Case Report

Epileptic Seizure as a Precipitating Factor of Vascular
Progressive Supranuclear Palsy: A Case Report
Giuseppe Lanza, MD,* Maurizio Papotto, MD,† Giovanni Pennisi, MD,‡
Rita Bella, MD,‡ and Raffaele Ferri, MD*

Background: Vascular progressive supranuclear palsy (vPSP) is an uncommon
akinetic-rigid syndrome characterized by asymmetric lower body involvement,
predominant corticospinal and pseudobulbar signs, urinary incontinence, cognitive impairment, and increased frequency of stroke risk factors, together with neuroimaging evidence of vascular disease. Case Report: We report a case of a patient
with a PSP-like phenotype and marked cognitive impairment who significantly
worsened after a generalized epileptic seizure that occurred a few months after
its clinical onset. Results: Signs of widespread ischemic subcortical vascular
disease, together with atrophy of the midbrain tectum, corpus callosum, and cerebral cortex, were evident on brain magnetic resonance imaging. Conclusions: vPSP
is a condition that should be considered when a patient presents with a gradually
progressive clinical picture suggestive of idiopathic PSP associated with neuroimaging evidence of cerebrovascular disease. The occurrence of epileptic seizures
has not been reported before in vPSP but they might trigger the onset or precipitate
the course of the PSP-like disorders. Key Words: Leukoaraiosis—parkinsonism—
epilepsy—cognitive impairment—neuroimaging.
Ó 2014 by National Stroke Association

Introduction
Vascular progressive supranuclear palsy (vPSP) is an
uncommon akinetic-rigid syndrome. We report a case of
a patient with a PSP-like disorder who showed a sudden

From the *Department of Neurology I.C., Oasi Institute for
Research on Mental Retardation and Brain Aging (IRCCS), Troina
(EN); †Department of Neurorehabilitation, Oasi Institute for Research
on Mental Retardation and Brain Aging (IRCCS), Troina (EN); and
‡Department of Neurosciences, University of Catania, Catania, Italy.
Received October 25, 2013; revision received December 22, 2013;
accepted December 29, 2013.
Address correspondence to Giuseppe Lanza, MD, Department of
Neurology I.C., Oasi Institute for Research on Mental Retardation
and Brain Aging (IRCCS), Via Conte Ruggero 73, 94018 Troina (EN),
Italy. E-mail: giuseppelanza2003@yahoo.it.
1052-3057/$ - see front matter
Ó 2014 by National Stroke Association
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.12.043

worsening after an epileptic seizure associated with a significant vascular pathology on brain magnetic resonance
imaging (MRI).

Case Report
A 66-year-old man was referred because of an atypical
akinetic-rigid syndrome. Family and past medical history
were unremarkable except for a number of vascular risk
factors, including smoking, hypertension, diabetes, bilateral carotid stenosis, previous minor stroke. One year
earlier he noticed progressive gait disturbance, consisting
of start hesitation, shuffling gait and instability, leading to
backward falls, followed, a few weeks later, by diffuse
slow movements, reduced manual dexterity, depression,
poor motivation, cognitive decline. Two months after, a
generalized convulsive seizure occurred, characterized
by loss of consciousness, diffuse muscular rigidity, bitten
tongue and cyanosis, lasting for a few minutes and after

Journal of Stroke and Cerebrovascular Diseases, Vol. -, No. - (---), 2014: pp 1-3

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G. LANZA ET AL.

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which he was confused and drowsy. The electroencephalogram at the emergency room demonstrated diffuse
slowing without continued seizure activity or an ictal
focus. He was discharged under valproic acid and no
other episodes recurred. However, motor slowing, rigidity, cognitive impairment and behavioral disturbances
worsened significantly. At examination, he had a staring
and hypomimic expression, hypophonic speech, very
rare blinking, and limited and slow vertical saccades.
The doll’s head maneuver demonstrated the supranuclear origin of the gaze palsy. Frontal release signs were
present. In the arms, there was a jerky tremor and he
got easily fatigued on repetitive movements, more
evident on the left side. The patient had marked neck
rigidity, flexed posture, and slightly curved on the right
side with significantly impaired postural reflexes, a positive ‘‘sitting in block’’ sign, and a neurogenic bladder
dysfunction. Lower limb involvement was prominent:
the gait was diffusely slow, with creeping steps, freezing,
start hesitation and tendency to back falls. Signs of pseudobulbar palsy, including brisk jaw jerk, emotional
lability (pathological crying), a degree of dysphagia and
mild paraparesis, were also evident. He showed
depressed mood, emotional lability and apathy, and
cognitive impairment. Brain MRI showed a leukoaraiosis
in the periventricular and pons white matter (Fig 1, A),
atrophy of the midbrain with a relative sparing of the
pons (the so-called ‘‘penguin sign’’) (Fig 1, B), and diffuse
brain and callosal atrophy (Fig 1, C). Despite anti-parkinsonian treatment (l-dopa 1 carbidopa 200 1 50 mg three
times daily and selegiline 10 mg daily), he progressively
worsened.

Discussion

Figure 1. (A) Axial fluid attenuated inversion recovery (FLAIR) MRI
showing diffuse periventricular leukoaraiosis; (B) midsagittal T1-weighted
MRI demonstrating the silhouette of the penguin sign and corpus callosum
atrophy; (C) coronal T2-weighted MRI showing lateral and third ventricle
dilatation together with subarachnoid space enlargement. Abbreviation:
MRI, magnetic resonance imaging.

Although the vPSP is considered extremely rare,
almost one third of patients with a clinical diagnosis of
PSP have evidence of a multi-infarct state.1 In addition
to an increased frequency of vascular risk factors, vPSP
can be differentiated from idiopathic PSP by a relatively
higher degree of asymmetry, predominant lower body
involvement, corticospinal and pseudobulbar signs,
urinary incontinence,2 cognitive impairment, and rapid
progression.3 Clinical-pathological evidence supports
the concept that diffuse brain vascular changes in subcortical regions, especially the bilateral frontal lesions,
can be sufficient to cause a PSP-like phenotype.4,5
Interestingly, substantia nigra, subthalamic nuclei and
periacqueductal gray matter, which are prominently
affected by tau-protein deposition in PSP, are not
directly involved in vPSP.4 Patients with vPSP might
have a tendency to develop vPSP triggered by acquired
insults,6 such as stroke, trauma, or seizures. Ischemic
destruction of multiple cortical, basal ganglia, and
thalamic structures may also cause a lack of response to
l-dopa in patients with vPSP more than in those with

VASCULAR PROGRESSIVE SUPRANUCLEAR PALSY
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idiopathic PSP. In Parkinson’s disease and in other
parkinsonian syndromes, including PSP,7 seizures do
not seem to be a common feature,8 although they might
be related to the same pathogenetic processes responsible
for neurodegeneration.8
After an epileptic seizure, an increase of neural death
might also be the consequence of the impaired regulation
of arterial blood flow and shunt to the venous system
within the brain due to severe cerebrovascular disease.
Although any causal relationship between subcortical
vascular disease and epileptogenicity is still speculative,
vascular burden might be associated with disruption of
cortical-subcortical circuits and consequently underlie
epileptogenicity.9 Recently, alterations in both structural
and haemodynamic cerebrovascular measures in patients
with leukoaraiosis and late onset epilepsy have been
described.10 Moreover, white matter lesion volume correlated with increased blood-brain barrier permeability,
which is important in epileptogenesis.10 Finally, it is
worth to highlight that both late onset seizures and leukoaraiosis in patients with no obvious mental deterioration are premonitory signs of subsequent cognitive
decline,11 as reported in this patient. Parkinsonism in
the context of subcortical vascular disease rises the possibility of an alternative diagnosis. Although there are similarities with a vascular parkinsonism, the prominent
involvement of vertical gaze and postural reflexes,
together with the ‘‘penguin sign’’ at MRI, seems to be
more concordant with a vPSP. A PSP-like phenotype
represents also one of the potential manifestations of
the Cerebral Autosomal-Dominant Arteriopathy with
Subcortical Infarcts and Leukoencephalopathy;12 however, although we did not perform investigations to rule
out this possibility, common clinical features and typical
neuroradiological findings are not present in this case.
vPSP should be considered when progressive clinical features suggestive of idiopathic PSP are associated with
neuroimaging evidence of cerebrovascular disease. The
occurrence of epileptic seizures might trigger the onset
or precipitate the course of PSP-like disorders.

3
Acknowledgment: The authors do not have any conflict
of interest or sponsorship to disclose.

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