Journal ofNeurology, Neurosurgery, and Psychiatry, 1979, 42, 1038-1045

Nocardia cerebral abscess: new concepts in diagnosis,management, and prognosisE. BYRNE, B. P. BROPHY, AND L. V. PERRETT

From the Neurology and Neurosurgery Units, Royal Adelaide Hospital, Adelaide, South Australia

S U MM A R Y Three cases of multiple cerebral nocardial abscess are presented. All were cured bya combination of chemotherapy and surgery, a unique experience. Early detection, appropriatechemotherapy, absence of underlying immune malfunction, and surgically remediable diseaseare good prognostic indices in cerebral nocardiosis. If other adverse prognostic factors are absent,however, multiple abscess formation does not preclude the possibility of cure. Accurate localisa-tion of nocardia cerebral abscesses by computerised axial tomography is a great help inmanagement if multiple lesions are present.

Cerebral nocardiosis is an uncommon and usuallyfatal infection, some 50 cases having been docu-mented of whom only one-fifth have survived.Krueger et al. reviewed the literature in 1954 andnoted that of 18 cases of cerebral nocardiosis re-ported to that date, only one, a case of meningitis,had survived the illness. Occasional cures havebeen reported since then but have not been suffi-ciently frequent to dim the pessimistic prognosisusually given to cerebral nocardiosis. Nocardialorganisms are opportunistic pathogens whichusually produce infection in immunocompromisedhosts, and 75% of cases in the United States occurin this group (Beaman et al., 1976). Cerebral no-cardiosis occurs less commonly in patients with anintact immune system who do not have an under-lying disorder, such as disseminated carcino-matosis, which is likely to prove fatal in itself.Prognostic information in this group is limitedand the main purpose of this report is to clarifythis area. Our recent experience with cerebral no-cardiosis is presented in which three cases all withmultiple abscess cavities survived the illness. Thesecases, together with the other published reportsof cured nocardia cerebral abscess, are analysedand favourable prognostic features reviewed.

Case reports

CASE 1A 44 year old Caucasian man was admitted to theAddress for reprint requests: Dr E. Byrne, Neurology Unit, RoyalAdelaide Hospital, North Terrace, Adelaide, South Australia 5000.Accepted 17 April 1979

Royal Adelaide Hospital under the care of MrT. A. R. Dinning for investigation of focal seizuresinvolving his right face, impairment of speech, andright faciobrachial weakness all of recent onset.He had a past history of chronic bronchitis and hada heavy alcohol intake. He was afebrile and ab-normal findings were confined to the centralnervous system. A mild right hemiparesis andfacial weakness were noted. There was no papil-loedema or evidence of meningism.Blood haemoglobin level was 13.5 g/dl, white

blood count 10 000 cells/mm3, erythrocyte sedi-mentation rate 93 mm/hour. Liver function testswere normal. Chest radiography showed consoli-dation in the anterior segment of the right lowerlobe but no organism was cultured from thesputum. A nuclear brain scan (99Tc) showed anincreased uptake of radionuclide in the leftparietal area. Left carotid angiography andpneumoencephalography were considered to bewithin normal limits. A provisional diagnosis ofleft parietal neoplasm was made and craniotomyundertaken (surgeon Mr J. B. North). At opera-tion an abscess cavity was found and aspirated, anda subtemporal decompression carried out. Nocardiaspecies were identified in the aspirate so sulpha-diazine 1 g six hourly was started immediately.Dysphasia and hemiparesis remitted completelywithin six weeks. Chemotherapy was stopped aftersix months. He presented again one year after thecessation of sulphadiazine with paresis of the leftleg. Isotope brain scan (99Tc) showed a smallright parasagittal focus of nuclide uptake andsome enlargement of the original left parietal

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focus. This was attributed to extension of theNocardia asteroides infection and sulphonamidetherapy was restarted and maintained for fouryears. Serial brain scans showed a steady decreasein the size of both lesions, and four years laterthe isotope brain scan was completely normal.Paresis of the left leg rapidly improved. Thepatient continued to drink alcohol heavily anddied six years after presentation. At necropsy themeninges were adherent to the left cerebral cor-tex and reactive gliosis was noted at the site of theoriginal abscess cavity. No evidence of persistentnocardia infection was found on histologicalexamination. Gross cardiomegaly was noted, anddeath was attributed to congestive heart failureprobably related to abuse of ethanol.

CASE 2A 43 year old Caucasian woman was admitted tothe Royal Adelaide Hospital under the care ofthe Professorial Medical Clinic and subsequentlytransferred to the care of Mr T. A. R. Dinning. Shehad a three week history of continuous headache,nausea, and vomiting, and over the week pre-ceding referral had developed a progressive righthemiparesis. She had a heavy alcohol intake anda past history of treated hypothyroidism. A mildpleuritic illness four months earlier had been fol-lowed by malaise, weight loss, and night sweats.Chest radiography at that time was said to showconsolidation of a lung.On admission she was febrile (38.80C), dis-

orientated in time and place, and had mild men-ingism. Severe expressive dysphasia and righthemiparesis were noted. Both plantar responseswere extensor. The chest was clinically clear.

Initial investigations showed a haemoglobinlevel of 14 g/dl and white blood count of 10 500cells/mm3. A chest radiograph showed consolida-tion in the posterior basal segment of the leftlower lobe. Plain skull radiographs were normal.Computerised axial tomography of the head re-vealed multiple low density lesions with enhancingperipheries consistent with multiple abscess cavi-ties although metastases were also considered(Fig. 1). A lumbar puncture was performed usinga small needle. Turbid CSF was encountered with580 lymphocytes, 310 polymorphonuclear cells,and 10 red blood cells/mm3. The CSF protein was1.17 g/l and glucose 3 mmol/l. Cultures of CSFwere negative after two days, and empirical treat-ment with penicillin and chloramphenicol wasbegun.

Further investigation was started. Bronchos-copy (Dr R. Antic) revealed mucosal oedema atthe orifice of the left posterior basal bronchus.

(a

(I?

Fig. 1 Multiple abscesses in left parietal (a) and rightoccipitoparietal region (b). The ring shadows arecaused by enhancement of the capsules and aresurrounded by oedema, particularly the left sidedlesions. There is further oedema in the right frorntalregion above another abscess (cut not shown).

No endobronchial lesion was seen. Mucosal biopsysamples were taken and the posterior basal bron-chus brushed and washed. Examination of thehistology revealed small numbers of branchingGram positive filamentous hyphae which wereacid fast. Nocardiosis was diagnosed with reason-able certainty, and co-trimoxazole, six tablets perday, begun. After a week of treatment no definite

F

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improvement was noted, and high fever recurred.A left parietal burrhole was cut, and at a depthof 70 mm a small quantity of pus was aspiratedwhich contained nocardia organisms. Intraventri-cular dissemination of pus complicated the pro-cedure, and the patient's conscious state deterio-rated postoperatively. A ventricular catheter wasinserted and an Ommaya reservoir attached thenext day. Intraventricular gentamycin 8 mg dailywas given for a week. The patient's consciousstate deteriorated further over the next week untilshe was unresponsive to oral commands. Bio-chemical studies suggested a syndrome of inappro-priate secretion of antidiuretic hormone with theserum sodium falling to 120 meq/l. Fluid restric-tion to 500 ml/day resulted in rapid improvementin serum biochemistry and in conscious state. Oneweek later, the patient again became deeplycomatose. Repeat CAT scan demonstrated a largehaematoma in the right frontal region along thecatheter tract (Fig. 2). This was decompressedsurgically (Mr P. G. Carney) and later the encapsu-lated haematoma was totally excised. Co-trimoxa-zole therapy was continued and over the nextmonth the patient gradually became more alert.Serial CAT scans (Fig. 3) showed resolution ofremaining cerebral abscesses but communicatinghydrocephalus developed and the insertion of apermanent shunt was necessary. Further immuno-logical studies, including T cell function tests,revealed no abnormality of cellular or humoralimmunity.

Fig. 2 One month later. The ventricular system hasenlarged and there is a large right frontal haematomawhich has extended into the right lateral ventricle.There is extensive frontal oedema around thehaematoma and shift of midline structure to the left.

.... ., , ,

Fig. 3 Three months after admission. Furtherventricular enlargement has occurred withdisplacement to the left by right frontal and temporo-parietal surface fluid collections. There is only a smallarea of residual enhancement above the body of theleft lateral ventricle.

The patient is well eight months after herpresentation and is living with her family in arural area. Co-trimoxazole therapy will be con-tinued for two years.

CASE 3A seven year old Caucasian boy was admitted tothe Adelaide Children's Hospital and subsequentlytransferred to the care of Mr D. A. Simpson. Forone week previously he had noted clumsiness in theleft hand. A fluctuant abscess in the right buttockwas drained, and the pus reported to be sterile.One year earlier he had had a febrile illness diag-nosed as viral meningoencephalitis. For sixmonths before presentation he had complained ofheadache, backache, and intermittent visualdisturbance.

Examination on admission revealed gross bi-lateral papilloedema with concentric constrictionof the left visual field and diminished vision in theright eye with perception of hand movements only.Left hemiparesis and left sided sensory ataxiawere decumented. The left plantar response wasextensor. A chest radiograph was normal. Anechogram demonstrated shift of the brain to theleft, and on electroencephalography a slow wavefocus in the right parietal region was noted. Aright parietal burrhole (Mr D. A. Simpson) was cut,and an encapsulated abscess was found. Two milli-litres of yellow pus were aspirated and found tocontain Nocardia asteroides. A left frontal burr-

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hole was cut under the same anaesthetic in anendeavour to reduce the intracranial pressure andenable a right osteoplastic craniotomy to be per-formed more easily. A second abscess in the leftfrontal area was found while attempting to tapthe left frontal horn. After an infusion of urea,a large right lateral decompression was carriedout. Sulphadiazine was continued postoperativelybut over the next eight weeks the right lateraldecompression increased in size and left hemi-paresis worsened. Pneumoencephalography demon-strated an indentation in the left frontal horn andevidence of a much larger mass in the rightfrontoparietal area. An attempt was then made toenucleate the right sided abscess. At operationfour abscesses were found in the right hemisphere,extending from the parietal area to the frontalpole. All were removed, a number of major middlecerebral vessels being sacrificed during the pro-cedure. Postoperatively the patient made an excel-lent recovery and the left frontal abscess resolvedwith long-term sulphadiazine therapy. Consider-able sensory and motor deficit, however, has per-sisted in the left arm and the left hand is oflimited functional utility. A titanium cranioplastywas performed two years later, and review fouryears after presentation showed the patient to bein good health.

Discussion

As survival in patients with cerebral nocardiosisis unusual, it is surprising that no fatalities wereencountered in three cases recently treated. In thefirst case, aspiration of the abscess coupled withsulphonamide therapy produced an excellentinitial response. Relapse occurred one year afterdiscontinuation of sulphonamide drugs, confirm-ing the sometimes indolent nature of cerebralnocardial infection and the need for a prolongedcourse of antimicrobial treatment. Fortunatelyreinstitution of sulphonamides led to rapid resolu-tion of symptomatology and normalisation of thetechnetium brain scan. It is possible that a neuro-surgical approach could have been avoided in thiscase if efforts to isolate an organism from the lunghad been successful.

In the second case, an attempt to needle one ofthe abscess cavities led to intraventricular dis-semination of organisms, nocardial meningitis,and later communicating hydrocephalus. Accumu-lation of a haematoma around the ventricularcatheter tract, necessitating drainage, was anadditional complication. Meanwhile continuedantimicrobial therapy led to resolution of residualabscess cavities. In retrospect, it is possible that

in this case surgery may have been prematureand some added disability resulted from it. Theinvaluable information provided by computerisedaxial tomography (CAT) scanning of the head isexemplified by this case. Widely disseminatedmultiple lesions were apparent on the first scan,discouraging any attempt at radical surgical re-moval. Cerebral haemorrhage and later hydro-cephalus were identified early by CAT scanning,enabling definite treatment to be undertaken with-out delay. It is possible that this patient would nothave survived without the accurate serialvisualisation of pathology provided bytomodensimetry.Advanced intracranial hypertension with visual

loss in our third case necessitated early surgicaldecompression and partial excision of the abscesscavities. A residual left frontal abscess resolvedcompletely with antimicrobial drugs. Symptomsof intracranial infection were present in thispatient for at least six months before presentationand it is possible that earlier diagnosis and in-stitution of sulphonamides might, in view of theexcellent response eventually made, have reducedthe residual disability. It is essential that thediagnosis of nocardiosis be established as early aspossible, enabling time for a reasonable trial ofchemotherapy to be given before intracranialhypertension necessitates radical neurosurgicalintervention.

It is constructive to review the clinical featuresof the three cases presented here and of 13 othersurviving cases of cerebral nocardiosis reportedin the literature (Table) and to contrast these withsome fatal cases. With two exceptions, all surviv-ing cases received antimicrobial therapy specificfor nocardia organisms. One case with unusualantimicrobial susceptibility received only peni-cillin and aureomycin (Krueger et al., 1954), andone penicillin and streptomycin (Munslow, 1954).There is no doubt that the latter cass sufferedfrom nocardiosis and not from actinomymosis,and presumably surgery rather than penicillintherapy was curative in each. Where it is re-corded, the duration of sulphonamide therapy hasvaried from eight weeks to several years. The factthat cases given shorter courses do not relapseuniformly suggests that the indolence of cerebralnocardiosis is variable. None of the cured caseshad serious underlying disease such as lymphomaor carcinomatosis, a striking contrast with thefatal group. The extent of infection was relativelylimited in most of the cured cases. Seven did nothave clinically apparent pulmonary disease, whichis unusual as the lung is the usual portal of entryfor Nocardia asteroides (Frazier et al., 1975).

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1042 E. Bryne, B. P. Brophy, and L. V. Perrett

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Multiple cerebral abscesses, with the exceptionof the three cases documented here, are un-

common in cured cases and if preEent usuallyrepresent a major abscess with several satellitelesions. That our cases did survive, however, sug-

gests that although the prognosis in cases withmultiple dispersed cerebral abscesses is bad, it isnot uniformly hopeless if other bad prognosticindices are absent. Finally, all the cured cases

listed underwent a neurosurgical procedure. In themajority a single abscess amenable to radicalextracapsular excision was present, and thisoperation was performed. However, simple aspira-tion led to cure in one case (Turner and Whitby,1969), and our experience confirms that totalsurgical removal of all infected material is notalways necessary to achieve cure as this was notattempted in any of the three cases presented. Incases 1 and 2 sizeable abscess cavities were fol-lowed with 99Tc scans in one case and with CATscans in the second to complete resolution on

antimicrobial therapy.Consideration of some fatal cases of cerebral

nocardiosis enables ready contrast with the suc-

cessfully treated group. Often the diagnosis hasbeen made preterminally or at necropsy (Kruegeret al.. 1954) or specific chemotherapy has beenstarted only a few days before death (Pizzolatoet al., 1961; Lee et al., 1963). Some of the fatalcases did not receive any specific nocardial chemo-therapy even when a neurosurgical approach was

made on an abscess (Teleghani-Far et al., 1964).Stevens' case (1953) underwent several neuro-

surgical procedures but was not given sulphona-mides. In other cases, an inadequate course ofsulphonamides has been given after early diag-nosis, resulting in clinical relapse and death as intwo cases of Murray et al. (1961). As might be ex-

pected, therefore, the prognosis is poor in patientswho are diagnosed late in their course, in cases

who do not receive specific chemotherapy and incases in whom appropriate antimicrobial treat-ment is discontinued prematurely. Early diagnosisand appropriate treatment do not, however, en-

sure success (Turner, 1954). In reports of fatalcases the frequent occurrence of an underlyingillness with grave prognostic implications is strik-ing. Disseminated carcinomatosis is a common

finding. The case of Arroyo et al. (1977) had dis-seminated renal carcinoma, case 5 in Larsen'sseries had breast carcinomatosis (Larsen et al.,1959), and case 3 of Adams et al. (1971) hadHodgkin's disease. It has been estimated thatthree-quarters of all cases of nocardiosis inAmerica occur in immunodepressed hosts(Beaman et al., 1976), and it has been reported in

patients receiving steroid and cytotoxic therapyafter renal transplantation (Back et al., 1973a), andcardiac transplantation (Krick et al., 1975), inchronic granulomatous disease (Breed et al.,1948), dysgammaglobulinaemia (Neu et al., 1967),as well as complicating malignant disease (Younget al., 1971). It has been suggested that immuno-depression is a bad prognostic factor in nocardiainfections of any sort (Presant et al., 1973), andcertainly this is the case in cerebral infection.

In many fatal cases nocardial infection has beenwidespread, involving multiple organs (Carlile etal., 1963; Adams et al., 1971; Arroyo et al., 1977).Multiple cerebral abscesses are commonly foundin cases coming to necropsy (Stevens, 1953;Cupp et al., 1960; Murray et al., 1961; Shusteret al., 1967) or any abscess may involve vital brain-stem structures as in case 3 in the series of Adamset al. (1971). In one earlier report, complicatingsubdural haemorrhage proved fatal which todaymight have been diagnosed more rapidly withCAT scanning and treated effectively (Pizzolatoetal., 1961).Good prognostic features in cerebral infection

are, therefore, early diagnosis, administration ofappropriate chemotherapy, restricted disease and,most important of all, the absence of underlyingchronic illness. Although the outlook is better insurgically treatable cases, our personal series sug-gests that if the other favourable prognosticfeatures are present, widely disseminated intra-cranial disease does not preclude the possibility ofcure.

Diagnosis of nocardiosis may be difficult, asthe large number of cases identified at necropsytestifies, and can only be achieved by identifica-tion of organism in tissue sections or in culturemedia. Bacteriological pitfalls have been discussedelsewhere (Fetter et al., 1967). In the usual situa-tion where pulmonary and cerebral infectioncoexist, every effort should be made to obtaindiagnostic material from the lung. Bronchoscopy,percutaneous lung biopsy, and transtrachealaspiration may all be necessary (Frazier et al.,1975). Needling of a cerebral mass lesion in con-firmed pulmonary nocardiosis is not usually indi-cated for diagnosis and may be followed bymeningeal contamination as in our second caseand elsewhere (Turner, 1954; Kremer, 1972).

Accurate localisation of nocardia cerebralabscesses is a great aid in management if multiplelesions are present. In case 2 early CAT scanningshowed multiple abscesses and excluded radicalextracapsular excision as a practical therapeuticalternative. In case 3, by contrast, who wastreated before the CAT scan era, a left sided

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abscess cavity was encountered unexpectedly inthe process of an attempted ventricular tap. Com-puterised tomography also has the advantage thatit can be repeated easily, allowing close andaccurate radiological monitoring of the responseto therapy. In nocardia abscess, plane CAT scan

cuts usually show an area of decreased densityat the centre of the lesion. Sometimes the abscesscavity is visualised as a ring of increased densitybetween the low density centre and low densityoedema in the adjacent white matter. It isessential that intravenous contrast medium begiven after the plane cuts as more than 80% ofabscesses show a ring of enhancement (Schieferand Huk, 1976). If no enhancement occurs, pre-sumably a capsule has not yet been formed and theappearances are caused by a focal suppurativecerebritis. The case of nocardia abscess reportedby Lott et al. (1977) did not show a ring shadowbut contrast medium was not given. Three cases

described by Claveria et al. (1976) all showedenhancement, two with ring shadows and theother with multiple uniformly enhancing lesions.It is sometimes difficult to distinguish betweenabscess and glioma or metastases with scanning.An abscess generally has a smooth capsule ofuniform thickness as distinct from the more

irregular margin of a neoplasm. Also, the contentsof an abscess are usually of lower density thanthe central area of a necrotic glioma. SerialCAT scanning is the best way to follow patientswith intracranial abscess, however treated(Claveria et al., 1976), and enables the attendingphysician to monitor therapy more closely thanwas possible in the past.The best therapy in cerebral nocardiosis involves

a judicious use of antibiotics and of neurosurgicalintervention. Sulphonamides were the anti-microbial drugs of choice for many years andsome authors still dispute that more recentlydeveloped drugs offer any additional advantages(Goodman and Koenig, 1970; Krick et al., 1975).Minocycline which is useful in pulmonary in-fections (Back et al., 1973b) does not cross theblood-brain barrier easily and should not be usedalone in cerebral disease. Co-trimoxazole is now

the agent of choice in cerebral nocardiosis. Bothtrimethaprim and sulphamethoxazole diffusereadily across the blood-brain barrier, achievinghigh CSF levels (Maderazo and Quintiliani,1974). To ensure against the ever present risk ofrelapse, Goodman and Koenig (1970) suggest thatchemotherapy be continued for at least 12 monthsand the late relapse noted in case 1 supports thiscontention.

E. Bryne, B. P. Brophy, and L. V. Perrett

We wish to thank Mr T. A. R. Dinning, Mr D. A.Simpson, and Mr P. G. Carney for permission toreport these patients, and Dr J. F. Hallpike forhelpful advice in compiling this report.

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