Keywords
gnathostomiasis - transient cerebral vasculopathy - cerebral gnathostomiasis - intracerebral
hemorrhage - meningitis - neuroimaging
Introduction
Gnathostomiasis is a parasitic infection caused by Gnathostoma spp., which is endemic in Southeast Asia, especially in Thailand, Japan, and Latin America.[1]
[2]
[3]
[4]
[5]
[6] Of the five Gnathostoma species that cause human disease, the most common is Gnathostoma spinigerum, whose definitive hosts are vertebrates such as dogs and cats.[7]
[8] Human can be infected with Gnathostoma by consuming raw or undercooked fish, snake, and frog. Gnathostoma infection can
manifest as a cutaneous form and/or in visceral organs. The most serious manifestation
of gnathostomiasis involves the central nervous system (CNS). Radiculomyelitis, radiculomyeloencephalitis,
eosinophilic meningitis, and subarachnoid hemorrhage are common in afflicted individuals
with CNS involvement, resulting in a high mortality rate (8–25%) and severe morbidity
(30%).[1] This study reports for the first time a transient cerebral vasculopathy associated
with meningitis and intracerebral hemorrhage in a patient with cerebral gnathostomiasis.
Case
An 11-year-old girl living in Nakhon Ratchasima Province, Northeast of Thailand, presented
with acute severe headache with high-grade fever for 5 days. She experienced nausea
and vomiting. She had no alteration of consciousness, weakness, or seizure. She denied
history of trauma or consumption of raw fish, freshwater shrimp, snails, frog, and
snake, and had no underlying diseases.
Physical examination showed normal and stable vital signs except for the high body
temperature (39°C). Neurological examinations revealed normal cranial nerve examination,
no papilledema, no muscle weakness, normal muscle tone, and normal sensory examination.
Deep tendon reflexes were graded 2+ in all extremities. Babinski's sign was absent
bilaterally, but stiffness of the neck was positive. Other systemic examinations were
unremarkable.
The complete blood count showed no eosinophilia (hematocrit 40.9%, platelet 873,000/μL,
white blood cell 9,000/μL; neutrophil 79.6%, lymphocyte 17.5%, and monocyte 2.9%).
The cerebrospinal fluid (CSF) appeared xanthochromic, and open/close pressures were
60/33 cm H20. The biochemical analysis revealed 20,500 cells/mm3 of red blood cell, 47 cells/mm3 of white blood cells (100% polymorphonuclear), 163 mg/dL of protein, and 23 mg/dL
of glucose. No bacterial growth in hemoculture and CSF culture was detected. Although
there was no evidence of eosinophilia, the serological testing in the CSF and serum
using the enzyme-linked immunosorbent assay (ELISA) technique was positive for G. spinigerum (immunoblot test, 24 kDa of molecular test for G. spinigerum). The test for Angiostrongylus cantonensis and repeated CSF analysis were not evaluated in this patient.
A computed tomography (CT) of the brain with contrast was performed and showed acute
hematoma at the splenium of corpus callosum (track-like appearance) and the adjacent
right parietal lobe with intraventricular hemorrhage, no mass effect was observed
on CT, and no demonstrable abnormal enhancing portion or obvious vascular malformation
as shown in [Fig. 1]. A magnetic resonance imaging (MRI) and magnetic resonance angiogram (MRA) of the
brain were done 2 weeks after the clinical onset and demonstrated late subacute hematoma
at the splenium of corpus callosum and the adjacent right parietal lobe with subacute
intraventricular hematoma. Additionally, the imaging studies showed multiple T2/fluid-attenuated
inversion recovery (FLAIR) hyperintensity foci at the subcortical white matter of
the bilateral frontal and parietal lobes. Mild irregular narrowing of the bilateral
supraclinoid internal carotid arteries (ICAs), ICAs bifurcation, and proximal bilateral
M1 and A1 segments of the middle cerebral arteries (MCAs) and anterior cerebral arteries
(ACAs), respectively, as well as left P2 segment of the posterior cerebral artery
(PCA) were also observed as shown in [Fig. 2]. The follow-up MRA at 3 months after the onset showed a normal vascular structure;
however, the abnormal white matter lesion remained unchanged as shown in [Fig. 3].
Fig. 1 (A) Noncontrast CT of brain showed acute hematoma at the splenium of corpus callosum
(track-like lesions) and the adjacent right parietal lobe with intraventricular hemorrhage.
(B) Postcontrast image showed no demonstrable abnormal enhancing portions or obvious
vascular malformations. CT, computed tomography.
Fig. 2 Magnetic resonance imaging and MRA of the brain. (A) Axial T1WI and (B) axial T2WI/FLAIR showed late subacute hematoma at the splenium of the corpus callosum
and the adjacent right parietal lobe with subacute intraventricular hematoma. (C) Axial T2WI/FLAIR demonstrated multiple T2/FLAIR hyperintensity foci at the subcortical
white matter of bilateral frontal and parietal lobes. (D) 3D-TOF MRA of the brain showed mild irregular narrowing of the bilateral supraclinoid
ICAs, ICAs bifurcation, and proximal bilateral M1 and A1 segments of MCAs and ACAs,
respectively, as well as left P2 segment of PCA (as the arrows). 3D-TOF, three-dimensional
time-of-flight; ACAs, anterior cerebral arteries; ICAs, internal carotid arteries;
FLAIR, fluid-attenuated inversion recovery; MCAs, middle cerebral arteries; MRA, magnetic
resonance angiogram; MRI, magnetic resonance imaging; PCA, posterior cerebral artery;
WI, weighted image.
Fig. 3 Follow-up MRI and MRA of the brain. (A) Axial T2WI and (B) axial T2WI/FLAIR. (C) T2WI/GRE showed complete resolution of the hematoma with cystic encephalomalacic
change and hemosiderin deposit at the splenium of the corpus callosum. (D, E) 3D-TOF MRA of the brain showed complete resolution of the prior mild irregular narrowing
of the intracranial vessels (as the arrows). 3D-TOF, three-dimensional time-of-flight;
FLAIR, fluid-attenuated inversion recovery; GRE, gradient recalled echo; MRA, magnetic
resonance angiogram; WI, weighted image.
Since the serological testing for Gnathostoma was reported 4 weeks after admission, the patient only received supportive treatment
without corticosteroid or albendazole. She had spontaneous recovery within 3 months
after the onset of symptoms without neurological deficits.
Discussion
Our study first reported an atypical neurological manifestation of gnathostomiasis,
a transient cerebral vasculopathy, which spontaneously resolved at 3 months' follow-up.
This patient showed atypical CSF profiles and complete blood count as there was no
eosinophilia. The clue for diagnosis of gnathostomiasis in this case was according
to the CT brain showing nontraumatic intracerebral hemorrhagic lesions which were
suspected hemorrhagic tracks from Gnathostoma. The definitive diagnosis was confirmed by the positive result of Gnathostoma titer in the CSF and serum. From previous studies, there was no report of cerebral
vasculopathy as the complication of Gnathostoma infection. However, the common neurological manifestations in both adult and pediatric
patients are nontraumatic subarachnoid hemorrhage, intracerebral hemorrhage, subdural
hemorrhage, and intraventricular hemorrhage.[1]
[2]
[3]
[4]
[5]
[6]
[9] The typical finding from CT brain is multiple intracerebral hemorrhages with a track-like
appearance at uncommon sites for hypertensive hemorrhage such as the frontal lobe,
unexplained subarachnoid hemorrhages, and nontraumatic subdural hemorrhage.[10]
[11]
[12] The MRI of brain in gnathostomiasis showed white matter lesions as subcortical enhancement
and high signal intensity on T2-weighted image involved in the periventricular area.[13] These results were correlated with our patient's neuroimaging study showing hemorrhagic
tracks at the corpus callosum with abnormal white matter lesions. The pathogenesis
of abnormal neuroimaging studies could be explained by the migration of parasite through
the brain parenchyma causing multiple hemorrhagic and track-like lesions with the
inflammatory or demyelinating process, which ultimately lead to abnormal white matter
lesions. Since the larvae enter the spinal cord along the nerve roots and then ascend
to the brain, penetrating the meninges at the base of the skull, and reaching the
subarachnoid space, the transient cerebral vasculopathy could be explained by the
proximity of the larvae to the great vessels of the base during its migration, causing
vasospasm or arteritis, as described in subarachnoid neurocysticercosis.[14]
[15] Although other CNS manifestations such as eosinophilic meningitis and radiculomyelitis
are typical in gnathostomiasis, CSF eosinophilia and symptoms of radicular pain or
signs of spinal cord involvement were not observed in this patient. The explanation
of no motor weakness in this patient was due to the abnormal lesion on CT or MRI brain
had no mass effect. The absence of eosinophilia could be attributed to the absence
of cutaneous and visceral manifestations.
Conclusion
Gnathostomiasis should be in a differential diagnosis in children presenting with
nontraumatic intracerebral hemorrhage, especially in endemic areas for Gnathostoma spp. Transient cerebral vasculopathy is one of the rare CNS manifestations of gnathostomiasis.
