Discussion
Sarcoidosis is a multi-systemic disease, characterized by cellular
immunity activity with formation of noncaseating granuloma in various
organ systems. Diagnosis of sarcoidosis is often a complex,
time-consuming trajectory due to the variety of clinical presentations
and the fact that laboratory blood and CSF examination is frequently
unspecific. As seen in our patient; mononuclear inflammatory cells,
elevated protein and occasionally low glucose. Three criteria are
required to diagnose sarcoidosis: clinical and matching radiologic
manifestations, a histological prove of a noncaseating granuloma and the
exclusion of alternative diseases. The Neurosarcoidosis Consortium
Consensus Group has developed a diagnostic criterion for
neurosarcoidosis3,9. Cranial and peripheral
neuropathies are the major presenting symptoms, together with myopathy,
seizures, gait disorders and cognitive decline. In 1-7 % the
vestibulocochlear nerve is affected 12,13. In the
present case, involvement of VIIIth cranial nerve could be suspected due
to her unsteadiness with walking.
Neurosarcoidosis in the basal leptomeninges appears as thickening and
enhancement (either focal, multifocal or diffuse) on gadolinium-enhanced
T1-weighted MRI. It is usually indistinguishable from the pattern seen
in tuberculous meningitis or CNS lymphoma 8, which
both may have a similar clinical presentation. Therefore, a histological
diagnosis of the radiological aberrant tissue is necessary. In
tuberculous meningitis, the basal leptomeningeal involvement is known to
be due to extension and/ or rupture of a Rich focus (subpial or
subependymal focus) to the subarachnoid spaces and ventricular system,
which causes enhancement of the exudate14. A similar
mechanism in neurosarcoidosis has not been described.
Parenchymal involvement often follows a perivascular spread, with
T2/FLAIR hyperintense white matter changes and / or perivascular
enhancement 15. The progressive T2 hyperintensities in
the deep white matter, observed in our patient, should be interpreted as
parenchymal involvement.
The question remains whether the ischemic strokes and progressive
vascular white matter changes in our patient, as a consequence of
small-vessel disease, can be attributed to neurosarcoidosis. Although
rarely, it has been reported that neurosarcoidosis can cause arterial
and venous ischemic and hemorrhagic strokes or TIA’s due to
granulomatous inflammation of intracranial blood vessels15. This has mainly been described in medium and small
vessels, literature of large vessel involvement is scarce and is thought
to be due to compression by granuloma’s rather than granulomatous
inflammation or vasculitis 1516.
There is still some uncertainty about the underlying pathophysiological
mechanism of stroke-like symptoms in patients with sarcoidosis. A
retrospective study evaluated patients with sarcoidosis-related strokes
and concluded that a stroke was the first presenting symptom in 40% of
the patients 16. In about 92% of neurosarcoidosis
patients presenting with stroke, sarcoidosis appeared to be present in
other non-nervous systems after additional examination. The authors
suggest that the granulomatous invasion of the blood vessel walls is the
mechanism behind sarcoidosis related cerebrovascular events rather than
sarcoidosis related vasculitis. It is thought that vasculitis due to
sarcoidosis is more commonly resulting in a slowly progressive
encephalopathy than an ischemic stroke 17. A mortality
rate of 23% is reported in sarcoidosis patients presenting with stroke16.
Due to the three-year time interval between stroke and diagnosis of
neurosarcoidosis, it remains debatable whether this could have been a
first warning sign of neurosarcoidosis in our patient.
Hydrocephalus is described to emerge in the course of neurosarcoidosis
in 5 to 12% of affected individuals 4. Usually this
is a communicating hydrocephalus as a consequence of a decrease in CSF
resorption due to leptomeningeal involvement. Though, CSF outflow
obstruction caused by involvement of the basal leptomeninges in the
inflammatory process and consequent adhesions, loculations in the
ventricular system or infiltration of the choroid plexus can also lead
to hydrocephalus 18,8.
Scarce literature is available on the treatment of neurosarcoidosis and
is mainly based on expert opinion and small retrospective studies.
Typically, initial treatment consists of corticosteroids, although the
exact mechanism is still unknown. It is hypothesized that the benefit is
due to the anti-inflammatory and immune-modulating effects11,19. The benefit of this treatment varies widely
from substantial improvement to no improvement at all. As a second step,
a steroid-sparing or second-line agent, like Methotrexate (MTX) or
mycophenolate can be considered. When the need for immunosuppressive
treatment is chronic, upfront start of combination therapy of both
corticosteroids and a steroid-sparing or second-line agent can be
preferred. Further treatment options include TNF-alpha inhibitors such
as infliximab, although treatment is expensive and poses a higher risk
for infections and other toxicities 9,19.