- Email: [email protected]
Encephalomyeloradiculoneuropathy following exposure to an industrial solvent
Clinical Neurology and Neurosurgery 101 (1999) 199 – 202 www.elsevier.com/locate/clineuro
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
1. Introduction
2. Case report
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.
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) (CASc 106-94-5;\ 95.5% by weight), butylene oxide (CASc106-88-7;B 0.5%), 1,3 dioxolane
E-mail address: [email protected] (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: S 0 3 0 3 - 8 4 6 7 ( 9 9 ) 0 0 0 3 4 - 7
200
G. Sclar / Clinical Neurology and Neurosurgery 101 (1999) 199–202
(CASc 646-06-0;B 2.5%) and nitromethane (CAS c 75-52-5;B0.25%). Also included are two proprietary components (CASc 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 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
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
201
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.
References [1] Ahmad S. Lovastatin and peripheral neuropathy. Am Heart J 1995;130:1321. [2] Arrowsmith JB, Milstein JB, Kuritsky JN, Murano G. Streptokinase and the Guillian Barre´ syndrome (letter). Ann Int Med 1985;103:302. [3] Atkinson AB, Brown JJ, Lever AF. Neurologic dysfunction in two patients receiving captopril and cimetidine. Lancet 1980;2:36 – 7. [4] AuBuchon J, Robins HI, Viseskul C. Peripheral neuropathy after exposure to methyl-isobutyl ketone in spray paint. Lancet 1979;2:363 – 4. [5] Charness ME, Morady F, Scheinman MM. Frequent neurologic toxicity associated with amiodarone. Neurology 1984;34:669 – 71. [6] Chu CC, Huang CC, Chu NS, Wu TN. Carbon disulfide induced polyneuropathy: sural nerve pathology, electrophysiology, and clinical correlation. Acta Neurol Scand 1996;94:258–63. [7] Donofrio PD, Albers JW. AAEM Minimonograph c 34: polyneuropathy: classification by nerve conduction studies and electromyography. Muscle Nerve 1990;13:889–903. [8] Dumitru D. Electrodiagnostic medicine. Philadelphia: Hanley and Belfus, 1995.
.
[9] Dyck PJ, Thomas PK, editors. Peripheral neuropathy. 3rd ed. Philadelphia: WB Saunders, 1993. [10] Fagius J, Osterman PO, Siden A, Wiholm BE. Guillian-Barre syndrome following zimelidine treatment. J Neurol Neurosurg Psych 1985;48:65 – 9. [11] Herbert R, Gerr F, Luo J, Harris-Abbott D, Landrigan PJ. Peripheral neurologic abnormalities among roof workers: sentinel case and clinical screening. Arch Environ Health 1995;50:349 – 54. [12] Ichihara M, Takeuchi Y, Shibata E, Kitoh J. Abstract included in Environmental Protection Agency Report 8EHQ-0598-14093, May 11, 1998. [13] Jacobs JM, Costa-Jussa FR. The pathology of amiodarone neurotoxicity. Brain 1985;108:753 – 69. [14] Jacobs MB. HMG-CoA reductase inhibitor therapy and peripheral neuropathy (letter). Ann Int Med 1994;120:970. [15] Savolainen H. Some aspects of the mechanisms by which industrial solvents produce neurotoxic effects. Chem-Biol Interact 1977;18:1 – 10. [16] Seppalainen AM. Solvents and peripheral neuropathy. Prog Clin Biol Res 1986;220:247 – 53. [17] Spencer PS, Schaumburg HH. Organic solvent neurotoxicity. Facts and research needs. Scand J Work, Environ Health 1985;11(Suppl. 1):53 – 60. [18] Triebig G, Bestler W, Baumeister P, Valentin H. Neurotoxicity of workplace substances. IV Determination of motor and sensory nerve conduction velocity in persons exposed to solvent mixtures. Int Arch Occup Environ Health 1983;52:139 –50. [19] Yu X, Ichihara G, Kitoh J, Xie Z, Shibata E, Kamijima M, Asaeda N, Takeuchi Y. Preliminary report on the neurotoxicity of 1-bromopropane, an alternative solvent for chlorofluorocarbons. J Occup Health 1998;40:234 – 5.
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
1. Introduction
2. Case report
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.
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) (CASc 106-94-5;\ 95.5% by weight), butylene oxide (CASc106-88-7;B 0.5%), 1,3 dioxolane
E-mail address: [email protected] (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: S 0 3 0 3 - 8 4 6 7 ( 9 9 ) 0 0 0 3 4 - 7
200
G. Sclar / Clinical Neurology and Neurosurgery 101 (1999) 199–202
(CASc 646-06-0;B 2.5%) and nitromethane (CAS c 75-52-5;B0.25%). Also included are two proprietary components (CASc 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 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
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
201
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.
References [1] Ahmad S. Lovastatin and peripheral neuropathy. Am Heart J 1995;130:1321. [2] Arrowsmith JB, Milstein JB, Kuritsky JN, Murano G. Streptokinase and the Guillian Barre´ syndrome (letter). Ann Int Med 1985;103:302. [3] Atkinson AB, Brown JJ, Lever AF. Neurologic dysfunction in two patients receiving captopril and cimetidine. Lancet 1980;2:36 – 7. [4] AuBuchon J, Robins HI, Viseskul C. Peripheral neuropathy after exposure to methyl-isobutyl ketone in spray paint. Lancet 1979;2:363 – 4. [5] Charness ME, Morady F, Scheinman MM. Frequent neurologic toxicity associated with amiodarone. Neurology 1984;34:669 – 71. [6] Chu CC, Huang CC, Chu NS, Wu TN. Carbon disulfide induced polyneuropathy: sural nerve pathology, electrophysiology, and clinical correlation. Acta Neurol Scand 1996;94:258–63. [7] Donofrio PD, Albers JW. AAEM Minimonograph c 34: polyneuropathy: classification by nerve conduction studies and electromyography. Muscle Nerve 1990;13:889–903. [8] Dumitru D. Electrodiagnostic medicine. Philadelphia: Hanley and Belfus, 1995.
.
[9] Dyck PJ, Thomas PK, editors. Peripheral neuropathy. 3rd ed. Philadelphia: WB Saunders, 1993. [10] Fagius J, Osterman PO, Siden A, Wiholm BE. Guillian-Barre syndrome following zimelidine treatment. J Neurol Neurosurg Psych 1985;48:65 – 9. [11] Herbert R, Gerr F, Luo J, Harris-Abbott D, Landrigan PJ. Peripheral neurologic abnormalities among roof workers: sentinel case and clinical screening. Arch Environ Health 1995;50:349 – 54. [12] Ichihara M, Takeuchi Y, Shibata E, Kitoh J. Abstract included in Environmental Protection Agency Report 8EHQ-0598-14093, May 11, 1998. [13] Jacobs JM, Costa-Jussa FR. The pathology of amiodarone neurotoxicity. Brain 1985;108:753 – 69. [14] Jacobs MB. HMG-CoA reductase inhibitor therapy and peripheral neuropathy (letter). Ann Int Med 1994;120:970. [15] Savolainen H. Some aspects of the mechanisms by which industrial solvents produce neurotoxic effects. Chem-Biol Interact 1977;18:1 – 10. [16] Seppalainen AM. Solvents and peripheral neuropathy. Prog Clin Biol Res 1986;220:247 – 53. [17] Spencer PS, Schaumburg HH. Organic solvent neurotoxicity. Facts and research needs. Scand J Work, Environ Health 1985;11(Suppl. 1):53 – 60. [18] Triebig G, Bestler W, Baumeister P, Valentin H. Neurotoxicity of workplace substances. IV Determination of motor and sensory nerve conduction velocity in persons exposed to solvent mixtures. Int Arch Occup Environ Health 1983;52:139 –50. [19] Yu X, Ichihara G, Kitoh J, Xie Z, Shibata E, Kamijima M, Asaeda N, Takeuchi Y. Preliminary report on the neurotoxicity of 1-bromopropane, an alternative solvent for chlorofluorocarbons. J Occup Health 1998;40:234 – 5.