Keywords
craniocerebral maduromycosis - Madura head - “dot-in-circle” sign
Introduction
Eumycetoma is a chronic granulomatous infection of fungal origin characterized by
extensive subcutaneous nodules, associated with sinuses draining pus, blood, and fungal
grains. Although commonly depicted as “Madura foot” because of its affinity for lower
extremities, other parts such as the hand, back, perineum, and paranasal sinus are
also frequently affected. Craniocerebral involvement by this fungus involving the
scalp, skull bone, and brain is very uncommon and restricted to few case reports in
medical literature. The story of a small infective focus over scalp, which gradually
progressed to cause disastrous effect in the skull bone, dura, and brain, resulting
in hemiparesis with intractable seizure, is depicted in this case report with review
of literature.
Case Description
A 32-year-old man presented to us with multiple episodes of generalized seizure and
left sided weakness for last 1 year. About 2 years back the patient noticed a gradually
enlarging nodular mass over the scalp, which subsequently burst out with discharging
pus. Since then numerous small nodular scalp lesions have appeared and burst, eventually
leading to multiple discharging sinuses with different stages of healing. For the
last 1 year he has been having multiple episodes of generalized convulsions with loss
of consciousness, which became more frequent in recent months. Simultaneously he noticed
weakness of both the upper and lower limbs in left half of the body. Now he could
barely walk without support.
Being a wood picker by profession, he showed history of scalp injury several times
while carrying wood over his bare head in the past. He was not a known case of tuberculosis,
diabetes, and human immunodeficiency virus (HIV).
Local examination of the scalp revealed multiple nodular masses with discharging sinuses
and discolored, healed scars ([Fig. 1A–C]). Multiple cervical lymph nodes were enlarged with overlying discolored skin.
Fig. 1 (A–C) Multiple nodular scalp lesions over frontal/parietal/temporal/occipital region with
discharging pus from sinus (yellow arrow). (D) X-ray of skull bone showing petrous bone sclerosis (red arrow) along with punched
out lytic lesions (yellow arrows). (E) T2W MRI coronal section showing multiple “dot-in-circle” signs (red arrows) all
over scalp with a hyperintense area over scalp (blue arrows) suggesting an abscess
with bony changes (yellow arrows).
Neurologic examination showed bilateral papilledema with left hemiparesis (grade 4/5).
All the remaining cranial nerves were intact with no sensory deficit. There were no
cerebellar or meningeal signs.
Routine laboratory investigations were normal except high erythrocyte sedimentation
rate (ESR) and C-reactive protein. X-ray of the skull bone revealed multiple radiolucent
areas suggestive of bone erosion along with petrous bone sclerosis ([Fig. 1D]). Magnetic resonance imaging (MRI) of the brain revealed an extra-axial lesion over
right frontoparietal region abutting superior sagittal sinus, featuring T1 hyperintensity,
T2 hypointensity with irregular contrast enhancement and perilesional edema ([Fig. 1D], [Fig. 2A–C]). Multiple contrast-enhancing lesions were found all over the scalp ([Fig. 2B]). Multiple fungal grains surrounded by granuloma and fibrous septa were typically
seen as “dot-in-circle” sign in T2W/FLAIR (fluid-attenuated inversion recovery) sequence
of MRI ([Fig. 1E]). Restriction in diffusion-weighted image (DWI) suggests microabscess ([Fig. 2C]).
Fig. 2 (A) T1 contrast sagittal MRI showing rim-enhancing dural-based lesion with perilesional
edema. (B) T1 contrast MRI axial view showing rim-enhancing lesion over right motor cortex
along with multiple enhancing scalp lesions. (C) Diffusion restriction in DWI sequence of MRI (yellow arrow). (D) Multiple fungal hyphae with peripheral cement-like eosinophilic material. (E) Multiple fungal hyphae with chlamydospores (blue arrows) enclosed within Splendore-Hoeppli
material (red arrows) and variable inflammatory cells.
In view of extensive infected scalp lesions, the plan for complete excision of the
lesion was not a viable option at that time. An excisional biopsy of the scalp nodule
was performed under local anesthesia to plan further course of management. A grayish-black
colored mass with pus-filled cavity was excised and sent for histopathologic biopsy.
Histopathology revealed presence of multiple abscess composed of neutrophils and mononuclear
cells surrounding fungal grains (tangled masses of fungal hyphae up to 1–2 mm in size
held together by cement-like material) in the dermis ([Fig. 2D]). Masses of fungal hyphae/filaments with peripheral widened chlamydospores enclosed
by a rim of eosinophilic Splendore-Hoeppli material (in vivo antigen antibody precipitation
around clumps of hyphae) are characteristic of Madurella mycetomi, from subgroup Monosporium epispermosum ([Fig. 2E]).
After being diagnosed as a case of craniocerebral maduromycosis, the patient was treated
with a regimen of injection amphotericin B (1 mg/kg/d) for 1 week and discharged with
oral itraconazole (200 mg twice daily) along with oral antiepileptics for 6 weeks.
Unfortunately the patient was lost to the next follow-up.
Discussion
Dr. John Gill is credited for his first description of “Madura foot” in 1842, though
the term was introduced by Colebrook as a distinct disease entity of Madurai region
in 1846.[1]
[2]
[3]
[4] This fungal disease is prevalent in Africa, India, Mexico, Argentina, and many other
tropical countries.[2] In his series of 184 cases of maduromycosis, Grantham Hill in 1931 recorded only
one case of cranial maduromycosis in Khartoum.[5] In 1950, Hickey reported on three patients of cranial eumycetoma without penetration
of the dura.[5]
Mycetoma is a chronic granulomatous destructive lesion involving the skin, subcutaneous
tissue, and bone, which can be caused by fungi (eumycetoma) or actinomycetes (actinomycotic
mycetoma).[1]
[3]
[6] Traumatic subcutaneous inoculation of this microorganism is manifested by painless
nodules, which swell up and rupture to form sinus tract with discharging fungal grains
(aggregates of fungal hyphae embedded in a cement-like material), pus, and blood.[2] This infection spreads through fascial planes to destroy the skin, subcutaneous
tissue, bone, and underlying structures.[2] Madurella mycetomatis is known to produce black colored grains, which was an indirect evidence of this
fungal infection in our case.[1]
[2]
Common sites of maduromycosis include dorsum of the feet (70%) followed by the hands
(12%).[2] Craniocerebral involvement is very uncommon and confined to only six case reports
in medical literature till date, excluding the index case ([Table 1]).[1]
[3]
[4]
[6]
[7]
[8] Common presentations in craniocerebral maduromycosis are due to mass effect, which
may present as seizure, focal neurologic deficit, discharging scalp lesions, or ear/nasal
discharge.[1]
[3]
[7]
[9]
Table 1
Previous cases of craniocerebral maduramycosis
|
Sl. no
|
Case reports
|
Age/sex
|
Chief complaints
|
History
|
Imaging features
|
Organism
|
Treatment
|
|
Abbreviations: ACA, anterior cerebral artery; CECT, contrast-enhanced computed tomography;
CPA, cerebellopontine angle; CT, computed tomography; F, female; M, male; MRI, magnetic
resonance imaging.
|
|
1
|
Natarajan et al, 1975
|
25/M
|
Focal seizure, left hemiplegia, discharging scalp sinus.
|
Carrying overhead material
|
X-ray—right parietal bone defect with loculated air.
Carotid angio—left side shift of right ACA.
|
Madurella mycetomatis
|
Surgery-twice. Chloromycetin, streptomycin penicillin.
|
|
2
|
Sai Kiran et al, 2007
|
21/F
|
Left ear discharge with hearing loss, right hemiparesis
|
Nothing suggestive
|
CT—left CPA solid-cystic lesion with erosion of petrous. MRI-T1 hypointense with contrast
enhancement.
|
Pseudallescheria boydii
|
Surgery, amphotericin-B, ketoconazole.
|
|
3
|
Beeram V et al, 2008
|
18/M
|
Discharging scalp sinus, generalized seizure
|
Farm labor, no history of trauma
|
CECT—parietal punched-out bony lesion with enhancing intra- and extradural mass.
|
M. mycetomatis
|
Surgery, itraconazole.
|
|
4
|
Ahmed et al, 2011
|
31/M
|
Scalp mass, seizure, right hemiparesis
|
History of trauma to scalp
|
CECT—dural-based enhancing lesion with osteomyelitis of skull bone.
MRI—left parasagittal enhancing dural-based mass.
Dot-in-circle sign in T2W.
|
Madurella grisea
|
Surgery, itraconazole.
|
|
5
|
Goel et al, 2012
|
17/F
|
Scalp mass, seizure, discharging sinus
|
Carrying wooden sticks overhead
|
X-ray—right parietal lytic skull lesions.
CECT—hyperdense, enhancing extra-axial mass with scalloping and erosion of overlying
bone.
|
M. mycetomatis
|
Surgery, voriconazole, terbinafine
|
|
6
|
Rao et al, 2015
|
26/M
|
Generalized seizure, blurring of vision, no scalp lesion
|
No history of trauma
|
CECT—left parieto-occipital enhancing dural-based lesion with bone hyperostosis along
with punched-out lesion.
|
P. boydii
|
Surgery, itraconazole.
|
None of the blood investigations are specific for maduromycosis, although a polymerase
chain reaction (PCR) assay has evolved recently to detect the microorganism in patient
as well as from the environment.[2] Conventional X-ray of the skull bone features sclerotic changes with punched-out
rarefaction, which are characteristically small in number and large in size with clear
margin.[1]
[2] Similar X-ray findings are seen in the index case. Hypointense dots within hyperintense
granuloma separated by hypointense septa, giving rise to the characteristic “dot-in-circle”
sign in T2W magnetic resonance images, correlate histologically with central fungal
grains surrounded by dense granulomatous inflammation partitioned by fibrocollagenous
tissue.[6]
[8] Similar findings were evident in the index case. Although culture of the fungus
is gold standard for diagnosis of eumycetoma, it takes long time with false-positive
results due to contamination of sample.[10]
Craniocerebral maduromycosis should be treated with adequate antifungal therapy complemented
by complete surgical excision of the small, localized mass lesion, as either surgery
or antifungal therapy alone has high recurrence rates.[2] Complete surgical excision must be attempted to address the mass effect and focal
neurologic deficit caused by the lesion.[2]
[6] Surgical excision also helps in reducing the recurrence rate and limiting the long
term use of antifungal therapy.[2] Both itraconazole (400 mg/d) or ketoconazole (400–800 mg/d) are equally effective
first-line medical management with a duration that may continue for years, depending
on the severity of the disease and health status of the individual,[2] as no strict recommendations citing the duration of medical therapy are found in
the existing literature. Though newer drugs such as caspofungin and posaconazole are
available in market, their high cost and no specific advantage over itraconazole have
questioned their long-term use.[2]
Long-term follow-up revealed discordant results among the existing literatures as
far as the sinus healing and radiologic changes are concerned.
In our report, we must acknowledge few limitations such as (1) biopsy was taken from
scalp lesions only, (2) culture of the organism was not done, and (3) lack of long-term
follow-up.
Conclusion
Craniocerebral maduromycosis is a rare entity. Only six cases have been reported in
the literature. In view of this rare cranial involvement of maduromycosis, we propose
a word “Madura head” for description of similar lesions in future. Early diagnosis
followed by antifungal therapy combined with surgical debridement may be a reasonable
treatment, though long-term follow-up is necessary.
