J Occup Health 2002; 44: 1–7

Journal of

Occupational Health

Neurological Disorders in Three Workers Exposed to

1-Bromopropane

Gaku ICHIHARA1, Joseph Keith MILLER2, Aldona ZIOLKOWSKA3,

Seiichiro ITOHARA1

, Yasuhiro TAKEUCHI1

1

Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine,

2

Department of Neurology, Johnson Neurological Clinic, High Point, North Carolina and

3

High Point Regional Hospital, High Point, North Carolina, USA

Abstract: Neurological Disorders in Three Workers

Exposed to 1-Bromopropane: Gaku ICHIHARA, et al.

Department of Occupational and Environmental

Health, Nagoya University Graduate School of

Medicine—A 35-yr-old female worker developed sore

throat, stumbling, dysphagia, incontinence of urination

and numbness with a burning sensation in the legs,

thighs, hips and lower back as well as numbness in

the perineum. She was spraying a glue to compose a

cushion with polyurethane foam parts. One year after

beginning to use a glue containing mainly 1-

bromopropane, she became unable to stand up by

herself. The second case, a 30-yr-old female worker

developed a staggering gait, paresthesia, urinary

incontinence, slurred voice, dysphagia, numbness or

paresthesia in the hands, legs, lower back, hips and

perineum, six months after beginning the same task.

The third case, a 50-yr-old female worker showed signs

of staggering, and numbness and paresthesias in the

feet, thighs, lower back and hips, and headache, two

months after starting the work. The daily time-weighted

average of exposure concentrations ranged from 60

to 261 ppm (mean 133, N=11) after the ventilation was

improved. The common signs in the three workers were

staggering, numbness with paresthesia/dysesthesia,

as well as a remarkable decrease in vibration sense in

the legs and various symptoms in the central nervous

system. Abnormal sensation was distributed to the area

covered by pantyhose, rather than glove-stocking. Not

only peripheral nerves, but also the spinal cord or

brainstem was suspected to be impaired, given the

paresthesia/dysesthesia and the distribution of sense

deficits. Their diarrhea, incontinence of urination and

abnormal sweating also suggested disorders in the

Received Oct 17, 2001; Accepted Dec 12, 2001

Correspondence to G. Ichihara, Department of Occupational and

Environmental Health, Nagoya University Graduate School of

Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan

autonomous nervous system. 1-Bromopropane might

induce neurological disorders in the peripheral nerves

and/or the central nervous system in humans.

(J Occup Health 2002; 44: 1–7)

Key words: Intoxication cases, Neurological disorders,

1-Bromopropane, Alternative solvent to ozone-layer

depleting, Intoxication

1-Bromopropane is a new alternative to ozonedepleting solvents. It is less destructive to the ozone

layer, but nonflammable and moderately volatile, which

are important properties for metal cleaning agents. Other

alternatives have been phased out because of their ozonedepleting potency or toxicity, so the demand for 1-

bromopropane as a solvent is now increasing in industry,

but it was recently revealed to have neurotoxicity and

reproductive toxicity in animal experiments1–4). Although

one case report suggests the neurotoxicity of 1-

bromopropane in a worker5), its neurotoxicity in humans

is generally not well understood. We report neurological

disorders in three workers exposed to 1-bromopropane

in a cushion company, because we consider these cases

very important in understanding the neurotoxicity of 1-

bromopropane in humans.

Case Reports

Three workers, who used 1-bromopropane as a solvent

with a spray gun, showed abnormal neurological

symptoms or signs. In a cushion company in North

Carolina in the U.S., 1-bromopane was introduced in the

workplace to replace dichloromethane as a solvent in glue

in July 1999. The workers sprayed glue on polyurethane

foam parts, then pressed them together by hand to form a

bond as a part of the cushion production process. Fifteen

workers were engaged in spraying glue in the same

workroom at the time that case 1 became ill in June of

Rapid Communication
2 J Occup Health, Vol. 44, 2002

2000. The workbenches for the fifteen workers were

arranged along one long side and one short side of a

rectangular room. Each worker, including both case 1

and case 2, did their jobs, while facing a wall equipped

with a ventilator, but the ventilators were operated only

15 min per hour in the summer of June, 2000. The

ventilator in front of case 3 was not operating at all up

through June. Some workbenches had no ventilators from

the very start for other workers. The workers used spray

guns, and the glue sometimes spattered on their faces.

They wore only thin latex gloves for work, but no proper

gloves or masks able to protect them from the solvents.

The Material Safety Data Sheet (MSDS) indicated that

the glue contained 1-bromopropane 55%, ethyl acetate

8% and aliphatic petroleum distillates 2%.

Case 1: The patient, a 35-yr-old female was carried to

the local emergency Room on June 30, 2000, because

she could not walk by herself in the morning. She had

dystaxia and dysesthesia with a burning sensation or

tingling with numbness in both feet, legs, thighs and lower

back. On admission she could not walk without

assistance. It was difficult for her to use stairs.

Dysesthesia was noted by touching. Her vaginal area

felt numb both inside and outside, as if she had been

given local anesthesia. She walked with a wide spread

gait. She had been engaged in spraying glue in a cushion

factory since 1998. From April to June, just prior to

developing the above mentioned neurological symptoms,

she went to the emergency room four times for a sore

throat, earache, sinus irritation and hoarseness. Urinary

incontinence was also noted during this period. She

usually worked eight hours a day from Monday to Friday,

but in June 2000, she worked nine hours per day. At the

beginning of that month, she experienced difficulty in

swallowing as if something was stuck in her throat. On

June 23, she began to stumble, feel dizzy and lose her

balance. She stayed home from work for two days, but

the symptoms worsened. On June 26, she consulted her

primary care doctor, because of the dizziness, sore throat,

eyeache and numbness in the perineum. She was

prescribed antibiotics and anti-allergic agents (Nasonex,

mometasone furoate monohydrate) for ten d. On June

27–29, she worked for eight or nine h per d. The

stumbling worsened, and her sore throat, earache and

malaise in the sinuses failed to improve. She felt

numbness and muscle pain in her feet, legs, thighs and

lumbar area. Numbness in the thighs was more

remarkable at the front than at the back, but in the legs,

conversely, more remarkable at the back than at the front.

She also sometimes had headaches. She found it more

difficult to walk with each passing day. She lost 11

pounds (about 5 kg) during the four days from 26 to 30

June, 2000.

Neurologic examination on admission revealed that the

patient was alert and oriented with clear speech and

sensorium. No intranuclear ophthalmoplegia was

identified. The pupils were round and reactive to light.

The left pupil seemed slightly larger than the right one,

and there was some hippus noted bilaterally. Both

tympanic membranes appeared clear. Tongue movements

were intact. No carotid bruit was noted and the heartbeat

was regular. Tone did not increase and deep tendon

reflexes were equal, symmetric and active throughout.

There was no clear weakness in her upper and lower

extremities. Plantar responses were flexor bilaterally. Her

prick sensory level was about T6, and her vibration sense

was distally diminished. The patient did not show any

sings of spastic gait, but she was unsteady and had to

hang onto the wall. Romberg sign was negative. There

was no abnormality in the nose-finger-nose, heel-shin,

line-drawing or pronation-supination test. Her spouse

said that the patient was originally cheerful and active,

but her mood had been changed to be depressive. The

patient felt tired even after working for a short time. She

was depressive but sometimes irritated and tended to get

angry.

Past and family history: Hypertension, migraine

headaches. The patient was allergic to penicillin and

codeine. She had had a tonsillectomy, bunionectomy,

cholecystectomy and tubal ligation. Her family history

included diabetes mellitus (grandfather and sister), heart

attack (father) and ovarian cancer (sister). Drinking

history: one or two glasses of beer per two wk. Smoking

history: 20 cigarettes per d for 18 years. She felt recently

that she had become unable to drink much. Her

cholesterol was 224 with HDL of 29 (mg/dl). Her

respiratory rate was sedate and 12. ANA was negative.

The MRIs of the brain and cervical and thoracic portions

of the spinal cord did not show any particular findings.

No Lhermitte’s phenomenon was observed.

On July 3 (3 days after admission), her walking had

improved a little, but she still stumbled and her throat

remained sore. On July 4, serum vitamin B12 was 442

mg/dl and Lyme disease antibody, IgG and IgM were

negative. No urinary lead or mercury was detected and

urinary arsenic was within normal limits (48.3 μg/l, 150.9

μg/g creatinine). On July 6, lumbar puncture produced

clear, colorless fluid. Cell counts of cerebrospinal fluid

(CSF) were all within normal limits (RBC 2, WBC 2,

Lymphocyte 70, Monocyte-macrophage 30 but no other

cells were found). The serum protein pattern was normal

(total protein 7.2, albumin 4.19, alpha-1 0.46, alpha-2

0.75, beta 0.74, gamma 1.06 g/dl). On July 19, a

gynecologist found mild cystocele and rectocele, which

suggested mild pelvic relaxation. In July, her

menstruation began 2 wk earlier than usual. On August

23, an electrophysiological study showed values within

normal limits in motor nerve conduction velocity on both

sides of the peroneal nerve and left posterior tibial nerve,

and sensory nerve conduction velocity on both sides of
Gaku ICHIHARA, et al.: Workers Exposed to 1-Bromopropane 3

the sural nerve. On November 21, MRI of lumbar

portions of the spinal cord showed only degenerative

change with facet hypertrophy and mild central bulging

of the intervertebral disc at L5-S1.

Case 2: The patient, a 30-yr-old female, worked in

the same cushion company from February to June 30,

2000. On June 30, she developed a staggering gait as if

she were in a drunken stupor. The patient was seen at

the same local emergency room and was noted to have

paresthesias. She had difficulty in noticing the need to

defecate or void and could tell only by a sense of

discomfort in her abdomen. She had numbness in the

perineum and lacked sensation during sexual intercourse.

At first, there was some numbness in her hand, but it

resolved later. She had some lower back pain, but no

trouble with fever or chills. She had some difficulty in

speaking, and her words were somewhat slurred. Her

lower extremities usually felt tired. She lost 5 pounds

(about 2 kg) in the last week of June.

Past illness: kidney infection (1998), cholelithotomy

(1993), Family history: heart attack (grandmother), brain

attack (grandfather), diabetes mellitus (mother) Smoking:

forty cigarettes per week. Drinking: 2 times per yr. The

former work: packing mail staples for four yr. She had a

Cesarean section in the past. She was not allergic to any

medications, nor was she taking any medications on a

daily basis.

Neurological examination revealed her to be alert and

oriented with clear speech and sensorium. The pupils

were round and reactive to light. Extraocular muscle

movements and tongue movements were intact. The

patient had the full range of motion of the cervical spine.

She had no Lhermitte’s phenomenon. There was no

definite focal motor weakness in her upper or lower

extremities. Plantar responses were flexor bilaterally.

Deep tendon reflexes were equal, symmetric and active

throughout. There was peripheral diminution to vibratory

and pin prick sensation on the right lower extremity to

the knee. The sensation was less impaired up toward the

waist. It was less severe on the left side than the right

side both in the legs and in the thighs. There was no

spasticity, no fasciculations nor clear muscle atrophy.

Finger-nose and heel-shin testing was normal. Gait and

station were normal. Tandem gait was done without any

difficulty. Romberg sign was negative. Rectal exam

showed fair rectal tone. On July 19, 2000, the patient

noted at times that her feet sensation easily changed from

hot to cold. On August 9, 2000, the symptoms had

improved, but she was still having paresthesias in both

her lower extremities. No focal motor weakness was

identified. MRIs of cervical, thoracic and lumbar spine

did not show any particular findings. On August 24, 2000,

she still had urinary incontinence. She had difficulty in

swallowing solid food. She had a very poor appetite and

abdominal pain. She felt hot and sometimes cold in her

feet. She felt hot but not really hot and just flushed. On

6 September 2000, the patient had some pain in her lower

back, as well as in her stomach. She felt hot at night and

her stomach sometimes felt hot in the morning. She felt

her stomach bloated and also felt as if she were pregnant.

She also had some repeated diarrhea and nausea/vomiting.

Although there was nothing to void, she found herself

repeatedly trying to do so. She suffered somewhat from

insomnia. The patient also had bifrontal headache and at

times her head felt like popping. Higher cortical

functioning was normal. Funduscopic examination

showed no particular findings. There was no abnormality

in the line-drawing or pronation-supination test.

Menstruation began one wk later than usual in June 2000.

The patient tired easily and was misunderstood as lazy

by her spouse. The patient was depressive, but sometimes

irritated and tended to get angry. In June this patient

fought with the former patient in case 1, though she had

never done so before.

Case 3: The patient, a 50-yr-old female, started the

work in March, 2000. She became aware of weight loss,

staggering, numbness in the feet and pain in her wrists,

elbows and shoulders from May to June, 2000. She also

felt pain in the front of her thighs at night. During the

week, she felt better on Monday, but on Tuesday she felt

pain in her feet and shoulders, headache, and sore throat.

On Wednesday and Thursday, rhinorrhea, and stumbling

occurred, and her headaches became more severe. These

symptoms were reduced over the weekend holidays. This

change in symptoms was repeated every week. She could

call up words, but sometimes felt difficulty in speaking.

Neurological examination revealed her to be alert and

oriented with clear speech and sensorium. The pupils

were round and reactive to light. Extraocular muscle

movements and tongue movements were intact. She had

no definite focal motor weakness in her upper or lower

extremities. Plantar responses were flexor bilaterally.

Deep tendon reflexes were equal, symmetric and active

throughout. There was peripheral diminution of response

to vibratory and pin prick sensation in both lower

extremities to about the level of the thighs, hips and lower

back, but tactile sense was lowered only in the toes and

was comparatively well preserved in the upper levels.

She could not maintain a standing position when her knees

were bent even slightly by others. Romberg sign was

negative. There was no abnormality in the nose-fingernose, heel-shin, line-drawing or pronation-supination test.

She said that she could stare but could not concentrate.

The exposure level of the worker to 1-bromopropane

was estimated with a passive sampler (passive gas tube

for organic solvents, Sibata Scientific Technology Ltd.,

Tokyo, Japan). A passive sampler was attached to the

worker for eight h during work on October 23–26, 30

and 31, 2000. Immediately after each day’s work, the

sampler was sealed in an aluminum bag and kept at 4°C
4 J Occup Health, Vol. 44, 2002

until analysis. On analysis, coal particles were taken from

the samplers and then immersed in 2 ml carbon disulfide

(Wako Pure Chemicals, Osaka, Japan) in a glass tube

with a screw cap. The tube was shaken for 5 min and left

for 2 h and the supernatant liquid was injected into GCMS (GCD system G1800A, Hewlett Packard). 1-

Bromopropane was quantified by the single-ion mode at

43.1 (m/z) with a qualifier at 41.15 (m/z). The value of

0.134 was used in calculation as the sampling rate for 1-

bromopropane. The daily time-weighted average ranged

from 60 ppm (min.) to 261 ppm (max.). The average of

the daily values and the standard deviation (S.D.) for

eleven d (N=11) was 133 ± 67 (mean ± S.D.) ppm.

Questionnaire to three workers

Three workers were interviewed based on the check

up form for organic solvent intoxication at Nagoya

University School of Medicine (Tables 1 and 2). The

common symptoms or signs of the three workers were

staggering, weakness in legs, and numbness and

paresthesia with a similar distribution in their feet, legs,

thighs, lower back and hips, along with various symptoms

in the central nervous system such as headache, dizziness,

nausea, insomnia, anxiety, irritation, light headedness,

muddle-headedness, forgetfulness, difficulty in

concentrating and listlessness. They also complained of

weakness in the legs, tremor in the legs, dizziness when

standing up, thirst, indigestion, diarrhea, weight loss,

rough skin, a strange feeling in throat and frequent cough.

Discussions

The three workers showed the common symptoms of

staggering, numbness and paresthesia/dysesthesia with a

similar distribution in their feet, legs, thighs, lower back

and hips as well as a remarkable decrease in vibration

sense, along with various symptoms of the central nervous

system and autonomic symptoms. There were no

laboratory data supporting Lyme disease, multiple

sclerosis, Guillan-Barre syndrome, lack of Vitamin B12

or metal intoxications in Case 1, but no such data were

available in the other cases. Although other causes were

not completely ruled out, common work-related causes

were suspected in the three cases. This is because

common symptoms and signs were found in these three

among the fifteen workers engaged in the same work

almost at the same time and during the busiest months.

The weekly changes in neurological symptoms in case 3

also strongly suggested solvent involvement.

Our previous animal experiments showed 1-

bromopropane exposure induced myelin degeneration in

the peripheral nerves, swelling of preterminal axons in the

gracile nucleus in the medulla oblongata at 800 ppm or

over1, 3, 4) and pyknotic shrinkage of Purukinje cells in the

cerebellum at 1000 ppm3), as well as electrophysiological

changes in the peripheral nerves and weight loss of the

brain at 800 ppm1). Recent animal studies also revealed

a decrease in neuro-specific γ-enolase in the brain6, 7).

These animal studies, which provide definite evidences

of the neurotoxicity of 1-bromopropane, suggest the

involvement of 1-bromopropane in the cases under study.

The present cases provided some implications as to

vulnerable regions in the nervous system, which had not

been found in previous animal studies. The neurological

signs and symptoms suggesting abnormal regions are

summarized from our three cases and the previous case5)

in Table 3. The present three cases showed abnormal

sensation not only in distal portions of the lower

extremities, but also in the thighs, back, hips and genital

area. The present cases were not the typical glovestocking type neuropathy observed in hexane

intoxication8, 9), but as it were, pantyhose type. The

paresthesia and dysesthesia like a burning sensation could

Table 1. Worker symptoms while using organic solvent

Case 1 Case 2 Case 3

Working period 12 months (99.7–00.6) 5 months (00.2–00.6) 9 months (00.3–00.12)

Eye pain + – –

Nose stimulation + + –

Sore throat + + –

Strange taste + + –

Hot face + + –

*Vertigo or dizziness + + +

* Light-headedness + + +

*Feel intoxicated + + +

Heavy-headedness + – –

* Headache + + +

*Items common to all three workers. No worker complained of “dim eyesight” or “strange smell” in

answer to the questions regarding symptoms while using organic solvent.
Gaku ICHIHARA, et al.: Workers Exposed to 1-Bromopropane 5

Table 2. Recent symptoms and signs after 1-bromopropane exposure in three workers

Case 1 Case 2 Case 3

Working period 12 months (99.7–00.6) 5 months (00.2–00.6) 9 months (00.3–00.12)

Heavy-headedness + + –

* Headache + + +

*Vertigo or dizziness + + +

*Nausea + + +

Vomitting – + –

* Insomnia + + +

Frequent nightmares – + +

*Anxious about various things + + +

* Irritated by various things + + +

* Light-headed + + +

*Feel muddle-headed + + +

*Forgetful + + +

*Difficulty in concentrating + + +

* Tremor in hands or legs + (leg) + (leg) + (leg)

Cramp in hands or legs + (leg) – + (leg)

*Feel dizzy when standing up + + +

Palpitation – – +

Feel as though chest is compressed + – –

Feel as though choking or suffocating + + –

* Listlessness + + +

* Hands or legs feel heavy + + +

No appetite + + –

Abdominal pain (Stomachache) – + –

*Thirsty + + +

* Indigestion (digestive trouble) + + +

*Likely to have diarrhea + + +

*Lost weight + + +

Changed the way you sweat + – –

Irregular periods + + –

Lost sexual desire + + –

Dim eyesight – – +

Eye strain + – +

Difficulty in hearing – – +

Difficulty in speaking – – +

Taste strange – + –

*Pain in joints or elsewhere + + +

*Numbness in hands and legs + + +

Chilly hands and legs + + –

*Smarting or abnormal feeling in hands and legs + (leg) + (leg) + (leg)

Weakened grip + + –

* Weakness in the hands or legs + + +

*Tend to stumble + + +

*Rough skin + + +

*Throat feels strange + + +

*Frequent cough + + +

Unable to drink much + + –

*Items common to all three workers. No worker complained of “Sometimes lose consciousness”, “Have convulsive fits”,

“Likely to have constipation”, “Have a slight fever”, “Ringing or buzzing in my ears”, “Difficulty in smelling”, “Difficulty in

tasting” or “Gums bleed easily”.
6 J Occup Health, Vol. 44, 2002

indicate peripheral nerve, spinal cord or probably

brainstem origin10). They also showed symptoms of the

central nervous system such as memory loss, headache

or mood changes. Sclar reported a patient5) exposed to

1-bromopropane and with distal dominant neuropathy in

the limbs, but there was no description of the presence of

abnormal sensation in other areas or symptoms of the

central nervous system. Nevertheless, the Sclar’s case

showed abnormality of neural formina near the root

ganglion and periventricular white matter of the brain in

MRI. Somatosensory-evoked potential studies did not

produce any cortical potentials, suggesting a lesion in

the dorsal column or lemniscal level. These findings in

Sclar’s case suggest possible deficits in more central

regions of the nervous system than the distal peripheral

nerve. Moreover, the abnormality near the root ganglion

and the somatosensory-evoked potential studies might

explain the distribution of abnormal sensation in the

present cases. The three cases also suggested abnormality

of the autonomic nervous system as indicated by diarrhea

and the change in sweating. It was not clear if the urinary

incontinence in cases 1 and 2 were the same as “urinary

difficulty” in Sclar’s case, but this also suggested deficits

in the autonomic nervous system. However, there could

be other impaired regions; deficits in the somatic sensory

nerves in the bladder, for example, were suggested by

the unawareness of urination in case 2.

Deep sensation was diminished but the Romberg sign

was negative. Since a positive Romberg sign requires a

severe loss of deep sensation, the negative Romberg sign

does not necessarily rule out ataxia due to lesions in the

spinal cord or peripheral nerves. The decrease in deep

sensation suggested ataxia due to spinal cord or peripheral

nerve rather than cerebellular ataxia, but the possibility

of cerebellular involvement was not disproved

completely. In rats, pyknotic atrophy of Purukinje cells

in the cerebellum was found at 1000 ppm for 4–5 wk,

although this change was not remarkable below 800 ppm.

Extrapolation of this result in the animal experiment to

humans is difficult at this point. Dysphagia in cases 1

and 2, which was also reported in Sclar’s case, suggested

a disorder in the glossopharyngeal or vagus nerve, or

medulla oblongata. This disorder might also be suggested

by articulatory disturbance in case 2 and possibly 3,

though differential diagnosis was not completed.

Case 1 did not demonstrate any abnormality in distal

latency or nerve conduction velocity, nor did it show

significant MRI findings explaining her symptoms, as

different from the previous case5). This might be due to

the difference in the degree of impairment or the

Table 3. Neurological signs or symptoms suggesting abnormal regions of the nervous system

Case 1 Case 2 Case 3 (Sclar’s case)

Working period 12 months 5 months 9 months 2 months

(99.7–00.6) (00.2–00.6) (00.3–00.12) (98.1–98.2)

Weakness in limbs + (subjective) + (subjective) + (subjective) +

Tremor in legs + + + ?

*Numbness in low back + + + ?

*Numbness in frontal thighs + + + ?

* Decrease in temperature sensation in foot + + + ?

*Decrease in vibration sense in feet + + + +

* Decrease in superficial sense in feet + + + +

Numbness in perineum + + – ?

* Paresthesia or dysesthesia + + + ?

Dysphagia + + – +

Difficulty in speaking + + + ?

Urinary difficutly + + – +

* Diarrhea + + + ?

* Dizziness when standing up + + + ?

*Thirsty + + + ?

*Memory loss + + + ?

* Headache + + + ?

Dizziness + + + ?

Insomnia + + + ?

Brain and cervical MRI – – Not examined +

Electrophysiology in legs – Not examined Not examined +

*Items common to cases 1–3.
Gaku ICHIHARA, et al.: Workers Exposed to 1-Bromopropane 7

observation time, or whether gadolinium enhancement

was applied.

Menstrual cycles were disrupted temporarily in cases

1 and 2. This might accord with the previous animal

experiment11).

The daily individual exposure levels were estimated

to range from 60 to 261 ppm in case 3. As this evaluation

was done after the ventilation was improved, the workers

might have been exposed to higher 1-bromopropane than

the above levels in June.

In conclusion, 1-bromopropane might induce deficits

in the peripheral nerves and/or the central nervous system

in humans. The symptoms of diarrhea, abnormal sweating

and urinary incontinence also suggested disorders in the

autonomic nervous system.

Acknowledgements: Our sincere thanks to Dr. Thomas

G. Braun, Department of Neurology, University of North

Carolina, North Carolina, USA, Dr. Charles C. Goodno, Dr.

Dennis Darcey, Division of Occupational and Environmental

Medicine, Department of Community & Family Medicine,

Duke University Medical Center, Dr. William M. Valentine,

Dr. Holly L. Valentine, Department of Pathology, Vanderbilt

University Medical Center, Dr. Sahoko Ichihara, Department

of Internal Medicine, Nagoya University Graduate School

of Medicine, Dr. Gen Sobue, Dr. Naoki Hattori, Dr. Yideng

Liang, Department of Neurology, Nagoya University

Graduate School of Medicine, Dr. Yasuo Koike, Department

of Medical Technology, Nagoya University School of Health

Sciences and Dr. Junzoh Kitoh, Professor Emeritus of

Nagoya University.

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