a 63-year - old woman was assessed for rapid functional decline over 2 months , with cognitive impairment , multiple falls , incontinence , and dependence for most basic daily activities . medical history included stroke 10 months previously with mild residual left - sided weakness , depression , rheumatoid arthritis , and hypertension . she smoked heavily , did not abuse alcohol or injection drugs , and had never received blood products . medications included prednisone 5 mg daily , paroxetine , amlodipine , clopidogrel , estrogen , calcium , vitamin d , bromazepam , and acetaminophen . she was white and had spent all her life within the great lakes area of southern ontario . she had once worked in a plant manufacturing leather components for automobiles , and her husband worked briefly as a meat packer . she did not consume raw meat and had no contact with livestock but used sheep manure in her garden . cognitive testing showed impaired abstract thinking , memory , and attention but no affective or psychotic disturbance . complete blood count , blood urea nitrogen , creatinine , electrolytes , calcium , alkaline phosphatase , bilirubin , thyroid - stimulating hormone , and serum b12 were normal . g / l ) , serum glutamic oxaloacetic transaminase 54 u / l ( normal 540 u / l ) , serum glutamic pyruvate transaminase 58 u / l ( normal 540 u / l ) , and erythrocyte sedimentation rate 74 mm / h . serum antinuclear antibodies , extractible nuclear antibodies , antineutrophil cytoplasmic antibodies , venereal disease research laboratory test , and complement levels were unremarkable . serologic tests for hepatitis b and c and enzyme - linked immunosorbent assay for hiv were negative . electroencephalograph ( eeg ) demonstrated intermittent irregular slow delta waves in the right frontal and left temporal regions but no biphasic or triphasic waves . magnetic resonance scan of the brain showed multiple areas of remote and recent infarction involving right frontal cortical and subcortical regions , pons and cerebellum , and right parasagittal frontal cortex . a diagnosis of recurrent strokes was made , but she continued to decline after discharge to a rehabilitation hospital . a lumbar puncture obtained shortly before her death showed cerebrospinal fluid ( csf ) glucose of 4.8 g / l ) , and 8 x 10 lymphocytes / l with no malignant cells . protein 14 - 3 - 3 ( centre for research in neurodegenerative disease at the university of toronto ) was present in the csf . the brain weighed 1,530 g. the circle of willis was normal with no atheroma or occlusions . external examination showed focal areas of yellow exudate on the convexities and multiple bilateral infarcts affecting the cortices , pons , thalamus , middle temporal gyrus , and putamen . histologically , some infarcts were bland while others were associated with a thick exudate characterized by granulomatous inflammation with caseation necrosis and foreign body numerous vascular occlusions with no atheroma were noted ( figure 2 ) . a proliferative endarteritis was observed . in some areas , gram stains , fungus stains , and prion protein immunostains ( 3h4 , prionics , zurich , switzerland ) were negative . a moderate degree of diffuse arteriolosclerosis was observed . is surrounded by a mononuclear cell infiltrate ( occipital lobe , x250 , stained with hematoxylin and eosin  luxol - fast blue ) . the residual lumen is almost completely occupied by recent thrombus ( frontal lobe , x160 , stained with hematoxylin and eosin  luxol - fast blue ) . broad - range pcr identification was performed on frozen brain tissue by using the modified method of heritz et al . pcr ( perkinelmer , foster city , ca ) and lysis buffers were pretreated with 8-methoxypsoralen at a final concentration of 25 g / ml and exposed to long - wave ( 360 nm ) uv light for 15 min to destroy preexisting dna contaminants . tissue samples ( approximately 2 mm ) were lysed in 50 l 1x pcr buffer containing 1% polyoxyethylene 10 lauryl ether and 200 g / ml proteinase k at 56c overnight . lysate , in 1- and 5-l aliquots , was used as template for pcr amplification with universal primers for bacterial 16s rdna ( 515fpl and 13b ) . pcr mixture without lysate was used as a negative control , and a cloned 16s rdna amplification product was used as a positive control ( 20 ng dna ) . the pcr protocol involved a 3-min hot start at 95c , followed by addition of primers at 50 pmol per 50-l mixture . thirty cycles of pcr were performed ( 94c , 45s ; 55c , 45s ; 72c , 1 min ) followed by a final extension step at 72c for 10 min , and the amplification products were stored at 4c . the pcr products were separated on a 1.5% agarose gel and visualized on a uv transilluminator after being stained with ethidium bromide ( 0.5 g / ml ) for 15 min at room temperature . amplification products were cloned into the plasmid vector pcr2.1topo ( invitrogen , burlington , ontario ) . cloned products were fingerprinted by endonuclease digestion with taqi or rsai , and unique clones were sequenced by using dye terminator methods ( abi prism bigdye terminator cycle sequencing kit , applied biosystems , foster city , ca ) . the resulting dna sequences were identified by comparison with the nonredundant database at the national center for biotechnology information ( 3 ) and showed a match of 577 of 581 nt ( 99% ) to m. neoaurum ( genbank accession no . m. neoaurum , first described in 1972 , belongs to the m. parafortuitum complex of the genus mycobacterium ( 4 ) . eight cases of human infection from m. neoaurum have been described in the english - language literature ( 511 ) . six of these cases were associated with central venous catheters , one was associated with intravenous drug use , and another involved urinary isolation of m. neoaurum during an investigation of a catheter - associated urinary tract infection . second , a mild csf lymphocytic pleocytosis is consistent with an infectious or inflammatory cns disorder , though rare occurrences have been reported in pathologically confirmed creutzfeldt - jacob disease ( cjd ) ( 12 ) . third , histologic examination demonstrated a caseating granulomatous process with accompanying endarteritis , consistent with mycobacterial infection . m. neoaurum is relatively difficult to culture ; therefore , inability to cultivate the organism or visualize it on ziehl - nielsen and auramine rhodamine stains is not unexpected . the patient had no known risk for parenteral exposure to bloodborne pathogens and was not apparently immunocompromised . although the epidemiology of her case suggests mycobacterial infection through direct exposure , the mode of acquisition is speculative . the patient was diagnosed with cjd . in patients with rapidly progressive dementia , probable cjd may be diagnosed if myoclonus or typical eeg tracings are present , according to brown et al . possible cjd is diagnosed when rapidly progressive dementia is associated with a movement disorder or periodic eeg activity . masters proposed that probable cjd may be diagnosed in patients with rapidly progressive dementia , biphasic or triphasic waves on eeg , and at least two of myoclonus , visual or cerebellar symptoms , pyramidal or extrapyramidal signs , and akinetic mutism ( 14 ) . recent efforts to improve diagnostic accuracy for cjd have focused on measuring csf protein 14 - 3 - 3 . thought to reflect neuronal injury , reported sensitivities and specificities of csf protein 14 - 3 - 3 for cjd in patients with rapidly progressive dementia are 84%96% and 87%100% , respectively ( 1521 ) . the masters criteria have been revised to reclassify possible cjd as probable if csf protein 14 - 3 - 3 is present ( 18 ) . in the case described , revised masters criteria for probable cjd and brown criteria for possible cjd were met . the false - positive rate of csf protein 14 - 3 - 3 for cjd can be as high as 12% , however , with other causes including vascular disorders , infectious encephalitis , anoxia , malignancy , and even alzheimer s , lewy body , and frontotemporal dementias ( 15,1721 ) . in this patient , the presence of csf protein 14 - 3 - 3 likely reflected ischemic injury mediated by the proliferative arteritis . in summary , we have described a case of rapidly progressive dementia with prominent neurologic features attributable to chronic granulomatous meningitis and arteritis . despite negative stains and cultures , the identification of dna from m. neoaurum suggests that this case may represent the first reported cns infection from this organism , as well as the first documented fatality . the absence of any clear mode of infection or predisposing risk factors for developing such a devastating infection is unusual . this case highlights the difficulties in achieving a causative diagnosis in patients with rapidly progressive dementia . csf protein 14 - 3 - 3 does not entirely rule out potentially treatable causes , and in this case an angiogram would likely not have been able to differentiate inflammatory from infectious vasculitis . more definitive diagnostic methods are required , including a possible role for pcr analysis of csf samples , as well as earlier consideration of biopsy .
dementia developed in a patient with widespread neurologic manifestations ; she died within 5 months . 
 pathologic findings showed granulomatous inflammation with caseation necrosis , foreign body 
 type giant cells , and proliferative endarteritis with vascular occlusions . 
 broad - range polymerase chain reaction identified mycobacterium neoaurum as the possible pathogen . 
 central nervous system infection by m. neoaurum may result in rapidly progressive dementia .