Neurologic complications of systemic cancer.
Neurologic complications occur frequently in patients with cancer. After routine chemotherapy, these complications are the most common reason for hospitalization of these patients. Brain metastases are the most prevalent complication, affecting 20 to 40 percent of cancer patients and typically presenting as headache, altered mental status or focal weakness. Other common metastatic complications are epidural spinal cord compression and leptomeningeal metastases. Cord compression can be a medical emergency, and the rapid institution of high-dose corticosteroid therapy, radiation therapy or surgical decompression is often necessary to preserve neurologic function. Leptomeningeal metastases should be suspected when a patient presents with neurologic dysfunction in more than one site. Metabolic encephalopathy is the common nonmetastatic cause of altered mental status in cancer patients. Cerebrovascular complications such as stroke or hemorrhage can occur in a variety of tumor-related conditions, including direct invasion, coagulation disorders, chemotherapy side effects and nonbacterial thrombotic endocarditis. Radiation therapy is the most commonly employed palliative measure for metastases. Chemotherapy or surgical removal of tumors is used in selected patients. (+info)
Loss of 123I-MIBG uptake by the heart in Parkinson's disease: assessment of cardiac sympathetic denervation and diagnostic value.
Myocardial imaging with 123I-metaiodobenzylguanidine (MIBG) was performed on 35 patients with Parkinson's disease and 24 control subjects to evaluate cardiac sympathetic function in patients with Parkinson's disease, verify this phenomenon and examine whether myocardial MIBG uptake and clearance are correlated with the clinical severity of Parkinson's disease. METHODS: We studied 35 patients with Parkinson's disease and 24 control subjects with other central nervous system diseases. The latter group consisted of 12 subjects with other neurodegenerative disorders (4 with spinocerebellar degeneration, 2 with amyotrophic lateral sclerosis, 3 with progressive supranuclear palsy and 3 with corticobasal degeneration and 12 patients with cerebral infarction (CI), 6 with vascular parkinsonism and 6 without it. Early and delayed images of the anterior view were obtained 15 min and 4 h after injection of 123I-MIBG, respectively. MIBG uptake was quantified by calculating a heart-to-mediastinum count (H/M) ratio. RESULTS: The H/M ratio was markedly reduced in the patients with Parkinson's disease (II to V on the Hoehn and Yahr scale) compared with the control subjects. None of the subjects with neurodegenerative diseases showed a marked decrease in myocardial MIBG uptake nor did any subject with CI. CONCLUSION: Our findings indicate that, in Parkinson's disease, a reduction in myocardial MIBG uptake is a very common, specific phenomenon that can be used to detect cardiac autonomic dysfunction to diagnose Parkinson's disease, particularly in patients without typical signs and symptoms. (+info)
A five-year assessment of controlled trials of in-patient and out-patient treatment and of plaster-of-Paris jackets for tuberculosis of the spine in children on standard chemotherapy. Studies in Masan and Pusan, Korea. Fifth report of the Medical Research Council Working Party on tuberculosis of the spine.
In two centres in Korea 350 patients with a diagnosis of tuberculosis of the thoracic and/or lumbar spine were allocated at random: in Masan to in-patient rest in bed (IP) for six months followed by out-patient treatment or to ambulatory out-patient treatment (OP) from the start; in Pusan to out-patient treatment with a plaster-of-Paris jacket (J) for nine months or to ambulatory treatment without any support (No J). All patients recieved chemotherapy with PAS with isoniazid for eighteen months, either supplemented with streptomycin for the first three months (SPH) or without this supplement (PH), by random allocation. The main analysis of this report concerns 299 patients (eighty-three IP, eighty-three OP, sixty-three J, seventy No J; 143 SPH, 156 PH). Pre-treatment factors were similar in both centres except that the patients in Pusan had, on average, less extensive lesions although in a greater proportion the disease was radiographically active. One patient (J/SPH) died with active spinal disease and three (all No J/SPH) with paraplegia. A fifth patient (IP/PH) who died from cardio respiratory failure also had pulmonary tuberculosis. Twenty-three patients required operation and/or additional chemotherapy for the spinal lesion. A sinus or clinically evident abscess was either present initially or developed during treatment in 41 per cent of patients. Residual lesions persisted in ten patients (four IP, two OP, one J, three No J; six SPH, four PH) at five years. Thirty-two patients had paraparesis on admission or developing later. Complete resolution occurred in twenty on the allocated regimen and in eight after operation or additional chemotherapy or both. Of the remaining four atients, all of whom had operation and additional chemotherapy, three died and one still had paraparesis at five years. Of 295 patients assessed at five years 89 per cent had a favourable status. The proportions of the patients responding favourably were similar in the IP (91 per cent) and OP (89 per cent) series, in the J (90 per cent) and No J (84 per cent) series and in the SPH (86 per cent) and PH (92 per cent) series. (+info)
Fatal outcome due to cyclosporine neurotoxicity with associated pathological findings.
We present a case of death likely to be directly due to cyclosporine (CsA) neurotoxicity. To date, there have been no reports of deaths directly due to CsA neurotoxicity, nor has an associated histological lesion been described independent of confounding processes. A 54-year-old male received an HLA-matched-unrelated BMT for CML. He developed progressive encephalopathy and on day +79 had a generalized seizure. All CSF studies were negative for infectious causes. MRI revealed diffuse, symmetrical white matter abnormalities located in the occipital sub-cortex, thalamus, mid brain, pons, and cerebellum which were typical of CsA toxicity. The patient died of central respiratory failure within 72 h of discontinuing CsA. Autopsy revealed diffuse patchy white matter edema and astrocytic injury without evidence of axonopathy, demyelination, microvascular injury, or infectious/inflammatory process. This case demonstrates previously undescribed lethal CsA neurotoxicity and may reveal an associated primary pathological lesion. (+info)
Molecular pathway involved in HIV-1-induced CNS pathology: role of viral regulatory protein, Tat.
The broad range of histological lesions associated with HIV-1 are somewhat subtle relative to the clinical manifestations that occur as a result of HIV infection. Although it is clear that HIV has a causative role in CNS disease, dementia appears to be a consequence of the infiltration of inflammatory cells and cytokine dysregulation rather than the amount of virus in CNS. The HIV transregulatory protein Tat plays an important intracellular as well as extracellular role in the dysregulation of cytokines. The cytokines and possibly chemokines that are induced by Tat modify the action of astrocytes such that the survival of neurons is compromised. Pathogenetic alteration induced by Tat involves a series of interactions between circulating monocyte/macrophages, endothelial cells, and astrocytes. Cytokine dysregulation induced by viral infection and extracellular Tat leads to alterations in expression of adhesion molecules and promotes migration of non-infected inflammatory cells into the CNS compartment. We demonstrate here that recombinant HIV-1 Tat protein introduced by stereotaxic injection into mouse brain can induce pathologically relevant alterations including macrophage invasion as well as astrocytosis. The mechanism of destruction of the CNS by Tat appears to involve autocrine and paracrine pathways that depend not only on Tat, but cytokine and chemokine signaling pathways that are altered by viral infection. In this review, we discuss various pathogenic effects of Tat in brain cells and provide experimental evidence for an increased TNF-alpha level in CSF in mice injected intracerebrally with Tat protein. (+info)
Central nervous system sarcoidosis--diagnosis and management.
A series of 68 patients with neurosarcoidosis is reported, with particular emphasis on clinical aspects, diagnosis and treatment. A classification system based on clinical diagnostic probability is proposed, consisting of probable and definite disease, the latter being dependent on finding sarcoid granulomas on nervous system histology, which was obtained in 12 patients (18%). The role of investigations, including magnetic resonance imaging (MRI), chest radiography, Kveim skin test, Gallium 67 isotope scanning and cerebrospinal fluid (CSF) studies, is considered. Sixty-two percent of patients presented with nervous system disease, most commonly affecting the optic nerve and chiasm. Other common presentations included cranial nerve palsies, spinal cord and brainstem manifestations. Investigations yielding most diagnostic information included the Kveim test (41/48, 85% positive), raised CSF protein and/or cells (50/62, 81%) and gallium 67 scan (14/31, 45%). Eleven out of 29 patients (38%) patients showed meningeal enhancement on MRI scanning and 43% of scans demonstrated multiple white-matter lesions. Mean follow-up for the group was 4.6 years. Forty-seven patients were seen for > 18 months, and over half of these patients progressed despite corticosteroid and other immunosuppressive therapies. The benefit of a large patient database prospectively studied, with extended follow-up is discussed in order to learn more about prognosis and advance therapy in neurosarcoidosis. (+info)
Complications of varicella in a defined central European population.
AIMS: To describe complications of varicella requiring hospitalisation in a defined population (canton of Bern) and to compare the hospitalisation rates for varicella with published data. METHODS: Retrospective analysis of hospital records of patients less than 16 years of age admitted with complications of varicella to the hospitals serving this population (University Children's Hospital of Bern and the Wildermeth Children's Hospital of Biel, Switzerland), and calculation of hospitalisation rates for varicella and its complications based on birth rates and varicella antibody prevalence rates. RESULTS: From 1986 to 1996, 113 cases (median age, 5.6 years) were identified. Younger siblings were overrepresented (odds ratio (OR), 1.42; 95% confidence interval (CI), 1.09 to 1.84). Central nervous system (CNS) complications (26 patients; 23%) were found predominantly in previously healthy children (relative risk, 7.1; 95% CI, 1.01 to 49.86). Group A beta haemolytic streptococci were recovered from only one of 35 patients with bacterial complications. The hospitalisation rates for primary varicella (9.2/10(4) cases; 95% CI, 7.4 to 11/10(4), skin infections (2.0/10(4) cases; 95% CI, 1.2 to 2.9/10(4), and pneumonia (0.8/10(4) cases; 95% CI, 0.3 to 1.3/10(4)) were significantly lower than reported previously. The CNS complication rate (2.2/10(4) cases; 95% CI, 1.3 to 3.1/10(4) was among the highest rates reported. CONCLUSIONS: The low hospitalisation rate in comparison with studies from elsewhere indicates that there is a large regional variability in complications associated with varicella. Such data should be taken into consideration when local varicella immunisation strategies are developed. (+info)
C10 is a novel chemokine expressed in experimental inflammatory demyelinating disorders that promotes recruitment of macrophages to the central nervous system.
Chemokines may be important in the control of leukocytosis in inflammatory disorders of the central nervous system. We studied cerebral chemokine expression during the evolution of diverse neuroinflammatory disorders in transgenic mice with astrocyte glial fibrillary acidic protein-targeted expression of the cytokines IL-3, IL-6, or IFN-alpha and in mice with experimental autoimmune encephalomyelitis. Distinct chemokine gene expression patterns were observed in the different central nervous system inflammatory models that may determine the phenotype and perhaps the functions of the leukocytes that traffic into the brain. Notably, high expression of C10 and C10-related genes was found in the cerebellum and spinal cord of GFAP-IL3 mice with inflammatory demyelinating disease and in mice with experimental autoimmune encephalomyelitis. In both these neuroinflammatory models, C10 RNA and protein expressing cells were predominantly macrophage/microglia and foamy macrophages present within demyelinating lesions as well as in perivascular infiltrates and meninges. Intracerebroventricular injection of recombinant C10 protein promoted the recruitment of large numbers of Mac-1(+) cells and, to a much lesser extent, CD4(+) lymphocytes into the meninges, choroid plexus, ventricles, and parenchyma of the brain. Thus, C10 is a prominent chemokine expressed in the central nervous system in experimental inflammatory demyelinating disease that, we show, also acts as a potent chemotactic factor for the migration of these leukocytes to the brain. (+info)