Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
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Nervous system involvement by sarcoidosis has been considered rare, yet more than 400 cases have been reported. We present 23 additional cases here, including 14 with autopsies, and we review the literature. The overall frequency of neurologic involvement is 5%. Patients usually have other stigmata of sarcoidosis; however, neurologic dysfunction is frequently the presenting finding. The protean manifestations of central nervous system (CNS) involvement usually occur in the early phase of the disease, while those of peripheral nervous system and skeletal muscle involvement are characteristically seen in the chronic stages. Basal granulomatous meningitis causes most of the CNS manifestations either by infiltration or compression of adjacent structures. Steroids are the mainstay of therapy, and the overall response is quite variable. The course is also variable, being transient in some and chronic in others. The prognosis is better with peripheral than with central nervous system involvement.
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PMID:Neurologic manifestations in sarcoidosis: review of the literature, with a report of 23 cases. 19 63

Tuberculosis meningitis (TBM) is the most serious form of infection with Mycobacterium tuberculosis. Between 1968 and 1986 15 children (five boys and 10 girls) were seen at the Royal Hospital for Sick Children, Glasgow, because of TBM. Fourteen children were Caucasian and one was Asian. The mean age at presentation was two years. None had been given BCG vaccination. In 12 children close contact with other cases of tuberculosis was reported. The signs and symptoms which helped in the diagnosis are discussed together with the initial CSF findings, results of mantoux testing and chest X-rays. Three children had unusual modes of presentation. All children were treated with chemotherapy though the drug combinations, route of administration and therapy varied from case to case. Steroids were used in nine children. Five children required neurosurgical intervention. Two children died and of the survivors six had serious sequelae. Five children made a complete recovery. The outcome of TBM depended on the duration of symptoms prior to the onset of therapy, on the neurological status reached at the time of diagnosis and the age of the child. The roles of chemotherapy, steroids and neurosurgery in the management of TBM are discussed. The need for routine BCG vaccination of all neonates is examined.
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PMID:Tuberculous meningitis in children: a review of 15 cases. 338 99

Tuberculous meningitis is a rare, treatable neurologic disorder, in which early recognition is paramount because outcome depends greatly on the speed with which therapy is initiated. Patients with meningitis and CSF findings of low glucose, elevated protein and pleocytosis with evidence of tuberculosis elsewhere in the body (chest radiographs, positive tuberculin skin test), or a history of exposure to tuberculosis should be treated immediately with antituberculous medication. When the diagnosis remains uncertain, serial examination of the CSF for tuberculous organisms will often yield positive results. The CT scan may show hydrocephalus, a basilar arachnoiditis, or intraparenchymal lesions: tuberculomas. Hydrocephalus may respond to early shunting. Tuberculomas are best treated medically. Therapy should include INH and rifampin; ethambutol and pyrazinamide are suggested for the first 2 months of therapy. Steroids may be useful in diminishing the inflammatory response when altered consciousness or focal neurologic signs are present.
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PMID:CNS tuberculosis. 352 99

Chemotherapy studies were undertaken in 180 patients with tuberculous meningitis. They were treated for 12 months with 1 of 3 regimens: the first consisted of streptomycin, isoniazid and rifampicin daily for the first 2 months, followed by ethambutol plus isoniazid for 10 months; in the second, pyrazinamide was added for the first 2 months, and in the third, rifampicin was reduced to twice weekly in the first 2 months. Steroids were prescribed for all the patients in the initial weeks of treatment. Approximately 50% of the patients were aged less than 3 years. On admission, 13% of the patients were classified as stage I, 77% as stage II and 9% as stage III. Cerebrospinal fluid (CSF) culture results were available for all the 180 patients and M. tuberculosis was isolated in 59 (33%). CSF smear results for acid fast bacilli were available only for the 103 patients admitted to the second and the third studies, and of these in 60 (58%) the CSF was positive either by smear or culture. The response to therapy was similar in the 3 studies. Despite administration of rifampicin for 2 months, the mortality was high. In all, 27% of the patients died of tuberculous meningitis, 39% had neurological sequelae and 34% recovered completely. There was a strong association between the stage on admission and the mortality rate, the deaths being highest in stage III. In the first study, when isoniazid was prescribed daily in a dosage of 20 mg/kg, 39% of the patients developed jaundice; however, when the dosage was reduced to 12 mg/kg, the incidence fell to 16%. In the third study, where rifampicin was administered twice a week, the incidence of jaundice was much lower (5%).
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PMID:Three chemotherapy studies of tuberculous meningitis in children. 371 80

A study of 170 patients with juvenile rheumatoid arthritis and a review of the literature indicate that this disease can significantly affect the central nervous system. Signs of CNS dysfunction were observed in 13 children. During the acute toxic stages the EEG is abnormal in many cases. Other manifestations of toxic encephalopathy such as irritability, drowsiness, stupor, convulsions and marked meningismus may be evident in severe cases. Meningitis is often suspected but ruled out by the finding of normal CSF. Steroids can rapidly improve the condition of these children. If ;unexplained' seizures occur during the chronic stage, the diagnosis of cerebral vasculitis should be entertained.
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PMID:Cerebral complications in juvenile rheumatoid arthritis. 466 94

A detailed review of the TJUH experience and the published literature on gunshot and stab wounds to the spine has been presented. The following statements are supported. (1) Military (high-velocity) gunshot wounds are distinct entities, and the management of these injuries cannot be carried over to civilian (low-velocity) handgun wounds. (2) Gunshot wounds with a resultant neurologic deficit are much more common than stab wounds and carry a worse prognosis. (3) Spinal infections are rare following a penetrating wound of the spine and a high index of suspicion is needed to detect them. (4) Extraspinal infections (septic complications) are much more common than spinal infections following a gunshot or stab wound to the spine. (5) Steroids are of no use in gunshot wounds to the spine. In fact, there was an increased incidence of spinal and extraspinal infections without a difference in neurologic outcome compared with those who did not receive steroids. (6) Spinal surgery is rarely indicated in the management of penetrating wounds of the spine. The recommendations for treatment at TJUH of victims of gunshot or stab wounds with a resultant neurologic deficit are as follows. (1) Spine surgery is indicated for progressive neurologic deficits and persistent cerebrospinal fluid leaks (particularly if meningitis is present), although these situations rarely occur. (2) Consider spine surgery for incomplete neurologic deficits with radiographic evidence of neural compression. Particularly in the cauda equina region, these surgeries may be technically demanding because of frequent dural violations and nerve root injuries/extrusions. These cases must be evaluated in an individual case-by-case manner. The neurologic outcomes of patients with incomplete neurologic deficits at TJUH who underwent acute spine surgery (usually for neural compression secondary to a bullet) were worse than the outcomes for the patients who did not have spine surgery. A selection bias against the patients undergoing spine surgery was likely present as these patients had evidence of ongoing neural compression. (3) A high index of suspicion is necessary to detect spinal and extraspinal infections. (4) Do not use glucorticoid steroids for gunshot wound victims. (5) Conservative (nonoperative) treatment with intravenous broad spectrum antibiotics and tetanus prophylaxis is the sole therapy indicated in the majority of patients who sustain a penetrating wound to the thoracic or lumbar spines.
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PMID:Thoracolumbar infections in penetrating injuries to the spine. 853 54

Treatment of tuberculous meningitis should begin with an anti-tuberculous regimen of at least three drugs: isoniazid, pyrazinamide, and rifampin. Early in the course of therapy, ethambutol or streptomycin may be of some added benefit. If the local incidence of drug resistance to Mycobacterium tuberculosis is greater than 4%, or is unknown, then a fourth drug (ethambutol or streptomycin) should be added. If the patient is from an area with organisms resistant to multiple drugs, or is likely to be infected with a multiply resistant organism for any reason, then the patient should be on enough drugs to insure that at least two active anti-tubercular drugs are included in the therapy. An expert should be consulted Length of therapy is not standardized. For sensitive organisms, a regimen of three drugs daily for 2 months, followed by two-drug therapy (isoniazid and rifampin) has been recommended. The American Thoracic Society (ATS) and the Centers for Disease Control (CDC) have recommended a minimum of 12 months of therapy for tuberculous meningitis. If cultures remain positive for extended periods, or signs or symptoms respond slowly, therapy should be extended to 18 months. Patients with HIV also may need longer courses of therapy. The severity of tuberculous meningitis can be classified based on a system devised by the British Medical Research Council. Stage I patients are fully conscious, rational, and do not have neurologic signs. Stage II patients are confused or have neurologic signs such as cranial nerve palsy or hemiparesis. Stage III patients are comatose or stuporous with more severe neurologic signs. Corticosteroids are recommended if the patient is mentally confused, has neurologic signs, or is comatose (Stages II and III). In patients with moderate disease (Stage II), corticosteroids appear to improve neurologic sequelae and survival. Dexamethasone 6 to 12 mg per day and prednisone 60 to 80 mg per day tapered over 4 to 8 weeks has been used. Symptoms of central nervous system (CNS) inflammation may recur if the corticosteroid taper is implemented too soon or too fast. Steroids and diuretics such as furosemide and acetazolamide are sometimes used to treat hydrocephalus. Ventriculoperitoneal or ventriculoatrial shunting may be required to relieve signs and symptoms of hydrocephalus.
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PMID:Tuberculosis Meningitis. 1148 56

Initial empiric treatment for central nervous system (CNS) tuberculosis should include four antituberculous drugs until results of cultures and sensitivities are available. Treatment should include isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin. Total treatment should extend for 12 months. Daily therapy should be used for the first 2 months, followed by either twice a week treatment or continued with daily therapy for the duration with directly observed therapy (DOT). Pyrazinamide should be included in all treatment regimes for the first 2 months of therapy. Corticosteroids should be used in the management of children with tuberculous meningitis. Corticosteroids have been shown to decrease mortality, long-term neurologic complications, and permanent sequelae. Prednisone is often used at a dosage of 1 to 2 mg/kg per day. Steroids should be used for 4 to 6 weeks, and then tapered over the next 2 to 3 weeks. Cerebrospinal fluid (CSF) cultures and other infected sites must be aggressively pursued in order to obtain an organism for identification and sensitivities testing. Cranial CT scans with contrast should be included in the early diagnostic work-up of a child with suspected CNS tuberculosis infection. Hydrocephalus is often an early finding and may be helpful in establishing the diagnosis of CNS tuberculosis. Treatment of CNS tuberculosis should be for 12 months. All children with CNS tuberculosis should be promptly reported to the local public health department. Public health will facilitate the case-contact study and assist with follow-up and DOT after discharge. Directly observed therapy should be given for the entire treatment course. This is best accomplished with the collaboration of local public health services. Children with tuberculous meningitis should be evaluated in follow-up monthly. Monitoring should include determining adherence to drug treatment, an interval history for signs and symptoms of disease progression, careful physical examinations and evaluation for adverse effects of drugs. Liver function tests should be obtained at baseline, 2-, 4-, 6-, and 8 weeks, and then monthly for the first several months of treatment. Children with tuberculous meningitis should be tested for HIV infection, including pre- and post-test counseling.
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PMID:Tuberculous Meningitis in Children. 1193 32

Between 1995 and 2000, 22 cases with low velocity missile injuries of the spine and spinal cord were treated in three service hospitals. All were adult males, with a mean age of 30.7 years. The wounds were caused by splinters in 18 (82%) and bullets in 4 (18%). Twelve patients received more than one splinter. The cervical and thoracic spines were most frequently involved. In 7 cases, there were injuries to other organs. There was extensive initial deficit (quadriplegia, paraplegia) in 18 (82%) cases, while 4 (18%) had partial deficits. The patients were evaluated by spine radiographs. Myelography was done in 4, CT myelography in 11 and MRI in 4 patients. Two patients had intramedullary hematoma without any skeletal injury, and were treated conservatively. Seventeen patients were treated operatively, and associated injuries of other organs received priority management. Surgery was in the form of debridement, exploration of the spinal cord, hemostasis, decompression and dural repair. Steroids and antibiotics were given routinely. Three patients (2 with cervical and 1 with thoracic spine injury) died preoperatively, and 1 (with dorsolumbar injury) died in the postoperative period due to multi-organ injury. Patients with complete injury remained completely paralyzed, while those with an incomplete injury showed improvement in their neurological grades. The initial neurological grade is the best prognostic indicator, and these injuries are often accompanied by multi-organ injuries. There was no instance of postoperative meningitis or CSF leak. These injuries should be explored for debridement and dural repair.
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PMID:Missile injuries of the spine. 1474 34

Infectious diseases of the CNS lead to overwhelming inflammatory processes within the brain and spinal cord that contribute substantially to patient morbidity and mortality. Pharmacological strategies to modulate inflammation have been investigated, although the resulting guidelines have sometimes been contradictory. Steroids have been proposed as adjunctive treatments for bacterial meningitis, tuberculous meningitis and herpes simplex virus encephalitis. Well-designed randomized controlled trials have established dexamethasone as an adjunctive therapy for adult patients receiving antibiotics for bacterial meningitis, and physicians prescribing the initial antibiotics need to be aware of current guidelines. Morbidity and mortality in patients with tuberculous meningitis exceeds 50%. Steroid treatments reduce mortality through an as yet unknown mechanism, although their effects on morbidity are less clear. Herpes simplex virus encephalitis is also associated with considerable morbidity and mortality. Despite a lack of randomized trials, there is some evidence that steroids used alongside antiviral therapy might be beneficial in this condition. As we discuss in this Review, systemic steroid treatment is an important aspect of treatment regimens for CNS infectious diseases, and the recent literature provides guidelines for the use of steroids in combination with appropriate antimicrobial therapy.
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PMID:Drug Insight: steroids in CNS infectious diseases--new indications for an old therapy. 1825 81


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