400

Case Reports
Sarcoidosis Presenting With Stroke
Martin M. Brown, MD, MRCP, A.J. Thompson, MD, MRCPI,
J.A. Wedzicha, MD, MRCP, and M. Swash, MD, FRCP, MRCPath

A 25-year-old black man with sarcoidosis presented with transient ischemic attacks followed by
sudden, persistent right hemiparesis. He gave a history of recent, recurrent lower motor neuron
facial palsy. Computed tomography demonstrated an infarct in the left internal capsule. Chest
x-ray film showed bilateral hilar and mediastinal lymphadenopathy and multiple opacities in the
lung fields. Serum angiotensin converting enzyme concentration was raised, and a Kveim test
was positive for sarcoidosis. Despite clear pathologic reports of cerebral vasculitis in neurosarcoidosis, the occurrence of stroke is extremely rare. (Stroke 1989;20:400-405)

S
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arcoidosis involves the nervous system in approximately 5% of cases.1"3 The most common presentation of neurosarcoidosis is a
cranial neuropathy, usually facial, followed in frequency by meningoencephalitis and, less often, intracranial mass lesions. Despite clear evidence of granulomatous involvement of cerebral vessels in sarcoidosis
from pathologic studies,4 stroke-like events in sarcoidosis are extremely rare. We therefore describe a case
of sarcoidosis in a young man who presented with
transient ischemic attacks (TIAs) followed by completed stroke resulting from a capsular infarct.
Case Report

A 25-year-old black man was admitted to the
hospital for investigation of five episodes of sudden
weakness and numbness of his right arm and leg,
which had occurred without higher function deficit
during the previous 24 hours. The patient recovered
from his first four attacks completely within 10
minutes; the symptoms of the fifth attack persisted.
Direct questioning was otherwise negative.
At the age of 6 years, the patient had developed
right-sided lower motor neuron facial weakness,
diagnosed as Bell's palsy, from which he recovered
within 4 weeks. At the age of 16 years, the rightsided lower motor neuron facial palsy recurred;
again the patient recovered within 4 weeks. Four
months before his current admission, the patient
developed a third recurrence of right lower motor
neuron facial weakness and recovered completely
within 2 weeks. Neither he nor his family had other
From the Departments of Neurology (M.M.B., A.J.T., M.S.)
and Thoracic Medicine (J.A.W.), the London Hospital, London,
England.
Address for correspondence: Dr. Martin M. Brown, Department of Neurology, the London Hospital, London El IBB,
England.
Received June 2, 1988; accepted August 15, 1988.

significant medical history. Both of his parents were
born in the West Indies, but the patient was born in
the United Kingdom and had never been abroad. He
worked as a heavy-goods vehicle driver. He smoked
20 cigarettes a day and drank 2 pints of beer per
week. He was not taking any medication or drugs.
General examination was normal. His speech was
slurred but not dysphasic. He could not support his
own weight because of right-sided weakness. There
was upper motor neuron right-sided facial weakness
and a severe flaccid right hemiparesis affecting the
arm more than the leg, with ipsilateral hyperreflexia
and extensor plantar response. Although he complained ofright-sidednumbness, sensory examination
was normal. There were no other abnormalities.
Cranial computed tomography (CT) performed 24
hours after the onset of hemiparesis showed an area
of nonenhancing low attenuation in the left internal
capsule extending into the corona radiata, consistent with infarction (Figure 1). These CT appearances were unchanged 4 weeks later. Chest x-ray
film and thoracic CT scan showed bilateral hilar and
mediastinal lymphadenopathy and multiple rounded
opacities in both lung fields (Figure 2). The erythrocyte sedimentation rate was 1 mm/hr, and complete blood count was normal. The corrected serum
calcium concentration was 2.69 (laboratory normal
range 2.10-2.60) mmol/1. Serum IgG concentration
was elevated at 1710 (normal range 660-1320) mg/
dl. Serum immunoelectrophoresis showed a mild
polyclonal increase in y-globulin. Serum angiotensin converting enzyme concentration was elevated
to 100 (normal range 16-53) units/ml. Pulmonary
function tests showed a restrictive defect with a
vital capacity of 66% of predicted values and a
reduced transfer factor (diffusion capacity) of 61%
of predicted values. Flexible bronchoscopy revealed
erythematous areas in the main bronchi of both
lungs, but bronchial and transbronchial biopsies

Brown et al

Sarcoidosis With Stroke

401

FIGURE 1. Contrast-enhanced cranial computed tomograms showing area of low attenuation in left internal capsule
(left) extending into corona radiata (right) consistent with cerebral infarction.
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and attempted percutaneous lung biopsy of a peripheral opacity obtained normal lung. A Mantoux test
at 1:1000 was negative. A forearm Kveim test
biopsied at 6 weeks was positive for sarcoidosis.
Findings from the following investigations were
normal or negative: autoantibody screen, clotting
screen, infectious diseases screen including VDRL,
thyroid function, vitamin B|2, serum folate, ophthalmologic examination, electrocardiogram, echocardiogram, left carotid angiogram, and cerebrospinal
fluid (CSF) examination. The patient was unable to
tolerate magnetic resonance imaging (MR1).
His right hemiparesis slowly resolved spontaneously, and 1 month after its onset the patient had fully
recovered. He remained well without medication 12
months after the onset of hemiparesis. Follow-up
investigations showed spontaneous improvement of
the peripheral pulmonary opacities and lung function.
Discussion
This young man presented with a history of recent
lower motor neuron facial palsy followed by TIAs,
culminating in a completed stroke due to cerebral
infarction. He was found to have mediastinal lymphadenopathy with rounded pulmonary opacities, and
erythematous nodules were found on bronchoscopy.
The association of these features with increased
serum IgG, mildly raised serum calcium, and markedly raised angiotensin converting enzyme concentrations and a positive Kveim test is diagnostic of
sarcoidosis.1 Facial palsy is one of the most common

manifestations of neurosarcoidosis. The close temporal relation of the patient's stroke and his most
recent facial palsy and the maximum extent of pulmonary shadowing suggested that the TIAs and
cerebral infarct were also caused by sarcoidosis
involving the central nervous system.
Stroke is an extremely rare complication of sarcoidosis, and no cases were encountered in two recent
large series.1-2 In contrast, neuropathologic studies
of sarcoidosis have consistently shown evidence of
vascular involvement.46-12 These studies characteristically show granulomatous meningitis involving
predominantly the basal meninges, with frequent
parenchymal and occasional ependymal involvement.4 The parenchymal granulomas tend to invade
the cerebral substrate along the Virchow-Robin spaces
and are distributed perivascularly.6 In addition, granulomatous invasion of the blood vessel walls is
frequent, with vasculitic disruption of the media and
internal elastic lamina. Several cases have shown
granulomatous vessel stenosis or occlusion sometimes clearly associated with small cerebral infarcts. 46 - 912 Microscopic and lacunar infarction is a
common finding.46-ia-12 In a few cases the granulomatous angiitis has been accompanied by acute
necrotizing arteritis, resulting in fibrinoid necrosis,
obliteration of the arterial lumen, and intense leukocyte infiltration similar to that of polyarteritis
nodosa. 469 Granulomatous vasculitis preferentially
involves vessels the caliber of the perforating
arteries,4 although in one report larger arteries

402

Stroke

Vol 20, No 3, March 1989

FIGURE 2. Chest x-ray (top) and thoracic computed tomogram (bottom)
showing bilateral hilar and mediastinal lymphadenopathy and multiple
rounded opacities in both lung fields.

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(including the middle cerebral artery) were affected.8
Veins may be involved, particularly in the periventricular regions.9
Table 1 summarizes the published pathology reports
of neurosarcoidosis in which information is adequate
for comparing the clinical features with the neuropathology. Despite the consistent finding of vasculitis
in the brain, most patients with vasculitis at autopsy
did not have a history of stroke; instead, they pre-

sented with a slowly progressive encephalopathy
characterized by headache, seizures, confusion,
dementia, or coma, associated with multifocal neurologic signs. Nevertheless, a few case reports confirm occasional stroke-like events in neurosarcoidosis. Herring and Urich4 described the sudden onset
of a brainstem stroke in a 29-year-old black man
(Case 6, Table 1) with sarcoidosis subsequently
found to have a pontine infarct associated with

+
+

1

1

1

Manz12

TLA, transient ischemic attack; PAN, polyarteritis nodosa.

3
4

2

1
2

Caplan
et aJ"

4
5
6
7

1
2
3

1
1

+

Granulomatous
meningitis

1

Cranial
Encepha- Sei- neurop- Mass
Case
no. TLA Stroke lopathy zures athy lesion

Clinical features

Neuropathologic features

+

+

Perivascular
SmallParen- roundPerivessel
Microcell
chymal
vascular Granulostenosis scopic
infilgranugranumatous PAN-like Arteries
Veins
inor octration
loraas
lomas vasculitis vasculitis involved involved clusion farction

Associated Clinical and Pathologic Features in Case Reports of Neurosarcoidosis

Author
Meyer
et al6
Camp and
Frierson7
ReskeNielsen
and
Harmsen8
Robert9
Schonell
et al10
Herring
and
Urich*

TABLE 1.

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Hemor
rhage

3
5"

«3
D3

404

Stroke Vol 20, No 3, March 1989

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granulomatous vasculitis. The patient of ReskeNielsen and Harmsen8 presented with the sudden
onset of aphasia and right-sided sensory and motor
symptoms, followed some months later by progressive encephalopathy. In his recent series of 50 cases
of neurosarcoidosis, Oksanen3 mentions hemiparesis
as developing acutely in three patients without giving
further details.
TIAs have also been occasionally reported in
sarcoidosis. Case 1 of Herring and Urich4 developed attacks of "giddiness" associated with numbness of the face and right limbs; these attacks were
probably TIAs, but migraine is another possibility
as the attacks were followed by headache and
vomiting. In their early postwar series of 300 cases
of sarcoidosis, Ricker and Clark13 described one
patient who suffered multiple attacks lasting 30-60
minutes and characterized by "loss of comprehension of events"; these attacks may have been
aphasic TIAs. Case 2 of Caplan et al" (Table 1)
suffered recurrent spells lasting up to 20 minutes of
right arm and facial numbness, slurred speech, and
difficulty in controlling the right arm. Wells14 mentioned two additional cases of TLA. Recurrent TIAs
have also been reported as the presenting manifestation of an ipsilateral subdural sarcoid mass lesion.15
Stroke may also occasionally occur in sarcoidosis
as a result of vasculitic intracranial hemorrhage.
Case 1 of Caplan et al" died of a cerebellar hemorrhage with extensive granulomatous vasculitis involving mainly the veins. In his series of 50 patients,
Oksanen3 also reported two intracerebral hematomas. In a few other cases, autopsy has revealed
hemorrhages not clearly associated with stroke-like
events. In one other reported case, recurrent cerebral infarction resulted from cardiac thomboembolism secondary to sarcoid cardiomyopathy.16 Thus,
several different mechanisms may be responsible
for stroke in sarcoidosis. In our patient, the TIAs,
stroke, and CT findings are consistent with lacunar
ischemia and then infarction secondary to granulomatous vasculitis involving the perforating arteries
as described in the pathology reports discussed
above. The discrepancy between the frequent neuropathologic finding of vasculopathy and the rarity
of clinical stroke in sarcoidosis is surprising but
may reflect the chronic nature of the inflammation,
the diffuse pathology, or the common feature of
involvement of only the very smallest arteries.
Our patient illustrates the difficulty of substantiating the diagnosis of neurosarcoidosis without cerebral or meningeal biopsy. In many cases (including
our own), the diagnosis must rest on the association
of appropriate neurology with other features diagnostic of sarcoidosis. CSF examination may be
helpful but not diagnostic, revealing pleocytosis,
low glucose or raised protein concentrations, or
evidence of intrathecal synthesis of IgG in some
patients; however, the CSF is completely normal in
30% of confirmed cases. 13 Ophthalmologic examination may demonstrate suggestive abnormalities

including vitreous lesions, uveitis, periphlebitis, or
conjunctival nodules, but it is normal in a third or
more patients." Cerebral angiography may occasionally show evidence of vasculitis,317 but it is
usually normal, even in the presence of proven
vessel involvement, probably because of the small
caliber of the affected vessels. 1 - 8 " CT scan may
show basal enhancement, mass lesions, or hydrocephalus, but the appearances are nonspecific and
rarely diagnostic.18 In addition, CT and MRI appearances of diffuse white-matter lesions, small cerebral
infarcts, and lacunar infarction similar to the findings in our patient have been clearly demonstrated,
supporting the occurrence in neurosarcoidosis of
small-vessel disease.1920
The role of steroids in the treatment of neurosarcoidosis has not been clearly established. Because
he had recovered substantially by the time the
diagnosis was established, our patient was not
treated. He has remained well for 12 months after
presentation, demonstrating spontaneous remission
of neurologic involvement paralleling the course of
the systemic disease. Such spontaneous remission
is well described.13 Benefit of steroid treatment has
not been proven. In one recent series the course of
the disease in steroid-treated patients did not differ
significantly from that in untreated patients.3 Nevertheless, some patients appear to respond dramatically to steroids and, although not supported by
control studies, an empirical trial of steroid therapy
may be justified in patients with severe or progressive neurologic disease.
References
1. Delaney P: Neurologic manifestations in sarcoidosis. Ann
Intern Med 1977;87:336-345
2. Stem BJ, Krumholz A, Carol J, Scott P, Nissim J: Sarcoidosis and its neurological manifestations. Arch Neurol 1985;
42:909-917
3. Oksanen V: Neurosarcoidosis: Clinical presentations and
course in 50 patients. Ada Neurol Scand 1986;73:283-290
4. Herring AB, Urich H: Sarcoidosis of the central nervous
system. J Neurol Sci 1969;9:405-422
5. James DG, Turiaf J, Hosoda Y: Description of sarcoidosis:
Report of the subcommittee on classification and definition.
Ann NYAcad Sci 1976;278:742
6. Meyer JS, Foley JM, Campagna-Pinto D: Granulomatous
angiitis of the meninges in sarcoidosis. Arch Neurol Psychiatry 1953;69:587-600
7. Camp WA, Frierson JG: Sarcoidosis of the central nervous
system. Arch Neurol 1962;7:432-441
8. Reske-Nielsen E, Harmsen A: Periangiitis and panangiitis as
a manifestation of sarcoidosis of the brain. J Nerv Mem Dis
1962;135:399-412
9. Robert F: Sarcoidosis of the central nervous system. Arch
Neurol 1962;7:442-449
10. Schonell ME, Gillespie WJ, Maloney AFJ: Cerebral sarcoidosis. BrJDis Chest 1968;62:195-199
11. Caplan L, Corbett J, Goodwin J, Thomas C, Shcnker D,
Schatz N: Neuro-ophthalmologic signs in the angiitic form of
neurosarcoidosis. Neurology 1983;33:1130—1135
12. Manz HJ: Pathobiology of neurosarcoidosis and clinicopathologic correlation. Can J Neurol Sci 1983;lO:5O-55
13. Ricker W, Clark M: Sarcoidosis: A clinicopathologic review
of three hundred cases, including twenty-two autopsies. Am
J Clin Pathol 1949; 19:725-749

Brown et al
14. Wells CEC: The natural history of neurosarcoidosis. Proc R
SocMed 1967;69:1172-1174
15. Sethi KD, Gammal TE, Patel BR, Swift TR: Dural sarcoidosis presenting with transient neurological symptoms. Arch
Neurol 1986;43:595-597
16. Scully RF, Galdabini JJ, McNeely BU (eds): Case records of
the Massachusetts General Hospital: Case 46-1975. N Engl J
Med \915;293:1138-1145
17. Lawrence WP, Gammal TE, Pool WH, Apter L: Radiological manifestations of neurosarcoidosis: Report of 3 cases
and review of the literature. Clin Radiol 1974^5:343-348
18. Brooks BS, Gammal TE, Hungerford GD, Acker J, Trevor
RP, Russell W: Radiological evaluation of neurosarcoidosis:

Sarcoidosis With Stroke

405

Role of computed tomography. Am J Neuroradiol 1982;
3:513-521
19. Ketonen L, Oksanen V, Kuvliala 1: Preliminary experience
of magnetic resonance imaging in neurosarcoidosis. Neuroradiology 1987;29:127-129
20. Miller DH, Kendall BE, Barter S, Johnson G, MacManus
DCR, Logsdail SJ, Ormerod 1EC, McDonald WI: Magnetic
resonance imaging in central nervous system sarcoidosis.
Neurology 1988;38:378-383
KEY WORDS • cerebral ischemia, transient • cerebrovascular
disorders • sarcoidosis

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