Keywords
sarcoidosis - ocular sarcoidosis
Palavras-Chave
sarcoidose - sarcoidose ocular
Introduction
Sarcoidosis is a chronic multisystemic disease of unknown etiology in which there
is an accumulation of non-caseating granulomas in the various tissues of the human
body. It is a rare disease, and involvement of the central nervous system occurs in
5% to 10% of the cases. Therefore, the suspicion of involvement of the central nervous
system should be considered in all patients diagnosed. However, according to Stern
et al, in ∼ 48% of the cases of neurosarcoidosis, the symptomatology started with
neurological alterations without previous diagnosis of sarcoidosis. Thus, the mass
effect as the cause of the pathology is the only information available, which makes
the diagnosis a challenge in the medical practice. Sarcoidosis lesions may resemble
brain tumors, especially meningioma, so this pathology should be taken into consideration
for the differential diagnosis of brain lesions. We report a case of neurosarcoidosis
in a 79-year-old patient whose first symptom was progressive visual loss.
Case Story
A female patient, 79 years old, previously hypertensive, with hypothyroidism and depression,
who was also being treated for Parkinson disease, started with a progressive picture
of decrease in visual acuity to the right in the previous four years. Upon physical
examination, the patient had: a score of 15 on the Glasgow scale; mydriatic pupils;
amaurosis on the right, counting fingers to the left; decreased campimetry in the
nasal field of the left eye, without other cranial nerve injuries; tremor in the right
hand; bradykinesia to the right greater than to the left; bilateral Babinski sign;
non-sustained clonus on the right; bilateral dysdiadochokinesia; preserved tactile,
painful and vibratory sensibility and absence of meningism.
The patient was submitted to an investigation with computed tomography (CT) of the
skull and magnetic resonance imaging (MRI) of the orbits ([Fig. 1]), which evidenced an expansive lesion in the anterior fossa, obliterating the optic
canal to the right. The lesion was initially treated as optic neuritis, and corticotherapy
was performed. Lost in the follow-up, the patient presented worsening of the condition
within 1 year, and a new investigation was necessary. In this interval, the patient
presented complete loss of vision to the right and partial loss to the left, and underwent
imaging exams that evidenced a nodular lesion to the right and hypersignal in the
sheaths of the optic nerves bilaterally.
Fig. 1 Thickening with signs and enhancement by contrast of the sheaths of the optic nerve.
An expansive lesion with intense homogeneous contrast enhancement in the right optic
nerve with apparent implantation base on the sphenoid bone adjacent to the optic canal,
measuring 1.3 × 0.9 cm.
An investigation with cerebrospinal fluid (CSF) collection and a serological survey
was performed, none of which evidenced alterations. The patient was submitted to the
microsurgical approach of the lesion. Intraoperatively, a whitish lesion was observed
near the optic nerve, with important adhesion and infiltration of the nerve, and we
opted for partial resection. The anatomopathological analysis with classic non-caseating
granulomas, consisting of densely arranged epithelioid cells associated with Langhans
giant cells and/or foreign-body giant cells, was compatible with neurosarcoidosis
([Fig. 2]).
Fig. 2 Classic non-caseating granulomas consisting of densely-arranged epithelioid cells
associated with Langhans giant cells and/or foreign-body giant cells.
Magnetic Resonance of the Skull
Histology
Discussion
Also called Heerfordt syndrome, sarcoidosis is a chronic granulomatous disease of
unknown etiology that affects young adults and reaches the nervous system in the systemic
form in ∼ 5% of the patients.[1]
The neurological manifestations described are paralysis of the cranial nerves, aseptic
meningitis, peripheral neuropathy and myopathy.[2] Histologically, the development of granulomas, the activation of T cells and macrophages
occur by a pathway mediated by the classic histocompatibility II complex, with an
excessive Th1 response, leading to an overproduction of tumor necrosis factor-α (TNF-α)
and interferon-gamma (IFN-γ), as well as interleukin-2 (IL-2) and interleukin-15 (IL-15),
and the development of varying degrees of non-caseous necrosis.[3]
Clinically, the patients present diabetes insipidus, hypopituitarism and hyperprolactinemia
due to hypothalamic involvement. According to a study by Fritz et al,[4] all cranial nerves may be affected, but the facial nerve and optic nerve present
a higher prevalence, and unilateral involvement accounts for up to 65% of the cases,
and bilateral involvement accounts for 35%.[4]
In association with these manifestations, vasculitis, convulsive seizures and hearing
loss may occur.[5] Granulomas can coalesce, forming isolated intraparenchymal masses that are differential
diagnoses of gliomas, Guillain-Barré syndrome, as well as HIV infection, mononucleosis,
syphilis, acute porphyria, amyloidosis and multiple sclerosis.[3]
Usually, in neurosarcoidosis there is involvement of basal leptomeninges, causing
abnormalities in the cranial nerves or hydrocephalus.[6]
[7] It is important in these cases to perform the differential diagnosis with carcinomatous
meningitis and syphilis.[6]
[7] Neurosarcoidosis rarely presents itself solely mimicking a brain tumor, such as
a meningioma.[8]
[9]
[10] Complementary exams, such as dosing of angiotensin-converting enzyme, serum alkaline
phosphatase, and liquor and serum calcium, help in the diagnosis, but they are unspecific.
The CSF has a mononuclear pleocytosis pattern, elevated proteins, and the presence
of oligoclonal bands.[5] Imaging exams, such as cranial CT and MRI, may reveal hydrocephalus, meningeal enhancement
and parenchymal mass, but are unspecific for the diagnosis.[3] Lesions with increased intensity in T2 at the junction of the gray and white substances
are highly suggestive of this diagnosis, especially when associated with the enhancement
of the meninges and with the hypothalamus lesion.[7]
[8]
[10] Only a minority of cases need histological confirmation with non-caseating granulomas
in the affected nervous system tissue.[4]
[9] The diagnosis is of exclusion, but a probable diagnosis is defined as evidence of
inflammation of the nervous system on the MRI or CSF with high protein and cellularity,
G index of immunoglobin or the presence of oligoclonal bands in combination with evidence
of systemic sarcoidosis with histological confirmation.[4]
[9]
Isolated cranial nerve abnormalities and aseptic meningitis present low risk of progression,
with the exception of occasional cases of progressive optic neuropathy, and they respond
well to corticosteroids.[7] However, patients with mass lesions, with leptomeningeal involvement with multiple
anomalies of the cranial nerves, with spinal cord disease and with hydrocephalus often
require high doses and prolonged course of corticoids associated with immunosuppressants.[7] Among the immunosuppressants used are methotrexate (MTX), azathioprine (AZA) and
mycophenolate mofetil (MMF), which are equally efficient. Infliximab is a monoclonal
antibody, but with caveats for oncologic patients and the possibility of increased
risk of tuberculosis reactivation.[7] The diagnosis and management of neurosarcoidosis are still challenging aspects of
the disease, as well as its recognition as a differential diagnosis.
It is important to consider the possibility of neurosarcoidosis in the differential
diagnosis of brain expansive lesions pre- and intraoperatively. Thus, recognizing
this condition leads to the proper clinical treatment with corticosteroids, avoiding
an unnecessary extensive surgical treatment.
