August 2004: 64-year-old man with intermittent paresthesia of the abdomen and of the legs

A 64-year-old-man had a 2-year history beginning with a sense of abdominal "constriction." Additional slowly rising symptoms, such as tingling of the legs, mild gait ataxia and painful micturition, led to MRI investigation of the spinal cord. A fusiform enlargement of the cord extending from T5 to T8 was shown. The space occupying lesion infiltrated diffusely the spinal cord. A contrast medium enhancing exophytic tumor pellet was approached via a 2-level laminoplasty and resected. Biopsies were taken from different exophytic tumor areas whereas the intramedullary part was spared. The histologic examination confirmed the typical pattern of a pilocytic astrocytoma in all specimens. In our surgical experience with 226 intramedullary tumors and with 117 patients affected by intracranial pilocytic astrocytoma this case is unique because of its combination of tumor location, growth pattern and age of the patient.     

Recurrent primary leptomeningeal astrocytoma of the lumbosacral spinal cord resembling schwannoma. A case report

Primary leptomeningeal astrocytoma has been considered to be derived from ectopic glial cells in the leptomeninges. A case of recurrent primary leptomeningeal astrocytoma of the lumbosacral spinal cord is described. The original tumor was localized in the extramedullary space at the level of the 12th thoracic vertebra, and was solely composed of interlacing bundles of monomorphous spindle-shaped cells. The tumor was therefore diagnosed as schwannoma. The recurrent tumor removed one year after the first operation showed two distinct histologic patterns with increased nuclear atypia and mitosis. Namely, both schwannoma-like areas and astrocytomatous areas were observed. Silver impregnation clearly demonstrated an alveolar pattern in the schwannoma-like area. Immunohistochemically, the tumor cells revealed a positive reaction for glial fibrillary acidic protein. This case particularly emphasizes the usefulness of silver impregnation in differential diagnosis from schwannoma.     

RECURRENT PRIMARY LEPTOMENINGEAL ASTROCYTOMA OF THE LUMBOSACRAL SPINAL CORD RESEMBLING SCHWANNOMA. A Case Report

Primary leptomeningeal astrocytoma has been considered to be derived from ectopic glial cells in the leptomeninges. A case of recurrent primary leptomeningeal astrocytoma of the lumbosacral spinal cord is described. The original tumor was localized in the extramedullary space at the level of the 12th thoracic vertebra, and was solely composed of interlacing bundles of monomorphous spindle-shaped cells. The tumor was therefore diagnosed as schwannoma. The recurrent tumor removed one year after the first operation showed two distinct histologic patterns with increased nuclear atypia and mitosis. Namely, both schwannoma-like areas and astrocytomatous areas were observed. Silver impregnation clearly demonstrated an alveolar pattern in the schwannoma-like area. Immunohistochemically, the tumor cells revealed a positive reaction for glial fibrillary acidic protein. This case particularly emphasizes the usefulness of silver impregnation in differential diagnosis from schwannoma.     

Tanycytic ependymoma: two case reports and review of the literature

Two cases of tanycytic ependymoma are reported, one in a woman aged 33 years and one in a man aged 36 years. The woman presented with lesions at L2 and L3 in the spinal cord and clinical symptoms suggested spinal cord compression, such as movement and sensory dysfunction. The man had a lesion located in the lateral ventricle and presented with headache, vomiting, and impaired vision. Both of these patients developed gradual increases in the intensity of their symptoms over a few months prior to admission. A spinal cord MRI of the woman showed a well-defined, solid cystic mass measuring 1.0 × 6.5 cm at L2 and L3 of the spinal cord. The mass showed low signal intensity on T2-weighted images in the intervertebral disc with equal signal intensity T1-/T2-weighted images. The signal was uniform and enhanced scanning showed a light strengthening of signal. A brain MRI of the man showed a well-defined mass measuring 4 cm in diameter invading the right ventricle. The mass showed low signal intensity on right T1-weighted images and high signal intensity on T2-weighted images. Histopathologically, the tumors were rich with significant and uniform proliferation of long spindle cells, which were arranged in fasciculate and knitted patterns with bipolar and spindled processes focally forming perivascular pseudorosettes. The cell nuclei showed minor pleomorphism. A few tumor cells centered on the vessels resulted in a nuclear-free zone, which was characteristic of ependymoma. Immunohistochemically, the tumor cells were positive for GFAP, EMA, and CD99, but negative for S-100. A review of the cases reported in the literature shows that tanycytic ependymoma occurs more often in the spinal cord. As it can resemble pilocytic astrocytoma and schwannoma, tanycytic ependymoma should be differentially diagnosed to exclude some of the benign spindle cell tumors of the central nervous system.     

Theiler''s virus infection in mice: an unusual biphasic disease process leading to demyelination.

An unusual biphasic central nervous system disease developed in 3-week-old Swiss outbred mice after intracerebral inoculation of the DA strain of Theiler's murine encephalomyelitis virus. Nine to 20 days postinfection 86% of mice became paralyzed, and approximately one-half of these animals survived. During this period neuronal necrosis and microglial proliferation were seen in thalamus, brainstem, and spinal cord. There was an initial phase of virus growth in spinal cord followed by persistent infection at a lower concentration. Virus antigen was readily found in the cytoplasm of neurons by immunofluorescent staining early in the course of infection, whereas after 30 days there was a paucity of cells containing virus antigen which were present only in the spinal cord white matter. Between 1 and 5 months, an intense mononuclear inflammatory cell lesion evolved in the spinal cord leptomeninges and white matter, which coincided with a mild gait disturbance in some surviving mice, and patchy demyelination was found in areas of inflammation. The acute gray matter pathology would appear to be the result of direct virus lytic effect. Although the late white matter lesion culminating in demyelination probably represents a cytocidal infection similar to the situation that exists in certain picornavirus carrier culture systems, a virus-induced immunopathological process merits further study.     

Local and diffuse spread of juvenile cerebellar astrocytomas in subarachnoid space. Light and electron microscopic study.

Based on 5 cases of juvenile astrocytomas the unusual behaviour of this type of tumor is described. It is expressed by local and/or diffuse spread of the neoplasms in the subarachnoid space of the brain hemispheres, cerebellum and spinal cord. The light and electron microscopic examinations have revealed the morphological features of well differentiated tumors of astrocytic origin and of fibrillary type which in a great number of cases have a favourable prognosis. The cause of break through into the subarachnoid space, despite its morphology which indicates on a high degree of differentiation of the tumors, is not known. The relation of primary to secondary infiltration of the subarachnoid space or of the leptomeninges is discussed.     

Microscopic morphology and histology of the human meninges

The meninges comprise the dura mater and the leptomeninges (arachnoid and pia mater). Dura forms an outer endosteal layer related to the bones of the skull and spine and an inner layer closely applied to the arachnoid mater. Leptomeninges have multiple functions and anatomical relationships. The outer parietal layer of arachnoid is impermeable to CSF due to tight intercellular junctions; elsewhere leptomeningeal cells form demosomes and gap junctions. Trabeculae of leptomeninges compartmentalize the subarachnoid space and join the pia to arachnoid mater. In bacterial meningitis leptomeningeal cells secrete cytokines. Pia mater is reflected from the surface of the brain and spinal cord onto arteries and veins, thus separating the subarachnoid space from the brain and cord. A sheath of leptomeninges accompanies arteries into the brain and is related to the pathways for the drainage of interstitial fluid that play a role in inflammatory responses in the brain and appear to be blocked by amyloid-beta in Alzheimer's disease. Specialised leptomeningeal cells in the stroma of the choroid plexus form collagen whorls that become calcified with age. Leptomeningeal cells also form channels in the core and apical cap of arachnoid granulations for the drainage of CSF into venous sinuses. In the spine, leptomeninges form highly perforated intermediate sheets of arachnoid and delicate ligaments that compartmentalize the subarachnoid space; dentate ligaments anchor subpial collagen to the dura mater and stabilize the spinal cord. Despite the multiple anatomical arrangements and physiological functions, leptomeningeal cells retain many histological features that are similar from site to site.     

Immune regulatory mechanisms influence early pathology in spinal cord injury and in spontaneous autoimmune encephalomyelitis

Injuries to the central nervous system (CNS) trigger an inflammatory reaction with potentially devastating consequences. In this report we compared the characteristics of the inflammatory response on spinal cord injury (SCI) caused by a stab wound between the T7 and T9 vertebrae and spontaneous experimental autoimmune encephalomyelitis (EAE). SCI and EAE were compared in two types of myelin basic protein Ac1-11-specific T-cell receptor transgenic mice: T/R+ mice harbor regulatory T cells, and T/R- mice lack regulatory T cells. Our results show that 8 days after SCI, T/R- mice developed a strong T-cell infiltrate in the spinal cord, with remarkable down-modulation of CD4 expression that was accompanied by a local increase in Mac-3+ and F4/80+ reactivity and diffuse local and distal astrogliosis. In contrast, T/R+ mice exhibited a modest increase in CD4+ cells localized to the site of injury, without CD4 down-modulation; focal astrogliosis was restricted to the site of the lesion, although Mac-3+ and F4/80+ cells were also present. Similarly to T/R- mice that underwent SCI, T cells displaying down-modulated CD4 expression were found in the CNS of older T/R- mice afflicted by spontaneous EAE. Overall, our results suggest that common mechanisms regulate T-cell accumulation in CNS lesions of different causes, such as mechanic lesion or autoimmune-mediated damage.     

Abnormalities of the spinal meninges in anencephalic fetuses

The spinal cord and meninges were examined, at all levels, in seven anencephalic fetuses of between 19 and 24 weeks of gestation. Four of the seven anencephalics showed dense collections of cells resembling immature neural tissue throughout the spinal subarachnoid space. The leptomeninges were excessively vascular and contained many active macrophages and small round cells in all the anencephalics and the cord was more slender than normal. Control fetuses did not show these features, although inactive macrophages were seen occasionally. It is concluded that the abnormal collections are made up of heterotopic neural tissue which may have been dislodged downwards from the skull during earlier development and that the spinal leptomeninges show an inflammatory response. The significance of both the heterotopia and the phagocytic activity in these anencephalic fetuses is discussed. In particular, the findings are compared with those in patients with the “respirator brain” syndrome, in whom displacement of brain tissue is associated with raised intracranial pressure.     

Acute transverse myelitis caused by Coxsackie virus B4 infection: a case report.

Acute transverse myelitis is a rare clinical manifestation of Coxsackie virus infection which cause acute and progressive debilitating illness associated with loss of spinal cord function in the affected patients. A 62 year-old female developed symptoms of rapidly progressive paraplegia with sensory loss. On spinal MRI, T2 sagittal image showed increased signal intensity with cord swelling at T11-L2 level and 8 folds or greater rise of Coxsackie virus B4 neutralizing antibody titers was observed in the CSF. There is only one previous report of acute transverse myelitis caused by Coxsackie virus B4 infection to our knowledge. The presence of specific viral antibody titers change in the CSF and a corresponding spinal cord lesion are sufficient to suggest a causal relationship between the virus and the illness. This article is a case report of an unusual acute transverse myelitis caused by Coxsackie virus B4 infection.     

Intradural extramedullary tuberculoma of the spinal cord: a case report

Intradural extramedullary (IDEM) tuberculoma of the spinal cord is uncommon entity and moreover, few reports have been documented on concurrent IDEM and intracranial tuberculomas. Authors report a case of IDEM spinal tuberculoma having intracranial lesion simultaneously. A 49-year-old woman suffered from paraparesis and urinary incontinence while being given medical treatment for tuberculous meningitis. Magnetic resonance imaging (MRI) revealed an IDEM mass lesion between the T1 and T2 spinal levels, and multiple intracranial tuberculous granulomas. Surgical resection of the IDEM tuberculoma followed by anti-tuberculous medication resulted in good outcome.     

兔颈脊髓半侧挫伤模型的建立及其MRI和组织学表现的研究

目的 建立兔颈脊髓半侧挫伤模型,观察不同程度损伤24小时后其MRI及组织学表现。方法 22只成年雄性新西兰兔,随机分为中度损伤组（n=9）、重度损伤组（n=9）和假手术组（n=4）。直径为3.0 mm的打击头由电磁伺服材料试验机驱动,对准C5脊髓左侧行高速挫伤（500 mm/s）。根据打击头的位移距离分为位移2.0 mm组（中度损伤组）和位移2.8 mm组(重度损伤组)。假手术组仅暴露C5脊髓,不进行挫伤。损伤后24小时每组随机取两例行MRI影像学检查,所有动物均取材进行组织学观察,测量横断面脊髓出血面积。 结果 中度损伤组打击力和位移分别为(2.47±0.39) N和(1.99±0.02) mm,重度损伤组打击力和位移分别为(5.16±0.82) N和(2.76±0.02) mm,中度损伤组的打击力明显小于重度损伤组（P<0.05）。MRI结果显示,中度及重度损伤组均可见C5左侧脊髓信号改变。HE染色显示脊髓左侧有明显的出血及脊髓组织结构破坏,中度损伤组损伤中心横截面出血面积（0.012±0.006）mm2明显小于重度损伤组（0.039±0.006）mm2（P<0.05）。 结论 本文建立的兔颈脊髓半侧挫伤模型能够控制挫伤位移,实现对脊髓的高速打击。不同程度的颈脊髓半侧挫伤在打击力、MRI影像学及组织学上均有不同。     

Tissue calcium levels following spinal cord transection in rats

Adult rats were subjected to midthoracic spinal cord transections. Three segments of spinal cord, each approximately 5 mm in length, were removed from each animal at intervals from 5 min to 48 h postlesion; one from the lesion site and one each immediately rostral and caudal to the transection. Total tissue calcium concentrations ([Ca]t) for each spinal cord segment were determined using atomic absorption spectrophotometry and compared to control segments from untransected animals. [Ca]t levels in the segment at the lesion site was significantly elevated above control values at 30 min post-lesion, but decreased to control levels by 1 h. All other segments remained at control levels for the duration of the postlesion period. The rapid rise and fall of [Ca]t at the lesion site differs from spinal cord contusion studies in which [Ca]t remains at elevated levels for extended periods. It is postulated that the "open" transection injury permits the rapid clearance of calcium from the injury site.     

46-year-old man with a spinal cord mass

Medulloblastoma accounts for only 1% of all adult CNS tumors. Likewise, recurrence of adult medulloblastoma greater than 20 years after initial diagnosis is extremely rare.We describe a case of adult medulloblastoma with late relapse of disease. The patient was 24 years old when first diagnosed and was treated with total tumor resection and craniospinal radiation. At the age of 45, an enhancing 1.3 cm intradural extramedullary spinal cord lesion at T5 was discovered on MRI. This was presumed to be recurrent medulloblastoma in the form of drop metastasis and the patient was treated with spinal radiation. Several months following treatment, at the age of 46, a follow-up MRI demonstrated an enhancing 1.4 cm intradural extramedullary spinal cord lesion at T7. The lesion was resected and histopathologic examination was most consistent with medulloblastoma, late drop metastasis. Although rare, adult medulloblastoma recurring 20 years after initial diagnosis should always be considered in the main differential diagnosis when working up CNS lesions at or outside the primary tumor site.     

Feline non-suppurative meningoencephalomyelitis. A clinical and pathological study.

A spontaneous neurological disease in cats characterized by behavioural and motor disturbances was investigated by clinical, morphological and immunological methods. Neuropathological examination showed a marked inflammatory reaction in the cerebral leptomeninges and the grey matter of the brain. In the white matter, the reaction was moderate. The changes consisted of perivascular cuffing by mononuclear cells and neuronal damage. The brain stem (thalamus, mesencephalon, caudal colliculus) was most severely affected. The spinal cord and its leptomeninges were involved to a lesser degree. The histopathological picture as well as the laboratory findings suggests a viral cause of the disease. The morphology of the disease and serological as well as immunohistochemical results indicate that this disorder is different from previously known feline viral encephalitides.     

Therapeutic approaches for spinal cord injury

This study reviews the literature concerning possible therapeutic approaches for spinal cord injury. Spinal cord injury is a disabling and irreversible condition that has high economic and social costs. There are both primary and secondary mechanisms of damage to the spinal cord. The primary lesion is the mechanical injury itself. The secondary lesion results from one or more biochemical and cellular processes that are triggered by the primary lesion. The frustration of health professionals in treating a severe spinal cord injury was described in 1700 BC in an Egyptian surgical papyrus that was translated by Edwin Smith; the papyrus reported spinal fractures as a “disease that should not be treated.” Over the last two decades, several studies have been performed to obtain more effective treatments for spinal cord injury. Most of these studies approach a patient with acute spinal cord injury in one of four manners: corrective surgery or a physical, biological or pharmacological treatment method. Science is unraveling the mechanisms of cell protection and neuroregeneration, but clinically, we only provide supportive care for patients with spinal cord injuries. By combining these treatments, researchers attempt to enhance the functional recovery of patients with spinal cord injuries. Advances in the last decade have allowed us to encourage the development of experimental studies in the field of spinal cord regeneration. The combination of several therapeutic strategies should, at minimum, allow for partial functional recoveries for these patients, which could improve their quality of life.     

Dynorphin A content in the rat brain and spinal cord after a localized trauma to the spinal cord and its modification with p-chlorophenylalanine. An experimental study using radioimmunoassay technique.

The distribution of dynorphin A in the spinal cord and brain of normal rats and of rats subjected to a focal injury of the spinal cord was examined in a rat model using a radioimmunoassay (RIA) technique. The validity of RIA was checked by high performance liquid chromatography (HPLC). Furthermore, the possibility that the peptide is somehow functionally related with endogenous 5-hydroxytryptamine (5-HT, serotonin), was also evaluated using a pharmacological approach. In normal animals, the peptide content was very similar in the spinal cord segments (T9, T10-11, and T12) examined whereas, the dynorphin content of the whole brain was about two-fold higher compared with that in the spinal cord. A focal injury to the spinal cord in the right dorsal horn (about 1.5 mm deep, 2.5 mm long and 1.5 mm to the right of the midline) of the lower thoracic cord (T10-11) in urethane anaesthetised animals significantly altered the peptide content in the whole brain as well as in the spinal cord. Thus, a decrease in the peptide level in whole brain, T10-11 and in the T12 segments of the spinal cord was observed 1 and 2 h after trauma. At 5 h, the peptide had accumulated markedly in the T9 segment (about a two-fold increase) as compared with the controls. At this time, the peptide content had been restored in the T10-11 and T12 segments. On the other hand, the whole brain dynorphin level continued to remain low (by 55%) as compared to the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Venous congestive myelopathy: a mimic of neoplasia.

Venous congestive myelopathy is a progressive disorder frequently associated with arteriovenous fistulas, usually dural. By causing diffuse spinal cord enlargement and enhancement on imaging, it may simulate a neoplasm and prompt a biopsy. We evaluated the biopsy findings in seven such patients (M=5, F=2, mean age 59+/-11 years) who presented variably with progressive lower extremity weakness (86%), bowel and bladder dysfunction (86%), sensory changes (86%) or pain (29%). Preoperative magnetic resonance imaging showed spinal cord enlargement with T2-hyperintensity (86%) and contrast enhancement (57%) at the cervical (14%), thoracolumbar (57%), and/or conus medullaris (57%) level. Prebiopsy spinal angiogram, performed in two patients, was negative. Spinal cord biopsy showed architecturally distorted parenchyma with gliosis and thick hyalinized vessels (100%), variable myelin loss (71%), mild glial atypia (57%), hemosiderin deposition (71%), Rosenthal fibers (43%), vascular thrombosis (29%), and necrosis (29%), features highly suggestive of venous congestive myelopathy. Postbiopsy spinal angiograms were performed in five patients. A dural arteriovenous fistula was identified by selective angiography in three patients, including the two with a negative preoperative angiogram. Additional postbiopsy angiographic studies in two patients were negative, and two patients were followed up without angiography. Mean follow-up after biopsy was 13.6 months. Histologic changes characteristic of venous congestive myelopathy may be seen in spinal cord biopsies with or without an associated fistula. Recognition of this entity by surgical pathologists is important, leading to the correct identification of a non-neoplastic lesion as well as of a surgically treatable disease.     

Multicentric astrocytomas of the optic chiasm, brain stem and spinal cord

Autopsy was performed on a 52-year-old man with a 20-year history of neurological symptoms. At autopsy, both a brain stem tumor and a spinal cord tumor were found. These showed the features of pilocytic astrocytoma histologically. A pilocytic astrocytoma was also found in the optic chiasm upon microscopical examination. These three tumors were thought to be multicentric astrocytomas, because there was no continuity among them and no evidence of dissemination or metastasis by any pathway. From a review of the literature, the present case is considered to be an exceedingly rare one because of the multicentric sites of occurrence.     

B cell rich meningeal inflammation associates with increased spinal cord pathology in multiple sclerosis

Increased inflammation in the cerebral meninges is associated with extensive subpial cortical grey matter pathology in the forebrain and a more severe disease course in a substantial proportion of secondary progressive multiple sclerosis (SPMS) cases. It is not known whether this relationship extends to spinal cord pathology. We assessed the contribution of meningeal and parenchymal immune infiltrates to spinal cord pathology in SPMS cases characterized in the presence (F+) or absence (F−) of lymphoid‐like structures in the forebrain meninges. Transverse cryosections of cervical, thoracic and lumbar cord of 22 SPMS and five control cases were analyzed for CD20+ B cells, CD4+ and CD8+ T cells, microglia/macrophages (IBA‐1+), demyelination (myelin oligodendrocyte glycoprotein+) and axon density (neurofilament‐H+). Lymphoid‐like structures containing follicular dendritic cell networks and dividing B cells were seen in the spinal meninges of 3 out of 11 F+ SPMS cases. CD4+ and CD20+ cell counts were increased in F+ SPMS compared to F− SPMS and controls, whilst axon loss was greatest in motor and sensory tracts of the F+ SPMS cases (P < 0.01). The density of CD20+ B cells of the spinal leptomeninges correlated with CD4+ T cells and total B and T cells of the meninges; with the density of white matter perivascular CD20+ and CD4+ lymphocytes (P < 0.05); with white matter lesion area (P < 0.05); and the extent of axon loss (P < 0.05) in F+ SPMS cases only. We show that the presence of lymphoid‐like structures in the forebrain is associated with a profound spinal cord pathology and local B cell rich meningeal inflammation associates with the extent of cord pathology. Our work supports a principal role for B cells in sustaining inflammation and tissue injury throughout the CNS in the progressive disease stage.