Prominent Perivascular Spaces Research Articles

P-444. Cerebral Small Vessel disease risk in people with HIV and substance use disorder

Abstract Background Cerebral small vessel disease (CSVD) is associated with an increased risk of stroke, dementia, and death. The risk of CSVD in people with HIV (PWH) is twice the general population but the CSVD risk in PWH with substance abuse is poorly defined. With national surveys showing approximately two-thirds of PWH admitting to using an illicit drug in their lifetime, the evaluation of CSVD risk in this population is needful.Table 1:Demographic and Clinical information of CSVD in PWH with substance use disorder (N=23) Methods We retrospectively analyzed brain magnetic resonance imaging (MRI) findings of PWH attending our ambulatory HIV needle exchange clinic. Brain MRIs done in the previous 5 years before study analysis were included. CSVD was determined by Cerebral small vessel disease score (0 to 4), assigning 1 point each for the following: (i) presence of lacunar infarct, (ii) microbleeds, (iii) prominent perivascular spaces, and (iv) white matter hyperintensities. The findings suggestive of CSVD such as age-related white matter changes and chronic microvascular ischemia were also included in the CSVD assessment. Substance use disorder (uncontrolled use of a substance despite harmful consequences) was determined to be present if this was included on the patient diagnosis list.Table 2:Cerebral Small Vessel disease Score in PWH with substance use disorder. 5 participants had a CSVD score of 0 but "age related white matter disease" on Brain MRI Results 51 patients (PWH with substance use disorder) were included in the analysis. 23 participants out of this group had brain MRI imaging out of which 12 (52.2%) had CSVD. The mean age was 50 years. The demographic and clinical data of the cohort are shown in Table 1. The CSVD score ranged from 0 to 3 with an average score of 1. Table 2 illustrates the CSVD score of the cohort. 5 participants had a CSVD score of 0 but a brain MRI report of “age-related white matter changes”. The Pearson Correlation between age and CSVD score was 0.057 with a p-value of 0.86. Conclusion 52% of PWH who use substance have CSVD on MRI brain imaging. This could translate to an increased risk of stroke, cognitive impairment, and death if not recognized early and aggressively addressed. CSVD score provides objective quantification of CSVD but age-related white matter changes, which are not captured on this score may be equally important especially as PWH continues to age. A systematic approach for screening for CSVD in PWH with substance use disorder is warranted to minimize the unfavorable outcomes associated with this cohort. Disclosures All Authors: No reported disclosures

Exploring the neurological features of individuals with germline PTEN variants: A multicenter study.

PTEN, a known tumor suppressor gene, is a mediator of neurodevelopment. Individuals with germline pathogenic variants in the PTEN gene, molecularly defined as PTEN hamartoma tumor syndrome (PHTS), experience a variety of neurological and neuropsychiatric challenges during childhood, including autism spectrum disorder (ASD). However, the frequency and nature of seizures and the utilization of allied health services have not been described. Young patients with PHTS and sibling controls were recruited across five centers in the United States and followed every 6-12 months for a mean of 2.1 years. In addition to the history obtained from caregivers, neurodevelopmental evaluations and structured dysmorphology examinations were conducted, and brain MRI findings, received therapies, and epilepsy characteristics were reported. One hundred and seven patients with PHTS (median age 8.7 years; range 3-21 years) and 38 controls were enrolled. ASD and epilepsy were frequent among patients with PHTS (51% and 15%, respectively), with generalized epilepsy strongly associated with ASD. Patients with epilepsy often required two antiseizure medications. Neuroimaging revealed prominent perivascular spaces and decreased peritrigonal myelination in individuals with PHTS-ASD. Allied therapy use was frequent and involved physical, occupational, speech, and social skills therapies, with 89% of all patients with PHTS, regardless of ASD diagnosis, utilizing at least one service. This prospective, longitudinal study highlights the wide neurological spectrum seen in young individuals with PHTS. ASD is common in PHTS, comorbid with epilepsy, and allied health services are used universally. Our findings inform care discussions with families about neurological outcomes in PHTS.

Association of deep medullary veins with the neuroimaging burden of cerebral small vessel disease

This study aimed to explore the association between deep medullary veins (DMVs) and the neuroimaging burden of cerebral small vessel disease (CSVD). In this cross-sectional study based on a retrospective analysis, a total of 248 patients (183 males and 65 females; mean age ± standard deviation, 69.5±14.8 years) diagnosed with CSVD with complete imaging and clinical data were enrolled. Neuroimaging markers of CSVD, including white matter hyperintensities, lacunes, prominent perivascular spaces (PVSs), and cerebral microbleeds (CMBs), were identified, and the total burden of CSVD was scored. Both DMV number and DMV score were used for assessment using susceptibility-weighted imaging (SWI). With the exception of perivascular spaces, more severe neuroimaging markers were observed in patients with a higher DMV score. After adjustments were made for age and body mass index (BMI), a higher DMV score (β=1.39; P<0.001) and smaller DMV number (β=-2.55; P=0.001) were associated with an increased CSVD burden. The degree of CMBs was independently correlated with both DMV score (β=1.60; P<0.001) and DMV number (β=-2.27; P=0.009). The association between lacunes and DMV score was also significant (β=0.97; P=0.026). Both DMV score and DMV number are potential imaging indicators of CSVD.

EP296: Familial MECP2 variants: a report of 4 affected families highlighting the variable phenotypic spectrum and implications for genetic counseling

Pathogenic variants in MECP2 cause a spectrum of neurodevelopmental disorders, most commonly Rett syndrome (RTT; 312750). Although historically this was considered an X-linked dominant diagnosis with male lethality, it is now known that males can also be affected, with a disease spectrum ranging from severe neonatal encephalopathy to intellectual disability (ID). Other features commonly seen in RTT are inconsistently present in males. A qualified genotype-phenotype correlation exists, with variants that are known to cause RTT in females most often leading to more severe phenotypes in males. Additionally, whereas pathogenic MECP2 variants identified in affected females with classic and atypical RTT are most often de novo variants, pathogenic variants in males may be either de novo or maternally inherited. Here we report 4 novel families with pathogenic MECP2 variants. In all 4 families, the affected probands were male and maternal inheritance was identified. Family 1: The proband is a now 8-year-old male with mild global developmental delay, epilepsy, ataxia, and hypotonia. He also has significant anxiety. Epilepsy gene panel identified a hemizygous pathogenic variant in MECP2 (c.491C>T; p.Ala140Val); targeted testing confirmed maternal inheritance. His mother has no significant medical issues or learning issues, but endorses a history of anxiety. He has four clinically unaffected siblings; one brother has been tested and is negative. His other brother and sisters have not been tested. Family 2: The proband is a now 47-year-old male with mild-moderate intellectual disability. Genetic testing was initiated after MRI performed in the context an episode of confusion and shaking concerning for a panic attack revealed signal abnormalities in the bilateral cerebral peduncles possibly concerning for Fragile X Associated Tremor Ataxia Syndrome (FXTAS). He also experienced a motor regression and onset of dystonia after an episode of rhabdomyolysis in his mid 40’s and has not returned to baseline. Trio exome sequencing identified a maternally inherited hemizygous pathogenic variant (c.499C>T; p.Arg167Trp) in MECP2. Cascade testing identified that his sister and niece also both carry the familial MECP2 variant. His sister has a history of learning difficulties, significant anxiety, obsessive compulsive disorder, and has developed progressive spasticity with hyperreflexia and sustained clonus over time. His niece also has anxiety, obsessive compulsive disorder, and bipolar disorder. Family 3: The proband is a now 37-year-old male with mild intellectual disability and autism spectrum disorder. He also has a history of anxiety and depression. Trio exome sequencing identified a maternally inherited hemizygous pathogenic variant (c. 1136_1151del16; p.Pro379HfsX25) in MECP2. Testing was initiated after the onset of abnormal movements in his thirties suggestive of dystonia. Exam was notable for kyphosis and shuffling gait. His mother reports a history of anxiety, but no learning or cognitive concerns and no other neurologic symptoms. He has one clinically unaffected sister who has not yet been tested. Exome sequencing also identified a de novo, heterozygous c.1672C>T (p.Arg558Cys) variant of uncertain significance in ALDH18A1, though it is unclear whether or not this is contributing to his phenotype. Family 4: The proband is a now 8-year-old male who initially presented for evaluation due to concern for global developmental delay, hypotonia, and macrocephaly. Family history was unremarkable. MRI identified prominent perivascular spaces. Trio exome sequencing identified a maternally inherited likely pathogenic hemizygous variant (c.1244delC; p.Pro415LeufsX6) in MECP2. The proband’s younger brother subsequently presented with expressive language delay and was also macrocephalic. Targeted testing confirmed the presence of the familial MECP2 variant. These 4 familial reports of pathogenic MECP2 variants add to the data provided by previous publications describing the phenotypic spectrum in affected males and supporting that many of the variants may be maternally inherited. Affected male probands in all cases presented with developmental delay and/or intellectual disability. Only 1/4 probands had epilepsy. Anxiety was present in 3/4. Cascade testing identified carrier female relatives with a prominent neuropsychiatric phenotype in one family. Anxiety was also reported in the mothers of two other families, without any other cognitive or neurologic features. Although two families harbored pathogenic missense variants previously known to be associated with an X-linked intellectual disability phenotype, two families with mildly affected male probands and unaffected female carrier mothers had novel, predicted loss of function variants that would have been expected to result in a RTT phenotype. These families highlight the clinical variability that can be seen with pathogenic MECP2 variants and challenge reported genotype-phenotype correlations, providing important information for genetic counseling.

Small Vessel Disease, a Marker of Brain Health: What the Radiologist Needs to Know.

Small vessel disease, a disorder of cerebral microvessels, is an expanding epidemic and a common cause of stroke and dementia. Despite being almost ubiquitous in brain imaging, the clinicoradiologic association of small vessel disease is weak, and the underlying pathogenesis is poorly understood. The STandards for ReportIng Vascular changes on nEuroimaging (STRIVE) criteria have standardized the nomenclature. These include white matter hyperintensities of presumed vascular origin, recent small subcortical infarcts, lacunes of presumed vascular origin, prominent perivascular spaces, cerebral microbleeds, superficial siderosis, cortical microinfarcts, and brain atrophy. Recently, the rigid categories among cognitive impairment, vascular dementia, stroke, and small vessel disease have become outdated, with a greater emphasis on brain health. Conventional and advanced small vessel disease imaging markers allow a comprehensive assessment of global brain heath. In this review, we discuss the pathophysiology of small vessel disease neuroimaging nomenclature by means of the STRIVE criteria, clinical implications, the role of advanced imaging, and future directions.

The role of MRI and CT of the brain in first episodes of psychosis and behavioural abnormality

To investigate whether computed tomography (CT)/magnetic resonance imaging (MRI) brain imaging is associated with detection of structural causes of a first episode of psychosis (FEP) or first episode of behavioural abnormality (FEB) in the paediatric population, as this has not been previously documented in the literature. Individuals with FEP/FEB but no neurological signs referred to a tertiary children's centre for cerebral MRI or CT were reviewed retrospectively. Individuals were evaluated independently with one technique (CT or MRI) only. Thirty-four consecutive cerebral MRI and six consecutive CT examinations were identified between 2017 and 2020. No patients were identified as having an organic cause for the psychosis at MRI or CT. Four patients (9%) had incidental findings on MRI, unrelated to the psychosis, such as prominent perivascular spaces, hypoplastic transverse sinus, and sinonasal mucosal wall thickening. No abnormal findings were seen on CT. There was therefore no obvious difference between MRI and CT imaging in detecting organic disease potentially responsible for FEP. Routine structural MRI or CT of the brain is unlikely to reveal disease leading to a significant change in management. MRI demonstrated only a few incidental findings, unrelated to the child's clinical history. Therefore, routine brain structural imaging of FEP/FEB in paediatric patients without focal neurology may not be routinely required. If imaging is requested, then there is no significant difference between CT and MRI in detecting clinically significant lesions.

Brain MR Imaging Findings in Woodhouse-Sakati Syndrome

Woodhouse-Sakati syndrome is a rare autosomal recessive disorder characterized by hypogonadism, alopecia, diabetes mellitus, and progressive extrapyramidal signs. The disease is caused by biallelic pathogenic variants in the DCAF17 gene. The purpose of this study was to describe the spectrum of brain MR imaging abnormalities in Woodhouse-Sakati syndrome. We reviewed brain MR images of 26 patients with a clinical and genetic diagnosis of Woodhouse-Sakati syndrome (12 males, 14 females; age range, 16-45 years; mean age, 26.6 years). Follow-up studies were conducted for 6 patients. All patients had abnormal MR imaging findings. The most common abnormalities were a small pituitary gland (76.9%), pronounced basal ganglia iron deposition (73%), and white matter lesions in 69.2%. White matter lesions showed frontoparietal and periventricular predominance. All white matter lesions spared subcortical U-fibers and were nonenhanced. Prominent perivascular spaces (15.3%) and restricted diffusion in the splenium of the corpus callosum (7.6%) were less frequent findings. Follow-up studies showed expansion of white matter lesions with iron deposition further involving the red nucleus and substantia nigra. Older age was associated with a more severe degree of white matter lesions (P < .001). Small pituitary gland, accentuated iron deposition in the globus pallidus, and nonenhancing frontoparietal/periventricular white matter lesions were the most noted abnormalities seen in our cohort. The pattern and extent of these findings were observed to correlate with older age, reflecting a possible progressive myelin destruction and/or axonal loss. The presence of pituitary hypoplasia and white matter lesions can further distinguish Woodhouse-Sakati syndrome from other neurodegenerative diseases with brain iron accumulation subtypes.

Visual Rating Scales of White Matter Hyperintensities and Atrophy: Comparison of Computed Tomography and Magnetic Resonance Imaging

GoalMagnetic resonance imaging (MRI) is the preferred modality for research on structural age-related brain changes. However, computed tomography (CT) is widely available and has practical and cost advantages over MRI for large-scale brain imaging research studies in acutely unwell patients. However, the relationships between MRI and CT measures of white matter hyperintensities (WMH) and atrophy are unclear. We examined the relationships between visual ratings of WMH, atrophy, and old infarcts in patients who had both CT and MRI scans.Materials and MethodsPatients who had both CT and MRI scans in the International Stroke Trial-3 were studied. In both modalities, 2 raters independently completed standardized visual rating scales for WMH, and for central and superficial atrophy using a 5-point scale. In addition, 1 rater recorded old infarcts according to size and location.FindingsSeventy patients with a mean age of 69 years were studied. There were moderate to substantial intrarater CT–MRI agreements for periventricular components of WMH scales (weighted Κappa = .55-.75). Agreements for basal ganglia ratings were lower (weighted Κappa = .18-.44), partly because of the misclassification of prominent perivascular spaces. Atrophy scales showed moderate to substantial CT–MRI agreements (weighted Κappa = .44-.70). MRI was more sensitive in the detection of smaller infarcts and cavitated lesions.ConclusionsStandardized visual rating scales of white matter lesions and atrophy mostly show substantial agreement between CT and MRI. Clinical CT scans have a strong potential for wider exploitation in research studies, particularly in acutely unwell populations.

Neuroimaging in cerebral small vessel disease: Update and new concepts.

ABSTRACT.In recent years, small vessel disease (SVD) has been recognized for its major impact on cognitive impairment in elderly people, where it is often difficult to separate its effects from those of neurodegenerative diseases individually. SVD is a systemic disease, probably related to diffuse endothelial dysfunction, which affects the perforating arterioles, capillaries and venules in the brain. Although often asymptomatic, it is responsible for almost half of all dementia cases and a significant proportion of stroke cases. Imaging features found on magnetic resonance include recent small subcortical infarctions, lacunes of presumed vascular origin, white matter hyperintensity of presumed vascular origin, prominent perivascular spaces and cerebral microbleeds. The recognition of these imaging findings as a spectrum of the same disease caused by endothelial dysfunction of small cerebral vessels can allow an overall analysis of the disease and thus the development of more effective preventive and therapeutic strategies.

Structural brain anomalies in healthy adolescents in the NCANDA cohort: relation to neuropsychological test performance, sex, and ethnicity.

Structural MRI of volunteers deemed "normal" following clinical interview provides a window into normal brain developmental morphology but also reveals unexpected dysmorphology, commonly known as "incidental findings." Although unanticipated, these anatomical findings raise questions regarding possible treatment that could even ultimately require neurosurgical intervention, which itself carries significant risk but may not be indicated if the anomaly is nonprogressive or of no functional consequence. Neuroradiological readings of 833 structural MRI from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) cohort found an 11.8% incidence of brain structural anomalies, represented proportionately across the five collection sites and ethnic groups. Anomalies included 26mega cisterna magna, 15 subarachnoid cysts, 12 pineal cysts, 12 white matter dysmorphologies, 5 tonsillar ectopias, 5 prominent perivascular spaces, 5gray matter heterotopias, 4 pituitary masses, 4 excessively large or asymmetrical ventricles, 4 cavum septum pellucidum, 3 developmental venous anomalies, 1 exceptionally large midsagittal vein, and single cases requiring clinical followup: cranio-cervical junction stenosis, parietal cortical mass, and Chiari I malformation. A case of possible demyelinating disorder (e.g., neuromyelitis optica or multiple sclerosis) newly emerged at the 1-year NCANDA followup, requiring clinical referral. Comparing test performance of the 98 anomalous cases with 619 anomaly-free no-to-low alcohol consuming adolescents revealed significantly lower scores on speed measures of attention and motor functions; these differences were not attributed to any one anomaly subgroup. Further, we devised an automated approach for quantifying posterior fossa CSF volumes for detection of mega cisterna magna, which represented 26.5% of clinically identified anomalies. Automated quantification fit a Gaussian distribution with a rightward skew. Using a 3SD cut-off, quantification identified 22 of the 26 clinically-identified cases, indicating that cases with percent of CSF in the posterior-inferior-middle aspect of the posterior fossa ≥3SD merit further review, and support complementing clinical readings with objective quantitative analysis. Discovery of asymptomatic brain structural anomalies, even when no clinical action is indicated, can be disconcerting to the individual and responsible family members, raising a disclosure dilemma: refrain from relating the incidental findings to avoid unnecessary alarm or anxiety; or alternatively, relate the neuroradiological findings as "normal variants" to the study volunteers and family, thereby equipping them with knowledge for the future should they have the occasion for a brain scan following an illness or accident that the incidental findings predated the later event.

Correlation between morphological MRI findings and specific diagnostic categories in fetal alcohol spectrum disorders

Fetal alcohol spectrum disorders (FASD) include physical and neurodevelopmental abnormalities related to prenatal alcohol exposure. Some neuroimaging findings have been clearly related to FASD, including corpus callosum and cerebellar anomalies. However, detailed studies correlating with specific FASD categories, that is, the fetal alcohol syndrome (FAS), partial FAS (pFAS) and alcohol related neurodevelopmental disorders (ARND), are lacking. We prospectively performed clinical assessment and brain MR imaging to 72 patients with suspected FASD, and diagnosis was confirmed in 62. The most frequent findings were hypoplasia of the corpus callosum and/or of the cerebellar vermis. Additional findings were vascular anomalies, gliosis, prominent perivascular spaces, occipito-cervical junction and cervical vertebral anomalies, pituitary hypoplasia, arachnoid cysts, and cavum septum pellucidum.

Myotonic Dystrophy Type 1 with Syringomyelia in a Young Patient

Myotonic Dystrophy Type 1 with Syringomyelia in a Young Patient

Does Rubella Cause Autism: A 2015 Reappraisal?

In the 1970s, Stella Chess found a high prevalence of autism in children with congenital rubella syndrome (CRS), 200 times that of the general population at the time. Many researchers quote this fact to add proof to the current theory that maternal infection with immune system activation in pregnancy leads to autism in the offspring. This rubella and autism association is presented with the notion that rubella has been eliminated in today’s world. CRS cases are no longer typically seen; yet, autistic children often share findings of CRS including deafness, congenital heart defects, and to a lesser extent visual changes. Autistic children commonly have hyperactivity and spasticity, as do CRS children. Both autistic and CRS individuals may develop type 1 diabetes as young adults. Neuropathology of CRS infants may reveal cerebral vasculitis with narrowed lumens and cerebral necrosis. Neuroradiological findings of children with CRS show calcifications, periventricular leukomalacia, and dilated perivascular spaces. Neuroradiology of autism has also demonstrated hyperintensities, leukomalacia, and prominent perivascular spaces. PET studies of autistic individuals exhibit decreased perfusion to areas of the brain similarly affected by rubella. In both autism and CRS, certain changes in the brain have implicated the immune system. Several children with autism lack antibodies to rubella, as do children with CRS. These numerous similarities increase the probability of an association between rubella virus and autism. Rubella and autism cross many ethnicities in many countries. Contrary to current belief, rubella has not been eradicated and globally affects up to 5% of pregnant women. Susceptibility continues as vaccines are not given worldwide and are not fully protective. Rubella might still cause autism, even in vaccinated populations.

Cerebral Lesions on 7 Tesla MRI in Patients with Sickle Cell Anemia

Background: Patients with sickle cell anemia (SCA) are at a high risk to develop cerebral damage. Most common are silent cerebral infarctions (SCIs), visible as white matter hyperintensities (WMHs) on MRI in a patient without neurological deficits. The etiology of SCIs remains largely unclear. In addition, patients are at an increased risk for overt stroke, which is associated with large vessel disease. This classification based on the presence or absence of neurological deficits may not be the most fitting for research purposes, as it does not match the different underlying pathology. A classification based on imaging findings may therefore be a more straightforward approach for research purposes. We explored the feasibility to identify imaging features of SCIs in young, asymptomatic patients with SCA using ultra high-field 7 Tesla (7T) MRI. 7T MRI has a high resolution, which offers a unique chance to investigate small subclinical brain lesions in detail. To explore the superiority of 7T in identifying imaging abnormalities, we compared our results with 3T MRI. Methods: Ten young, neurologically asymptomatic patients with SCA underwent 7T and 3T MRI; 10 healthy, age-matched controls underwent 7T MRI. We used existing neuroimaging standards to classify the brain lesions. We scored 7T and 3T scans separately, blinded for all other results. Results: Using 7T MRI, we identified more patients with intracerebral lesions (9/10 vs. 5/10), a higher total count of WMHs (203 vs. 190, p = 0.016) and more lacunes (5 vs. 4) compared to 3T MRI. Abnormalities seen on 7T, which could not be identified on 3T, were cortical hyperintensities (in 3/10) and a different aspect of irregular WMHs, closely associated with cortical hyperintensities in a patient with large vessel stenosis. In 7 controls, a total of 13 WMHs were present. Conclusion: Using 7T MRI, we identified more intracerebral lesions compared to 3T, and found several abnormalities not visible on 3T. 7T MRI in SCA seems of particular interest to study the cortical involvement and the relation between WMHs and the cortex. We found some imaging features that are thought to be representative for small vessel disease, including WMHs, lacunes and prominent perivascular spaces; to understand whether small vessel disease plays a role in SCA requires further research.

LIS1-Related Isolated Lissencephaly

With the largest data set of patients with LIS1-related lissencephaly, the major cause of posteriorly predominant lissencephaly related to either LIS1 mutation or intragenic deletion, described so far, we aimed to refine the spectrum of neurological and radiological features and to assess relationships with the genotype. Retrospective study. Subjects A total of 63 patients with posteriorly predominant lissencephaly. Of the 63 patients, 40 were found to carry either LIS1 point mutations (77.5%) or small genomic deletions (20%), and 1 carried a somatic nonsense mutation. On the basis of the severity of neuromotor impairment, epilepsy, and radiological findings, correlations with the location and type of mutation were examined. Most patients with LIS1 mutations demonstrated posterior agyria (grade 3a, 55.3%) with thin corpus callosum (50%) and prominent perivascular spaces (67.4%). By contrast, patients without LIS1 mutations tended to have less severe lissencephaly (grade 4a, 41.6%) and no additional brain abnormalities. The degree of neuromotor impairment was in accordance with the severity of lissencephaly, with a high incidence of tetraplegia (61.1%). Conversely, the severity of epilepsy was not determined with the same reliability because 82.9% had early onset of seizures and 48.7% had seizures more often than daily. In addition, neither the mutation type nor the location of the mutation were found to predict the severity of LIS1-related lissencephaly. Our results confirm the homogeneity profile of patients with LIS1-related lissencephaly who demonstrate in a large proportion Dobyns lissencephaly grade 3a, and the absence of correlation with LIS1 mutations.

MRI reveals structural abnormalities in patients with idiopathic generalized epilepsy

To evaluate MRI findings in a large group of patients with idiopathic generalized epilepsies. Idiopathic generalized epilepsies were diagnosed according to clinical and EEG criteria following International League Against Epilepsy recommendations. MRI was performed in a 2.0 T scanner using a previously established epilepsy protocol. Images were reviewed, and any abnormality was reported. Patients were divided in those with and without MRI abnormalities. Comparisons were made between these groups concerning age, age at seizure onset, subsyndrome, EEG findings, and seizure control. Of the 134 MRIs evaluated, 33 (24%) showed abnormalities, most of which (88%) were nonspecific. There were eight main abnormalities: arachnoid cyst, diffuse cortical atrophy, basal ganglia abnormalities (signal alterations and prominent perivascular spaces), ventricular abnormalities (uni- or bilateral increased volume of the lateral ventricles), white matter abnormalities (increased T2 signal in the frontal lobes), reduced hippocampal volume, focal gyral abnormality, and area of gliosis in the frontal lobe. Comparisons between the groups showed a higher proportion of EEG focalities in patients with abnormal MRI, which were in most part concordant with the location of the MRI abnormalities. Twenty-four percent of patients with idiopathic generalized epilepsies had MRI abnormalities. However, the majority of these abnormalities were nonspecific.

Thymoma Arising Within Cardiac Myxoma

Hematopoietic, glandular, and mesenchymal elements can be found within cardiac myxomas; ectopic endocrine tissues and "thymic rests" have also rarely been described. Atrial tumors (one right and one left) from 2 patients (a 69-year-old man and a 77-year-old woman) were encountered among the atrial myxoma cases in one of the author's consultation files. Both tumors were comprised of classic cardiac myxoma (with characteristic rings and syncytial chains of myxoma cells in a loose myxoid matrix) and cellular thymoma-like elements (characterized by a lobulated sheet-like growth of epithelioid spindle cells admixed with small lymphocytes punctuated by vessels with prominent perivascular spaces). Neither patient had evidence of thymoma elsewhere. Immunophenotypically, the thymoma-like component reacted strongly with antibodies to keratins (AE1/AE3, Cam 5.2, wide spectrum, CK19, CK7) and CD57 and weakly with antibodies to CD31, CD34, and calretinin. This intermediate phenotypic expression of both epithelial and vascular antigens likely reflects the multipotential nature of the cells comprising this lesion. The most likely explanation for this extremely unusual finding is neoplastic transformation of thymic rests within a myxoma.

Primary Intrapulmonary Thymoma

We describe eight cases of primary intrapulmonary thymoma occurring in seven women and one man between the ages of 25 and 77 years. Clinically, all patients had initial radiographic findings of a parenchymatous intrapulmonary mass without evidence of mediastinal involvement either radiologically or at surgery. The lesions varied from 0.5 to 10 cm in greatest diameter. Five tumors were located close to the hilum, while the other three were discovered deep within the lung and in subpleural locations. In one case, the lesion appeared to arise endobronchially and infiltrate the surrounding parenchyma. In another case, in addition to the main hilar mass, there were two smaller tumor nodules found deep within the same lung. Histologically, the lesions were characterized by the classic biphasic cellular composition of thymomas, i.e., an admixture in varying proportions of epithelial cells and lymphocytes. Four cases were characterized by sheets of lymphocytes admixed with scattered epithelial cells that were separated by fibrous bands into lobules. Three cases were composed predominantly of sheets of epithelial cells admixed with scattered small lymphocytes and containing prominent perivascular spaces. In two of these cases, focal areas of spindling of the cells were noted. One case was composed predominantly of a spindle cell proliferation with perivascular spaces and numerous small lymphocytes. Immunohistochemical stains for keratin and epithelial membrane antigen in six cases highlighted the epithelial cells scattered against the lymphoid cell background. Seven patients were treated by surgery. In one patient the tumor was deemed inoperable at the time of exploration owing to extensive pleural infiltration and was treated by postoperative radiation; the lesion recurred locally in the pleura 8 years later. Clinical follow-up in three patients after surgical incision showed them to ba alive and well without evidence of disease at 10 months, 2 years, and 8 years, respectively. Two of the patients had been followed clinically for 2 and 4 years following discovery of their lung masses on routine chest radiograph before resection of their tumors. Two patients died of unrelated conditions; in one of them, the lesions had been followed clinically for 6 years before surgery; this patient died 6 months later from coronary artery disease, without evidence of recurrence or metastasis. Our findings suggest that intrapulmonary thymomas are slow-growing tumors that may respond well to surgical resection when confined to the lung. As with their mediastinal counterparts, invasive tumors will require additional treatment for the possibility of recurrence of metastasis.