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NAL M EDICINE N. W .: Secondary n Congenital H eart 1947. and Bauer, W .: '.rthropathy, Amer. trophic Pulmonary and in Children, 7. {. P., J r.: Hypermonary MalignanJ53. gue, H. B .: The a Case in a Noted s Sixtieth Year, Fingers and Hyropathy, Int. Gin. k, T. P . : Chronic :1043, 1922. O'Leary, J .: The ypertrophic Osteo- : ern. Med. 99:431, ; and Gutner, L. B. : . nary Hypertrophic . 18:51, 1955. R. S .: Pulmonary T.A.M.A. 178:977, !ie, A .: The E x? of Cyanosis and Which Are Ast Disease, Amer. on the Peripheral ^ulmonary Osteo35, 1958. and Osteoarthrop390, 1959. D., and Behnke, ; with Reversal of d. 56:865, 1962. 132 '*'I Um \. Neuropathy Following Exposure to a Dimethylamine Salt of 2, 4-D MARY C. BERKLEY, M.D. AND KENNETH R. MAGEE, M.D. ANN ARBOR. MICH. A case of peripheral neuritis followed ex include details of the preparation of the posure to the dimethylamine salt of 2,4- solution of 2,4-D. dichlorophenoxyacetic acid. 2,4-D is widely used as a weed killer. In minute doses, plant Report of a Case j 1 3^ growth is stimulated; but in concentrations A 39-year-old farmer was seen at the University employed in ordinary commercial herbicides, this chemical causes excessive stimulation resulting in death to the plant.' Although 2,4-D is usually nontoxic, in 1959, Goldstein, Jones, and Brown reported 3 cases of peripheral neuropathy following of Michigan Medical Center during July, 1961; he complained of numbness and tingling of the hands and feet of 2 weeks' duration. Four days before the onset of symptoms he was spraying weeds in his cornfield with a liquid solution of 2,4-D. He used an automatic feprayer behind his tractor and repeatedly used his bare hands to correct exposure to an ester of 2,4-D.1 The neuropa plugging-up of the sprayer. Exposure to the 2,4-D thy began shortly after the exposure to the skin; therefore, absorption seemed to be percutaneous. Disability was prolonged, and recovery was incomplete. Prior to this report there had been no evidence of serious toxic apparently was excessive, as he made no attempt to wash his hands after each exposure. He thought it possible that he inhaled some of the solution, as it was a windy day. Initial symptoms were constant pricking of both fifth fingers and toes. Within a day, a similar effect in humans. However, 'various toxic sensation spread to all fingers and toes and also reactions had been reported in animals, in cluding renal edema with tubular changes, liver damage, myotonia, stiffness of the ex tremities, ataxia, lethargy, paralysis, and developed in areas in the midabdomen, the upper chest, and the anterior thighs. Despite numbness, he noted hypersensitivity to touch. He complained of aching in his arms and a feeling of stiffness in the hands and knees: During the second week of his coma. illness, he developed difficulty buttoning his shirt Goldstein, Jones, and Brown did not de and tying his shoes. He lost proper control of his scribe details of manufacture or purity of the hands; his handwriting deteriorated. 2.4- D ester preparations. Therefore, it might Past medical history disclosed one attack of low be suggested that some other agent used in back pain with sciatic radiation and weakness of the right foot, occurring 5 years before his present preparing or making a solution of the 2,4-D illness and clearing within 1 year. A gastric ulcer produced the neuritis and not the 2,4-D it self. It seems likely, however, that these i developed one year before the present illness which responded to medical treatment. There was no his i ' v.; authors were correct in assuming that th e / tory of exposure to any other toxin known to pro 2.4- D caused the neuritis. This report will dh. ueacevy-nmeuetraitlis.sprSapyescifoicnallhyi,s he had farm. not used There was ary no Received for publication Oct, 9, 1962; accepted-1 1 family history of neuritis or other nervous or mental Nov. 12. ' disease. t From the Department of Neurology, University ,rfiimaiion.--The general physical examination of Michigan Medical Center: . was normal. Mental status was normal. Neurological 133 :JU 'il II.* Y ni 'B? ai. v i :i I! 352 examination disclosed normal cranial nerve function. Strength in all extremities was normal, and there was no atrophy. The biceps and triceps reflexes were hypoactive; the knee jerks were normal. The ankle jerks were hypoactive. There were no pathologic reflexes. Gait was normal. Fine movements of the hands were incoordinate: He had difficulty buttoning his shirt, tying his shoelaces, and his handwriting was unsteady. Position, motion, and vibratory sen sation-were impaired in the distal extremities; vibration was most severely affected. Light touch was decreased in the distal extremities in a neuritic pattern. There was a similar, mild decrease in distal perception of painful stimuli except that he was hyperalgesic over the fifth fingers. Laboratory Studies.--Chest x-ray demonstrated a calcified lung scar and old calcified nodes. Skull x-rays were normal. Spine x-rays disclosed reduc tion of the L-S S-l disc space with sclerosis of the intervertebral margins. Blood studies disclosed hematocrit, 37.5%; hemoglobin, 16.5 gm .; leuko cytes, initially 3,600 with a repeat of 4,900 and a normal differential count; blood urea nitrogen, 13 mg/100 cc; fasting blood sugar, 81 mg/100 cc with a normal glucose tolerance curve; serum .calcium, 9.3 mg/100 cc; phosphorus, 3.3 mg/100 cc; blood . Kahn, negative. Cerebrospinal fluid ( CSF) exami nation disclosed 100 mm. C SF pressure; 2 cells; protein, 47 mg/100 cc; globulin, negative; colloidal gold, 0122100000; mastic, 0000000; serology, nega tive. ! f Electromyographic studies, including motor peroneal nerve conduction times were within normal limits; however, in view of the short duration of the illness, the results are of questionable signifi; cance. Course o f Illness,--A diagnosis of primarily sensory, peripheral polyneuropathy was made, and 2 multivitamin capsules (Zymacap, Upjohn) and 200 mg. of thiamine hydrochloride daily were pre scribed. Several weeks later gradual improvement began and has continued. When last seen in April, 1962, he complained only of mild intermittent numb ness of the hands after prolonged use. H e handled tools and small objects normally. The deep tendon reflexes in the upper extremities remained hypo active. Vibratory sensation was normal in the lower extremities and only slightly reduced in the fingers, i Mild hypalgesia was evident only on the fourth and .fifth fingers of the right hand. Otherwise the neu rological examination was normal. Com m ent This farmer used an aqueous solution of the dimethylamine salt of 2,4-D. The 2,4-D was obtained as concentrated solutions of dimethylamine salts of 2,4-D or as 2,4-D AR C H IV E S OF IN T E R N A L MEDICINE acid, which was made into solution through interaction with dimethylamine' and water. The 'result was a 40% solution of the di methylamine salt of 2,4-D and water. Small percentages of antifreeze, isopropanol, were added; traces of a sequestering agent, citric acid, which formed the dimethylamine salt of citric acid were also added for hard water solubility. The 2,4-D acid is 98%-99% pure, and the other traces of impurities are probably the bis-form of 2,4-D; i.e., the interaction of dichloroacetic acid with 2,4dichlorophenol to form a double-substituted acetic add. Most 2,4-D acid is made from monochloroacetic acid and dichlorophenol, which are readily available in pure form; consequently most 2,4-D acid is very pure. Conclusions It is probable that 2,4-D dimethylamine salt produced a primary sensory neuropathy in this 39-year-old farmer. It is unlikely that a contaminant could be present in sufficient quantities to produce a neuropathy, but even admitting this possibility, it seems likely that preparations containing 2,4-D may produce neuropathy. Therefore, the recommendations of Goldstein, Jones, and Brown are empha sized; shorter periods of exposure, frequent washing of the skin after exposure, and changing of clothes when they become wet with the solution. 1 Despite the extensive use of 2,4-D prepara tions, resultant peripheral neuropathy is very rare, and an afflicted individual probably has some predisposition to neuropathy or sus ceptibility to the toxin. Nevertheless, as it cannot be determined who is predisposed or susceptible, and as no antidote to 2,4-D in toxication is known, prevention is simpler than treatment. Mary C Berkley, M.D., University of Michigan Medical Center, University Hospital, Department of Neurology, Ann Arbor, Mich. / REFERENCE 1. Goldstein, N. P. ; Jones, P. H., and Brown, J. R.^ Peripheral Neuropathy A fter Exposure to an Ester of Dichlorophenoxyacetic Acid, J.A.M.A. 171:1306-1309, 1959. 134 In 1958, Astn described a de> from multiple si ing disorders w multifocal leuko tion is character neurologic deti alterations in i $ language disord evidence of pyi Pathologically, ' focal destructio* gradations of s with relative sp ``These foci havency to become clike lesions ma} myelin destructireaction consisti cytes into bizan Received for pu' Nov. 19. -! Instructor, Dcp: of Michigan Me> Physician, Departi General Hospital, |: Assistant Profess { Michigan Medical Pulmonary Diseast tion Hospital, Ami an Instructor, Dep; of Michigan Mer jHeadington). From the Medic jierans Administrate of Medicine and F: Medical Center, fell-- S >j.