- Email: [email protected]
Focal cerebral deficits in severe hypomagnesemia
Case Reports
Focal Cerebral Deficits in Severe Hypomagnesemia C a r o l R. L e i c h e r , M D *~, A d a m G. M e z o f f , M D * , a n d J e f f r e y S. H y a m s , M D *
Hypomagnesemia has been associated with multiple neurologic abnormalities, including irritability, seizures, paralysis, and choreiform movements. A patient with short gut syndrome who developed severe hypomagnesemia during an intercurrent diarrheal illness is reported. This patient had a transient neuroiogic syndrome consisting of hemiparesis, mental status changes, and aphasia which resolved as the magnesium levels returned to normal. Neurologic abnormalities of this child were largely secondary to severe hypomagnesemia and should be included in the list of neurologic abnormalities that can result from this metabolic derangement. Leicher CR, Mezoff AG, Hyams JS. Focal cerebral deficits in severe hypomagnesemia. Pediatr Neurol 1991;7:380-1.
Introduction Hypomagnesemia has been associated with multiple neurologic manifestations, including neuromuscular irritability and cerebral disturbances (e.g., seizures, abnormal movements, changes in level of consciousness) [1-6]. Focal neurologic abnormalities have not previously been recognized as part of the clinical syndrome of hypomagnesemia. We report a patient with short gut syndrome and hypomagnesemia who developed mental status changes and hemiparesis. Case Report This 3-year-old boy with short gut syndrome was admitted to Hartford Hospital because of a change in mental status and right hemiparesis. He was born with severe jejuno-ileal atresia and volvulus; following surgery he was left with only 8 cm of duodenum which was anastomosed to the transverse colon. Subsequently, he had been maintained on total parenteral nutrition at home since 8 months of age and
From the Departments of *Pediatrics and tNeurology; Hartford Hospital; Hartford, Connecticut; and University of Connecticut Health Center; Fannington, Connecticut.
380
PEDIATRIC NEUROLOGY
Vol. 7 No. 5
had displayed normal growth (both height, weight at 50th percentile) and neurologic development. A gastrostomy tube had b,zen in place for g&stric decompression and drained approximately 60(t cc each day. Serum electrolytes, calcium, magnesium, and Irate elements had been monitored on a regular basis and had been normal, tie had no prior neurologic abnormalities. Two days prior to admission the patient developed diarrhea with the passage of 4-5 large, watery stools each day. Prior to this he normally passed one small mucoid stool daily. There was no w)miting, tever, or previous antibiotic exposure. Over the 6 hours prior to admission he exhibited progressive drowsiness and then became unresponsive to voice command. Movements were decreased in the right am~. No tonic or clonic movements were observed. His g ~ e was wandering. On admission vital signs included pulse I I0/min. respiratory rate 24/min, blood pressure 116/70 mm Hg, and temperature 37"('. Examination of the head and chest revealed no abnormalities. The abdomen was soft and nontender; there was no organomegaly. Neurologic examination revealed a right gaze preference, decreased movement of the right side, mad hyperreflexia. He alternated between lethargic apathy and agitation and was nonverbal with no clear response to verbal commands. Laboratory data on admission included sodium 133 mEq/L, potassium 3.4 mEq/L, chloride 95 mEq/L bicarbonate 26 mEq/L, glucose 92 mg/dl, blood urea nitrogen 15 mg/dl, creatinine (1.7 mg/dl, albumin 3.7 g/dl, ammonia 50 gmol/L, AST 148 U/L, phosphorus 1.2 mmol/L (normal: 1.4-1.9 mmol/L), magnesium 0.08 mmol/L (normal: 0.7-1.0 mmol/L), ionized calcium 0.73 mmol/L (normal: 1.2-t.35 mmol/L), and a negative toxicology screen on blood and urine. Unenhanced cranial computed tomography revealed no abnormalities. Electroencephalography (EEG) demonstrated diffuse slowing of background rhythms over the left hemisphere with no epileptiform activity. The patient was treated with intravenous magnesium sulfate and calcium and serum magnesium and calcium values became normal over the next 8 hours. Approximately 30 hours after admission his neurologic examination continued to reveal an apathetic and sluggish child. He responded to questions monosyllabically and was able to name objects. Dysarthria was evident. No Chvostek sign was present. There were no twitching or abnormal movements. Cranial nerve examination revealed a right central facial palsy. There was a right hemiparesis evident primarily by increased spontaneous movement of his left side. He could move both arms against gravity and could pick up and hold objects with his right hand. Hyperreflexia was present on the right side with an extensor plantar response. He could walk with ~pport despite a degree of truncal ataxia: circumduction was observed on the right. Sensation was normal. On the third hospital day stool and gastrostomy fluid cultures contained Plesiomonas shigelloides (formerly known as Aeromoruls); trimethoprim/sulfamethoxazole was administered. A blood culture obtained on admission was negative. Over the fourth and fifth hospital days his sensorium improved and within 1 week he demonstrated gradual improvement of right-sided weakness and ataxia. His personality also returned to his normal outgoing and active state; the quantity and clarity of speech also returned. Two weeks after admission his parents reported that he had returned to normal. A repeat EEG and neurologic examination were performed 6 months after the episode. The neurologic examination revealed an alert, responsive 4-year-old male. He spoke fluently with an age-appropriate vocabulary. He had no naming difficulties and he followed l-step commands. He had no dysarthria. There were no cranial nerve abnormalities and his motor examination and stretch reflexes were symmetric with respect to power, tone, and dexterity. There was no tremor or
Communications should be addressed to: Dr. Leicher; Division of Pediatric Neurology; Department of Pediatrics; Hartford Hospital; 80 Seymour Street; Hartford, CT 06115. Received March 11, 1991; accepted May 15, 1991.
ataxia. EEG documented normal background activity with no focal slowing or epileptiform activity.
Discussion Magnesium is an essential mineral that plays an important role in the function of enzymes involved in glycolysis, energy metabolism, and transport [7]. Magnesium is stored primarily in bone and muscle with remaining stores in liver, heart, pancreas, and erythrocytes [4,7,8]. Absorption of magnesium occurs through both the small and large bowels and may be adversely affected by fat malabsorption, diarrhea, and excessive dietary fiber [7,8]. Although slightly less than one-half of magnesium in serum is bound to serum proteins, such as albumin, serum levels do not always reflect body stores [4,9]. CSF concentrations of magnesium tend to be considerably higher than those in serum [5]. Deficiency states of magnesium were observed in animals early in this century. Tetany and seizures were demonstrated in hypomagnesemic rats and cattle. Vallee et al. described a clinical syndrome of magnesium-deficiency tetany in humans in 1960 [2]. They studied adults with severe malnutrition secondary to malabsorption or chronic alcoholism who had low magnesium levels and developed tetany (i.e., carpopedal spasm and Chvostek signs) with normal calcium levels. In addition, seizures and athetoid movements were also observed. Later, Fishman reviewed several patients who also became clinically symptomatic with low magnesium levels [1]. One of his patients was a child with multifocal seizures. In 1967, Savage and McAdam reported an infant with hypomagnesemia and prolonged seizures [3]. There was a persistent focal component and an asymmetrically abnormal EEG but no associated focal motor deficit was found. The varied clinical picture of symptomatic hypomagnesemia has been attributed to concomitant disturbances in other ions. Magnesium plays a role in calcium metabolism as magnesium deficiency produces failure of calcium mobilization from the bone pool and interferes with secretion and end organ response to parathormone; therefore, magnesium deficiency is often associated with hypocalcemia as well [9,10]. It has also been postulated that hypocalcemia and hypokalemia will potentiate the effects of hypomagnesemia [1,7,10]. Several authors believe that low magnesium levels alone are associated with vertigo, ataxia, nystagmus, and movement disorders [4,8,9]. The additional presence of hypocalcemia then is marked by mental status changes ranging from apathy and personality changes to coma.
Further complication by hypokalemia may precipitate neuromuscular irritability and cardiac abnormalities. Our patient has severe short gut syndrome and is dependent upon parenteral magnesium to replace losses and maintain magnesium balance. When he developed an intercurrent infection with Plesiomonas, increased magnesium losses due to diarrhea likely resulted in the gradual development of severe hypomagnesemia. He became symptomatic, resulting in mental status changes, focal motor deficits, and dysarthria/aphasia. These symptoms gradually resolved after replacement therapy. It is likely that the symptoms may have been exacerbated by the hypocalcemia associated with hypomagnesemia. There was no evidence of a thrombotic or embolic etiology to his transient focal motor deficits, although other causes of "stroke" have not been totally excluded. Although it is possible that he had unobserved seizures with a focal component resulting in a postictal impairment, there is no evidence that such activity occurred. Plesiomonas shigelloides infection has not been associated with neurologic abnormalities. We believe that focal cerebral deficits should be added to the list of possible manifestations of hypomagnesemia. In addition, our observations should heighten awareness of the possibility of hypomagnesemia in the patient with short gut syndrome who presents with new onset of neurologic symptoms. References
[1] Fishman RA. Neurological aspects of magnesium metabolism. Arch Neurol 1965; 12:562-9. [2] Vallee BL, Wackcr EC, Ulmer DD. The magnesium-deficiency tetany syndrome in man. N Engl J Med 1960;262:155-61. [3] Savage DCL, McAdam WAF. Convulsions due to hypomagnesemia in an infant recovering from diarrhea. Lancet 1967;2:234-6. [4] Shils ME. Experimental human magnesium depletion. Medicine 1968;46:61-85. [5] Fishman RA. Neurologic manifestations of electrolyte disorders. In: Asbury AK, McKhann GM, McDonald WI, eds. Diseases of the nervous system. Philadelphia: WB Saunders, 1986:1491-8. [6] Harmon M. Parathyroid adenoma in a child. Am J Dis Child 1956;9:313-25. [7] Sutphen JL. Nutritional biochemistry of minerals-macronutrient. In: Grand 1LI, Sutphen JL, Dietz WH, eds. Pediatric nutrition, theory and practice. Boston: Butterworths, 1987;93-4. 18] Lau K. Magnesium metabolism- Normal and abnormal. In: Arieff AJ, Defronzo RA, eds. Fluid, electrolyte and acid-base disorders. New York: Churchill Livingstone, 1985;575-623. [9] Martin HE. Clinical magnesium deficiency. Ann NY Acad Sci 1969; 162:891-900. [10] Shils ME. Magnesium, calcium and parathyroid hormone interactions. Ann NY Acad Sci 1980;355:165-80.
Leicher et al: Focal Deficits in Hypomagnesemia
381
Focal Cerebral Deficits in Severe Hypomagnesemia C a r o l R. L e i c h e r , M D *~, A d a m G. M e z o f f , M D * , a n d J e f f r e y S. H y a m s , M D *
Hypomagnesemia has been associated with multiple neurologic abnormalities, including irritability, seizures, paralysis, and choreiform movements. A patient with short gut syndrome who developed severe hypomagnesemia during an intercurrent diarrheal illness is reported. This patient had a transient neuroiogic syndrome consisting of hemiparesis, mental status changes, and aphasia which resolved as the magnesium levels returned to normal. Neurologic abnormalities of this child were largely secondary to severe hypomagnesemia and should be included in the list of neurologic abnormalities that can result from this metabolic derangement. Leicher CR, Mezoff AG, Hyams JS. Focal cerebral deficits in severe hypomagnesemia. Pediatr Neurol 1991;7:380-1.
Introduction Hypomagnesemia has been associated with multiple neurologic manifestations, including neuromuscular irritability and cerebral disturbances (e.g., seizures, abnormal movements, changes in level of consciousness) [1-6]. Focal neurologic abnormalities have not previously been recognized as part of the clinical syndrome of hypomagnesemia. We report a patient with short gut syndrome and hypomagnesemia who developed mental status changes and hemiparesis. Case Report This 3-year-old boy with short gut syndrome was admitted to Hartford Hospital because of a change in mental status and right hemiparesis. He was born with severe jejuno-ileal atresia and volvulus; following surgery he was left with only 8 cm of duodenum which was anastomosed to the transverse colon. Subsequently, he had been maintained on total parenteral nutrition at home since 8 months of age and
From the Departments of *Pediatrics and tNeurology; Hartford Hospital; Hartford, Connecticut; and University of Connecticut Health Center; Fannington, Connecticut.
380
PEDIATRIC NEUROLOGY
Vol. 7 No. 5
had displayed normal growth (both height, weight at 50th percentile) and neurologic development. A gastrostomy tube had b,zen in place for g&stric decompression and drained approximately 60(t cc each day. Serum electrolytes, calcium, magnesium, and Irate elements had been monitored on a regular basis and had been normal, tie had no prior neurologic abnormalities. Two days prior to admission the patient developed diarrhea with the passage of 4-5 large, watery stools each day. Prior to this he normally passed one small mucoid stool daily. There was no w)miting, tever, or previous antibiotic exposure. Over the 6 hours prior to admission he exhibited progressive drowsiness and then became unresponsive to voice command. Movements were decreased in the right am~. No tonic or clonic movements were observed. His g ~ e was wandering. On admission vital signs included pulse I I0/min. respiratory rate 24/min, blood pressure 116/70 mm Hg, and temperature 37"('. Examination of the head and chest revealed no abnormalities. The abdomen was soft and nontender; there was no organomegaly. Neurologic examination revealed a right gaze preference, decreased movement of the right side, mad hyperreflexia. He alternated between lethargic apathy and agitation and was nonverbal with no clear response to verbal commands. Laboratory data on admission included sodium 133 mEq/L, potassium 3.4 mEq/L, chloride 95 mEq/L bicarbonate 26 mEq/L, glucose 92 mg/dl, blood urea nitrogen 15 mg/dl, creatinine (1.7 mg/dl, albumin 3.7 g/dl, ammonia 50 gmol/L, AST 148 U/L, phosphorus 1.2 mmol/L (normal: 1.4-1.9 mmol/L), magnesium 0.08 mmol/L (normal: 0.7-1.0 mmol/L), ionized calcium 0.73 mmol/L (normal: 1.2-t.35 mmol/L), and a negative toxicology screen on blood and urine. Unenhanced cranial computed tomography revealed no abnormalities. Electroencephalography (EEG) demonstrated diffuse slowing of background rhythms over the left hemisphere with no epileptiform activity. The patient was treated with intravenous magnesium sulfate and calcium and serum magnesium and calcium values became normal over the next 8 hours. Approximately 30 hours after admission his neurologic examination continued to reveal an apathetic and sluggish child. He responded to questions monosyllabically and was able to name objects. Dysarthria was evident. No Chvostek sign was present. There were no twitching or abnormal movements. Cranial nerve examination revealed a right central facial palsy. There was a right hemiparesis evident primarily by increased spontaneous movement of his left side. He could move both arms against gravity and could pick up and hold objects with his right hand. Hyperreflexia was present on the right side with an extensor plantar response. He could walk with ~pport despite a degree of truncal ataxia: circumduction was observed on the right. Sensation was normal. On the third hospital day stool and gastrostomy fluid cultures contained Plesiomonas shigelloides (formerly known as Aeromoruls); trimethoprim/sulfamethoxazole was administered. A blood culture obtained on admission was negative. Over the fourth and fifth hospital days his sensorium improved and within 1 week he demonstrated gradual improvement of right-sided weakness and ataxia. His personality also returned to his normal outgoing and active state; the quantity and clarity of speech also returned. Two weeks after admission his parents reported that he had returned to normal. A repeat EEG and neurologic examination were performed 6 months after the episode. The neurologic examination revealed an alert, responsive 4-year-old male. He spoke fluently with an age-appropriate vocabulary. He had no naming difficulties and he followed l-step commands. He had no dysarthria. There were no cranial nerve abnormalities and his motor examination and stretch reflexes were symmetric with respect to power, tone, and dexterity. There was no tremor or
Communications should be addressed to: Dr. Leicher; Division of Pediatric Neurology; Department of Pediatrics; Hartford Hospital; 80 Seymour Street; Hartford, CT 06115. Received March 11, 1991; accepted May 15, 1991.
ataxia. EEG documented normal background activity with no focal slowing or epileptiform activity.
Discussion Magnesium is an essential mineral that plays an important role in the function of enzymes involved in glycolysis, energy metabolism, and transport [7]. Magnesium is stored primarily in bone and muscle with remaining stores in liver, heart, pancreas, and erythrocytes [4,7,8]. Absorption of magnesium occurs through both the small and large bowels and may be adversely affected by fat malabsorption, diarrhea, and excessive dietary fiber [7,8]. Although slightly less than one-half of magnesium in serum is bound to serum proteins, such as albumin, serum levels do not always reflect body stores [4,9]. CSF concentrations of magnesium tend to be considerably higher than those in serum [5]. Deficiency states of magnesium were observed in animals early in this century. Tetany and seizures were demonstrated in hypomagnesemic rats and cattle. Vallee et al. described a clinical syndrome of magnesium-deficiency tetany in humans in 1960 [2]. They studied adults with severe malnutrition secondary to malabsorption or chronic alcoholism who had low magnesium levels and developed tetany (i.e., carpopedal spasm and Chvostek signs) with normal calcium levels. In addition, seizures and athetoid movements were also observed. Later, Fishman reviewed several patients who also became clinically symptomatic with low magnesium levels [1]. One of his patients was a child with multifocal seizures. In 1967, Savage and McAdam reported an infant with hypomagnesemia and prolonged seizures [3]. There was a persistent focal component and an asymmetrically abnormal EEG but no associated focal motor deficit was found. The varied clinical picture of symptomatic hypomagnesemia has been attributed to concomitant disturbances in other ions. Magnesium plays a role in calcium metabolism as magnesium deficiency produces failure of calcium mobilization from the bone pool and interferes with secretion and end organ response to parathormone; therefore, magnesium deficiency is often associated with hypocalcemia as well [9,10]. It has also been postulated that hypocalcemia and hypokalemia will potentiate the effects of hypomagnesemia [1,7,10]. Several authors believe that low magnesium levels alone are associated with vertigo, ataxia, nystagmus, and movement disorders [4,8,9]. The additional presence of hypocalcemia then is marked by mental status changes ranging from apathy and personality changes to coma.
Further complication by hypokalemia may precipitate neuromuscular irritability and cardiac abnormalities. Our patient has severe short gut syndrome and is dependent upon parenteral magnesium to replace losses and maintain magnesium balance. When he developed an intercurrent infection with Plesiomonas, increased magnesium losses due to diarrhea likely resulted in the gradual development of severe hypomagnesemia. He became symptomatic, resulting in mental status changes, focal motor deficits, and dysarthria/aphasia. These symptoms gradually resolved after replacement therapy. It is likely that the symptoms may have been exacerbated by the hypocalcemia associated with hypomagnesemia. There was no evidence of a thrombotic or embolic etiology to his transient focal motor deficits, although other causes of "stroke" have not been totally excluded. Although it is possible that he had unobserved seizures with a focal component resulting in a postictal impairment, there is no evidence that such activity occurred. Plesiomonas shigelloides infection has not been associated with neurologic abnormalities. We believe that focal cerebral deficits should be added to the list of possible manifestations of hypomagnesemia. In addition, our observations should heighten awareness of the possibility of hypomagnesemia in the patient with short gut syndrome who presents with new onset of neurologic symptoms. References
[1] Fishman RA. Neurological aspects of magnesium metabolism. Arch Neurol 1965; 12:562-9. [2] Vallee BL, Wackcr EC, Ulmer DD. The magnesium-deficiency tetany syndrome in man. N Engl J Med 1960;262:155-61. [3] Savage DCL, McAdam WAF. Convulsions due to hypomagnesemia in an infant recovering from diarrhea. Lancet 1967;2:234-6. [4] Shils ME. Experimental human magnesium depletion. Medicine 1968;46:61-85. [5] Fishman RA. Neurologic manifestations of electrolyte disorders. In: Asbury AK, McKhann GM, McDonald WI, eds. Diseases of the nervous system. Philadelphia: WB Saunders, 1986:1491-8. [6] Harmon M. Parathyroid adenoma in a child. Am J Dis Child 1956;9:313-25. [7] Sutphen JL. Nutritional biochemistry of minerals-macronutrient. In: Grand 1LI, Sutphen JL, Dietz WH, eds. Pediatric nutrition, theory and practice. Boston: Butterworths, 1987;93-4. 18] Lau K. Magnesium metabolism- Normal and abnormal. In: Arieff AJ, Defronzo RA, eds. Fluid, electrolyte and acid-base disorders. New York: Churchill Livingstone, 1985;575-623. [9] Martin HE. Clinical magnesium deficiency. Ann NY Acad Sci 1969; 162:891-900. [10] Shils ME. Magnesium, calcium and parathyroid hormone interactions. Ann NY Acad Sci 1980;355:165-80.
Leicher et al: Focal Deficits in Hypomagnesemia
381