Neurology India Medknow Publications on behalf of the Neurological Society of India ISSN: 0028-3886 EISSN: 1998-4022 Vol. 58, Num. 6, 2010, pp. 951-953

Neurology India, Vol. 58, No. 6, November-December, 2010, pp. 951-953

Letter to Editor

Periventricular leukomalacia - Fungal mimicker in newborn brain: A case report with review of literature

Kirti Gupta¹, Nidhi Sharma¹, Venkataseshan Sundaram², Rakesh Kumar Vasishta¹, Nandita Kakkar¹

¹ Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
² Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Correspondence Address: Kirti Gupta, Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India kirtigupta10@yahoo.co.in

Date of Acceptance: 19-Aug-2010

Code Number: ni10266

PMID: 21150068
DOI: 10.4103/0028-3886.73757

Sir,

Periventricular leukomalacia (PVL) is a cerebral lesion typical for a preterm neonate. It occurs following an arterial infarct of the areas supplied by the end arteries, which is a "watershed" zone between the ventriculofugal vessels and the vessels penetrating the cortex. Lower the gestation, higher is the risk of PVL; as the area of the watershed zone increases as gestation decreases. PVL is characterized by areas showing white matter necrosis with axonal swelling, mineralization, collection of lipid-laden macrophages, activated microglia, reactive astrocytes and formation of small cysts. PVL can have varied morphological subtypes, and the type II morphological category of PVL mimics fungal infection. An autopsy case of a late-preterm neonate with bilateral pulmonary hypoplasia, bilateral renal with ureteric agenesis (Potter's sequence) and PVL is described, with the gross and microscopic lesions of PVL mimicking as fungal infection.

A late-preterm male neonate was born to a 24-year-old second gravida mother. Her antenatal ultrasonography (USG) of abdomen at 23 weeks of gestation (WOG) revealed oligohydramnios, amniotic fluid index (AFI) of 3 and fetal biometric parameters corresponding to 20 WOG. Her ultrasonograms at 30 and 32 WOG revealed a reduced fetal growth with a gestational age-fetal biometry disparity of 3 weeks, persistence of oligohydramnios and placenta previa. The USG prior to delivery, in addition, showed nonvisualization of both kidneys. At 35 ⁺³ WOG, she presented with bleeding per vaginum due to placenta previa. The baby required resuscitation for 30 seconds, with Apgar scores of 3, 5 and 7 at 1, 5 and 10 minutes of life, respectively. The cord umbilical artery pH (7.12) was indicative of moderate intrapartum acidosis. There were persistent features of dorsiflexion of feet, posteriorly rotated ears, and flat nostrils - all suggestive of Potter's phenotype. He developed respiratory distress, severe hypoxemia and died at 8 hours of life.

At autopsy, his weight was 1,250 g; with crown-heal length of 35 cm; crown-rump length, 20 cm; head circumference, 25 cm; chest circumference, 21 cm; and foot length, 4.5 cm. The Potter's facies were confirmed. The brain (weight, 170 g; normal for age, 256 g) showed subarachnoid hemorrhage over left frontal lobe. ^[1] Coronal sections revealed large areas of hemorrhagic necrosis in the white matter extending over all the lobes, resembling fungal infection [Figure - 1]a. There was no intraventricular/cortical/germinal matrix hemorrhage. Microscopically, affected areas revealed areas of hemorrhagic necrosis, with lesions close to the ventricle characteristically consisting of masses of gitter cells and more peripheral areas composed of a central acellular core of coagulation necrosis [Figure - 1]b. There were broad and slender basophilic calcified fibers closely resembling the fungal mycelium [[Figure - 1]c, arrow]. However, these hyphae-like filaments had no septations [[Figure - 2]a and b] and failed to stain with periodic acid-Schiff's (PAS) and Grocott's methamine silver. Additionally, adjacent brain showed ischemic neurons and axonal retraction balls [[Figure - 3]a and b]. There was bilateral renal and ureteric agenesis with normal urinary bladder. Both lungs were hypoplastic weighing 14 g (with lung weight-body weight ratio= 0.011 and radial alveolar count= 3.5). Other organs examined were normal.

PVL is a cerebral lesion typical for a preterm neonate, with prevalence rates reported to be between 2% and 25%. ^[2] The predisposing factors include birth trauma, asphyxia, cardiopulmonary defects, premature birth/ low birth weight, associated immature cerebrovascular development and lack of appropriate autoregulation of cerebral blood flow in response to hypoxic-ischemic insults. ^[3] In undeveloped brain, the periventricular white matter represents a "watershed" zone between the ventriculofugal vessels and vessels penetrating from cortex. Infants weighing less than 1,500 g are especially at risk for ischemic injury to this location due to immature oligodendroglia in the cerebral white matter and subplate neurons immediately below the neocortex. This results in loss of white matter, most pronounced in the peritrigonal regions, abutting the lateral ventricles. The final result seems to be calcium influx due to glutamatergic overactivation triggered by cytokines, infection and inflammation. The intrinsic vulnerability of oligodendrocyte precursors is considered as central to the pathogenesis of PVL. ^[4]

Three morphological types of PVL described in the literature ^[5] are as follows: type I, most common, showing focal necrosis centered on the ventricles or the subcortical zone; type II, with linear diffuse necrosis, is quite rare and resembles a fungal mycelium microscopically, as seen in this case, with large areas of hemorrhagic necrosis; and type III, which has variegated necroses. Valsiuk et al.^[6] have described 4 cases of PVL, wherein the basophilic fibers were mimicking as fungal hyphae, which are damaged non-myelinated axons with mineralization. In conclusion, this case highlights the gross and microscopic lesions of PVL as rare fungal mimickers; and the need for awareness of this resemblance to avoid misinterpretation.

References

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