Table 1.
Characteristics of patients with Aspergillus meningitis.
| Author, year [Reference] | Age/sex | Risk factor/Underlying disease | Sign and symptoms (time duration)/Time from TX | Syndrome | Diagnosis/methods | CSF characteristics | Aspergillus species | CSF Ag GMN (method) | Antifungal treatment (time duration) | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|
| Meningitis | ||||||||||
| Atkinson & Israel, 19739 | 27/M | None/Sarcoidosis | Headache, blurred vision | Meningitis | L/CSF | WBC 144/μL (PMNs 10%) | Aspergillus fumigatus (CSF) | NA | 5-FLU (3 months) | Alive 2 years after stopping antifungal therapy |
| Feely et al., 197710 | 57/F | Neurosurgery (Trans-sphenoidal Yttrium90 implant)/Acromegaly | Meningeal signs, left hemiparesis/11 months | Meningitis | Pm/Autopsy (purulent basal leptomeningitis + multiple infarcts) | WBC 138/μL (PMNs 96%); proteins 850 mg/L | Aspergillus spp. (autopsy culture) | NA | None | Death after 1 day |
| 37/M | Neurosurgery (Trans-sphenoidal Yttrium90 implant)/Diabetic retinopathy | Fever, stiff neck, headache, blurred vision/9 months | Meningitis | L/Biopsy (tissue adherent to the screws) | WBC 8800/μL (PMNs 90%); protein 330 mg/L | Aspergillus spp. (biopsy) | NA | AMFB (NR)+ removal of implant | Alive | |
| Mohandas et al., 197811 | 38/M | Neurosurgery/Maxillary sinusitis | Meningeal irritation, coma/6 days post-operatively | Meningitis | L/Surgery of fungal granuloma | WBC 100/μL (PMNs 0%); glucose 35 mg/dL; protein 1160 mg/L | Aspergillus spp. (biopsy) | NA | AMFB (7 days) ev + intratechal (1 day) | Death after 7 days |
| Aung et al., 197912 | 22/F | Pregnancy/None | Headache, retrobulbar pain, blurred vision, ophthalmoplegia (22 days after delivery) | Meningitis | L/Biopsy leptomeninges | ND | Aspergillus spp. (biopsy) | NA | Antifungal drugs (not mentioned) | Death after 1 month |
| Beal et al., 198213 | 47/F | None/Sphenoid sinusitis | Frontal headache (5 months); nuchal rigidity, fever, hydrocephalus | Meningitis | L/biopsy sinus | WBC 120/μL (PMNs 63%); glucose 25 mg/dL; protein 620 mg/L | Aspergillus spp. (sinus biopsy) | NA | AMFB (NR) | Alive 2 years later |
| 22/F | Neurosurgery/Medullo-blastoma | Fever (38.8 °C), severe headache, meningismus 12 days after neurosurgey | Meningitis | L/CSF; Autopsy (basilar Aspergillus meningitis with exudate in the subarachnoid space of spinal cord) | WBC 2650/μL (PMNs 10%); glucose 26 mg/dL; protein 1750 mg/L | Aspergillus spp. (CSF culture after multiple attempts) | NA | AMFB (3 days) | Death after 20 days | |
| Diendogh et al., 198314 | 60/M | Neurosurgery (Trans-sphenoidal Yttrium90 implant)/Diabetic retinopathy | Drowsy, disoriented in time and space, neck stiffness, positive Kernig sign | Meningitis | PM/Autopsy (meningitis; necrotizing vasculitis (pons); fungal invasion of basilar and middle cerebral arteries) | WBC 323/μL (PMNs 60%) | Aspergillus spp. (autopsy histology) | NA | None | Death after 2 weeks |
| Walsh et al., 19858 | 64/F | Steroid treatment/Cushing syndrome | Meningismus,headache, hemiparesis | Meningitis | Pm/Autopsy : mycotic Aspergillus aneurism & subarachnoid hemorrhage | WBC 15/μL (PMNs 0%); glucose 90 mg/dL; protein 1450 mg/L | Aspergillus spp. (autopsy histology) | NA | None | Death after 9 days |
| Hajjar et al., 198715 | 28/M | Neurosurgery/Acoustic neurinoma | NR/9 days | Meningitis | L/Wound culture | NR | Aspergillus fumigatus (wound culture) | NA | AMFB + 5-FLU (2 months) | Death after 2 months |
| Asnis et al., 198816 | 44/M | None/AIDS | Confusion, generalized seizures | Meningitis | Pm/Autopsy (Aspergillus leptomeningites) | NR | Aspergillus spp. (autopsy histology) | NA | AMFB (20 days) | Death |
| Carrazana et al., 199117 | 44/M | None/AIDS; sphenoid sinusitis | Headache, fever, nausea, ataxia, hemiparesis, seizures | Meningitis | Pm/Autopsy (Aspergillus meningeal infiltration; thrombosis of basilar artery) | NR | Aspergillus spp. (autopsy histology) | NA | None | Death |
| Komatsu et al., 199118 | 61/F | Neurosurgery/Rathke’cleft cyst | High fever and meningeal signs/12 days after surgery | Meningitis | Pm/Autopsy (Aspergillus meningitis & mycotic aneurism, subarachnoid hemorrhage) | WBC 881/μL (PMNs 70%); glucose 46 mg/dL; protein 540 mg/L | Aspergillus spp. (autopsy histology) | NA | ND | Death after 23 days |
| Lammens et al., 199219 | 39/F | Immunosuppressive therapy/SLE | Headache (1 month), fever (39.5 °C), neck stiffness, Horner syndrome | Meningitis | Pm/Autopsy (Aspergillus basal meningitis & subarachnoid hemorrhage) | WBC 3750/μL (PMNs 84%); glucose 32 mg/dL; protein 1000 mg/L | Aspergillus spp. (autopsy histology) | NA | None | Death after 15 days |
| Torre-Cisneros et al., 199320 | 31/F | Liver transplant/End stage liver disease | Seizurea | Meningitis | Pm/Autopsy (ischemic infarct; leptomeningeal aspergillosis) | NR | Aspergillus spp. (autopsy histology) | NA | NR | Death |
| 21/F | Liver transplant/End stage liver disease | NRa | Meningitis | Pm/Autopsy (ischemic infart; leptomeningeal aspergillosis) | NR | Aspergillus spp. (autopsy histology) | NA | NR | Death | |
| 24/F | Liver transplant/End stage liver disease | Seizurea | Meningitis | Pm/Autopsy (acute leptomeningitis) | NR | Aspergillus spp. (autopsy histology) | NA | NR | Death | |
| 38/M | Kidney transplant/End stage kidney disease | Seizurea | Meningitis | Pm/Autopsy (acute leptomeningitis; haemorrhagic infarcts) | NR | Aspergillus spp. (autopsy histology) | NA | NR | Death | |
| Miaux et al., 199521 | 41/M | Bone marrow transplant; steroid therapy/CML | Fever (38 °C), hemiplegia/2 months | Meningitis | Pm/Autopsy (thickening and meningeal inflammation with haemorrhagic necrosis; lung & heart involvement) | WBC 2000/μL (PMNs 95%); protein 900 mg/L | Aspergillus spp. (autopsy histology) | NA | NR | Death after 5 days |
| 39/F | Bone marrow transplant; steroid therapy/RAEB | Mental confusion/3.5 months | Meningitis | Pm/Autopsy (brain hemorrhagic necrosis; lung involvement) | WBC 2560/μL (PMNs 98%); | Aspergillus spp. (autopsy histology) | NA | NR | Death after 8 days | |
| Adunsky et al., 199622 | 74/M | None/None | Fever (38.3°), stuporous, left hemiplegia, dysarthria (1 day) | Meningitis | L/CSF | WBC 2400/μL (PMNs 94%); glucose 10 mg/dL; protein 1500 mg/L | Aspergillus flavus (CSF culture) | NA | AMFB (few days) | Death after few days |
| Darras-Joly et al., 199623 | 68/M | Neurosurgery/Metastatic cancer | Allucinations, disorientation, hemyanopsia/5 months after surgery | Meningitis; extradural empyema; abscesses | L/Surgery extradural abscess | NR | Aspergillus fumigatus (extradural abscess) | Negative (NR) | AMFB (2 months)+ itraconazole (2 months) | Death after 12 months |
| 29/M | Neurosurgery/Acoustic neurinoma | Fever (38 °C), severe headache/3 days after surgery | Meningitis; abscess; | L/CSF | WBC 830/μL (PMNs 53%); glucose 48 (s 155) mg/dL; protein 830 mg/L | Aspergillus fumigatus (CSF culture) | Positive (NR) | L-AMB (5 weeks)+ 5-FLU (7 weeks); itraconazole (6 months) | Alive after 12 months | |
| Monlun et al., 199724 | 75/F | Steroid therapy/Asthma | Fever (38 °C); acute respiratory failure (22 days) | Meningitis | Pm/Autopsy (right haemorragic infarct with subcortical vessel invasion and meningeal diffusion by Aspergillus; pulmonary involvement) | ND | Aspergillus spp. (autopsy histology) | ND | AMFB (3 weeks) | Death 22 days later |
| Verweij et al., 199925 | 73/F | Mastoidectomy/Otitis media | Fever (39 °C), headache, vomiting, drowsiness, meningismus/NR | Meningitis | L/CSF (sixth attempt) | WBC 2130/μL; glucose 27 mg/dL (47 mg/dL serum); protein 150 mg/L | Aspergillus fumigatus (CSF culture, 6th attempt + PCR) | 10.4 (Platelia) | Itraconazole 1 week; AMFB (4weeks + AMFB intraventricular; voriconazole (9 weeks) | Alive 12 months after voriconazole discontinuation |
| Mariushi et al., 199926 | 43/F | None/None | Headache, neck stiffness (11 days), fever (37.6 °C), nausea, chills | Meningitis | L/CSF | WBC 329/μL (PMNS 0%); glucose 46 mg/dl; protein 500 mg/L | Aspergillus spp. (CSF culture, 5th attempt) | ND | Fluconazole (2 years) | Alive after 2 years |
| Arabi, 200127 | 58/M | None/Maxillary sinusitis | Confusion, progressive unresponsiveness, 4th nerve palsy 8 days after pneumonia | Meningitis | L/Sinus aspirate/Autopsy (Aspergillus ventriculitis, meningitis; focal encephalitis; pneumonia) | WBC 3500/μL (PMNs 91%); glucose 77 mg/dL(s 102); protein 3370 mg/L | Aspergillus fumigatus (sinus culture) | ND | AMFB (3 weeks) | Death 20 days later |
| Nenoff et al., 200128 | 74/M | Ethmoidectomy and orbitotomia (for A.fumigatus orbital and sinus infection)/Diabetes mellitus | Vomiting, nausea, exophthalmus, somnolent and disoriented/7 months | Meningitis | L/Biopsy (orbital apex)/Autopsy (Aspergillus meningitis, vasculitis internal carotid, mycotic aneurism with subarachnoid hemorrhage) | NR | Aspergillus fumigatus (biopsy) | 1:2 (Pastorex) | AMFB+ 5-FLU (few days) | Death 3 weeks after surgical procedure |
| Moling et al., 200229 | 24/M | Kidney transplant (reject); Hemodialysis + steroid therapy/complement 4 deficiency | Fever (39 °C); confusion; disorientation; right motor hemi-syndrome (2 weeks) | Meningitis | L/CSF | WBC 3200/μL; glucose 4 mg/dL | Aspergillus fumigatus (CSF culture, 4th attempt + PCR) | ND | Fluconazole (2 weeks): L-AMB (3 weeks); itraconazole (4 months) | Alive after 7 months; Death after 6 yearsb |
| Kleinschmidt-De Masters, 200230 | 40/F | Steroid therapy/Wegener's granulomatosis | NR | Meningitis | Pm/Autopsy (Aspergillus acute and chronic basilar granulomatous meningitis; mycotic aneurism; lung, skin, heart involvement) | NR | Aspergillus spp. (autopsy histology) | ND | NR | Death after 68 days |
| 51/M | Chemotherapy/Lymphoma | NR | Meningitis | Pm/Autopsy (Aspergillus basilar meningitis; thrombotic occlusion of arteries | NR | Aspergillus spp. (autopsy histology) | ND | NR | Death after 4 days | |
| Pandian et al., 200431 | 34/F | Spinal anaesthesia/None | Fever, headache, vomitingc | Meningitis | Pm/Autopsy (Aspergillus meningitis; mycotic aneurism with subarachnoid hemorrhage) | WBC 640/μL (PMNs 76%); glucose 32 mg/dL; protein 3600 mg/L | Aspergillus spp. (autopsy histology) | ND | None | Death |
| 21/F | Spinal anaesthesia/None | Fever, headache, vomitingc | Meningitis | Pm/Autopsy (Aspergillus meningitis; mycotic aneurism with subarachnoid hemorrhage) | WBC 678/μL (PMNs 65%); glucose 23 mg/dL; protein 3600 mg/L | Aspergillus spp. (autopsy histology) | ND | None | Death | |
| 42/F | Spinal anaesthesia/None | Fever, headache, vomitingc | Meningitis | Pm/Autopsy (Aspergillus meningitis; mycotic aneurism with subarachnoid hemorrhage) | WBC 240/μL (PMNs 68%); glucose 23 mg/dL; protein 2400 mg/L | Aspergillus spp. (autopsy histology) | ND | None | Death | |
| 32/F | Spinal anaesthesia/None | Fever, headache, vomitingc | Meningitis | Pm/Autopsy (Aspergillus meningitis; mycotic aneurism with subarachnoid hemorrhage) | WBC 345/μL (PMNs 76%); glucose 23 mg/dL; protein 1230 mg/L | Aspergillus spp. (autopsy histology) | ND | None | Unknown | |
| 24/F | Spinal anaesthesia/None | Fever, headache, vomitingc | Meningitis | Pm/Autopsy (Aspergillus meningitis; mycotic aneurism with subarachnoid hemorrhage) | WBC 435/μL (PMNs 96%); glucose 32 mg/dL; protein 4200 mg/L | Aspergillus spp. (autopsy histology) | ND | None | Death after 18 months | |
| Larson Kolbe et al., 200732 | 51/F | Epidural steroid injections/COPD | Mental status changes; 3rd nerve palsy/2 months | Meningitis | L/Disc aspiration | NR | Aspergillus fumigatus (disc aspiration + vpsoas abscess culture) | ND | Caspofungin + oriconazole (4 months) | Death after 5 months |
| Gunaratne et al., 200733, 78 | 26/F | Spinal anesthesia (Pregnancy)/None | Low grade fever; headache; nausea; vomiting 12 days after sa | Meningitis | Pm/Autopsy | WBC 302/μL (PMNs 99%); glucose 56 mg/dl (s 115 mg/dL)d; protein 680 mg/L | Aspergillus fumigatus (autopsy culture) | ND | Fluconazole | Death after 4 weeks |
| 21/Fe | Spinal anesthesia (Pregnancy)/None | Fever, chills, neck stiffness 10 days after sa | Meningitis | Pm/Autopsy | WBC 575/μL (PMNs 70%); glucose 25 mg/dl (s 90 mg/dL)d; protein 490 mg/L | Aspergillus fumigatus (autopsy culture) | ND | AMFB (4 days) | Death after 4 weeks | |
| 27/F | Spinal anesthesia (Pregnancy)/None | Fever, headache, neck stiffness; diplopia, photophobia 15 days after sa | Meningitis | L/CSF (microscopy) | WBC 720/μL (PMNs 3%); glucose 21 mg/dl (s 133 mg/dL)d; protein 680 mg/L | Aspergillus spp. (CSF) | ND | AMFB iv + it (4 weeks) voriconazole (4 weeks) | Alive after 12 months (residual 6th cranial nerve palsy and impaired hearing) | |
| 29/F | Spinal anesthesia (Pregnancy)/None | Fever, headache, vomiting, neck stiffness, photophobia 11 days after sa | Meningitis | L/CSF | WBC 1430/μL (PMNs 40%); glucose 45 mg/dl; protein 330 mg/L | Aspergillus fumigatus (CSF culture) | ND | AMFB iv + it (2 weeks); voriconazole (16 weeks) | Alive after 12 months (no disability) | |
| 38/F | Spinal anesthesia (Pregnancy)/None | Fever, neck stiffness 8 days after sa | Meningitis | Pm/Autopsy | WBC 225/μL (PMNs 0%); glucose 61 mg/dL (s 109 mg/dL)e; protein 280 mg/L | Aspergillus fumigatus (autopsy culture) | ND | AMB (9 days) | Death after 24 days | |
| Saitoh et al., 200734 | 33/M | Chemotherapy/AML | Fever, headache, neck stiffness/14 days post-chemotherapy | Meningitis | L/CSF | WBC 15/μL; glucose 30 mg/dL; protein 760 mg/L | Aspergillus spp. (PCR + Ag on CSF) | 2.2 (s 0.1) (Platelia) | AMFB (1 week); voriconazole (12 months) | Alive after 1 year |
| Sundaram et al., 200735 | 22/M | Spinal anesthesia (1 month prior)/None | Fever, headache, vomiting (2 months), neck stiffness | Meningitis | Pm/Autopsy (Aspergillus purulent meningitis & mycotic aneurism with subarachnoid hemorrages) | WBC 720/μL (PMNs 90%); glucose 37 mg/dL; protein 850 mg/L | Aspergillus fumigatus (CSF culture, 5th attempt)f | ND | ND | Death after 68 days |
| Van de Beek et al., 200836 | 56/M | Kidney-pancreas transplant/End stage disease; sphenoid sinusitis | Headache, fever (6 weeks); neck stiffness, dysarthria, hemiparesis | Meningitis | L/sphenoid biopsy/Autopsy (Aspergillus meningitis; midline herniation, subarachnoid hemorrhage) | WBC 1200/μL (PMNs 94%); glucose 64 mg/dL; protein 7300 mg/L | Aspergillus fumigatus (sphenoid biopsy + autopsy) | 6.47 (s 0.39) (Platelia) | Voriconazole (NR) | Death after 4 weeks |
| [PR], 2011 | 35/M | IVDA (heroin)/Chronic hepatitis C | Fever (37.5 °C), headache, back pain (1 month) | Meningitis & spinal arachnoiditis | L/CSF | WBC 260/μL (PMN 70%); glucose 1 mg/dL (s 76 mg/dL); protein 7900 mg/L | Aspergillus flavus (CSF culture) | 7.4 (s 2.5) (Platelia) | Voriconazole 5 months (+1 month caspofungin); L-AMB 3 months | Alive after 9 months |
| Chronic meningitis/pachimeningitis | ||||||||||
| Palo et al., 197537 | 69/M | None/Diabetes | Headache, fever, diplopia, vertigo hearing loss (6 months) | Chronic meningitis | Pm/CSF; autopsy: (granulomatous leptomeningitis and spinal cord involvement) | WBC 103/μL (PMNs 8%); glucose 45 mg/dL; protein 1400 mg/L | Aspergillus fumigatus (CSF culture, 6th attempt)f | NA | None | Death 1 month later |
| Gordon et al., 19763, 79 | 34/F | IVDA (heroin, cocaine)/None | Bifrontal headache, neck stiffness (weeks), low-grade fever | Chronic meningitis | L/CSF | WBC 2892/μL (PMNs 80%); glucose 16 (s 110) mg/dL; protein 990 mg/L; | Aspergillus oryzae (CSF culture, 7th attempt) | NA | AMFB+ 5-FLU (12 months) | Alive (6 year later; episode of bilateral necrotizing scleritis due to A.orizae)g |
| Mielke et al., 198138 | 58/F | Neurosurgery/Acromegaly | Severe headache (4 months), retro-orbital pain, blindness, ophalthalmoplegia/10 months | Chronic meningitis | Pm/Autopsy (chronic basilar meningitis by A.fumigatus & C.albicans; mycotic aneurism of the basilar artery with subarachnoid hemorrhage) | ND | Aspergillus fumigatus (autopsy culture) | NA | None | Death after 7 days |
| Weinstein et al., 198239 | 67/M | None/none | Retro-orbital and periorbital pain, vertigo (months); decrease eye vision; weakness; malaise | Chronic meningitis | L/biopsy sphenoid wing | WBC 88/μL (PMNs 6%); glucose 53 (s 97) mg/dL; protein 1130 mg/L | Aspergillus fumigatus (biopsy + culture sphenoid) | NA | AMFB + rifampicin (2 weeks) | Death after 18 days from surgery |
| Salaki et al., 198440 | 32/M | Steroid treatment/SLE | Fever (38 °C), frontal headache, lethargy (3 weeks), stiff neck, 6th nerve palsy | Chronic meningitis | L/CSF + spinal aspirate | WBC 1400/μL (92%); glucose 33 mg/dL; protein 1100 mg/L | Aspergillus fumigatus (CSF culture, 4th attempt) | NA | AMFB +5-FLU (NR) | Alive |
| Woods et al., 199041 | 44/M | None/AIDS | Headache, fever, nausea, vomiting, lethargy, slurred speech, severe back pain (4 months) | Chronic meningitis | Pm/Autopsy (Aspergillus acute and chronic basilar meningitis; spinal arachnoiditis; pleural, brain, lumbar spinal cord involvement) | WBC 80/μL (PMNs 80%); glucose 19 mg/dL; protein 2000 mg/L | Aspergillus fumigatus (autopsy culture) | NA | None | Death after 18 days |
| Murai et al., 199242 | 59/F | None/Diabetes; Liver cirrhosis; Mondini's anomaly; otitis media | Headache; hearing loss; multiple nerve palsy (6th, 8th, 9th, 10th, 11th) | Chronic pachymeningitis | L/surgery maxillary sinus | WBC 7/μL; protein 660 mg/L | Aspergillus flavus (surgery culture) | NA | Miconazole (2 months); 5-FLU, fluconazole (1 month) | Alive after 4 months |
| Kurino et al., 199343 | 63/M | None/Diabetes; otitis media | Fever, headache, hyperesthesia of face, abducens palsy, deafness | Chronic meningitis | Pm/Biopsy granuloma + autopsy | WBC 138/μL (PMNs 50%); glucose 87 mg/dL; protein 1007 mg/L | Aspergillus spp. (biopsy + autopsy) | NA | None | Death 30 days post-surgery |
| Mochizuki et al., 200044 | 75/M | None/Otitis media | Multiple cranial nerve palsy (2nd, 3rd, 4th), impaired vision (4 months) | Chronic pachymeningitis | L/Biopsy | NR | Aspergillus flavus (biopsy culture) | ND | Fluconazole (4 weeks); AMFB (4 months)+5-FLU (4 months); itraconazole (5 months) | Alive after 36 months |
| Moling et al., 200229 | 48/M | Alcohol abuse/None | Headache, fever, gait instability, apathy (5 months) | Chronic meningitis + ventriculitis + arachnoiditis | L/CSF | WBC 1880/μL; glucose 20 mg/dL | Aspergillus candidus group (CSF culture) | 6.7 (s 1.7) (Platelia) | AMFB (1 week); rifampicin (several months); voriconazole (10 days); itraconazole (10 months) | Alive after 24 months |
| Kowacs et al., 200445 | 26/M | Near drowning/None | Fever (37.2 °C), mild meningismus (4 weeks) | Chronic meningitis | L/CSF | WBC 165/μL (PMNs 69%); glucose 64 mg/dL; protein 778 mg/L | Aspergillus fumigatus (CSF culture, 3rd attempt) | ND | Fluconazole (12 days); itraconazole + AMFB (44 days) | Death after 56 days |
| Ismail et al., 200746 | 73/M | None/Diabetes mellitus; pulmonary asbestosis | Headache, left-sided visual loss, scalp tenderness, fatigue (3 weeks) | Hypertrophic pachymeningitis | L/Meningeal biopsy | WBC 0/μL; protein 5670 mg/L | Aspergillus flavus (biopsy culture) | ND | Antifungal treatment (NR) | Death 3 months later |
| Kagawa et al., 200847 | 33/F | Spinal cord mass lesion | Headache, low grade fever (5 months), hydrocephalus | Chronic meningitis | L/Biopsy VA shunt | WBC 1340/μL; glucose 8 mg/dL; protein 1580 mg/L | Aspergillus spp. (VA shunt biopsy) | ND | AMFB (NR); fluconazole (NR) | Alive after 15 years (multiple recurrences) |
| Chan et al., 201148 | 59/M | Diabetes; impaired renal function | Headache, diplopia, hoarseness (2 months) | Pachymeningitis | L/Dural biopsy | Glucose 102 mg/dL; protein 1270 mg/L | Aspergillus flavus (culture from dural biopsy) | Positive (β-d-glucan + Platelia) | Voriconazole (2 weeks); caspofungin (4 weeks); voriconazole | Alive after 7 months |
| Kato et al., 201149 | 42/M | None/None | Headache, right nucal pain, cranial nerve palsies9, 10, 11, 12 (2 months) | Hypertrophic pachymeningitis | L/CSF | WBC 43/μL (PMNs 4%); glucose 56 mg/dL; protein 1000 mg/L | Aspergillus spp. (CSF PCR positive) | β-d-glucan (Fungitell) 164 pg/mL; serum < 5 pg/mL | Voriconazole (8 week)s; L-AMB+ 5-FLU( 2 week)s; fluconazole 8 weeks | Alive after 30 months |
| Meningoencephalitis | ||||||||||
| Goldhammer et al., 197450 | 45/M | None/none | Headache (9 months), blurred vision (3 weeks) | Meningoencephalitis | Pm/Autopsy (disseminated meningoencephalitis with pituitary abscess and left optic nerve involvement) | ND | Aspergillus spp. (microscopy smear of pituitary abscess + autopsy) | NA | None | Death 4 days postoperatively |
| Naidoff et al., 197551 | 29/F | Kidney transplant/End stage kidney disease | NR | Meningoencephalitis | Pm/Autopsy.disseminated aspergillosis (heart, lung, liver, spleen, thyroid, brain, eye, meninges) | ND | Aspergillus fumigatus (autopsy culture) | NA | None | Death in a few days |
| Kaufman et al., 197652 | 31/F | IVDA (heroin)/None | Headache (9 months), blurred vision (2 months), intermittent diplopia, hearing loss | Meningo-encephalitis | L/Lobectomy; CSF/Autopsy (granulomatous basilar leptomeningitis; aspergilloma left frontal gyrus; transtentorial and tonsillar herniation) | WBC 1150/μL (PMNs 83%); glucose 20 (s 119) mg/dL; | Aspergillus fumigatus (CSF + frontal granuloma culture) | NA | AMFB (2 weeks) | Death after 3 weeks |
| Horton et al., 197653 | 17/F | Fungal endocarditis/Aortic stenosis | Headache, incoordination, right-sided numbness, seizure | Meningoencephalitis | Pm/Autopsy (mycotic aneurism of the middle cerebral artery with subarachnoid hemorrhage) | NR | Aspergillus fumigatus (CSF culture) | NA | None | Death after 9 days |
| Galassi et al., 197854 | 59/F | Neurosurgery/Meningioma | Intermittent fever, seizures, aphasia, hemiparesis/12 months | Meningoencephalitis | L/Surgery of dura granulomas; CSF/Autopsy (diffuse purulent meningo-enecephalitis) | NR | Aspergillus fumigatus (CSF culture) | NA | AMFB (3 months) | Death after 3 months |
| Peacock et al., 198455 | 23/M | Post-chemotherapy/Refractory anemia | Fever, headache, lethargia (57 days post-chemo) | Meningoencephalitis | L/Biopsy (pulmonary); Autopsy (Aspergillus leptomeningitis; necrotizing vasculitis (pons and basal ganglia); tonsillar herniation; necrotizing pneumonia) | WBC 117-1126/μL (PMNs 88–99%); glucose 13–48 mg/dL; protein 540–3460 mg/L | Aspergillus terreus (culture lung biopsy); CSF Aspergillus antigen | Positive (RIA) | AMFB +5-FLU + rifampicin (NR) | Death after 65 days |
| Ouammou et al., 198656 | 3/M | Neurosurgery/Encephalomeningocele | Fever (37.8 °C), frontal subcutaneous abscess/3 days | Meningoencephalitis | L/CSF; surgery: meningeal mycetoma. Autopsy: encephalitis (cerebral hemispheres, brain stem) | WBC 52/μL (PMNs 70%); glucose 10 mg/dL; protein 1200 mg/L; | Aspergillus fumigatus (CSF culture) | NA | Griseofulvin (3 months) | Death after 3 months |
| Cox et al., 199057 | 31/M | None/AIDS | Headache, fever (38.2 °C), confusion, vomiting | Meningoencephalitis | PM/Autopsy (Aspergillus meningitis; mycotic aneurysms; endocarditis; myocarditis) | ND | Aspergillus spp. (autopsy histology) | NA | None | Death after few days |
| Breneman et al., 19925 | 50/M | IVDA; steroid therapy/COPD | Fever (38.6 °C), dyspnea, headache; stiff neck, progressive mental status change (3 days) | Meningoencephalitis | L/brain biopsy | WBC 4100/μL (PMNs 96%); glucose 33 mg/dL; protein 1340 mg/L | Aspergillus fumigatus (Brain biopsy culture) | NA | AMFB (few days) | Death after few days |
| Van der Knaap et al., 199358 | 3/M | None/Galactosemia | Fever (40 °C), nuchal rigidity, convulsions, left hemiparesis | Meningoencephalitis | L/CSF positive antigen | Normal | Aspergillus spp. | Positive (NR) | AMFB + 5-FLU (NR) | Improvement |
| Mikolich et al., 19966 | 25/F | None/None | Worsening headache (3 months); vomiting; photophobia (1 month); papilledema | Meningoencephalitis | L/brain biopsy | WBC 200/μL (PMNs 2%); glucose 40 mg/dL; protein 920 mg/L | Aspergillus fumigatus (brain biopsy) | NA | Itraconazole (24 months) | Alive after 4 years |
| Darras-Joly et al., 199623 | 17/F | Neurosurgery/Ependymoma | Fever (40 °C), neck stiffness/7 days after surgery | Meningoencephalitis; ventricultis | L/Surgical drainage | WBC 1900/μL (PMNs 97%); glucose 36 mg/dL; protein 1100 mg/L | Aspergillus fumigatus (surgical culture) | Negative (NR) | AMFB (72 days) + itraconazole (30 days) | Death after 96 days |
| Schwartz et al., 199759 | 18/M | Chemotherapy/ALL | Meningism, fever/(92 days post-chemotherapy) | Meningoencephalitis | L/Brain biopsy | WBC 1056/μL (PMNs 96%) | Aspergillus spp. (Brain biopsy) | ND | Itraconazole (4 weeks); voriconazole (6 months) | Death after 6 months |
| Koh et al., 199860 | 15/F | Chemotherapy/ALL | Flaccid weakness lower extremities, slurred speech, urinary retention | Meningomieloencephalitis | Pm/Autopsy (Multifocal leptomeningeal exudates; fungal abscess/necrosis in spinal cord) | ND | Aspergillus spp. (autopsy histology) | ND | ND | Death 21 days later |
| Payot et al., 199961 | 29/M | None/AIDS | Headache (3 weeks), nausea (1 week), fever (39 °C), nuchal rigidity | Meningoencephalitis | Pm/Autopsy (Aspergillus purulent basal meningitis + bulbar encephalitis) | WBC 19/μL (PMN 50%); protein 1080 mg/L | Aspergillus spp. (autopsy histology) | ND | None | Death after 7 days |
| Fasciano et al., 199962 | 26/M | Steroid treatment/Chronic asthma | Fever, quadriplegia, areflexia; hydrocephalus (2 weeks) | Meningoencephalitis | L/Brain biopsy/Autopsy: (Aspergillosis of brain, meninges, cauda equina, lungs, thyroid; bilateral uncal herniation) | WBC 1300/μL (PMNs 98%); glucose 40 mg/dl; protein 1100 mg/L | Aspergillus fumigatus (brain biopsy) | ND | AMFB iv and intratechal + 5-FLU (2 weeks) | Death after 6 weeks |
| Chandra et al., 200063 | 40/F | None/Ethmoid and sphenoid sinusitis | Headache, fever, vomiting (1 week); left proptosis | Meningoencephalitis | L/Brain biopsy | NR | Aspergillus fumigatus (biopsy) | ND | NR | NR |
| Viscoli et al., 200264 | NR | BMT/Acute lymphoblastic leukemia | Fever, neurological deficit, seizures/5 days post-BMT | Meningoencephalitis | Pm/Autopsy (diffuse meningeal and parenchimal infiltration) | NR | Aspergillus spp. (meningeal and parenchimal) | 578 (s 25.7) (Platelia) | NR | Death |
| Wang et al., 200365 | 39/M | Steroid treatment/SARS | Tentorial herniation | Meningoencephalitis | Pm/Autopsy: (Aspergillus meningitis; multiple brain abscess containing aspergillus; disseminated aspergillosis heart, kidney, spleen, pancreas, adrenal glands) | ND | Aspergillus spp. (autopsy histology and culture) | ND | None | Death |
| Roberts et al., 200466 | 71/F | None/Sinusitis | Fever (38.3 °C), severe headache, diplopia, confusion (5 weeks) | Meningoencephalitis | Pm/Autopsy (Aspergillus granulomatous meningitis; thrombosis of basilar artery) | WBC 286/μL (PMNs 38%); glucose 23 mg/dL (s 99); protein 850 mg/L | Aspergillus spp. (autopsy histology) | ND | None | Death after 10 days |
| Botturi et al., 200667 | 59/F | Steroid treatment/Sphenoid sinusitis/ | Headache, diplopia; bilateral 6th nerve palsy (5 weeks) | Meningoencephalitis | L/Brain biopsy | WBC 920/μL (PMNs 96%); glucose 0 mg/dL; protein 180 mg/L | Aspergillus spp. (biopsy) | ND | AMFB (8 weeks); voriconazole (6 months) | Alive after 23 months |
| Gabelmann et al., 200768 | 43/F | Chemotherapy/AML; sinusitis | NR | Meningoencephalitis | Pm/Autopsy | NR | Aspergillus spp. (autopsy histology) | ND | NR | Death after 41 days |
| Van de Beek et al., 200836 | 62/F | Kidney-pancreas transplant/End stage disease | Headache (6 months), altered consciousness | Meningoencephalitis | L/Autopsy (cerebral aspergillosis) | WBC 286/μL (PMNs 90%); glucose 27 mg/dL; protein 830 mg/L | Aspergillus spp. (autopsy histology) | 2.72 (s 0.06) (Platelia) | ABLC | Death after 12 days |
| Spinal arachnoiditis | ||||||||||
| Bryan et al., 198069 | 26/M | IVDA (heroin)/None | Headache, nausea, vomiting (weeks), low back pain; hydrocephalus | Spinal arachnoiditis | L/Lumbar biopsy (lesion L3-5) | WBC 1857/μL (PMNs 43%); glucose 6 mg/dL; protein 5170 mg/L | Aspergillus flavus (immunofluorescence on biopsy) (CSF) | NA | AMFB + rifampicin (10 weeks) | Alive after 14 months |
| Stein et al., 198270 | 24/F | IVDA (heroin)/Chronic alcoholism | Low back pain (4 months), left leg weakness, frequent headache fever (38 °C); confusion and signs of meningeal irritation | Spinal arachnoiditis | L/CSF | WBC 62/μL (PMNs 30%); glucose 70 (105) mg/dL; protein 350 mg/L | Aspergillus terreus (2 CSF cultures)f | NA | AMFB (NR) | Death 26 days after laminectomy |
| Van de Wyngaert et al., 198671 | 30/M | None (splinter stuck on his hand)/None | High fever, painful stiffness of spine, headache, photophobia, nausea | Spinal arachnoiditis | L/CSF | WBC 3200/μL (PMNs 90%); glucose 30 mg/dL; protein 1530 mg/L | Aspergillus fumigatus (CSF) precipitin | NA | AMFB (3 months)+ rifampin (10 days)+ 5-FLU (3 months) | Alive after 229 days |
| Endo et al., 200172 | 55/M | Neurosurgery/Pituitary adenoma | Diplopia, retro-orbital pain (1 year), loss of vision/9 years | Arachnoiditis; subdural abscess | L/Abscess aspiration | NR | Aspergillus fumigatus (abscess culture) | ND | AMFB + fluconazole (4 weeks) | Death after 1 month |
| Genzen et al., 200973 | 37/F | Spinal anesthesia (12 months prior pregnancy) | Headache (months); fever (37.4 °C), blurred vision, numbness left lower extremity | Arachnoiditis | L/Laminectomy & tissue biopsy | WBC 970/μL (PMN 92%); glucose 50 mg/dL; protein 1010 mg/L | Aspergillus terreus (biopsy culture) | ND (s 0.47) | Voriconazole (78 days); voriconazole + caspofungin (54 days); AMFB (6 days); ABLC (50 days) | Alive after 9 months |
| Ventriculitis | ||||||||||
| Morrow et al., 19834 | 36/M | IVDA (heroin)/None | Fever, generalized seizures, nuchal rigidity (1 day) | Ventriculitis | Pm/Autopsy (ventriculitis & hydrocephalus) | WBC 549/μL (PMNs 27%); glucose 29 (s 90) mg/dl; protein 1200 mg/L | Aspergillus flavus (serology)h | NA | None | Death after 40 days |
| Hummel et al., 200674 | 4/F | Chemotherapy/ALL | NR | Ventriculitis & multiple abscess | L/CSF (Ommaya reservoir) | NR | Aspergillus fumigatus (PCR CSF) | Positive (Platelia) | Voriconazole + caspofungin (5 weeks); intraventricular AMFB (4 weeks); voriconazole (2 months) | Alive after 3 months |
| Sutton et al., 200975 | 18/M | Lung transplant/End stage pulmonary disease | Headache, seizure, low grade fever, altered mental status | Ventriculitis | Pm/Autopsy (necrotizing granulomatous inflammation of meninges) | WBC 1100/μL (PMN 79%); glucose 41 mg/dL (s 122); protein 1090 mg/L | Aspergillus granulosus (autopsy culture) | ND | Voriconazole then ABLC and posaconazole | Death after 87 days |
| Antachopoulos et al., 201176 | 5/F | VP shunt | Fever (40 °C), tonic/clonic seizures | Ventriculitis | L/VP | WBC 400/μL (Neutrophil predominance); glucose 25 mg/dL (s 110 mg/dL); protein 1000 mg/L | Aspergillus fumigatus (Culture VP catheter; PCR CSF) | 5.5 (Platelia) | L-AMB (4 months)+ voriconazole (5 months) | Death after 9 months |
M = male; F = female; IVDA = intravenous drug abuser; CSF = cerebrospinal fluid; L = life; Pm = post-mortem; Ag GMN = galactomannan antigen; s = serum; WBC = white blood cells; PMNs = polymorphonuclear; NA = not available; ND = not done; NR = not reported; AMB = amphotericin B dehoxycholate; 5FLU = 5-fluorocytosine; L-AMB = liposomal amphotericin B; ABLC = amphotericin B lipid complex; ALL = acute lymphoblastic leukaemia; CML = chronic myelogenous leukemia; RAEB = refractory anemia with excess blasts; C4def = hereditary complete C4 deficiency; PR = present report; PCR = polymerase chain reaction; VP = ventriculoperitoneal; sa = spinal anaesthesia.
a
One of these four patients had meningism and headache.
b
Reported also in reference 77 (updated the follow-up).
c
Symptoms appeared 2–21 days after spinal anaesthesia (mean 7.8 days).
d
Random values of blood glucose were reported.
e
Reported also in reference 78.
f
Discarded as contaminant.
g
Reported also in reference 79 (updated the follow-up).
h
Serological speciation made a result compatible with A. flavus.