Unusual association of diseases/symptoms

CASE REPORT

Cerebral-autoregulatory dysfunction syndrome
Ravindra Kumar Garg,1 Hardeep Singh Malhotra,1 Tushar B Patil,1 Avinash Agrawal2
1

Department of Neurology,
Chhatrapati Shahuji Maharaj
Medical University, Lucknow,
Uttar Pradesh, India
2
Department of Internal
Medicine, Chhatrapati Shahuji
Maharaj Medical University,
Lucknow, Uttar Pradesh, India
Correspondence to
Dr Hardeep Singh Malhotra,
drhsmalhotra@gmail.com

SUMMARY
Reversible cerebral vasoconstriction syndrome and
reversible posterior leukoencephalopathy syndrome are
distinct clinicoradiological disorders which share certain
features in terms of aetiology, pathogenesis and
symptomatology. We present a case of a young
primigravida with eclampsia who developed severe
headache, vision loss and hemiparesis in the postpartum
phase. MRI of the brain was suggestive of the
involvement of anterior as well as posterior circulation
and reversibility of widespread angiographic constrictions
could be documented on follow-up. Despite the
resolution of vascular changes, vision loss did not
improve significantly in our case. Such an overlap of
findings is unusual and probably represents the spectrum
of cerebral-autoregulatory dysfunction occurring in these
two syndromes.

BACKGROUND
Reversible cerebral vasoconstriction syndrome
(RCVS) is a clinicoangiographic entity characterised
by severe headaches occurring in varying combinations of neurological symptoms, and the constriction of large-sized and medium-sized cerebral
arteries which resolves spontaneously within
12 weeks.1 Reversible posterior leukoencephalopathy syndrome (RPLS) is a rapidly evolving neurological condition identified by headache, nausea
and vomiting, seizures, visual disturbances and
altered sensorium with reversible vasogenic oedema
involving the parieto-occipital areas of the brain.2
Considerable overlap, in terms of aetiology, pathogenesis and clinical features, exists between both
these syndromes hence segregating the two is not
always possible. RCVS and RPLS commonly occur
in the postpartum phase which complicates the
issue further.

CASE PRESENTATION

To cite: Garg RK,
Malhotra HS, Patil TB, et al.
BMJ Case Rep Published
online: [ please include Day
Month Year] doi:10.1136/
bcr-2013-201592

A 25-year-old primigravida, admitted in the department of obstetrics, developed three episodes of
generalised tonic–clonic seizures with loss of consciousness 5 days prior to delivery of a child per
vaginum. The patient was diagnosed as having
eclampsia and was managed conservatively with
parenteral magnesium sulfate. On the fourth postpartum day, the patient experienced a severe headache associated with multiple episodes of vomiting
and blurring of vision. Over the ensuing 18 h she
developed altered sensorium and was transferred to
the department of neurology for further management. Her history was not suggestive of migraine,
vasculitis or connective tissue disorder; medication
history was non-corroborative. At the time of
admission the patient was drowsy (Glasgow Coma

Garg RK, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2013-201592

Scale 10/15) and movements were asymmetrical
between the two sides of the body. Neurological
examination revealed normal-sized reactive pupils,
right-upper motor neuron facial palsy and right
hemiparesis (Medical Research Council grade 2/5)
with a right extensor plantar response. Other systemic examinations did not reveal any abnormality.

INVESTIGATIONS
Laboratory investigations revealed a normal haemogram, blood sugar, liver function tests, kidney function tests and coagulation profile; urine was
positive for protein. Antinuclear antibody, extractable nuclear antibody profile and sepsis screen were
negative. Chest x-ray and ultrasound of the
abdomen did not reveal any abnormality. MRI of
the brain showed involvement of the parietooccipital regions, extending into the frontal lobes,
and cerebellar hemispheres, left more than right,
with evidence of restriction in the corresponding
areas on diffusion-weighted images; apparent diffusion coefficient maps were suggestive of low values.
There was no contrast extravasation on postcontrast
T1-weighted images. MR angiography (MRA)
revealed lack of visualisation of the left internal
carotid artery and its divisions along with segmental constriction of the right vertebral artery; segmental narrowing and dilation of superior
cerebellar and posterior cerebral arteries were additionally noted (figure 1). Ultrasound of the carotids in the neck did not reveal any abnormality.
Cerebrospinal fluid examination was normal and
was tested negative for varicella zoster virus, herpes
simplex, Japanese encephalitis, dengue and
enterovirus.

TREATMENT
In view of the clinical setting and angiographic
findings the patient was initiated on nimodipine in
anticipation of the development of ischaemia in the
left internal carotid territory. The patient regained
consciousness within 48 h and an improvement in
weakness was observed; at 2 weeks no perceptible
weakness existed on examination.

OUTCOME AND FOLLOW-UP
Follow-up MRI with MRA, carried out after
3 weeks, showed a decrease in the extent of
involvement, and normalisation of flow in the left
internal carotid artery (and its divisions), a resolution of the segmental constriction of the right
vertebral artery, superior cerebellar arteries and
posterior cerebral arteries (figure 2). A significant
improvement in the patient’s vision was not
observed till the time of discharge at 4 weeks.
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Unusual association of diseases/symptoms

Figure 1 Baseline MRI of the brain depicts hyperintensities involving the bilateral cerebellar hemispheres and the parieto-occipital regions on axial
fluid-attenuated inversion recovery (A and B) and T2-weighted images (C and D), with corresponding diffusion-weighted images (F and G) showing
restriction and apparent diffusion coefficient images (H and I) displaying low values. MR angiography (E and J) showing non-visualisation of the left
internal carotid artery (arrows) and its divisions along with segmental constriction of the right vertebral artery (arrow head); segmental narrowing
and dilation of superior cerebellar and posterior cerebral arteries is also evident (asterisk).

DISCUSSION
In the background of eclampsia, our patient developed a severe
headache and blurring of vision in the postpartum phase followed by hemiparesis. MRI with MRA of the brain demonstrated changes occurring beyond the conventional observation
of parieto-occipital involvement with a striking non-visualisation
of the left carotid artery along with changes observable in the
right vertebral and both posterior cerebral and superior cerebellar arteries. Follow-up imaging revealed a persistence of, albeit
decreased, cerebral-parenchymal changes but with remarkable

angiographic normalisation of the previously involved vessels.
In view of the setting, symptomatology, the location of cerebral
parenchymal changes with an admixture of vasogenic and cytotoxic oedema, and reversibility of angiographic changes the
patient was classified as an overlap of RCVS and RPLS.
RCVS is a clinicoangiographic entity characterised by an
acute-onset of severe headache (thunderclap headache), which
may or may not be associated with neurological dysfunction,
with reversible constriction of the large-sized and medium-sized
cerebral arteries.1 It is an underdiagnosed condition and the

Figure 2 Follow-up MRI of the brain depicts hyperintensities, which have reduced in extent, involving the left cerebellar hemisphere and the
parieto-occipital regions on axial fluid-attenuated inversion recovery (A and B) and T2-weighted images (C and D). Diffusion-weighted images
(F and G) showing reduction in size while apparent diffusion coefficient (H and I) have increased from the baseline. MR angiography (E and J)
showing normalisation of flow in left internal carotid artery (and its divisions), resolution of segmental constriction of the right vertebral artery,
superior cerebellar arteries and posterior cerebral arteries.
2

Garg RK, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2013-201592

Unusual association of diseases/symptoms
exact incidence of the syndrome is not known; data available
have been obtained from the various published case series.3–7 It
is an umbrella term comprising all aetiologically diverse disorders, viz. Call-Fleming syndrome, postpartum angiopathy,
benign angiopathy of the central nervous system, migrainous
vasospasm and drug-induced cerebral vasculopathy, where
similar clinical and radiological findings are observed.8 9 The
key word ‘reversible’ in RCVS applies to the complete or nearcomplete normalisation of the angiographic findings within
12 weeks, and this may not necessarily be associated with the
resolution of the clinical or cerebral-parenchymal findings.1
MRI with MRA of the brain are the usual first-line imaging
techniques to evaluate for RCVS; conventional catheter-based
angiography, however, is the gold standard. The most specific
evidence for RCVS is the demonstration of complete or nearcomplete reversibility of vasoconstriction, invariably within
3 months.1 Besides angiography, transcranial Doppler study is
an excellent tool for the initial assessment and follow-up of
patients with RCVS. Since cut-off values similar to that in sicklecell disease are not available for such patients, it is recommended that sequential studies be performed to look for the
suggestion of vasospasm or improvement in the same.6
RPLS is identified by headaches, visual perception defect,
altered sensorium and seizures, with the involvement of the
parieto-occipital areas of the brain usually occurring in the
setting of eclampsia, renal disease and hypertensive encephalopathy.2 Most evident radiological findings on T2-weighted MRI
are the hyperintense lesions located at the grey-white junction
and involve the parieto-occipital regions bilaterally. Lesions can
involve the frontal and temporal lobes, as well as the basal
ganglia and cerebellar hemispheres; more extensive lesions have
been associated with more severe clinical findings.10 Resolution
of the clinical symptomatology is evident as soon as the precipitant event is removed or managed, usually within a week, but
the MRI findings resolve over a mean duration of 2–4 weeks.
Although the aetiopathogenesis of RCVS and RPLS is not
known precisely, a transient disturbance in the control of cerebral vascular tone has been hypothesised which leads to segmental and multifocal arterial constriction and dilatation.1 11 The

development of these syndromes may be spontaneous, without
any evidence of a trigger or underlying state, or secondary to
eclampsia/pre-eclampsia and exposure to vasoactive substances
(sympathomimetic/serotoninergic) or systemic states mimicking
the same. Several medical conditions including hypertensive
encephalopathy and uraemia, and the use of cytotoxic and
immunosuppressive drugs have also been associated with these
syndromes.1 2 8
At the vascular front, RCVS seems to be associated with the
constriction and/or dilation of large-sized and medium-sized
cerebral arteries while RPLS has been related to endothelial dysfunction and cerebral-autoregulatory failure at the level of distal
arterioles and capillaries.1 11–13 As a corollary, we find actual
strokes constituted by cytotoxic oedema in RCVS, but only
changes attributed to vasogenic oedema are observed in RPLS;
infarcts corresponding to arterial territories may therefore be
more evident in cases with RCVS. The combination of changes,
as observed in our case, can be explained if the pathophysiology
is considered as a continuum of changes involving different parts
of the cerebral vasculature ( proximal vs distal) and the severity of
cerebral-autoregulatory dysfunction. A mild-to-moderate grade
dysfunction will thus lead to reversible ischaemia when proximal
vessels are involved in RCVS, or vasogenic oedema upon involvement of the distal vasculature in RPLS. Similarly, severe dysfunction will lead to the development of stroke and manifest at
locations depending on the location of arteries affected. The
imaging findings in our case and the angiographic reversal attest
that the pathophysiological mechanisms in these two syndromes
represent a continuum manifesting as an overlap of RCVS and
RPLS. A simple diagnostic algorithm to approach cases suspected
of RCVS is depicted in figure 3.
RCVS can be associated with RPLS, regardless of the aetiology,
in approximately 10% of the cases. A report of four cases of
RCVS, described as postpartum angiopathy, and RPLS details the
abnormalities in such patients similar to what was observed in
our case.11 In a recent larger series, 12 cases of RCVS in the postpartum phase have been described in one-third of those in which
ischaemic changes were observed.7 The present case reiterates
the overlap between these two syndromes and also highlights the

Figure 3 Diagnostic algorithm to
approach a case of reversible cerebral
vasoconstriction syndrome.

Garg RK, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2013-201592

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Unusual association of diseases/symptoms
probability of extensive reversible vascular involvement. We have
therefore preferred using the term ‘cerebral-autoregulatory dysfunction’ for appropriate categorisation.
The management of a patient with RCVS or RPLS depends
upon the treatment of the underlying pathology or the removal
of the triggering event. Adequate amount of fluids with maintenance of blood pressure help in limiting the cerebral hypoperfusion as well as vasospasm. Calcium channel blockers,
nimodipine and verapamil, may be used in cases where vasoconstriction has been documented.1 Stroke is seen in half of the
patients with RCVS and seems to be the most important determinant of short-term and long-term morbidity; lethal fulminant
course may also be seen in some patients.3 14 15 The prognosis,
otherwise, in RCVS and RPLS is good. Our patient had significant improvement in weakness but her vision did not improve
significantly even after 1 month.

Competing interests None.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.

REFERENCES
1
2
3

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7

Learning points

8
9

▸ Reversible cerebral vasoconstriction syndrome is an
underdiagnosed condition and its documentation with
reversible posterior leukoencephalopathy syndrome is sparse.
▸ Such an overlap probably represents the spectrum of the
extent and severity of angiographic involvement occurring
secondary to cerebral-autoregulatory dysfunction, central to
both the syndromes.
▸ Residual defects may be seen even after complete reversal of
cerebral angiographic findings.
▸ Appropriate fluid management and use of calcium channel
blockers may help these patients.

10

11
12

13
14
15

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Garg RK, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2013-201592