Clinical Neurology and Neurosurgery 101 (1999) 199

– 202



## Case report 

# Encephalomyeloradiculoneuropathy following exposure to an industrial solvent

Gary Sclar 1

Department of Neurosciences

, Uni**6**ersity of Medicine and Dentistry of New Jersey

, MSB H

- 506

, 185 South Orange A **6**enue, 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) (CAS c 106-94-5; **\** 95.5% by weight), butylene oxide (CAS c 106-88-7; **B** 0.5%), 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]G

. Sclar **/** Clinical Neurology and Neurosurgery 101 (1999) 199–202 200

(CAS c 646-06-0; **B** 2.5%) and nitromethane (CAS c 75-52-5; **B** 0.25%). Also included are two proprietary components (CAS c s 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 coronaradiata. 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 patientto be alert and oriented. Speech was fluent, and language function was normal. Extraocular eye movements were full with no nystagmus. The pupils were 4mm, equal, round and reactive to light and accommodation. The remaining cranial nerves were grossly intact. Mild (4 **+ /** 5) weakness of the right biceps andtriceps 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 wereboth 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 corpuscallosum 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 standardnerve 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 **m**V). 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 theright 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 **m**V). 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 extensordigitorum 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 unitpotentials). 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 beobtained 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 H 2O). Protein (0.28 g**/**l), glucose (3.6 mmol**/**l), and lactic acid (1.6 meq**/**l) determinations and cell counts (RBC **=** 12

c**/ m** l, WBC **=** 0 c**/ m** l) 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. Lumbarpuncture 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 B 12 (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 wastreated 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 lowerextremities, 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 demyelinatingetiology: although they may be found in normal muscles, in conditions like muscular dystrophy their presence is sometimes taken as suggesting re-innervation ofsegments 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 ofthe 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 deteriorationwas merely coincidental with his exposure to the solvent in question. However, exposure to the primarycomponent 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 thecommon 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 ofYu 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 recentEPA 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 ofneurotoxicity 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 solventG

. Sclar **/** Clinical Neurology and Neurosurgery 101 (1999) 199–202 202

and cleaning agent may result in the development ofboth 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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