A 64-year-old female presented to the emergency department with a four-day history of a 39°C fever. Her medical history included epilepsy and mild intellectual disability, both of which had been present since childhood. She had been seizure-free for the past 10 years while on phenytoin medication, which had been prescribed by a local hospital. According to her family, she had been informed of a lesion in the left cerebral white matter two years earlier, following a brain CT performed at a local clinic.

Hematologic analysis, urinalysis and CT of the chest, abdomen and brain were performed to determine the fever focus. The results indicated a systemic infection, and urinalysis revealed pyuria with abdominal CT findings consistent with acute pyelonephritis. Brain CT revealed confluent low-attenuated lesions in the left cerebral hemisphere (Figure 1A). Subsequently, a brain MRI was performed, demonstrating nonenhancing, infiltrative T1 low, T2 and fluid-attenuated inversion recovery high signal intensity lesions occupying the left periventricular white matter, with multiple internal cystic foci and few microbleeds (Figure 1 B–G). Given the presence of polymicrogyria, these cystic foci were most likely focally enlarged perivascular spaces, a common finding in this context.^{Reference Rauch, Lachner and Frickel1} Apparent diffusion coefficient images showed diffusion restrictions in parts of the lesion, and perfusion imaging demonstrated no increase in cerebral blood volume (Figure 1 H–J). The underlying cortex of the left cerebral hemisphere showed an abnormal configuration of polymicrogyria (Figure 1 B–C). Therefore, the initial diagnosis was diffuse glioma, such as astrocytoma.

Figure 1.

Radiologic findings of dense accumulation of corpora amylacea in the periventricular white matter of the left cerebral hemisphere. CT of the brain (A) reveals confluent, ill-defined, low-attenuation lesions in the left periventricular white matter. MRI demonstrates diffuse and infiltrative lesions, which show hyperintense signal intensity (SI) on 3D T2-weighted (B) and fluid-attenuated inversion recovery (C) and hypointense SI on T1-weighted images (D) without evidence of contrast enhancement (E). The sagittal 3D T2-weighted image (F) well depicts the periventricular distribution of the lesion, and internal small cystic foci are noted on axial and sagittal 3D T2-weighted images (thin arrows in B and F). A few punctate dark SI foci of microbleeds are noted on the susceptibility-weighted image (G). The diffusion-weighted and apparent diffusion coefficient images reveal small areas of diffusion restriction within the lesion (arrows in H and I). The dynamic susceptibility contrast perfusion image (J) shows no evidence of increased relative cerebral blood volume. The gyrus of the left cerebral hemisphere shows an abnormal configuration of polymicrogyria (arrowheads on B and C).

Figure 1 Long description

Panel A: A CT scan of the brain in axial view showing confluent, ill-defined, low-attenuation lesions in the left periventricular white matter. Panel B: A 3D T2-weighted MRI scan in axial view showing hyperintense signal intensity lesions in the left cerebral hemisphere with internal small cystic foci indicated by thin arrows. Panel C: A fluid-attenuated inversion recovery MRI scan in axial view showing hyperintense signal intensity lesions in the left cerebral hemisphere. Panel D: A T1-weighted MRI scan in axial view showing hypointense signal intensity lesions in the left cerebral hemisphere. Panel E: A T1-weighted MRI scan in axial view with contrast showing no evidence of contrast enhancement. Panel F: A sagittal 3D T2-weighted MRI scan showing the periventricular distribution of the lesion and internal small cystic foci indicated by a thin arrow. Panel G: A susceptibility-weighted MRI scan showing a few punctate dark signal intensity foci of microbleeds. Panel H: A diffusion-weighted MRI scan showing small areas of diffusion restriction within the lesion indicated by an arrow. Panel I: An apparent diffusion coefficient MRI scan showing small areas of diffusion restriction within the lesion indicated by an arrow. Panel J: A dynamic susceptibility contrast perfusion MRI scan showing no evidence of increased relative cerebral blood volume.

Following appropriate treatment for acute pyelonephritis, the patient’s fever improved, and she was transferred to the neurosurgery department for further evaluation of the brain lesion. A stereotactic biopsy of the lesion was performed, and a total of seven specimens were obtained. Histopathological assessment of the specimens revealed accumulated corpora amylacea (CA) with reactive gliosis, without any tumor cells (Figure 2 A–B). Dense aggregates of CA were predominantly observed near the deep margin of the lesion, adjacent to the ventricular surface. At this location, the accumulation was nearly twice as abundant compared to specimens obtained from the lateral side, approximately 1 cm away from the deepest specimen. Additionally, CA accumulation was more prominent in posterior regions compared to anterior regions of the lesion, consistent with the imaging findings. Immunohistochemical analysis showed positivity for glial fibrillary acidic protein (Figure 2C), negativity for isocitrate dehydrogenase 1 and a low Ki-67 proliferative index (< 1%) (Figure 2D), supporting the absence of neoplastic activity. Postoperative brain CT imaging demonstrated expected changes without complications. The patient was subsequently evaluated in the outpatient clinic one month after surgery, during which no new neurological or systemic abnormalities were noted.

Figure 2.

Histopathological examination reveals numerous dense accumulations of corpora amylacea (CA) in the brain parenchyma, characterized by their distinctive spherical and laminated appearance on hematoxylin-eosin stain, indicated by arrows, with no evidence of neoplasia; magnification × 40 (A) and × 200 (B). Immunostaining with glial fibrillary acidic protein (C) shows reactive gliosis with CA formations, with a proliferation index of less than 1% on Ki-67 staining (D); magnification × 200.

CA are aggregations of polyglucosan bodies that accumulate in astrocytic processes, predominantly in the subpial, perivascular and subependymal regions of the human brain, as a result of normal aging and stress.^{Reference Chung and Horoupian2,Reference Nishio, Morioka, Kawamura, Fukui, Nonaka and Matsushima3} Abnormal CA accumulation has been documented in various neurological conditions, including multiple sclerosis, mesial temporal sclerosis and Alzheimer’s disease.^{Reference Chung and Horoupian2–Reference van de Pol, Hensel and van der Flier5} The exact pathophysiological roles of CA remain unclear, although it has been postulated that they may serve as containers for waste products in the brain.^{Reference Xu, Owen, Gislason, Benediktsdottir and Robinson6,Reference Riba, Del Valle, Molina-Porcel, Pelegrí and Vilaplana7}

The accumulation of CA in this case is most likely a secondary or reactive phenomenon. Extensive T2 hyperintense white matter changes in the left cerebral hemisphere may be related to the underlying polymicrogyria, a finding reported in approximately 12% of polymicrogyria cases.⁸ These signal abnormalities are typically attributed to gliosis resulting from widespread dysmyelination and abnormal development of gray and white matter.^{Reference Leventer, Jansen and Pilz8} However, in our case, histopathological examination revealed an exceptionally dense accumulation of CA, particularly in the periventricular region, suggesting that CA deposition itself may have contributed to the observed imaging findings.

While the relationship between the patient’s underlying cortical abnormality and the lesion remains unclear, two potential mechanisms warrant consideration. First, the structural abnormalities of polymicrogyria may disrupt glymphatic clearance – a system critical for the removal of metabolic waste, particularly in the periventricular region.^{Reference Riba, Del Valle, Molina-Porcel, Pelegrí and Vilaplana7} Impairment of this clearance mechanism could facilitate the accumulation of metabolic byproducts, promoting CA accumulation. Second, cortical disorganization in polymicrogyria may induce a chronic state of neuronal excitatory-inhibitory imbalance,^{Reference Sarnat and Flores-Sarnat9} further exacerbating CA formations as reactive astrocytic responses. Without definitive pathological evidence, the precise mechanisms remain speculative. Nonetheless, this hypothesis underscores the need for further investigation into the interplay between cortical developmental anomalies and CA deposition.

CA accumulation has primarily been reported in the hippocampus of patients with mesial temporal sclerosis.^{Reference Nishio, Morioka, Kawamura, Fukui, Nonaka and Matsushima3,Reference Abel, Hebb, Keene, Born and Silbergeld10} Reports of CA accumulation outside the hippocampus, mimicking other brain lesions such as glioma or focal cortical dysplasia, are rare, with only a few cases of small lesions documented in the frontal and temporal lobes.^{Reference Pimentel, Roque and Cunha11–Reference Matsuo, Fujimoto, Komori and Nakata13} To our knowledge, this is the first reported case of such diffuse and extensive CA accumulation, predominantly near the periventricular region, which was initially misidentified as a glioma. Although CA accumulation has not previously been described in association with polymicrogyria, we hypothesize that structural abnormalities in this condition may contribute to impaired glymphatic clearance and chronic astrocytic stress, potentially facilitating the formation of CA aggregates.

This case highlights the importance of considering CA accumulation as a secondary phenomenon associated with broader neurodevelopmental abnormalities. The radiologic identification of CA might be challenging due to its rarity and the lack of widespread awareness among clinicians. By presenting this rare case, we aim to enhance understanding and promote greater awareness of this pathology. Further studies are required to elucidate the relationship between cortical anomalies and CA deposition and associated pathophysiological processes.