3 in breast cancer and CEA and Cyfra 21.1 in nonsmall cell lung cancer, may assist in diagnosis. Isolation and quantification of circulating tumor cells can detect malignant cells in CSF through the use of immunoflow cytometry technique with fluorescently labeled antibodies. In epithelial tumors, an antibody against epithelial cell adhesion molecule (EpCAM) is used, as this protein is expressed in various epithelial cancers such as breast, lung, and gastrointestinal cancers; high-molecular-weight melanoma-associated antigen/melanoma chondroitin sulfate proteoglycan (HMW-MAA/MCSP) is used for melanoma. Available studies on circulating tumor cells in the CSF of patients with leptomeningeal metastases have a reported sensitivity of 78 to 100 percent, compared to 44 to 67 percent with cytology at first lumbar puncture. The specificity of circulating tumor cells ranged between 84 and 100 percent. However, prospective studies with larger samples are required to validate these findings. 14,15

Treatment

Goals of treatment are to improve or stabilize neurologic function, maintain quality of life, and prolong survival. Treatment optimally should be directed toward the entire neuraxis, as tumor cells are disseminated widely throughout the CSF. However, craniospinal radiotherapy is rarely employed because of its significant adverse effects such as gastrointestinal toxicity, mucositis, and bone marrow suppression, and the lack of significant improvement in survival compared to chemotherapy. Involved-field radiotherapy to sites of symptomatic or bulky disease provides palliation of symptoms, treatment of bulky disease, and restoration of CSF flow. Whole-brain radiation therapy and/or placement of a ventriculoperitoneal shunt may be required for patients with communicating hydrocephalus. Patients with breast cancer, leukemia, and lymphoma have a higher likelihood than those with other malignancies of responding to radiotherapy. 14

Chemotherapy can be given systemically or by the intrathecal route. Systemic chemotherapy can treat both leptomeningeal and systemic disease. Since the blood–brain barrier is intact or only partially disrupted in leptomeningeal disease, agents that are lipid soluble and can be administered safely and achieve a therapeutic level of CSF penetration at higher doses are utilized, such as methotrexate (3 to 8   g/m2) or cytarabine (3   g/m2). Other drugs that can cross the blood–brain barrier are capecitabine, thiotepa, and temozolomide. Tumor histology and response to prior drug exposure guide the choice of chemotherapeutic agent.

Intrathecal delivery has several advantages over systemic chemotherapy, including circumvention of the blood–brain barrier and reduction of systemic adverse effects because the drug is delivered directly into the subarachnoid space, and reduced overall dosage. This approach is not appropriate for bulky leptomeningeal diseases as drug concentration is only 1 to 2 percent of the CSF concentration at 1 to 2   mm from the surface. Agents primarily given by the intrathecal route are methotrexate and cytarabine (Ara-C). Randomized trials demonstrated no difference in survival using single-agent methotrexate or thiotepa compared to a combination of methotrexate, thiotepa, and cytarabine in patients with leptomeningeal carcinomatosis from solid tumors. Intrathecal administration of rituximab, an anti-CD20 monoclonal antibody, and trastuzumab, an antihuman epidermal growth factor receptor (HER-2) monoclonal antibody, have been investigated for lymphomatous meningitis and HER-2-positive breast leptomeningeal metastases, respectively, but are not considered standard yet. Intrathecal agents can be delivered via lumbar puncture or intraventricular (Ommaya) reservoir. Repeated lumbar punctures are inconvenient for patients, may result in inadvertent delivery of drugs outside the thecal sac, and produce a more variable drug concentration than intraventricular administration. Although ventricular reservoirs are usually well tolerated, complications such as misplacement, catheter tip occlusion, and infection may occur. 14

Systemic administration of targeted therapies has shown clinical benefits, such as epidermal growth factors (EGFR) tyrosine kinase inhibitors (erlotinib, gefitinib, and osimertinib) in patients with nonsmall cell lung cancer, anaplastic lymphoma kinase (ALK) inhibitors (crizotinib, ceritinib and alectinib) in ALK fusion-positive nonsmall cell lung cancer patients, trastuzumab in HER2-positive breast cancer, and BRAF inhibitors (dabrafenib and vemurafenib) for melanoma. Prospective trials are needed to validate these findings. Due to limited CNS penetration at standard daily dosing, an intermittent "pulsatile" administration of high-dose tyrosine kinase inhibitors can boost CSF drug concentration. Pulsatile erlotinib is a reasonable alternative in EGFR-positive nonsmall cell lung cancer patients with new or worsening leptomeningeal or brain metastases, without evidence of systemic progression during standard erlotinib dose. 14

Aggressive supportive treatment should be given to all patients with leptomeningeal metastases including corticosteroids for vasogenic edema and increased ICP, AEDs for seizures, opioid drugs for adequate analgesia, and antidepressants and anxiolytics as needed.

Prognosis

The median survival for untreated leptomeningeal metastases is 4 to 6 weeks, and death often results from progressive neurologic dysfunction. With treatment, median survival is increased to 4 to 8 months. Patients with hematologic tumors have improved survival (median of 4.7 months) compared with solid tumors (median of 2.3 months). Tumor histology and molecular types are also important prognostic factors. The National Comprehensive Cancer Network suggests stratifying patients into either good- or poor-risk groups to guide decision-making regarding treatment. Patients with poor risk are those with low KPS, multiple, serious, or major neurologic deficits, extensive systemic disease with few treatment options, bulky CNS disease, leptomeningeal disease-related encephalopathy, and the presence of CSF block. The goal of treatment for these poor-risk patients is palliation of symptoms. For patients with better risk factors, a more aggressive treatment approach is recommended.

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Case 142

In The Teaching Files: Brain and Spine, 2012

Definition/Background

Meningeal metastases result from diffuse infiltration of the pachymeninges (dura-mater) and leptomeninges (pia-mater and arachnoid-mater) by malignant cells originating from a primary tumor site. Their incidence seems to be rising; this is likely associated with an increase in the overall survival of many cancer types. Hematogenous spread to the meninges is the most frequent cause. Direct extension from contiguous extracranial neoplasms, secondary invasion of the meninges by calvarial and skull base metastases, and migration along perineural or perivascular structures are less common.

Leptomeningeal metastases are often caused by breast carcinoma, acute lymphocytic leukemia, and malignant high-grade non-Hodgkin's lymphomas. Dural metastases are more likely to be caused by tumors from prostate, breast, and lung. Dural metastases is also seen in carcinomas arising from the nasopharynx or the sinonasal tract, but this is likely related to contiguous spread of the tumor or, less likely, secondary to perineural invasion.

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Chronic Meningitis

Prashanth S. Ramachandran , Michael R. Wilson , in Aminoff's Neurology and General Medicine (Sixth Edition), 2021

Definition

The meninges are composed of the dura mater, the arachnoid, and the inner most layer, the pia mater. The term "meningitis" typically refers to inflammation of the leptomeninges (i.e., the arachnoid and pia mater) and can be detected by a pleocytosis in the cerebral spinal fluid (CSF), enhancement on contrast magnetic resonance imaging (MRI), or through the discovery of inflammatory cells on meningeal biopsy. Meningitis is considered chronic when the CSF pleocytosis, or the symptoms found to be associated with the meningitis, last greater than 1 month. However, the strict definition of 1 month should not dissuade the clinician from considering the differential diagnosis associated with chronic meningitis if there is clearly chronicity to the symptoms. The category of subacute meningitis encompasses almost all of the same etiologic agents as chronic meningitis and frequently progresses to chronic meningitis if not treated. Chronic meningitis symptoms may sometimes wax and wane, making it appear as if the patient is suffering from recurrent attacks of acute meningitis; however, there is usually no resolution of the CSF pleocytosis in between these attacks. This situation differs from recurrent meningitis in which there is a clear resolution of symptoms and CSF pleocytosis in between symptom worsening.

Pachymeningitis is inflammation of the dura. As this layer of the meninges is not in direct contact with the CSF space, which lies between the arachnoid and pia, CSF pleocytosis is rare unless there is also leptomeningeal involvement. Pachymeningitis is diagnosed based on neuroimaging and sometimes meningeal biopsy; its differential diagnosis is distinct from chronic leptomeningitis (Table 47-2).

Table 47-2. Differential Diagnosis of Chronic Pachymeningeal Enhancement

Infection
Mycobacterium species
Syphilis
Lyme disease
Viral meningitis (HTLV-1, herpes viruses)
Fungal meningitis
Primary amoebic meningitis
Autoimmune/Inflammatory
Neurosarcoidosis
Rheumatoid arthritis
Sjögren syndrome
Vogt–Koyanagi–Harada syndrome and other uveomeningitis syndromes
IgG4-related disorders
Histiocytosis
Granulomatosis with polyangiitis
Neoplasm
Leptomeningeal carcinomatosis
Glioneuronal tumor
Lymphoma
Focal pachymeningeal enhancement: meningioma, calvarial lesions
Iatrogenic
Lumbar puncture
Shunt placement
Craniotomy
Intrathecal chemotherapy
Other
Spontaneous intracranial hypotension due to trauma, connective tissue disorder, transdural spinal osteophytes, CSF venous fistula or Gorham–Stout disease 1
Venous sinus thrombosis
Extramedullary hematopoiesis
Postsubarachnoid hemorrhage
Idiopathic

HTLV, human T-cell leukemia virus; IgG4, immunoglobulin G4.

Adapted from Table 3-2 in Continuum (Minneap Minn) 24:1298, 2018.

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