Case Report

Sporadic Creutzfeldt–Jakob disease
presenting as a stroke mimic
Introduction

Creutzfeldt–Jakob disease is a rare neurodegenerative disease in which there is an
abnormal accumulation of prion protein.
It occurs with an incidence of approximately 1 per million per year. Sporadic
Creutzfeldt–Jakob disease occurs in
approximately 85% of cases, with familial,
variant and iatrogenic forms less common.
Typically sporadic Creutzfeldt–Jakob disease presents with a rapidly progressive
dementia, but sub-variants include the
Heidenhain and Oppenheimer–Brownell
variants. The former presents with visual
disturbance and the latter with ataxia. This
article describes a 75-year-old man with a
Heidenhain variant of sporadic
Creutzfeldt–Jakob disease who presented
with a sudden onset of homonymous
hemianopia mimicking a stroke.

Discussion

Sporadic Creutzfeldt–Jakob disease typically presents in patients aged 50–75 years,
with prodromal symptoms of depression,
apathy, paranoia or self neglect. These are
often followed by a progressive dementia,
myoclonus, ataxia and visual disturbance.
The Heidenhain variant refers to a subgroup of patients with sporadic Creutzfeldt–
Jakob disease who present with prominent
visual symptoms at onset. It was first
described by Heidenhain in 1929.
The exact definition of the Heidenhain
variant is unclear. Although all agree that
there is visual disturbance at onset, some
suggest this has to be in isolation (Cooper
et al, 2005) whereas others include those
with visual disturbance and other neurological deficits such as dementia (Appleby
et al, 2009; Kher et al, 2009). Using the
definition of purely visual onset in the
absence of cognitive, behavioural and
physical symptoms for at least 2 weeks the
Heidenhain variant made up only 3.7% of
cases of sporadic Creutzfeldt–Jakob disDr Claire L Hirst is Specialist Registrar in
Neurology in the Department of Neurology,
Morriston Hospital, Swansea SA6 6NL
(clairehirst_uk@yahoo.co.uk)

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ease (Cooper et al, 2005). However, others
report Heidenhain variant features in 20%
of cases of sporadic Creutzfeldt–Jakob
disease (Kropp et al, 1999).
The visual disturbance can be present
for a few weeks before the onset of further
neurological deficits. As the illness
progresses features such as myoclonus,
ataxia and pyramidal signs commonly
occur (Cooper et al, 2005).
In one study of patients with the
Heidenhain variant 86.7% presented with
cortical blindness or occulomotor dys-

function and 13.3% with visual hallucinations (Appleby et al, 2009). However, disturbed colour perception, field restriction,
blurred vision or visual neglect can occur
(Kropp et al, 1999).  
It is thought that patients with this clinical phenotype have a significantly shorter
disease duration than classical sporadic
Creutzfeldt–Jakob disease (Kropp et al,
1999). The majority of patients display
periodic sharp waves on electroencephalogram and often magnetic resonance imaging shows increased signal in the basal gan-

Case Report

A 75-year-old male presented with a 2-week history of blurred vision and had a right homonymous
hemianopia on visual field testing (Figure 1). Following this he started to develop unsteadiness and was
seen in the transient ischaemic attack clinic. His past medical history consisted of hypertension, chronic
obstructive pulmonary disease, gastro-oesophageal reflux disease and a cholesteatoma and mastoidectomy
in 1984. There was no significant family history. Examination at this time was normal apart from the right
homonymous hemianopia. A computed tomography brain scan and carotid Dopplers were unremarkable.
He was started on stroke secondary prevention and discharged with a diagnosis of probable stroke.
He re-presented 4 weeks later with a progressive worsening of vision, difficulty with speech and increasing
confusion which had been noticed by his family over the past few weeks. He described oscillopsia and that
objects all appeared green in colour (xanthopsia). He had developed some expressive dysphasia and confusion.
His wife had noticed some personality change. He had become aggressive, paranoid and anxious. The speech
and language therapist noted fluctuating comprehension, perseveration and word-finding difficulties with word
substitutes. Eight days after admission he became increasingly agitated and aggressive. The following day
he was responding to visual hallucinations and trying to catch medicine tablets that he thought were floating
around the room. At this time he also developed generalized myoclonus. A magnetic resonance imaging scan
of his brain showed subtle hyperintensity within the cortical gyri in the left occipital and parietal region on fast
fluid attenuated inversion recovery sequence and diffusion weighted imaging showed striking hyperintensity
within the corresponding area (Figure 2). An electroencephalogram showed persistent lateralized periodic sharp
waves, 205–300 ms in duration over the left hemisphere at rate of 1–2.5 Hz. These were also present over
the right hemisphere to a lesser degree, otherwise background rhythm was preserved (Figure 3). A lumbar
puncture was performed. Owing to lack of patient cooperation this was blood stained and therefore protein
14-3-3 was unable to be tested, but protein, glucose and cell counts were all normal.
He rapidly became cortically blind, incoherent and bed bound. Examination at this point revealed a
Glasgow coma score of 9/15, pupils were equal and reactive but there was no response to visual menace
and dolls eye movements were normal. Upper limb gegenhalten, a right grasp reflex and brisk reflexes
with spontaneous myoclonus were noted. He continued to decline rapidly and died 3 weeks after his
admission and 2 months after symptom onset. A post mortem was performed and revealed generalized
spongiform degeneration particularly present in the parietal and occipital cortex, with a prion protein
deposition of the synaptic type consistent with a diagnosis of Creutzfeldt–Jakob disease. There was also
evidence of neurofibrillary tangles that were characteristic for Alzheimer’s disease. The PRNP genotyping
on brain tissue did not show any mutations which ruled out any possibility of an inherited prion disease. A
definite diagnosis of sporadic Creutzfeldt–Jakob disease was therefore made.

British Journal of Hospital Medicine, October 2011, Vol 72, No 10

Case Report

Figure 1. Visual fields showing a right
homonymous hemianopia.

glia or hyperintensities in the occipital and
visual cortices (Kropp et al, 1999). In some
patients magnetic resonance imaging can be
normal but abnormalities may be detected
on diffusion weighted imaging (Lee et al,
1998; Zeidler and Green, 2004). While in
this patient the abnormalities are seen on
magnetic resonance imaging they are more
marked on diffusion weighted imaging.
CSF examination often reveals the presence of protein 14-3-3 and a review has
suggested that this has a sensitivity of 86%.
Other CSF markers include s100b (an

a

b

Figure 2. Magnetic resonance imaging of the brain. a. Fluid-attenuated inversion recovery sequence showing
subtle hyperintensity in the cortical gyri of the left parietal and occipital lobe. b. Diffusion weighted imaging
showing hyperintensity involving the left temporal lobe, the occipital lobe and the parietal lobe.

astrocyte marker) and tau (a neuronal
marker). It has been suggested that the
combination of a positive CSF 14-3-3 or
an elevated tau protein with a raised S100b
had the highest positive predictive power
for sporadic Creutzfeldt–Jakob disease
(Chohan et al, 2010). This patient did not
have CSF 14-3-3 measured as the sample

Figure 3. Electroencephalogram showing lateralized periodic sharp waves over the left hemisphere.

Learning Points
n Creutzfeldt–Jakob disease is a rare neurodegenerative disease in which there is abnormal accumulation
of prion protein. The Heidenhain variant presents with prominent visual symptoms at onset.
n Most patients display periodic sharp waves on electroencephalogram and magnetic resonance imaging
often shows increased signal in the basal ganglia or hyperintensities in the occipital and visual cortices.
n Sporadic Creutzfeldt–Jakob disease can occasionally present as a stroke mimic and should be
considered in a patient presenting with a possible stroke who goes on to have a progressive course.
n Sporadic Creutzfeldt–Jakob disease should be considered in a patient presenting with isolated visual
disturbance in whom a cause cannot be found, particularly if there is subsequent neurological impairment.

British Journal of Hospital Medicine, October 2011, Vol 72, No 10

was blood stained and it was felt that there
was enough evidence without it to diagnose Creutzfeldt–Jakob disease.
The most common cause of an isolated
homonymous hemianopia is stroke,
accounting for 70% of cases. Other nonstroke causes include head injury, tumour
and rarely neurosurgical procedures or
multiple sclerosis. Infarction of the occipital lobe frequently may not produce
other neurological manifestations and so
can be confused with an early case of
Heidenhain variant sporadic Creutzfeldt–
Jakob disease. BJHM
Appleby BS, Appleby KK, Crain BJ, Onyike CU,
Wallin MT, Rabins PV (2009) Characteristics of
established and proposed sporadic CreutzfeldtJakob disease variants. Arch Neurol 66: 208–15
Chohan G, Pennington C, Mackenzie JM et al
(2010) The role of cerebrospinal fluid 14-3-3 and
other proteins in the diagnosis of sporadic
Creutzfeldt-Jakob disease in the UK: a 10-year
review. J Neurol Neurosurg Psychiatry 81: 1243–8
Cooper SA, Murray KL, Heath CA, Will RG,
Knight RS (2005) Isolated visual symptoms at
onset in sporadic Creutzfeldt-Jakob disease: the
clinical phenotype of the "Heidenhain variant".
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Kher M, Rao MY, Acharya PT, Mahadevan A,
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Lee KE, Loh NK, Tan AK, Lee WL, Tjia HT (1998)
Creutzfeldt-Jakob disease presenting with visual
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variant. Ann Acad Med Singapore 27: 854–6
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