Multiple myeloma invasion of the central nervous system

BACKGROUND: Although neurologic manifestations often complicate the course of patients with multiple myeloma (MM), direct central nervous system invasion is rare. OBJECTIVE: To describe the neurologic symptoms and signs, imaging, cerebrospinal fluid findings, and the clinical course of patients with central nervous system myeloma invasion, all of whom had leptomeningeal myelomatosis.Design and PARTICIPANTS: Review of 23 patients with MM and leptomeningeal myelomatosis proven by malignant plasma cells in their cerebrospinal fluid. SETTING: Tertiary-care university medical center. RESULTS: Twenty-one patients had advanced-stage MM. Leptomeningeal myelomatosis was diagnosed up to 29 months (median, 13 months) after diagnosis of MM. Symptoms precipitating neurologic evaluation included manifestations of diffuse cerebral dysfunction, cranial nerve palsies, and spinal radiculopathies. Cerebrospinal fluid was abnormal in all patients, usually exhibiting pleocytosis and elevated protein content, plus positive cytologic findings. Specific magnetic resonance imaging findings suggestive of central nervous system invasion were found in 70% of the patients. These included leptomeningeal contrast enhancement and evidence of meningeal-based lesions sometimes masquerading as intraparenchymal lesions. Despite aggressive systemic and local treatment, the outcome was poor, reflecting the aggressiveness of the underlying MM. CONCLUSION: Leptomeningeal myelomatosis, although rare, should be considered in patients with MM and symptoms suggestive of widespread nervous system involvement.     

Primary diffuse leptomeningeal gliomatosis

A review of the literature on primary diffuse meningeal gliomatosis (DMG) yielded three cases and we report a fourth. DMG is a syndrome characterized by extensive basal and spinal chronic meningitis with mental confusion, headaches, diplopia, papilledema and cranial nerve palsies. The cerebrospinal fluid (CSF) has a markedly elevated protein content, moderate mononuclear pleocytosis and a normal or low glucose. This picture invariably leads to the diagnosis and treatment of tuberculous or fungal meningitis despite persistently negative cerebrospinal fluid (CSF) cultures. Reaction of exfoliated CSF cells with glial fibrillary acidic protein (GFAP) immunoperoxidase labelled antibody is suggested as a diagnostic tool. A basal meningeal biopsy appears to be the only alternative diagnostic approach.     

Meningitis revealing pancreatic carcinoma

Meningeal carcinomatosis is an uncommon metastatic complication of systemic solid tumors. The diagnosis is based on the presence of malignant cells in the cerebrospinal fluid. The sensibility of cerebrospinal fluid testing in detecting the neoplastic cells improves when repeating lumbar punctures. Magnetic resonance imaging could help in establishing the diagnosis. The prognosis of carcinomatous meningitis is poor, especially when the primitive neoplasm is initially unknown. We report the case of a patient presenting with sudden bilateral visual decrease, headaches, and vomiting. Signs of meningeal irritation were found. Cerebrospinal fluid analysis showed malignant cells consistent with an adenocarcinoma. Abdominal echography and MRI concluded in a nodule of the cephalic portion of the pancreas. Carcinomatous meningitis rarely complicates pancreatic cancers.     

Myeloma cells in the cerebrospinal fluid in plasma cell neoplasia

Myeloma cells were detected in the cerebrospinal fluid of two patients with plasma cell neoplasia during the myelographic studies of 38 patients whose myeloma was associated with extensive neurological complications. The myeloma cells were looked for in Wright stained centrifuged deposit of 2–5 ml samples of the cerebrospinal fluid obtained during myelography. The possibility that occult traumatic lumbar puncture had allowed entry of circulating myeloma cells from the peripheral blood into the subarachnoid space was excluded by the absence of myeloma cells in smears of peripheral blood and its buffy coat. Up to the end stages of the disease the meningeal myeloma lesions remained microscopical and no signs of raised intracranial tension were manifested by either patient.     

Paracoccidioidomycosis meningitis: case report

The involvement of the central nervous system in paracoccidioidomycosis and its meningeal form of clinical presentation have rarely been described. This is a case report of a 23 years old man who developed paracoccidioidomycosis meningitis achieved by fungus' presence in direct research and culture of cerebrospinal fluid. The meningeal form of paracoccidioidomycosis, its laboratorial and imaging diagnostic are discussed, and the importance of the routine investigation of the fungus is emphasized.     

Triptans reduce the inflammatory response in bacterial meningitis.

Severe headache and meningism provide clear evidence for the activation of trigeminal neurotransmission in meningitis. The authors assessed the antiinflammatory potential of 5HT1B/D/F receptor agonists (triptans), which inhibit the release of proinflammatory neuropeptides from perivascular nerve fibers. In a 6-hour rat model of pneumococcal meningitis, zolmitriptan and naratriptan reduced the influx of leukocytes into the cerebrospinal fluid, and attenuated the increase of regional cerebral blood flow. Elevated intracranial pressure as well as the brain water content at 6 hours was reduced by triptans. These effects were partially reversed by a specific 5HT1D as well as by a specific 5HT1B receptor antagonist. Meningitis caused a depletion of calcitonin gene-related peptide (CGRP) and substance P from meningeal nerve fibers, which was prevented by zolmitriptan and naratriptan. In line with these findings, patients with bacterial meningitis had significantly elevated CGRP levels in the cerebrospinal fluid. In a mouse model of pneumococcal meningitis, survival and clinical score at 24 hours were significantly improved by triptan treatment. The findings suggest that, besides mediating meningeal nociception, meningeal nerve fibers contribute to the inflammatory cascade in the early phase of bacterial meningitis. Adjunctive treatment with triptans may open a new therapeutic approach in the acute phase of bacterial meningitis.     

Glioblastoma multiforme and the meningeal syndrome.

Brain tumors rarely may produce acute steile meningitis (the meningeal syndrome) resulting from the spillage of blood, lipid products of tumor necrosis, or malignant cells into the cerebrospinal fluid (CSF). The frequency of the associated meningeal syndrome is a function of tumor type and of the tproximity of tumor necrosis to the ventricles. The meningeal syndromes of lipid-induced chemical inflammation are seen most commonly with epidermoids, craniopharyngiomas, and infarcted pituitary adenomas. I report a patient with the rare association of the meningeal syndrome with glioblastoma multiforme. The lipid irritants of glioblastomas and craniopharyngiomas are similar chemically and can be detected in the CSF. The anti-inflammatory and immunosuppressant properties of steroids provide a rational basis for their efficacy in treatment of the syndrome.     

Leptomeningeal metastases

Leptomeningeal metastasis, also known as neoplastic meningitis, carcinomatous meningitis, and meningeal carcinomatosis, occurs when cancer cells gain access to cerebrospinal fluid pathways, travel to multiple sites within the central nervous system, settle, and grow. This disease has become an increasingly important late complication in oncology as patients survive longer, develop more brain metastases, and newer chemotherapies fail to penetrate the blood-brain barrier. The hallmark of clinical presentation is a cancer patient who complains of focal neurologic dysfunction and is found to have multifocal signs on neurologic examination. The clinical course is relentlessly progressive; treatment is limited and cures are the subject of case reports. This article reviews the clinical course of leptomeningeal metastasis and addresses recent developments in its pathophysiology, diagnosis, and treatment.     

Quasi-normal cerebrospinal fluid in patients with acquired immunodeficiency syndrome and cryptococcal meningitis

We report eight patients with cryptococcal meningitis and a cerebrospinal fluid characterized by few or no white blood cells and chemistries that may be near normal. In four of these patients, only testing for cryptococcal antigen allowed the initial diagnosis. Seven of the patients had a certain diagnosis of AIDS. Six have died. Autopsies performed in two cases indicated a poor meningeal inflammatory response. Contrary to the findings in most immunodeficient patients, in AIDS cryptococcal meningitis may present with few cellular or biochemical abnormalities in the cerebrospinal fluid. In AIDS patients presenting with headache and fever or change in mental status, examination of the cerebrospinal fluid should not be limited to routine studies.     

Diagnosis and treatment of carcinoid meningitis: a challenge to the neurologist and oncologist

BACKGROUND: Two clinical types of leptomeningeal metastases from solid tumors are observed: local and disseminated. The former (meningeal carcinomatosis) consists in nodular infiltration of leptomeninges, while the latter (carcinomatous meningitis)--in tumor cells free floating in the cerebrospinal fluid and adhering as a monolayer to the surface of neural structures. Despite the same etiology, the two types of metastasis differ in their clinical manifestation and prognosis. Meningeal carcinomatosis is more frequently diagnosed nowadays due to advances in neuroimaging techniques and the long survival of breast cancer patients. Patients with local, nodular infiltration of leptomeninges may survive many years without symptoms of the disease. On the other hand, carcinomatous meningitis, with its usually violent course and short survival, has become a major problem for oncologists and neurologists because of limited efficacy and considerable toxicity of the treatment. AIMS: The purpose of this article is to review the current knowledge about carcinomatous meningitis in breast cancer patients, taking into account pathophysiology, clinical symptoms, diagnosis, treatment and prognosis. The second aim was to present the authors' experience with the treatment of breast cancer patients suffering from carcinomatous meningitis. MATERIAL AND METHODS: 37 patients with breast cancer and carcinomatous meningitis were treated in the Oncology Center, Warsaw, in the years 2000-2002. Their mean age was 51. The diagnosis was based on results of neurological examination, MRI scan, and the presence of neoplastic cells in the cerebrospinal fluid. In a majority of cases combined treatment was applied, including intrathecal administration of cytostatics, intravenous systemic chemotherapy and radiotherapy. RESULTS: The observation period ranged from 2 to 33 months. A response to the treatment was achieved in 76% of the patients. Their median overall survival was 19 weeks, mean 18 weeks. Seven patients (19%) survived for over 6 months. CONCLUSIONS: The ever-growing incidence of carcinomatous meningitis in the course of breast cancer has become a serious clinical problem for neurologists and oncologists. Treatment results are disappointing, although the combined modality treatment appears to be the best option. New pharmacological approaches to the treatment of meningeal malignancy are required to improve the outcome of patients with carcinomatous meningitis.     

Aseptic meningitis after transsphenoidal management of Rathke’s cleft cyst: case report and review of the literature

Aseptic meningitis after transsphenoidal surgery (TSS) for treatment of Rathke’s cleft cyst (RCC) is a rare complication caused by the leakage of the cyst contents within the subarachnoid space. We present a case of aseptic meningitis occurring after TSS for a RCC. During surgery, the cyst wall was subtotally removed, and intraoperative cerebrospinal fluid (CSF) leakage was observed. The patient developed meningeal signs and symptoms on the first postoperative day. CSF examinations were highly suggestive of aseptic meningitis. Histological examination confirmed a granulomatous inflammatory reaction of the RCC wall. Preexisting inflammation, subtotal cyst wall resection, intraoperative erosion of the diaphragma sellae and placement of a lumbar drain may be risk factors for the development of aseptic meningitis.     

Clinical and laboratory characteristics of cerebral infarction in tuberculous meningitis: a comparative study.

Cerebral infarction as a complication of tubercular (TB) meningitis is not uncommon, but an adequate comparison of patients with and without stroke has not been carried out. This study was performed to evaluate the clinical characteristics of cerebral infarction secondary to TB meningitis, and to investigate predictive factors for cerebral infarction in patients with TB meningitis. Patients with TB meningitis were recruited over a period of 56 months. They were divided into two groups, those with and those without stroke. Demographic features and clinical, laboratory, and neuroradiological findings were compared between the two groups. We classified strokes into subtypes using neuroimaging findings. Of the 38 patients who were diagnosed with TB meningitis, eight also experienced cerebral infarction. The percentage of cerebrospinal fluid leukocytes that were neutrophils was significantly higher in patients with stroke (68%) than in patients without stroke (31%; p=0.0001). Upon initial CT imaging, meningeal enhancement was found in 11 patients, and of these patients, six experienced stroke. There were no significant differences between the groups with respect to other clinical and laboratory features, including demographic features, time between meningitis onset and treatment initiation, peripheral white blood cell count, and cerebrospinal fluid findings. Five of the eight patients who developed stroke had lacunar infarcts. One of the three patients with territorial nonlacunar infarction died due to herniation. When treating patients with TB meningitis, the possibility of cerebral infarction should be considered when patients develop focal neurological signs, meningeal enhancement on a CT scan, and sustained polymorphic cerebrospinal fluid pleocytosis.     

Irreversible papillitis and ophthalmoparesis as a presenting manifestation of neurobrucellosis

A 35-year-old man presented with a meningeal syndrome and acute onset of visual blurring. Clinical investigations revealed bacterial meningitis with bilateral papillitis and ophthalmoparesis. Serum and cerebrospinal fluid serology confirmed the diagnosis of chronic active neurobrucellosis. Following therapy there was no improvement and he developed optic atrophy. Extensive literature review revealed, one case of bilateral irreversible papillitis resulting from neurobrucellosis. However no cases of neurobrucellosis have been reported with meningitis, irreversible papillitis and ophthalmoparesis. This case demonstrates that in endemic areas, acute meningitis is a potential manifestation of neurobrucellosis and that bilateral irreversible papillitis with ophthalmoparesis can be a potential serious complication.     

Intrathecal cytostatic chemotherapy of meningitis carcinomatosa. Clinical manifestation and cerebrospinal fluid cytology in a case of metastatic carcinoma of the breast.

Effects of intrathecal cytostatic chemotherapy on the clinical symptoms and cerebrospinal fluid (CSF) findings are being demonstrated in a case of metastatic carcinoma of the breast with sighns of meningeal irritation and cranial nerve involvement. Clinical symptoms disappeared after repeated intrathecal applications of methotrexate. CSF cell counts were reverted to normal but tumor cells were found to be persistant in CSF over a period of 19 months. Risks of combined intrathecal and systemic cytostatic therapy and possible effects of parenteral citrovorum factor applications are being discussed. The importance of continued intrathecal chemotherapy and of regular and thorough examination of CSF cells in meningitis carcinomatosa is emphasized. Cytological methods included investigations on viable CSF cells.     

新型隐球菌性脑膜炎与结核性脑膜炎的临床特点比较

目的对比和分析综合性医院新型隐球菌性脑膜炎(CNM)与结核性脑膜炎(TBM)的临床特点。方法分析62例CNM及219例TBM患者的一般资料、临床症状、脑脊液细胞学(CSFC)、头颅影像学的特点。结果两种脑膜炎均呈亚急性或慢性起病相对于TBM,CNM延误诊断时间更长、临床症状中癫痫出现比率(24.2%)、头颅影像学中脑膜强化出现比率(17.7%)较高,腰穿脑脊液(CSF)压力(268.7±67.6mmH_2O)、CSF单核细胞占比(21.0±17.5%)高,CSF白细胞计数(84.8±88.1×10~6/L)、CSF糖(1.9±1.4mmol·L~(-1))较低。结论两种脑膜炎临床表现不典型,两者之间不易鉴别,容易误诊漏诊。临床上需综合判断,CSF瑞氏吉姆萨染色和改良抗酸染色有助于两者病原学确诊。     

Neurosyphilis

Syphilis and its consequent central nervous system sequelae remain clinical problems, especially when presenting in the unfamiliar acute meningeal forms of syphilitic meningitis and meningovascular syphilis. The diagnosis of neurosyphilis of all types depends on evaluation of spinal fluid reactivity as evidenced by pleocytosis and increased protein content with reactive serology. The cerebrospinal fluid is always abnormal in active disease, and only active disease responds to treatment. Penicillin remains the drug of choice for all forms of neurosyphilis, but disease progression has been frequently reported following the use of penicillin G benzathine. Documentation of cerebrospinal fluid resolution over the months following penicillin therapy is required to confirm curative treatment.     

Melanocytic meningitis and large congenital melanocytic naevus: neurocutaneous melanosis

Neurological symptoms in a patient with large congenital melanocytic naevus are highly suggestive of cerebromeningeal melanoma metastasis. The presence of melanocytic cells in cerebrospinal fluid confirms this diagnosis If their malignant nature is shared with cutaneous naevocytic cells. Conversely, neurocutaneous melanosis is diagnosed when benign melanocytosis meningitis is found in patients with multiple and/or large congenital melanocytic naevus, whether cutaneous naevus cells are benign or not, or when cerebrospinal fluid cells are malignant with benign cutaneous melanocytic naevus.We report the case of a young man aged 19 presenting with multiple and large congenital melanocytic naevus who experienced transcient neurological signs and increased intracranial pressure. Cerebral neuroimaging evoked meningeal infiltration which benign melanocytic nature was supposed on CSF analysis and confirmed by necropsy findings, only 3 month after neurological onset, leading to neurocutaneous melanosis diagnosis. This rare neuroectodermal dysembryoplasia finds expression in various neurological signs, depending on patient's age and leptomeningeal and/or cerebral proliferation localization. Lumbar puncture, cerebral scanography and MRI may help diagnosis, but only histological examination can prove neurocutaneous melanosis, more often by necropsy because of poor prognosis.     

Angiostrongylus cantonensis infection mimicking a spinal cord tumor

Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis and meningoencephalitis. Almost all cases are self-limiting and are diagnosed by cerebrospinal fluid eosinophilia and enzyme-linked immunosorbent assay; pathology reports are restricted to postmortem samples from lethal cases. We report on what we believe is the first case of A. cantonensis infection diagnosed by biopsy in a living patient. The spinal cord was biopsied because of the unusual clinical presentation of a myelopathy without meningeal symptoms, together with a mass lesion that was clinically and radiologically diagnosed as a spinal cord tumor.     

Experimental pneumococcal meningitis: Cerebrovascular alterations,brain edema,and meningeal inflammation are linked to the production of nitric oxide

We investigated whether treatment with the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA) and the free radical scavenger superoxide dismutase influences cerebral blood flow changes, brain edema, and cerebrospinal fluid pleocytosis in early experimental pneumococcal meningitis. Compared to untreated infected rats, superoxide dismutase given 3 hours after infection significantly attenuated the increase of brain water content, intracranial pressure, and cerebrospinal fluid white blood cell count, but did not modulate the increase in regional cerebral blood flow. N-Nitro-L-arginine treatment (5 mg/kg intravenously, followed by 5 mg/kg/hour) reversed the increase in regional cerebral blood flow; prevented an increase in brain water content, intracranial pressure, and cerebrospinal fluid nitrite concentrations; and reduced cerebrospinal fluid white blood cell count. With a closed cranial window preparation, N-nitro-L-arginine prevented pneumococci-induced dilatation of pial arterioles. When the effective dose was increased twofold, the effects of N-nitro-Lvarginine became more pronounced but resulted in the death of 4 of 5 rats, probably due to hemodynamic side effects. In primary cultures of rat cerebral endothelial cells, nitrite concentrations increased after pneumococcal stimulation, which could be prevented by NvnitrovLvarginine and cycloheximide. These data suggest that (a) nitric oxide accounts for regional cerebral blood flow changes and pial arteriolar dilatation in the early phase of experimental pneumococcal meningitis; (b) both superoxide radical and nitric oxide are involved as mediators of brain edema and meningeal inflammation; and (c) cerebral endothelial cells can be stimulated by pneumococci to release nitric oxide presumably via the inducible nitric oxide synthase.     

Primary leptomeningeal melanocytosis presenting as chronic meningitis

We report a patient with primary leptomeningeal melanocytosis presenting as chronic meningitis. A previously healthy 27-year-old man presented with 2 months of severe headaches and photophobia. A lumbar puncture was notable for a highly elevated cerebrospinal fluid (CSF) protein level without pleocytosis. Imaging at the time of admission suggested only meningitis without the presence of parenchymal lesions. On the basis of the CSF findings, early meningeal biopsy was performed, leading to the diagnosis of a meningeal melanocytic neoplasm. Early meningeal biopsy should be considered in patients with meningitis when the CSF profile suggests the possibility of a central nervous system neoplasm.