Arsenic and Antique Copper: A Potential Source for lntoxication and Development of Peripheral Neuropathy H. Royden Jones, Jr, M D

Although arsenic is known for its ubiquitous distribution in the environment, it is no longer a frequent cause of periph- eral neuropathy. Heightened awareness of its toxic poten- tial has led to measures that have decreased the public’s exposure. Because of its notoriety as a surreptitious means of committing homicide, when excess quantities of arsenic appear to be the cause of a patient’s symptoms, suspicion may inappropriately be directed to other individuals if no apparent source is found. A case is reported of a patient with arsenical peripheral neuropathy secondary to leaching of arsenic from an “antique” copper kettle.

A 42-year-old man presented with increasingly frequent episodes of sweats, fevers, headaches, unsteadiness, fa- tigue, blurred vision, and nausea. H e had associated numb- ness in all four extremities, increasing in degree, occur- ring on a daily basis. The patient admitted to substantial chronic alcohol ingestion. Past history was not otherwise remarkable.

Abnormal findings on examination included a mild static finger tremor, symmetrical decrease in ankle reflexes, dim- inution in pinprick and vibration sensation in a stocking and glove distribution, and alcohol on his breath.

Abnormal laboratory results included serum glutamic oxaloacetic transaminase, 12 5 units; 3-hour glucose toler- ance test (fasting, 102 mgldl; 1 hour, 277; 2 hour, 239; and 3 hour, 167 mg/dl); and 24-hour urine collection contain- ing 720 p g of arsenic (normal, 20 pg) with concomitant increased arsenic levels in the hair and nails. Nerve con- duction study and needle electromyography demonstrated a mild axonal neuropathy.

Search for sources of arsenic exposure was unsuccessful until his wife recalled that he was the only family member who used an antique copper teakettle. A specimen of Bos- ton water boiled in this kettle contained 200 p g of arsenic per liter. Concomitantly, water from the same source was boiled in a modern copper teakettle and had no arsenic.

Six weeks after the patient stopped using this kettle, no arsenic was detectable in his urine. His symptoms disap- peared within ten weeks. None have recurred in a six-year follow-up period.

Comment In patients with arsenical peripheral neuropathy, sources such as insecticides or industrial exposure may be apparent. However, in many patients the origin of the toxin may be enigmatic [3].

Arsenic has a diffuse natural distribution in soil and

water, especially ocean water. Copper ores contain various mineral impurities, of which arsenic is the most trouble- some [l]. It is speculated that ancient humans became aware of the toxic properties of arsenic and thus searched for other copper alloys [41. Modern copper manufacturing techniques eliminate inorganic arsenic [23. The age of this patient’s antique kettle could not be determined. Presum- ably, its copper did not meet modern standards of metal- lurgic technique.

This case emphasizes the need to consider arsenic as a cause for peripheral neuropathy in (1) patients with associ- ated intermittent, poorly defined systemic symptoms, in- cluding fever, sweats, blurred vision, and recurrent nausea or vomiting; (2) any patient with a new onset of peripheral neuropathy, even when other problems such as glucose intolerance or ethanol excess are present; and ( 3 ) patients using antique copper kettles that may contain arsenic.

Department of Neurology Lahey Clinic Medical Center 41 Mall Rd Burlington, M A 0180.3

References Arsenic. Encyclopaedia Britannica 2:478-481, 1967 Baker EL Jr, Hayes CG, Landrigan PJ, et al: A nation-wide sur- vey of heavy metal absorption in children living near primary copper, lead, and zinc smelters. Am J Epidemiol 106:261-273, 1977 Heyman A, Pfeiffer JB, Willett RW, er al: Peripheral neu- ropathy caused by arsenic intoxication. N Engl J Med 254:

Wertime TA: The beginnings of metallurgy: a new look. Sci- ence 182:875-887, 1973

401-409, 1956

Normal Muscle Pyruvate Oxidation in Spinocerebellar Degenerations Owen B. Evans, MD

Spinocerebellar degenerations (SCD) are a group of ge- netic disorders characterized by progressive ataxia and other neurological dysfunctions. Although the patho- physiology of SCD is unknown, disordered carbohydrate metabolism and reduced pyruvate dehydrogenase com- plex (PDHC) activity have been demonstrated in some patients [3]. The SCD patients were clinically similar to pa- tients with Friedreich’s ataxia, and subsequent work showed that an altered Michaelis-Menten constant for lipoamide dehydrogenase, the third component of PDHC, was the responsible enzyme abnormality 141. Other lab- oratories have failed to confirm deficient lipoamide dehydrog- e n a e activity [l, 51. PDHC is a regulatable enzyme that exists in an active or inactive state, and abnormal pyruvate oxidation in SCD could result from disordered PDHC reg-

Letters 93

ulation rather than a specific enzyme deficiency. This study examined muscle PDHC activation in patients with SCD.

Nine adult patients with progressive ataxia were selected for study after obtaining informed consent. Four patients had typical Friedreich’s ataxia [2]. The remaining five pa- tients had late-onset progressive ataxia alone or in combi- nation with polyneuropathy, spastic paraparesis, or bulbar paresis. Six of the nine patients had siblings with similar diseases.

Each patient had an open muscle biopsy. Control tissue was obtained from 33 patients undergoing muscle biopsy for diagnostic purposes; 10 of the 33 controls were normal histologically and 23 were abnormal. All tissues were stored at - 70°C until studied. PDHC was assayed in mus- cle homogenates by measurement of I4CO, production from 14C-l-pyruvate. The percentage activation was calcu- lated as PDHCdPDHC, where PDHCh represents basal activity and PDHC,, total activity after in vitro activation.

PDHCh was similar in the SCD and control groups. There was a reduction in PDHC, in the SCD group (2.279 nmol/min/mg protein * 0.412 SEM) compared to normal biopsy controls (3.181 * 0.421) and abnormal biopsy con- trols (2.834 * 0.353); however, this did not achieve statis- tical significance. Activation was 14.5 * 3.5% in the SCD group and 13.3 t 1.7% in the total control group. Two SCD patients had significantly reduced PDHC, activity compared to normal biopsy controls. One of these pa- tients, who had Friedreich’s ataxia, had two siblings with normal PDHC, activity. Three abnormal biopsy control patients-one each with polymyositis, phosphorylase defi- ciency, and polyneuropathy syndrome-had similar low PDHC, values.

This study does not show a significant difference in mus- cle pyruvate oxidation or PDHC activation in vitro be- tween SCD patients and non-SCD controls. Because three patients in the abnormal biopsy control group showed re- duced PDHC, activity, disordered pyruvate oxidation may not be a specific finding for SCD, but rather a secondary event in neuromuscular disorders.

Supported by a grant from the Muscular Dystrophy Association.

Department of Neurology Vanderbilt University Medical Center Nashville, T N 37232

References 1. Barbeau A, Butterworth RF, Ngo T, et al: Pyruvate metabolism

in Friedreich’s ataxia. Can J Neurol Sci 4:379-388, 1976 2. Geoffroy G, Barbeau A, Breton G, et al: Clinical description

and roentgenologic evaluation of patients with Friedreich’s ataxia. Can J Neurol Sci 3:279-286, 1976

3. Kark RAP, Blass JP, Engel WK: Pyruvate oxidation in neuromuscular disease. Neurology 24964-97 1, 1974

4. Rodriguez-Budelli M, Kark P: Kinetic evidence for a structural abnormality of lipoamide dehydrogenase in two patients with Friedreich ataxia. Neurology 28:1283-1286, 1978

5 . Stumpf DA, Parks J K Friedreich ataxia: 11. Normal kinetics of lipoamide dehydrogenase. Neurology 29:820-826, 1979

Measurement of ErvthroDoietin Levels in PollOw-up of Patients with Cerebellar Hemangioblas toma Linda Pololi-Anagnostou, MRCP,* and Athanasius Anagnostou, MD’t

We recently reported the case of a 22-year-old woman with cerebellar hemangioblastoma in whom rising plasma eryth- ropoietin (Ep) titers, followed by erythrocytosis, preceded any clinical or brain scan changes suggestive of tumor re- currence. We suggested that in similar cases serial plasma Ep determinations could serve as a useful early marker of tumor activity [l]. After several years free of disease, this patient was readmitted to our hospital complaining of pro- gressive weakness and sensory loss in the fingers and legs. The complete blood count was normal, and injection of the patient’s plasma into the exhypoxic polycythemic mouse assay [2] did not show an increase in plasma Ep titers. However, a pheumoencephalogram and a bilateral verte- bral angiogram revealed tumor recurrence in the cerebel- lum and cervical spine. Erythropoietin levels were elevated in the patient’s cerebrospinal fluid (CSF); assay results, ex- pressed as percentage of 48-hour incorporation of ferrous citrate Fe 59 into newly formed red cells of the assay mice, were: normal saline control, 0.84%; patient’s plasma, 1.19%; patient’s CSF, 7.2%. The patient was treated with irradiation to the posterior fossa and spinal cord, but soon afterward she aspirated and died.

The literature on erythropoietin does not contain reports of assay of the hormone in CSF. We therefore tested CSF samples from 16 patients who had undergone a lumbar puncture for diagnostic purposes. The group included pa- tients with diagnoses of neoplasia or infectious disease, or simply patients complaining of a seizure disorder or headaches. We did not find increased CSF Ep titers in any of these patients. We cannot explain why, in our patient with hemangioblastoma, Ep was unable to diffuse from the CSF into the bloodstream during this tumor recurrence. In view of our findings, however, it seems advisable that follow-up of the rare patient with hemangioblastoma and erythrocytosis should include determination of not only plasma but also CSF Ep titers.

Departments of ‘Medicine and +Pathology Abraham Lincolz School of Medicine University of Illinois Medical Center PO Box 6998 Chicago, fL 60680

References 1. Anagnostou A, Chawla MS, Pololi L, Fried W: Determination

of plasma erythropoietin levels-an early marker of tumor ac- tivity. Cancer 44:1014-1016, 1979

2. DeGowin RL, Holstra D, Gurney CW: The mouse with hypoxia-induced erythremia, an erythropoietin bioassay ani- mal. J Lab Clin Med 60:846-852, 1962

94 Annals of Neurology Vol 7 No 1 January 1781