Clinical Neurology and Neurosurgery 101 (1999) 199–202

Case report

Encephalomyeloradiculoneuropathy following exposure to an

industrial solvent

Gary Sclar 1

Department of Neurosciences, Uni6ersity of Medicine and Dentistry of New Jersey, MSB H-506, 185 South Orange A6enue, Newark, NJ,

07103, USA

Received 10 November 1998; received in revised form 22 December 1998; accepted 3 May 1999

Abstract

A 19-year-old male developed complaints including weakness of the lower extremities and right hand, numbness, dysphagia and

urinary difficulties following a 2 month exposure to an industrial solvent constituted mainly of 1-bromopropane, but also

containing butylene oxide, 1,3 dioxolane, nitromethane, and other components. Nerve conduction studies revealed evidence of a

primary, symmetric demyelinating polyneuropathy. Evidence of CNS involvement came from gadolinium enhanced MRI scans of

the brain, showing patchy areas of increased T2 signal in the periventricular white matter, similar scans of the spinal cord revealing

root enhancement at several lumbar levels, and SSEP studies. The patient’s symptoms had started to resolve following the

discontinuation of the exposure, before he was lost to follow-up. Similar findings have been reported following 1-bromopropane

exposure in rats. I hypothesize that this patient’s symptoms may have been due to 1-bromopropane-induced neurotoxicity. © 1999

Elsevier Science B.V. All rights reserved.

Keywords: Polyneuropathy; Demyelination; Neurotoxicity; 1-bromopropane

www.elsevier.com/locate/clineuro

1. Introduction

Peripheral neuropathies are a well-known outcome of

exposure to drugs, [1–5,10,13,14] chemicals, [6,11,15–

18] and heavy metals. Most of these acquired neuropathies are distinctly axonal in character [7–9].

Exposures resulting in primary demyelination are less

common. This case report describes a patient with a

demyelinating disorder which developed following exposure to an industrial solvent. Although it’s primary

manifestation was as a peripheral neuropathy, it also

entailed radiological and clinical signs of central white

matter involvement in the brain and spinal cord, and of

some dorsal root ganglia, and so would more properly

be termed an encephalo-myelo-radiculoneuropathy.

2. Case report

The patient, a 19-year-old Hispanic male without

significant past medical history, was transferred to our

hospital in February, 1998, after 1 week at another

institution. In mid-January he had developed numbness

and mild but progressive weakness of the proximal

lower extremities and right hand. On admission here he

could not stand without assistance. Other symptoms

included a transient dysphagia and urinary difficulties.

Just prior to developing these symptoms, he had been

employed for 2 months as a metal ‘stripper’. This

occupation involved the use of an industrial solvent

used as a degreasing and cleaning agent2

. According to

the manufacturer’s Material Safety Data Sheet, the

agent is a mixture of chemicals including 1-bromopropane (1-BP) (CASc106-94-5;\95.5% by weight),

butylene oxide (CASc106-88-7;B0.5%), 1,3 dioxolane

E-mail address: sclarga@umdnj.edu (G. Sclar) 1 MD, Ph.D.

2 The trade name and the company’s name are withheld at their

request.

0303-8467/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved.

PII: S0303-8467(99)00034-7

This material may be protected under Copyright Law [Title 17 U.S. Code]
200 G. Sclar / Clinical Neurology and Neurosurgery 101 (1999) 199–202

(CASc646-06-0;B2.5%) and nitromethane (CASc

75-52-5;B0.25%). Also included are two proprietary

components (CAScs not noted), one of which was

denoted as a saturated terpene blend. About the time

his symptoms began, he had noted darkening of the

skin of his right hand, which was preferentially exposed

to this solvent. Protective gloves had been used as a

precaution, but may not have been sufficient to keep

out the solvent, and may have enhanced dermal uptake

by occlusion effect.

Prior to admission, a brain MRI revealed a non-enhancing lesion, without mass effect, in the right corona

radiata. Lumbar puncture revealed normal protein, glucose, cell count and the absence of oligoclonal banding.

He was treated with three grams of i.v. solumedrol, for

presumptive multiple sclerosis. This was without effect,

but he was still taking 75 mg of oral prednisone daily

on transfer to our hospital.

Neurologic exam on admission revealed the patient

to be alert and oriented. Speech was fluent, and language function was normal. Extraocular eye movements were full with no nystagmus. The pupils were 4

mm, equal, round and reactive to light and accommodation. The remaining cranial nerves were grossly intact. Mild (4+ /5) weakness of the right biceps and

triceps was present, but all other upper extremity muscle groups were rated 5/5, and tone was normal. Upper

extremity reflexes were all at 2+.

There was dramatic and symmetric weakness of all

lower extremity muscle groups. Distally the dorsi- and

plantar flexors were rated 0/5, quadriceps 3/5, hamstrings 2+ /5, and iliopsoas 2+ /5. Tone was mildly

increased. The knee reflexes were 3+, while the ankle

jerks were diminished (trace to absent) and the plantar

reflexes neutral. Sensation was profoundly affected in a

stocking distribution. Pinprick and position sense were

both markedly decreased–absent at the toes and ankles. Vibration sense was deficient (the right hand and

both lower extremities, with the right leg being more

affected then the left).

A gadolinium enhanced MRI of the brain revealed

several patchy areas of increased T2 signal in the periventricular white matter, mostly outside the corpus

callosum and asymmetrically distributed (more prominent on the right). There was no evidence of mass effect

or abnormal enhancement, while MRI imaging of the

spinal cord revealed enhancement at multiple thoracic

and lumbar levels in the region of the neural formina,

in the proximity of the nerve root ganglia.

All four extremities were studied using standard

nerve conduction techniques and a Dantec Counterpoint system. These studies included two motor nerve

conductions with F wave response latencies and two

sensory nerve conductions per extremity.

Lower extremity distal motor latencies were

markedly prolonged (range: 8.0–9.6 ms), but only for

the peroneal segment below the knees were the motor

conduction velocities mildly slowed (left: 39.3, right:

38.3 ms). The right F-EDB and both F-AHs were

prolonged (57.6–62 ms). The left F-EDB could not be

obtained. There was marked slowing of all the lower

extremity sensory conduction velocities (sural-left: 36.2,

right: 31.8 ms; superficial peroneal-left: 31.2, right: 29.4

ms) but the corresponding sensory evoked response

amplitudes were all normal except for the left sural

(mildly attenuated at 3.1 mV). The lower extremity

motor-evoked response amplitudes were within normal

limits.

The distal motor latencies, motor and sensory conduction velocities, motor evoked response amplitudes

and F-response latencies were within normal limits for

both arms. Sensory evoked response amplitudes for the

right arm were within normal limits, but were attenuated compared with the left (right-median: 10, ulnar:

10.6, left-median: 23.3, ulnar: 23.0 mV). There was no

evidence of conduction block or temporal dispersion

for either the upper or lower extremities.

EMG of selected lower extremity muscles revealed

increased insertional activity only in the left extensor

digitorum longus, and no sustained spontaneous activity in any of the muscles studied. Non-quantitative

studies showed a tendency toward prolonged duration

(i.e. 17–20 ms) for numerous MUPs (i.e. motor unit

potentials). In several muscles satellite potentials amplitudes and morphologies varied from discharge to discharge (Fig. 1). No MUPs could be recruited in the

right tibialis anterior or left EDB muscles. In most

muscles, recruitment was full, but with a noticeable lag

between the onset of patient effort and muscle

recruitment.

Somatosensory-evoked potential studies revealed

normal amplitudes and latencies for the arms (median

Fig. 1. Five sequential traces of a MUP (on the left) from the left

extensor digitorum longus showing a satellite potential of variable

morphology following the main MUP peak. The averaged trace is

shown on the lower right.
G. Sclar / Clinical Neurology and Neurosurgery 101 (1999) 199–202 201

nerve stimulation), but no cortical potentials could be

obtained following bilateral peroneal stimulation, suggesting a lesion at the dorsal column or lemniscal level.

The lumbar latency values (left: 12.2, right: 10.6 ms)

suggested an additional abnormality on the left, at or

distal to the lumbar cord. Brainstem auditory and

visual evoked potentials were within normal limits.

Lumbar puncture produced clear colorless fluid with

an opening pressure of 230 mm Hg (31.5 cm H2O).

Protein (0.28 g/l), glucose (3.6 mmol/l), and lactic acid

(1.6 meq/l) determinations and cell counts (RBC=12

c/ml, WBC=0 c/ml) were all within normal limits, as

were myelin basic protein levels, Lyme titers, CSF ACE

level, HSV PCR, and antibody determinations for

CMV, VCA, echo, Coxsackie, and polio viruses, except

for the finding, now, of one oligoclonal band. Lumbar

puncture and serology were negative for VDRL, cryptococcal antigen, CSF bacterial, fungal and AFB cultures, ANA titer, IgM for EBV, and ANCA C & P

antibodies (IgG for EBV was positive). Serum B12 (1.25

ng/ml) and folate (17.2 ng/ml) levels were elevated.

Total serum cholesterol was elevated (2.6 and 2.83 g/l).

The patient continued on tapering doses of prednisone. Intermittent hypertension developed, and was

treated with hydrochlorothiazide and quinapril. He received physical and occupational therapy and by the

time of discharge (3/6/98) displayed remarkable improvement in lower extremity strength. Right

plantarflexor strength remained 0/5, left improved to

2/5, dorsiflexors were both 3/5, iliopsoas muscles 4+ /5,

the quadriceps were 5/5, and hamstring muscles 4/5.

Unfortunately following discharge the patient was lost

to follow-up.

3. Discussion

This patient appears to have had a primary demyelinating condition, predominantly affecting the lower

extremities, in the distribution of an acquired neuropathy, but with evidence of CNS involvement as well.

Although the relevant motor nerve conduction velocities were only mildly affected, all the corresponding

distal motor latencies were prolonged by more then

150% of the upper limit of normal. Three out of four

lower extremity sensory nerve conduction velocities

were slowed to less than 80% of the lower limit of

normal and all three F response latencies obtained for

the lower extremities were also prolonged (although by

less then 110% of the upper limit of normal). Most of

these responses were obtained in the context of good

preservation of response amplitude. These results are

consistent, then, with a primary demyelinating etiology.

The EMG results also support this notion as there was

almost no evidence suggestive of denervation in any of

the muscles tested. The finding of satellite potentials in

some muscles is also consistent with a demyelinating

etiology: although they may be found in normal muscles, in conditions like muscular dystrophy their presence is sometimes taken as suggesting re-innervation of

segments of muscle tissue by poorly myelinated collateral sprouts [8]. Demyelination may also account for

some of the prolonged MUAP durations which were

noted.

Other studies performed on this patient, supporting a

primary demyelinating etiology, included an MRI of

the brain which revealed lesions limited to the periventricular white matter and the somatosensory evoked

potential studies which suggested dysfunction consistent

with a lesion of myelinated central nervous system

tracts.

It may be that the onset of this patient’s deterioration

was merely coincidental with his exposure to the solvent in question. However, exposure to the primary

component of the solvent, 1-bromopropane, has recently been shown to be neurotoxic in rats [19]. The

findings in that study strikingly mirror those reported

in this patient. Five to 6 weeks’ exposure to 1-BP (1000

ppm) resulted in pareparesis in all of the test animals.

Motor nerve conduction studies revealed mild slowing

of motor nerve conduction velocities (sensory studies

were not performed in these animals) but significant

prolongation of the distal motor latencies. Finally,

pathological studies in these animals revealed destruction of the myelin sheaths of teased fibers from the

common peroneal nerve and also degeneration of Purkinje cells from the cerebellum (i.e. both peripheral and

central nervous damage). Although formal reports of

1-BP neurotoxicity in humans are lacking, the work of

Yu et al. [19] was motivated by reports of hand numbness in Korean workers exposed to this chemical, suggesting the possibility of a polyneuropathy.

Development of toxicity may be a function of exposure

level however, Yu et al. [19] tested their rats at only one

exposure level and this information is not available for

our patient. However, other data suggest this; in an

abstract presented in a recent conference in Japan

(April 20–24, 1998) and included as part of a recent

EPA report [12] Ichihara et al. replicated the electrophysiologic findings of Yu et al. [19] in rats, and

appeared to find a threshold for these effects at an

exposure level of 800 ppm.

There do not appear to be any similar reports of

neurotoxicity in connection to the other known components of this solvent, however, it is also possible that

the different components of the mixture may have

interacted to result in the lesions found in our patient,

or that toxicity might be related to the unknown proprietary components of the solvent.

To summarize, data available from an animal model

and this case report raise the possibility that exposure

to 1-bromopropane, a widely used industrial solvent
202 G. Sclar / Clinical Neurology and Neurosurgery 101 (1999) 199–202

and cleaning agent may result in the development of

both central and peripheral nerve demyelination. Further testing may be in order to confirm this hypothesis

and, if so, to define the limits of safe exposure in

humans.

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