Thieme Mumenthaler, Neurology - part 2 ppt

Fig. 2.15a, b Chronic meningitis. The patient is a 49-year-old woman. The pathogenic organism could not be identified. a Coronal T1-weighted MRI withcontrast.b Axial T1-weighted MRI with contrast. Note the abnormal contrast enhancement in the meninges. Fig. 2.16a, b Acute bacterial meningitis. The patient is a 10-year-old boy. a Coronal T1-weighted MRI with contrast demonstrates sphenoid sinusitis (arrows) spreading in the epidural space under the left temporal lobe and causing meningitis by direct extension with involvement of the temporal lobe (arrow- heads). b T1-weighted MRI with contrast in acoronal section posterior to a shows a prob- able epidural empyema over the left temporal lobe (arrowheads). There is also extensive signal change in the left thalamus, probably due to an arterial infarction as a complication of meningitis. Infectious Diseases of the Brain and Meninges 85 Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. Prognosis The prognosis of acute bacterial men- ingitis depends on: the pathogenic organism, the severity of the infection, concomitant illnesses, the state of the immune system, and the typeoftreatmentandtimeat which it is instituted. Mortality is highest in the newborn (over 50%). Meningitis accompanied by meningococcal sepsis also confers ahighmortality,because it is fre- quently complicated by bilateral ad- renal hemorrhage and subsequent circulatory collapse (Waterhouse- Friderichsen syndrome). The mortal- ity of other forms ofmeningitisisap- proximately 20% (1014). Surviving patients often suffer from permanent sequelae including deafness, malre- sorptive hydrocephalus, epilepsy, and intellectual deficits, particularly in children. Treatment (Fig. 2.17)(777a) If a lumbar puncture cannot be per- formed immediately because of clinical signs of intracranial hyper- tension, “blind” parenteral antimi- crobial treatment should be initi- ated at once, as afewminutes may make the differencebetweenlifeand death. If the pathogenic organism is unknown, the antimicrobial treat- ment is chosen empirically (Ta- ble 2.23). It can then be modified in accordance with the findings of the cerebrospinal fluid and blood cul- tures, including sensitivity and re- sistance testing. The duration of treatment is based on the findings of serial clinical ex- amination and cerebrospinal fluid analysis. Some general recommen- dations are: for meningococci and H. influen- zae, 7–10 days; for pneumococci, 10–14 days; for Listeria and Gram-negative aerobes, 3 weeks. Steroids (dexamethasone 0.4 mg/kg every 12 hours in thefirst2daysof treatment) favorably affect the course of the inflammatory process in children and probably also in adults, and should be given inaddi- tion to antimicrobial agents (560, 83 1). 86 2DiseasesMainlyAffecting the Brain and its Coverings Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. Suspicion of meningitis Papilledema or focal neurologic deficits Specific antibiotic treatment Gram stain, antigen tests, cultures Immediate empirical antibiotic treatment Meningitis confirmed, or normal; no evidence of intracranial hypertension Blood cultures CT or MRI Other diagnosis found Other specific therapy Other diagnosis Positive Positive Yes No Positive Blood cultures Lumbar puncture Lumbar puncture Diagnosis confirmed Immediate empirical antibiotic treatment Diagnosis not confirmed Fig. 2.17 Management flowchart for meningitis. The essential element of treatment is immediateinstitution of antimicrobial therapy, at first empirical and then tailored to the specific pathogen identified by culture. Infectious Diseases of the Brain and Meninges 87 Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. Table 2.23 Antimicrobial therapy of bacterial meningitis (824, 831, 836) Patient group Most likely organism Agent(s) of first choice 1 Alternatives Newborn Group B streptococci, E. coli, Listeria monocytogenes Ampicillin and cefotaxime 2 Ampicillin and aminoglycoside Infants 1–3 months Same and H. influenzae, menin- gococci, pneumococci Ampicillin and ceftriaxone or cefotaxime Chloramphenicol and aminogly- coside Infants 3months, toddlers H. influenzae, meningococci, pneumococci Ceftriaxone or cefotaxime Chloramphenicol and ampicillin Children and adults Pneumococci, meningococci, Listeria monocytogenes Ceftriaxone or cefotaxime and ampicillin or penicillin G Chloramphenicol and ampicillin, vancomycin if penicillin- resistant Adults 60 years, alcoholics, patients with systemic disease Pneumococci, E. coli, Haemophi- lus influenzae, Listeria monocyto- genes, Pseudomonas aeruginosa, anaerobes 3 Vancomycin andceftriaxone 2 and rifampicin Chloramphenicol and trimethoprim-sulfamethoxazole Traumatic brain injury, neurosurgical procedures Staphylococcus aureus, E. coli, Pseudomonas aeruginosa, 4 pneumococci Vancomycin andceftriaxone Cerebrospinal fluid leak Pneumococci Cefotaxime or ceftriaxone 1Unless otherwise specified, these recommendations are applicable to themostlikely pathogens affecting the group of patients in ques- tion. If the responsible pathogen is known, the treatment should be correspondingly tailored. Dosages may be found in drug compendia. 2Orother (third-generation) cephalosporin. 3Chloramphenicol or metronidazole. 4Addgentamicin. 88 2DiseasesMainlyAffecting the Brain and its Coverings Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. Fig. 2.18 Tuberculousmeningitis. This contrast-enhanced T1-weighted MR image reveals enhancement of the in- flamed meninges at the basal cisterns and anterior to the brainstem. The asymmetri- cal extension of inflammation along the course of the middle cerebral artery is also typical. Prevention The administration of Haemophilus vaccine to infants confers 90% protec- tion against this type of meningitis. Inoculation against the meningococ- cus isrecommendedfortravelersto endemic areas. After exposure to Haemophilus or meningococcus, anti- microbial prophylaxis is recom- mended (10 mg/kg in children or 600 mg in adults, b.i.d. for 2 days). Tuberculous Meningitis (1051) Mycobacterium tuberculosis causes a chronic bacterial infection character- ized by granulomaformation. The lung is usually affected. The menin- ges may become involved during the primary infection in children, or years afterward in adults. Meningitis comes about by reactivation of clinically si- lent granulomas and secondary de- posits in the subarachnoid space, even in the absence of simultaneous pulmonary tuberculosis. HIV-positive persons are at particularly high risk of infection both by M. tuberculosis and by atypical mycobacteria. Pathological Anatomy An exudative basilar meningitis and vasculitis is found, particularly in the vicinity of the anterior and middle ce- rebral art eries. Meningeal involve- ment and vasculitis may lead to cra- nial nerve deficits and to cerebral in- farction. Hydrocephalus is commonly seen. Clinical Features Over the course of several days or, more rarely, weeks,thesepatientsex- hibit progressive symptoms and signs including subfebrile temperature, fatigue, depression, personality changes, and (sometimes) confusion. One-third of patients develop head- ache, meningism, asymmetrical cra- nial nerve deficits, and ischemic stroke. Coma is a badprognosticsign. For miliary tuberculosis, see p. 91. Diagnosis Cerebrospinal fluid examination re- veals a picture of c hronic meningeal inflammation with at first granulo- cytic and then monocytic pleocytosis of 100–500 cells, elevated protein concentration, and low glucose con- centration. The diagnosis is con- firmed by the demonstration of acid- fast bacilli by the Ziehl-Neelsen method or with auramine– rhodamine staining, either in the fresh cerebrospinal fluid sample or after 4–6 weeks o f culture. Infectious Diseases of the Brain and Meninges 89 Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. In addition to the cerebrospinal fluid, the sputum, gastric juice, and urine should be examined and cultured for acid-fast bacilli. Contrast-enhanced CT and MRI reveal meningeal involve- ment at the skull base and along the course of the middlecerebralartery (151) (Fig. 2.18). Differential Diagnosis The differential diagnosis includes all types of chronic lymphocytic menin- goencephalitis (see below). Treatment The treatment consists of a combi- nation of four tuberculostatic medi- cations: rifampicin, isoniazid, pyra- zinamide, and ethambutol. At the same time, steroids and vitamin B 6 should be given. The latter pre- vents t he pyridoxine deficiency that may otherwise result from long-term use of isoniazid. This therapy should be continued until the resultsofcultureare available. If culture is positive for tubercle bacilli, acombination of three medications is given for a fur- ther 2 months, and then two medi- cations for 8–10 months more. Once the culture results are nega- tive and the cerebrospinal fluid pic- ture has renormalized, treatment may be discontinued. If the patient fails to improve on this regimen, other etiologies of chronic meningitis should be sought, and, even if cultures for M. tuberculosis are negative, it is pru- dent to continue the tuberculo- static therapy. The currently used tuberculostatic agents have only minor side effects even in long- term use. Prognosis Tuberculous meningitis isfatal if un- treated, curable without sequelae if treated in time. The diagnosis should be made, and treatment initiated, before the onset of cranial nerve defi- cits or of impaired consciousness. Thus: when tuberculous meningitis is strongly suspected, obtain fluid sam- ples for culture and then begin antitu- bercular therapy immediately. Meningoencephalitis Listeriosis (957, 959, 695b) Listeria are aerobic or facultatively anaerobic bacilli that are usually in- gested orally in food. They preferen- tially infect the newborn, diabetics, alcoholics, and aged or immune- suppressed persons. The clinical pic- ture is generally that of a typical bac- terial meningitis, but the cerebrospi- nal fluid cell count may be so low as to arouse suspicion of viral meningi- tis. Listeria also causes encephalitis, often withbrainstemmanifestations, as well as meningoencephalitis and cerebral or spinal abscesses (Fig. 2.19). Treatment The antimicrobial agents of first choice are ampicillin and penicillin G. An alternative is trimethoprim/ sulfamethoxazole.Cephalosporins do not eliminate Listeria. Brucella Meningitis (127) Brucellosis is transmitted in milk or other animal products and usually presents nonspecifically with fever, arthralgias and myalgias, though it causes localized disease in some cases, and its manifestations are sometimes restricted to the central 90 2DiseasesMainlyAffecting the Brain and its Coverings Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. Fig. 2.19 Listeria meningoencephalitis. A45-year-oldwomanwithmultiplecranial nerve deficits and left ataxia. a The FLAIR sequence reveals a plate-like signal abnormality in the brainstem and left cer- ebellar hemisphere. b The T1-weighted image shows several foci of contrast enhancement. Fig. 2.20 Miliary tuberculosis. A28-year-oldwomanwith miliary tubercu- losis. Cerebrospinal fluid examination re- vealed a mild monocytic pleocytosis, a markedly elevated protein concentration, and a low glucose concentration. The MRI reveals multiple pinhead-sized foci of con- trast enhancement in the brain paren- chyma and mild contrast enhancement of the meninges as well. nervous system. These usually consist of subacute or chronic meningitis, more rarely meningoencephalitis, myeloradiculitis or neuritis. Twenty to 500 cells are found in the cerebrospinal fluid. The diagnosis is confirmed by the demonstration of specific antibodies in the CSF. Treatment The treatment consists of doxycy- cline and rifampicin for 4 months, with surveillance of the cerebrospi- nal fluid. Meningoencephalitis in Miliary Tuberculosis In miliary tuberculosis, hematoge- nous spread of tubercle bacilli leads to the formation of millet-seed-sized granulomas throughout the body. The clinical manifestations are not spe- cific to this disease but rather reflect Infectious Diseases of the Brain and Meninges 91 Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. the predominantly involved organ(s). Symptoms and signs may include fe- ver, night sweats, anorexia, general- ized weakness and fatigue, hepato- splenomegaly, lymphadenopathy, and (if the brain is affected) headache and progressive impairment of con- sciousness. Miliary tuberculosis usually affects the brain parenchyma more than the meninges. The cere- brospinal fluid findings are the same as for tuberculous meningitis, except that pleocytosis is usually only mild. MRI reveals multiple pinhead- sized, contrast-enhancing nodules (Fig. 2.20). For diagnosis and treatment, see “Tu- berculous meningitis,” abov e (p. 90). Focal Embolic Encephalitis (148, 315, 819) Neurological symptoms and signs de- velop in at least one-third of patients with infectious endocarditis and may be the presenting manifestations of the disease. Streptococcus is the most common pathogen, followed by staphylococ- cus and Gr am-negati ve bacilli. Cen- tral nervous manifestations arise by several different pathogenetic mecha- nisms: occlusion of cerebral arteries by septic and thrombotic emboli aris- ing from heart valve vegetations; infection of the meninges, brain parenchyma, or vascular walls by septic emboli or by bacteremia; “toxic” and probably also immune- mediated injury. Pathological Anatomy There may be blandorhemorrhagic cerebral infarcts, intracerebral, sub- arachnoid or subdural hemorrhage, meningitis, abscesses, mycotic aneu- rysms, or anycombination of these entities. Clinical Features The symptoms and signs depend on the pathological processes occur ring in each individual case. Embolic events are prominent in 20% of cases, encephalitis due tomultiplemicro- emboli a nd microabscesses in 10%, hemorrhage due to mycotic aneu- rysms in 5%, and meningitis in 5%. Emboli produce focal manifestations, while the other types of lesion cause adiffuse encephalopathy with behav- ioral and cognitive disturbances, im- pairment of consciousness, focal or generalized seizures, andsometimes headache and meningism. Important diagnostic clues include subfebrile or (in acute endocarditis) septic temper- ature, a feeling of severe illness and prostration, anemia, splenomegaly, subungual, palmar and r etinal pete- chiae, andheartmurmur. Diagnosis The completebloodcountreveals acute inflammation, and the erythro- cyte sedimentation rate and C- reactive protein are elevated. The re- sponsible organismcanusually be demonstrated by blood culture, and endocarditis by transesophageal echo- cardiography (212). The cerebrospinal fluid may be sterile, purulent or hem- orrhagic, depending on the nature of CNS involvement (772). MRI is particularly useful for the demonstration of embolic and infec- tious processes affecting the central nervous system. Angiography is the most reliable waytodemonstrate mycotic aneurysms,butneednot be performed routinely in every patient (819). 92 2DiseasesMainlyAffecting the Brain and its Coverings Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. Treatment The most important initial step is the prompt institution of empiric antimicrobialtreatment.Penicil- linase-resistant penicillins (e.g., flu- cloxacillin or methicillin) are given together with gentamicin until the results of culture are available, whereupon the treatment can be specifically tailored. Vancomycin should be given with gentamicin initially whenever the presence of penicillinase-resistant staphylococ- cus islikelyonclinicalgrounds(e.g., in intravenous drug users and pa- tients with artificial heart valves). If emboli continue to form despite antimicrobial treatment, surgical heart valve replacement may be necessary. Anticoagulants should be withheld till at least 48 hours after the procedure, unless the infected valve is itself a previously i m- planted prosthesis, in which case anticoagulation should generally not be interrupted. Mycotic aneurysms pose a special problem. Many regress spontane- ously under antimicrobial therapy, but persistent aneurysms may need to be obliterated neurosurgically (722) or by endovascular treatment. Encephalitis Whipple’s Disease Pathological Anatomy This is a bacterial infection of the in- testinal mucosa, mesenteric lymph nodes, and reticuloendothelial sys- tem. The responsible pathogen, Tro- pheryma whippelii,generally cannot be cultured. Clinical Features The manifestations include arthral- gias, diarrhea, intestinal malabsorp- tion and weight loss. Some 40% of pa- tients show neurological signs, which are the sole finding in 5%. These con- sist of a progressive encephalopathy with personality changes, apathy, memory impairment, and cognitive deficits that may reach theseverityof dementia. Extrapyramidal signs, ataxia, ophthalmoplegia, and hypo- thalamic dysfunction may also be found. Oculomasticatory myorhyth- mia with a frequency of 1 Hz is char- acteristic. Diagnosis These clinical signs are the conse- quence of aperivascularnodularen- cephalitis that is well seen in CT and MRI. The cerebrospinal fluid may be normal, or there may be pleocytosis of up to 200 cells/ Landanelevated protein concentration of up to 2 g/L. The diagnosis rests on the demon- stration of PAS-positive material in the mucosa of the small intestine or (in cases of isolated CNS disease) in the brain. Treatment Clinical improvement follows treatment with trimethoprim- sulfamethoxazole (Bactrim), which must be given for 1 year. Focal Purulent Infections Brain Abscess Abrainabscessisafocal purulent process in t he brain parenchyma. These rarely occurring lesions are found more commonly in persons with HIV (see p. 117), bronchiectasis, hereditary hemorrhagic telangiecta- sia (Osler-Weber-Rendu disease), or congenital heart anomalies with a right-to-left shunt. Infectious Diseases of the Brain and Meninges 93 Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. Pathogenesis, Sites and Responsible Organisms Approximately one-half ofbrainab- scesses arise by contiguous spread of infection, generally from otitis media or sinusitis; the means of spread is hematogenous in a further one- quarter of cases, and undetermined in the remainder. Dental abscesses are found in 10% of patients. Direct inoc- ulation of pathogens into the brain is relatively rare. Abscesses are multiple in 10% to 50% of cases (the numbers in published series vary).Hematoge- nous abscesses are commonly found at the junction of gray and white matter in the territory of the middle cerebral artery, but may be anywhere in the brain. The source of infection is commonly the lungs, abdomen, pel- vis, or bones (osteomyelitis). Tempo- ral lobe abscesses most commonly re- sult from otitis media, mastoiditis, and sphenoidsinusitis,andfrontal lobe abscesses fromfrontaland eth- moidal sinusitis or dental abscess. Cerebellar abscesses are otog enic in 90% of cases. Two-thirds of the re- sponsible organisms are aerobic, and one-third anaerobic; different flora are typically associated with each source of infection. In general, strep- tococci, Gram-negative bacilli, and Staphylococcus aureus are the most common aerobes, and Bacteroides sp. and streptococci the most common anaerobes. Some 30–60% of ab- scesses contain mixed flora (two or more species). Pathology An abscess develops through succes- sive stages of early and late cerebritis followed by early and late capsule formation. At first, there is cerebritis with a necrotic focus, marked edema, and a perifocalzoneofinflammation. Table 2.24 Differential diagnosis of ring- enhancement on CT and MRI Primary brain tumor Metastasis Abscess Granuloma Hematoma in the process of being re- sorbed Infarct Thrombosed arteriovenous malformation Thrombosed aneurysm Plaque of demyelination The focus then becomes demarcated as surrounding neovascularization and f ibrosis gradually lead to the for- mation of a capsule. Over the course of several weeks or months, the ne- crotic center is replaced by granula- tion tissue and correspondingly shrinks in size. An abscess may also give rise to satellite abscesses or rup- ture into a ventricle or the subarach- noid space, causing an acute ventri- culitis or meningitis. Neuroradiology The stages of abscess development can be followedwithCTorMRI (282). CT initially shows a poorly de- marcated area of hypodensity with diffuse contrast enhancement. The central hypodense zone is sur- rounded by edema with consequent mass effect. Later, ring-enhancement appears and the abscess capsule be- comes visible in the nonenhanced views aswell.OntheMRI,cerebritis is T2-hyperintense and enhances dif- fusely with contrast. Necrosis and edema are hypointense on T1- and hyperintense on T2-weighted ima- 94 2DiseasesMainlyAffecting the Brain and its Coverings Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. [...]... during which the virus mul- Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms and conditions of license 118 Table 2. 34 2 Diseases Mainly Affecting the Brain and its Coverings Revised CDC classification of HIV infection CD4+ Clinical stage T-lymphocyte count A X 20 0/ ‘ L Table 2. 35 Clinical manifestations are present, but neither A nor B symptoms AIDS-defining clinical manifestations... confluent The overlying gray matter is thinned but usually of normal signal intensity Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms and conditions of license 104 2 Diseases Mainly Affecting the Brain and its Coverings Treatment Fig 2. 22 Progressive multifocal leukoencephalopathy A 75-year-old man with leukemia and cortical blindness The signal change in the white matter... cerebrospinal fluid examination usually reveals a chronically inflammatory picture (p 84 and Table 2. 22) , which may be only mild in the presence of Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms and conditions of license 108 2 Diseases Mainly Affecting the Brain and its Coverings Table 2. 32 Fungi causing CNS infections, in order of frequency (after Bell and McGuinness, 80) In... b Fig 2. 23a, b Cerebral cysticercosis a Parasagittal T1-weighted image Two cysts are visible as hypodense areas in the parietal lobe A larva can be seen in the larger cyst b Axial T2-weighted image Two cysts can be seen as areas of increased signal lateral to the left posterior horn Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms and conditions of license 110 2 Diseases... Viruses (344) The family of herpes viruses includes: > herpes simplex virus, types I and II (HSV-I and HSV-II), > varicella-zoster virus (VZV), > cytomegalovirus (CMV), and > Epstein-Barr virus (EBV) Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms and conditions of license 1 02 2 Diseases Mainly Affecting the Brain and its Coverings Herpes simplex encephalitis Herpes simplex... serves as a barrier between the supra- and infratentorial compartments Epidural abscesses cannot spread across the cranial sutures Both of these types of infection usually arise as complications of sinusitis Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms and conditions of license Antimicrobial therapy of brain abscess ( 824 , 836) 96 Table 2. 26 Probable organism Treatment... headache, and meningism These are Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms and conditions of license 100 2 Diseases Mainly Affecting the Brain and its Coverings Table 2. 28 Clinical manifestations of viral encephalitis (1 021 ) Manifestation Frequency (%) Impairment of consciousness 97 Fever 87 Personality change 81 Headache 79 Dysphasia 72 Autonomic dysfunction 58 Ataxia... roentgenogram should be obtained in every patient Cutaneous lesions may point to the correct diagnosis in borreliosis, sar- Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms and conditions of license Infectious Diseases of the Brain and Meninges Table 2. 29 27 2) 105 Common etiologies and differential diagnoses of chronic meningitis (after Infectious > Bacterial and mycobacterial... malresorptive hydrocephalus Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms and conditions of license 1 12 2 Diseases Mainly Affecting the Brain and its Coverings | Cerebrovascular Syphilis ( 426 ) Cerebrovascular syphilis produces a marked inflammation of the meninges and cerebral blood vessels, leading to infarction, usually in the distribution of middle-sized arteries Infarction... (Weil disease due to Leptospira icterohaemorrhagiae) Treatment (21 5) Acute neuroborrelioses are treated parenterally with ceftriaxone (2 g i.v./day), cefotaxime (2 g i.v t.i.d.), or penicillin G (20 24 million units i.v./day) for 2 weeks Lymphocytic meningoradiculitis may also be treated with doxycycline 100 mg p.o b.i.d for 2 weeks (4 92) Chronic neuroborreliosis requires at least 3–4 weeks of treatment . Meninges 103 Mumenthaler, Neurology © 20 04 Thieme All rights reserved. Usage subject to terms and conditions of license. Fig. 2. 22 Progressive multifocal leu- koencephalopathy. A75-year-oldman with. telangiecta- sia (Osler-Weber-Rendu disease), or congenital heart anomalies with a right-to-left shunt. Infectious Diseases of the Brain and Meninges 93 Mumenthaler, Neurology © 20 04 Thieme All. II (HSV-I and HSV-II), varicella-zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus ( EBV). Infectious Diseases of the Brain and Meninges 101 Mumenthaler, Neurology © 20 04 Thieme All