- Email: [email protected]
Idiopathic renal vein thrombosis in a healthy young woman with flank pain and fever
Correspondence
417
induced hypertriglyceridemia. In all cases (with or without diabetes), 5% or 10% of intravenous dextrose was given concomitantly with insulin to prevent hypoglycemia. In addition, glucose may be required for insulin to increase the level of synthesis and secretion of lipoprotein lipase [1]. Unfortunately, data regarding the use of insulin for management of severe hypertriglyceridemia in nondiabetic patients are very limited. Our review of the English and non-English literature only revealed 2 cases [3,4] of severe hypertriglyceridemia without a diagnosis of diabetes treated with insulin (Table 1). Because heparin is another potent activator of lipoprotein lipase, it has been used for the same purpose either alone [3,5] or in conjunction with insulin [4,6,7] in 11 patients, 4 of them did not have a diagnosis of diabetes [3,6,7] (Table 2). One important advantage of using insulin in this setting is the fact that patients may not be able to tolerate oral medications initially because of the accompanying abdominal pain. Moreover, the triglyceride-lowering action of fibrate drugs and fish oil preparations, which can only be given orally, may take several weeks to become evident. In contrast, the described cases in Tables 1 and 2 clearly showed that insulin was highly effective in decreasing serum levels of triglycerides to a safe range within few days. No complications related to insulin treatment were reported in any case. However, the efficacy of insulin compared to the standard therapy of severe hypertriglyceridemia (intravenous fluids and nothing by mouth) in nondiabetic patients remains unclear. Randomized controlled trials are required to evaluate better the effectiveness and safety of insulin for treatment of severe hypertriglyceridemia in nondiabetic patients, and to determine the optimum protocol for its use with or without heparin.
References [1] Eckel RH. Lipoprotein lipase. A multifunctional enzyme relevant to common metabolic diseases. N Engl J Med 1989;320:1060 - 8. [2] Durrington P. Dyslipidemia. Lancet 2003;362:717 - 31. [3] Berger Z, Quera R, Poniachik J, Oksenberg D, Guerrero J. Heparin and/ or insulin treatment of acute pancreatitis caused by hypertriglyceridemia. Rev Med Chil 2001;129:1373 - 8. [4] Jabbar M, Zuhri-Yafi M, Larrea J. Insulin therapy for a non-diabetic patient with severe hypertriglyceridemia. J Am Coll Nutr 1998;17: 458 - 61. [5] Sharma P, Lim S, James D, Horne M, James D, Orchard RT, et al. Pancreatitis may occur with a normal amylase concentration in hypertriglyceridemia. BMJ 1996;313:1265 [letter]. [6] Monga A, Arora A, Makkar R, Gupta A. Hypertriglyceridemia-induced acute pancreatitis-treatment with heparin and insulin. Indian J Gastroenterol 2003;22:102 - 3. [7] Henzen C, Rock M, Schnieper C, Heer K. Heparin und insulin in der therapie der akuten hypertriglyzeridamie-induzierten pankreatitis. Schweiz Med Wochenschr 1999;129:1242 - 8.
Nasser Mikhail MD, MSc Kash Trivedi MD Christina Page MD
Soma Wali MD Dennis Cope MD Department of Medicine Olive View-UCLA Medical Center, Sylmar CA 91342, USA E-mail address: [email protected] doi:10.1016/j.ajem.2005.02.036 Idiopathic renal vein thrombosis in a healthy young woman with flank pain and fever To the Editor, Renal vein thrombosis (RVT) is a rare disorder that is found most commonly in adults with nephrotic syndrome and in children as part of an acute illness with prolonged volume loss. Patients with this condition are at risk for significant renal impairment and other arterial and venous thromboembolic complications. We present a case of a young healthy woman who presented to our ED with classic signs and symptoms of pyelonephritis that was subsequently found to have an idiopathic unilateral RVT without acute infection. A 24-year-old woman reported to the ED complaining of 5 days of left flank and abdominal pain. Her pain was described as throbbing and sharp, originating in the left lower back and radiating into the upper back. These symptoms were accompanied by left lower-quadrant abdominal pain, nausea, and vomiting. She reported a fever of 102.88F without urinary symptoms. Her past and family histories were negative. Her physical examination was notable for a temperature of 101.88F, tachycardia, dry mucous membranes, left cost vertebral angle tenderness, and mild suprapubic tenderness. The working diagnosis at this point was pyelonephritis. She received intravenous (IV) fluids, antibiotics, and an antiemetic. Laboratory data included a normal complete blood count, electrolytes, serum urea nitrogen, and creatinine. Urinalysis showed large ketones, moderate hemoglobin level, and moderate protein. Her urine pregnancy test was negative. Given the lack of definitive laboratory findings and increased flank and abdominal pain during her ED course, a noncontrasted abdominal computed tomography (CT) scan was obtained to evaluate for renal calculi. The scan revealed an enlarged left kidney with perinephric stranding. There was a hyperdensity in the left renal vein suspicious for thrombus. An IVcontrasted CT scan confirmed a left RVT extending to the inferior vena cava with evidence of impaired renal function on that side (Fig. 1). Anticoagulation therapy with heparin and warfarin was started and the patient recovered without incident on the inpatient service. Her serum creatinine remained normal throughout her stay and urinary protein losses were negligible. A chest CT for pulmonary embolus was negative and hypercoaguable panels were normal. She is currently
418
Fig. 1 A, Nonconstrasted abdominal CT. An enlarged left kidney with perinephric stranding (large arrow) secondary to venous obstruction. There is also a distinct hyperdensity within the left renal vein (small arrow) representing acute thrombus. B, IVcontrasted abdominal CT. Note the extensive thrombus involving the entire left renal vein (large arrow) without extension into the lumen of the interior vena cava (small arrow).
completing a 6-month course of oral anticoagulation for idiopathic RVT. Renal vein thrombosis is most common in patients with nephrotic syndrome but also occurs in those with hypercoaguable disease (including pregnancy and the pueperium) [1], abdominal, back, or flank trauma [2], abdominal surgery, renal transplantation, drugs that predispose to procoagulation (such as oral contraceptives, steroids, and cyclophosphamide), infectious suppuration, and, as in this case, an idiopathic or spontaneous etiology. These etiologic risk factors are commonly encountered by emergency medicine physicians. Although its clinical manifestations are variable, this disorder generally presents in either a chronic or acute form. The more common chronic presentation tends to be asymptomatic. Acute presentations tend to occur in younger patients with resultant cost vertebral angle tenderness and macroscopic hematuria [3,4]. Missed or delayed diagnoses can result in significant morbidity and mortality from renal and thromboembolic complications. In this particular
Correspondence patient, the presumed diagnosis of pyelonephritis almost precluded the timely diagnosis and treatment of RVT. The pathophysiology of this disorder has not been fully elucidated but is believed to be multifactorial, impacting the coagulation cascade at numerous sites [3]. Most models have focused on patients with the nephrotic syndrome. Interestingly, these patients tend to have elevated levels of fibrinogen which significantly increases plasma viscosity and hence the risk of thrombosis. They also have increased urinary losses of the coagulation inhibitor antithrombin III, an enzyme whose activity is increased in the presence of heparin [3,4]. This endogenous anticoagulant is the main inhibitor of activated factors IX, X, XI, XII, and plasmin [3]. In addition, renal losses of protein S may result in an acquired form of this syndrome. Protein S is a protease that stimulates the inactivation of factor V by protein C [3]. Other less rigorously tested observations include findings of defective fibrinolysis and increased platelet aggregation in those with RVT and nephrotic syndrome [3]. The diagnostic gold standards for RVT include either renal venogram or arteriogram, which allows visualization of acute large vessel clots. Less invasive testing, however, with IV-contrasted abdominal CT, abdominal Doppler ultrasonography, and magnetic resonance imaging [5] are reported to be as effective [3,6]. Treatment of acute RVT centers on clot dissolution. The most widely accepted therapy is the use of heparin followed by oral anticoagulation. The use of thrombolytics [7,8] and surgical thrombectomy have also proven to be successful in adults and children but is usually reserved for individuals with progressive deterioration despite appropriate anticoagulation [3,9,10]. Perhaps the most difficult factor in this disease process for EM physicians is making the diagnosis. Left untreated, the progression of this disorder can be devastating. Renal complications include acute oliguric renal failure and/or infarction. Thromboembolic complications include deep vein thrombosis, pulmonary embolism, arterial thrombosis, acute ischemic stroke [4], and acute myocardial infarction [3,6].
References [1] Mansi MK. Postpartum renal infarction secondary to spontaneous renal vein thrombosis. J Urol 2001;165:893 - 4. [2] Berkovich GY, Ramchandani P, Preate Jr DL, et al. Renal vein thrombosis after martial arts trauma. J Trauma Inj Infect Crit Care 2001;50:144 - 5. [3] Brenner BM, editor. The kidney. Philadelphia (Pa): Saunders;, 2004. p. 1584 - 93. [4] Llach F, Papper S, Massry SG. The clinical spectrum of renal vein thrombosis: acute and chronic. Am J Med 1980;69:819 - 27. [5] Kanagasundaram NS, Bandyopadhyay D, Brownjohn AM, et al. The diagnosis of renal vein thrombosis by magnetic resonance angiography. Nephrol Dial Transplant 1998;13:200 - 2. [6] Llach F. Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int 1985;28:429 - 39.
Correspondence
419
[7] Bromberg WD, Firlit CF. Fibrinolytic therapy for renal vein thrombosis in the child. J Urol 1990;143:86 - 8. [8] Markowitz GS, Brignol F, Burns ER, et al. Renal vein thrombosis treated with thrombolytic therapy: case report and brief review. Am J Kidney Dis 1995;25:801 - 6. [9] Jaar BG, Kim HS, Samaniego MD, et al. Percutaneous mechanical thrombectomy: a new approach in the treatment of acute renal-vein thrombosis. Nephrol Dial Transplant 2002;17:1122 - 5. [10] Renoult E, Cormier L, Claudon M, et al. Successful surgical thrombectomy of renal allograft vein thrombosis in the early postoperative period. Am J Kidney Dis 2000;35:E21.
Rawle A. Seupaul MD Tyler M. Stepsis MD Marla C. Doehring Department of Emergency Medicine Indiana University School of Medicine Indianapolis, IN 46022, USA E-mail address: [email protected] doi:10.1016/j.ajem.2005.02.039 Seizure and elevated blood aluminum in a remelt furnace operator: connection or coincidence? To the Editor, Aluminum is a known neurotoxin, associated with cognitive, psychological, and motor abnormalities [1], most publicized in relation to patients with renal insufficiency, bdialysis dementia,Q and plasma aluminum concentrations ([Al]b) of 7 to 392 lg/L (mean, 82 F 56; normal, V7) [2,3]. Occupationally exposed workers with seizures, tremor, and cognitive impairment have also been described, usually without accompanying [Al]b values [4-6], except for the report of aluminum welders with high [Al]b levels (81-1728 and 380-1248) who frequently had electroencephalographic (EEG) abnormalities, including epileptiform changes in 7% to 17% [7]. Aluminum foundry workers with lower [Al]b (14.1 F 3.5 lg/L, SD) were reported to have cognitive impairment not present in unexposed matched control subjects with [Al]b of 8.2 F 1.2 [8]. Aluminum applied to cerebral cortical tissue has provided an animal model of seizure disorders for many years [9,10]. We evaluated a patient with a single grand mal seizure, whose [Al]b was 22 lg/L (normal less than 9) whose evaluation rendered known causes of seizure activity unlikely. The 30-year-old white married male furnace operator sustained a tonic-clonic seizure after breakfast at home. His wife witnessed the event and found his seizure activity to be like that of her uncle before his anticonvulsant therapy. Our patient was previously well except for 5 years of asthma that began 6 months after starting to work in a plant that makes cast aluminum truck wheels. He was taking no bronchodilator or other medications at the time of the seizure. He used no recreational drugs but smoked 1 to 2 packs of cigarettes daily and drank 1 to 2 six-packs of
beer weekly. There was no history of atopy. His family history was negative for asthma, allergies, or seizures. Examination was that of a postictal, confused, obese man with a sore tongue. Vital signs were normal including oxygen saturation of 96% to 98% in room air. He had generalized wheezing but satisfactory air movement. Examination was otherwise normal except for diminished sensation in a stocking-glove distribution. Normal laboratory results included complete blood count, serum glucose, glycated hemoglobin, electrolytes, creatinine, calcium, magnesium, creatine kinase, liver function tests, lipoproteins, except for low high-density lipoprotein (30 mg/dL, normal N40), vitamins B-6 and B-12, folate, protein electrophoresis, erythrocyte sedimentation rate, Lyme antibodies, antinuclear antibody, homocysteine and thrombophilia panel, serologic test for syphilis, arsenic, cadmium, lead, and mercury. Urine routine and microscopic analysis and drug screening panel were also normal as was an electrocardiogram. Radiographic imaging included normal chest films and computed tomography of the head. Magnetic resonance imaging of the brain was normal except for single tiny foci of increased signal in the left frontal lobe and pons consistent with gliosis, ischemia, or multiple sclerosis. An electroencephalogram showed generalized high-voltage sharp theta activity with photic stimulation and drowsiness, without focal abnormality. The patient’s job involved removing slag from furnaces (4-ft diameter, 22-ft height), which melted aluminum scrap and bar stock at 24008F, using a powdered flux of aluminum silicon fluoride. The work was hot and dusty. Only a plastic visor, leather gloves, and apron were used for protection with no respirator or local exhaust ventilation. A typical shift required charging 18 furnaces 6 times each, adding flux by hand. Slag was removed with a long shovel. About 48 hours had elapsed between his work shift and the seizure. A 36-year-old coworker doing the same job for 6 years had died of bstiff lungs.Q Phenytoin was given by vein and the patient had no further seizure activity. A neurologist recommended continued phenytoin therapy, follow-up EEG, no further alcohol or smoking, and no driving until seizure free for 6 months. Other recommendations were the use of improved work practice and protective equipment to reduce exposure to aluminum and fluoride dust, with repeat aluminum levels. Repeat [Al]b levels were 16 and 5 over the next 15 weeks, but the patient declined further phenytoin or other anticonvulsant therapy or EEG testing. He remained seizure free at 1 year, when his [Al]b was 4. The differential diagnosis includes alcohol withdrawal, multiple sclerosis, and idiopathic epilepsy. Although the patient’s [Al]b at the time of his hospitalization was only modestly elevated (22 vs 9 lg/L) — far lower than those reported in welders with EEG abnormalities — it is possible that his aluminum exposure played a causal role in his seizure. Some evidence indicates that inhaled aluminum can reach the brain via the olfactory nerve [11-13]. Once
417
induced hypertriglyceridemia. In all cases (with or without diabetes), 5% or 10% of intravenous dextrose was given concomitantly with insulin to prevent hypoglycemia. In addition, glucose may be required for insulin to increase the level of synthesis and secretion of lipoprotein lipase [1]. Unfortunately, data regarding the use of insulin for management of severe hypertriglyceridemia in nondiabetic patients are very limited. Our review of the English and non-English literature only revealed 2 cases [3,4] of severe hypertriglyceridemia without a diagnosis of diabetes treated with insulin (Table 1). Because heparin is another potent activator of lipoprotein lipase, it has been used for the same purpose either alone [3,5] or in conjunction with insulin [4,6,7] in 11 patients, 4 of them did not have a diagnosis of diabetes [3,6,7] (Table 2). One important advantage of using insulin in this setting is the fact that patients may not be able to tolerate oral medications initially because of the accompanying abdominal pain. Moreover, the triglyceride-lowering action of fibrate drugs and fish oil preparations, which can only be given orally, may take several weeks to become evident. In contrast, the described cases in Tables 1 and 2 clearly showed that insulin was highly effective in decreasing serum levels of triglycerides to a safe range within few days. No complications related to insulin treatment were reported in any case. However, the efficacy of insulin compared to the standard therapy of severe hypertriglyceridemia (intravenous fluids and nothing by mouth) in nondiabetic patients remains unclear. Randomized controlled trials are required to evaluate better the effectiveness and safety of insulin for treatment of severe hypertriglyceridemia in nondiabetic patients, and to determine the optimum protocol for its use with or without heparin.
References [1] Eckel RH. Lipoprotein lipase. A multifunctional enzyme relevant to common metabolic diseases. N Engl J Med 1989;320:1060 - 8. [2] Durrington P. Dyslipidemia. Lancet 2003;362:717 - 31. [3] Berger Z, Quera R, Poniachik J, Oksenberg D, Guerrero J. Heparin and/ or insulin treatment of acute pancreatitis caused by hypertriglyceridemia. Rev Med Chil 2001;129:1373 - 8. [4] Jabbar M, Zuhri-Yafi M, Larrea J. Insulin therapy for a non-diabetic patient with severe hypertriglyceridemia. J Am Coll Nutr 1998;17: 458 - 61. [5] Sharma P, Lim S, James D, Horne M, James D, Orchard RT, et al. Pancreatitis may occur with a normal amylase concentration in hypertriglyceridemia. BMJ 1996;313:1265 [letter]. [6] Monga A, Arora A, Makkar R, Gupta A. Hypertriglyceridemia-induced acute pancreatitis-treatment with heparin and insulin. Indian J Gastroenterol 2003;22:102 - 3. [7] Henzen C, Rock M, Schnieper C, Heer K. Heparin und insulin in der therapie der akuten hypertriglyzeridamie-induzierten pankreatitis. Schweiz Med Wochenschr 1999;129:1242 - 8.
Nasser Mikhail MD, MSc Kash Trivedi MD Christina Page MD
Soma Wali MD Dennis Cope MD Department of Medicine Olive View-UCLA Medical Center, Sylmar CA 91342, USA E-mail address: [email protected] doi:10.1016/j.ajem.2005.02.036 Idiopathic renal vein thrombosis in a healthy young woman with flank pain and fever To the Editor, Renal vein thrombosis (RVT) is a rare disorder that is found most commonly in adults with nephrotic syndrome and in children as part of an acute illness with prolonged volume loss. Patients with this condition are at risk for significant renal impairment and other arterial and venous thromboembolic complications. We present a case of a young healthy woman who presented to our ED with classic signs and symptoms of pyelonephritis that was subsequently found to have an idiopathic unilateral RVT without acute infection. A 24-year-old woman reported to the ED complaining of 5 days of left flank and abdominal pain. Her pain was described as throbbing and sharp, originating in the left lower back and radiating into the upper back. These symptoms were accompanied by left lower-quadrant abdominal pain, nausea, and vomiting. She reported a fever of 102.88F without urinary symptoms. Her past and family histories were negative. Her physical examination was notable for a temperature of 101.88F, tachycardia, dry mucous membranes, left cost vertebral angle tenderness, and mild suprapubic tenderness. The working diagnosis at this point was pyelonephritis. She received intravenous (IV) fluids, antibiotics, and an antiemetic. Laboratory data included a normal complete blood count, electrolytes, serum urea nitrogen, and creatinine. Urinalysis showed large ketones, moderate hemoglobin level, and moderate protein. Her urine pregnancy test was negative. Given the lack of definitive laboratory findings and increased flank and abdominal pain during her ED course, a noncontrasted abdominal computed tomography (CT) scan was obtained to evaluate for renal calculi. The scan revealed an enlarged left kidney with perinephric stranding. There was a hyperdensity in the left renal vein suspicious for thrombus. An IVcontrasted CT scan confirmed a left RVT extending to the inferior vena cava with evidence of impaired renal function on that side (Fig. 1). Anticoagulation therapy with heparin and warfarin was started and the patient recovered without incident on the inpatient service. Her serum creatinine remained normal throughout her stay and urinary protein losses were negligible. A chest CT for pulmonary embolus was negative and hypercoaguable panels were normal. She is currently
418
Fig. 1 A, Nonconstrasted abdominal CT. An enlarged left kidney with perinephric stranding (large arrow) secondary to venous obstruction. There is also a distinct hyperdensity within the left renal vein (small arrow) representing acute thrombus. B, IVcontrasted abdominal CT. Note the extensive thrombus involving the entire left renal vein (large arrow) without extension into the lumen of the interior vena cava (small arrow).
completing a 6-month course of oral anticoagulation for idiopathic RVT. Renal vein thrombosis is most common in patients with nephrotic syndrome but also occurs in those with hypercoaguable disease (including pregnancy and the pueperium) [1], abdominal, back, or flank trauma [2], abdominal surgery, renal transplantation, drugs that predispose to procoagulation (such as oral contraceptives, steroids, and cyclophosphamide), infectious suppuration, and, as in this case, an idiopathic or spontaneous etiology. These etiologic risk factors are commonly encountered by emergency medicine physicians. Although its clinical manifestations are variable, this disorder generally presents in either a chronic or acute form. The more common chronic presentation tends to be asymptomatic. Acute presentations tend to occur in younger patients with resultant cost vertebral angle tenderness and macroscopic hematuria [3,4]. Missed or delayed diagnoses can result in significant morbidity and mortality from renal and thromboembolic complications. In this particular
Correspondence patient, the presumed diagnosis of pyelonephritis almost precluded the timely diagnosis and treatment of RVT. The pathophysiology of this disorder has not been fully elucidated but is believed to be multifactorial, impacting the coagulation cascade at numerous sites [3]. Most models have focused on patients with the nephrotic syndrome. Interestingly, these patients tend to have elevated levels of fibrinogen which significantly increases plasma viscosity and hence the risk of thrombosis. They also have increased urinary losses of the coagulation inhibitor antithrombin III, an enzyme whose activity is increased in the presence of heparin [3,4]. This endogenous anticoagulant is the main inhibitor of activated factors IX, X, XI, XII, and plasmin [3]. In addition, renal losses of protein S may result in an acquired form of this syndrome. Protein S is a protease that stimulates the inactivation of factor V by protein C [3]. Other less rigorously tested observations include findings of defective fibrinolysis and increased platelet aggregation in those with RVT and nephrotic syndrome [3]. The diagnostic gold standards for RVT include either renal venogram or arteriogram, which allows visualization of acute large vessel clots. Less invasive testing, however, with IV-contrasted abdominal CT, abdominal Doppler ultrasonography, and magnetic resonance imaging [5] are reported to be as effective [3,6]. Treatment of acute RVT centers on clot dissolution. The most widely accepted therapy is the use of heparin followed by oral anticoagulation. The use of thrombolytics [7,8] and surgical thrombectomy have also proven to be successful in adults and children but is usually reserved for individuals with progressive deterioration despite appropriate anticoagulation [3,9,10]. Perhaps the most difficult factor in this disease process for EM physicians is making the diagnosis. Left untreated, the progression of this disorder can be devastating. Renal complications include acute oliguric renal failure and/or infarction. Thromboembolic complications include deep vein thrombosis, pulmonary embolism, arterial thrombosis, acute ischemic stroke [4], and acute myocardial infarction [3,6].
References [1] Mansi MK. Postpartum renal infarction secondary to spontaneous renal vein thrombosis. J Urol 2001;165:893 - 4. [2] Berkovich GY, Ramchandani P, Preate Jr DL, et al. Renal vein thrombosis after martial arts trauma. J Trauma Inj Infect Crit Care 2001;50:144 - 5. [3] Brenner BM, editor. The kidney. Philadelphia (Pa): Saunders;, 2004. p. 1584 - 93. [4] Llach F, Papper S, Massry SG. The clinical spectrum of renal vein thrombosis: acute and chronic. Am J Med 1980;69:819 - 27. [5] Kanagasundaram NS, Bandyopadhyay D, Brownjohn AM, et al. The diagnosis of renal vein thrombosis by magnetic resonance angiography. Nephrol Dial Transplant 1998;13:200 - 2. [6] Llach F. Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int 1985;28:429 - 39.
Correspondence
419
[7] Bromberg WD, Firlit CF. Fibrinolytic therapy for renal vein thrombosis in the child. J Urol 1990;143:86 - 8. [8] Markowitz GS, Brignol F, Burns ER, et al. Renal vein thrombosis treated with thrombolytic therapy: case report and brief review. Am J Kidney Dis 1995;25:801 - 6. [9] Jaar BG, Kim HS, Samaniego MD, et al. Percutaneous mechanical thrombectomy: a new approach in the treatment of acute renal-vein thrombosis. Nephrol Dial Transplant 2002;17:1122 - 5. [10] Renoult E, Cormier L, Claudon M, et al. Successful surgical thrombectomy of renal allograft vein thrombosis in the early postoperative period. Am J Kidney Dis 2000;35:E21.
Rawle A. Seupaul MD Tyler M. Stepsis MD Marla C. Doehring Department of Emergency Medicine Indiana University School of Medicine Indianapolis, IN 46022, USA E-mail address: [email protected] doi:10.1016/j.ajem.2005.02.039 Seizure and elevated blood aluminum in a remelt furnace operator: connection or coincidence? To the Editor, Aluminum is a known neurotoxin, associated with cognitive, psychological, and motor abnormalities [1], most publicized in relation to patients with renal insufficiency, bdialysis dementia,Q and plasma aluminum concentrations ([Al]b) of 7 to 392 lg/L (mean, 82 F 56; normal, V7) [2,3]. Occupationally exposed workers with seizures, tremor, and cognitive impairment have also been described, usually without accompanying [Al]b values [4-6], except for the report of aluminum welders with high [Al]b levels (81-1728 and 380-1248) who frequently had electroencephalographic (EEG) abnormalities, including epileptiform changes in 7% to 17% [7]. Aluminum foundry workers with lower [Al]b (14.1 F 3.5 lg/L, SD) were reported to have cognitive impairment not present in unexposed matched control subjects with [Al]b of 8.2 F 1.2 [8]. Aluminum applied to cerebral cortical tissue has provided an animal model of seizure disorders for many years [9,10]. We evaluated a patient with a single grand mal seizure, whose [Al]b was 22 lg/L (normal less than 9) whose evaluation rendered known causes of seizure activity unlikely. The 30-year-old white married male furnace operator sustained a tonic-clonic seizure after breakfast at home. His wife witnessed the event and found his seizure activity to be like that of her uncle before his anticonvulsant therapy. Our patient was previously well except for 5 years of asthma that began 6 months after starting to work in a plant that makes cast aluminum truck wheels. He was taking no bronchodilator or other medications at the time of the seizure. He used no recreational drugs but smoked 1 to 2 packs of cigarettes daily and drank 1 to 2 six-packs of
beer weekly. There was no history of atopy. His family history was negative for asthma, allergies, or seizures. Examination was that of a postictal, confused, obese man with a sore tongue. Vital signs were normal including oxygen saturation of 96% to 98% in room air. He had generalized wheezing but satisfactory air movement. Examination was otherwise normal except for diminished sensation in a stocking-glove distribution. Normal laboratory results included complete blood count, serum glucose, glycated hemoglobin, electrolytes, creatinine, calcium, magnesium, creatine kinase, liver function tests, lipoproteins, except for low high-density lipoprotein (30 mg/dL, normal N40), vitamins B-6 and B-12, folate, protein electrophoresis, erythrocyte sedimentation rate, Lyme antibodies, antinuclear antibody, homocysteine and thrombophilia panel, serologic test for syphilis, arsenic, cadmium, lead, and mercury. Urine routine and microscopic analysis and drug screening panel were also normal as was an electrocardiogram. Radiographic imaging included normal chest films and computed tomography of the head. Magnetic resonance imaging of the brain was normal except for single tiny foci of increased signal in the left frontal lobe and pons consistent with gliosis, ischemia, or multiple sclerosis. An electroencephalogram showed generalized high-voltage sharp theta activity with photic stimulation and drowsiness, without focal abnormality. The patient’s job involved removing slag from furnaces (4-ft diameter, 22-ft height), which melted aluminum scrap and bar stock at 24008F, using a powdered flux of aluminum silicon fluoride. The work was hot and dusty. Only a plastic visor, leather gloves, and apron were used for protection with no respirator or local exhaust ventilation. A typical shift required charging 18 furnaces 6 times each, adding flux by hand. Slag was removed with a long shovel. About 48 hours had elapsed between his work shift and the seizure. A 36-year-old coworker doing the same job for 6 years had died of bstiff lungs.Q Phenytoin was given by vein and the patient had no further seizure activity. A neurologist recommended continued phenytoin therapy, follow-up EEG, no further alcohol or smoking, and no driving until seizure free for 6 months. Other recommendations were the use of improved work practice and protective equipment to reduce exposure to aluminum and fluoride dust, with repeat aluminum levels. Repeat [Al]b levels were 16 and 5 over the next 15 weeks, but the patient declined further phenytoin or other anticonvulsant therapy or EEG testing. He remained seizure free at 1 year, when his [Al]b was 4. The differential diagnosis includes alcohol withdrawal, multiple sclerosis, and idiopathic epilepsy. Although the patient’s [Al]b at the time of his hospitalization was only modestly elevated (22 vs 9 lg/L) — far lower than those reported in welders with EEG abnormalities — it is possible that his aluminum exposure played a causal role in his seizure. Some evidence indicates that inhaled aluminum can reach the brain via the olfactory nerve [11-13]. Once