LETTER TO THE EDITOR

Familial Creutzfeldt–Jakob disease with M232R mutationpresented with corticobasal syndrome

Jung Geol Lim • Eungseok Oh • Sangmin Park •

Yong-Sun Kim • Aeyoung Lee

Received: 10 September 2014 / Accepted: 8 December 2014

� Springer-Verlag Italia 2014

Dear Editor-in-Chief,

Creutzfeldt–Jakob disease (CJD) mimicked various

neurodegenerative diseases among them corticobasal syn-

drome (CBS) is very rare as an initial manifestation of

CJD. There are some cases of sporadic CJD (sCJD) pre-

sented as CBS, but none of familial CJD (fCJD) case is

reported yet. In addition, the only one case of M232R

mutation in fCJD was reported in South Korea [1]. We

report a case of 73-year-old woman who diagnosed CBS

with dystonic posturing of unilateral arm and finally con-

firmed as fCJD.

A 73-year-old right-handed South Korean woman vis-

ited with severe gait disturbance, bradykinesia and dystonic

posturing of left arm. Three months before the admission,

she diagnosed parkinsonism with bradykinesia and gait

disturbance at another hospital. Brain magnetic resonance

image (MRI) was normal and has been taking levodopa

constantly. But levodopa was not effective and her par-

kinsonism was getting worse rapidly. At the time of

admission, she showed gait disturbance, postural instabil-

ity, stuttering, swallowing difficulty, severe rigidity of axial

and limb muscles, and jerky dystonic tremor and posturing

of left arm. In addition, bilateral esotropia and vertical gaze

palsy were observed. Ideomotor and buccofacial apraxia,

alien hand syndrome, right-left disorientation, frontal lobe

releasing sign were also observed. Laboratory studies

including cerebrospinal fluid (CSF) examination were all

Table 1 Results of neuropsychological test

Tests Results

Language and related functions

Calculation

Addition 3/3

Subtraction 3/3

Multiplication 2/3

Division 1/3

Writing Abnormal

Body part identification Abnormal

Right-left orientation Abnormal

Ideomotor praxis 2/5 (abnormal)

Buccofacial praxis Abnormal

Visuospatial functions

Interlocking pentagon 0/1

Copy of rey-CFT 1.5/36

Memory

Seoul verbal learning test-free recall (1st/2nd/3rd

trial/20 min delay recall/recognition score)

3/4/4/2/20

Rey-CFT copy/immediate recall/20 min delayed

recall/recognition score

1.5/2/2/14

Frontal/executive function

Contrasting program/go-no-go test 15/8

Fist-edge-palm Abnormal

Alternating hand movement Abnormal

Luria loop Perseveration

Alternating square and triangle Deformed

Word fluency: category items (animal/

supermarket)

6/14

Word fluency: letter 0/2/2

Stroop (word reading, color reading) 46/112,

13/112

K-MMSE 19/30

J. G. Lim � E. Oh � S. Park � A. Lee (&)

Department of Neurology, Chungnam National University

Hospital, Daejeon, Korea

e-mail: aelee@cnu.ac.kr

Y.-S. Kim

Ilsong Institute of Life Science, Hallym University,

Anyang, Korea

123

Neurol Sci

DOI 10.1007/s10072-014-2038-4

within normal limit. Of the cognitive functions, attention,

fluency, and comprehension were relatively preserved but

visuospatial function, memory, and frontal executive

function were decreased severely, and apraxia was noted

on a comprehensive neuropsychological assessment (Seoul

neuropsychological screening battery, SNSB) (Table 1).

Although she showed hypomimia, she smiled frequently

during ordinary conversation. Follow-up brain MRI dem-

onstrated gyriform high-signal intensities in the frontal

cortex, insula, bilateral parietal lobes, perirolandic gyrus,

and occipitotemporal areas of the diffusion-weighted ima-

ges(DWI). An electroencephalography (EEG) revealed

generalized intermittent 6–8 Hz of slow waves in all leads.

The 12th day of admission, 14-3-3 protein was detected

weakly positive in CSF analysis. Tau protein level was

increased as 1,501.9 pg/ml (normal range \ 200 pg/ml)

and Ab42 was 76.1 pg/ml in CSF. The sequencing of

PRNP revealed a M232R mutation (ATG ? AGG)

(Fig. 1). She died with aspiration pneumonia about

6 months after the onset of symptoms in nursing home.

As a rapidly progressive neurodegenerative disorder,

CJD are characterized by progressive dementia, ataxia, and

myoclonus. The typical subtype of CJD is sCJD, which

accounts for over 85 % of CJD. CJD presented with CBS is

very rare, besides even if the fCJD. This is the first case of

fCJD who showed compatible extrapyramidal symptoms

and apraxia with cognitive dysfunctions of CBS in the

South Korea. The genetic mutation seems to play an

important role in the pathogenesis of fCJD but ethnic

Fig. 1 a Western blot finding

of 14-3-3 protein. b The

sequencing of PRNP revealed a

M232R mutation

(ATG ? AGG)

Table 1 continued

Tests Results

CDR/GDS/Barthel ADL 2/5/9

GDS 5

K-BNT Korean version of Boston naming test, Rey-CFT rey complex

figure test, K-MMSE Korean version of mini-mental state examina-

tion, CDR clinical dementia rating, GDS global deterioration scale,

Barthel ADL Barthel activities of daily living, GDS geriatric

depression scale

Neurol Sci

123

differences exist [1]. The M232R mutation was the fourth

most common genetic types of fCJD in Japan, but it is very

rare in European countries. Also the only one case of the

M232R mutation was reported in South Korea so far [1].

The M232R mutation was reported in eight Japanese

patients and their clinical features were similar to those of

sCJD [1] like progressive memory impairment, gait dis-

turbance, and myoclonus, and a typical EEG with periodic

spike and wave (PSW) complexes [2]. The M232R muta-

tion divided with two groups by progression and clinical

features such as rapidly progressive type and slowly pro-

gressive type [3]. Our case was more similar to rapidly

progressive type but interesting point is that neither our

case nor all cases of the Japanese M232R mutation had

family history of CJD and any neurodegenerative diseases

[4]. Accordingly, the role of M232R mutation could be a

rare polymorphism [5], not a causative point mutation in

fCJD. In conclusion, the role of DWI and sequencing of

PRNP in CSF is well justified for the early diagnosis of

fCJD. It is important to keep the possibility of CJD in mind

when evaluating patients who showed extrapyramidal

symptoms and apraxia with cognitive dysfunctions which

are unusually rapid in progression.

Conflict of interest The authors claim no conflict of interest.

References

1. Choi BY, Kim SY, Seo SY et al (2009) Mutations at codons 178,

200-129, and 232 contributed to the inherited prion diseases in

Korean patients. BMC Infect Dis 9:132

2. Hitoshi S, Nagura H, Yamanouchi H et al (1993) Double mutations

at codon 180 and codon 232 of the PRNP gene in an apparently

sporadic case of Creutzfeldt-Jakob disease. J Neurol Sci 120(2):

208–212

3. Shiga Y, Satoh K, Kitamoto T et al (2007) Two different clinical

phenotypes of Creutzfeldt–Jakob disease with a M232R substitu-

tion. J Neurol 254(11):1509–1517

4. Hoque MZ, Kitamoto T, Furukawa H et al (1996) Mutation in the

prion protein gene at codon 232 in Japanese patients with

Creutzfeldt–Jakob disease: a clinicopathological, immunohisto-

chemical and transmission study. Acta Neuropathol 92(5):441–446

5. Nozaki I, Hamaguchi T, Sanjo N et al (2010) Prospective 10-year

surveillance of human prion diseases in Japan. Brain 133(10):

3043–3057

Neurol Sci

123