Rare disease

Neurosarcoidosis presenting with a partial
Claude syndrome
Hao Meng Yip ‍ ‍,1 Kirtana Vallabhaneni,1 David Williams2
1

Nephrology, North Middlesex
University Hospital NHS Trust,
London, UK
2
Neurology, North Middlesex
University Hospital NHS Trust,
London, UK
Correspondence to
Dr Hao Meng Yip;
​meng.​yip@​nhs.​net
Accepted 5 November 2019

SUMMARY
Neurosarcoidosis when encountered by neurologists
most commonly presents as cranial neuropathy,
peripheral mononeuropathy,polyneuropathy, myopathy,
meningitis or myelopathy. There are limited reports in
the current literature on the cases of neurosarcoidosis
patients presenting with ischaemic stroke. We discuss
a 52-­year-­old patient with a known previous history of
cutaneous sarcoidosis presenting with an acute third
nerve palsy, facial weakness and ataxia. His magnetic
resonance imaging (MRI) brain demonstrated focal
signal changes in the midbrain consistent with an
acute ischaemic event in the region of his third nucleus,
suggesting a partial Claude syndrome presentation.
Cerebrospinal fluid (CSF) examination demonstrated
an elevated angiotensin-­converting enzyme (ACE) level.
We discuss the difficulties associated with confirming a
diagnosis for his presentation and consider distinctions
in stroke in neurosarcoid and its management in
comparison to more common causes.

theorised to be due to a combination of different
mechanisms including small or large vessel vasculitis and embolism secondary to sarcoid cardiomyopathy.1 Despite its rarity in the overall context of
stroke causes, ischaemic infarct secondary to neurosarcoidosis remains an important differential diagnosis for the younger population of stroke patients.
In these patients, embolic infarcts are less likely, and
therefore, it is important to consider other vasculopathic processes with underlying autoimmune,
infective, drug-­related or malignant aetiologies.
In this report, we describe the case of a 52-­year-­old
man who presented with ischaemic stroke with a
known background of sarcoidosis. We outline his
clinical manifestations, our approach to diagnosis
and management. We discuss his case in relation to
the current literature and highlight important diagnostic considerations in this rare presentation of
neurosarcoidosis.

Case presentation
Background

© BMJ Publishing Group
Limited 2019. No commercial
re-­use. See rights and
permissions. Published by BMJ.
To cite: Yip HM,
Vallabhaneni K,
Williams D. BMJ Case
Rep 2019;12:e232317.
doi:10.1136/bcr-2019232317

Sarcoidosis is a multiorgan granulomatous disease
that commonly affects the lungs, skin and lymph
nodes.1 It is characterised pathologically by the
formation of non-­caseating granulomas.1 Its annual
incidence is 7 cases per 100 000; this is consistent
with the range of 5–40 per 100 000 reported from
other northern European countries.2
Neurosarcoidosis occurs when the sarcoid granulomata affect the nervous system. It has a symptomatic incidence of 5%–15% in patients with
sarcoidosis.3 Common clinical presentations of
neurosarcoidosis include aseptic meningitis, cranial
neuropathy, spinal cord syndromes, uveoparotid
fever and seizures.3 The gold standard for the
diagnosis of neurosarcoidosis would be a nervous
system biopsy, although this is not always feasible.3
The investigative approach should otherwise be
focused on confirming a neuroinflammatory basis
behind the clinical presentation via radiology and
cerebrospinal fluid (CSF) examination.3
Cases of acute stroke in patients with neurosarcoidosis are infrequently reported in the literature.
Symptomatic ischaemic infarcts have historically
been thought to be rare in patients with neurosarcoidosis, despite post-­
mortem studies frequently
demonstrating granulomatous vascular infiltration.1
There is, however, evidence to suggest that ischaemic
and haemorrhagic events may be more common
than previously believed.4 Their pathophysiology is

A 52-­
year-­
old right-­
handed man presented after
having three episodes of sudden onset double vision
and profound dizziness throughout the day. While
two episodes resolved completely, the third was
persistent and he developed a dull frontal headache.
He also reported a transient episode of left-­sided
lower facial weakness. He had no history of similar
symptoms.
On examination, he had mild bilateral proptosis
with left eye deviation upwards and outwards in
the primary position (figure 1). His right nasolabial
fold was slightly reduced. His pupils were anisocoric (left 5 mm, right 2 mm) and his left pupil was
unresponsive to light. Visual fields and acuity were
unchanged. He had no pain on eye movements. The
left eye had weakness in downward gaze, and abduction, and the right eye had weakness in upward gaze
(figure 1). Fundoscopy showed no papilloedema but
evidence of left optic disc atrophy. No other acute
cranial nerve dysfunction was elicited. His cognition and memory were unchanged. His gait became
broad-­based and ataxic with veering to the right
over a few days after admission. The remaining
neurological examination was unremarkable.
His medical history was significant. Having
developed cutaneous ring lesions in his left lateral
thigh in 1999, he underwent biopsy, resulting
in him being given a histological diagnosis of
sarcoidosis. He initially responded well to corticosteroid therapy but developed total anosmia in
2004. Magnetic resonance imaging (MRI) showed

Yip HM, et al. BMJ Case Rep 2019;12:e232317. doi:10.1136/bcr-2019-232317

1

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Case report

Rare disease

meningeal thickening of his olfactory nerves. His symptoms had
mainly been managed by courses of corticosteroids, as he felt
that steroid-­sparing agents were not as effective. Over the past
few months, he had noticed a slightly worsening vision. It was
noted by his optician that he had mild right-­sided proptosis.
Investigations excluded retro-­orbital sarcoidosis and thyroid eye
disease. He works full-­time and is independent in activities of
daily living. He has no other medical history. He is a non-­smoker
and only drinks alcohol socially.
Given his medical history and presentation with cranial
neuropathy, the initial impression was of an inflammatory
central nervous system (CNS) presentation of neurosarcoid with
possible basal meningeal involvement.

Investigations

He was extensively investigated with magnetic resonance angiography (MRA) head and neck, bubble contrast echocardiography and blood tests, including human immunodeficiency
virus (HIV), antinuclear antibodies (ANA), anti-­neutrophil cytoplasmic antibody (ANCA), treponemal serology, lupus anticoagulant, anticardiolipin, beta-2-­
glycoprotein and homocysteine.
All results were negative. The only finding of note was that he
had hypercholesterolaemia. Brain natriuretic peptide (BNP) and
troponin were checked to rule out any cardiac sarcoid involvement; neither were elevated. Blood tests showed an increased
serum angiotensin-­converting enzyme (ACE) level of 66.4 U/L
(8–52 U/L).
Computerized tomography (CT) head showed a mature
lacunar infarct in the left basal ganglia and mild chronic small
2

vessel disease. MRI head with contrast showed focal signal
changes in the midbrain on the diffusion-­weight imaging (DWI)
sequence, with appearances consistent with an acute ischaemic
event (figure 2). There were also subtle signal changes on the
fluid-­attenuated inversion recovery (FLAIR) sequence at the base
of the left cerebral peduncle which were not present previously.
The combination of left-­sided features of a third nerve palsy
with contralateral apparent superior rectus paresis was suggestive of left third nerve nucleus pontine localisation of his primary
lesion. A Claude syndrome was further suggested with the development of his ataxia suggesting superior cerebellar peduncle
involvement. We note that this is a very rare stroke presentation that is infrequently reported in the current literature.5 The
only definitive way to confirm the diagnosis would have been
via biopsy; an impractical measure considering the location of
the infarct.

Differential diagnosis

While the initial impression was of CNS sarcoid involvement,
prior to his imaging being available this was not assumed, and
alternative causes of cranial neuropathies were investigated and
excluded (including vasculitic screening, Lyme serology, treponemal serology and HIV). Once a vascular cause had been established, further investigations considering alternate causes of
stroke other than sarcoid were considered.

Yip HM, et al. BMJ Case Rep 2019;12:e232317. doi:10.1136/bcr-2019-232317

BMJ Case Rep: first published as 10.1136/bcr-2019-232317 on 19 November 2019. Downloaded from http://casereports.bmj.com/ on February 24, 2020 at Serials Division La Trobe
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Figure 1 3×3 arrangement of patient’s eye positions on examination with the primary position at the centre. Note upward and outward deviation
of his left eye in the primary position with the discrepancy in light reflection. When looking left, there is incomplete left eye deviation. On looking
downwards, there is restriction of left eye depression. On looking upwards, there is markedly restricted right eye elevation.

Rare disease

Treatment

Due to a high clinical suspicion of a neurosarcoidosis flare, he
was given intravenous methylprednisolone with high-­dose oral
prednisolone maintenance subsequently. In addition to his maintenance immune steroid therapy, initiation of steroid-­
sparing
immunosuppression was coordinated. He was also managed for
stroke with dual antiplatelet therapy and statin.

Outcome and follow-up

Post-­discharge, our patient was arranged to have a local stroke
clinic follow-­
up in our hospital. His high-­
dose maintenance
steroid therapy will also be reviewed in a specialist clinic at a
tertiary centre for ongoing management from the neurosarcoidosis perspective.

Discussion

It is noteworthy that our patient presented with a relatively rare
ischaemic stroke presentation, that is, Claude syndrome.5 This
likely resulted from the tendency for neurosarcoid to involve
small perforating arteries causing an increased frequency of
lacunar infarcts presentations involving the basal ganglia, thalamus and brainstem.1 Such presentations in the appropriate clinical context may raise the index of suspicion of neurosarcoid
involvement.
Yip HM, et al. BMJ Case Rep 2019;12:e232317. doi:10.1136/bcr-2019-232317

It is, however, difficult to ascertain neurosarcoidosis as a cause
of ischaemic stroke in sarcoidosis patients with symptomatic
infarcts, given its rarity and the fact that a definitive diagnosis
via brain biopsy is not always feasible. At present, there is also no
single non-­invasive investigation that could serve as a diagnostic
gold standard. It is also difficult to measure the usefulness of
non-­invasive tests for neurosarcoidosis given the understandable
tendency by clinicians to avoid further investigations once there
is a histological diagnosis of systemic sarcoidosis. There is, therefore, a subjective component to the diagnosis of neurosarcoidosis as a cause of ischaemic stroke, which currently relies on a
combination of clinical suspicions and generic non-­invasive tests
to establish an inflammatory basis to stroke symptoms.
Despite the diagnostic difficulties, it is important to consider
neurosarcoidosis in younger stroke patients with focal neurology
presentations. This is because it entails different management
(immunosuppression) compared with other more common
differentials, such as vascular infarcts (stroke protocol with antiplatelets), and infective processes (antibiotics). We noted a lack of
evidence of the effectiveness of immunosuppressive therapy on
patients with ischaemic lesions in the current literature.1 Besides
excluding differentials of ischaemic stroke, we also noted the
importance of ruling out other cerebrovascular manifestations of
neurosarcoidosis, such as haemorrhagic stroke or dural venous
3

BMJ Case Rep: first published as 10.1136/bcr-2019-232317 on 19 November 2019. Downloaded from http://casereports.bmj.com/ on February 24, 2020 at Serials Division La Trobe
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Figure 2 Top images: Two consecutive slices from the patient’s apparent diffusion coefficient (ADC) and DWI sequences in the midbrain. (A and
C) ADC map and (B and D) DWI sequence. Restricted diffusion consistent with cytotoxic oedema, suggesting infarction in the region of his left
oculomotor nerve complex, is observed.

Rare disease

Patient’s perspective
I understand that neurosarcoidosis, as a chronic health condition,
can have long-­term impacts on my autonomy and well-­being.
Occasionally, I experience some amount of frustrations with the
unpredictability of such a condition. The non-­specific nature of
sarcoid presentation meant that sometimes I was unsure if the
symptoms I was experiencing were independent of the diagnosis
or not; and more than once, this had lead to a lack of clarity and
confusion on how best to manage this condition.
However, I am able to adapt my lifestyle to cope with
my condition with minimal disruption to my day-­to-­day life.
This is largely due to several health professionals who have
accompanied me in my journey and empowered me to actively
battle against the relentless consequences of such a chronic
condition. I am also grateful to have a supportive family network
who had strongly advocated for me in this tough journey.

The approach taken to diagnosing our patient aimed to bear
these principles in mind. While a diagnosis of small vessel vasculopathy secondary to neurosarcoidosis could be elicited by
his medical history, presenting complaint and imaging, it was
important to rule out more common causes of thromboembolic
stroke. He underwent extensive investigations to exclude both
common and rare causes of stroke due to his relatively young
age. We excluded other cerebrovascular manifestations of neurosarcoidosis via neuroimaging for our patient which only showed
ischaemic infarcts. We also excluded any cardiac sarcoid involvement. We offered our patient active treatment for both embolic
stroke and neurosarcoidosis flare until a definitive diagnosis
could be made.
Given the diagnostic difficulties, there might be value in establishing a clear screening criterion that could be widely adopted
in clinical practice to screen for neurosarcoidosis as a cause of
ischaemic infarcts. For example, the Zajicek criteria have been
used in previous case series to assess the likelihood of neurosarcoidosis and to differentiate those with the definite disease from
the probable and possible disease.6 Our patient would be classified as a probable disease based on these criteria.
Contributors HMY and KV contributed equally in writing the manuscript. DW
revised the manuscript. HMY, KV and DW provided clinical care for the patient.
Funding The authors have not declared a specific grant for this research from any
funding agency in the public, commercial or not-­for-­profit sectors.
Competing interests None declared.
Patient consent for publication Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.

Learning points
►► While neurosarcoidosis is historically believed to be a rare

cause of ischaemic stroke; it may not be that uncommon
in the context of neurosarcoid given recent evidence. Case
identification is, therefore, important as it may fundamentally
change management.
►► Stroke secondary to neurosarcoidosis differs from the more
common causes of stroke in its predilection for perforating
vessel involvement resulting in an increased likelihood of
presentations with brainstem or cerebral lacunar syndromes.
►► Establishing a definitive diagnosis of neurosarcoidosis
in known sarcoidosis patients presenting with ischaemic
infarcts may not be possible and alternate causes should
be thoroughly screened for as management may be
fundamentally altered.

ORCID iD
Hao Meng Yip http://​orcid.​org/​0000-​0002-​3089-​3933

References

1 Bathla G, Watal P, Gupta S, et al. Cerebrovascular manifestations of neurosarcoidosis:
an underrecognized aspect of the imaging spectrum. AJNR Am J Neuroradiol
2018;39:1194–200.
2 Snell N, Strachan D, Hubbard R, et al. Burden of lung disease in the UK; findings from
the British Lung Foundation’s ’respiratory health of the nation’ project. Eur Resp J
2016;48.
3 Ibitoye RT, Wilkins A, Scolding NJ. Neurosarcoidosis: a clinical approach to diagnosis
and management. J Neurol 2017;264:1023–8.
4 Bathla G, Watal P, Gupta S, et al. Cerebrovascular manifestations in neurosarcoidosis:
how common are they and does perivascular enhancement matter? Clin Radiol
2018;73:907.e15–e23.
5 Bateman JR, Murty P, Forbes M, et al. Pupil-­Sparing third nerve palsies and hemiataxia:
Claude’s and reverse Claude’s syndrome. J Clin Neurosci 2016;28:178–80.
6 Zajicek JP, Scolding NJ, Foster O, et al. Central nervous system sarcoidosis--diagnosis
and management. QJM 1999;92:103–17.

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Yip HM, et al. BMJ Case Rep 2019;12:e232317. doi:10.1136/bcr-2019-232317

BMJ Case Rep: first published as 10.1136/bcr-2019-232317 on 19 November 2019. Downloaded from http://casereports.bmj.com/ on February 24, 2020 at Serials Division La Trobe
University Library. Protected by copyright.

sinus thrombosis.3 This is because these manifestations respond
to treatment differently compared with ischaemic stroke; for
instance, there were case reports of haemorrhagic lesions that
responded to early aggressive immunosuppressive therapy.1