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Query: UMLS:C0038454 (stroke)
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Most frequently, chronic granulomatous meningitis (CGM) is caused by infectious agents. However, in some cases the cause of CGM remains undetermined. It is unclear whether antimicrobial agents, including antituberculous drugs, are helpful in such cases. We describe a 61-year-old man who had multiple cranial nerve lesions, epilepsy, sinus thrombosis, stroke, and hydrocephalus attributable to CGM. Repeated extensive search for a causative agent in the cerebrospinal fluid (CSF) and the meninges remained negative. Only a single culture of the sputum revealed growth of Mycobacterium tuberculosis, which prompted antituberculous therapy with isoniazid, rifampicin, and ethambutol. After 6 months of therapy, neurologic abnormalities were slightly improved. We conclude that antimicrobial/ antituberculous agents have only a minor short-term effect in long-lasting CGM of undetermined cause.
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PMID:Chronic granulomatous meningitis with multiple cranial nerve lesions hydrocephalus, stroke, sinus thrombosis, and epilepsy. 1109 65

Reperfusion injury is defined as the enhancement of the damage that occurs in ischaemic cells during the reperfusion period. Cellular damage to the brain occurs not only during the ischaemic period, but also during the reperfusion period. Such injury occurs when blood flow is restored to heart, brain or other tissue after flow has been blocked. Several mechanisms appear to play a role in the generation of reperfusion injury. To a greater or lesser extent, most involve neutrophils. The infiltration of neutrophils into the previously ischaemic area has been implicated as playing major role following reperfusion. Microscopic examination of tissue has shown a direct correlation between the duration of oxygen deprivation with the amount of damage, and the extent of activated neutrophil recruitment. Activated neutrophils are responsible for the release of serine proteases, which directly lead to tissue damage. Activated neutrophils also contain a newly assembled enzyme that produces tissue damaging free radicals. However, a preliminary and necessary step is to attach the activated neutrophil on to the lining of the blood vessels, a process requiring proteolytic activity. Administration of a drug that prevents neutrophil transmigration would reduce reperfusion injury. SuperGen is developing a drug, LEX 032, with a unique spectrum of activities, including the ability to inhibit binding of neutrophils to the vascular surface by blocking this proteolytic activity. In addition, this drug inhibits free radical production by neutrophils, and inhibits the activity of released serine proteases. Therefore, LEX 032 is expected to prevent or minimise neutrophil mediated reperfusion injury. Blockade of all three destructive inflammatory responses should limit the amount of damaged tissue and save viable tissue. A drug with these capabilities might find use in the treatment of myocardial infarction, shock-resuscitation, replantation surgery, frostbite, burns and organ transplantation. Since LEX 032 has no inhibitory activity against thrombin and plasmin, it represents an ideal drug for use in the treatment of ischaemic stroke. Recently, data have been published demonstrating that ischaemic stroke patients given the thrombolytic drug tPA were at least 30% more likely to have minimal or no disability at three months, as measured by outcome scales, when compared to placebo-treated patients. Presumably, this action was because of the hastening of brain reperfusion, and may have been limited due to reperfusion injury. The FDA approved the use of tPA for the limited treatment of acute ischaemic stroke. Since LEX 032 has been shown to limit neutrophil mediated reperfusion damage, it may find use either alone, to ameliorate damage occurring spontaneously during ischaemic stroke, or in combination therapy with tPA to reduce reperfusion injury secondary to thrombolytic therapy. This unique approach may have broad therapeutic potential in the treatment of neutrophil mediated diseases since, unlike a monoclonal antibody for example, it is independent of the specific adhesion molecule(s). These diseases include inflammatory diseases which are, at least in part, caused or exacerbated by excessive neutrophil proteases, such as acute pancreatitis, arthritis, allograft rejection, sepsis, meningitis, acute pulmonary inflammation, psoriasis and damage caused by burns. This is in addition to reperfusion-related diseases such as myocardial infarction, stroke, shock-resuscitation, replantation surgery, frostbite, burns and organ transplantation.
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PMID:LEX 032: a novel recombinant human protein for the treatment of ischaemic reperfusion injury. 1113 33

Acute headache may be the presenting symptom of several conditions. Sometimes, a headache with an abrupt onset and unusual severity may occur, experienced by the patient as the worst headache ever. The diagnostic evaluation primarily aims at ruling out subarachnoid haemorrhage (SAH), as well as other serious causes of acute headache, such as meningitis or stroke. The clinical examination should immediately be followed by cerebral computed tomography (CT). A CT scan will reveal 95% of SAHs, provided that it is performed within the first 24 hours after headache onset. If the CT scan is normal, a lumbar puncture should follow, preferably 12 hours after the onset of headache, unless infectious meningitis is suspected. If infectious meningitis is strongly suspected, lumbar puncture should be performed without delay. The spinal fluid should be investigated by spectrophotometry, in order to obtain optimal diagnostic accuracy for SAH. This article briefly reviews the various conditions that may present with an acute headache.
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PMID:[Acute headache--diagnostic considerations]. 1118 83

Successful reconstruction after cranial base tumor ablation is paramount in preventing potentially life-threatening complications. The purpose of this study was to evaluate experiences of cranial base reconstruction and to identify reconstructive management principles that may assist in achieving successful cranial base reconstruction. All cranial base reconstructions performed by the Department of Plastic Surgery at the University of Texas M. D. Anderson Cancer Center between January of 1993 and September of 1999 were reviewed. Analyses were performed to assess the impact of location of defect, type of reconstruction, type of dural repair, and history of preoperative radiation and chemotherapy on rates of complications, and patient survival. The 77 patients who underwent cranial base reconstruction after tumor ablation during the study period had a mean age of 52 years (6 to 84 years). The mean follow-up period was 28.7 months (1 to 76 months). Squamous cell carcinoma, the most common histopathologic type, was present in 24 patients (31 percent), and 35 patients (45 percent) presented with recurrent disease. Location of defects involved region I (anterior) in 31 patients (40 percent), region II (anterior-lateral) in 18 (23 percent), region III (lateral-posterior) in six (8 percent), and more than one region in 22 (29 percent). Reconstructive methods included free flaps in 52 patients (68 percent), temporalis muscle flaps in 14 (18 percent), pericranial flaps in eight (10 percent), and other local flaps (two galeal, one scalp) in three (4 percent). Of the 52 free flaps, 18 (35 percent) were used in region I, 14 (27 percent) in region II, six (12 percent) in region III, and 14 (27 percent) in defects involving more than one region. Of the 14 temporalis muscle flaps, 13 (93 percent) were used for defects involving regions I or II and one (7 percent) was used for a defect involving region III. Of the 11 pericranial and other local flaps, nine (82 percent) were used in region I, one (9 percent) in region II, and one (9 percent) in a combination of regions II and III. Complications occurred in 21 patients (27 percent): three total flap losses (4 percent), three partial flap losses (4 percent), two cerebrospinal fluid leaks (3 percent), two cases of meningitis (3 percent), two abscesses (3 percent), five cases of delayed wound healing (6 percent), two hematomas (3 percent), one wound infection (1 percent), and one cerebrovascular accident (1 percent). Overall survival was 77 percent at 2 years and 58 percent at 4 years. The type of reconstruction, location of defect, type of dural repair, and history of preoperative radiation and chemotherapy had no significant association with the incidence of complications. Neither the type of reconstruction nor the location of defect showed a significant effect on patient survival. In this experience, local flaps, such as pericranial or temporalis muscle flaps, are good choices for reconstruction of smaller anterior or lateral cranial base defects. For defects that require larger amounts of soft tissue, free flaps are appropriate. With proper patient selection, successful cranial base reconstruction can be performed with either local or free flaps with a low incidence of complications.
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PMID:Reconstructive management of cranial base defects after tumor ablation. 1133 98

The diagnostic approach to the compromised host with CNS infection depends on an analysis of the patient's clinical manifestations of CNS disease, the acuteness or subacuteness of the clinical presentation, and an analysis of the type of immune defect compromising the patient's host defenses. Most patients with CNS infections may be grouped into those with meningeal signs, or those with mass lesions. Other common manifestations of CNS infection include encephalopathy, seizures, or a stroke-like presentation. Most pathogens have a predictable clinical presentation that differs from that of the normal host. CNS Aspergillus infections present either as mass lesions (e.g., brain abscess), or as cerebral infarcts, but rarely as meningitis. Cryptococcus neoformans, in contrast, usually presents as a meningitis but not as a cerebral mass lesion even when cryptococcal elements are present. Aspergillus and Cryptococcus CNS infections are manifestations of impaired host defenses, and rarely occur in immunocompetent hosts. In contrast, the clinical presentation of Nocardia infections in the CNS is the same in normal and compromised hosts, although more frequent in compromised hosts. The acuteness of the clinical presentation coupled with the CNS symptomatology further adds to limit differential diagnostic possibilities. Excluding stroke-like presentations, CNS mass lesions tend to present subacutely or chronically. Meningitis and encephalitis tend to present more acutely, which is of some assistance in limiting differential diagnostic possibilities. The analysis of the type of immune defect predicts the range of possible pathogens likely to be responsible for the patient's CNS signs and symptoms. Patients with diseases and disorders that decrease B-lymphocyte function are particularly susceptible to meningitis caused by encapsulated bacterial pathogens. The presentation of bacterial meningitis is essentially the same in normal and compromised hosts with impaired B-lymphocyte immunity. Compromised hosts with impaired T-lymphocyte or macrophage function are prone to develop CNS infections caused by intracellular pathogens. The most common intracellular pathogens are the fungi, particularly Aspergillus, other bacteria (e.g., Nocardia), viruses (i.e., HSV, JC, CMV, HHV-6), and parasites (e.g., T. gondii). The clinical syndromic approach is most accurate when combining the rapidity of clinical presentation and the expression of CNS infection with the defect in host defenses. The presence of extra-CNS sites of involvement also may be helpful in the diagnosis. A patient with impaired cellular immunity with mass lesions in the lungs and brain that have appeared subacutely or chronically should suggest Nocardia or Aspergillus rather than cryptococcosis or toxoplasmosis. Patients with T-lymphocyte defects presenting with meningitis generally have meningitis caused by Listeria or Cryptococcus rather than toxoplasmosis or CMV infection. The disorders that impair host defenses, and the therapeutic modalities used to treat these disorders, may have CNS manifestations that mimic infections of the CNS clinically. Clinicians must be ever vigilant to rule out the mimics of CNS infections caused by noninfectious etiologies. Although the syndromic approach is useful in limiting diagnostic possibilities, a specific diagnosis still is essential in compromised hosts in order to describe effective therapy. Bacterial meningitis, cryptococcal meningitis, and tuberculosis easily are diagnosed accurately from stain, culture, or serology of the CSF. In contrast, patients with CNS mass lesions usually require a tissue biopsy to arrive at a specific etiologic diagnosis. In a compromised host with impaired cellular immunity in which the differential diagnosis of a CNS mass lesion is between TB, lymphoma, and toxoplasmosis, a trial of empiric therapy is warranted. Antitoxoplasmosis therapy may be initiated empirically and usually results in clinical improvement after 2 to 3 weeks of therapy. The nonresponse to antitoxoplasmosis therapy in such a patient would warrant an empiric trial of antituberculous therapy. Lack of response to anti-Toxoplasma and antituberculous therapy should suggest a noninfectious etiology (e.g., CNS lymphoma). Fortunately, most infections in compromised hosts are similar in their clinical presentation to those in the normal host, particularly in the case of meningitis. The compromised host is different than the normal host in the distribution of pathogens, which is determined by the nature of the host defense defect. In compromised hosts, differential diagnostic possibilities are more extensive and the likelihood of noninfectious explanations for CNS symptomatology is greater. (ABSTRACT TRUNCATED)
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PMID:Central nervous system infections in the compromised host: a diagnostic approach. 1144 10

Herpesviruses cause various acute, subacute, and chronic disorders of the central (CNS) and peripheral (PNS) nervous systems in adults and children. Both immunocompetent and immunocompromised individuals may be affected. Zoster (shingles), a result of reactivation of varicella zoster virus (VZV), is the most frequent neurologic complication. Other neurological complications include encephalitis produced by type I herpes simplex virus (HSV-1), and less frequently HSV-2, as well as by VZV and cytomegalovirus (CMV). Acute meningitis is seen with VZV and HSV-2, and benign recurrent meningitis with HSV-2. Combinations of meningitis/ encephalitis and myelitis/radiculitis are associated with Epstein Barr Virus (EBV); myelitis with VZV, CMV, EBV, and HSV-2; and ventriculitis/encephalitis with VZV and CMV. Brainstem encephalitis due to HSV and VZV, and polymyeloradiculitis due to CMV are well documented. HHV-6 produces childhood exanthem subitum (roseola) and febrile convulsions. Immunocompetent and immunocompromised hosts manifest different incidences and patterns of herpesvirus infections. For example, stroke due to VZV-mediated large vessel disease (herpes zoster ophthalmicus) occurs predominantly in immunocompetent hosts, while small vessel disease (leukoencephalitis) and ventriculitis develop almost exclusively in immunocompromised patients. EBV-associated primary CNS lymphomas also are restricted to immunosuppressed individuals. Recent large CSF PCR studies have shown that VZV, EBV, and CMV more frequently produce meningitis, encephalitis, or encephalopathy in immunocompetent hosts than was formerly realized. We review herpesvirus infections of the nervous system and illustrate the expanding spectrum of disease by including examples of a 75-year-old male on steroid treatment for chronic lung disease with fatal HSV-2 meningitis and an 81-year-old male with myasthenia gravis, long-term azathioprine use, and an EBV-associated primary CNS lymphoma.
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PMID:The expanding spectrum of herpesvirus infections of the nervous system. 1155 90

Acute sinusitis is a prevalent and generally uncomplicated infection that is normally resolved by medical therapy. However, severe neurological complications are known, and comprise of cerebral abscess, cavernous sinus thrombosis, meningitis, and epidural or subdural empyema. We report a case about a 10-year-old girl with a severe acute pansinusitis and ischemic stroke in the right lentiform nucleus and the anterior part of the right internal capsule. Possible explanations for this rare combination are discussed.
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PMID:Sinusitis and ischemic stroke. 1172 11

Of 204 patients with infectious endocarditis (IE) treated in the hospital in 1980-2000, 43(21.2%) developed neurological complications. These were: ischemic stroke (72.1%), hemorrhagic stroke (9.3%), both (7%), abscess and subarachnoidal hemorrhage (2.3% for each), meningitis (7%), toxic encephalopathy (11.6%). Neurological complications of IE arose prior to treatment and within the first week of antibacterial therapy in 63% cases, more frequently in the left carotid territory. Neurological complications in IE debute manifested acutely, pareses were more frequent than paralyses, with elevated temperature, low hemoglobin and red cell levels, leukocytosis. MRT detected 8 +/- 4.6 foci in the brain, CT--2 +/- 1.1, on the average. Lethality of IE patients with neurological complications reached 58.1% and was significantly higher than in those without such complications (14.9%, p < 0.001). Overall acturial survival 1 year after the discharge from the hospital was 94.4%, 5-year survival--61.1%, 10-year survival--11%.
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PMID:[Neurological complications of infectious endocarditis]. 1189 17

Interleukin (IL)-10 is synthesized in the central nervous system (CNS) and acts to limit clinical symptoms of stroke, multiple sclerosis, Alzheimer's disease, meningitis, and the behavioral changes that occur during bacterial infections. Expression of IL-10 is elevated during the course of most major diseases in the CNS and promotes survival of neurons and all glial cells in the brain by blocking the effects of proapoptotic cytokines and by promoting expression of cell survival signals. Stimulation of IL-10 receptors regulates numerous life- or death-signaling pathways--including Jak1/Stat3, PI 3-kinase, MAPK, SOCS, and NF-kappaB--ultimately promoting cell survival by inhibiting both ligand- and mitochondrial-induced apoptotic pathways. IL-10 also limits inflammation in the brain; it does so by three major pathways: (1) reducing synthesis of proinflammatory cytokines, (2) suppressing cytokine receptor expression, and (3) inhibiting receptor activation. Finally, IL-10 induces anergy in brain-infiltrating T cells by inhibiting cell signaling through the costimulatory CD28-CD80/86 pathway. The multiple functions of IL-10 in the brain will create new and intriguing vistas that will promote a better understanding of neurodegenerative diseases. These discoveries could lead to development of innovative approaches for the use of antiinflammatory cytokines in major debilitating diseases of the CNS.
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PMID:Interleukin-10 in the brain. 1194 58

Spinal cord dysfunction is a rare complication of Neisseria meningitidis (meningococcal) meningitis. We report a 17-year-old patient who had a 3-day history of fever, headache and vomiting, agitation, and unresponsiveness. Cerebrospinal fluid showed a marked polymorphonuclear pleocytosis. Latex particle agglutination was positive for meningococci. The patient was given intravenous antibiotics and intravenous dexamethasone. Over the next 4 days, he developed weakness of the lower extremities, with areflexia and extensor plantar responses. MRI revealed contiguous hyperintensities on T2-weighted images involving the thoracic spinal cord from T4 to T9 and 4 brain abscesses. Five months later, he recovered brain function, but the paraparesis remained. This case illustrates that myelopathy may complicate acute meningococcal meningitis, possibly due to a vasculitis, stroke, autoimmune myelopathy, or direct infection of the spinal cord. Patients with myelopathy associated with acute meningitis should receive spinal MRI. In addition, meningitis should be considered in patients presenting with acute myelopathy.
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PMID:Thoracic myelopathy complicating acute meningococcal meningitis: MRI findings. 1201 69


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