Online newspaper of professor Yasser Metwally

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

September 29, 2009 — Encephalitis is an inflammatory disease of the brain and may be caused by bacteria, fungi, protozoa or viruses. The majority of diffuse infections of the CNS are viral in origin. The infection of the brain typically occurs during the initial exposure; however, some viruses like the herpes virus can cause disease many years after the primary exposure.Virulent organisms are able to bypass the body’s defense mechanism and produce general inflammation. The brain responds to these virulent organisms with an infiltrate of inflammatory cells along a perivascular distribution. Neuronal destruction results in cytotoxic and vasogenic edema with the subsequent formation of glial nodules.

• Herpes simplex encephalitis

Herpes simplex virus (HSV) type I is an important cause of encephalitis producing a fatal fulminant necrotizing meningoencephalitis in 50-70% of cases. The onset of symptoms may be abrupt or evolve over several days, with headache and fever being the most common early findings. Studies have shown that early diagnosis and treatment increases survival and decreases morbidity. Pathologically, HSV encephalitis is characterized by hemorrhagic necrosis involving one or both temporal and frontal lobes. This pattern is thought to result from the entry of the virus into the trigeminal ganglia which lie near the temporal lobes.

Extensive brain edema is very common in herpes encephalitis .Brain infarction, secondary to vasculitis,is not infrequent and might be localized to either the frontal or temporal lobes. HSV type 11 is an important cause of encephalitis in neonates and does not have preference for the temporal lobes.

The CT scan may be normal in early encephalitis. Specific CT findings of temporal lobe or frontal lobe edema with mass effect and contrast enhancement may appear later.

Magnetic resonance imaging is able to detect subtle changes in brain water due to edema, which aids in earlier diagnosis and shows the extent of the disease more fully. Findings on MR imaging of abnormal signal in the temporal lobes and variable extension into the frontal lobes with sparing of the basal ganglia are highly characteristic of HSV infections. Also, MR imaging is better able to monitor the resolution of the disease as a result of early treatment. Brain infarctions might be demonstrated in some cases of herpes encephalitis

Figure 3. MRI T1,T2 study of a patient with herpes encephalitis,notice the massive brain edema,periventricular [more on the right side] and pontine encephalitic patches,those are hyperintense on the T2 images

• Treatment of herpes encephalitis

Patients with herpes encephalitis should be given acyclovir I.V. for Infusion in doses of 10mg/ kg every 8 hours provided renal function is not impaired. Patients with renal impairment should be administered acyclovir I.V. for Infusion with caution.

The required dose of acyclovir I.V. for Infusion should be administered by slow intravenous infusion over a one hour period. A course of treatment with acyclovir I.V. for Infusion usually lasts 5 days, but this may be adjusted according to the patient’s condition and response to therapy. Treatment for herpes encephalitis may lasts 10 days

CHRONIC ACTIVE ENCEPHALITIS: HISTOPATHOLOGICAL FINDINGS.

1. Neuronal cell bodies are involved to a variable degree resulting in
2. Destruction of the cell bodies
3. Perivascular lymphocytic and plasma cell infiltration
4. Microglial cell proliferation with rod cell formation
5. Extensive demyelination and marked astrocytic proliferation

• SSPE

Subacute sclerosing panencephalitis is a slowly progressive and fatal encephalitis. The disease usually occurs 3-10 years following a measles infection and is believed to be caused by this virus. Pathologically both grey and white matter are involved. In the grey matter, gliosis and perivascular infiltration by lymphocytes are found. Demyelination of variable degrees and gliosis are usually seen in the white matter. Eosinophilic inclusion bodies are often found in oligodendrocytes and neural cells in the cortex. These changes are also found in the caudate nucleus, putamen, globus pallidus, pons and thalamus.

Magnetic resonance imaging of subacute sclerosing panencephalitis shows lesions in the white matter of decreased intensity on the Tl-and increased intensity on the T2-weighted images. Lesions of increased signal are seen in the white matter on the T2-weighted images that are not seen on CT.

• Rubella panencephalitis

Rubella virus,like measles virus,has been recognized to cause a slowly progressive panencephalitis. Most causes have occurred in patients with congenital rubella syndrome. The disease is characterized by inflammation with perivascular round cell infiltration associated with extensive demyelination and reactive gliosis, Pathological changes are most marked in the cerebellum .Intracellular inclusion bodies and virus particles have been recognized.immune-mediated vasculitic damage have been recognized and is thought to represent the primary pathogenic mechanism

IMMUNE DEFICIENCY RELATED VIRAL ENCEPHALITIC DISEASES

The frequency of neurologic symptoms from infections has become more evident with the current increase in immunosuppression due to organ transplantation, aggressive cancer chemotherapy and AIDS. Approximately one-third of AIDS patients have neurologic signs and symptoms during the course of the illness and 10-20% have neurologic complaints prior to the manifestation of AIDS. Neurologic involvement is even higher in autopsy cases where 73-80% have histologic evidence of severe disease. Neurologic involvement may be related to the direct effects of the human immunodeficiency virus (HIV), or secondary to infections or neoplasms. It is often difficult to ascribe a particular problem to a specific agent because multiple pathogens may be present. Both systemic and CNS infections contracted by AIDS patients are usually not bacterial in origin, but caused by opportunistic organisms.

The most common CNS infection in AIDS is caused by the neurotropic HIV virus. This virus causes both a subacute encephalitis (producing a progressive dementing encephalopathy) and a chronic meningitis. The centrum semiovale is the most common site of involvement, but all white matter tracks may be affected.Clinically, the subacute encephalitis progresses to a subcortical dementia known as AIDS dementia complex (ADC) which occurs in more than one-half of the patients with AIDS.

Magnetic resonance imaging in early HIV encephalitis shows bilateral areas of increased signal intensity in the deep white matter on the T2-weighted images. Late findings included atrophy and areas of diffuse increased signal intensity in the periventricular region, centrum semiovale and frontal lobes. No mass effect or enhancement with gadolinium is seen. Early CT findings may be normal. Late findings include atrophy and diffuse decreased attenuation of the deep white matter, which does not enhance. For detecting these abnormalities, MR imaging is significantly more sensitive than CT. A diffuse periventricular white matter pattern on MR imaging in patients with AIDS strongly suggests AIDS and further evaluation is usually not indicated.

Progressive multifocal encephalopathy (PML) is a viral infection affecting 2-7% of all AIDS patients. The disease is caused by a papovavirus and results in demyelination with necrosis of the white matter. Electron microscopy shows the oligodendrocyte nuclei to be filled with viral particles. These oligodendrocytes are the cells responsible for the maintenance and production of myelin.

Clinically, PML develops insidiously and evolves relentlessly until the patient’s death in about 6 months or more.The centrum semiovale is frequently affected with extension into the cortical and subcortical areas of the cerebral hemispheres with a predilection for the parietooccipital areas. This involvement may help explain many of the neurologic symptoms seen with PML such as visual loss, aphasia, hemiparesis, ataxia and other focal findings.

The T2-weighted MR images are more sensitive than CT or the TI-weighted images in detecting the extent and number of white matter lesions. PML lesions usually do not enhance. PML should be considered in any patient with AIDS who has focal high intensity intracerebral lesions on the T2-weighted scans.Contrast is frequently helpful in PML patients because this lesion does not enhance and can be distinguished from toxoplasmosis which does enhance.

Cytomegalovirus (CMV) is a member of the herpes virus group which often causes CNS abnormalities in immunosuppressed patients. The infection is frequently asymptomatic, although ventriculitis and/or focal, multifocal or diffuse encephalitis may occur. CMV has a predilection for involvement of the ependymal or subependymal regions. Magnetic resonance imaging shows both grey and white matter disease, ventriculitis and cortical atrophy.Studies done postmortem show focal hyperintense lesions without mass effect on the T2-weighted images . These lesions most frequently represent necrosis or infarction often associated with CMV infections. The high rate of infarction is believed due to infection of the endothelial cells causing occlusion of the vascular lumen.

References

1-Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 10.3a July 2009 [Click to have a look at the home page]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

September 29, 2009 — Benign nerve sheath tumors can be categorized into schwannoma and neurofibroma based on histopathologic characteristics. Schwannomas are solitary encapsulated tumors located along cranial or spinal nerves or nerve roots. These tumors consist of Schwann cells and do not contain nerve tissue. Histologically the tumor contains a mixture of two clear-cut patterns: Antoni A tissue has a compact arrangement of lipid rich Schwann cells and reticulin fibers. Antoni B tissue is loose textured, mucinous, and free of fibrillary background. These lesions can be seen in association with neurofibromatosis.

Figure 1. A, Antoni A tissues, B, Antoni B tissues

Neurofibromas are tumors of the cranial, spinal, or peripheral nerves and are intimately continuous with the nerve proper. The affected nerve is circumferentially compressed and diffusely penetrated by elements of tumor. Histopathologically neurofibromas contain all elements of the nerve, including Schwann cells, myelinated and unmyelinated nerve fibers, and fibroblasts. Thus it is difficult to remove the tumor without sacrificing the nerve. Plexiform neurofibromas are pathognomonic of von Recklinghausen’s disease. These tumors appear as tortuous entanglements or fusiform enlargements of the peripheral nerves.They often trap soft tissues, such as adipose tissue and muscle. Malignant nerve sheath tumors are seen in association with neurofibromatosis

Figure 3. Left schwannoma, right neurofibroma

Table 2. Differences between Schwannomas and neurofibromas (Click to enlarge table)

• Imaging Findings
  • CT-Pathology Correlation

Schwannomas with Antoni A tissue containing lipid- rich Schwann cells appear lucent on noncontrast CT scan. Schwannomas with Antoni B tissue appear cystic on CT scan as a result of loosely textured stroma that has a cystic component. The cells are separated by large amounts of edematous fluid, which coalesce to form cystic spaces.

Neurofibromas with predominantly lipid- rich Schwann cells are lucent on CT scan. Neurofibromas composed predominantly of compactly arranged collections of fibroblasts with abundant production of dense bundles of collagen appear dense on CT scan. Tumors show minimal to intense, homogeneous to inhomogeneous, or peripheral ringlike enhancement on postcontrast study.

Table 3. CT-Pathology Correlation of schwannomas (Click to enlarge table)

Neurofibromas Usually has a central area of decreased density that corresponds to the central fibrocollagenous core and a and a peripheral hyperdensity that corresponds to the Peripheral myxomatous tissues.

• · MR Imaging

Benign nerve sheath tumors are isointense to slightly hyperintense to muscle in TI-weighted pulse sequences. These tumors show variable hyperintensity in T2-weighted images; and commonly demonstrate the target sign (a peripheral hyperintense rim and a central low intensity) in T2-weighted sequences . This target pattern is attributed to peripheral myxomatous tissue and central fibrocollagenous tissue. This pattern is absent in lesions with cystic, hemorrhagic, or necrotic degeneration. A target sign was not seen in malignant lesions. A mass with a target appearance if seen by MR imaging is a useful sign in diagnosis of benign nerve sheath tumors. This sign is seen in both neurofibromas and schwannomas. Neither CT nor MR imaging can always accurately differentiate benign from malignant nerve sheath tumors. If masses are seen with irregular contour and and with disruption of soft tissue planes, this favor malignant neoplasm.

1. Schwannomas with Antoni A type of tissues commonly appears iso to hypointense on The T1 images, and hyperintense on the T2 images. Occasionally T1 hyperintensity might be related to increased lipid content of the lipid rich Schwann cells.
2. Schwannomas with Antony B fibers appear predominately hypointense on the T1 images and hyperintense on the T2 images .the T2 hyperintensity is partially related to the cystic formations occasionally T2 hypointensity might be found and represents intratumoural haemorrhage,dense cellularity or collagen deposition.

In neurofibromas cystic changes are uncommon .the tumours are uniformly hypointense on the t1 images ,while on the T2 images the target appearance might be seen with a relatively peripheral hyperintensity that corresponds to the peripheral myxomastous tissue and a central hypointensity that relates to the fibrocollagenous core

Figure 5.  MRI T2 image showing the target sign

• Schwannomas

Schwannomas of the inferior cranial nerves are the second most frequent tumor type in the jugular foramen. Hypoglossal schwannomas appear as circular or oval homogeneous masses of soft tissue with marked uptake of contrast agents. An important diagnostic criterion in this regard is the ipsilateral hemiatrophy of the lingual muscles due to paresis.

In contrast to glomus jugulare tumors, schwannomas grow only expansively, often with involvement of the parapharyngeal area. These growth patterns typically show an hourglass-shaped configuration of the tumor when visualized with coronal and sagittal sections.

References

1-Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 10.3a July 2009 [Click to have a look at the home page]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

September 29, 2009 — Cryptococcosis neoformans: Cryptococcal meningitis occurs both in normal and in immunocompromised hosts. It is the most frequently encountered CNS fungal infection and the most frequent infectious cause of chronic meningitis in referral hospitals with large numbers of immunocompromised patients. Ill Patients with cryptococcal meningitis may have nodular pulmonary infiltrates on chest radiographs. Meningoencephalitis and cryptococcomas are the most common neurologic manifestations. Subtle cognitive deficits without meningismus may, however, be the only findings. Optic disk swelling with visual loss reflects optic nerve or tract invasion; optic disk swelling without visual loss suggests increased intracranial pressure. Focal signs suggest granuloma or abscess formation, which usually is intracranial but also can involve the spinal cord.

Table 1. Types of fungi (Click on table to enlarge)

Meningitis is the most common form of CNS disease caused by C. neoformans, but the organism may also cause brain abscesses and granuloma, either alone or in association with meningitis. Most frequently, these present with focal weakness or hemiparesis, papilledema, or cranial nerve signs, The pathology ranges from mild congestion to meningeal thickening and distention of the subarachnoid spaces by abundant mucoid exudate. Fungi may enter the subarachnoid spaces and accompany the perforating arteries in the Virchow- Rubin spaces, These give rise to small soap-bubble or gelatinous pseudo-cysts in the adjacent parenchyma. The T2 images show bilateral small well-defined foci of high signal intensity in the region of basal ganglia.These lesions appear hypointense to isointense on the T1 images and may not enhance after contrast injection.Dilated perivascular spaces of Virchow- Rubin are characteristic of cryptococcal infection.

• Blastomycosis

Brain abscess and epidural abscesses are a common manifestation of blastomycotic CNS infection. Skin abscesses on the face may spread by direct extension to involve the brain or the epidural space.

• Histoplasmosis

Histoplasmosis is usually a benign, asymptomatic infection. A mild pulmonary disease is the usual manifestation in those who have symptoms. A small percentage of patients, however, have disseminated disease involving the bone marrow, spleen, and other organs including the CNS. Disseminated disease to the CNS may take the form of meningitis, milliary granulomas, or a solitary histoplasmoma.

• Aspergillosis

Aspergillus infection of the CNS is usually caused by hematogenous spread from the lung, but direct extension from the sinuses or the orbit has been reported. CNS infection has also occurred as a complication of pituitary surgery.

Aspergillus invades blood vessel walls, producing thrombosis or hemorrhagic necrosis, predisposing to subarachnoid hemorrhage or intracerebral hemorrhage. Granulomata may produce headache, papilledema, and visual loss (involvement of the optic nerve). A stroke-like picture also may predominate and seizures, headache, or lethargy may occur. Fever often is absent. The CSF cell count is usually less than 600 cells per VLI and may be predominantly neutrophilic or lymphocytic.

Patients are often afebrile or have only a low-grade fever. Their symptoms are usually those of a cerebral mass lesion, although the propensity of the fungus to invade blood vessels may lead to extensive necrosis and sometimes to intracranial bleeding. The disease is usually slowly progressive, and symptoms may persist for months.Diagnosis of aspergillosis of the CNS is difficult. The organism is rarely cultured from the CSF. Diagnosis may be made by histology and culture of biopsy material.

CT scanning is helpful in documenting orbital or sinus portals of entry and identifying abscesses or granulomas often found in the frontal and temporal regions. Angiography may be useful in defining the extent of fungal invasion of blood vessels. The only way to establish the diagnosis of CNS aspergillosis is to identify the organism invading tissue. Transbronchial, open-lung, or paranasal sinus biopsy may be the most direct mean of obtaining extraneural tissue.

References

1-Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 10.3a July 2009 [Click to have a look at the home page]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

September 29, 2009 — A nice lecture on sleep disorders

References

1-Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 10.3a July 2009 [Click to have a look at the home page]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

September 29, 2009 — A nice lecture on movement disorders

References

1-Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 10.3a July 2009 [Click to have a look at the home page]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

September 28, 2009 — A nice lectures on brain tumors

References

1-Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 10.3a July 2009 [Click to have a look at the home page]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

September 28, 2009 — Lymphomatous leptomeningitis (LLM) due to primary central nervous system (CNS) lymphoma is an uncommon problem in neurooncology and can occur at time of diagnosis or recurrence. Notwithstanding frequent focal signs and symptoms, Lymphomatous leptomeningitis is a disease affecting the entire neuraxis, and therefore staging and treatment need to encompass all cerebrospinal fluid (CSF) compartments. Central nervous system staging of Lymphomatous leptomeningitis includes contrast agent–enhanced cranial computed tomography (CT) or Gd-enhanced magnetic resonance (MR) imaging, Gd-enhanced spinal MR imaging, CT myelography, and radionuclide CSF flow study. Treatment of Lymphomatous leptomeningitis includes involved-field radiotherapy of bulky or symptomatic disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic therapy can benefit patients with LM and can obviate the need for intra-CSF chemotherapy. At present, intra-CSF drug therapy is confined to three chemotherapeutic agents (methotrexate, cytosine arabinoside, and thiotepa) administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Although treatment of Lymphomatous leptomeningitis is palliative and the expected median survival of patients is 4 to 6 months, it often provides stabilization and protection from further neurological deterioration. In patients with primary CNS lymphoma, CNS prophylaxis has been recommended (using a combination of high-dose systemic chemotherapy and intra-CSF chemotherapy), but the strategy remains controversial because high-dose systemic methotrexate is commonly used as an adjuvant therapy. Patients with primary CNS lymphoma at high risk as defined by positive CSF cytology or neuroradiography consistent with LM may benefit from the inclusion of intra-CSF chemotherapy.

Primary CNS lymphomas are uncommon primary brain tumors that represent 1 to 2% of all brain tumors.^{[1,4-6,27-30,32,42,44,52-55,61,70]} Primary CNS lymphomas occur in both immunocompetent and immunocompromised patients, especially in those who have undergone organ transplantation and in those with acquired immunodeficiency syndrome.^[5,70] The clinical presentation of patients with primary CNS lymphomas is a reflection of tumor topography within the CNS and most commonly one of several cerebral syndromes such as raised intracranial pressure, evolving stroke, or encephalopathy.^{[1,4-6,27-30,32,42,44,52-55,61,70]} In approximately one third of patients, however, an atypical presentation occurs, including that of LM.^[44,55] Primary CNS lymphoma recurs in the majority of patients, and in 40% of patients when restaging is undertaken following recurrence, LM is shown to be present.^[3,16,48]

Because the definition of LM and the methods of assessment differ from study to study, defining its incidence in newly diagnosed patients with primary CNS lymphoma is problematic. The authors of the majority of studies have defined Lymphomatous leptomeningitis by a positive CSF cytopathology, which is the traditional method of assessment. The authors of other studies, however, have reported incidences based on CSF flow cytometry, polymerase chain reaction, neuroimaging, or autopsy results as alternative methods of assessment. Another issue that likely affects the variability in incidence encountered between studies is the timing of surgery, volume of the lesion, site of sampling (ventricular or lumbar region), and frequency of CSF assessment. Cerebrospinal fluid sampling and yield of CSF cytology may, in addition, be affected by treatment, and the authors of most studies have not elaborated on how or when CSF sampling is performed.

In studies in which investigators define LLM as a positive CSF cytopathological finding, the results are similar.^[3,29] Balmaceda and colleagues^[3] each reported a prevalence of 27%, whereas other investigators, including Ferreri and colleagues^[29] who reported on a larger series of patients, noted a prevalence of Lymphomatous leptomeningitis of 12 to 16%. When other methods of assessment, such as biopsy sampling and MR imaging, are integrated with CSF cytopathological examination, the reported prevalence increases, and in one study of patients with newly diagnosed primary CNS lymphomas it was 42%. The authors of other studies using different modalities, including polymerase chain reaction for a component of immunoglobulin G heavy chain or contrast agent-enhanced brain and spinal imaging alone, have reported lower prevalence values for Lymphomatous leptomeningitis : 13 and 12.5%, respectively.^[41,47] Thus, on the basis of published reports the frequency of Lymphomatous leptomeningitis ranges from 12.5 to 42% in patients with newly diagnosed primary CNS lymphomas. Isolated leptomeningeal relapse is uncommon in patients with primary CNS lymphomas; however, simultaneous disease in the brain and leptomeninges has been reported in up to 40% of patients with primary CNS lymphoma at the time of relapse.^[3,5,53]

In summary, LLM is sufficiently common that leptomeningeal-directed therapy is indicated as part of the treatment regimen in patients with newly diagnosed primary CNS lymphomas. Leptomeningeal-directed therapy takes several forms: intra-CSF chemotherapy, radiotherapy, or high-dose systemic chemotherapy that in addition treats the leptomeningeal compartment (for example, high-dose intravenous methotrexate).^[36]

• Clinical picture of lymphomatous leptomeningitis

Lymphomatous meningitis classically presents with pleomorphic clinical manifestations encompassing symptoms and signs in the following three domains of neurological function: 1) the cerebral hemispheres; 2) the cranial nerves; and 3) the spinal cord and roots. Signs on examination generally exceed the symptoms reported by the patient.^{[2,11,36,69,71]}

The most common manifestations of cerebral hemisphere dysfunction are headache and mental status changes. Other signs include confusion, dementia, seizures, and hemiparesis. These findings often overlap with signs of parenchymal primary CNS lymphomas and therefore the clinical distinction between parenchymal and CSF compartment disease can be challenging. Diplopia is the most common symptom of cranial nerve dysfunction, with the sixth cranial nerve being the most frequently affected, followed by the third and fourth cranial nerves. Trigeminal sensory or motor loss, cochlear dysfunction, and optic neuropathy are also common findings. Spinal signs and symptoms include weakness (lower extremities more often than upper), dermatomal or segmental sensory loss, and pain in the neck, back, or following radicular patterns. Nuchal rigidity is only present in 15% of cases.^{[2,11,36,69,71]}

A high index of suspicion is required to make the diagnosis of Lymphomatous leptomeningitis . The finding of multifocal neuraxis disease in a patient with primary CNS lymphoma is strongly suggestive of LM, but it is also common for patients with Lymphomatous leptomeningitis to present with isolated syndromes such as symptoms of raised intracranial pressure, cauda equina syndrome, or cranial neuropathy.

New neurological signs and symptoms may represent progression of Lymphomatous leptomeningitis but must be distinguished from the manifestations of parenchymal disease, from side effects of chemotherapy or radiotherapy, and, rarely, from paraneoplastic syndromes.

• Diagnosis of LM
  • Cerebrospinal Fluid Examination

The most useful laboratory test for diagnosing Lymphomatous leptomeningitis is investigation of the CSF. Abnormalities include increased opening pressure (> 26 mm H₂O), increased leukocytes (> 4/mm³), elevated protein (> 50 mg/dl), or decreased glucose (< 60 mg/dl), parameters that, although suggestive of Lymphomatous leptomeningitis , are not diagnostic. The presence of malignant cells in the CSF is diagnostic of Lymphomatous leptomeningitis .

• Neuroimaging studies

Magnetic resonance imaging with Gd enhancement is the modality of choice to evaluate patients with suspected leptomeningeal metastasis.^[23,59,66] Because Lymphomatous leptomeningitis involves the entire neuraxis, whole-CNS imaging is required in patients considered for further treatment. Both contrast agent-enhanced and unenhanced T₁-weighted sequences, combined with fat suppression T₂-weighted sequences, constitute the standard MR imaging examination. Magnetic resonance imaging has been shown to have a higher sensitivity than cranial contrast medium-enhanced CT scanning in several series and is similar to CT myelography for the evaluation of the spine, but is significantly better tolerated.^[12,31,58]

Any irritation of the leptomeninges will result in their enhancement on MR imaging, which is seen as a fine signal intense layer that follows the gyri and superficial sulci. Subependymal involvement of the ventricles often results in enhancement of the ventricles. Some changes such as cranial nerve enhancement and intradural extramedullary enhancing nodules (most frequently seen in the cauda equina) can be considered diagnostic of Lymphomatous leptomeningitis in patients with cancer. Because lumbar puncture itself rarely causes a meningeal reaction leading to dural-arachnoidal enhancement, imaging should be conducted preferably prior to the procedure.^[50] The incidence of false-negative results on Gd-enhanced MR imaging remains 30% so that a normal study does not exclude the diagnosis of an LM. In cases involving a typical clinical presentation, however, abnormal results on Gd-enhanced MR imaging alone are adequate to establish the diagnosis of Lymphomatous leptomeningitis .

• Management of lymphomatous leptomeningitis

The treatment of Lymphomatous leptomeningitis is complicated by the lack of standard therapy, the difficulty of determining response to treatment because of the suboptimal sensitivity of the diagnostic procedures, the fact that most patients die of progressive parenchymal disease, and the fact that most studies of Lymphomatous leptomeningitis are small, nonrandomized, and retrospective. However, it is clear that treatment of Lymphomatous leptomeningitis can provide effective palliation and in some cases result in prolonged survival. Treatment in most cases requires the combination of surgery, radiotherapy, and chemotherapy.

• Surgical Management

Surgery is used in the treatment of Lymphomatous leptomeningitis for the placement of 1) intraventricular catheters and subgaleal reservoirs for administration of cytotoxic drugs and 2) ventriculoperitoneal shunts in patients with symptomatic hydrocephalus.

Drugs can be instilled into the subarachnoid space by lumbar puncture or via an intraventricular reservoir system. The latter is the preferred approach because it is simpler, more comfortable for the patient, and safer than repeated lumbar punctures. It also results in a more uniform distribution of the drug in the CSF space and produces the most consistent CSF levels. In up to 10% of lumbar punctures the drug is delivered to the epidural space, even if there is CSF return after placement of the needle, and the distribution of the drug has been shown to be better after reservoir-based drug delivery.

Lymphomatous meningitis often causes communicating hydrocephalus leading to symptoms of raised intracranial pressure. Relief of sites of CSF flow obstruction with involved-field radiation should be attempted to avoid the need for placing a CSF shunt. If hydrocephalus persists, a ventriculoperitoneal shunt should be placed to relieve the pressure because relief of pressure often results in clinical improvement. If possible, an in-line on/off valve and reservoir should be used to permit the administration of intra-CSF chemotherapy, although some patients cannot tolerate having the shunt turned off to allow the circulation of the drug.

Finally, in patients with a persistent blockage of ventricular CSF flow, a lumbar catheter and reservoir can be used in addition to a ventricular catheter, to allow treatment of the spine with intra-CSF chemotherapy (although as discussed earlier, cases involving post-irradiation persistent CSF flow blocks are probably best managed using supportive care alone).

• Radiotherapy Management

Radiotherapy is used in the treatment of Lymphomatous leptomeningitis for several reasons: 1) palliation of symptoms, such as a cauda equina syndrome, 2) to decrease space-occupying disease such as large-volume subarachnoid metastases, and 3) to correct CSF flow abnormalities demonstrated by radionuclide ventriculography. Patients may exhibit significant symptoms despite the absence of imaging evidence of space-occupying disease and still benefit from radiotherapy. For example, patients with low-back pain and leg weakness should be considered for radiotherapy of the cauda equina, and those with cranial neuropathies should be offered whole-brain or base skull radiotherapy.

Radiotherapy of large-volume disease is indicated because intra-CSF chemotherapy is limited by diffusion to 2 to 3 mm penetration into tumor nodules. In addition, involved-field irradiation can correct CSF flow abnormalities, and this has been shown to improve patient outcome. Whole-neuraxis radiotherapy is rarely indicated in the treatment of LM from solid tumors because it is associated with significant systemic toxicity (severe myelosuppression and mucositis, among other complications) and is not curative.

• Chemotherapy Management
  

Chemotherapy is the only modality that can treat the entire neuraxis and can be administered systemically or intrathecally.^{[11,36,60,63,70]} The most effective drug used in patients with newly diagnosed primary CNS lymphoma is high-dose methotrexate.^{[1,4-6,27-30,32,42,44,52-54,55,61,70]} When this drug is administered in gram quantities (high dose), cytotoxic CSF levels are achieved. Following a single dose of intravenous methotrexate at 8 g/m², CSF methotrexate levels greater than 1.0 μM are obtained and sustained for 24 to 48 hours.^[36]

The treatment of concomitant LM in the setting of recurrent parenchymal primary CNS lymphomas is challenging. Most systemic chemotherapy treats LM inadequately due to the insufficient CSF drug levels as seen in cases in which temozolomide, PCV (procarbazine, CCNU, and vincristine), rituximab, or topotecan are used. Exceptions are seen when using high-dose methotrexate, cytosine arabinoside, or thiotepa—chemotherapy agents with demonstrated activity against leptomeningeal metastases. Alternatively, intraventricular chemotherapy can be used, which, although limited to three agents (methotrexate, cytosine arabinoside, and thiotepa), has demonstrated activity and palliative benefit in patients with LM.^[16,26,71] However, intra-CSF chemotherapy is primarily effective against small tumor burden and disease involving the CSF and 1 to 2 mm of the leptomeningeal surface.^[16,26,71] Larger subarachnoid or parenchymal tumors are ineffectively treated by intra-CSF chemotherapy and, if present, require concomitant systemic chemotherapy or involved-field radiotherapy.^{[16,17,26,71]}

Complications of intra-CSF chemotherapy include those related to the ventricular reservoir and those related to the chemotherapy agent(s) administered.^[19,64] The most frequent complications of ventricular reservoir placement are malposition (range of reported rates 3-12%), obstruction, and infection (usually skin flora). Cerebrospinal fluid infection occurs in 2 to 13% of patients undergoing intra-CSF chemotherapy. Patients with CSF infection commonly present with headache, changes in neurological status, fever, and malfunction of the reservoir. Cerebrospinal fluid pleocytosis is commonly encountered. The most frequently isolated organism is Staphylococcus epidermidis. Treatment requires intravenous administration of antibiotics with or without oral and intraventricular agents. Some authors have advocated the routine removal of the ventricular reservoir, whereas others believe that removal of the device should be reserved for cases in which antibiotic therapy does not resolve the infection. Routine culturing of CSF samples is not recommended because of the high rate of contamination with skin flora in the absence of infection. Myelosuppression can occur after administration of intra-CSF chemotherapy agents, and it is recommended that folinic acid rescue (10 mg every 6 hours for 24 hours) be given orally after the administration of methotrexate to avoid this complication. Chemical aseptic meningitis occurs in nearly 50% of patients treated by intra-CSF administration, and its symptoms manifest as fever, headache, nausea, vomiting, meningismus, and photophobia. In most patients, this inflammatory reaction can be treated in the outpatient setting with oral antipyretic, antiemetic, and corticosteroid agents. Rarely, treatment-related neurotoxicity occurs and can result in a symptomatic subacute leukoencephalopathy or myelopathy. In patients with LM and prolonged survival, however, the combination of radio- and chemotherapy frequently results in a late-onset leukoencephalopathy evident on imaging studies and occasionally causing symptoms.^{[34,38,39,43,46,62]}

The rationale for giving intra-CSF chemotherapy is based on the presumption that most chemotherapeutic agents, when administered systemically, have poor CSF penetration and do not reach therapeutic levels. Exceptions to this would be systemic high-dose methotrexate, cytarabine, and thiotepa, all of which result in cytotoxic CSF levels. Their systemic administration is limited, however, by systemic toxicity and by the difficulty of integrating these regimens into other chemotherapeutic programs being used to manage a patient’s systemic disease. Additionally, in patients with recurrent primary CNS lymphomas and previous treatment with high-dose methotrexate, alternative systemic therapies are used without compelling evidence of CSF penetration or the ability to eradicate the CSF compartment. Some authors have argued that intra-CSF chemotherapy does not add to improved outcome in the treatment of LM, because systemic therapy can reach the subarachnoid deposits through tumor vascular supply.^[62]

Nonetheless, intrathecal chemotherapy remains the preferred treatment route for LM at this time. New intra-CSF drugs are being explored to try to improve efficacy, including mafosphamide, diaziquone, topotecan, interferon-α, etoposide, rituximab, and temozolomide. Gene therapy and immunotherapy using interleukin-2 and interferon-α, ¹³¹I-radiolabeled monoclonal antibodies are other modalities being explored in clinical trials.

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The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

September 28, 2009 — Primary CNS  lymphomas have a peculiar clinical presentation and a characteristic topographic brain localization.

Many patient with PCNSL are presented initially, with a history that simulates cerebro-vascular disorders. (TIAs, Rinds, Stroke, multi-infarct dementia). Also increased intracranial pressure is absent in many cases despite the fact that the tumours may be large enough and surrounded by massive edema in some of those cases.

The second point is the topographic localization of those lesions. Lymphomas starts either in the subependymal tissues and the periventricular grey matter and then fungates centrifugally outward into the periventricular white matter. or spread subependymally to ensheathe the ventricular system. The second site is the cortico-meningeal site and the disease spreads either alongside the meninges or invades the brain parenchyma in a centripetal way.

• Topographic subtypes of PCNL

These two points (the clinical presentation and topographic localization) are best explained by considering the cellular origin of lymphoma and the brain microvascular system.

PCNSL is derived from the microglial cells and was previously called microglioma. the microglial cells are more numerous in the cortical and the subcortical gray mater. (Thalamus and basal ganglia). The micro glial cells are not of neural origin. They are derived from the blood monocytes and migrate through the small perforating blood vessels to invade the neural tissue either from the pial or the subependymal arterial system. The microglial cells lies very close to the peri-adventitial spaces of the small penetrating blood vessels, They are phagocytic and function as macrophages. They represent a defense mechanism and are considered as a part of the reticuloendothelial system. To sum up the microglial cells and the penetrating blood vessels are very closely coupled together.

With regard to the brain microvascular system, 2 systems were described. The centrifugal subependymal system and the centripetal pial system. The centrifugal subependymal vascular system originates from the subependymal arteries which are terminal branches of the choroidal arteries, then extends centrifugally outward into the periventricular white mater. The centripetal pial vascular system originates from the pial arteries then extends centripetally inward towards the ventricular system. As an artery penetrates the brain it carries a sheath of pia with it resulting in a potential perivascular space called Virchow Robin space.

Table 1. Topographic subtypes of PCNL (Click on table to enlarge)

To put things together, it is possible to state that the malignant lymphoma cells (being derived from the micro glial cells) originate primarily in the periadentitial spaces of either the subependymal or the pial vascular systems, then the lymphoma cells creep alongside the penetrating arteries either centrifugally outward from the subependymal system, or centripetally inward from the pial system. This view point is consistent with the pathological findings of marked perivascular cuffing by lymphoma cells and tendency to spread along Virchow- Robin spaces. This also should support the theory that CNS lymphomas arise from the periadentitial microglial cells of the penetrating arterioles

Figure 1. MRI T1 postcontrast studies showing a case of CNS lymphoma, notice the cerebellar butterfly lesion, The periventricular lymphomatous sheath and the deposits in the corpus callusum, hypothalamus, and midbrain

The periventricular butterfly lesions that are demonstrated in some cases represent centrifugal tumour cells fungation alongside the periventricular subependymal arteriolar system. It should also be mentioned that around 50% of cases with periventricular lymphoma have bilateral lesions, while most the corticomeningeal lymphomas are strictly unilateral. This probably should point to the fact that the subependymal vascular systems of both hemisphere are more richly interconnected compared with the pial vascular system.

Figure 2. MRI T1 postcontrast showing the periventricular lymphomatous sheath (A) that showed periventricular centrifugal fungation of follow up study (B)

It should also be pointed out that the subependymal spread of lymphoma that is observed in some cases most probably represent either spread alongside the subependymal arteriolar system or CSF seedling.The subependymal disease is only demonstrated after contrast injection and commonly takes the shape of a hyperdense [CT scan] or hyperintense [MRI T1] bands that ensheathe the ventricular system

Figure 3. MRI T1 postcontrast showing the characteristic periventricular lymphomatous sheath

The second point is why more than half of the cases of PCNL were presented clinically with a history suggestive of cerebro-vascular disease. This point is best explained by putting forward the intimate relationship between the lymphoma cells and the penetrating arterioles. The lymphoma cells by infiltrating the wall of the penetrating arterioles can produce thrombo-occlusive changes that can give rise, clinically, to TIAs, Rinds or stroke.

The lower incidence of increased intracranial pressure in PCNL patients is difficult to explain. It occurs in around 50% of cases, most of them belong to the cortico-meningeal subtype. Absence of increased intracranial pressure should not divert the attention from the diagnosis of PCNL. However the mere fact that increased intracranial tension occurs mainly in the cortico-meningeal group could be explained by fact that the cortico-meningeal lymphomas tend to spread centripetally inward resulting in early encroachment upon the ventricular system, while the central lymphomas tend to spread centrifugally outward away from the ventricular system; resulting in relatively late compromise of the ventricular system and subsequently relatively late manifestations of increased intracranial pressure.

Figure 4. CT scan postcontrast showing a thalamic lymphoma with periventricular fungation [right]

From the radiological point of view, the existence of butterfly lesions and the subependymal disease are the most characteristic radiological criteria of PCNL.. In central lymphomas the thalamus is the most frequently involved site.

Figure 5. MRI T1 postcontrast showing the periventricular fungation forming the characteristic butterfly lesions around the 4TH ventricle

The cortico-meningeal lymphomas are the most challenging, both radiologically and during surgery. Primary meningeal involvement appears as mass lesions that are commonly misdiagnosed as meningiomas. In some cases the lesions appear by CT scan as a peripherally enhanced elongated band with mass effect. At surgery the meningeal lesions usually have the appearance of nodular or plaque-like dural thickening with frequent dural penetration and brain infiltration.

Figure 6. CT scan postcontrast showing two example of the corticomeningeal [peripheral] lymphoma.(A, band -like and B, rounded in shape)

In general meningeal lymphomatous lesions are densely enhanced, with mass effect and situated between the skull bone and the brain. The lesion could be rounded, band like or nodular. Penetration of the dura and infiltration of the brain parenchyma is frequently demonstrated . At surgery, the lesions appear as diffuse or loculated areas of dural thickening; with frequent dural penetration and with or without a demonstrable mass lesion.

Figure 7. CT postcontrast showing two examples of thalamic lymphomas, notice the dense enhancement and the coexistence of peripheral disease infiltrating the brain in a centripetal way (B)

PCNSL is almost invariably coupled with absence of any extraneural dissemination of the disease. In fact there is no need to subject any patient with the pathological diagnosis of PCNL to undue staging procedures such as staging laparotomy, splenic or hepatic biopsy since they are less likely to yield positive findings.

The male to female ratio of patients with PCNSL is (4,3). Central lymphomas are more common in males while cortico-meningeal lymphomas are more common in females. Patients with cortico-meningeal lymphomas are younger than those with central lesions,

PCNL commonly shows initial good response to steroid. However following histopathological confirmation of PCNL, whole brain irradiation must be done. The steroid responsiveness of the lesions could be regarded as an initial therapeutic diagnostic test for PCNL; since complete disappearance of the lesions by steroids is unlikely to occur in other brain tumours.

Figure 8.  CT scan postcontrast before steroid therapy (A,C) and after steroid therapy (B,D) notice complete resolution of the periventricular lymphomatous disease after steroid therapy

• Orbital lymphoma
  • Pathology

The majority of orbital lymphoproliferative disease is composed of non-Hodgkin’s orbital lymphoid neoplasms. Hodgkin’s disease is rarely encountered in the adnexal and orbital structures.

Benign reactive lymphoid hyperplasia or pseudolymphoma is characterized by benign appearing lymph follicles with reactive germinal centers surrounded by lymphocytes, histiocytes, and plasma cells. The division between the germinal centers and the adjacent mantle zone is well defined.

The cell type has some predictive importance in that the highest percentage of systemic disease is encountered in the highest grades of lymphoma (large cell and follicular cleaved cell lesions). Lesions of the eyelid carry the highest incidence of histopathologic malignancy.

• CT and MRI imaging analysis of lymphoid tumors

CT and MR imaging make significant contributions in the localization and distribution of lymphoproliferative infiltrates. A common feature of these lymphoid tumors is their tendency to mold or plaster themselves along the globe where such contact exists . Often, they are fairly well defined, round to oval in shape , lobulated, and often elongated along the extraconal space . In some cases, however, the margins are less well defined secondary to infiltrations that extend from the bulk of the mass into adjacent potential spaces defined by the fascial planes. These densities are linear or band-like and arise from the edges of the mass in an angular or perpendicular fashion.

Figure 9. MRI T1 images showing intraorbital lymphomatous deposits

If the lesion extends along the extraconal space from anterior to posterior, the medial and lateral rectus muscles are often obliterated and the contour of the tumor is straight or If tumor tissue is in the intraconal space, either primarily or as an extension of an extraconal mass, the tumor follows the contour of the posterior aspect of the globe with no indentation of the globe . Infiltrations within Tenon’s space cause diffuse thickening of the sclero-uveal coat. Occasionally, there may be small polypoid projections from Tenon’s space into the adjacent orbital fat, usually intraconally . Lymphoma may be limited to the perioptic space causing diffuse enlargement of the optic nerve sheath complex. Tumors may arise anteriorly from the conjunctiva reflected by a homogeneous mass conforming to the anterior globe margin . Lymphomatous infiltrations may also occur primarily within the lid manifesting as an anterior mass adjacent to the globe . Because of volume averaging, lymphomas arising from the conjunctiva or the lid cannot be separated on axial CT sections.

Less frequently, lymphomatous infiltrations may be scattered throughout the entire orbit, either as multiple, ill-defined infiltrations , or as a diffuse, homogeneous mass causing complete obliteration of the intraorbital spaces. Intraconal mass lesions may cause displacement of the optic nerve. This is optimally evaluated by coronal CT scans. Lacrimal gland involvement (unilateral or bilateral) is characterized by diffuse enlargement of the lacrimal gland, which is elongated in shape in the axial views and conforms to the adjacent contour of the globe . On the coronal CT scan, there is superoinferior elongation of the lacrimal gland molding itself along the lateral orbital wall and along the adjacent globe . If the tumor progresses in size, there may be elongation posteriorly along the lateral rectus muscle . Bilateral involvement of the orbits, including the lacrimal glands, is not an uncommon occurrence . Lymphoproliferative disease in the medial orbit may cause stretching of the lacrimal sac, as can be demonstrated by dacryocystography. There are, however, instances where the lymphoproliferative process arises within the lacrimal sac with diffuse distention of the lumen .

Because of the lymphocytic predominance of orbital lymphoma, there is usually no bone destruction and the lymphoma is confined to the orbital cavity or adnexal area. There are, however, some cases where the orbital lymphoma demonstrates an extraorbital component as manifested by extension through the inferior orbital fissure into the pterygopalatine fossa, infratemporal fossa, or extension via the superior orbital fissure

There are no CT or MR imaging features of lymphoma that allow differentiation between pseudolymphoma and malignant lymphoma. Following the introduction of iodinated contrast material, there is usually no significant enhancement. The preferred method for evaluation of lymphoproliferative disease is CT. This modality depicts, in great contrast, the muscles, orbital fat, optic nerve, globe, and bony structures.

MR imaging depicts the lymphocytic infiltrations within the orbit, but less conspicuously than CT. The TI-weighted images reveal infiltrations in the high intensity fat . Lymphoproliferative disease reveals low signal intensity on the Tl-weighted images. The signal intensities in the T2-weighted images vary according.to the cellular composition of the lymphoma. The pattern usually is from low-to-intermediate, which is a reflection of the increased cellularity of these tumors . Following the introduction of gadolinium, there is often moderate and, in some cases, marked enhancement of the tumor .

• Spinal lymphoma

Because spinal lymphomas are never primary, staging is Justified and must be done for every patient and because spinal lymphomas involve multiple asymptomatic levels, screening the whole vertebral column is mandatory since this will help to define the exact parts of the vertebral column to be irradiated.

In general spinal lymphomas and lymphomatous lyptomeningitis are diseases that respect the dura. Spinal lymphomas starts in the epidural spaces and usually extensively spread up and down to involve multiple levels, yet it remained confined to the epidural spaces,and infiltration or penetration of the dura never occur. On the other hand PCNSL showed a higher incidence of dural infiltration or penetration with frequent central intraparenchymatous involvement.

Table 2. Characteristic features of spinal lymphomas (Click on table to enlarge)

Accordingly spinal lymphomas, being confined to the extra dural spaces, are not primarily a CNS disease. The disease usually extends to the epidural spaces after more extensive extra-neural dissemination.

Figure 10. MRI T1 postcontrast [left image] and CT myelography [right image] showing two examples of spinal lymphomas ,notice the extradural, retromedullay location of the masses, absence of bony involvement and the dense enhancement (B)

PCNSL is of the histiocytic subtype which is consistent with the microglial origin of the PCNSL (microglia cells are derived from blood monocytes) while spinal lymphomas is of the lymphocytic subtype , and this is probably due to the fact that spinal lymphomas are secondary to a more systemic disease,lymphocytic lymphomas are the most common systemic lymphomas.

Although the histiocytic subtype is more aggressive than the lymphocytic subtype, the prognosis of PCNSL is much better compared with other CNS lymphomas. However, it should be noted that all patients with PCNSL are in stage one disease. (disease confined to a single extra lymphocytic site), while all patients with spinal lymphomas are in stage IV disease. It looks like that it is the stage of the disease, rather than the histopathological subtype, that ultimately determines the prognosis.

However, it should be noted that the initial good therapeutic response of PCNSL patients to radiation and/or chemotherapy does not necessarily mean cure of the disease since the incidence of late recurrence is very high.

References

1-Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 10.3a July 2009 [Click to have a look at the home page]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

September 27, 2009 — The spinal cord is formed by invagination of a tube of ectoderm, around which the mesoderm and scleroderm close to form the meninges and vertebral column. This process when interrupted before completion, results in malformations ranging from minor radiological abnormalities to those incompatible with life. The general term for these malformations is dysraphism. In order of severity, the grades of dysraphism are:-

OVERT SPINAL DYSRAPHISM

1. Simple Spina Bifida:

It is a bony defect, without herniation of meninges or nervous tissue. It occurs most commonly at the lumbosacral and first cervical levels. It is frequently asymptomatic incidental finding, but in appropriate clinical content, should alert to the possibility of an underlying malformation of the neuraxis.

2. Meningocele and meningomyelocele

This refers to protrusion of meninges and nervous tissue, it occurs most frequently near the foramen magnum, and in the lumbosacral region, the thoracolumbar junction is another common site. A posterior defect and widening of the spinal canal are common associated abnormalities.

Two specific types of meningoceles without a posterior defect may be encountered: -

1-Anterior sacral meningocele:

Presents no external stigmata, and is usually discovered accidentally. The sacrum is bypoplastic with a defect in its anterior wall which is easily overlooked on plain films. Contrast medium may passes into the lesion slowly and delayed filming is necessary.

2-Lateral meningocele:

It commonly occurs in the dorsal spine and protrudes through an intervertebral foramen. Lateral meningoceles are frequently encountered in patients with neurofibromatosis.

OCCULT SPINAL DYSRAPHISM

This term is applied to cases in which intraspinal anomalies are more striking than manifestation of impaired closure.

The most common anatomical abnormality of the spinal cord in occult spinal dysraphism is diastematomyelia which is a sagittal division or pseudoduplication of a segment of the spinal cord, diastematomyelia most commonly occurs in the lower dorsal and upper lumbar region. In many cases, the two cords are contained within a single dural tube, but in others, each of the two cords has its own dural sheath and the two are separated by a bony or fibrocartilagenous septum. Low cord termination, below L 2 posterior tethering of the cord and thick filum terminate are common associated anomalies .

The cord is commonly transfixed at the point of diastases by the osseous or fibrocatilagenous septum which is attached anteriorly to one or more vertebral bodies and posteriorly to the dura. It passes through the spinal cord and fixes it at low anatomical position. Arnold- Chiari malformation may be encountered as the normal ascend of the spinal cord will be arrested

Congenital anomalies of the vertebral column are frequently encountered in spinal dysraphism. Widening of the vertebral canal is a common finding and might extend for as many as six vertebral segments. The interpedicular distance is increased in a fusiform manner over these segments. Numerous developments abnormalities of the vertebral bodies and arches may be present in association with the widening of the vertebral canal . A congenital tumour, commonly dermoid or lipoma might be present and might fill the lower spinal canal The cord or the film terminate may pass directly into the tumour which might be intra-dural or extra dura . On rare occasion diastematomyelia may occur in the cervical region and may give a clinical picture resembling that of syringomyelia .

CLINICAL PICTURE

Lumbosacral spinal dysraphism has been held responsible for a variety of disturbances which are occasionally familiar. The principle symptoms are impairment of sphincter control; deformities of the feet; wasting of the muscles below the knees, with impairment of the ankle-jerks; dissociated sensory loss of a syringomyelic character over one or both legs and trophic disturbance of the feet such as delayed healing of wounds; chronic ulceration and gangrene.

RADIOLOGICAL EVLAUATION

Plain X-ray commonly demonstrates spina bifida, widening of interpedicular distance, scoliosis, and bony spurs.

Pantopaque myelography was used in the past to confirm occult cases of spinal dysraphism. The contrast material was so dense that many of the subtle features of these anomalies are not demonstrated until the time of surgical exploration. More recently metrizimide myelography, especially in combination with CT scanning has offered significantly better visualization of the often multiple features of spinal dysraphism.

The pathognomonic CT finding in diastematomyelia is two hemicords of abnormally small and often unequal size within the spinal canal. Because diastematomyelia is usually associated with a large subarachnoid space, the abnormal hemicords can be demonstrated by plain CT as well as after intrathecal enhancement. he rostrocaudal extent of diastematomyelia can be determined by inspecting contiguous CT slices or by generating sagittal and coronal reconstructions.

The more sensitive density discrimination afforded by CT has resulted in the identification of both extraspinal and intraspinal lipomas and in their clear demarcation from an associated tethered cord.

Figure 2. CT myelography showing diastematomyelia, notice the bony spur (A) and the fibrous band (B) that separate the two cords

Lipomas are the most frequent tumour in spinal dysraphism. Although, they are occasionally limited to the intradural compartment, these lesions are commonly present at birth as subcutaneous collection of fat in the midline over the lumbosacral area and extend through a spinal bifida defect to and usually through the dura. The intraspinal portion of the lipoma might exert a considerable mechanical pressure against nerve roots and spinal cord. Pre-operative demonstration of these Lipomas is best carried out by CT scan.

Although ossified spurs can be detected by plain radiographs, but they are unmistakable in CT cross sectional analysis. Fibrocartilagenous soft tissue spurs can only be detected by CT scan. CT scan is also the best diagnostic modality to visualize a thick film terminate tethering the cord from below. If this goes undetected, then even though the diastematomyelic spure is removed satisfactorily, the cord may remain tethered from below .

Figure 3. Myelography (A) and MRI T1 (C,D) showing spinal dysraphism, notice the dilated ,fusiform, subarachnoid spaces

References

1-Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 10.3a July 2009 [Click to have a look at the home page]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

September 27, 2009 — Pleomorphic xanthoastrocytoma (WHO grade II astrocytomas) are histologically characterized by pleomorphic and lipid laden cells. When high mitotic activity or areas of necrosis are present, the term anaplastic pleomorphic xanthoastrocytoma is used.

Pleomorphic xanthoastrocytoma is a recently described tumor that belongs to the well-circumscribed variety of astrocytic glial neoplasms (2). It is considered to have a neuroectodermal origin as the cytoplasm of tumor cells shows the presence of both glial fibrillary acid protein (GFAP) and S-100 protein (3).

The peak age of onset is 20 years and 90% of the reported cases are below 30 years of age. Cases in the pediatric age group have been described. However, only one case in the pediatric age group has so far been reported in the Indian literature (4). PXA is a slow growing tumor and seizures constitute the initial manifestation. As the tumor grows, focal deficits and signs of raised intra-cranial pressure may appear (5,6).

Figure 1. Pleomorphic xanthoastrocytoma appears as a hypodense cystic mass with distinct borders. An ecentric mural nodule attached to the meninges is seen. The nodule enhances uniformly and brilliantly on contrast. Mild edema may be present around the mass but calcifications are unusual. Usually, the cyst wall does not enhance.

The tumor has classical neuroimaging characteristics. The CT scan reveals a hypodense cystic mass with distinct borders. An ecentric mural nodule attached to the meninges is seen. The nodule enhances uniformly and brilliantly on contrast. Mild edema may be present around the mass but calcifications are unusual. Usually, the cyst wall does not enhance. MRI shows a well-delineated cystic mass that appears hypo-or-iso-intense on T1-weighted images. The peripheral nodule enhances on contrast administration (7,8). Histopathologically, the pleomorphic tumor cells have multi-lobed nuclei, multi-nucleated giant cells, spindle cells and foamy lipid laden xanthomatous astrocytes are also seen (8,9). The tumor despite its pleomorphic appearance, has a low-grade malignant potential (8,10) and complete excision is usually curative. It does not require post-operative radiation therapy or chemo-therapy (11,12). Uncommonly though, the tumor may recur or demonstrate aggressive clinical behavior with a mortality rate between 15% and 20%.

Key features

• Pleomorphic Xanthoastrocytoma is a rare slowly growing tumor with 
  seizures as an initial manifestation.

• It can be diagnosed on the basis of classical neuroimaging characteristics.

• Treatment with surgical excision, if carried out early, usually provides 
  gratifying results.

References 

1. Keeps JJ. Pleomorphic xanthoastrocytoma: The birth of a diagnosis and a concept. Brain Pathol 1993; 3: 269-274.
2. Kleiheus P, Burger PC, Scheichaver BW. The New WHO classification of brain tumors. Brain Pathol 1993; 3: 255-268.
3. Kobyashi S, Hirakawa E, Haba R. Squash cytology of pleomorphic xanthoastrocytoma mimicking glioblastoma. A case report. Acta Cytol 1999; 43: 632-658.
4. Pai MR, Kini H, Raghuveer CV. Pleomorphic xanthoastrocytoma. Indian J Pathol Microbiol 1996; 39: 329-331.
5. Bucciero A, De Caro M, De Stefano V, Te deschi E, Monticalli A, Siciliana A, et al. Pleomorphic xanthoastrocytoma: Clinical imaging and pathological features of four cases. Clin Neurol Neurosurg 1997; 99: 40-45.
6. Pahapill PA, Ramsay DA, De Maestro RF. Pleomorphic xanthoastrocytoma: Case report and analysis of the literature concerning the efficacy of resection and the significance of necrosis. Neurosurgery 1996; 38: 822-828.
7. Tien RD, Cardenas CA, Rajagopalan S. Pleomorphic xanthoastrocytoma of the brain: MR findings in six patients. Am J Roentgenol 1992; 159: 1287-1290.
8. Obsorn A. Diagnostic Neuroradiology. Missouri, Mosby Year Book Inc., 1994; pp 558-561.
9. Mc Keever PE, Blaivas M. The brain, spinal cord and meninges. In: Diagnostic Surgical Pathology, Ed Sternberg SS. 2nd edn. Phila-delphia, Lippincott Raven Publisher, 1996; pp 431-436.
10. Glannini C, Scheithauer BW, Burger PC, Brat DJ, Wallan PC, Lach B, et al. Pleomorphic xanthoastrocytoma: What do we really know about it? Cancer 1999; 85: 2033-2045.
11. Thomas C. Golden B. Pleomorphic xantho-astrocytoma; Report of two cases and brief review of the literature. Clin Neuropathol 1993; 12: 97-101.
12. Tom JC, Paulus W, Warmuth-Metz M, Schachenmayr W, Sorensen N, Roosen K. Pleomorphic astrocytoma: Report of six cases with special consideration of diagnostic and therapeutic pit falls. Surgical Neurology 1997; 47: 162-163.
13. 1-Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 10.3a July 2009 [Click to have a look at the home page]