Yonago Acta medica 2014;57:1–14

Original Article

Pathologic Reappraisal of Wallenberg Syndrome: A Pathologic Distribution
Study and Analysis of Literature
Shinsuke Kato,*† Miki Takikawa,*† Sho Ishihara,† Atsushi Yokoyama† and Masako Kato§†Division of Neuropathology, Department of Pathology, School of Medicine, Tottori University Faculty of Medicine, Yonago, 683-8503,
Japan and §Division of Molecular Pathology, Department of Pathology, School of Medicine, Tottori University Faculty of Medicine,
Yonago 683-8503, Japan

ABSTRACTcal obstruction of the PICA or VA; ii) infarction in thelateral MO based on PICA or VA obstruction; and iii) a
1-to-1 correspondence between clinical symptoms andneuropathological lesions.

Background Wallenberg syndrome was first reported
by Adolf Wallenberg as arising due to the obstructionof the posterior inferior cerebellar artery (PICA), whichcaused an infarct in the lateral medulla oblongata (MO).
Methods This study was carried out on brain tissue
from 2 patients with typical Wallenberg syndrome and
10 autopsy cases without central nervous system disturbances.
Results Patient 1 exhibited the 3 major neurologicalsymptoms of right crossed sensory disturbance, rightcerebellar ataxia and bulbar palsy. There was the pathological obstruction of the right vertebral artery (VA).
Regarding the histopathlogical distribution, the infarct
extended on the right side to the lateral spinothalamic
tract, nucleus of the spinal tract of the trigeminal nerve,
spinal tract of the trigeminal nerve, inferior cerebellar
peduncle, spinocerebellar tract and nucleus ambiguous. Moreover, a clear infarct in the left lateral MO was
pathologically identified, but pathological obstructionof the left PICA or left VA could not be found. The left
cerebellar ataxia and bulbar palsy were observed among
these 3 major symptoms. Patient 2 showed the 3 major
symptoms of right crossed sensory disturbance, rightcerebellar ataxia and bulbar palsy. A pathological luminal occlusion was identified in the right PICA. Regarding the histopathological lesion, the infarct disturbed on
the right side the lateral spinothalamic tract, nucleus of
the spinal tract of the trigeminal nerve, spinal tract of
the trigeminal nerve, spinocerebellar tract, inferior cerebellar peduncle and nucleus ambiguus.
Conclusion Based on our investigation of pathological lesions using our 2 autopsies, we suggest calling thecases that satisfy the following 3 criteria “definite pathologic Wallenberg syndrome”: i) identifiable pathologi-

Key words infarct; lateral medulla oblongata; posterior

inferior cerebellar artery; vertebral artery; Wallenberg
syndrome
Wallenberg syndrome was first mentioned in a report by
Adolf Wallenberg in 1895 on only the clinical symptomsof an alive case of lateral medulla oblongata (MO) infarct. He performed a pathological analysis on this same
autopsy case in 1901, reporting a detailed pathologicallesion. In this autopsy report, Adolf Wallenberg verified that the disease is caused by the obstruction of theposterior inferior cerebellar artery (PICA).1 After 1901,
this disease was called Wallenberg syndrome. However,there have been few reports on autopsy cases with Wallenberg syndrome. Hata et al. reported 3 of their own
surviving cases of Wallenberg syndrome from Japan.
They also analyzed 153 cases from the Japanese literature, including the 3 cases they experienced, of which
only 16 cases were autopsies.2 To date, literature studies
have reported that in addition to PICA, the vertebral artery (VA) can also serve as the blocked blood vessel responsible for Wallenberg syndrome.3–6 Adolf Wallenberg
originally described the typical 3 major symptoms thatare characteristic of Wallenberg syndrome: i) crossed
sensory disturbance or alternative hemianesthesia (disturbance of thermal and pain sensibility on one side of
the face as well as on the opposite side of the body except the face), ii) cerebellar ataxia and iii) bulbar palsy.
These typical 3 major symptoms have been considered
the core clinical symptoms of Wallenberg syndrome. As
more case reports were accumulated, the cases without
facial sensory disturbance have come to be considered
Wallenberg syndrome. Currently, even cases devoid of
1 symptom out of the typical 3 major symptoms are
considered as Wallenberg syndrome, showing that thedefinition of the disease has widened. This wider interpretation is thought to come from individual variationsin the vascular supply regions of the MO, which lead toa wide variety of symptoms in Wallenberg syndrome*S.K. and M.T. contributed equally to this study.
Corresponding author: Shinsuke Kato, MD, PhD
kato@med.tottori-u.ac.jp
Received 2013 November 18
Accepted 2013 November 26
Abbreviations: ABC, avidin-biotin-immunoperoxidase complex;
BA, basilar artery; ELVG, elastica van Gieson; GFAP, glial fibrillary acidic protein; HE, hematoxylin and eosin; KB, KlüverBarrera; LFB, luxol fast blue; MO, medulla oblongata; PICA,
posterior inferior cerebellar artery; VA, vertebral artery1

S. Kato et al.

patients.2 In this study, we report 2
autopsy cases with typical Wallenberg
syndrome. Based on these 2 autopsies,
we reappraised Wallenberg syndromefrom a pathological standpoint throughan analysis of the past 24 autopsy reports
from the literature.
MATERIALS AND METHODS
Subjects and histopathology

No. Anatomical region
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21

Hypoglossal N.
Sublingual N. (Roller)
Dorsal vagal N.
Hypoglossal intrafascicular N.
Dorsal central medullary N.
Dorsal paragigantocellular N.
Medial vestibular N. (Schwalbe)
N. of solitary tract
N. ambiguus
Lateral paragigantocellular N.
Lateral or accessory cuneate N. (von Monakow)
N. of spinal tract of trigeminal nerve
Medial longitudinal fascicle
Medial lemniscus
Solitary tract
Spinal tract of trigeminal nerve

7

11
18

3

1

8
16
12
19 17
20

5

21 9
6
10

13
2

15

4

14

This study was carried out on brain
tissue from 2 patients with Wallenberg
Inferior cerebellar peduncle
Lateral spinothalamic tract
syndrome. The brain was fixed in 10%
Spinocerebellar tract
buffered formalin. The brain stem andSympathetic discending tract
cerebellum were removed from the ce- Fig. 1. Schematic diagram of nerve nuclei and tracts in MO. MO, medulla oblonrebrum at the midbrain level. Routine gata; N, nucleus.
control sectioning of the cerebrum was
performed. The brain was cut starting from the level of the mammillary body of the basetibody for 18 h at 4 ˚C. Bound antibody was visualized
aspect of the cerebrum. The brain stem was cut transby the avidin-biotin-immunoperoxidase complex (ABC)method using the appropriate Vectastain ABC kit (Vector
versely along the long axis resulting in sections parallel
Laboratories, Burlingame, CA) and 3,3'-diaminobenzito the midbrain, pons and MO. The thickness of these
section slices was about 5 mm thick. The cut was condine tetrahydrochloride (Dako, Glostrup, Denmark) as
the final chromogen.
tinuous and severed the 5-mm thick sections completely.
The specimens of the brain tissue including MO wereAnalysis about the correlation between the clinembedded in paraffin, and cut into 6-µm thick sections.
The sections were stained by the following routine
ical symptoms and pathologic legions
methods: hematoxylin and eosin (HE) and HE-luxol fast
A diagram of the neuroanatomical locations of nerve nublue (HE-LFB) double stains as well as Klüver-Barrera
clei and tracts was created from the MO sections from 10(KB) stain. In addition, special histochemical stains
normal controls using a light microscope (Olympus BXwere performed on the sections with Holzer, Bodian and
50 F4, Tokyo, Japan) (Fig. 1) with digital camera (Olympus
modified Hirano-Bielschowsky stains. Five-millimeter
D12). Then, the locations of infarcts were identified in the
thick slices of the major arteries of the brain including
MO sections from the 2 Wallenberg syndrome autopsies
the circle of Willis were also embedded in paraffin, andand were recorded on the MO diagram, using a light micut into 5-µm thick sections: the sections were stained
croscope with digital camera. We analyzed the relationby HE, HE-LFB and elastica van Gieson (ELVG) stains.
ship between clinical symptoms and areas damaged by theHistologically, normal MO from 10 individuals without
infarcts.
central nervous system disturbances (ages: 50–85 years)
severed as normal controls. The protocols of this study
RESULTS
were approved by the Ethics Committee of Tottori UniPatient 1
Clinical history
versity (No. 2261: 2013).
The patient was male and 59 years old at death. At age
Immunohistochemical analysis
56, he experienced a brain-stem and cerebellar infarct.
The neurological symptoms were right crossed sensory
Representative paraffin sections were used for an imdisturbance (simultaneous disturbance of thermal andmunohistochemical assay. An IgG1 mouse monoclonal
pain sensibility on the right face as well as on the left
antibody to purified glial fibrillary acidic protein (GFAP)
side of the body except the face), right cerebellar ataxia,(high performance, ready-to-use; BioGenex, San Rabulbar palsy, right Horner’s syndrome and vertigo. Anmon, CA) was used as a primary antibody. Sections
infarct in the right lateral MO was suspected and then hewere deparaffinized, and endogenous peroxidase activwas clinically diagnosed with Wallenberg syndrome. At
ity was quenched for 30 min with 0.3% H2O2. Sections
age 58, he was hospitalized due to left cerebellar ataxia
were then washed in PBS, pH 7.4. Normal serum homoland the exacerbation of both bulbar palsy and vertigo. At
ogous with the secondary antibody was used as blocking
age 59, he developed aspiration pneumonia due to severe
reagents. Sections were incubated with the primary an2

Reappraisal of Wallenberg syndrome
Fig. 2. Macroscopic findingsof the MO in Patient 1. An oldand cavitated infarct can beseen on the right side. On theother hand, a recent infarctwith a softened lesion on theleft side in this formalin-fixed
wet tissue is not clear. Bar = 5
mm. MO, medulla oblongata.
Fig. 3. Macroscopic findings of the major arteries ofthe brain in Patient 1. With2
respect to the left-right difference in thickness in VA, theright VA (double arrowheads
and double small arrows) ismuch thinner than the left
VA. The lumen of the right
VA is obstructed 3 mm (doublearrowheads) down toward
the heart side from the PICA
bifurcation (large arrow withasterisk). In addition, theright VA exhibits a dysplasia
called “a VA-PICA variation”:
4
the diameter of the right VA
down toward the heart side (double arrowheads) before the right
PICA bifurcation is about twice the diameter of the right VA
after the right PICA bifurcation (double small arrows) until the
BA. The right PICA has almost the same diameter as the right
VA (double small arrows) after the bifurcation until the BA. The
diameter of the right VA (double small arrows) becomes thinnerfrom the right PICA bifurcation (large arrow with asterisk) to the
BA. Marked atherosclerosis can be observed in the left VA. No
thrombi or other pathological findings of occlusion are evident in
the left VA or left PICA. In order to remove the vertebrobasilar
arterial structure without damaging from the cerebrum, both posterior communication arteries that make up the circle of Willis
are severed on purpose. The photographic left is corresponding
to the right side of Patient 1, because of the observation from thecerebral base. Bar = 2 cm. BA, basilar artery; PICA, posterior
inferior cerebellar artery; VA, vertebral artery.

3

5A

Fig. 4. Klüver-Barrera (KB) staining of the MO in Patient 1. A
cavitary lesion originated from an old infarct can be seen in theright lateral medulla oblongata. A recent infarct exhibiting decreased stainability is also evident on the left side. Bar = 5 mm.
MO; medulla oblongata.

dysphagia based on bulbar palsy, and died of respiratory
failure.

5B

Macroscopic findings
The brain weighed 1,220 g after fixation. The macroscopic distribution of the MO included an old and cavitated infarct on the right side (Fig. 2). A recent infarct witha softened lesion on the left side was observed (Fig. 2).
An old infarct was also observed on the right cerebellar
hemisphere. A macroscopic analysis of the major arteries

Fig. 5. Pathological findings of the old infarct in the right lateral
MO in Patient 1.
A: Histopathological finding of an old infarct with fibrillary
gliosis observed around the cavitation (HE staining). Bar =50 μm.
B: GFAP-positive fibrillary gliosis around the cavitation (GFAP
immunostaining). Bar = 50 μm.
GFAP, glial fibrillary acidic protein; HE, hematoxylin and eosin;
MO, medulla oblongata.

3

S. Kato et al.

of the brain showed that the right VA was much thinner than the left VA. The lumen of the right VA wasobstructed 3 mm toward the heart side from the right
PICA bifurcation. Additionally, the right VA exhibited adysplasia called “a VA-PICA variation” (Fig. 3): the diameter of the right VA on the heart side before the right
PICA bifurcation was about twice the diameter of theright VA after the right PICA bifurcation until the basilar artery (BA). The right PICA maintained the same diameter as the right VA after the bifurcation until the BA.
The right VA diameter became thinner after the right
PICA bifurcation until the BA. Severe atherosclerosis
was observed in the left VA. There were no significant
thrombi in the left VA or left PICA.

sis was observed around the cavitation and there wereastrocytic demarcation areas surrounding the cavitation(Fig. 5A). There were few reactive astrocytes and foamy
macrophages. Astrocytic demarcation area positive for
GFAP were observed around the cavitation in GFAP
immunostaining (Fig. 5B). The histopathological distribution of the old lesion on the right side extended tonucleus of the spinal tract of the trigeminal nerve (No.
12 in Fig. 6), spinal tract of the trigeminal nerve (No. 16

Histological findings
In HE, HE-LFB and KB stainings, a cavitary lesion wasobserved in the right lateral MO due to an old infarct(Fig. 4). As for pathohistological findings, fibrillary glio-

7A

Clinical sign Pathological legion
Crossed sensory disturbance N. of spinal tract of trigeminal nerve 12
Spinal tract of trigeminal nerve
16
Lateral spinothalamic tract
19
Cerebellar ataxia Inferior cerebellar peduncle
18
Spinocerebellar tract20
Dysphagia N. Ambiguus
9Horner’s syndrome Sympathetic discending tract
21

7B

Fig. 6. Diagram of the relationship between clinical symptoms
and the pathological distribution impaired by the old infarct in
the right lateral MO in Patient 1. The nucleus of the spinal tractof the trigeminal nerve (No. 12), spinal tract of the trigeminal
nerve (No. 16), lateral spinothalamic tract (No. 19), inferior cerebellar peduncle (No. 18), spinocerebellar tract (No. 20), nucleus
ambiguus (No. 9) and sympathetic descending tract (No. 21) are
impaired. There is also partial impairement of the inferior olivary nucleus. The clinical symptom of right crossed sensory disturbance is considered to be due to the infarct in the nucleus of
the spinal tract of the trigeminal nerve (No. 12), and spinal tractof the trigeminal nerve (No. 16), the lateral spinothalamic tract(No. 19). Right cerebella ataxia is considered to be due to theinfarct in the inferior cerebellar peduncle (No. 18) and spinocerebellar tract (No. 20). Dysphagia is considered to be due to disturbance of the nucleus ambiguus (No. 9). The symptom of right
Horner’s syndrome is considered to be caused by disturbance ofthe sympathetic descending tract (No. 21). MO, medulla oblongata; N, nucleus.

7C
Fig. 7. Pathological findings of the recent infarct in the left MO
in Patient 1.
A: A large number of foamy macrophages (arrow) are observed(HE-LFB double staining). Bar = 50 μm.
B: Reactive astrocytes (arrow) around the recent infarct arealso seen (HE-LFB staining). Bar = 50 μm.
C: Reactive astrocytes (arrow) around the recent infarct arestrongly positive for GFAP (GFAP immunostaining). Bar =100 μm.
GFAP, glial fibrillary acidic protein; HE, hematoxylin and eosin;
LFB, luxol fast blue; MO, medulla oblongata.

4

Reappraisal of Wallenberg syndrome
Clinical sign Pathological legion
Cerebellar ataxia Inferior cerebellar peduncle
Dysphagia N. Ambiguus

18
9

9A

Fig. 8. Diagram of the relationship between clinical symptoms
and the pathological distribution disturbed by the recent infarctin the left lateral MO in Patient 1. There is disturbance of theinferior cerebellar peduncle (No. 18) and nucleus ambiguus (No.
9). Left cerebellar ataxia is due to disturbance to the inferior
cerebellar peduncle (No. 18). An exacerbation of dysphagia isobserved due to disturbance to the left nucleus ambiguus (No. 9).
MO, medulla oblongata; N, nucleus.

9B
in Fig. 6), the lateral spinothalamic tract (No.19 in Fig. 6),
inferior cerebellar penduncle (No. 18 in Fig. 6), spinocerebellar tract (No. 20 in Fig. 6), nucleus ambiguus (No.
9 in Fig. 6) and sympathetic descending tract (No. 21 inFig. 6).
An accumulation of a large number of foamy macrophages was observed in the recent infarct that exhibiteda softening lesion on the left side (Fig. 7A). Reactive astrocytes were also observed around the left recent infarctlesion (Fig. 7B). These reactive astrocytes were strongly
positive for GFAP (Fig. 7C). The distribution of the recent infarct on the left extended to the inferior cerebellar
penduncle (No. 18 in Fig. 8) and nucleus ambiguus (No.
9 in Fig. 8). Neither the left or right infarct lesion extended to the dorsal vagal nucleus, solitary tract, nucleusof the solitary tract, hypoglossal nucleus, medial longitudinal fascicle, medial lemniscus or pyramid of MO.
A histopathological analysis of the major arteries ofthe brain showed an organized thrombus blocking thelumen of the right VA (Fig. 9A). With respect to the right
VA, there was severe degeneration of the tunica media:
the smooth muscle cells in the tunica media had almost
disappeared, having been replaced with fibroblasts
and collagen fibers. Severe fibrous hypertrophy of thevascular intima was also observed, with the infiltrationof some foamy macrophages (Fig. 9B). An increase in
ELVG-positive elastic fibers was observed in the vascular intima (Fig. 9C). The normal wavy corrugation in theinternal elastic lamina disappeared (Fig. 9C). Althoughsevere atherosclerosis was observed in the left VA and

9C
Fig. 9. Histopathological findings of the right VA in Patient 1.
A: A thrombus accompanied by organization is blocking the lumen (ELVG staining). Bar = 500 μm.
B: Severe degeneration of the tunica media can be seen (arrows).
Histologically, the smooth muscle cells in the tunica media
almost disappear, having been replaced with fibroblasts andcollagen fibers. Severe fibrous hypertrophy of the vascular
intima is also observed, with the infiltration of some foamy
macrophages (arrowheads) (HE-LFB staining). Bar = 100μm.
C: An increase in ELVG-positive elastic fibers is observed in
the vascular intima (arrowheads). The normal wavy corrugation disappears in the internal elastic lamina (arrows) (ELVG
staining). Bar = 100 μm.
ELVG, elastica van Gieson; HE, hematoxylin and eosin; LFB,
luxol fast blue; VA, vertebral artery.

left PICA, obstruction was not observed in the left VA orleft PICA.
5

S. Kato et al.

Results of analysis about the correlation between theclinical symptoms and pathologic legions
Right crossed sensory disturbance (simultaneous disturbances of thermal and pain sensibility on the right headas well as on the rest of the left body except the head)
was observed at the 1st attack. The responsibility lesion
corresponding to this right crossed sensory disturbancewas considered to be the right infarct in the nucleus of
the spinal tract of the trigeminal nerve (No. 12 in Fig.
6), spinal tract of the trigeminal nerve (No. 16 in Fig. 6)
and lateral spinothalamic tract (No.19 in Fig. 6). Right
cerebellar ataxia was considered to be the disturbancesof the right inferior cerebellar penduncle (No. 18 in
Fig. 6) and spinocerebellar tract (No. 20 in Fig. 6). The
symptoms of dysphagia were considered to be due todisturbance of the nucleus ambiguus (No. 9 in Fig. 6),
and the symptoms of right Horner’s syndrome were considered to be due to disturbance of the right sympathetic
descending tract (No. 21 in Fig. 6). Left cerebellar ataxia
was observed at the 2nd attack. This was thought to havearisen from disturbance of the left inferior cerebellar
penduncle (No. 18 in Fig. 8). An exacerbation of dysphagia was also observed at the 2nd attack. This dysphagia
symptom had already occurred with the 1st attack due
to disturbance of the right nucleus ambiguus (No. 9 inFig. 6), and this 1st attack dysphagia was thought to havecontinued until the 2nd infarct. In the patient with this
1st attack dysphagia, the 2nd infarct lesion disturbed theleft nucleus ambiguus (No. 9 in Fig. 8), which made thedysphagia worse: i.e., an exacerbation of dysphagia wasobserved after the 2nd attack.
Patient 2
Clinical history
The patient was male and 79 years old at the time ofdeath. At age 74, he was diagnosed with chronic heart
failure. At age 79, he was hospitalized after the appearance of vertigo, vomiting and headache. His neurological symptoms were right crossed sensory disturbance,right cerebellar ataxia, bulbar palsy and right Horner’s
syndrome. An infarct in the right lateral MO was suspected from the only clinical symptoms, and thus he
was given a clinical diagnosis of Wallenberg syndrome.
Aspiration pneumonia occurred on day 2 of the illness.
On day 4 of the illness, he was put on a ventilator after
the respiratory arrest, but his heart rate decreased. He
died on the 10th day of the illness due to heart failure.
Macroscopic findings
The brain weighed 1,300 g after fixation. The macroscopic distribution of the lesion was a fresh infarct accompanied by severe edema in the right lateral MO (Fig.
10). The right cerebellar hemisphere also exhibited a
fresh infarct with severe edema. A macroscopic analysisof the major arteries of the brain revealed occlusion of
the lumen of the right PICA about 3 mm distal from its
bifurcation with the right VA (Fig. 11).

Fig. 10. Macroscopic findings of the MO in Patient
2. A fresh infarct is seen in
the right lateral MO. Since
the acute infarct region of
the right MO becomes veryfragile, the upper part of theinfarct region is artificiallydestroyed on the occasion ofbrain cutting. Bar = 5 mm.
MO, medulla oblongata.
Fig. 11. Macroscopic findings of the major arteries ofthe brain in Patient 2. The
right PICA is obstructed
about 3 mm distal from theright bifurcation (double arrowheads). The photographic left is corresponding to
the right side of Patient 2,
because of the observationfrom the cerebral base. Bar= 2 cm. PICA, posterior inferior cerebellar artery.

10

11

12

Fig. 12. KB staining of the
MO in Patient 2. A fresh infarct is observed in the right lateral MO. A strong decrease in stainability can be seen. Bar = 5 mm. KB,
Klüver-Barrera; MO, medulla oblongata.

6

Reappraisal of Wallenberg syndrome

red neurons showing Spielmeyer’s acute ischemic change
were not stained with KB staining. Severe edematous
tissue change was observed in neuropils around the acuteinfarct. There was no structure positive for GFAP in andaround the acute infarct area in GFAP immunostaining(Fig. 13C). This acute infarct lesion extended to disturb
the nucleus of the spinal tract of the trigeminal nerve (No.
12 in Fig. 14), spinal tract of the trigeminal nerve (No.16
in Fig. 14), the lateral spinothalamic tract (No. 19 in Fig.
14), inferior cerebellar penduncle (No. 18 in Fig. 14), spinocerebellar tract (No. 20 in Fig. 14), nucleus ambiguus(No. 9 in Fig. 14), sympathetic descending tract (No. 21
in Fig. 14), medial vestibular nucleus (No. 7 in Fig. 14),
nucleus of the spinal tract of the trigeminal nerve (No.

Histological findings
In HE, HE-LFB and KB staining, a fresh acute infarct
was observed in the right lateral MO and exhibited astrong decrease in stainability (Fig. 12). Macrophagesor reactive astrocytes were not observed in the area of
infarction (Fig. 13A). Neurons in the infarct area wereidentified as “red neurons” by HE staining: the typicalneuropathological finding of these red neurons is called“Spielmeyer’s acute ischemic change” (Fig. 13B). These

Clinical sign Pathological legion
Crossed sensory disturbance N. of spinal tract of trigeminal nerve 12
Spinal tract of trigeminal nerve
16
Lateral spinothalamic tract
19
18
Cerebellar ataxia Inferior cerebellar peduncle
Spinocerebellar tract20
9Dysphagia N. Ambiguus
21
Horner’s syndrome Sympathetic discending tract
7
Vertigo Medial vestibular N.
Headache N. of spinal tract of trigeminal nerve 12
Spinal tract of trigeminal nerve
16

13A

13

11
18

8

2

14

7

3

1

15

5
4

6

16

12
9 21
17 19
20
10

13B
Fig. 14. Diagram of the relationship between clinical symptoms
and the pathological distribution disturbed by the acute infarct in
the right lateral MO in Patient 2. There is disturbance of the nucleus of the spinal tract of the trigeminal nerve (No. 12), spinal
tract of the trigeminal nerve (No. 16), lateral spinothalamic tract(No. 19), inferior cerebellar peduncle (No. 18), spinocerebellar
tract (No. 20), nucleus ambiguus (No. 9), sympathetic descending tract (No. 21), medial vertebular nucleus (No. 7), nucleus of
the spinal tract of the trigeminal nerve (No. 12) and spinal tractof the trigeminal nerve (No. 16). There is also disturbance of thedorsal vagal nucleus (No. 3) and inferior olivary nucleus. The
clinical symptom of right crossed sensory disturbance is basedon an infarct in the nucleus of the spinal tract of the trigeminal
nerve (No. 12), spinal tract of the trigeminal nerve (No. 16) andlateral spinothalamic tract (No. 19). Right cerebellar ataxia isdue to disturbance of the inferior cerebellar peduncle (No. 18)
and spinocerebellar tract (No. 20). Dysphagia is due to disturbance of the nucleus ambiguus (No. 9). The symptom of right
Horner’s syndrome is due to disturbance of the sympathetic
descending tract (No. 21). Vertigo is thought to be due to disturbance of the medial vestibular nucleus (No. 7). Headache isthought to be due to disturbance of the nucleus of the spinal tractof the trigeminal nerve (No. 12) and spinal tract of the trigeminal nerve (No. 16). MO, medulla oblongata; N, nucleus.

13C
Fig. 13. Pathological findings of the fresh infarct in the right lateral MO in Patient 2.
A: Histopathological finding of a fresh infarct. Macrophages orreactive astrocytes are not observed (HE staining). Bar = 50μm.
B: A red neuron showing Spielmeyer’s acute ischemic change(arrow) can be observed (HE staining). Bar = 50 μm.
C: There is no structure positive for GFAP (GFAP immunostaining). Bar = 50 μm.
HE, hematoxylin and eosin; GFAP, glial fibrillary acidic protein;
MO, medulla oblongata.

7

S. Kato et al.

12 in Fig. 14) and spinal tract of the trigeminal nerve(No. 16 in Fig. 14). Portions of the dorsal vagal nucleus(No. 3 in Fig. 14) and inferior olivary nucleus were also
disturbed (Fig. 14). However, no significant pathologicalchange was identified in the hypoglossal nucleus, medial
longitudinal fascicle, medial lemniscus or pyramid ofMO.

A pathological analysis of the major arteries of thebrain showed occlusion of the lumen of the right PICA
by fresh erythrocytes (Fig. 15A). Vascular endothelial
cells had almost disappeared from the vascular intima,
and fibroblasts were observed from the vascular intima
toward the thrombus (Fig. 15B). Namely, these tissue
findings showed the organization of the thrombus started from the side of the vascular intima. Thickening of
the vascular intima was also observed. In ELVG staining, there was an increase in the ELVG-positive elastic
fibers within the vascular intima (Fig. 15C). Foamy
macrophages were also observed within the vascular intima. Partial stretching of the internal elastic lamina wasobserved (Fig. 15A). Decreased smooth muscle cells aswell as increased fibroblasts and collagen fibers were observed in the tunica media. Occlusion were not observedin the right VA.
Results of analysis about the correlation between
the pathologic legions and clinical symptoms

15A

Right crossed sensory disturbance was considered to be
due to the infarct in the nucleus of the spinal tract of thetrigeminal nerve (No. 12 in Fig. 14), spinal tract of thetrigeminal nerve (No. 16 in Fig. 14) and lateral spinothalamic tract (No. 19 in Fig. 14). Right cerebellar ataxia
was considered to be due to the infarct in the inferior
cerebellar penduncle (No. 18 in Fig. 14) and spinocerebellar tract (No. 20 in Fig. 14). Dysphagia was considered to be due to disturbance of the nucleus ambiguus(No. 9 in Fig. 14). The symptoms of right Horner’s syndrome were considered to be due to disturbance of thesympathetic descending tract (No. 21 in Fig. 14). Vertigo
was thought to be due to disturbance of the medial vestibular nucleus (No. 7 in Fig. 14). Headache was thought
to be due to disturbance of the nucleus of the spinal tractof the trigeminal nerve (No. 12 in Fig. 14) and spinal
tract of the trigeminal nerve (No. 16 in Fig. 14).

15B

DISCUSSION
In this study, we analyzed 2 autopsy cases with typical
Wallenberg syndrome. In the 1st case, occlusion of theright VA was confirmed by pathological analyses. In the
2nd case, occlusion of the right PICA was pathologicallyconfirmed. In a search of the literature from 1933 to2013, we could only find 24 autopsy case reports of Wallenberg syndrome in Japan (Table 1). A literature analysis of overseas reports from 1946 to 2013 using PubMed
resulted in only 4 autopsies of Wallenberg syndrome.7–10
Of 2,200 autopsy cases performed at our Neuropathology Division, only 2 cases (0.09%) had a pathologicallydefinite diagnosis of Wallenberg syndrome. As shownin the report by Hata et al.,2 Wallenberg syndrome has

15C
Fig. 15. Histopathological findings of the right PICA in Patient 2.
A: The lumen of the right PICA is occluded by fresh erythrocytes. Partial stretching of the internal elastic lamina isobserved (arrowheads) (ELVG staining). Bar = 300 μm.
B: Vascular endothelial cells almost disappear from the vascular intima, and fibroblasts is observed from the vascular
intima toward the thrombus (arrowheads). Thickening of
the vascular intima is also seen (HE staining). Bar = 30 μm.
C: There is an increase in the ELVG-positive elastic fibers
within the vascular intima (ELVG staining). Bar = 30 μm.
ELVG, elastica van Gieson; HE, hematoxylin and eosin; PICA,
posterior inferior cerebellar artery.

8

Reappraisal of Wallenberg syndromea good prognosis. The authors suggest the following
hypothesis: even when there is dysphagia due to the
disturbed nucleus ambiguus, only the dyspnea based onWallenberg syndrome is not considered to be the directcause of death. The main reason is that there could becompensation from the nucleus ambiguous on the normal side and the non-disturbed hypoglossal nuclei on
the both sides. Further, recent advancements in MRI
and other neuroradiological imaging examinations havemade it possible to identify vessel occlusion and infarctin the lateral MO, while Wallenberg syndrome patientsare still alive. Good prognosis and easy-to-diagnose
neuroradiological imaging in Wallenberg syndrome arethought to have reduced the number of autopsy reports.
The main clinical symptoms in the original case reported by Adolf Wallenberg in 1895 were crossed sensory disturbance, cerebellar ataxia and bulbar palsy. However, a variety of symptoms in Wallenberg syndrome
have been reported as more case reports have been
accumulated. Hata et al. classified clinical symptoms ofWallenberg syndrome into 5 group categories.2 Group
1 is crossed sensory disturbance; Group 2 is cerebellar
ataxia; Group 3 is bulbar palsy; Group 4 is autonomic
symptoms and Group 5 is other symptoms. Group 1
involves disturbance to thermal and pain sensibilities on
the face on the same side of the infarct lesion and disturbance to thermal and pain sensibilities on the trunkand limbs on the opposite side of the infarct. According
to Hata et al., Group 1 is observed in 97% of cases, andthey considered crossed sensory disturbance an essential
symptom. Sensory disturbances of the limbs and trunk
are considered to be caused by impairment of the lateralspinothalamic tract, while sensory disturbances of theface are considered to be due to impairment of both thespinal tract of the trigeminal nerve and the nucleus of
the spinal tract of the trigeminal nerve. The cerebellar
ataxia symptoms of Group 2 include ataxia, vertigo,
nystagmus and giddiness. Ataxia of the limbs is causedby disturbance of the inferior cerebellar peduncle andspinocerebellar tract, while vertigo and nystagmus arecaused by disturbance of the vestibular nucleus. Bulbar
palsy in Group 3 is considered to be due to disturbanceof the nucleus ambiguus. Kurono et al. reported thatthe rostral region within the nucleus ambiguus had thestrong relationship with swallowing.11 Of the autonomic
symptoms of Group 4, Horner’s syndrome is observedin 66% in cases, which is considered to be due to disturbance of the sympathetic descending tract. The
symptoms in Group 5 include a very wide variety ofmanifestations. Headache is reported to make up 60%of these symptoms, double vision 13% and facial palsy
11%.2 Headaches are supposed to arise from transient

vasospasms of the blood vessels that supply the nucleusof the spinal tract of the trigeminal nerve.2 As thesevasospasms are transient, the headaches disappear after
several days. Takahashi et al. reported that headache
was related to disturbance of both nucleus of the spinal
tract of the trigeminal nerve and the spinal tract of thetrigeminal nerve.12 In double vision, it is supported thatthe trochlear nucleus is disturbed as the infarct lesion
spreads rostrally upward to the trochlear nucleus of the
midbrain. Similarly in facial palsy, as the infarct spreads
rostrally upward to the facial nucleus of the pons, it
disturbs the facial nerve nucleus. Taken together, as ainfarct lesion expands, symptoms of the nerve nuclei
and tracts in the disturbed region could appear. Since
only the lateral MO is affected in Wallenberg syndrome,
there is no disturbance of the pyramidal tract or the medial lemniscus. This is the mechanism that hemiplegia
from disturbance of the pyramidal tract or deep sensory
disorder due to disturbance of the medial lemniscus do
not appear. Therefore, this mechanism results in only
the crossed sensory disturbance without hemiplegia anddeep sensory disturbance.
The 2 autopsy cases that we pathologically analyzed
in detail exhibited the 3 main symptoms reported by
Adolf Wallenberg—crossed sensory disturbance, cerebellar ataxia and bulbar palsy. As shown in the resultsof the analysis of the correlation between the clinicalsymptoms and the pathologic lesions, we confirmed thatthe appearance of crossed sensory disturbance was due
to pathological disturbance of the lateral spinothalmic
tract, nucleus of the spinal tract of the trigeminal nerveand spinal tract of the trigeminal nerve. We also verified
that cerebellar ataxia appeared due to pathological disturbance of the inferior cerebellar penduncle and spinocerebellar tract. Similarly, we showed that pathologicallyverifiable damage in the nucleus ambiguus caused theclinical symptom of bulbar palsy. In both autopsy cases,
we were able to verify a 1-to-1 correspondence between
the clinical symptoms and the neuropathological lesions.
Neuropathologically, our analysis of the correlation between the clinical symptoms and the neuropathologicallesions verified the validity of the clinical 5 symptom
categories reported by Hata et al. As shown in Table 1,
our analysis of the literature found 24 autopsy reportsthat provided neuropathological examinations of Wallenberg syndrome. An analysis of these 24 autopsies
with the 3 major symptoms verified a 1-to-1 correlation
between clinical symptoms and the neuropathologicallesions. However, it has been indicated that the clinicalsymptoms that are actually observed are more varied
than the putative symptoms based on the neuropathological disturbances.13 Among a wide variety of symptoms,
9S. Kato et al.
Table 1. Autopsy cases of Wallenberg syndrome in Japan
Clinical symptoms

r)
se
e (y
Ag Sex Cautyali
ter rigin
a
L
O

nce

rba

ry

nso

Se

tu
dis

a
xia
ata alsy nomi
r
e
a
l
p
o
l
t
r
e
o
u
ach ers
reb Bulba Dysa ertig Head
h
e
Ot
C
V

⃝: crssd⃝⃝		 ⃝		 lt facial palsy,
Case 1 67 m Thrombosis, lt PICA,			
anomaly		
hypoplasia in lt PICA							 lt hypoglosssal palsy⃝: crssd⃝⃝⃝⃝⃝
Dysuria
Case 2 84 f Thrombosis
lt PICA⃝: crssd⃝⃝				 Double vision, lt hemiplegia
Case 3 35 f nd
lt nd
⃝
⃝
⃝		 ⃝
⃝
Case 4 42 f Tumorrt Tumor compression
Double vision, lt hemiplegia,			(Neurinoma)									 memory disturbance⃝: ipsi⃝⃝⃝⃝⃝Double vision, dysuria						Case 5 64 m Thrombosis
lt PICA⃝: ipsi⃝⃝⃝		 ⃝
Case 6 62 m Thrombosis
rt PICA
Double vision, lt hemiplegia,
					
VA							eye movement disturbance									⃝⃝
⃝⃝⃝		 rt facial palsy,
Case 7 nd nd Thrombosis
rt nd												 rt hypoglossal palsy⃝: crssd⃝⃝⃝⃝⃝
lt facial palsy
Case 8 63 m Thrombosis
lt PICA⃝⃝⃝⃝⃝
Case 9 60 m Thrombosis
lt PICA, hypoplasia in rt PICA
: crssd			⃝: crssd⃝⃝⃝⃝			Case 10 40 f Anomaly,
rt Defect of PICA
			thrombosis
⃝
⃝
⃝
⃝
⃝
lt hypoglossal palsy
Case 11 54 m Thrombosis
lt nd		
⃝: crssd⃝⃝⃝⃝⃝
Case 12 48 m Thrombosis
rt VA
rt facial palsy,												 rt hypoglossal palsy									⃝					
Case 13 76 m Thrombosis, rt lt VA, hypoplasia in rt VA, 			
			anomaly		 rt PICA branched from lt VA
⃝
⃝		 ⃝
⃝
lt facial palsy,
Case 14 38 m Tumorlt Tumor infiltration					(astrocytoma)									 lt deafness
⃝: bi
⃝
⃝
⃝
⃝
⃝
Dysuria
Case 15 49 f Thrombosis
rt VA, no remarkable findings					in PICA
Case 16 58 m Embolism
nd PICA, VA
Typical type							⃝: ipsi⃝⃝⃝		 ⃝
Case 17 58 f Thrombosis
rt VA
lt hypoglossal palsy
⃝: bi
⃝
⃝
⃝
⃝		 bi deafness
Case 18 58 f Tumorrt Tumor infiltration
			(metastasis)⃝: crssd
⃝
⃝
⃝
⃝
⃝		
Case 19 70 m Embolism
rt Not detected emboli in VA
					and PICA⃝: ipsi⃝⃝⃝		 ⃝		Case 20 84 m nd
rt nd⃝: crssd⃝⃝⃝			 rt facial palsy, respiratory 		
Case 21 64 m nd
rt nd												 distress, hallucination⃝: crssd⃝⃝⃝⃝⃝
Double vision
Case 22 50 m Dissection
lt VA
			
of aneurysm⃝: ipsi⃝⃝				 lt facial palsy, apnea						Case 23 70 m Thrombosis
lt VA
Case 24 83 m Thrombosis, lt VA to BA, hypoplasia in rt VA, Wallenberg 										embolism, 		
rt PICA branched from BA,
syndrome			anomaly		 lt AICA branched from lt VA⃝: crssd⃝⃝⃝⃝			
Patient 1 56 m Thrombosis, rt VA, hypoplasia in rt VA⃝⃝		 ⃝									anomalylt			⃝: crssd
⃝
⃝
⃝
⃝
⃝		
Patient 2 79 m Embolism
rt PICA⃝, present; AICA, anterior inferior cerebellar artery; BA, basilar artery; bi, bilateral; crssd, crossed; f, female; ipsi, ipsilateral; lt, left; m, male; N,
nucleus; nd, no description; PICA, postterior inferior cerebellar artery; rt, right; V, trigeminal nucleus; VA, verteblar artery; VI, tolochler nucleus; VII,facial nuclues; X, dorsal vagal nucleus; XII, hypoglossal nucleus.
Continued on the following page10

Reappraisal of Wallenberg syndrome
Table 1—Continued
Neuropathological lesions
ve

ner

ve
t
ner
rac
cle
m
l
e
us
a
un
gt
g
n
i
d
n
i
r
i
cle
e
t
t
p
f
nd
em
nu
ct
ac
s
r
o
e
g
r
a
a
r
u
i
t
t
c
r
l
r
a
u
l
r
t
l
is
ac
ct
lla
of
big
ebe
ibu
cd
l tr
mi
am
eti
ebe
est
cer
act
ina
r
ala
r
h
v
s
r
t
t
e
p
h
l
u
t
o
s
a
c
l
s
eri
dia
of
cle
ino
mp
ina
ino
her
Inf
N.
Nu
Sp
Sy
Sp
Sp
Me
Ot

Referencend									

16

⃝
⃝
⃝
⃝
⃝			 lt cerebellar hemispherend									nd									

17
18
19

l
ina

⃝

						⃝			 lt cerebellar hemisphere
⃝
⃝
⃝
⃝
⃝
⃝			
V, VI, X, XII, pyramidal tract, medial									lemniscus, dentate N in rt cerebellumnd								lt cerebellar hemisphereVII, X
X, XII, medial lemniscusnd									
⃝

⃝

⃝

⃝

⃝

⃝

⃝

⃝		 ⃝		

⃝

⃝

⃝

⃝
⃝

⃝
⃝
⃝
⃝
⃝		
⃝
XII, lt cerebellar hemispherend								VII, lt cerebellar hemisphere									
⃝
⃝
⃝		 ⃝
⃝		
⃝
X, rt cerebellar hemisphere
⃝

20
21
22
23
24
25
26
27
28

nd									

29nd									

30nd								Cerebellumnd									⃝
⃝⃝⃝		 ⃝		
⃝
XII

31
32
33

nd								bi cerebellar hemisphere

34

⃝

		

⃝

⃝			 ⃝⃝			⃝		 ⃝		 ⃝				nd															⃝				nd								lt cerebellum

⃝

⃝

⃝

⃝

⃝

⃝

⃝		 rt cerebellar hemiephere						⃝		 ⃝
⃝

⃝

⃝

⃝

⃝

⃝

⃝

⃝

Footnotes, refer to the previous page

11

X, rt cerebellar hemisphere

35
36
37
38
39

S. Kato et al.

there were some symptoms that appeared transiently
in the initial stage of the disease and then eventuallydisappeared.13 Tissue edema is presumed to be a causeof symptoms that appear transiently only in the initialstages of the disease.13 This applies to our Patient 1, he
experienced vertigo at both the 1st and the 2nd attacks,
but the vertigo disappeared. No clear histopathologicalabnormalities were observed in the vestibular nucleus.
Tissue edema is presumed to be a pathological mechanism able to explain the discrepancy between the presence of this vertigo symptom and histopathologicallynormal findings. It is thought that edema occurred in
the vestibular nucleus at the initial stage of the disease,which caused a functional disturbance in this nucleus,
leading to the transient appearance of vertigo. As time
passed, edema itself disappeared from the vestibular
nucleus, which caused the vertigo to disappear.
In Adolf Wallenberg’s article in 1901, he recorded
an occlusion of PICA at the location of 4 mm distal fromthe PICA bifurcation, as well as an infarct of the lateral
MO.1 In Patient 2 that we describe above, the area ofright PICA occlusion was 3 mm distal from the PICA
bifurcation, only 1 mm different than in the original
autopsy case reported by Adolf Wallenberg. Therefore,
the autopsy case of Patient 2 is considered equal to theoriginal autopsy case reported by Adolf Wallenberg.
On the other hand, advancements in neuroradiologicaldiagnosis have led to reports that cases of Wallenberg
syndrome with the 3 major symptoms (crossed sensory
disturbance, cerebellar ataxia and bulbar palsy) more
often exhibit VA blockage.3–6 Of the 24 Wallenberg
syndrome autopsies in Table 1, 8 cases were caused by
PICA blockage, 9 cases by VA blockage, 1 case by BA
blockage, 4 cases by blood vessel dysplasia, 1 case by
dissection of an aneurysm, 3 cases by a tumor, 1 casewithout clear vessel blockage and 5 cases where thecausative vessel blockage was not recorded (including
overlap). Moreover, our search of the overseas literatureusing PubMed only yielded 4 autopsies of Wallenberg
syndrome.7–10 One case was caused by dissection of theVA,7 1 case by meningioma9 and 2 cases in which thecausative vessel blockage was not recorded.8, 10 Neuroradiologically, Matsumura et al. used angiography to
examine 10 patients with Wallenberg syndrome, finding
only 1 case of PICA blockage, with the other 9 cases exhibiting VA blockage.3 In an MRA investigation, Watanabe et al. reported that among 12 patients with Wallenberg syndrome, VA blockage was observed in 9 cases.4
The PICA supplies the lateral 1/3 of the MO, as wellas the lower part of the cerebellar hemisphere, including
the cerebellar tonsilla and vermis. Therefore, as recorded by Adolf Wallenberg, blockage of the PICA causes

an infarct in the lateral MO, leading to Wallenberg
syndrome. However, individual differences in the architecture of the PICA are frequent, with the defect of the
PICA itself even being reported.14 There are many variations in the arterial architecture system that supplies the
cerebellum.14 Among these variations, unilateral PICA
defect or hypoplasia is observed in 42%, and unilateralanterior inferior cerebellar artery defect or hypoplasia isobserved in 30%. In contrast, variation of the superior
cerebellar artery is rare. In 12% of cases with unilateral
PICA defect, the normal-side PICA alone supplies the
cerebellar region supplied by both PICA. The type ofblood vessel dysplasia called “a VA-PICA variation”,
which was observed in Patient 1, is reportedly seen in
21% of cases.14 In addition to many variations in the cerebellar arterial architecture system, there are also welldeveloped formations of arterial anastomosis. Based on
this arterial anastomosis, the frequent defects and hypoplasia found in cerebellar arteries are often compensatedby other arterial systems. Thus, a congenital PICA defect or hypoplasia would not necessarily directly causeclinical symptoms.14 However, acquired atherosclerotic
lesions in the PICA with variations are supposed to arise
earlier and be more severe compared to those in normal.15 Moreover, cases of VA-PICA variations exhibita small diameter in the thin VA portion from the PICA
bifurcation to the BA. In such cases, since BA is supplied only by the opposite-side VA, blood-flow dynamics
could easily lead to blockage lesions in the thin VA.14
Next, considering the arterial system that supplies
the MO from an anatomical standpoint, it has beenreported that the lateral MO is more often supplied bybranches from the VA than from the PICA.5, 6 For thisreason, congenital abnormalities in VA formation might
to play an important role in Wallenberg syndrome.
From the detailed analysis of the 2,200 autopsy cases
performed at our Neuropathology Division, however, weare convinced that only the differences in the diameterof the left and right VAs are normal variations with nopathological significance. The results of our literatural
analysis of 24 past autopsy cases found 4 cases of abnormal vessel formation (cases 1, 10, 13, 24 in Table 1).
Including overlap, the PICA abnormality was involved
in all 4 cases (cases 1, 10, 13, 24 in Table 1) and the VA
abnormality in 1 case (case 24 in Table 1). The vessel abnormality directly contributed to the Wallenberg
syndrome was involved in 3 cases (cases 1, 10, 13) of
the 4 cases. Analyzing our 2 autopsy cases, hypoplasiaof the right VA in a VA-PICA variation is considered to
be a factor that caused the 1st infarct in the right MO in
Patient 1. In contrast, the left VA was well developed,
and the lumen of the left VA was maintained despite
12

Reappraisal of Wallenberg syndrome

possible to identify occlusion to the left VA or the left
PICA in Patient 1, pathological infarct do exist in the leftlateral MO, which is the region supplied by these vessels. As shown in Table 1, the clinical symptoms of Wallenberg syndrome also appear in a case with no clear
vessel occlusion (case 19 in Table 1). Moreover, there arecases in which the cause is something besides a bloodvessel lesion, such as tumor infiltration (cases 15 and 18
in Table 1). It is possible to pathologically identify a disturbance other than an infarct in the lateral MO on theoccasion of autopsy analysis. Therefore, in the patientswith the typical 3 major symptoms (crossed sensory disturbance, cerebellar ataxia and bulbar palsy) recorded by
Adolf Wallenberg in 1895, an autopsy analysis might berequired.

the presence of severe atherosclerosis. If the left andright VAs had the same degree of atherosclerosis, the
1st would be a thin lumen of the right VA in a VA-PICA
variation. In fact, the right VA did become occluded
first, causing right Wallenberg syndrome.
The clinical symptoms corresponding to the 2nd infarct in the left lateral MO in Patient 1 were only ataxia
and exacerbated dysphagia. Since left crossed sensory
disturbance was not observed, a clinical diagnosis ofWallenberg syndrome was not able to be made while thepatient was alive. Pathologically, the infarct lesion in theleft lateral MO was disturbing the inferior cerebellar peduncle and nucleus ambiguus. At the time of the 2nd infarct onset of the left lateral MO, there had already been
disturbance to the right inferior cerebellar peduncle,
the right spinocerebellar tract and the right nucleus ambiguus. The 2nd infarct caused bilateral cerebellar ataxia
and severe dysphagia, leading to the 2nd hospitalization.
In the end, the patient died from aspiration pneumonia
caused by severe dysphagia. Regarding the vessel lesions
corresponding to the 2nd infarction in the left lateralMO, occlusion to the left VA or left PICA was not pathologically identified. Although a clinical diagnosis of left
Wallenberg syndrome was not able to be given, a pathological diagnosis of left Wallenberg syndrome should bemade in this case from a pathological standpoint. Patient
2 had an infarct in the lateral MO and showed the typical 3 major symptoms of crossed sensory disturbance,
cerebellar ataxia and bulbar palsy, which was caused by
occlusion of the PICA: this Patient 2 was the same as theoriginal case reported by Adolf Wallenberg. Of the 24
autopsy cases, only 3 cases displayed this kind of original Wallenberg syndrome (Table 1).
Taken together with the original Wallenberg syndrome, we would like to call the cases that fulfill thefollowing 3 criteria “definite pathologic Wallenberg
syndrome”. The 1st criterion is that a pathological obstruction of the PICA or VA can be confirmed. The 2nd
is that an infarct in the lateral MO based on obstructionof the PICA or VA can be pathologically identified. The
3rd is that there is a 1-to-1 correspondence between theclinical symptoms and the neuropatholoical lesions.
Both the 1st infarct in the right lateral MO in Patient 1
and the infarct in the right lateral MO in Patient 2 correspond to “definite pathologic Wallenberg syndrome”.
Although the 2nd infarct in the left lateral MO in Patient
1 was pathologically identified, pathological occlusionof the left VA or left PICA caused this infarct was notobserved. A variety of reasons could have caused the
2nd infarct in the left lateral MO, including transient
occlusion by a thrombus (or an embolus) that dissolved
naturally or a hypodynamic infarction. Although it is not

Acknowledgments: This study was supported in part by a Grantin-Aid for Scientific Research (c) from Ministry of Education, Culture, Sports, Science and Technology of Japan (S.K.: 24500420); a
Grant-in-Aid for Scientific Committee of CNS Degenerative Diseases from Ministry of Health, Labour and Welfare of Japan (S.K.);
a Grant-in-Aid for the physician-training project in Shimane Prefecture (S.K.) and a Grant-in-Aid for discretionary expenditure by
the president in Tottori University (S.K.).
The authors declare no conflict of interest.
references
1 Wallenberg A. Anastomischer Befund in rinen als “acute
Bulbaraffection (Embolie der Art. Cerebellar. Post. Inf.
Sinister.)?” beschriebenen Falle. Arch Psychiat Nervenkr.
1901;34:923-59. German.
2 Hata Y, Kawamura A, Suzuki K. [Two cases of Wallenberg
syndrome—an analysis of 151 cases from Japan]. Shindan To
Chiryo. 1969;57:1259-68. Japanese.
3 Matsumura K, Tamaoka A, Sonoh M, Sakuma M. Clinicaland neuroradiological investigation of Wallenberg’s syndrome.
Rinsho Shinkeigaku. 1986;26:1206-9. Japanese with English
abstract. PMID: 3829523.
4 Watanabe M, Takahashi A, Hashizume Y, Motegi Y, Furuse
M. Magnetic resonance angiography in 12 patients with
Wallenberg’s syndrome. Rinsho Shinkeigaku. 1992;32:118692. Japanese with English abstract. PMID: 1301318.
5 Fisher CM, Karnes WE, Kubik CS. Lateral medullary infarction – The pattern of vascular occlusion. J Neuropathol Exp
Neurol. 1961;20: 323-79. PMID: 13699936.
6 Currier RD, Schneider RC, Priston RE. Angiographic findings in Wallenberg’s lateral medullary syndrome. J Neurosurg. 1962;19:1058-67. PMID: 14024327.
7 De Caro R, Parenti A, Munari PF. Fenestration of the vertebrobasilar junction. Acta Neurochir. 1991;108:85-87. PMID:
2058433.
8 Amantini A, Arnetoli G, Rossi L, Fenzi, Salviati A, Rizzuto
N, et al. BAEP and autopsy findings in Wallenberg syndrome.
Ital J Neurol Sci. 1982;3:237-40. PMID: 7161039.
9 Kleinshmidt-DeMasters BK, Avakian JJ. Wallenberg syndrome caused CSF metastasis from malignant intraventricular meningioma. Clin Neuropathol. 1985;4:214-9. PMID:
4064387.
10 Moffie D, Hamburger HL. Pain and neuroma formation in13

S. Kato et al.
Wallenberg’s lateral medullary syndrome. Clin Neurol Neurosurg. 1986;88:217-21. PMID: 3780111.
11 Kurono H, Uesaka Y, Kunimoto M, Imafuku I. The correlation between dysphagia and involvement of the ambiguous
nucleus on MRI in acute-phase lateral medullary syndrome.
Rinsho Shinkeigaku. 2006;46:461-6. Japanese with English
abstract. PMID: 17061698.
12 Takahashi J, Jimi T, Wakayama Y. [An investigation of headache with Dejerine syndrome]. Nihon Zutsu Gakkai Zasshi.
1999;26:75-6. Japanese.
13 Wakayama Y, Takahashi A, Asano H, Kuriyama K, Ando
T. [Three cases of Wallenberg syndrome with diabetes—ananalysis of 213 cases of Wallenberg syndrome from the Japanese literature]. Saishin Igaku. 1973;28:336-43. Japanese.
14 Kameyama M. [Variations of the cerebellar arteries: a vascular pattern responsible for cerebellar infarction]. Rinsho
Shinkeigaku. 1966;6: 95-100. Japanese.
15 Moossy J. Development of cerebral atherosclerosis in various
age groups. Neurology. 1959;9:569-74. PMID: 14423917.
16 Asano K, Yamada T. [An interesting case with embolism of
the posterior inferior cerebellar artery]. Naigai Chiryo. 1933;
28:930-4. Japanese.
17 Nakamura H, Toyokura Y, Aki M, Kameyama M, Yamamoto
H, Kuroiwa Y, et al. [A case of Wallenberg syndrome (a clinicopathological study)]. Seishin Shinkeigaku Zasshi. 1953;55:
890. Japanese.
18 Murata T, Ushio H. [Infarct in Medulla oblongata, particularly
in Wallenberg’s lateral medullary syndrome]. Rinsho Naika
Shonika. 1957;12:1133-6. Japanese.
19 Tahara Y, Ito K. [A case of Wallenberg syndrome with a brain
tumor]. Seishin Shinkeigaku Zasshi. 1958;60:798. Japanese.
20 Nishino T, Oda K, Nakade R, Hatano S. [An autopsy case ofa Wallenberg syndrome]. Rinsho No Nippon. 1960:6:296-303.
Japanese.
21 Maekawa M, Sawami H, Seriu Y, Fujiwara T, Matsuoka T,
Inanami M, et al. [An autopsy case of Wallenberg syndrome].
Shinkei Shinpo. 1960;5:206-9. Japanese.
22 Ikeda T. [An autopsy case of Wallenberg syndrome]. Nagasaki
Igaku Zasshi. 1962;37:35. Japanese.
23 Nose J, Inoue J. [An autopsy case of Wallenberg syndrome].
Rinsho Naika Shonika. 1963;18:949-52. Japanese.
24 Tanabe H. [Wallenberg syndrome]. In: Okinaka S, editor.
Naika Rinsho To Boken. Tokyo: Nanzando; 1963. p. 50-67.
Japanese.
25 Kokubun K, Irei T, Hara K, Shiono K, Watari H, Koshikawa
T, et al. [Three cases of Wallenberg syndrome]. Fukushima
Igaku Zasshi. 1966;16:161-8. Japanese.
26 Abe M, Yamagami T, Gondo Y, Yano M. [Clinicopathologicalanalysis on nervous system. 3. An autopsy case of Wallenberg

syndrome]. Kyushu Shinkei Seishin Igaku. 1966;12:312-8.
Japanese.
27 Murakami F, Yasutake K, Yamamoto T, Honbo Z, Hirano
N, Tachikawa Y, et al. [An autopsy case of Wallenberg syndrome]. Chiryo. 1965;47:1755-61. Japanese.
28 Itahara K, Tominaga T, Kutsuzawa N, Suwa N, Arai S.
[Clinicopathological conference. 179. A case of Wallenberg’s
syndrome modified by a congenital arterial anomaly]. Saishin
Igaku. 1965;20:2622-8. Japanese. PMID: 5888325.
29 Murata J, Takamizawa K. [A case of astrocytoma with
Wallenberg syndrome-like symptoms]. Nihon Naika Gakkai
Zasshi. 1966;54:1227. Japanese.
30 Oshima M, Mikuni C, Ujiie T, Furuya K. [An autopsy case of
Wallenberg syndrome]. Nihon Naika Gakkai Zasshi. 1967;56:
291-2. Japanese.
31 Kodama R, Ota T, Ato N, Matsuoka K. [Four cases ofWallenberg syndrome]. Nihon Naika Gakkai Zasshi. 1967;56:
1046. Japanese.
32 Tazawa W. [An autopsy case with Wallenberg syndrome withabdominal angina]. Shindan To Chiryo. 1970;45:138-40. Japanese.
33 Ogawa M, Yamanouchi H, Togi H, Tomonaga M, Kameyama
M. Autopsy case of Wallenberg’s syndrome caused by metastasis of lung neoplasm to medulla oblongata. Rinsho
Shinkeigaku. 1977;17:25-30. Japanese with English abstract.
PMID: 191226.
34 Oiwake H, Kametani T, Miyamoto S, Imura M, Takeuchi N,
Shinozaki K, et al. [An autopsy case of Wallenberg syndrome
with a myocardial infarction]. Japanese Circulation Journal.
1982; 46(suppl 2):314. Japanese.
35 Tsuchiya I, Nakao N, Sahashi K, Takahashi A, Ikeda H. [Anautopsy case of Wallenberg syndrome with 13-year disease
duration]. Rinsho Shinkeigaku. 1983;23:628. Japanese.
36 Takehara M, Ishikawa K, Hiroi T, Fujimura H, Yorifuji S.
Central type of sleep apnea syndrome caused by unilateral lateral medullary infarction. Rinsho Shinkeigaku. 1992;32:511-5.
Japanese with English abstract. PMID: 1458729.
37 Abe H, Kamei H, Nobuhara K, Takebayashi S, Nishimaru
K. An autopsy case of idiopathic vertebral artery dissecting
aneurysm with analysis of MRI changes. No Socchu. 1993;15:
144-50. Japanese with English abstract.
38 Osano H, Terao S, Fukuoka T, Miura N, Yoshida M, Sobue
H. [An autopsy case of lateral medulla oblongata infarct with
rapid respiratory failure]. Rinsho Shinkeigaku. 2001;41:257.
Japanese.
39 Okamoto Y, Yamashita M, Yamamoto T. [An autopsy caseof Wallenberg syndrome with cerebellar infarction: an MRI
analysis]. Rinsho Shinkeigaku. 2007;47:545. Japanese.

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