Keywords
cerebral cavernous malformation - isolated cerebral mucormycosis - seizure - magnetic
resonance imaging - antiepileptic drugs
Introduction
Vascular malformations of central nervous system encompass a variety of lesions like
cerebral cavernous malformation (CCM), arteriovenous malformation, and capillary telangiectasia
and venous angiomas. CCMs are angiographically occult, well circumscribed, benign
hamartoma consisting of thin-walled sinusoidal vascular channels but lacking large
feeding arteries or large draining veins. They can be solitary or multiple (50% of
cases) and are usually detected on magnetic resonance imaging (MRI). Mucormycosis
is a rare, and fatal opportunistic fungal infection caused by members of Mucorales
family.[1] It often occurs in patients with immunocompromised state like hematological malignancies,
organ transplantation, diabetic ketoacidosis, or with history of intravenous drug
abuse.[2] Isolated cerebral mucormycosis (ICM) accounts for 8% of all mucormycosis cases.[3] The clinical symptoms of ICM are illusive and hence high index of suspicion should
be kept based on clinical and radiological findings. Here, we are reporting first
case of CCM with concomitant ICM in a young immunocompetent female without any risk
factors.
Case History
A 22-year-old female was presented with left-sided facial seizures since age of 7
years and headache for the past 3 years. Seizure was limited to left half of the face
and manifested in the form of twitching movements lasting for 1 to 2 minutes. Frequency
of seizure was one to two episodes per day. She was kept on two antiepileptic drugs,
oxcarbazepine 600 mg twice daily and clobazam 10 mg once daily from another treating
physician. Headache was holocranial, intermittent lasting for 3 to 4 hours and was
not associated with nausea, vomiting, photo, and phonophobia. There was no preceding
history of fever, loss of weight, and loss of appetite. Past history was negative
for tuberculosis, connective tissue disease, or glucocorticoid use. Family history
was negative for similar illness. Menstrual history was normal.
On general examination, her blood pressure was 120/70 mm Hg and pulse rate 80 per
minute. There was no pallor, icterus, cyanosis, pedal edema, or lymphadenopathy. Cardiovascular,
respiratory, and abdominal examinations were within normal limits. Neurological examination
also did not reveal any cranial nerves, motor, sensory, or cerebellar abnormality.
On laboratory evaluation, her complete blood count, liver, renal and thyroid function
test were unremarkable. MRI brain revealed a contrast enhancing lesion with evidence
of bleed in right posterior frontal lobe suggestive of cavernous malformation ([Fig. 1]).
Fig. 1 Magnetic resonance imaging brain showing right posterior frontal heterogeneously
hyperintense cortical lesion with intralesional hematoma and thrombosis (white arrow) suggestive of cavernous malformation (A). Resected specimen from right posterior frontal lobe showed a 4 × 3 cm capsulated
brownish yellow solid-cystic mass with mulberry like projections (white arrow; B).
Patient underwent right frontal craniotomy with excision of cavernoma. Gross examination
showed a 4 × 3 cm solid cystic mass with multiple mulberry protrusions ([Fig. 2]). Histopathological examination revealed features of cavernous malformation with
evidence of broad aseptate 90° branching fungal hyphae conforming to the morphology
of mucormycosis ([Fig. 3]). Adjacent scant brain parenchyma also revealed fungal infiltration along with reactive
gliosis. Few foci of angioinvasion were seen. Hence, a final diagnosis of cavernous
malformation with mucormycosis fungal infection was made.
Fig. 2 Resected lesion composed of many closely packed anastomosing congested vascular channels
having no muscularization. Some of the channels showed presence of fresh thrombus
(white arrow) (200 × , hematoxylin and eosin [H&E]) (A). Peripheral glial tissue showed presence of broad aseptate hyphae of mucormycosis
branching at 90 (white arrow) (400 × , H&E) (B).
Fig. 3 Few vessels were obliterated with the Mucor colonies and showed calcification (white arrow) (400 × , hematoxylin and eosin) (A). Gomori methenamine silver (GMS) staining highlights the broad aseptate hyphae of
mucormycosis and also the calcified vessel wall getting infiltrated by fungal hyphae
(white arrow) (400 × , GMS) (B).
Postoperatively patient was doing well without any apparent focal neurological deficit.
She was investigated in detail to rule out any source of the fungal infection. However,
her chest X-ray, ultrasound abdomen, and two-dimensional (2D) echocardiography did
not reveal any abnormality. Her blood and urine culture were sterile. She also underwent
detailed otorhinolaryngology evaluation to rule out occult source of infection that
came out negative. Patient was discharged on 2 antiepileptic drugs, oxcarbazepine
600 mg twice daily and clobazam 10 mg once daily. Opinion was taken from neurologist
and microbiologist regarding antifungals, which was not given considering no other
foci of infection evidenced by normal clinical and radiological evaluation. At 2 months
of follow-up, oxcarbazepine was tapered to 450 mg twice daily and clobazam was stopped.
She was doing well without any occurrence of fresh seizures.
Discussion
In the present case, a young female presented with left-sided focal seizure and was
not responsive to two antiepileptic drugs. MRI brain revealed right posterior frontal
cavernous malformation. However, on excision of cavernoma, histopathological examination
showed evidence of mucormycosis within the lesion as well as intervening glial tissue.
Such combination of cavernous malformation with ICM has not been found in the available
English literature.
ICM is rare in healthy and immunocompetent individuals.[4]
[5] ICM in immunocompetent adults must fulfil three criteria: (1) Isolated cerebral
localization; (2) identification of Mucorales by culture, polymerase chain reaction
or characteristic broad based aseptate hyphae on pathology from brain biopsy or autopsy
sample; (3) immunocompetent host.[6] Our case fulfilled all the above criteria of ICM in an immunocompetent individual.
Detailed clinical, laboratory, and radiological examination did not reveal any underlying
systemic disease or predisposing condition. Intravenous drug abuse has been reported
to be the commonest risk factor in patients with ICM, but in present case even such
history of addiction was absent.[6]
Concomitant CCM with fungal infection is an extremely rare occurrence. Sun et al reported
a case of 60-year-old male with a history of meningioma-induced seizure 3 years back.
MRI brain revealed brain abscess in addition to meningioma. Patient underwent antibiotic
treatment with resection of meningioma. Later on, due to appearance of new focal deficit
and expansion of the previous lesion, surgical resection was done. Resected specimen
revealed aspergillus fumigatus infection complicating cavernous haemangioma.[7] Similarly in our case, mucormycosis complicating cavernous malformation was detected.
Localization of fungal infection to the cerebral cavernoma without any other foci
of infection might be due to a state of equilibrium between mucor infection and body's
immunity as proposed by Sun et al.[7]
Conclusion
To the best of our knowledge, this is the first case report of a CCM with mucormycosis
in an immunocompetent patient without any risk factor.
