Incidental Findings from 16,400 Brain MRI Examinations of Research Volunteers.

BACKGROUND AND PURPOSE: Incidental findings are discovered in neuroimaging research, ranging from trivial to life-threatening. We describe the prevalence and characteristics of incidental findings from 16,400 research brain MRIs, comparing spontaneous detection by nonradiology scanning staff versus formal neuroradiologist interpretation. MATERIALS AND METHODS: We prospectively collected 16,400 brain MRIs (7782 males, 8618 females; younger than 1 to 94 years of age; median age, 38 years) under an institutional review board directive intended to identify clinically relevant incidental findings. The study population included 13,150 presumed healthy volunteers and 3250 individuals with known neurologic diagnoses. Scanning staff were asked to flag concerning imaging findings seen during the scan session, and neuroradiologists produced structured reports after reviewing every scan. RESULTS: Neuroradiologists reported 13,593/16,400 (83%) scans as having normal findings, 2193/16,400 (13.3%) with abnormal findings without follow-up recommended, and 614/16,400 (3.7%) with "abnormal findings with follow-up recommended." The most common abnormalities prompting follow-up were vascular (263/614, 43%), neoplastic (130/614, 21%), and congenital (92/614, 15%). Volunteers older than 65 years of age were significantly more likely to have scans with abnormal findings (P < .001); however, among all volunteers with incidental findings, those younger than 65 years of age were more likely to be recommended for follow-up. Nonradiologists flagged <1% of MRIs containing at least 1 abnormality reported by the neuroradiologists to be concerning enough to warrant further evaluation. CONCLUSIONS: Four percent of individuals who undergo research brain MRIs have an incidental, potentially clinically significant finding. Routine neuroradiologist review of all scans yields a much higher rate of significant lesion detection than selective referral from nonradiologists who perform the examinations. Workflow and scan review processes need to be carefully considered when designing research protocols.

Synthetic MRI for Clinical Neuroimaging: Results of the Magnetic Resonance Image Compilation (MAGiC) Prospective, Multicenter, Multireader Trial.

BACKGROUND AND PURPOSE: Synthetic MR imaging enables reconstruction of various image contrasts from 1 scan, reducing scan times and potentially providing novel information. This study is the first large, prospective comparison of synthetic-versus-conventional MR imaging for routine neuroimaging. MATERIALS AND METHODS: A prospective multireader, multicase noninferiority trial of 1526 images read by 7 blinded neuroradiologists was performed with prospectively acquired synthetic and conventional brain MR imaging case-control pairs from 109 subjects (mean, 53.0 ± 18.5 years of age; range, 19-89 years of age) with neuroimaging indications. Each case included conventional T1- and T2-weighted, T1 and T2 FLAIR, and STIR and/or proton density and synthetic reconstructions from multiple-dynamic multiple-echo imaging. Images were randomized and independently assessed for diagnostic quality, morphologic legibility, radiologic findings indicative of diagnosis, and artifacts. RESULTS: Clinical MR imaging studies revealed 46 healthy and 63 pathologic cases. Overall diagnostic quality of synthetic MR images was noninferior to conventional imaging on a 5-level Likert scale (P < .001; mean synthetic-conventional, -0.335 ± 0.352; Δ = 0.5; lower limit of the 95% CI, -0.402). Legibility of synthetic and conventional morphology agreed in >95%, except in the posterior limb of the internal capsule for T1, T1 FLAIR, and proton-density views (all, >80%). Synthetic T2 FLAIR had more pronounced artifacts, including +24.1% of cases with flow artifacts and +17.6% cases with white noise artifacts. CONCLUSIONS: Overall synthetic MR imaging quality was similar to that of conventional proton-density, STIR, and T1- and T2-weighted contrast views across neurologic conditions. While artifacts were more common in synthetic T2 FLAIR, these were readily recognizable and did not mimic pathology but could necessitate additional conventional T2 FLAIR to confirm the diagnosis.

Training for cytotechnologists and cytopathologists in the developing world.

Currently there is a major challenge to train sufficient cytopathologists and cytotechnicians in developing countries that have poor medical and pathology infrastructure. Cytology requires well trained pathologists and laboratory staff but it needs only minimal laboratory resources. Cytology can provide the material for rapid, accurate and inexpensive diagnoses of infections such as tuberculosis and of benign and malignant palpable and impalpable lesions. Cytology can achieve this in the developing world by utilizing fine needle aspiration biopsy cytology, general fluids cytology and cervical cytology, in the same manner as is currently done in the developed world where cytology specimens are used to make cytomorphological diagnoses and increasingly to provide material for the full range of ancillary testing including molecular pathology. There are a number of ways to develop sustainable training in cytology in developing countries, especially in fine needle aspiration biopsy cytology, and these are presented and discussed.

Traumatic brain injury imaging research roadmap.

The past decade has seen impressive advances in the types of neuroimaging information that can be acquired in patients with traumatic brain injury. However, despite this increase in information, understanding of the contribution of this information to prognostic accuracy and treatment pathways for patients is limited. Available techniques often allow us to infer the presence of microscopic changes indicative of alterations in physiology and function in brain tissue. However, because histologic confirmation is typically lacking, conclusions reached by using these techniques remain solely inferential in almost all cases. Hence, a need exists for validation of these techniques by using data from large population samples that are obtained in a uniform manner, analyzed according to well-accepted procedures, and correlated with closely monitored clinical outcomes. At present, many of these approaches remain confined to population-based research rather than diagnosis at an individual level, particularly with regard to traumatic brain injury that is mild or moderate in degree. A need and a priority exist for patient-centered tools that will allow advanced neuroimaging tools to be brought into clinical settings. One barrier to developing these tools is a lack of an age-, sex-, and comorbidities-stratified, sequence-specific, reference imaging data base that could provide a clear understanding of normal variations across populations. Such a data base would provide researchers and clinicians with the information necessary to develop computational tools for the patient-based interpretation of advanced neuroimaging studies in the clinical setting. The recent "Joint ASNR-ACR HII-ASFNR TBI Workshop: Bringing Advanced Neuroimaging for Traumatic Brain Injury into the Clinic" on May 23, 2014, in Montreal, Quebec, Canada, brought together neuroradiologists, neurologists, psychiatrists, neuropsychologists, neuroimaging scientists, members of the National Institute of Neurologic Disorders and Stroke, industry representatives, and other traumatic brain injury stakeholders to attempt to reach consensus on issues related to and develop consensus recommendations in terms of creating both a well-characterized normative data base of comprehensive imaging and ancillary data to serve as a reference for tools that will allow interpretation of advanced neuroimaging tests at an individual level of a patient with traumatic brain injury. The workshop involved discussions concerning the following: 1) designation of the policies and infrastructure needed for a normative data base, 2) principles for characterizing normal control subjects, and 3) standardizing research neuroimaging protocols for traumatic brain injury. The present article summarizes these recommendations and examines practical steps to achieve them.

Myositis due to the microsporidian Anncaliia (Brachiola) algerae in a lung transplant recipient.

Microsporidia are obligate intracellular parasites, more closely related to fungi than protozoa on molecular phylogenetic analysis, and are known to be a rare cause of opportunistic infection in immune compromised patients including human immunodeficiency virus-positive patients and solid organ transplant recipients. We report the first case to our knowledge of microsporidial myositis in a lung transplant recipient. He was 49 years old and had received a lung transplant in 2000 for cystic fibrosis. He presented in 2009 with fevers, chronic diarrhea, myalgia, and pancytopenia, and developed progressive weakness and neurological symptoms before his death 35 days after hospital admission. Multiple investigations, including stool culture, rectal biopsy, colonoscopy, cerebrospinal fluid examination, bone marrow biopsy, lung biopsy, and bronchoalveolar lavage, failed to reveal a definite cause for the patient's deterioration. The diagnosis of microsporidial infection was made on post-mortem light microscopic examination of tissue sections of the tongue and deltoid muscle. Light microscopy diagnosed a microsporidial myositis, confirmed by transmission electron microscopy, which suggested that the organism was Brachiola species. The identity of the organism was confirmed by polymerase chain reaction as Brachiola algerae (recently renamed Anncaliia algerae). The case highlights the need to consider protozoal organisms in the differential diagnosis of myalgia and multisystemic infections in immune compromised patients.

Assisting cytopathology training in medically under-resourced countries: defining the problems and establishing solutions.

Cytology is able to deliver rapid accurate diagnoses with minimal equipment and laboratory infrastructure at minimal cost, and this is especially so for fine needle biopsy (FNB), which is a powerful diagnostic tool in medically resource-poor environments, where histopathology laboratories are small in number and poorly supported financially. The crucial element in the development of cytology services is to train a sufficient number of well trained cytopathologists and cytotechnologists to create a 'critical mass' of personnel who not only provide routine diagnostic services, but also can train an ever expanding number of pathologists, cytotechnologists, and health workers. A review of practical programs to train cytopathologists and cytotechnologists in their own countries will be presented, including a recent series of FNB and cytology tutorials run in sub Saharan Africa. The need for local cytopathology programs and the potential for both local and visiting cytopathologists to provide a faculty will be discussed, as well as a range of possible programs which can bring African pathologists and trainee pathologists to Western institutions for periods of their training. Ideally, the regional Societies of Cytology, including the recently formed West African Society of Cytology, will establish their own diagnostic protocols, training programs, syllabuses, examinations and accreditation and career pathways for both cytopathologists and cytotechnologists, and organize tutorials where they will invite overseas faculty to contribute. Crucially, these new societies will empower cytopathologists and cytotechnologists to approach health services and governments to state the need for cytology services as a cost-effective accurate diagnostic service that enhances patient care.

Impact of brain tumor location on morbidity and mortality: a retrospective functional MR imaging study.

BACKGROUND AND PURPOSE: fMRI is increasingly used in neurosurgery to preoperatively identify areas of eloquent cortex. Our study evaluated the efficacy of clinical fMRI by analyzing the relationship between the distance from the tumor border to the area of functional activation (LAD) and patient pre- and postoperative morbidity and mortality. MATERIALS AND METHODS: The study included patients with diagnosis of primary or metastatic brain tumor who underwent preoperative fMRI-based motor mapping (n=74) and/or language mapping (n=77). The impact of LAD and other variables collected from patient records was analyzed with respect to functional deficits in terms of morbidity (paresis and aphasia) and mortality. RESULTS: Significant relationships were found between motor and language LAD and the existence of either pre- or postoperative motor (P < .001) and language deficits (P=.009). Increasing age was associated with motor and language deficits (P=.02 and P=.04 respectively). Right-handedness was related to language deficits (P=.05). Survival analysis revealed that pre- and postoperative deficits, grade, tumor location, and LAD predicted mortality. Motor deficits increased linearly as the distance from the tumor to the primary sensorimotor cortex decreased. Language deficits increased exponentially as the distance from the tumor to the language areas decreased below 1 cm. Postoperative mortality analysis showed an interaction effect between motor or language LAD and mortality predictors (grade and tumor location, respectively). CONCLUSIONS: These findings indicate that tumors may affect language and motor function differently depending on tumor LAD. Overall, the data support the use of fMRI as a tool to evaluate patient prognosis and are directly applicable to neurosurgical planning.

Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study.

BACKGROUND: Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease. OBJECTIVE: To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study. METHODS: Five subjects with newly diagnosed, treatment-naive relapsing-remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial. RESULTS: The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects. CONCLUSION: TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.

Effects of aging and calorie restriction on white matter in rhesus macaques.

Rhesus macaques on a calorie restricted diet (CR) develop less age-related disease, have virtually no indication of diabetes, are protected against sarcopenia, and potentially live longer. Beneficial effects of caloric restriction likely include reductions in age-related inflammation and oxidative damage. Oligodendrocytes are particularly susceptible to inflammation and oxidative stress, therefore, we hypothesized that CR would have a beneficial effect on brain white matter and would attenuate age-related decline in this tissue. CR monkeys and controls underwent diffusion tensor imaging (DTI). A beneficial effect of CR indexed by DTI was observed in superior longitudinal fasciculus, fronto-occipital fasciculus, external capsule, and brainstem. Aging effects were observed in several regions, although CR appeared to attenuate age-related alterations in superior longitudinal fasciculus, frontal white matter, external capsule, right parahippocampal white matter, and dorsal occipital bundle. The results, however, were regionally specific and also suggested that CR is not salutary across all white matter. Further evaluation of this unique cohort of elderly primates to mortality will shed light on the ultimate benefits of an adult-onset, moderate CR diet for deferring brain aging.

Age-related changes in neural volume and microstructure associated with interleukin-6 are ameliorated by a calorie-restricted diet in old rhesus monkeys.

Systemic levels of proinflammatory cytokines such as interleukin-6 (IL-6) increase in old age and may contribute to neural atrophy in humans. We investigated IL-6 associations with age in T1-weighted segments and microstructural diffusion indices using MRI in aged rhesus monkeys (Macaca mulatta). Further, we determined if long-term 30% calorie restriction (CR) reduced IL-6 and attenuated its association with lower tissue volume and density. Voxel-based morphometry (VBM) and diffusion-weighted voxelwise analyses were conducted. IL-6 was associated with less global gray and white matter (GM and WM), as well as smaller parietal and temporal GM volumes. Lower fractional anisotropy (FA) was associated with higher IL-6 levels along the corpus callosum and various cortical and subcortical tracts. Higher IL-6 concentrations across subjects were also associated with increased mean diffusivity (MD) throughout many brain regions, particularly in corpus callosum, cingulum, and parietal, frontal, and prefrontal areas. CR monkeys had significantly lower IL-6 and less associated atrophy. An IL-6xCR interaction across modalities also indicated that CR mitigated IL-6 related changes in several brain regions compared to controls. Peripheral IL-6 levels were correlated with atrophy in regions sensitive to aging, and this relationship was decreased by CR.

Fetal origin of the posterior cerebral artery produces left-right asymmetry on perfusion imaging.

BACKGROUND AND PURPOSE: Fetal origin of the PCA is a common anatomic variation of the circle of Willis. On perfusion imaging, patients with unilateral fetal-type PCA may demonstrate left-right asymmetry that could mimic cerebrovascular disease. The aim of this study was to characterize the relationship between a fetal-type PCA and asymmetry of hemodynamic parameters derived from MR perfusion imaging. MATERIALS AND METHODS: We retrospectively reviewed MR perfusion studies of 36 patients to determine the relationship between hemodynamic and vascular asymmetries in the PCA territory. Perfusion asymmetry indices for the PCA territory were computed from maps of rCBF, rCBV, MTT, T(max), and FMT. Vascular asymmetry indices were derived from calibers of the PCA-P1 segments relative to the posterior communicating arteries. RESULTS: Asymmetrically smaller values of FMT and T(max) were observed with unilateral fetal-type PCA, and these were strongly correlated with the degree of vascular asymmetry (Spearman's rho = 0.76 and 0.74, respectively, P < 1 x 10(-6)). Asymmetries of rCBF, MTT, and rCBV were neither significant nor related to vascular asymmetry. CONCLUSIONS: Faster perfusion transit times are seen for parameters sensitive to macrovascular transit effects (eg, FMT and T(max)) ipsilateral to fetal origin of the PCA in proportion to the degree of arterial asymmetry. Knowledge of this normal variation is critical in the interpretation of perfusion studies because asymmetry could mimic cerebrovascular pathology.

White matter reorganization after surgical resection of brain tumors and vascular malformations.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) and white matter tractography (WMT) are promising techniques for estimating the course, extent, and connectivity patterns of the white matter (WM) structures in the human brain. In this study, DTI and WMT were used to evaluate WM tract reorganization after the surgical resection of brain tumors and vascular malformations. METHODS: Pre- and postoperative DTI data were obtained in 6 patients undergoing surgical resection of brain lesions. WMT using a tensor deflection algorithm was used to reconstruct WM tracts adjacent to the lesions. Reconstructed tracts included corticospinal tracts, the corona radiata, superior longitudinal and inferior fronto-occipital fasciculi, cingulum bundles, and the corpus callosum. RESULTS: WMT revealed a series of tract alteration patterns including deviation, deformation, infiltration, and apparent tract interruption. In general, the organization of WM tracts appeared more similar to normal anatomy after resection, with either disappearance or reduction of the deviation, deformation, or infiltration present preoperatively. In patients whose lesions were associated with corticospinal tract involvement, the WMT reconstructions showed that the tract was preserved during surgery and improved in position and appearance, and this finding correlated with improvement or preservation of motor function as determined by clinical assessment. CONCLUSION: WMT is useful for appreciating the complex relationships between specific WM structures and the anatomic distortions created by brain lesions. Further studies with intraoperative correlation are necessary to confirm these initial findings and to determine WMT utility for presurgical planning and evaluation of surgical treatments.

Hormone replacement therapy use dramatically increases breast oestrogen receptor expression in obese postmenopausal women.

BACKGROUND: It is known that use of hormone replacement therapy (HRT) by postmenopausal women increases the risk of breast cancer. METHOD: In this study, oestrogen receptor (ER)-alpha expression is examined using standard immunoperoxidase technique. RESULTS: Normal breast samples of 11 Australian postmenopausal women have been included in the ER-alpha study; the result showed a strong correlation (r(2) = 0.80) between ER-alpha expression in normal breast epithelial cells and body mass index (BMI) in normal women who currently use HRT. CONCLUSION: This finding confirms that the possibility of increased risk of breast cancer associated with increased ER-alpha expression in normal breast epithelial cells, in turn associated with high BMI and the use of HRT.

Suggestions for HER-2/neu testing in breast carcinoma, based on a comparison of immunohistochemistry and fluorescence in situ hybridisation.

The arrival of Herceptin (Trastuzumab), an antibody against the HER-2 oncogene found in a proportion of breast carcinomas and other carcinomas, has emphasised the need for a standardised technique for demonstrating overexpression of HER-2. We compared the Dako A485 antibody and Dako HercepTest kit (HT) on a series of 122 breast carcinomas. Fluorescence in situ hybridisation (FISH) (Vysis) was performed on all cases with positive or equivocal immunohistochemical results. The Dako A485 showed HER-2 overexpression in 53% of carcinomas, while the HT showed 21% positive (HT 2+ 8%, HT 3+ 13%) and 79% negative (HT 0 67%, HT 1+ 12%). FISH for HER-2 gene amplification on all the HT 1+ and HT 2+ cases was negative, whereas FISH analysis of all HT 3+ cases was positive, with the exception of one case which could not be analysed for technical reasons. When histological subtype was analysed, only grade 3 infiltrating duct carcinomas were FISH-positive, suggesting that histological grading and subtyping may be able to triage carcinomas suitable for HER-2 testing. We suggest that the HT or a similar standardised immunohistochemical study for HER-2 can be used to screen breast carcinomas. We then recommend FISH where the carcinoma is HT 2+. FISH may also be appropriate in high grade, HT 1+ carcinomas where there are doubts regarding optimal tissue fixation or block storage conditions.

False cerebral activation on BOLD functional MR images: study of low-amplitude motion weakly correlated to stimulus.

BACKGROUND AND PURPOSE: Movements of the participant during blood oxygen level-dependent (BOLD) functional MR imaging cerebral activation studies are known to produce occasionally regions of false activation, especially when these movements are relatively large (>3 mm) and highly correlated with the stimulus. We investigated whether minimal (<1 mm), weakly correlated movements in a controlled functional MR imaging model could produce false activation artifacts that could potentially mimic regions of true activation in size, location, and statistical significance. METHODS: A life-size brain phantom was constructed by embedding vials of a dilute carboxylic acid solution within a gadolinium-doped gelatin mold. Imaging was performed at 1.5 T using a 2D spiral sequence (3,000/5 [TR/TE]; flip angle, 88 degrees; matrix, 64 x 64; field of view, 24 cm; section thickness, 5 mm). Controlled, in-plane, submillimeter movements of the phantom were generated using a pneumatic system and were made to correlate with a hypothetical "boxcar" stimulus over the range 0.31 < r < 0.96. Regions of false activation were sought using standard statistical methods (SPM96) that excluded phantom edges and accounted for spatial extent (regions tested at P < .05, corrected for multiple comparisons). A similar experiment was performed on a resting volunteer. RESULTS: The pneumatic system provided motion control with average in-plane displacements and rotations of 0.74 mm and 0.47 degrees, respectively, in the 18 data sets analyzed. No areas of false activation in the phantom were identified for poorly correlated motions (r < 0.52). Above this level, false activations occurred with increasing frequency, scaling in size and number with the degree of motion correlation. For motions with r > 0.67, areas of false activation were seen in every experiment. For a statistical threshold of P = .001, the median number of falsely activated regions was 3.5, with a mean size of 71.7 voxels (approximately 5 cc). Areas of possibly false activation of average size 72.5 voxels resulting from passive motion of the resting human participant were observed in two of four experiments. CONCLUSION: Participant movements of 1 mm or less that are only modestly correlated with a blocked stimulus paradigm can produce appreciable false activation artifacts on BOLD functional MR imaging studies, even when strict image realignment methods are used to prevent them.

Low oestrogen receptor alpha expression in normal breast tissue underlies low breast cancer incidence in Japan.

Among white Australians without breast cancer, the median of the percentage of oestrogen receptor alpha positive cells was 12% for women younger than 50 years and 17% for those 50 years or older; among Japanese women who had no breast cancer and are generally at low risk for this disease, the corresponding values were both significantly lower and around 9%.

Cyclin D1 protein is overexpressed in hyperplasia and intraductal carcinoma of the breast.

The cell cycle regulatory gene cyclin D1 is a candidate oncogene in breast cancer. It is overexpressed in 30-50% of invasive primary breast cancers and plays a key role in mediating mitogenic responses to steroids and growth factors in breast cancer cells in vitro. Because the role of cyclin D1 in the proliferative and early noninvasive stages of breast cancer is largely unknown, we examined normal breast epithelium (NBE), proliferative disease (PD), ductal carcinoma in situ (DCIS), and invasive carcinoma (IC) to evaluate the timing and possible importance of cyclin D1 expression in the development of breast cancer. Using immunohistochemistry, we examined cyclin D1 protein expression in 471 breast tissue samples. A quantitative scoring system for immunohistochemistry based on percentage of positive cells was developed that correlated with Western blot analysis of antigen concentration in paired samples (r2 = 0.91, P = 0.003). A sample was considered positive if >5% of relevant epithelial cells demonstrated nuclear staining. Cyclin D1 positivity was observed in 11.7% (7 of 60) samples of NBE, 25% (11 of 44) of PD without atypia, 39.4% (13 of 33) of atypical ductal hyperplasia, 43.6% (17 of 39) of low-grade DCIS, 47.9% (23 of 48) of high-grade DCIS, and 48.3% (99 of 205) of IC. Cyclin D1 expression was significantly higher in PD than NBE (P = 0.006) and in DCIS than PD (P = 0.038). There was no significant increase from DCIS to IC (P = 0.52). The increase in cyclin D1 expression in the overall progression from NBE to IC was also highly significant (P = 0.0001). Therefore, cyclin D1 expression was detected at levels significantly greater than in NBE in the earliest proliferative epithelial lesions of the breast with a further significant increase accompanying the progression to any form of cancer. This suggests that overexpression of cyclin D1 protein is important at the earliest stages of breast oncogenesis and continues to have a crucial role throughout the development of malignancy.

Myositis associated with a newly described microsporidian, Trachipleistophora hominis, in a patient with AIDS.

Microsporidia are zoonotic protozoa which were rare human pathogens prior to 1985, when Enterocytozoon bieneusi was described in human immunodeficiency virus-infected patients with chronic diarrhea. Another species, Encephalitozoon (Septata) intestinalis, is associated with diarrhea and chronic sinusitis, and approximately 25 cases have been reported in the literature. However, other microsporidial infections in human immunodeficiency virus-infected patients remain extremely rare. We report the first case of a Pleistophora sp.-like microsporidian infection presenting as a progressive severe myosotis associated with fever and weight loss. The organism was demonstrated by light microscopy and electron microscopy in corneal scrapings, skeletal muscle, and nasal discharge. Electron microscopy showed an electron-dense surface coat with "sunflare"-like projections surrounding all stages of development of meronts (two to four nuclei, dividing by binary fission), sporonts, and sporoblasts. Division of sporonts, in which sporonts separate from the thick outer coat, creating a sporophorous vesicle, is by binary fission, differentiating this organism from Pleistophora sp. The spore measures 4.0 by 2.5 microns and has a rugose exospore. A new genus and species, Trachipleistophora hominis, has been established for this parasite. The patient was treated with albendazole, sulfadiazine, and pyrimethamine, and the clinical symptoms resolved.

Development and ultrastructure of Trachipleistophora hominis n.g., n.sp. after in vitro isolation from an AIDS patient and inoculation into athymic mice.

Continuous culture was achieved in several cell lines of a microsporidium obtained from the skeletal muscle of an AIDS patient. Development in COS-1 and RK13 cells was prolific. Spores from the original biopsy were also inoculated into athymic mice by i.m. and i.p. routes. Infection was found in several organs as well as in skeletal muscle after a few weeks. All stages were surrounded by an electron-dense surface coat. Meronts had 2-4 nuclei and divided by binary fission. In sporogony the surface coat became separated from the plasma membrane to form a sporophorous vesicle, within which division into sporoblasts was effected by repeated binary fissions. The number of sporoblasts (and later spores) within the sporophorous vesicles varied from 2 to > 32 and the sizes of the vesicles varied, according to the number of spores contained therein, from 5 microns diameter to 14.0 x 11.0 microns. Spores measured 4.0 x 2.4 microns and had a prominent posterior vacuole. The parasite differs from the genus Pleistophora in that it does not form multinucleate sporogonial plasmodia and that the sporophorous vesicle enlarges during sporogony and its wall is not a multilayered structure. It is proposed to place it in a new genus and species Trachipleistophora hominis n.g., n.sp.